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Al-Shuhaib MBS, Al-Shuhaib JMB. Assessing Therapeutic Value and Side Effects of Key Botanical Compounds for Optimized Medical Treatments. Chem Biodivers 2025; 22:e202401754. [PMID: 39316731 DOI: 10.1002/cbdv.202401754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 09/21/2024] [Accepted: 09/23/2024] [Indexed: 09/26/2024]
Abstract
Due to the significance of variable chemical groups across a wide spectrum of modern medicine, it is imperative to determine what is the most widely used group in medical applications with the fewest side effects. Ten compounds from ten chemical groups that are most commonly known for their medical uses were compared in terms of their therapeutic potential and side effects. The comparison among the selected compounds indicated the superiority of the flavonoids over other groups in the multitude of their utilizations and the lower side effects. Kaempferol and quercetin showed higher medical utilization with lower side effects. Whereas alkaloid compounds showed the lowest levels of medical use and the highest levels of side effects. Based on the comparison conducted, it is concluded to give priority to flavonoid compounds being used in medical applications because they exhibit the highest medical uses with the lowest side effects. Within flavonoids, kaempferol and quercetin are the two compounds that are highly recommended to be used in the widest range of medical applications. Serious caution should be considered before applying alkaloids to any medical service. Understanding the characteristics of these compounds can aid in developing safer and more effective treatments for medicinal plants.
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Affiliation(s)
- Mohammed Baqur S Al-Shuhaib
- Department of Animal Production, College of Agriculture, Al-Qasim Green University, 8 Babil, Al-Qasim, 51013, Iraq
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2
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Ibacache-Chía AP, Sierralta JA, Schüller A. The Inhibitory Effects of the Natural Stilbene Piceatannol on Lactate Transport In Vitro Mediated by Monocarboxylate Transporters. Mol Nutr Food Res 2024; 68:e2400414. [PMID: 39344244 DOI: 10.1002/mnfr.202400414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 08/30/2024] [Indexed: 10/01/2024]
Abstract
SCOPE Lactate, a signaling molecule and energy source, crosses membranes through monocarboxylate transporters (MCTs). MCT1 and MCT4 are potential cancer drug targets due to their role in metabolic reprogramming of cancer cells. Stilbenes, plant secondary metabolites found in several food sources, have anticancer effects, though their mechanisms of action are not well understood. This study links the anticancer activity of natural stilbenes to tumor cell lactate metabolism. METHODS AND RESULTS The impact of resveratrol, pinostilbene, pterostilbene, rhapontigenin, and piceatannol on lactate transport is studied using a fluorescence resonance energy transfer (FRET)-based lactate sensor. The viability and migration of cells expressing MCT1 or MCT4 are also evaluated. Piceatannol inhibits MCT1 effectively at low micromolar concentrations, with less effect on MCT4. All stilbenes significantly reduce cell viability and migration. CONCLUSIONS These findings indicate that both MCTs are stilbene targets, with piceatannol highlighted as a cost-effective, low-toxicity compound for studying MCTs in cancer, providing a new mechanism of action of the therapeutic and nutraceutical effects of natural polyphenols. This enriches the understanding of dietary polyphenols in cancer prevention and therapy.
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Affiliation(s)
- Andrés P Ibacache-Chía
- School of Biological Sciences, Pontificia Universidad Católica de Chile, Av. Libertador General Bernardo O'Higgins 340, Santiago, 8331150, Chile
- Department of Neuroscience, School of Medicine, University of Chile, Av. Independencia 1027, Independencia, 8380000, Chile
- Institute of Biomedical Neurosciences (BNI), School of Medicine, University of Chile, Av. Independencia 1027, Independencia, 8380000, Chile
| | - Jimena A Sierralta
- Department of Neuroscience, School of Medicine, University of Chile, Av. Independencia 1027, Independencia, 8380000, Chile
- Institute of Biomedical Neurosciences (BNI), School of Medicine, University of Chile, Av. Independencia 1027, Independencia, 8380000, Chile
| | - Andreas Schüller
- School of Biological Sciences, Pontificia Universidad Católica de Chile, Av. Libertador General Bernardo O'Higgins 340, Santiago, 8331150, Chile
- Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Santiago, 7820244, Chile
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3
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Marzęta-Assas P, Jacenik D, Zasłona Z. Pathophysiology of Arginases in Cancer and Efforts in Their Pharmacological Inhibition. Int J Mol Sci 2024; 25:9782. [PMID: 39337272 PMCID: PMC11431790 DOI: 10.3390/ijms25189782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/02/2024] [Accepted: 09/05/2024] [Indexed: 09/30/2024] Open
Abstract
Arginases are key enzymes that hydrolyze L-arginine to urea and L-ornithine in the urea cycle. The two arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), regulate the proliferation of cancer cells, migration, and apoptosis; affect immunosuppression; and promote the synthesis of polyamines, leading to the development of cancer. Arginases also compete with nitric oxide synthase (NOS) for L-arginine, and their participation has also been confirmed in cardiovascular diseases, stroke, and inflammation. Due to the fact that arginases play a crucial role in the development of various types of diseases, finding an appropriate candidate to inhibit the activity of these enzymes would be beneficial for the therapy of many human diseases. In this review, based on numerous experimental, preclinical, and clinical studies, we provide a comprehensive overview of the biological and physiological functions of ARG1 and ARG2, their molecular mechanisms of action, and affected metabolic pathways. We summarize the recent clinical trials' advances in targeting arginases and describe potential future drugs.
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Affiliation(s)
| | - Damian Jacenik
- Molecure S.A., 101 Żwirki i Wigury St., 02-089 Warsaw, Poland
- Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland
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4
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Kujawowicz K, Mirończuk-Chodakowska I, Witkowska AM. Sirtuin 1 as a potential biomarker of undernutrition in the elderly: a narrative review. Crit Rev Food Sci Nutr 2024; 64:9532-9553. [PMID: 37229564 DOI: 10.1080/10408398.2023.2214208] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Undernutrition and inflammatory processes are predictors of early mortality in the elderly and require a rapid and accurate diagnosis. Currently, there are laboratory markers for assessing nutritional status, but new markers are still being sought. Recent studies suggest that sirtuin 1 (SIRT1) has the potential to be a marker for undernutrition. This article summarizes available studies on the association of SIRT1 and undernutrition in older people. Possible associations between SIRT1 and the aging process, inflammation, and undernutrition in the elderly have been described. The literature suggests that low SIRT1 levels in the blood of older people may not be associated with physiological aging processes, but with an increased risk of severe undernutrition associated with inflammation and systemic metabolic changes.
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Affiliation(s)
- Karolina Kujawowicz
- Department of Food Biotechnology, Medical University of Bialystok, Bialystok, Poland
| | | | - Anna Maria Witkowska
- Department of Food Biotechnology, Medical University of Bialystok, Bialystok, Poland
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5
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Gandhi H, Mahant S, Sharma AK, Kumar D, Dua K, Chellappan DK, Singh SK, Gupta G, Aljabali AAA, Tambuwala MM, Kapoor DN. Exploring the therapeutic potential of naturally occurring piceatannol in non-communicable diseases. Biofactors 2024; 50:232-249. [PMID: 37702264 DOI: 10.1002/biof.2009] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 08/28/2023] [Indexed: 09/14/2023]
Abstract
Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.
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Affiliation(s)
- Himanshu Gandhi
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
| | - Shikha Mahant
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
| | - Abhishek Kumar Sharma
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
| | - Deepak Kumar
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
| | - Kamal Dua
- Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, New South Wales, Australia
| | | | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India
- Center for Transdisciplinary Research, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Alaa A A Aljabali
- Department of Pharmaceutics and Pharmaceutical Technology, Yarmouk University, Irbid, Jordan
| | - Murtaza M Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS, England, UK
| | - Deepak N Kapoor
- School of Pharmaceutical Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India
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Goleij P, Sanaye PM, Babamohamadi M, Tabari MAK, Amirian R, Rezaee A, Mirzaei H, Kumar AP, Sethi G, Sadreddini S, Jeandet P, Khan H. Phytostilbenes in lymphoma: Focuses on the mechanistic and clinical prospects of resveratrol, pterostilbene, piceatannol, and pinosylvin. Leuk Res 2024; 138:107464. [PMID: 38422882 DOI: 10.1016/j.leukres.2024.107464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 02/05/2024] [Accepted: 02/19/2024] [Indexed: 03/02/2024]
Abstract
Lymphoma is a cancer affecting the lymphatic system that fights infections and diseases. In addition to surgery, radiotherapy, and chemotherapy, novel approaches have recently been investigated, such as phytostilbenes in treating lymphoma. Phytostilbenes are natural compounds present in various plants and have been shown to have different therapeutic effects, including anticancer properties. Resveratrol is a main phytostilbene with various derivates followed by pterostilbene and piceatannol. Studies have revealed that phytostilbenes can suppress the growth and proliferation of lymphoma cells by inducing apoptosis and inhibiting specific enzyme activity in cancer cell survival. The compounds also have antiinflammatory effects contributing to reducing lymphoma-associated inflammation. Additionally, phytostilbenes have been shown to increase the immune system's ability to fight cancer cells by activating immune cells (T-cells and natural killer cells). This review investigates the potential therapeutic effects of phytostilbenes, including resveratrol, pterostilbene, piceatannol, and pinosylvin, against lymphoma.
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Affiliation(s)
- Pouya Goleij
- Department of Genetics, Sana Institute of Higher Education, Sari, Iran; PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; USERN Office, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Pantea Majma Sanaye
- PhytoPharmacology Interest Group (PPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; USERN Office, Kermanshah University of Medical Sciences, Kermanshah, Iran; School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mehregan Babamohamadi
- USERN Office, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran; Stem Cell and Regenerative Medicine Innovation Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Amin Khazeei Tabari
- Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran; USERN Office, Mazandaran University of Medical Sciences, Sari, Iran
| | - Roshanak Amirian
- USERN Office, Kermanshah University of Medical Sciences, Kermanshah, Iran; Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran; Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Aryan Rezaee
- Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Alan Prem Kumar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Sarvin Sadreddini
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Philippe Jeandet
- University of Reims Champagne-Ardenne, Research Unit "Induced Resistance and Plant Bioprotection", RIBP-USC INRA 1488, Reims 51100, France
| | - Haroon Khan
- Department of Pharmacy, Faculty of Chemical and Life Sciences, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
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Li H, Zhang H, Chen L, Shen Y, Cao Y, Li X, Yao J. Indirubin alleviates retinal neurodegeneration through the regulation of PI3K/AKT signaling. J Biomed Res 2024; 38:256-268. [PMID: 38387889 PMCID: PMC11144936 DOI: 10.7555/jbr.37.20230078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/30/2023] [Accepted: 06/01/2023] [Indexed: 02/24/2024] Open
Abstract
Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries, including glaucoma, diabetic retinopathy, traumatic optic neuropathy and optic neuritis, etc. The current clinical treatment is not very effective. We investigated indirubin, one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill, in the present study for its role in retinal neurodegeneration. Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro. Moreover, indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo. Furthermore, indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro. In addition, indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress. Mechanically, indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling. In conclusion, indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury. The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.
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Affiliation(s)
- Huan Li
- Department of Ophthalmology, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Ophthalmology, the Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Huiying Zhang
- Department of Ophthalmology, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Ophthalmology, the Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Lushu Chen
- Department of Ophthalmology, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Ophthalmology, the Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Yaming Shen
- Department of Ophthalmology, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Ophthalmology, the Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Yuan Cao
- Department of Ophthalmology, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Ophthalmology, the Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Xiumiao Li
- Department of Ophthalmology, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Ophthalmology, the Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China
| | - Jin Yao
- Department of Ophthalmology, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
- Department of Ophthalmology, the Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210029, China
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Mendonça ELSS, Xavier JA, Fragoso MBT, Silva MO, Escodro PB, Oliveira ACM, Tucci P, Saso L, Goulart MOF. E-Stilbenes: General Chemical and Biological Aspects, Potential Pharmacological Activity Based on the Nrf2 Pathway. Pharmaceuticals (Basel) 2024; 17:232. [PMID: 38399446 PMCID: PMC10891666 DOI: 10.3390/ph17020232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 01/27/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Stilbenes are phytoalexins, and their biosynthesis can occur through a natural route (shikimate precursor) or an alternative route (in microorganism cultures). The latter is a metabolic engineering strategy to enhance production due to stilbenes recognized pharmacological and medicinal potential. It is believed that in the human body, these potential activities can be modulated by the regulation of the nuclear factor erythroid derived 2 (Nrf2), which increases the expression of antioxidant enzymes. Given this, our review aims to critically analyze evidence regarding E-stilbenes in human metabolism and the Nrf2 activation pathway, with an emphasis on inflammatory and oxidative stress aspects related to the pathophysiology of chronic and metabolic diseases. In this comprehensive literature review, it can be observed that despite the broad number of stilbenes, those most frequently explored in clinical trials and preclinical studies (in vitro and in vivo) were resveratrol, piceatannol, pterostilbene, polydatin, stilbestrol, and pinosylvin. In some cases, depending on the dose/concentration and chemical nature of the stilbene, it was possible to identify activation of the Nrf2 pathway. Furthermore, the use of some experimental models presented a challenge in comparing results. In view of the above, it can be suggested that E-stilbenes have a relationship with the Nrf2 pathway, whether directly or indirectly, through different biological pathways, and in different diseases or conditions that are mainly related to inflammation and oxidative stress.
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Affiliation(s)
- Elaine L. S. S. Mendonça
- Program of the Northeast Biotechnology Network (RENORBIO), Institute of Chemistry and Biotechnology, Federal University of Alagoas (UFAL), Maceió 57072-900, Brazil; (E.L.S.S.M.); (M.O.S.)
| | - Jadriane A. Xavier
- Institute of Chemistry and Biotechnology, UFAL, Maceió 57072-900, Brazil; (J.A.X.); (M.B.T.F.)
| | - Marilene B. T. Fragoso
- Institute of Chemistry and Biotechnology, UFAL, Maceió 57072-900, Brazil; (J.A.X.); (M.B.T.F.)
| | - Messias O. Silva
- Program of the Northeast Biotechnology Network (RENORBIO), Institute of Chemistry and Biotechnology, Federal University of Alagoas (UFAL), Maceió 57072-900, Brazil; (E.L.S.S.M.); (M.O.S.)
| | | | | | - Paolo Tucci
- Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy;
| | - Luciano Saso
- Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University, 00185 Rome, Italy
| | - Marília O. F. Goulart
- Program of the Northeast Biotechnology Network (RENORBIO), Institute of Chemistry and Biotechnology, Federal University of Alagoas (UFAL), Maceió 57072-900, Brazil; (E.L.S.S.M.); (M.O.S.)
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Arif M, Pandey P, Khan F. Review Deciphering the Anticancer Efficacy of Resveratrol and their Associated Mechanisms in Human Carcinoma. Endocr Metab Immune Disord Drug Targets 2024; 24:1015-1026. [PMID: 37929735 DOI: 10.2174/0118715303251351231018145903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 09/14/2023] [Accepted: 09/20/2023] [Indexed: 11/07/2023]
Abstract
The scientific world has recently shown wider attention to elucidating the anticancerous potential of numerous plant-based bioactive compounds. Many research studies have suggested that consuming foods high in polyphenols, which are present in large amounts in grains, legumes, vegetables, and fruits, may delay the onset of various illnesses, including cancer. Normal cells with genetic abnormalities begin the meticulously organized path leading to cancer, which causes the cells to constantly multiply, colonize, and metastasize to other organs like the liver, lungs, colon, and brain. Resveratrol is a naturally occurring stilbene and non-flavonoid polyphenol, a phytoestrogen with antioxidant, anti-inflammatory, cardioprotective, and anticancer properties. Resveratrol makes cancer cells more susceptible to common chemotherapeutic treatments by reversing multidrug resistance in cancer cells. This is especially true when combined with clinically used medications. Several new resveratrol analogs with enhanced anticancer effectiveness, absorption, and pharmacokinetic profile have been discovered. The present emphasis of this review is the modulation of intracellular molecular targets by resveratrol in vivo and in vitro in various malignancies. This review would help future researchers develop a potent lead candidate for efficiently managing human cancers.
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Affiliation(s)
- Mohd Arif
- Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, U.P., India
| | - Pratibha Pandey
- Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, U.P., India
| | - Fahad Khan
- Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, U.P., India
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Xiao J, Ma J, Khan MZ, Alugongo GM, Chen T, Liu S, Li S, Cao Z. Unlocking the potential of milk whey protein components in colorectal cancer prevention and therapy. Crit Rev Food Sci Nutr 2023; 64:12961-12998. [PMID: 37846905 DOI: 10.1080/10408398.2023.2258970] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2023]
Abstract
Extensive research from large prospective cohort studies and meta-analytical investigations over recent decades have consistently indicated that dairy foods have protective effects, reducing the risk of colorectal cancer. Most of the literature has explored the potential role of milk minerals and vitamins in managing colorectal cancer. Yet, there is a paucity of a comprehensive summary of the anticancer attributes of milk protein components and their underlying mechanisms of action. Recent advancements have spotlighted the potential of whey proteins, including β-lactoglobulin, α-lactalbumin, serum albumin, and lactoferrin, as promising candidates for both the prevention and treatment of colorectal cancer. Notably, whey proteins have demonstrated a more pronounced capacity for suppressing carcinogen-induced tumors when compared to casein. Their strong binding affinity enables them to serve as effective carriers for small molecules or drugs targeting colon cancer therapy. Furthermore, numerous studies have underscored the anti-inflammatory and antioxidant prowess of whey proteins in cancer prevention. Additionally, whey proteins have been shown to trigger apoptosis, hinder tumor cell proliferation, and impede metastasis. This comprehensive review, therefore, not only substantiates the significance of incorporating whey protein components into a balanced daily diet but also underscores their potential in safeguarding against the onset and progression of colorectal cancer.
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Affiliation(s)
- Jianxin Xiao
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
- Key Laboratory of Low Carbon Culture and Safety Production in Cattle in Sichuan, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China
| | - Jiaying Ma
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Muhammad Zahoor Khan
- Faculty of Veterinary and Animal Sciences, University of Agriculture Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan
| | - Gibson Maswayi Alugongo
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Tianyu Chen
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shuai Liu
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shengli Li
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zhijun Cao
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
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Ezz Eldeen N, Moustafa YM, Alwaili MA, Alrehaili AA, Khodeer DM. Synergistic Power of Piceatannol and/or Vitamin D in Bleomycin-Induced Pulmonary Fibrosis In Vivo: A Preliminary Study. Biomedicines 2023; 11:2647. [PMID: 37893021 PMCID: PMC10604873 DOI: 10.3390/biomedicines11102647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 09/12/2023] [Accepted: 09/18/2023] [Indexed: 10/29/2023] Open
Abstract
Oxidative stress and epigenetic alterations, including the overexpression of all class I and II histone deacetylases (HDACs), particularly HDAC2 and HDAC4, have been identified as key molecular mechanisms driving pulmonary fibrosis. Treatment with piceatannol (PIC) or vitamin D (Vit D) has previously exhibited mitigating impacts in pulmonary fibrosis models. The present study investigated the effects of PIC, Vit D, or a combination (PIC-Vit D) on the expression of HDAC2, HDAC4, and transforming growth factor-beta (TGF-β) in the lungs; the phosphatidylinositide-3-kinase (PI3K)/AKT signaling pathway; and the antioxidant status of the lungs. The objective was to determine if the treatments had protective mechanisms against pulmonary fibrosis caused by bleomycin (BLM) in rats. Adult male albino rats were given a single intratracheal dosage of BLM (10 mg/kg) to induce pulmonary fibrosis. PIC (15 mg/kg/day, oral (p.o.)), Vit D (0.5 μg/kg/day, intraperitoneal (i.p.)), or PIC-Vit D (15 mg/kg/day, p.o. plus 0.5 μg/kg/day, i.p.) were given the day following BLM instillation and maintained for 14 days. The results showed that PIC, Vit D, and PIC-Vit D significantly improved the histopathological sections; downregulated the expression of HDAC2, HDAC4, and TGF-β in the lungs; inhibited the PI3K/AKT signaling pathway; decreased extracellular matrix (ECM) deposition including collagen type I and alpha smooth muscle actin (α-SMA); and increased the antioxidant capacity of the lungs by increasing the levels of glutathione (GSH) that had been reduced and decreasing the levels of malondialdehyde (MDA) compared with the BLM group at a p-value less than 0.05. The concomitant administration of PIC and Vit D had a synergistic impact that was greater than the impact of monotherapy with either PIC or Vit D. PIC, Vit D, and PIC-Vit D exhibited a notable protective effect through their antioxidant effects, modulation of the expression of HDAC2, HDAC4, and TGF-β in the lungs, and suppression of the PI3K/AKT signaling pathway.
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Affiliation(s)
- Nehal Ezz Eldeen
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Yasser M. Moustafa
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Maha Abdullah Alwaili
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Amani A. Alrehaili
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Dina M. Khodeer
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
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12
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Duta-Bratu CG, Nitulescu GM, Mihai DP, Olaru OT. Resveratrol and Other Natural Oligomeric Stilbenoid Compounds and Their Therapeutic Applications. PLANTS (BASEL, SWITZERLAND) 2023; 12:2935. [PMID: 37631147 PMCID: PMC10459741 DOI: 10.3390/plants12162935] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/01/2023] [Accepted: 08/09/2023] [Indexed: 08/27/2023]
Abstract
The use of natural compounds as an alternative to synthetic molecules has become a significant subject of interest in recent decades. Stilbenoids are a group of phenolic compounds found in many plant species and they have recently gained the focus of a multitude of studies in medicine and chemistry, resveratrol being the most representative molecule. In this review, we focused on the research that illustrates the therapeutic potential of this class of natural molecules considering various diseases with higher incidence rates. PubChem database was searched for bioactivities of natural stilbenoids, while several keywords (i.e., "stilbenoids", "stilbenoid anticancer") were used to query PubMed database for relevant studies. The diversity and the simplicity of stilbenes' chemical structures together with the numerous biological sources are key elements that can simplify both the isolation of these compounds and the drug design of novel bioactive molecules. Resveratrol and other related compounds are heterogeneously distributed in plants and are mainly found in grapes and wine. Natural stilbenes were shown to possess a wide range of biological activities, such as antioxidant, anti-inflammatory, antihyperglycemic, cardioprotective, neuroprotective, and antineoplastic properties. While resveratrol is widely investigated for its benefits in various disorders, further studies are warranted to properly harness the therapeutic potential of less popular stilbenoid compounds.
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Affiliation(s)
| | - George Mihai Nitulescu
- Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania (O.T.O.)
| | - Dragos Paul Mihai
- Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania (O.T.O.)
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13
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Gołąbek-Grenda A, Kaczmarek M, Juzwa W, Olejnik A. Natural resveratrol analogs differentially target endometriotic cells into apoptosis pathways. Sci Rep 2023; 13:11468. [PMID: 37454164 PMCID: PMC10349804 DOI: 10.1038/s41598-023-38692-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 07/12/2023] [Indexed: 07/18/2023] Open
Abstract
The specific characteristics of endometriotic cells are their ability to evade the apoptotic machinery and abnormal response to apoptotic stimuli. Natural-originated compounds may constitute a beneficial strategy in apoptosis modulation in endometriosis. We investigated and compared the potency of natural resveratrol analogs, including piceatannol, polydatin, and pterostilbene, in targeting cell death pathways, including apoptosis-related morphologic and biochemical processes, alongside the modulation of the critical genes expression. Upon resveratrol and pterostilbene treatment, a significant reduction of endometriotic cell viability and an increased apoptotic proportion of cells were noted. The lower antiproliferative potential was found for piceatannol and polydatin. Endometrial stromal T HESC cells were significantly more resistant than endometriotic epithelial 12Z cells to the cytotoxic activity of all analyzed compounds. They differentially affected endometriotic cell viability, cell cycle, anti- and proapoptotic genes regulation, caspases expression and enzymatic activity, and DNA fragmentation. Pterostilbene-mediated endometriotic cell apoptosis modulation was confirmed to be most effective but without evident caspase 3 upregulation. Our study provides valuable insight into the apoptogenic activity of resveratrol and its natural analogs in endometriotic cells. Data obtained revealed the highest therapeutic potential of pterostilbene by effectively targeting cell death determinants in endometriosis, strengthening its optimization in further extensive research.
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Affiliation(s)
- Agata Gołąbek-Grenda
- Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, 48 Wojska Polskiego St., 60-627, Poznan, Poland
| | - Mariusz Kaczmarek
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, 61-866, Poznan, Poland
- Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, 61-866, Poznan, Poland
| | - Wojciech Juzwa
- Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, 48 Wojska Polskiego St., 60-627, Poznan, Poland
| | - Anna Olejnik
- Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, 48 Wojska Polskiego St., 60-627, Poznan, Poland.
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14
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Sie YY, Chen LC, Li CJ, Yuan YH, Hsiao SH, Lee MH, Wang CC, Hou WC. Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment. Antioxidants (Basel) 2023; 12:1362. [PMID: 37507902 PMCID: PMC10376691 DOI: 10.3390/antiox12071362] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/28/2023] [Accepted: 06/28/2023] [Indexed: 07/30/2023] Open
Abstract
Currently, no drug is effective in delaying the cognitive impairment of Alzheimer's disease, which ranks as one of the top 10 causes of death worldwide. Hydroxylated stilbenes are active compounds that exist in fruit and herbal plants. Piceatannol (PIC) and gnetol (GNT), which have one extra hydroxyl group in comparison to resveratrol (RSV), and rhapontigenin (RHA) and isorhapontigenin (isoRHA), which were metabolized from PIC in vivo and contain the same number of hydroxyl groups as RSV, were evaluated for their effects on Alzheimer's disease-associated factors in vitro and in animal experiments. Among the five hydroxylated stilbenes, PIC was shown to be the most active in DPPH radical scavenging and in inhibitory activities against acetylcholinesterase and amyloid-β peptide aggregations, with concentrations for half-maximal inhibitions of 40.2, 271.74, and 0.48 μM. The different interactions of the five hydroxylated stilbenes with acetylcholinesterase or amyloid-β were obtained by molecular docking. The scopolamine-induced ICR mice fed with PIC (50 mg/kg) showed an improved learning behavior in the passive avoidance tests and had significant differences (p < 0.05) compared with those in the control group. The RHA and isoRHA at 10 μM were proven to stimulate neurite outgrowths in the SH-SY5Y cell models. These results reveal that nutraceuticals or functional foods containing PIC have the potential for use in the treatment of neurodegenerative disorders.
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Affiliation(s)
- Yi-Yan Sie
- Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
| | - Liang-Chieh Chen
- Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
| | - Cai-Jhen Li
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, Taiwan
| | - Yu-Hsiang Yuan
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, Taiwan
| | - Sheng-Hung Hsiao
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, Taiwan
| | - Mei-Hsien Lee
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, Taiwan
| | - Ching-Chiung Wang
- School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
- Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan
| | - Wen-Chi Hou
- Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, Taiwan
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15
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Kim H, Rencoret J, Elder TJ, del Río JC, Ralph J. Biomimetic oxidative copolymerization of hydroxystilbenes and monolignols. SCIENCE ADVANCES 2023; 9:eade5519. [PMID: 36888720 PMCID: PMC9995074 DOI: 10.1126/sciadv.ade5519] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 02/07/2023] [Indexed: 06/18/2023]
Abstract
Hydroxystilbenes are a class of polyphenolic compounds that behave as lignin monomers participating in radical coupling reactions during the lignification. Here, we report the synthesis and characterization of various artificial copolymers of monolignols and hydroxystilbenes, as well as low-molecular-mass compounds, to obtain the mechanistic insights into their incorporation into the lignin polymer. Integrating the hydroxystilbenes, resveratrol and piceatannol, into monolignol polymerization in vitro, using horseradish peroxidase to generate phenolic radicals, produced synthetic lignins [dehydrogenation polymers (DHPs)]. Copolymerization of hydroxystilbenes with monolignols, especially sinapyl alcohol, by in vitro peroxidases notably improved the reactivity of monolignols and resulted in substantial yields of synthetic lignin polymers. The resulting DHPs were analyzed using two-dimensional NMR and 19 synthesized model compounds to confirm the presence of hydroxystilbene structures in the lignin polymer. The cross-coupled DHPs confirmed both resveratrol and piceatannol as authentic monomers participating in the oxidative radical coupling reactions during polymerization.
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Affiliation(s)
- Hoon Kim
- Department of Energy Great Lakes Bioenergy Research Center, Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI 53726, USA
| | - Jorge Rencoret
- Instituto de Recursos Naturales y Agrobiología de Sevilla (IRNAS), CSIC, Avenida de la Reina Mercedes, 10, 41012, Seville, Spain
| | - Thomas J. Elder
- USDA-Forest Service, Southern Research Station 521 Devall Dr. Auburn, AL 36849, USA
| | - José C. del Río
- Instituto de Recursos Naturales y Agrobiología de Sevilla (IRNAS), CSIC, Avenida de la Reina Mercedes, 10, 41012, Seville, Spain
| | - John Ralph
- Department of Energy Great Lakes Bioenergy Research Center, Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI 53726, USA
- Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA
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16
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Huangfu L, Wang X, Tian S, Chen J, Wang X, Fan B, Yao Q, Wang G, Chen C, Han J, Xing X, Ji J. Piceatannol enhances Beclin-1 activity to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer. SCIENCE CHINA. LIFE SCIENCES 2023; 66:298-312. [PMID: 36271983 DOI: 10.1007/s11427-022-2185-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 08/19/2022] [Indexed: 11/07/2022]
Abstract
The effects and regulation of Beclin-1-an autophagy-related protein-have not been fully defined, however, a negative correlation has been reported between Beclin-1 expression and carcinogenesis. Meanwhile, no compound has been shown to directly inhibit its activity. Here, we evaluate piceatannol, a naturally occurring polyphenolic compound, as a potential targeting agonist of Beclin-1, to assess its efficacy as an antitumor agent against gastric cancer. More specifically, we determine the effects of piceatannol treatment on cell viability using a monitoring system and colony forming assay. Piceatannol was found to efficiently inhibit the proliferation of several human gastric cancer cell lines. Autophagic flux is increased by piceatannol treatment, and correlates with inhibition of cell proliferation and colony formation. Additionally, microscale thermophoresis and surface plasmon resonance results show a direct interaction between piceatannol and Beclin-1, which reduces the phosphorylation activity of Beclin-1 at the Ser-295 site. Notably, piceatannol impairs the binding of Beclin-1 to Bcl-2 and enhances the recruitment of binding of UV radiation resistance-associated gene protein, which further triggers Beclin-1-dependent autophagy signaling. An increase in autophagic activity via treatment with the mTOR inhibitor, everolimus, effectively sensitizes piceatannol-induced antitumor effects. Xenograft models confirmed that piceatannol inhibits tumor development and elicits a potent synergistic effect with everolimus in vivo. Taken together, the findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.
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Affiliation(s)
- Longtao Huangfu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xiaoyang Wang
- Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Shanshan Tian
- National Institute on Drug Dependence, Peking University, Beijing, 100191, China
| | - Junbing Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China.,Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xueying Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China.,Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Biao Fan
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Qian Yao
- Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Gangjian Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China.,Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Cong Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China.,Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Jing Han
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xiaofang Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China. .,Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
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17
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Zhang S, Ye J, Wang L, Zhong X, Zou X, Qiu F, Huang Z. Piceatannol protects rat neuron cells from oxygen-glucose deprivation reperfusion injury via regulation of GSK-3β/Nrf2 signaling pathway. Zhejiang Da Xue Xue Bao Yi Xue Ban 2022; 51:552-562. [PMID: 36581571 PMCID: PMC10264976 DOI: 10.3724/zdxbyxb-2022-0328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 09/20/2022] [Indexed: 12/03/2022]
Abstract
OBJECTIVE To investigate the effect and mechanism of piceatannol on cerebral ischemia-reperfusion injury. METHODS The oxygen-glucose deprivation reperfusion (OGD/R) model was constructed in primary cultured suckling rat cortical neuron cells. After 2 h of oxygen-glucose deprivation, the cells were treated with piceatannol for 24 h. The cell survival rate was detected by MTT assay, and the degree of cell damage was detected by intracellular lactate dehydrogenase (LDH) release assay. The activity of superoxide dismutase (SOD) and the content of adenosine triphosphate (ATP) were detected by colorimetric method. The content of reactive oxygen species (ROS) was detected by flow cytometry or observed with inverted fluorescence microscope. The ultrastructure of mitochondria was observed with transmission electron microscopy. Western blotting was used to detect the phosphorylation levels of protein kinase B (AKT) and glycogen synthase kinase (GSK)-3β. Immunofluorescence staining was used to observe the nuclear localization of nuclear factor-erythroid 2-related factor (Nrf) 2. After OGD/R neuron cells were pretreated with Nrf2 inhibitor ML385 for 24 h, the effect of Nrf2 on the improvement of cell activity and antioxidant activity of piceatannol were investigated. Western blotting was used to detect the protein expression levels of Nrf2, heme oxygenase (HO) 1 and NADPH quinone oxidoreductase (NQO) 1. RESULTS Piceatannol significantly increased the survival rate of OGD/R neurons, decreased LDH release and reactive oxygen species content, increased SOD activity, ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and ATP level (all P<0.05), increased phosphorylation of AKT and GSK-3β protein, up-regulated the expression of Nrf2, HO-1 and NQO1 protein, increased the nuclear-to-plasma ratio of Nrf2, and promoted the nuclear transfer of Nrf2 (all P<0.05). ML385 could significantly reverse the rescue effect of paclitaxel on the model cells and the regulatory activities of SOD, ROS and LDH (all P<0.05). CONCLUSION Piceatannol can regulate Nrf2 by activating GSK-3β signaling pathway, promote its nuclear translocation, exert corresponding antioxidant effect, and protect mitochondrial structure and function in rat neuron cells.
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Affiliation(s)
- Shuyuan Zhang
- 1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Jiayi Ye
- 1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Lingfeng Wang
- 1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Xiaoming Zhong
- 1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Xiaowei Zou
- 1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Fengmei Qiu
- 1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Zhen Huang
- 1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
- 2. Zhejiang Provincial Key Laboratory of Neuropharmacology and Translational Medicine, Hangzhou 310053, China
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18
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Izuegbuna OO. Polyphenols: Chemoprevention and therapeutic potentials in hematological malignancies. Front Nutr 2022; 9:1008893. [PMID: 36386899 PMCID: PMC9643866 DOI: 10.3389/fnut.2022.1008893] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 09/02/2022] [Indexed: 01/25/2024] Open
Abstract
Polyphenols are one of the largest plant-derived natural product and they play an important role in plants' defense as well as in human health and disease. A number of them are pleiotropic molecules and have been shown to regulate signaling pathways, immune response and cell growth and proliferation which all play a role in cancer development. Hematological malignancies on the other hand, are cancers of the blood. While current therapies are efficacious, they are usually expensive and with unwanted side effects. Thus, the search for newer less toxic agents. Polyphenols have been reported to possess antineoplastic properties which include cell cycle arrest, and apoptosis via multiple mechanisms. They also have immunomodulatory activities where they enhance T cell activation and suppress regulatory T cells. They carry out these actions through such pathways as PI3K/Akt/mTOR and the kynurenine. They can also reverse cancer resistance to chemotherapy agents. In this review, i look at some of the molecular mechanism of action of polyphenols and their potential roles as therapeutic agents in hematological malignancies. Here i discuss their anti-proliferative and anti-neoplastic activities especially their abilities modulate signaling pathways as well as immune response in hematological malignancies. I also looked at clinical studies done mainly in the last 10-15 years on various polyphenol combination and how they enhance synergism. I recommend that further preclinical and clinical studies be carried out to ensure safety and efficacy before polyphenol therapies be officially moved to the clinics.
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Affiliation(s)
- Ogochukwu O. Izuegbuna
- Department of Haematology, Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, Ogbomoso, Nigeria
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19
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Li Z, Wang L, Ren Y, Huang Y, Liu W, Lv Z, Qian L, Yu Y, Xiong Y. Arginase: shedding light on the mechanisms and opportunities in cardiovascular diseases. Cell Death Dis 2022; 8:413. [PMID: 36209203 PMCID: PMC9547100 DOI: 10.1038/s41420-022-01200-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 09/17/2022] [Accepted: 09/23/2022] [Indexed: 11/30/2022]
Abstract
Arginase, a binuclear manganese metalloenzyme in the urea, catalyzes the hydrolysis of L-arginine to urea and L-ornithine. Both isoforms, arginase 1 and arginase 2 perform significant roles in the regulation of cellular functions in cardiovascular system, such as senescence, apoptosis, proliferation, inflammation, and autophagy, via a variety of mechanisms, including regulating L-arginine metabolism and activating multiple signal pathways. Furthermore, abnormal arginase activity contributes to the initiation and progression of a variety of CVDs. Therefore, targeting arginase may be a novel and promising approach for CVDs treatment. In this review, we give a comprehensive overview of the physiological and biological roles of arginase in a variety of CVDs, revealing the underlying mechanisms of arginase mediating vascular and cardiac function, as well as shedding light on the novel and promising therapeutic approaches for CVDs therapy in individuals.
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Affiliation(s)
- Zhuozhuo Li
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China.,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Liwei Wang
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China.,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Yuanyuan Ren
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China.,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Yaoyao Huang
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China.,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Wenxuan Liu
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China.,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Ziwei Lv
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China.,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China
| | - Lu Qian
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China. .,Department of Endocrinology, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Northwest University, Xi'an, Shaanxi, China.
| | - Yi Yu
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China. .,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China.
| | - Yuyan Xiong
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi, China. .,Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an, Shaanxi, China.
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20
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Sun BY, Sui HL, Liu ZW, Tao XY, Gao B, Zhao M, Ma YS, Zhao J, Liu M, Wang FQ, Wei DZ. Structure-guided engineering of a flavin-containing monooxygenase for the efficient production of indirubin. BIORESOUR BIOPROCESS 2022; 9:70. [PMID: 38647553 PMCID: PMC10991670 DOI: 10.1186/s40643-022-00559-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 06/10/2022] [Indexed: 11/10/2022] Open
Abstract
Indirubin is a bisindole compound for the treatment of chronic myelocytic leukemia. Here, we presented a structure-guided method to improve the activity of a flavin-containing monooxygenase (bFMO) for the efficient production of indirubin in Escherichia coli. A flexible loop interlocked with the active pocket through a helix and the substrate tunnel rather than the active pocket in bFMO were identified to be two reconfigurable structures to improve its activity, resulting in K223R and N291T mutants with enhanced catalytic activity by 2.5- and 2.0-fold, respectively. A combined modification at the two regions (K223R/D317S) achieved a 6.6-fold improvement in catalytic efficiency (kcat/Km) due to enhancing π-π stacking interactions stabilization. Finally, an engineered E. coli strain was constructed by metabolic engineering, which could produce 860.7 mg/L (18 mg/L/h) indirubin, the highest yield ever reported. This work provides new insight into the redesign of FMOs to boost their activities and an efficient approach to produce indirubin.
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Affiliation(s)
- Bing-Yao Sun
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Hua-Lu Sui
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Zi-Wei Liu
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Xin-Yi Tao
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Bei Gao
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Ming Zhao
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Yu-Shu Ma
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Jian Zhao
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Min Liu
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China.
| | - Feng-Qing Wang
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China.
| | - Dong-Zhi Wei
- State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
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21
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Chiou YS, Lan YM, Lee PS, Lin Q, Nagabhushanam K, Ho CT, Pan MH. Piceatannol Prevents Colon Cancer Progression via Dual-Targeting to M2-Polarized Tumor-Associated Macrophages and the TGF-β1 Positive Feedback Signaling Pathway. Mol Nutr Food Res 2022; 66:e2200248. [PMID: 35616191 DOI: 10.1002/mnfr.202200248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/18/2022] [Indexed: 01/10/2023]
Abstract
SCOPE M2 phenotype tumor-associated macrophages (M2-TAMs) play a key role in distant metastasis and poor clinical outcomes. Herein, a specific molecular mechanism that contributes to malignant progression is illuminated and investigates whether piceatannol (PIC) can target the crosstalk between M2-TAMs and cancer cells for potential colorectal cancer (CRC) therapy. METHODS AND RESULTS To mimic the tumor microenvironment (TME), direct and indirect coculture systems in vitro and in vivo mouse xenograft models are established. The results demonstrate that post-treatment with PIC in TME more effectively prevented the aggressive features and stemness of SW480 cells by restricting the polarization of M2-like macrophages and blocking the transforming growth factor β1 (TGF-β1) positive feedback autocrine/paracrine loop that exists between M2-like polarized macrophages and cancer cells. Furthermore, xenograft assays also observe significant repression in tumor growth and lung metastases with the administration of PIC. The key mechanism underlying the antimetastasis effects of PIC may include its directly inhibitory activity against TGF-β receptor type-1 (TGF-βR1) in the M2-like TAMs-created TME. CONCLUSION These novel findings demonstrate that PIC is a potent TGF-β1/TGF-βR1 pathway inhibitor and TME modulator for preventing tumor progression and metastasis in CRC by reeducating TAMs.
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Affiliation(s)
- Yi-Shiou Chiou
- Master Degree Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.,Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan
| | - Yi-Ming Lan
- Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan
| | - Pei-Sheng Lee
- Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan
| | - Qianyu Lin
- Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen, 518055, P. R. China
| | | | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, NJ, 08901, USA
| | - Min-Hsiung Pan
- Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan.,Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan.,Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan
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22
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Alpinetin: a Dietary Flavonoid with Diverse Anticancer Effects. Appl Biochem Biotechnol 2022; 194:4220-4243. [PMID: 35567708 DOI: 10.1007/s12010-022-03960-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 05/02/2022] [Indexed: 11/02/2022]
Abstract
Cancer is a global burden and mechanistically complex disease with a plethora of genetic, physiological, metabolic, and environmental alterations. The development of dietary nutraceuticals into cancer chemotherapeutics has emerged as a new paradigm in cancer treatment. Alpinetin (ALPI) is a novel flavonoid component of multiple edible and medicinal plants and possesses a wide range of biological and pharmacological activities including antibacterial, anti-hemostatic, anti-oxidative, anti-hepatotoxic, stomachic, immunosuppressive, and anti-inflammatory. Recently, ALPI has been reported as a bioactive dietary nutraceutical with promising anticancer activity in various human cancers through multiple mechanisms. The purpose of this review is to compile the data on natural sources of ALPI, and its anticancer activity including cellular targets and anticancer mechanism in various human cancers. Moreover, this review will set the stage for further design and conduct pre-clinical and clinical trials to develop ALPI into a lead structure for oncological therapy.
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23
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Niu F, Yu Y, Li Z, Ren Y, Li Z, Ye Q, Liu P, Ji C, Qian L, Xiong Y. Arginase: An emerging and promising therapeutic target for cancer treatment. Biomed Pharmacother 2022; 149:112840. [PMID: 35316752 DOI: 10.1016/j.biopha.2022.112840] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/03/2022] [Accepted: 03/16/2022] [Indexed: 11/19/2022] Open
Abstract
Arginase is a key hydrolase in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. Increasing number of studies in recent years demonstrate that two mammalian arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), were aberrantly upregulated in various types of cancers, and played crucial roles in the regulation of tumor growth and metastasis through various mechanisms such as regulating L-arginine metabolism, influencing tumor immune microenvironment, etc. Thus, arginase receives increasing focus as an attractive target for cancer therapy. In this review, we provide a comprehensive overview of the physiological and biological roles of arginase in a variety of cancers, and shed light on the underlying mechanisms of arginase mediating cancer cells growth and development, as well as summarize the recent clinical research advances of targeting arginase for cancer therapy.
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Affiliation(s)
- Fanglin Niu
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China
| | - Yi Yu
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China
| | - Zhuozhuo Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China
| | - Yuanyuan Ren
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China
| | - Zi Li
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China
| | - Qiang Ye
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China
| | - Ping Liu
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, China; Department of Endocrinology, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an 710018, Shaanxi, China
| | - Chenshuang Ji
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China
| | - Lu Qian
- Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, China; Department of Endocrinology, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an 710018, Shaanxi, China.
| | - Yuyan Xiong
- Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China; Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi, China.
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24
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Teka T, Zhang L, Ge X, Li Y, Han L, Yan X. Stilbenes: Source plants, chemistry, biosynthesis, pharmacology, application and problems related to their clinical Application-A comprehensive review. PHYTOCHEMISTRY 2022; 197:113128. [PMID: 35183567 DOI: 10.1016/j.phytochem.2022.113128] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 02/08/2022] [Accepted: 02/09/2022] [Indexed: 06/14/2023]
Abstract
Stilbenes are some of the important phenolic compounds originating from plant families like Vitaceae, Leguminaceae, Gnetaceae, and Dipterocarpaceae. Structurally, they have a C6-C2-C6 skeleton, usually with two isomeric forms. Stilbenes are biosynthesized due to biotic and abiotic stresses such as microbial infections, high temperatures, and oxidation. This review aims to provide a comprehensive overview of stilbenes' botanical sources, chemistry, biosynthetic pathways, pharmacology, and clinical applications and challenges based on up-to-date data. All included studies were collected from PubMed, ScienceDirect, Google Scholar, and CNKI, and the presented data from these indexed studies were analyzed and summarized. A total of 459 natural stilbene compounds from 45 plant families and 196 plant species were identified. Pharmacological studies also show that stilbenes have various activities such as anticancer, antimicrobial, antioxidant, anti-inflammatory, anti-degenerative diseases, anti-diabetic, neuroprotective, anti-aging, and cardioprotective effects. Stilbene synthase (STS) is the key enzyme involved in stilbene biosynthetic pathways. Studies on the therapeutic application of stilbenes pinpoint that challenges such as low bioavailability and isomerization are the major bottlenecks for their development as therapeutic drugs. Although the medicinal uses of several stilbenes have been demonstrated in vivo and in vitro, studies on the development of stilbenes deserve more attention in the future.
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Affiliation(s)
- Tekleab Teka
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China; Department of Pharmacy, College of Medicine and Health Sciences, Wollo University, P. O. Box 1145, Dessie, Ethiopia
| | - Lele Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China
| | - Xiaoyan Ge
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China
| | - Yanjie Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China
| | - Lifeng Han
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China.
| | - Xiaohui Yan
- State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, PR China.
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25
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Ahmad N, Qamar M, Yuan Y, Nazir Y, Wilairatana P, Mubarak MS. Dietary Polyphenols: Extraction, Identification, Bioavailability, and Role for Prevention and Treatment of Colorectal and Prostate Cancers. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27092831. [PMID: 35566182 PMCID: PMC9104150 DOI: 10.3390/molecules27092831] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 04/26/2022] [Accepted: 04/26/2022] [Indexed: 12/12/2022]
Abstract
Fruits, vegetables, and other edible plants in our diet have numerous health benefits, due to the bioactive compounds in these food items, including polyphenols. These plants are a rich and promising source of natural products and phytochemicals that can be used to treat and prevent numerous diseases and prevent the progression of cancer. Dietary polyphenols exhibit chemo-preventive and therapeutic effects against various ailments, including several types of cancer. The current study focuses on polyphenol’s traditional and advanced extraction methods, with supercritical extraction as a novel approach. It also deals with their identification, bioavailability, and role in preventing and treating colorectal and prostate cancers. Additionally, the article covers the literature that deals with the anticancer activities of polyphenols, as well as their potential use as anticancer agents.
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Affiliation(s)
- Naveed Ahmad
- Multan College of Food & Nutrition Sciences, Multan Medical and Dental College, Multan 60000, Pakistan
- Correspondence: (N.A.); (P.W.); (M.S.M.); Tel.: +962-791016126 (M.S.M.)
| | - Muhammad Qamar
- Institute of Food Science and Nutrition, Bahauddin Zakariya University, Multan 60800, Pakistan;
| | - Ye Yuan
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia;
| | - Yasir Nazir
- Department of Chemistry, Faculty of Sciences, University of Sialkot, Sialkot 51300, Pakistan;
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
- Correspondence: (N.A.); (P.W.); (M.S.M.); Tel.: +962-791016126 (M.S.M.)
| | - Mohammad S. Mubarak
- Department of Chemistry, The University of Jordan, Amman 11942, Jordan
- Correspondence: (N.A.); (P.W.); (M.S.M.); Tel.: +962-791016126 (M.S.M.)
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26
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Navarro-Orcajada S, Conesa I, Vidal-Sánchez FJ, Matencio A, Albaladejo-Maricó L, García-Carmona F, López-Nicolás JM. Stilbenes: Characterization, bioactivity, encapsulation and structural modifications. A review of their current limitations and promising approaches. Crit Rev Food Sci Nutr 2022; 63:7269-7287. [PMID: 35234546 DOI: 10.1080/10408398.2022.2045558] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Stilbenes are phenolic compounds naturally synthesized as secondary metabolites by the shikimate pathway in plants. Research on them has increased in recent years due to their therapeutic potential as antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective and anti-obesity agents. Amongst them, resveratrol has attracted the most attention, although there are other natural and synthesized stilbenes with enhanced properties. However, stilbenes have some physicochemical and pharmacokinetic problems that need to be overcome before considering their applications. Human clinical evidence of their bioactivity is still controversial due to this fact and hence, exhaustive basis science on stilbenes is needed before applied science. This review gathers the main physicochemical and biological properties of natural stilbenes, establishes structure-activity relationships among them, emphasizing the current problems that limit their applications and presenting some promising approaches to overcome these issues: the encapsulation in different agents and the structural modification to obtain novel stilbenes with better features. The bioactivity of stilbenes should move from promising to evident.
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Affiliation(s)
- Silvia Navarro-Orcajada
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | - Irene Conesa
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | - Francisco José Vidal-Sánchez
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | | | - Lorena Albaladejo-Maricó
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | - Francisco García-Carmona
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
| | - José Manuel López-Nicolás
- Departamento de Bioquímica y Biología Molecular-A, Facultad de Biología, Universidad de Murcia-Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain
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27
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Nabizadeh F, Momtaz S, Ghanbari-Movahed M, Qalekhani F, Mohsenpour H, Aneva IY, Bishayee A, Farzaei MH, Bishayee A. Pediatric acute lymphoblastic leukemia management using multitargeting bioactive natural compounds: A systematic and critical review. Pharmacol Res 2022; 177:106116. [PMID: 35122954 DOI: 10.1016/j.phrs.2022.106116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/19/2022] [Accepted: 02/01/2022] [Indexed: 11/16/2022]
Abstract
Pediatric acute lymphoblastic leukemia (pALL), a malignancy of the lymphoid line of blood cells, accounts for a large percentage of all childhood leukemia cases. Although the 5-year survival rate for children with ALL has greatly improved over years, using chemotherapeutics as its first-line treatment still causes short- and long-term side effects. Furthermore, induction of toxicity and resistance, as well as the high cost, limit their application. Phytochemicals, with remarkable cancer preventive and chemotherapeutic characteristics, may serve as old solutions to new challenges. Bioactive plant secondary metabolites have exhibited promising antileukemic and adjunctive effects by targeting various molecular processes, including autophagy, cell cycle, angiogenesis, and extrinsic/intrinsic apoptotic pathways. Although numerous reports have shown that numerous plant secondary metabolites can interfere with the progression of malignancies, including leukemia, there was no comprehensive review article on the effect of phytochemicals on pALL. This systematic review aims to provide critical and cohesive analysis of the potential of various naturally-occurring metabolites in the management of pALL with the understanding of underlying molecular and cellular mechanisms of action.
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Affiliation(s)
- Fatemeh Nabizadeh
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Saeideh Momtaz
- Medicinal Plants Research Center, Institute of Medicinal Plants, Karaj 141554364, Iran; Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences, and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran
| | - Maryam Ghanbari-Movahed
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran
| | - Farshad Qalekhani
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran; Medical Biology Research Center, Health Technologies Institute, Kermanshah University of Medical Sciences, Kermanshah 6714415185, Iran
| | - Hadi Mohsenpour
- Department of Pediatrics, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah 6742775333, Iran
| | - Ina Yosifova Aneva
- Institute of Biodiversity and Ecosystem Research, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
| | | | - Mohammad Hosein Farzaei
- Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah 6734667149, Iran.
| | - Anupam Bishayee
- College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.
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Kustiati U, Dewi Ratih TS, Dwi Aris Agung N, Kusindarta DL, Wihadmadyatami H. In silico molecular docking and in vitro analysis of ethanolic extract Ocimum sanctum Linn.: Inhibitory and apoptotic effects against non-small cell lung cancer. Vet World 2021; 14:3175-3187. [PMID: 35153410 PMCID: PMC8829409 DOI: 10.14202/vetworld.2021.3175-3187] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 11/01/2021] [Indexed: 01/17/2023] Open
Abstract
Background and Aim: Lung cancer, especially non-small cell lung cancer (NSCLC), has been identified as the leading cause of cancer deaths worldwide. The mortality rate from lung cancer has been estimated to be 18.4%. Until now, conventional treatments have not yielded optimal results, thus necessitating an investigation into the use of traditional herbal plants as potential candidates for its treatment. This study aimed to determine the inhibitory and apoptotic activity of the ethanolic extract from Ocimum sanctum Linn. (EEOS) by in silico molecular docking and through in vitro studies using NSCLC cells (A549 cell line). Materials and Methods: Dried simplicia of Ocimum sanctum was converted into EEOS using the maceration method. Spectrophotometry was then employed to analyze the EEOS compound. The known main active compounds were further analyzed for inhibitory and apoptotic effects on gene signaling using in silico molecular docking involving the downloading of active compounds from PubChem and target proteins from the Protein Data Bank; the active compounds and proteins were then prepared using the Discovery Studio software v. 19.0.0 and the PyRX 0.8 program, interacted with the HEX 8.0.0 program, and visualized with the Discovery Studio Visualizer v. 19.0. Finally, an in vitro analysis was performed using an antiproliferative-cytotoxic test (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay in the NSCLC A549 cell line). Results: The analysis revealed that the active compounds in the ethanolic extract were dominated by quercetin (flavonoids) (47.23% b/b) and eugenol (phenolic) (12.14% b/b). These active compounds interacted with the active sites (residual amino acids) of the αvβ3 integrin, a5b1 integrin, caspase-3, caspase-9, and vascular endothelial growth factor. Hydrogen bonds and Pi-cation and Pi-alkyl interactions were involved in the relationships between the active compounds and the active sites and thus may reveal an antioxidant property of the extract. Furthermore, in vitro analysis showed the inhibitory and antiproliferative effects of the EEOS against non-small cell cancer (A549). Conclusion: Taken together, our data showed the ability of EEOS as an inhibitor and apoptotic agent for lung cancer; however, further research is needed to determine the exact mechanism of EEOS as an herbal medication.
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Affiliation(s)
- Ulayatul Kustiati
- Post Graduate Student of Sain Veteriner, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - T. S. Dewi Ratih
- Department of Biology, Faculty of Mathematics and Natural Sciences, and Research center of Smart Molecule of Natural Genetics Resources, Brawijaya University, Indonesia
| | - N. Dwi Aris Agung
- Department of Pharmacology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - Dwi Liliek Kusindarta
- Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
| | - Hevi Wihadmadyatami
- Department of Anatomy, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
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29
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Hung WL, Hsiao YT, Chiou YS, Nagabhushanam K, Ho CT, Pan MH. Hepatoprotective effect of piceatannol against carbon tetrachloride-induced liver fibrosis in mice. Food Funct 2021; 12:11229-11240. [PMID: 34676843 DOI: 10.1039/d1fo02545g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Piceatannol (3,5,3',4'-trans-tetrahydroxystilbene) is a natural analog and a metabolite of resveratrol present in grapes and red wine. Previous studies have reported that piceatannol exerts a broad spectrum of health benefits including antioxidant, anti-inflammatory, chemopreventive, and neuroprotective effects. However, little is known about the hepatoprotective effect of piceatannol against toxin-induced liver fibrosis. Therefore, the objective of this study is to evaluate the protective effect of piceatannol in a mouse model of CCl4-induced hepatic fibrosis. Oral administration of piceatannol significantly improved the hepatic functions of CCl4-treated mice in both therapeutic and preventive models. Additionally, the immunohistochemical staining results revealed that collagen deposition in CCl4-injected mice was significantly reduced by treatment with piceatannol. Moreover, piceatannol remarkably suppressed the expressions of collagen I, α-smooth muscle protein (α-SMA), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) induced by CCl4. The anti-fibrotic mechanism of piceatannol was associated with the regulation of the transforming growth factor-β (TGF-β)/Smad signaling pathway. Finally, piceatannol also profoundly alleviated CCl4-induced hepatic oxidative damage by elevating the level of glutathione and catalase activity. Altogether, our current findings suggest that piceatannol may serve as a bioactive agent that inhibits or alleviates toxic-induced fibroproliferative diseases, especially in the prevention of liver fibrosis.
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Affiliation(s)
- Wei-Lun Hung
- School of Food Safety, Taipei Medical University, Taipei, 11031, Taiwan
| | - Yi-Ting Hsiao
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
| | - Yi-Shiou Chiou
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
| | | | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, USA
| | - Min-Hsiung Pan
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan. .,Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.,Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan
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Cassini C, Zatti PH, Angeli VW, Branco CS, Salvador M. Mutual effects of free and nanoencapsulated phenolic compounds on human microbiota. Curr Med Chem 2021; 29:3160-3178. [PMID: 34720074 DOI: 10.2174/0929867328666211101095131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 07/08/2021] [Accepted: 08/26/2021] [Indexed: 11/22/2022]
Abstract
Phenolic compounds (PC) have many health benefits such as antioxidant, anticarcinogenic, neuroprotective, and anti-inflammatory activities. All of these activities depend on their chemical structures and their interaction with biological targets in the body. PC occur naturally in polymerized form, linked to glycosides and requires metabolic transformation from their ingestion to their absorption. The gut microbiota can transform PC into more easily absorbed metabolites. The PC, in turn, have prebiotic and antimicrobial actions on the microbiota. Despite this, their low oral bioavailability still compromises biological performance. Therefore, the use of nanocarriers has been demonstrated to be a useful strategy to improve PC absorption and, consequently, their health effects. Nanotechnology is an excellent alternative able to overcome the limits of oral bioavailability of PC, since it offers protection from degradation during their passage through the gastrointestinal tract. Moreover, nanotechnology is also capable of promoting controlled PC release and modulating the interaction between PC and the microbiota. However, little is known about the impact of the nanotechnology on PC effects on the gut microbiota. This review highlights the use of nanotechnology for PC delivery on gut microbiota, focusing on the ability of such formulations to enhance oral bioavailability by applying nanocarriers (polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles). In addition, the effects of free and nanocarried PC or nanocarriers per se on gut microbiota are also described.
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Affiliation(s)
- Carina Cassini
- Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul. Brazil
| | | | | | - Catia Santos Branco
- Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul. Brazil
| | - Mirian Salvador
- Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul. Brazil
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Alessio N, Squillaro T, Lettiero I, Galano G, De Rosa R, Peluso G, Galderisi U, Di Bernardo G. Biomolecular Evaluation of Piceatannol's Effects in Counteracting the Senescence of Mesenchymal Stromal Cells: A New Candidate for Senotherapeutics? Int J Mol Sci 2021; 22:11619. [PMID: 34769049 PMCID: PMC8583715 DOI: 10.3390/ijms222111619] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 10/22/2021] [Accepted: 10/25/2021] [Indexed: 11/16/2022] Open
Abstract
Several investigations on senescence and its causative role in aging have underscored the importance of developing senotherapeutics, a field focused on killing senescent cells and/or preventing their accumulation within tissues. Using polyphenols in counteracting senescence may facilitate the development of senotherapeutics given their presence in the human diet, their confirmed tolerability and absence of severe side effects, and their role in preventing senescence and inducing the death of senescent cells. Against that background, we evaluated the effect of piceatannol, a natural polyphenol, on the senescence of mesenchymal stromal cells (MSCs), which play a key role in the body's homeostasis. Among our results, piceatannol reduced the number of senescent cells both after genotoxic stress that induced acute senescence and in senescent replicative cultures. Such senotherapeutics activity, moreover, promoted the recovery of cell proliferation and the stemness properties of MSCs. Altogether, our findings demonstrate piceatannol's effectiveness in counteracting senescence by targeting its associated pathways and detecting and affecting P53-dependent and P53-independent senescence. Our study thus suggests that, given piceatannol's various mechanisms to accomplish its pleiotropic activities, it may be able to counteract any senescent phenotypes.
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Affiliation(s)
- Nicola Alessio
- Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (N.A.); (T.S.); (I.L.)
| | - Tiziana Squillaro
- Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (N.A.); (T.S.); (I.L.)
| | - Ida Lettiero
- Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (N.A.); (T.S.); (I.L.)
| | - Giovanni Galano
- ASL Napoli 1 Centro P.S.I. Napoli Est-Barra, 80147 Naples, Italy; (G.G.); (R.D.R.)
| | - Roberto De Rosa
- ASL Napoli 1 Centro P.S.I. Napoli Est-Barra, 80147 Naples, Italy; (G.G.); (R.D.R.)
| | - Gianfranco Peluso
- Research Institute on Terrestrial Ecosystems, CNR, 80131 Naples, Italy;
| | - Umberto Galderisi
- Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (N.A.); (T.S.); (I.L.)
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA
| | - Giovanni Di Bernardo
- Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (N.A.); (T.S.); (I.L.)
- Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA
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Singh R, Kumar B, Sahu RK, Kumari S, Jha CB, Singh N, Mathur R, Hedau ST. Development of a pH-sensitive functionalized metal organic framework: in vitro study for simultaneous delivery of doxorubicin and cyclophosphamide in breast cancer. RSC Adv 2021; 11:33723-33733. [PMID: 35497517 PMCID: PMC9042314 DOI: 10.1039/d1ra04591a] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 10/09/2021] [Indexed: 01/10/2023] Open
Abstract
Exploration of an efficient dual-drug based nanocarrier with high drug loading capacity, specific targeting properties, and long-term stability is highly desirable in cancer therapy. Metal-organic frameworks (MOFs) have proven to be a promising class of drug carriers due to their high porosity, crystalline properties with defined structure information, and their potential for further functionalization. To enhance the drug efficacy as well as to overcome the burst effect of drugs, here we synthesized a pH responsive folic acid (FA) and graphene oxide (GO) decorated zeolitical imidazolate frameworks-8 (GO-FA/ZIF-8), for targeted delivery of doxorubicin (DOX) and cyclophosphamide (CP), simultaneously. In this system, DOX molecules were encapsulated in the pores of ZIF-8 during in situ synthesis of ZIF-8 and CP molecules have been captured by the GO surface via hydrogen bonding and π-π interactions as well. Furthermore, the resulting pH-responsive nanocarrier (DOX@ZIF-8/GO-FA/CP) showed in vitro sustained release characteristics (76% of DOX and 80% of CP) by cleavage of chemical bonding and disruption of the MOFs structure under acidic condition (at pH 5.6). Moreover, DOX@ZIF-8/GO-FA/CP has synergistic cytotoxic effects as compared to the combination of both the drugs without ZIF-8/GO-FA when treating MCF-7 and MDA-MB-231 breast cancer cell lines (with a combination index of 0.29 and 0.75 for MCF-7 and MDA-MB-231 cell-lines, respectively). Hence this system can be applied as an effective platform for smart dual drug delivery in breast cancer treatment through its remarkable manageable multidrug release.
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Affiliation(s)
- Ragini Singh
- Division of Molecular Oncology, ICMR-National Institute of Cancer Prevention and Research I-7, Sector 39, Gautam Buddha Nagar Noida-201301 U.P. India +91-0120-2446909
| | - Binayak Kumar
- Division of Molecular Oncology, ICMR-National Institute of Cancer Prevention and Research I-7, Sector 39, Gautam Buddha Nagar Noida-201301 U.P. India +91-0120-2446909
| | - Ram Krishna Sahu
- Division of Molecular Oncology, ICMR-National Institute of Cancer Prevention and Research I-7, Sector 39, Gautam Buddha Nagar Noida-201301 U.P. India +91-0120-2446909
| | - Soni Kumari
- Division of Molecular Oncology, ICMR-National Institute of Cancer Prevention and Research I-7, Sector 39, Gautam Buddha Nagar Noida-201301 U.P. India +91-0120-2446909
| | - Chandan Bhogendra Jha
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defense Research and Development Organization Brig. S.K. Mazumdar Marg Delhi 110054 India
| | - Nahar Singh
- CSIR-National Physical Laboratory New Delhi 110012 India
| | - Rashi Mathur
- Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defense Research and Development Organization Brig. S.K. Mazumdar Marg Delhi 110054 India
| | - Suresh T Hedau
- Division of Molecular Oncology, ICMR-National Institute of Cancer Prevention and Research I-7, Sector 39, Gautam Buddha Nagar Noida-201301 U.P. India +91-0120-2446909
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Jahan S, Mahmud MH, Khan Z, Alam A, Khalil AA, Rauf A, Tareq AM, Nainu F, Tareq SM, Emran TB, Khan M, Khan IN, Wilairatana P, Mubarak MS. Health promoting benefits of pongamol: An overview. Biomed Pharmacother 2021; 142:112109. [PMID: 34470730 DOI: 10.1016/j.biopha.2021.112109] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/22/2021] [Accepted: 08/23/2021] [Indexed: 12/24/2022] Open
Abstract
Plant-derived chemicals are a source of novel chemotherapeutic agents. Throughout the human civilization, these novel chemicals have led to the discovery of new pharmacological active agents. Research on herbal medicine is of great importance, as most of the active agents used for treating numerous diseases are from natural sources, while other agents are either semisynthetic or synthetic. Pongamol, a flavonoid, which is the main constituent of Pongamia pinnata, is one such active agents, which exhibits diverse pharmacological activities. Various in vivo and in vitro studies revealed that pongamol is a potentially active agent, as it exerts anticancer, anti-inflammatory, antioxidant, antimicrobial, and anti-diabetic activities. Accordingly, the aim of the present review was to give an up-to-date overview on the chemistry, isolation, bioavailability, pharmacological activity, and health benefits of pongamol. This review focuses on the medicinal and health promoting activities of pongamol, along with possible mechanisms of action. For this purpose, this review summarizes the most recent literature pertaining to pongamol as a therapeutic agent against several diseases. In addition, the review covers information related to the toxicological assessment and safety of this phytochemical, and highlights the medicinal and folk values of this compound against various diseases and ailments.
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Affiliation(s)
- Shamima Jahan
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh.
| | - Md Hasan Mahmud
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh.
| | - Zidan Khan
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh.
| | - Ashraful Alam
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh.
| | - Anees Ahmed Khalil
- University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Pakistan.
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Anbar 23430, Khyber Pakhtunkhwa, Pakistan.
| | - Abu Montakim Tareq
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh.
| | - Firzan Nainu
- Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia.
| | - Syed Mohammed Tareq
- Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh.
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh.
| | - Muneeb Khan
- Department of Human Nutrition and Dietetics, Riphah College of Rehabilitation and Allied Health Sciences, Riphah International University Lahore, Pakistan.
| | - Ishaq N Khan
- Institute of Basic Medical Sciences, Khyber Medical University, Peshawar 25100, Pakistan.
| | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Yun BD, Son SW, Choi SY, Kuh HJ, Oh TJ, Park JK. Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha. Int J Mol Sci 2021; 22:ijms22189819. [PMID: 34575983 PMCID: PMC8467787 DOI: 10.3390/ijms22189819] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 12/15/2022] Open
Abstract
Hypoxia-inducible factor-1 alpha (HIF-1α) is overexpressed in cancer, leading to a poor prognosis in patients. Diverse cellular factors are able to regulate HIF-1α expression in hypoxia and even in non-hypoxic conditions, affecting its progression and malignant characteristics by regulating the expression of the HIF-1α target genes that are involved in cell survival, angiogenesis, metabolism, therapeutic resistance, et cetera. Numerous studies have exhibited the anti-cancer effect of HIF-1α inhibition itself and the augmentation of anti-cancer treatment efficacy by interfering with HIF-1α-mediated signaling. The anti-cancer effect of plant-derived phytochemicals has been evaluated, and they have been found to possess significant therapeutic potentials against numerous cancer types. A better understanding of phytochemicals is indispensable for establishing advanced strategies for cancer therapy. This article reviews the anti-cancer effect of phytochemicals in connection with HIF-1α regulation.
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Affiliation(s)
- Ba Da Yun
- Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (B.D.Y.); (S.W.S.); (S.Y.C.)
| | - Seung Wan Son
- Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (B.D.Y.); (S.W.S.); (S.Y.C.)
| | - Soo Young Choi
- Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (B.D.Y.); (S.W.S.); (S.Y.C.)
| | - Hyo Jeong Kuh
- Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
| | - Tae-Jin Oh
- Department of Pharmaceutical Engineering and Biotechnology, SunMoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si 31460, Korea;
| | - Jong Kook Park
- Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chunchon 24252, Korea; (B.D.Y.); (S.W.S.); (S.Y.C.)
- Correspondence: ; Tel.: +82-33-248-2114
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Ren B, Kwah MXY, Liu C, Ma Z, Shanmugam MK, Ding L, Xiang X, Ho PCL, Wang L, Ong PS, Goh BC. Resveratrol for cancer therapy: Challenges and future perspectives. Cancer Lett 2021; 515:63-72. [PMID: 34052324 DOI: 10.1016/j.canlet.2021.05.001] [Citation(s) in RCA: 231] [Impact Index Per Article: 57.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 05/05/2021] [Accepted: 05/05/2021] [Indexed: 12/20/2022]
Abstract
Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been expected to ameliorate cancer and foster breakthroughs in cancer therapy. Despite thousands of preclinical studies on the anticancer activity of resveratrol, little progress has been made in translational research and clinical trials. Most studies have focused on its anticancer effects, cellular mechanisms, and signal transduction pathways in vitro and in vivo. In this review, we aimed to discern the causes that prevent resveratrol from being used in cancer treatment. Among the various limitations, poor pharmacokinetics and low potency seem to be the two main bottlenecks of resveratrol. In addition, resveratrol-induced nephrotoxicity in multiple myeloma patients hinders its further development as an anticancer drug. New insights and strategies have been proposed to accelerate the conversion of resveratrol from bench to bedside. In the interim, the most promising approach is to enhance the bioavailability of resveratrol with new formulations. Alternatively, more potent analogues of resveratrol could be developed to augment its anticancer potency. Given all the gaps mentioned, much work remains to be done. However, if remarkable progress can be made, resveratrol may finally be used for cancer therapy.
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Affiliation(s)
- Boxu Ren
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Marabeth Xin-Yi Kwah
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore
| | - Cuiliu Liu
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Zhaowu Ma
- School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, 434023, China
| | - Muthu K Shanmugam
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
| | - Lingwen Ding
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore
| | - Xiaoqiang Xiang
- Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, 201203, China
| | - Paul Chi-Lui Ho
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore
| | - Lingzhi Wang
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.
| | - Pei Shi Ong
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore.
| | - Boon Cher Goh
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117600, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore, 119228, Singapore.
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Ishida A, Furuya T. Diversity and characteristics of culturable endophytic bacteria from Passiflora edulis seeds. Microbiologyopen 2021; 10:e1226. [PMID: 34459555 PMCID: PMC8364935 DOI: 10.1002/mbo3.1226] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/10/2021] [Accepted: 07/16/2021] [Indexed: 01/21/2023] Open
Abstract
Defense compounds generally inhibit microbial colonization of plants. In this study, we examined the presence of endophytes in Passiflora edulis seeds that accumulate resveratrol and piceatannol at extremely high levels as defense compounds. Interestingly, although no microbial colonies appeared on an agar growth medium from the cut or homogenized seeds, colonies were generated from cut seedlings derived from the seeds. A total of 19 bacterial strains were isolated, of which 15 were classified as Gram-positive. As we hypothesized that extremely high levels of piceatannol in the seeds would inhibit the growth of endophytes cultured directly from the seeds, we examined the antimicrobial activity of this compound against the isolated bacteria. Piceatannol exerted bacteriostatic rather than bactericidal effects on most of the bacteria tested. These results suggest that the bacteria remain static in the seeds due to the presence of piceatannol and are transmitted to the seedlings during the germination process, enabling colonies to be established from the seedlings on the agar medium. We also investigated the biocatalytic activity of the isolated bacteria toward resveratrol and piceatannol. One bacterium, Brevibacterium sp. PE28-2, converted resveratrol and piceatannol to their respective derivatives. This strain is the first endophyte shown to exhibit such activity.
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Affiliation(s)
- Aoi Ishida
- Department of Applied Biological ScienceFaculty of Science and TechnologyTokyo University of ScienceNodaChibaJapan
| | - Toshiki Furuya
- Department of Applied Biological ScienceFaculty of Science and TechnologyTokyo University of ScienceNodaChibaJapan
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Yu B, Liu W, Hu MQ, Tang XF, Li CJ, Que L. Effect of piceatannol against malignant melanoma in vivo and in vitro. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2021; 39:413-418. [PMID: 34409796 PMCID: PMC8381120 DOI: 10.7518/hxkq.2021.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 05/07/2021] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To study the antitumor effect of piceatannol (PIC) on malignant melanoma in vitro and in vivo. METHODS B16F10 cells were cultured in vitro and treated with gradient concentrations of PIC. Cell viability was detected with methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), spleen tyrosine kinase (Syk), and p-Syk were detected with Western blot; migration ability was detected with wound healing assay; invasion ability was detected with Transwell assay. Syk expression was suppressed through RNA interference for the detection of the possible mechanism of PIC in melanoma. An in vivo study was established by creating B16F10-bearing mice with intraperitoneal injection of PIC. RESULTS The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. In vivo study revealed that different concentrations of PIC cangreatly inhibit melanoma progression. CONCLUSIONS PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.
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Affiliation(s)
- Bo Yu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Wei Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Min-Qi Hu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Xiu-Fa Tang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Chun-Jie Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Lin Que
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Hossain R, Islam MT, Mubarak MS, Jain D, Khan R, Saikat AS. Natural-Derived Molecules as a Potential Adjuvant in Chemotherapy: Normal Cell Protectors and Cancer Cell Sensitizers. Anticancer Agents Med Chem 2021; 22:836-850. [PMID: 34165416 DOI: 10.2174/1871520621666210623104227] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/18/2021] [Accepted: 04/18/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cancer is a global threat to humans and a leading cause of death worldwide. Cancer treatment includes, among other things, the use of chemotherapeutic agents, compounds that are vital for treating and preventing cancer. However, chemotherapeutic agents produce oxidative stress along with other side effects that would affect the human body. OBJECTIVE To reduce the oxidative stress of chemotherapeutic agents in cancer and normal cells by naturally derived compounds with anti-cancer properties, and protect normal cells from the oxidation process. Therefore, the need to develop more potent chemotherapeutics with fewer side effects has become increasingly important. METHOD Recent literature dealing with the antioxidant and anticancer activities of the naturally naturally-derived compounds: morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin has been surveyed and examined in this review. For this, data were gathered from different search engines, including Google Scholar, ScienceDirect, PubMed, Scopus, Web of Science, Scopus, and Scifinder, among others. Additionally, several patient offices such as WIPO, CIPO, and USPTO were consulted to obtain published articles related to these compounds. RESULT Numerous plants contain flavonoids and polyphenolic compounds such as morin, myricetin, malvidin, naringin, eriodictyol, isovitexin, daidzein, naringenin, chrysin, and fisetin, which exhibit antioxidant, anti-inflammatory, and anti-carcinogenic actions via several mechanisms. These compounds show sensitizers of cancer cells and protectors of healthy cells. Moreover, these compounds can reduce oxidative stress, which is accelerated by chemotherapeutics and exhibit a potent anticancer effect on cancer cells. CONCLUSIONS Based on these findings, more research is recommended to explore and evaluate such flavonoids and polyphenolic compounds.
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Affiliation(s)
- Rajib Hossain
- Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj-8100, Bangladesh
| | - Muhammad Torequl Islam
- Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj-8100, Bangladesh
| | | | - Divya Jain
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Rajasthan-304022, India
| | - Rasel Khan
- Pharmacy Discipline, Life Science School, Khulna University, Khulna-9280, Bangladesh
| | - Abu Saim Saikat
- Department of Biochemistry and Molecular Biology, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
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dos Santos LC, Mendiola JA, Sánchez-Camargo ADP, Álvarez-Rivera G, Viganó J, Cifuentes A, Ibáñez E, Martínez J. Selective Extraction of Piceatannol from Passiflora edulis by-Products: Application of HSPs Strategy and Inhibition of Neurodegenerative Enzymes. Int J Mol Sci 2021; 22:ijms22126248. [PMID: 34200696 PMCID: PMC8230382 DOI: 10.3390/ijms22126248] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/31/2021] [Accepted: 06/03/2021] [Indexed: 12/31/2022] Open
Abstract
Passiflora edulis by-products (PFBP) are a rich source of polyphenols, of which piceatannol has gained special attention recently. However, there are few studies involving environmentally safe methods for obtaining extracts rich in piceatannol. This work aimed to concentrate piceatannol from defatted PFBP (d-PFBP) by means of pressurized liquid extraction (PLE) and conventional extraction, using the bio-based solvents selected with the Hansen solubility parameters approach. The relative energy distance (Ra) between solvent and solute was: Benzyl Alcohol (BnOH) < Ethyl Acetate (EtOAc) < Ethanol (EtOH) < EtOH:H2O. Nonetheless, EtOH presented the best selectivity for piceatannol. Multi-cycle PLE at 110 °C was able to concentrate piceatannol 2.4 times more than conventional extraction. PLE exhibited a dependence on kinetic parameters and temperature, which could be associated with hydrogen bonding forces and the dielectric constant of the solvents. The acetylcholinesterase (AChE) and lipoxygenase (LOX) IC50 were 29.420 μg/mL and 27.682 μg/mL, respectively. The results reinforce the demand for processes to concentrate natural extracts from food by-products.
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Affiliation(s)
- Luana Cristina dos Santos
- Laboratory of High Pressure in Food Engineering (LAPEA), Department of Food Engineering and Technology, School of Food Engineering, University of Campinas, R. Monteiro Lobato 80, Campinas 13083-862, Brazil; (L.C.d.S.); (J.M.)
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain; (J.A.M.); (G.Á.-R.); (A.C.)
| | - Jose Antonio Mendiola
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain; (J.A.M.); (G.Á.-R.); (A.C.)
| | - Andrea del Pilar Sánchez-Camargo
- Department of Chemistry and Food Engineering, Faculty of Engineering, University of Los Andes, Carrera 1 No. 18A-12, Bogotá 111711, Colombia;
| | - Gerardo Álvarez-Rivera
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain; (J.A.M.); (G.Á.-R.); (A.C.)
| | - Juliane Viganó
- Department of Chemical Engineering, Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, R. São Nicolau 210, Diadema 09913-030, Brazil;
| | - Alejandro Cifuentes
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain; (J.A.M.); (G.Á.-R.); (A.C.)
| | - Elena Ibáñez
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, 28049 Madrid, Spain; (J.A.M.); (G.Á.-R.); (A.C.)
- Correspondence: ; Tel.: +34-(91)-0017956
| | - Julian Martínez
- Laboratory of High Pressure in Food Engineering (LAPEA), Department of Food Engineering and Technology, School of Food Engineering, University of Campinas, R. Monteiro Lobato 80, Campinas 13083-862, Brazil; (L.C.d.S.); (J.M.)
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Wahedi HM, Ahmad S, Abbasi SW. Stilbene-based natural compounds as promising drug candidates against COVID-19. J Biomol Struct Dyn 2021; 39:3225-3234. [PMID: 32345140 DOI: 10.1080/07391102.2020.1762743] [Citation(s) in RCA: 151] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 04/23/2020] [Indexed: 12/23/2022]
Abstract
The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a great threat to public health. Currently, no potent medicine is available to treat COVID-19. Quest for new drugs especially from natural plant sources is an area of immense potential. The current study aimed to repurpose stilbenoid analogs, reported for some other biological activities, against SARS-CoV-2 spike protein and human ACE2 receptor complex for their affinity and stability using molecular dynamics simulation and binding free energy analysis based on molecular docking. Four compounds in total were probed for their binding affinity using molecular docking. All of the compounds showed good affinity (> -7 kcal/mol). However, fifty nanoseconds molecular dynamic simulation in aqueous solution revealed highly stable bound conformation of resveratrol to the viral protein: ACE2 receptor complex. Net free energy of binding using MM-PBSA also affirmed the stability of the resveratrol-protein complex. Based on the results, we report that stilbene based compounds in general and resveratrol, in particular, can be promising anti-COVID-19 drug candidates acting through disruption of the spike protein. Our findings in this study are promising and call for further in vitro and in vivo testing of stiblenoids, especially resveratrol against the COVID-19. [Formula: see text] Communicated by Ramaswamy H. SarmaHighlightsStilbenoid analogs could be potential disruptors of SARS-CoV-2 spike protein and human ACE2 receptor complex.In particular, resveratrol revealed highly stable conformation to the viral protein: ACE2 receptor complex.The strong interaction of resveratrol is affirmed by molecular dynamic simulation studies and better net free energies.
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Affiliation(s)
- Hussain Mustatab Wahedi
- NUMS Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan
| | - Sajjad Ahmad
- National Center of Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan
| | - Sumra Wajid Abbasi
- NUMS Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan
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Molaei E, Molaei A, Abedi F, Hayes AW, Karimi G. Nephroprotective activity of natural products against chemical toxicants: The role of Nrf2/ARE signaling pathway. Food Sci Nutr 2021; 9:3362-3384. [PMID: 34136201 PMCID: PMC8194945 DOI: 10.1002/fsn3.2320] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/15/2021] [Accepted: 04/19/2021] [Indexed: 12/18/2022] Open
Abstract
Nephropathy can occur following exposure of the kidneys to oxidative stress. Oxidative stress is the result of reactive oxygen species (ROS) formation due to intracellular catabolism or exogenous toxicant exposure. Many natural products (NPs) with antioxidant properties have been used to demonstrate that oxidative damage-induced nephrotoxicity can be ameliorated or at least reduced through stimulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Nrf2 is a basic leucine zipper (bZip) transcription factor that regulates gene expression of the antioxidant response elements (ARE). Nrf2 is involved in the cellular antioxidant-detoxification machinery. Nrf2 activation is a major mechanism of nephroprotective activity for these NPs, which facilitates its entry into the nucleus, primarily by inhibiting Kelch like-ECH-associated protein 1 (Keap1). The purpose of this article was to review the peer-reviewed literature of NPs that have shown mitigating effects on renal disorder by stimulating Nrf2 and thereby suggesting potential new therapeutic or prophylactic strategies against kidney-damaging xenobiotics.
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Affiliation(s)
- Emad Molaei
- Faculty of PharmacyMashhad University of Medical SciencesMashhadIran
| | - Ali Molaei
- Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | - Farshad Abedi
- Faculty of PharmacyMashhad University of Medical SciencesMashhadIran
| | | | - Gholamreza Karimi
- Pharmaceutical Research CenterInstitute of Pharmaceutical TechnologyMashhad University of Medical SciencesMashhadIran
- Department of Pharmacodynamics and ToxicologyFaculty of PharmacyMashhad University of Medical SciencesMashhadIran
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Affiliation(s)
- Wen‐Sen He
- School of Food and Biological Engineering Jiangsu University 301 Xuefu Road Zhenjiang Jiangsu 212013 China
- School of Life Sciences The Chinese University of Hong Kong Shatin, New Territories Hong Kong China
| | - Jiaxin Rui
- School of Food and Biological Engineering Jiangsu University 301 Xuefu Road Zhenjiang Jiangsu 212013 China
| | - Qingzhi Wang
- School of Food and Biological Engineering Jiangsu University 301 Xuefu Road Zhenjiang Jiangsu 212013 China
| | - Zhen‐Yu Chen
- School of Life Sciences The Chinese University of Hong Kong Shatin, New Territories Hong Kong China
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Association of Mean Daily Polyphenols Intake with Mediterranean Diet Adherence and Anthropometric Indices in Healthy Greek Adults: A Retrospective Study. APPLIED SCIENCES-BASEL 2021. [DOI: 10.3390/app11104664] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Research data indicate the possible effect of both polyphenols consumption and Mediterranean diet adherence on metabolic diseases’ prevalence. The present retrospective study investigated the possible association of polyphenols mean daily intake with Mediterranean diet adherence and anthropometric indices in a sample of the Greek population. A total of 250 healthy volunteers, aged between 18 and 65 years, were randomly recruited from central and northern Greece. Total daily polyphenols intake was estimated using a semi-quantitative food frequency questionnaire (FFQ) based on the NHANES study, while Med Diet Score was used for the degree of Mediterranean diet adoption. Daily polyphenols intake was identified by the Phenol Explorer database, and anthropometric measurements (BMI, waist-to-hip circumference, and body composition) were performed. The mean daily polyphenols intake was determined to be 1905 mg, while most of the participants had moderate or high mean consumption last year (67.5% of the sample were consuming more than 1000 mg/d). Moderate adherence to the Mediterranean diet (higher Med Diet Score) was associated with increased mean daily polyphenols intake (p = 0.016). Increased polyphenols intake and higher Med Diet Score were associated with decreased waist-to-hip circumference (p = 0.027, 0.004, respectively). Specific functional foods rich in polyphenols, such as sour cherry, tomatoes, black tea, and cocoa were associated with improved body composition indices. Larger epidemiological studies need to be performed for safer conclusions about whole population polyphenols intake and its association with metabolic disease biomarkers.
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Alhakamy NA, Caruso G, Al-Rabia MW, Badr-Eldin SM, Aldawsari HM, Asfour HZ, Alshehri S, Alzaharani SH, Alhamdan MM, Rizg WY, Allam AN. Piceatannol-Loaded Bilosome-Stabilized Zein Protein Exhibits Enhanced Cytostatic and Apoptotic Activities in Lung Cancer Cells. Pharmaceutics 2021; 13:638. [PMID: 33947103 PMCID: PMC8146359 DOI: 10.3390/pharmaceutics13050638] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/21/2021] [Accepted: 04/23/2021] [Indexed: 12/12/2022] Open
Abstract
Piceatannol (PIC) is a naturally occurring polyphenolic stilbene, and it has pleiotropic pharmacological properties. Moreover, PIC has cytotoxic actions among various cancer cells. In this work, preparations of PIC-loaded bilosome-zein (PIC-BZ) were designed, formulated, and characterized, and the optimized PIC-BZ cytotoxic activities, measured as half maximal inhibitory concentration (IC50), against lung cancer cell line was investigated. Box-Behnken design was utilized in order to examine the effect of preparation factors on drug entrapment and particle size. PIC-BZ showed a spherical shape after optimization, and its particle size was determined as 157.45 ± 1.62 nm. Moreover, the efficiency of drug entrapment was found as 93.14 ± 2.15%. The cytotoxic activity evaluation revealed that the adjusted formulation, which is PIC-BZ formula, showed a substantially smaller IC50 versus A549 cells. Cell cycle analysis showed accumulation of cells in the G2-M phase. Moreover, it showed in the sub-G1 phase, a rise of cell fraction suggestion apoptotic improving activity. Increased early and late phases of apoptosis were demonstrated by staining of cells with annexin V. Furthermore, the cellular caspase-3 protein expression was significantly raised by PIC-BZ. In addition, the wound healing experiment confirmed the results. To conclude, compared to pure PIC, PIC-BZ demonstrated a higher cell death-inducing activity against A549 cells.
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Affiliation(s)
- Nabil A. Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (N.A.A.); (H.M.A.); (W.Y.R.)
- Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Giuseppe Caruso
- Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy;
| | - Mohammed W. Al-Rabia
- Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.W.A.-R.); (H.Z.A.)
| | - Shaimaa M. Badr-Eldin
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (N.A.A.); (H.M.A.); (W.Y.R.)
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Hibah M. Aldawsari
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (N.A.A.); (H.M.A.); (W.Y.R.)
- Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Hani Z. Asfour
- Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (M.W.A.-R.); (H.Z.A.)
| | - Samah Alshehri
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Sami H. Alzaharani
- Family Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.H.A.); (M.M.A.)
| | - Meshari M. Alhamdan
- Family Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.H.A.); (M.M.A.)
| | - Waleed Y. Rizg
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (N.A.A.); (H.M.A.); (W.Y.R.)
- Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Ahmed N. Allam
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
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Kutbi HI, Kammoun AK, Farag El-Telbany D. Amelioration of Pterostilbene Antiproliferative, Proapoptotic, and Oxidant Potentials in Human Breast Cancer MCF7 Cells Using Zein Nanocomposites. Int J Nanomedicine 2021; 16:3059-3071. [PMID: 33953555 PMCID: PMC8090986 DOI: 10.2147/ijn.s303975] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 03/18/2021] [Indexed: 01/26/2023] Open
Abstract
Purpose This study aimed to explain the influence of zein nanosphere (ZN NS) formulation on the pharmacotherapeutic profile of PTS in MCF7 cells. Methods Liquid–liquid phase separation was used to formulate PTS-ZN NSs. The formulations developed were evaluated for particle-size analysis, encapsulation efficiency, and in vitro diffusion. Also, assays of cytotoxicity, uptake, cell-cycle progression, annexin V, apoptotic gene mRNA expression and biochemical assays were carried out. Results The PTS-ZN NS formulation selected showed 104.5±6.2 nm, 33.4±1.8 mV, 95.1%±3.6%, and 89.1%±2.65% average particle size, zeta-potential, encapsulation efficiency and in vitro diffusion, respectively. With MCF7 cells, IC50 was reduced approximately 15-fold, with increased cellular uptake, accumulation in the G2/M phase, increased percentage of cells in the pre-G1 phase, amelioration of early and late apoptosis, raised mRNA expression of CASP3 and CASP7, lower expression of cyclin-CDK1, and enhanced oxidant potential through decreased glutathione reductase (GR) activity, and enhanced reactive oxygen–species generation and lipid-peroxidation products. Conclusion PTS-ZN NSs indicated enhanced antiproliferative, proapoptotic, and oxidant potential toward MCF7 cells compared to free PTS. Ameliorated results of nanosized carriers, cellular uptake, and sustained diffusion may contribute to these outcomes.
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Affiliation(s)
- Hussam I Kutbi
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Ahmed K Kammoun
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Dalia Farag El-Telbany
- Department of Pharmaceutics, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo, 11571, Egypt
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Xiang Y, Kuai L, Ru Y, Jiang J, Li X, Li F, Chen Q, Li B. Transcriptional profiling and circRNA-miRNA-mRNA network analysis identify the biomarkers in Sheng-ji Hua-yu formula treated diabetic wound healing. JOURNAL OF ETHNOPHARMACOLOGY 2021; 268:113643. [PMID: 33271241 DOI: 10.1016/j.jep.2020.113643] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/14/2020] [Accepted: 11/23/2020] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Sheng-ji Hua-yu (SJHY) formula is a traditional Chinese herbal which is effective in treating diabetic ulcers. It has been indicated to accelerate re-epithelialization and healing time of cutaneous wounds in a Streptozotocin (STZ)-induced diabetic mouse model. However, its mechanisms remain undetermined. AIM OF THE STUDY To reveal the molecular mechanisms of SJHY formula in treating diabetic wounds through transcriptional profiling and circRNA-miRNA-mRNA network analysis clues. MATERIALS AND METHODS Protein expressions of tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-1β in skin tissues of wounds from SJHY formula-treated and untreated mice were analyzed by Bio-Plex assay. Differentially expressed (DE) genes were detected by whole transcriptome sequencing (RNA-seq). Using predicted miRNA targets, circRNA-miRNA-mRNA networks were constructed. Furthermore, quantitative real-time PCR (qRT-PCR) was utilized to validate the circRNA-miRNA-mRNA networks. RESULTS Bio-Plex assay illustrated that the protein expressions of TNF-α, IL-1β, IL-6 were downregulated in SJHY formula-treated diabetic wounds compared with untreated wounds. RNA-seq identified 11 DE circRNAs and 476 DE mRNAs between SJHY formula-treated and diabetic mice, including 4 upregulated and 7 downregulated circRNAs, 311 upregulated and 165 downregulated mRNAs. CircRNA-Krt13/miR-665-3p/Itga3 and circRNA-Krt14/miR-706/Mylk4 pathways were built, which may contribute to the healing of SJHY formula-treated diabetic wounds. CONCLUSIONS Overall, this study suggests that these 2 circRNA-miRNA-mRNA networks are potential biomarkers for evaluation of SJHY formula efficacy in diabetic wound healing, which provides evidence to support its clinical applications.
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Affiliation(s)
- Yanwei Xiang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Le Kuai
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Yi Ru
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jingsi Jiang
- Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Xin Li
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Fulun Li
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Qilong Chen
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Bin Li
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
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Mirzaei S, Mohammadi AT, Gholami MH, Hashemi F, Zarrabi A, Zabolian A, Hushmandi K, Makvandi P, Samec M, Liskova A, Kubatka P, Nabavi N, Aref AR, Ashrafizadeh M, Khan H, Najafi M. Nrf2 signaling pathway in cisplatin chemotherapy: Potential involvement in organ protection and chemoresistance. Pharmacol Res 2021; 167:105575. [PMID: 33771701 DOI: 10.1016/j.phrs.2021.105575] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/20/2021] [Accepted: 03/21/2021] [Indexed: 12/14/2022]
Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a vital transcription factor and its induction is of significant importance for protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) stimulate Nrf2 signaling, enhancing the activity of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. These enzymes are associated with retarding oxidative stress. On the other hand, Nrf2 activation in cancer cells is responsible for the development of chemoresistance due to disrupting oxidative mediated-cell death by reducing ROS levels. Cisplatin (CP), cis-diamminedichloroplatinum(II), is a potent anti-tumor agent extensively used in cancer therapy, but its frequent application leads to the development of chemoresistance as well. In the present study, association of Nrf2 signaling with chemoresistance to CP and protection against its deleterious effects is discussed. Anti-tumor compounds, mainly phytochemicals, retard chemoresistance by suppressing Nrf2 signaling. Upstream mediators such as microRNAs can regulate Nrf2 expression during CP chemotherapy regimens. Protection against side effects of CP is mediated via activating Nrf2 signaling and its downstream targets activating antioxidant defense system. Protective agents that activate Nrf2 signaling, can ameliorate CP-mediated ototoxicity, nephrotoxicity and neurotoxicity. Reducing ROS levels and preventing cell death are the most important factors involved in alleviating CP toxicity upon Nrf2 activation. As pre-clinical experiments advocate the role of Nrf2 in chemoprotection and CP resistance, translating these findings to the clinic can provide a significant progress in treatment of cancer patients.
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Affiliation(s)
- Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Aliasghar Tabatabaei Mohammadi
- Asu Vanda Gene Research Company, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Science Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | | | - Farid Hashemi
- Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956 Istanbul, Turkey
| | - Amirhossein Zabolian
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Pooyan Makvandi
- Centre for Materials Interface, Istituto Italiano di Tecnologia, viale Rinaldo Piaggio 34, 56025 Pisa, Pontedera, Italy
| | - Marek Samec
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Alena Liskova
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Noushin Nabavi
- Department of Urological Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, V6H3Z6 Canada
| | - Amir Reza Aref
- Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Department of Translational Sciences, Xsphera Biosciences Inc., Boston, MA, USA
| | - Milad Ashrafizadeh
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956 Istanbul, Turkey; Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956 Istanbul, Turkey.
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan.
| | - Masoud Najafi
- Medical Technology Research Center, Institute of Health Technology, Kermanashah University of Medical Sciences, Kermanshah 6715847141, Iran; Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Algandaby MM, Al-Sawahli MM. Augmentation of anti-proliferative, pro-apoptotic and oxidant profiles induced by piceatannol in human breast carcinoma MCF-7 cells using zein nanostructures. Biomed Pharmacother 2021; 138:111409. [PMID: 33684694 DOI: 10.1016/j.biopha.2021.111409] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 02/06/2021] [Accepted: 02/16/2021] [Indexed: 12/17/2022] Open
Abstract
Piceatannol (PCT), a natural polyphenolic stilbene, has pleiotropic pharmacological potentials. It possesses cytotoxic activities toward variant cancerous cells. Zein nanospheres (ZN NSs) have been introduced as ideal nanostructures due to their natural origin, safety, histocompatibility. and convenient method of formulation. The purpose of this study was to explore the impact of PCT-ZN NSs formula on pharmacotherapy potential of PCT against human breast cancer MCF-7 cells. PCT-ZN NSs were formulated and characterized selectively to particle size, zeta potential, encapsulation efficiency and diffusion of PCT. The selected formula has a particle size of 84.4 ± 2.3 nm, zeta potential value of 33.8 ± 1.2 mV and encapsulation efficiency of 89.5 ± 4.1%. PCT-ZN NSs displayed significantly lower IC50 against MCF-7 cells by about 24 folds. Further, PCT-ZN NSs formula showed higher cellular uptake as compared to free PCT. Examination of cell cycle phases displayed cells accumulation in G2-M phase and increased percentage cells in pre-G1 phase indicating an apoptosis-enhancing activity. Annexin V staining indicated augmented early and late apoptosis. PCT-ZN NSs pro-apoptotic activity was confirmed by the observed significant increased mRNA expression of CASP3, p53, and Bax as well as decreased expression of Bcl2. In addition, PCT-ZN NSs induced oxidative stress as evidenced by depletion of glutathione reductase (GR) activity, increased generation of reactive oxygen species (ROS) and accumulation of lipid peroxidation products. Conclusively, ZN nanostructures of PCT revealed superior cell death-inducing activities against MCF-7 cells in comparison with free PCT. This is mediated, at least partly, by enhanced cellular uptake, pro-apoptotic activity, and oxidative stress potential.
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Affiliation(s)
- Mardi M Algandaby
- Faculty of Science, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; Medicinal Plants Research Group, Deanship of Scientific Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Majid M Al-Sawahli
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafr Elsheikh University, Kafr Elsheikh 33516, Egypt.
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Hosoda R, Hamada H, Uesugi D, Iwahara N, Nojima I, Horio Y, Kuno A. Different Antioxidative and Antiapoptotic Effects of Piceatannol and Resveratrol. J Pharmacol Exp Ther 2021; 376:385-396. [PMID: 33335015 DOI: 10.1124/jpet.120.000096] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 12/10/2020] [Indexed: 12/31/2022] Open
Abstract
Resveratrol affords protection against reactive oxygen species (ROS)-related diseases via activation of SIRT1, an NAD+-dependent deacetylase. However, the low bioavailability of resveratrol limits its therapeutic applications. Since piceatannol is a hydroxyl analog of resveratrol with higher bioavailability, it could be an alternative to resveratrol. In this study, we compared the cytotoxicity, antioxidative activity, and mechanisms of cytoprotection of piceatannol with those of resveratrol. In C2C12 cells incubated with piceatannol, electrospray ionization mass spectrometry analysis showed that piceatannol was present in the intracellular fraction. A high concentration (50 μM) of piceatannol, but not resveratrol, induced mitochondrial depolarization and apoptosis. However, piceatannol at 10 μM inhibited the increase in mitochondrial ROS level induced by antimycin A, and this ROS reduction was greater than that by resveratrol. The reduction in hydrogen peroxide-induced ROS by piceatannol was also greater than that by resveratrol or vitamin C. Piceatannol reduced antimycin A-induced apoptosis more than did resveratrol. SIRT1 knockdown abolished the antiapoptotic activity of resveratrol, whereas it blocked only half of the antiapoptotic activity of piceatannol. Piceatannol, but not resveratrol, induced heme oxygenase-1 (HO1) expression, which was blocked by knockdown of the transcription factor NRF2, but not by SIRT1 knockdown. HO1 knockdown partially blocked the reduction of ROS by piceatannol. Furthermore, the antiapoptotic action of piceatannol was abolished by HO1 knockdown. Our results suggest that the therapeutic dose of piceatannol protects cells against mitochondrial ROS more than does resveratrol via SIRT1- and NRF2/HO1-dependent mechanisms. The activation of NRF2/HO1 could be an advantage of piceatannol compared with resveratrol for cytoprotection. SIGNIFICANCE STATEMENT: This study showed that piceatannol and resveratrol were different in cytotoxicity, oxidant-scavenging activities, and mechanisms of cytoprotection. Protection by piceatannol against apoptosis induced by reactive oxygen species was superior to that by resveratrol. In addition to the sirtuin 1-dependent pathway, piceatannol exerted nuclear factor erythroid 2-related factor 2/heme oxygenase-1-mediated antioxidative and antiapoptotic effects, which could be an advantage of piceatannol compared with resveratrol.
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Affiliation(s)
- Ryusuke Hosoda
- Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo, Japan (R.H., N.I., I.N., Y.H., A.K.) and Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan (H.H., D.U.)
| | - Hiroki Hamada
- Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo, Japan (R.H., N.I., I.N., Y.H., A.K.) and Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan (H.H., D.U.)
| | - Daisuke Uesugi
- Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo, Japan (R.H., N.I., I.N., Y.H., A.K.) and Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan (H.H., D.U.)
| | - Naotoshi Iwahara
- Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo, Japan (R.H., N.I., I.N., Y.H., A.K.) and Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan (H.H., D.U.)
| | - Iyori Nojima
- Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo, Japan (R.H., N.I., I.N., Y.H., A.K.) and Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan (H.H., D.U.)
| | - Yoshiyuki Horio
- Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo, Japan (R.H., N.I., I.N., Y.H., A.K.) and Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan (H.H., D.U.)
| | - Atsushi Kuno
- Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo, Japan (R.H., N.I., I.N., Y.H., A.K.) and Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan (H.H., D.U.)
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El-Akad RH, Abou Zeid AH, El-Rafie HM, Kandil ZAA, Farag MA. Comparative metabolites profiling of Caryota mitis & Caryota urens via UPLC/MS and isolation of two novel in silico chemopreventive flavonoids. J Food Biochem 2021; 45:e13648. [PMID: 33559930 DOI: 10.1111/jfbc.13648] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 01/16/2021] [Accepted: 01/25/2021] [Indexed: 01/12/2023]
Abstract
Caryota mitis and Caryota urens (F. Arecaceae) are well reported in Ayurvedic medicine and involved in several edible food products. Herein, the first comparative profiling of their leaf and fruit metabolites of both species via HR-UPLC/PDA/ESI-MS and multivariate data analyses is presented. A total of 142 metabolites were detected with seven reported for the first time in F. Arecaceae and a novel O-caffeoylshikimic acid conjugate. Screening of plants' leaf crude extracts via in vitro DCPIP kinetic assay revealed the induction of phase II cytoprotective enzyme NQO1 by 4.5- to 5-fold versus control, suggestive of potential chemopreventive activity. Two novel sulfated flavonols that is quercetin-3-O-sulfate-4'-O-rhamnosyl (1→6)-β-d-glucoside (F1) and kaempferol-3-O-sulfate-4'-O-rhamnosyl(1→6)-β-d-glucoside (F3) in addition to another five known flavonoids were isolated from C. mitis ethanol extract and identified via MS and NMR spectroscopic techniques. Among isolated compounds, F1 and F3 exhibited the highest docking score as KEAP-1 inhibitors and Nrf2 activators posing them as potential chemopreventive drug leads. PRACTICAL APPLICATIONS: The study extends the usages of this edible less explored Caryota species to a potential cancer chemopreventive action. Guided by the extensive chemical information presented herein, additional uses could be suggested for these plants with 142 identified metabolites including androst-en-diol that has aphrodisiac and muscle building effects. The presented multivariate data analyses could aid phytochemists in plants classification and mapping (chemotaxonomy) since several metabolites are reported herein for the first time either in family or genus.
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Affiliation(s)
| | | | | | | | - Mohamed Ali Farag
- Pharmacognosy Department, College of Pharmacy, Cairo University, Cairo, Egypt.,Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, New Cairo, Egypt
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