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Eanes LA, Eldeeb M, Storholt D, Patel YM. Naringenin impairs mitochondrial function via ROS to induce apoptosis in tamoxifen resistant MCF-7 breast cancer cells. PLoS One 2025; 20:e0320020. [PMID: 40179084 PMCID: PMC11967926 DOI: 10.1371/journal.pone.0320020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 02/11/2025] [Indexed: 04/05/2025] Open
Abstract
Breast cancer is the second leading cause of cancer deaths among women. While tamoxifen, a commonly used drug therapy in breast cancer patients, is effective, many patients acquire tamoxifen resistance. Therefore, it is essential to identify alternative or combination therapeutics for the treatment of breast cancer. Naringenin, a naturally occurring flavonoid, has been reported to elicit antioxidant, anti-proliferative, and pro-apoptotic effects in cancer cells. The current study aimed to identify the mechanism by which naringenin induces apoptosis in tamoxifen-resistant breast cancer cells. The present study demonstrated that naringenin induced an increase in ROS, resulting in oxidative stress, impaired mitochondrial function, and apoptosis in tamoxifen-resistant breast cancer cells. Our study reports that naringenin specifically increases mitochondrial superoxide anions and hydrogen peroxide production while also causing mitochondrial dysfunction. These studies provide novel evidence for the mechanism by which naringenin induces apoptosis in tamoxifen-resistant breast cancer cells and supports the use of naringenin as a therapeutic on breast cancer cells and drug-resistant cancer cells.
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Affiliation(s)
- Lauren A. Eanes
- Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
| | - Mayar Eldeeb
- Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
| | - Darrell Storholt
- Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
| | - Yashomati M. Patel
- Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
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Zaheer Y, Ali MA, Rehman M, Iftikhar M, Anwar S, Ali A, Mobeen A, Iqbal M, Iqbal S, Younis MR, An R, Dong J, Ihsan A. Naringenin loaded solid lipid nanoparticles alleviate oxidative stress and enhance oral bioavailability of naringenin. Colloids Surf B Biointerfaces 2025; 247:114423. [PMID: 39662145 DOI: 10.1016/j.colsurfb.2024.114423] [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: 09/13/2024] [Revised: 11/28/2024] [Accepted: 12/03/2024] [Indexed: 12/13/2024]
Abstract
Naringenin (Nrg) is the most abundant natural dietary flavonoid with promising anti-inflammatory potential. However, its therapeutic application is limited due to poor absorption, low bioavailability, and inability to cross physiological barriers. Herein, we designed biocompatible solid lipid nanoparticles (SLNs) to overcome these challenges and to enhance the oral bioavailability and therapeutic potential of Nrg. Nrg-loaded solid lipid nanoparticles (Nrg-SLNs) were fabricated from natural fatty acids, stearic (Nrg-SANPs), or a combination of stearic and lauric acid as binary nanoparticles (Nrg-SLNPs) by the hot melt encapsulation technique. The optimized Nrg-loaded nanoparticles exhibited a hydrodynamic diameter of 74 nm for SANPs and 91 nm for SLNPs, a zeta potential of -25 mV to -37 mV, and entrapment efficiency ranging from 79 % to 85 %. Electron paramagnetic resonance (EPR) spectroscopy indicated an in vitro radical protection factor (RPF) of 215 ± 2 × 1014 radicals/mg for Nrg-SLNPs, which was significantly higher than free Nrg and Nrg-SANPs. Almost 87 % reduction in oxidative stress was recorded with Nrg-SLNPs in a stress-induced lymphocyte model. In vivo studies using the Wistar rat model exhibited around 9-12-fold higher oral bioavailability of Nrg after nanoencapsulation in SLNs, as determined by high-performance liquid chromatography (HPLC). Whereas, hematological and histopathological analysis did not show any damage to the vital organs in vivo. This study presents Nrg-SLNPs as an efficient and biocompatible carrier to enhance the oral bioavailability and therapeutic activity of the natural flavonoids and warrants their further exploration in humans.
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Affiliation(s)
- Yumna Zaheer
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Muhammad Asim Ali
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Mubashar Rehman
- Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Maryam Iftikhar
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Samina Anwar
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Asad Ali
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Ameena Mobeen
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Mazhar Iqbal
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Samina Iqbal
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan
| | - Muhammad Rizwan Younis
- Department of Chemical and Biomolecular Engineering, University of California - Los Angeles, Los Angeles, CA 90095, USA; Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Science, Taian, Shandong 271016, PR China.
| | - Ruibing An
- Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Science, Taian, Shandong 271016, PR China.
| | - Jian Dong
- Institute of Optical Functional Materials for Biomedical Imaging, School of Chemistry and Pharmaceutical Engineering, Shandong First Medical University & Shandong Academy of Medical Science, Taian, Shandong 271016, PR China.
| | - Ayesha Ihsan
- National Institute for Biotechnology and Genetic Engineering College, Pakistan Institute of Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad, Pakistan.
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Alfei S, Zuccari G. Last Fifteen Years of Nanotechnology Application with Our Contribute. NANOMATERIALS (BASEL, SWITZERLAND) 2025; 15:265. [PMID: 39997828 PMCID: PMC11858446 DOI: 10.3390/nano15040265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 01/25/2025] [Accepted: 02/04/2025] [Indexed: 02/26/2025]
Abstract
Currently, nanotechnology is the most promising science, engineering, and technology conducted at the nanoscale (nm), which is used in several sectors. Collectively, nanotechnology is causing a new industrial revolution, and nano-based products are becoming increasingly important for the global market and economy. The interest in nanomaterials has been strongly augmented during the last two decades, and this fact can be easily evaluated by considering the number of studies present in the literature. In November 2024, they accounted for 764,279 experimental studies developed in the years 2009-2024. During such a period, our group contributed to the field of applicative nanotechnology with several experimental and review articles, which we hope could have relevantly enhanced the knowledge of the scientific community. In this new publication, an exhaustive overview regarding the main types of developed nanomaterials, the characterization techniques, and their applications has been discussed. Particular attention has been paid to nanomaterials employed for the enhancement of bioavailability and delivery of bioactive molecules and to those used for ameliorating traditional food packaging. Then, we briefly reviewed our experimental studies on the development of nanoparticles (NPs), dendrimers, micelles, and liposomes for biomedical applications by collecting inherent details in a reader-friendly table. A brief excursus about our reviews on the topic has also been provided, followed by the stinging question of nanotoxicology. Indeed, although the application of nanotechnology translates into a great improvement in the properties of non-nanosized pristine materials, there may still be a not totally predictable risk for humans, animals, and the environment associated with an extensive application of NPs. Nanotoxicology is a science in rapid expansion, but several sneaky risks are not yet fully disclosed. So, the final part of this study discusses the pending issue related to the possible toxic effects of NPs and their impact on customers' acceptance in a scenario of limited knowledge.
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Affiliation(s)
- Silvana Alfei
- Department of Pharmacy (DIFAR), University of Genoa, Via Cembrano 4, 16148 Genoa, Italy;
| | - Guendalina Zuccari
- Department of Pharmacy (DIFAR), University of Genoa, Via Cembrano 4, 16148 Genoa, Italy;
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genoa, Italy
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Elwan AG, Mohamed TM, Beltagy DM, El Gamal DM. The therapeutic role of naringenin nanoparticles on hepatocellular carcinoma. BMC Pharmacol Toxicol 2025; 26:3. [PMID: 39754228 PMCID: PMC11697747 DOI: 10.1186/s40360-024-00823-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 12/10/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Naringenin, a flavonoid compound found in citrus fruits, possesses valuable anticancer properties. However, its potential application in cancer treatment is limited by poor bioavailability and pharmacokinetics at tumor sites. To address this, Naringenin nanoparticles (NARNPs) were prepared using the emulsion diffusion technique and their anticancer effects were investigated in HepG2 cells. METHODS The particle size of NARNPs was determined by transmission electron microscopy and scanning electron microscopy analysis. NARNP is characterized by Fourier transform infrared spectroscopy and X-ray diffraction. Study the cytotoxic effects of various doses of naringenin, NARNPs and DOX on HepG2 and WI38 cell lines after 24 h and 48 h using the MTT assay. Flow cytometric analysis was used to study the apoptotic cells. The study also examined the expression of apoptotic proteins (p53) and autophagy-related genes ATG5, LC3 after treatment with naringenin, NARNPs, doxorubicin, and their combinations in HepG2 cells. RESULTS The particle size of NARNPs was determined by transmission electron microscopy and scanning electron microscopy analysis, showing mean diameters of 54.96 ± 18.6 nm and 31.79 ± 6.8 nm, respectively. Fourier transform infrared spectroscopy confirmed successful conjugation between naringenin and NARNPs. NARNPs were in an amorphous state that was determined by X-ray diffraction. The IC50 values were determined as 22.32 µg/ml for naringenin, 1.6 µg/ml for NARNPs and 0.46 µg/ml for doxorubicin. Flow cytometric analysis showed that NARNPs induced late apoptosis in 56.1% of HepG2 cells and had no cytotoxic effect on WI38 cells with 97% viable cells after 48 h of incubation. NARNPs induced cell cycle arrest in the Go/G1 and G2/M phases in HepG2 cells. The results showed increased expression of ATG5, LC3, and p53 in HepG2 cells treated with IC50 concentrations after 48 h of incubation. NARNPs enhanced the cytotoxic effect of doxorubicin in HepG2 cells but decreased the cytotoxic effect of doxorubicin in WI38 cells. CONCLUSIONS The study demonstrated that NARNPs effectively inhibit cell proliferation and induce apoptosis in human hepatocellular carcinoma cells. Importantly, NARNPs showed no cytotoxic effects on normal cells, indicating their potential as a promising therapy for hepatocarcinogenesis. Combining NARNPs with chemotherapy drugs could present a novel approach for treating human cancers.
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Affiliation(s)
- Aya G Elwan
- Biochemistry Department, Faculty of Science, Tanta University, Tanta, Egypt.
| | - Tarek M Mohamed
- Biochemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
| | - Doha M Beltagy
- Biochemistry Department, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Doaa M El Gamal
- Biochemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
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Khan GS, Tahir MZ, Zahoor MY, Hifz-Ul-Rahman, Riaz A. Effect of naringenin on post-thaw quality, fertility-associated gene expression and fertilization potential of buffalo (Bubalus bubalis) bull sperm. Cryobiology 2024; 116:104953. [PMID: 39142616 DOI: 10.1016/j.cryobiol.2024.104953] [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: 04/17/2024] [Revised: 07/02/2024] [Accepted: 08/12/2024] [Indexed: 08/16/2024]
Abstract
Our objectives were to explore the effect of naringenin addition in the semen extender on the post-thaw 1) sperm quality, 2) fertility-associated gene expression, and 3) fertilization potential of buffalo bull sperm. In experiment 1, semen samples (n = 32) from four Nili-Ravi buffalo bulls were pooled (n = 8) and diluted with the tris-citric acid (TCF-EY) extender containing different concentrations of naringenin, i.e., placebo (DMSO), 0 (control), 50, 100, 150 and 200 μM naringenin. After dilution, semen samples were packed in 0.5 mL French straws, cryopreserved and analyzed for post-thawed sperm quality and gene expression. Computer-assisted Semen Analysis, Hypo-osmotic Swelling test, Normal Apical Ridge assay, Rhodamine 123, Acridine orange, Propidium iodide staining and Thiobarbituric Acid Reactive Substances assay were performed to assess sperm motility parameters, plasma membrane functionality, acrosome integrity, mitochondrial membrane potential, DNA integrity, viability and lipid peroxidation, respectively. Expression levels of sperm acrosome-associated SPACA3, DNA condensation-related PRM1, anti-apoptotic BCL2, pro-apoptotic BAX, and oxidative stress-associated ROMO1 genes were evaluated through qPCR. Results revealed that total and progressive motility, plasma membrane functionality, acrosome integrity, mitochondrial membrane potential, DNA integrity and viability were higher (P < 0.05) with 50, 100 and 150 μM naringenin compared to 200 μM naringenin, placebo and control groups. Moreover, all naringenin-treated groups improved catalase activity, and reduced lipid peroxidation compared to placebo and control groups (P < 0.05). Relative expression levels of SPACA3 and PRM1 genes were higher (P < 0.05) with 150 μM naringenin compared to all groups except 100 μM (P > 0.05). No difference (P > 0.05) in the expression level of BCL2 gene was observed among all groups. Furthermore, BAX gene was expressed higher (P < 0.05) in the 200 μM naringenin group, whereas no difference (P > 0.05) in expression was noticed among the remaining groups. In addition, ROMO1 gene was expressed lower (P < 0.05) in all naringenin-treated groups compared to the control. In experiment 2, the in vivo fertility of semen doses (n = 400; 200/group) containing optimum concentration of naringenin (150 μM; depicted better in vitro sperm quality in experiment 1) was compared with control during the breeding season. Buffaloes were inseminated 24 h after the onset of natural estrus and palpated transrectal for pregnancy at least 60 days post-insemination. The fertility rate of 150 μM naringenin group was higher (P = 0.0366) compared to the control [57.00 ± 0.03 % (114/200) vs. 46.50 ± 0.04 % (93/200), respectively]. Taken together, it is concluded that naringenin supplementation in semen extender improves post-thaw quality, fertility-associated gene expression and fertilization potential of buffalo bull sperm, more apparently at 150 μM concentration.
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Affiliation(s)
- Ghulam Shabbir Khan
- Department of Theriogenology, Faculty of Veterinary Science, University of Veterinary and Animal Sciences, Lahore, Pakistan.
| | - Muhammad Zahid Tahir
- Department of Theriogenology, Faculty of Veterinary Science, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Muhammad Yasir Zahoor
- Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Hifz-Ul-Rahman
- Department of Livestock Management, Faculty of Animal Production and Technology, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Amjad Riaz
- Department of Theriogenology, Faculty of Veterinary Science, University of Veterinary and Animal Sciences, Lahore, Pakistan.
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Ozkan G, Ceyhan T, Çatalkaya G, Rajan L, Ullah H, Daglia M, Capanoglu E. Encapsulated phenolic compounds: clinical efficacy of a novel delivery method. PHYTOCHEMISTRY REVIEWS 2024; 23:781-819. [DOI: 10.1007/s11101-023-09909-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 12/05/2023] [Indexed: 01/15/2025]
Abstract
AbstractEncapsulation is a drug or food ingredient loaded-delivery system that entraps active components, protecting them from decomposition/degradation throughout the processing and storage stages and facilitates their delivery to the target tissue/organ, improving their bioactivities. The application of this technology is expanding gradually from pharmaceuticals to the food industry, since dietary bioactive ingredients, including polyphenols, are susceptible to environmental and/or gastrointestinal conditions. Polyphenols are the largest group of plants' secondary metabolites, with a wide range of biological effects. Literature data have indicated their potential in the prevention of several disorders and pathologies, ranging from simpler allergic conditions to more complex metabolic syndrome and cardiovascular and neurodegenerative diseases. Despite the promising health effects in preclinical studies, the clinical use of dietary polyphenols is still very limited due to their low bioaccessibility and/or bioavailability. Encapsulation can be successfully employed in the development of polyphenol-based functional foods, which may improve their bioaccessibility and/or bioavailability. Moreover, encapsulation can also aid in the targeted delivery of polyphenols and may prevent any possible adverse events. For the encapsulation of bioactive ingredients, several techniques are applied such as emulsion phase separation, emulsification/internal gelation, film formation, spray drying, spray-bed-drying, fluid-bed coating, spray-chilling, spray-cooling, and melt injection. The present review aims to throw light on the existing literature highlighting the possibility and clinical benefits of encapsulated polyphenols in health and disease. However, the clinical data is still very scarce and randomized clinical trials are needed before any conclusion is drawn.
Graphical abstract
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Marinho A, Seabra CL, Lima SAC, Lobo-da-Cunha A, Reis S, Nunes C. Empowering Naringin's Anti-Inflammatory Effects through Nanoencapsulation. Int J Mol Sci 2024; 25:4152. [PMID: 38673736 PMCID: PMC11050564 DOI: 10.3390/ijms25084152] [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: 02/21/2024] [Revised: 04/04/2024] [Accepted: 04/07/2024] [Indexed: 04/28/2024] Open
Abstract
Abundant in citrus fruits, naringin (NAR) is a flavonoid that has a wide spectrum of beneficial health effects, including its anti-inflammatory activity. However, its use in the clinic is limited due to extensive phase I and II first-pass metabolism, which limits its bioavailability. Thus, lipid nanoparticles (LNPs) were used to protect and concentrate NAR in inflamed issues, to enhance its anti-inflammatory effects. To target LNPs to the CD44 receptor, overexpressed in activated macrophages, functionalization with hyaluronic acid (HA) was performed. The formulation with NAR and HA on the surface (NAR@NPsHA) has a size below 200 nm, a polydispersity around 0.245, a loading capacity of nearly 10%, and a zeta potential of about 10 mV. In vitro studies show the controlled release of NAR along the gastrointestinal tract, high cytocompatibility (L929 and THP-1 cell lines), and low hemolytic activity. It was also shown that the developed LNPs can regulate inflammatory mediators. In fact, NAR@NPsHA were able to decrease TNF-α and CCL-3 markers expression by 80 and 90% and manage to inhibit the effects of LPS by around 66% for IL-1β and around 45% for IL-6. Overall, the developed LNPs may represent an efficient drug delivery system with an enhanced anti-inflammatory effect.
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Affiliation(s)
- Andreia Marinho
- LAQV, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal; (A.M.); (C.L.S.); (S.R.)
- LAQV, REQUIMTE, Faculdade de Ciências, Universidade do Porto, R. do Campo Alegre s/n, 4169-007 Porto, Portugal
| | - Catarina Leal Seabra
- LAQV, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal; (A.M.); (C.L.S.); (S.R.)
| | - Sofia A. C. Lima
- LAQV, REQUIMTE, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal;
| | - Alexandre Lobo-da-Cunha
- Departamento de Microscopia, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal;
| | - Salette Reis
- LAQV, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal; (A.M.); (C.L.S.); (S.R.)
| | - Cláudia Nunes
- LAQV, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal; (A.M.); (C.L.S.); (S.R.)
- LAQV, REQUIMTE, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal;
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Ganesh P, Suresh V, Narasimhan MK, Sabarathinam S. A narrative review on Naringin and Naringenin as a possible bioenhancer in various drug-delivery formulations. Ther Deliv 2023; 14:763-774. [PMID: 38088094 DOI: 10.4155/tde-2023-0086] [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] [Indexed: 12/22/2023] Open
Abstract
Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables. Naringenin exhibits lipid-lowering and insulin-like characteristics and is used to treat osteoporosis, cancer and cardiovascular disorders. Their incorporation into drug formulations offers several advantages, including enhanced solubility, improved bioavailability and targeted delivery. Naringin-based formulations are beneficial in cancer, for example controlling breast and prostate cancer by inhibition of CYP19. Naringin suppresses the PI3K/AKT signalling pathway, it triggers autophagy, which effectively halts the proliferation of gastric cancer cells. Naringin and naringenin co-administration or pre-administration has enhanced the target drug's potency and produced a synergistic effect. This published study demonstrates the potential applications of Naringin and Naringenin as recognized bio-enhancers.
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Affiliation(s)
- Pradeepti Ganesh
- Department of Genetic Engineering, College of Engineering & Technology, SRM Institute of Science & Technology, Kattankulathur, Chennai, Tamil Nadu-603203, India
| | - Vanishree Suresh
- Department of Genetic Engineering, College of Engineering & Technology, SRM Institute of Science & Technology, Kattankulathur, Chennai, Tamil Nadu-603203, India
| | - Manoj Kumar Narasimhan
- Department of Genetic Engineering, College of Engineering & Technology, SRM Institute of Science & Technology, Kattankulathur, Chennai, Tamil Nadu-603203, India
| | - Sarvesh Sabarathinam
- Drug Testing Laboratory, Interdisciplinary Institute of Indian system of Medicine (IIISM), SRM Institute of Science & Technology, Kattankulathur, Chennai, Tamil Nadu-603203, India
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Naseri A, Taymouri S, Hosseini Sharifabadi A, Varshosaz J. Chrysin loaded bilosomes improve the hepatoprotective effects of chrysin against CCl4 induced hepatotoxicity in mice. J Biomater Appl 2023; 38:509-526. [PMID: 37632164 DOI: 10.1177/08853282231198948] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/27/2023]
Abstract
In the present work, chrysin loaded bilosomes were formulated, characterized and evaluated to enhance the hepatoprotective activity of drug. Accordingly, chrysin loaded bilosomes were prepared by applying the thin film hydration method; also, fractional factorial design was used to optimize the production conditions of nanoformulations. The prepared formulations were subjected to different methods of characterization; then the hepatoprotective activity of the optimized one was evaluated in the CCl4 hepatointoxicated mice model. Optimized chrysin loaded bilosomes showed a spherical shape with a particle size of 232.97 ± 23 nm, the polydispersity index of 0.35 ± 0.01, the zeta potential of -44.5 ± 1.27 mv, the entrapment efficiency of 96.77 ± 0.18%, the drug loading % of 6.46 ± 0.01 and the release efficiency of 42.25 ± 1.04 during 48 h. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay demonstrated the superiority of the anti-oxidant potential of chrysin loaded bilosomes, as compared to pure chrysin. This was in agreement with histopathological investigations, showing significant improvement in serum hepatic biomarkers of CCl4 intoxicated mice treated with chrysin loaded bilosomes, as compared with free chrysin. These results, thus, showed the potential use of bilosomes to enhance the hepatoprotective activity of chrysin via oral administration.
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Affiliation(s)
- Atefeh Naseri
- Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Somayeh Taymouri
- Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Hosseini Sharifabadi
- Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Jaleh Varshosaz
- Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
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Mishra AK, Neha S, Rani L, Jain A, Dewangan HK, Sahoo PK. Rationally designed nanoparticulate delivery approach for silymarin with natural bio-enhancer: In vitro characterization and in vivo evaluations of hepatoprotective effects in a mouse model. J Drug Deliv Sci Technol 2023; 86:104580. [DOI: 10.1016/j.jddst.2023.104580] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2024]
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Fatima M, Khan MR, Al-Keridis LA, Alshammari N, Patel M, Adnan M, Sahreen S. Pleurospermum candollei Methanolic Extract Ameliorates CCl 4-Induced Liver Injury by Modulating Oxidative Stress, Inflammatory, and Apoptotic Markers in Rats. ACS OMEGA 2023; 8:25999-26011. [PMID: 37521626 PMCID: PMC10373198 DOI: 10.1021/acsomega.3c02031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 06/22/2023] [Indexed: 08/01/2023]
Abstract
The main objective of this study was to investigate the hepatoprotective potency of the Pleurospermum candollei methanol extract against CCl4-induced liver damage in rats. HPLC technique was used to estimate the presence of polyphenols in the methanol extract of P. candollei (PCM), while proximate analysis revealed the presence of carbohydrates, lipids, and moisture in the extract. The antioxidant potential of PCM was evaluated by 2,2-diphenylpicrylhydrazyl (DPPH) and reducing power assay, which showed a high percentage of inhibition against free radicals. Hepatotoxicity was induced by carbon tetrachloride (CCl4). CCl4 administration reduced the activity of endogenous antioxidants, whereas it increased the production of nitrites and hydrogen peroxide (H2O2) in rats. Furthermore, the level of hepatic markers in serum was also elevated after CCl4 administration. Moreover, the expression of stress-related markers, proinflammatory mediators, and apoptotic genes was enhanced in CCl4-treated rats. Coadministration of PCM along with CCl4 in rats reduced the levels of free radicals and the above genes to normal levels. CCl4 administration caused histopathological alterations in liver tissues, while cotreatment with PCM mitigated liver injuries. These findings suggest that the methanol extract of P. candollei possesses antioxidant and anti-inflammatory properties and can prevent liver injury. Further pharmacological research will be helpful in determining the effectiveness of P. candollei in humans. Development of FDA-approved plant-based anti-inflammatory drugs can help treat patients and reduce the chances of toxicity.
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Affiliation(s)
- Mehreen Fatima
- Department
of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Muhammad Rashid Khan
- Department
of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 44000, Pakistan
| | - Lamya Ahmed Al-Keridis
- Department
of Biology, College of Science, Princess
Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Nawaf Alshammari
- Department
of Biology, College of Science, University
of Ha’il, P.O. Box 2440, Ha’il 81481, Saudi Arabia
| | - Mitesh Patel
- Department
of Biotechnology, Parul Institute of Applied Sciences and Centre of
Research for Development, Parul University, Vadodara 391760, India
| | - Mohd Adnan
- Department
of Biology, College of Science, University
of Ha’il, P.O. Box 2440, Ha’il 81481, Saudi Arabia
| | - Sumaira Sahreen
- Botanical
Sciences Division, Pakistan Museum of Natural
History, Garden Avenue, Shakarparian , Islamabad 44000, Pakistan
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12
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Macit M, Duman G, Cumbul A, Sumer E, Macit C. Formulation development of Silybum marianum seed extracts and silymarin nanoparticles, and evaluation of hepatoprotective effect. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
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13
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Anwar I, Ashfaq UA. Impact of Nanotechnology on Differentiation and Augmentation of Stem Cells for Liver Therapy. Crit Rev Ther Drug Carrier Syst 2023; 40:89-116. [PMID: 37585310 DOI: 10.1615/critrevtherdrugcarriersyst.2023042400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023]
Abstract
The liver is one of the crucial organs of the body that performs hundreds of chemical reactions needed by the body to survive. It is also the largest gland of the body. The liver has multiple functions, including the synthesis of chemicals, metabolism of nutrients, and removal of toxins. It also acts as a storage unit. The liver has a unique ability to regenerate itself, but it can lead to permanent damage if the injury is beyond recovery. The only possible treatment of severe liver damage is liver transplant which is a costly procedure and has several other drawbacks. Therefore, attention has been shifted towards the use of stem cells that have shown the ability to differentiate into hepatocytes. Among the numerous kinds of stem cells (SCs), the mesenchymal stem cells (MSCs) are the most famous. Various studies suggest that an MSC transplant can repair liver function, improve the signs and symptoms, and increase the chances of survival. This review discusses the impact of combining stem cell therapy with nanotechnology. By integrating stem cell science and nanotechnology, the information about stem cell differentiation and regulation will increase, resulting in a better comprehension of stem cell-based treatment strategies. The augmentation of SCs with nanoparticles has been shown to boost the effect of stem cell-based therapy. Also, the function of green nanoparticles in liver therapies is discussed.
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Affiliation(s)
- Ifrah Anwar
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
| | - Usman Ali Ashfaq
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
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14
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Dadwal V, Gupta M. Recent developments in citrus bioflavonoid encapsulation to reinforce controlled antioxidant delivery and generate therapeutic uses: Review. Crit Rev Food Sci Nutr 2023; 63:1187-1207. [PMID: 34378460 DOI: 10.1080/10408398.2021.1961676] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Citrus fruits contain numerous antioxidative biomolecules including phenolic acids, flavonols, flavanones, polymethoxyflavones (PMFs), and their derivatives. Previous in vitro and in vivo studies thoroughly investigated the antioxidant and therapeutic potential of bioflavonoids extracted from different citrus varieties and fruit fractions. Major bioflavonoids such as hesperidin, naringin, naringenin, and PMFs, had restricted their incorporation into food and health products due to their poor solubility, chemical stability and bioavailability. Considering these limitations, modern encapsulation methodologies such as hydrogelation, liposomal interactions, emulsifications, and nanoparticles have been designed to shield bioflavonoids with improved target distribution for therapeutic enhancements. The size, durability, and binding efficiency of bioflavonoid-loaded encapsulates were acquired by the optimized chemical and instrumental parameters such as solubility, gelation, dispersion, extrusion, and drying. Bioflavonoid-enriched encapsulates have been also proven to be effective against cancer, inflammation, neurodegeneration, and various other illnesses. However, in the future, newer natural binding agents with higher binding capacity might accelerate the encapsulating potential, controlled release, and enhanced bioavailability of citrus bioflavonoids. Overall, these modern encapsulation systems are currently leading to a new era of diet-based medicine, as demand for citrus fruit-based nutritional supplements and edibles grows.
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Affiliation(s)
- Vikas Dadwal
- CSIR- Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Mahesh Gupta
- CSIR- Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
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15
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Naringenin Prevents Oxidative Stress and Inflammation in LPS-Induced Liver Injury through the Regulation of LncRNA-mRNA in Male Mice. Molecules 2022; 28:molecules28010198. [PMID: 36615393 PMCID: PMC9821796 DOI: 10.3390/molecules28010198] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/23/2022] [Accepted: 12/23/2022] [Indexed: 12/28/2022] Open
Abstract
Inflammation accompanies hepatic dysfunction resulting from tissue oxidative damage. Naringenin (Nar), a natural flavanone, has known antioxidant and anti-inflammatory activities, but its mechanism of action in the regulation of liver dysfunction requires further investigation. In this study, the role of naringenin in lipopolysaccharide (LPS)-induced hepatic oxidative stress and inflammation was explored, as well as its mechanism by transcriptome sequencing. The results indicated that compared with the LPS group, Nar treatment caused a significant increase in the mRNA levels of antioxidant factors glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM), yet the expression of related inflammatory factors (MCP1, TNFα, IL-1β and IL-6) showed less of an increase. RNA sequencing identified 36 differentially expressed lncRNAs and 603 differentially expressed mRNAs. KEGG enrichment analysis indicated that oxidative stress and inflammation pathways are meticulously linked with naringenin treatment. The Co-lncRNA-mRNA network was also constructed. Tissue expression profiles showed that lncRNA played a higher role in the liver. Subsequently, expression levels of inflammatory factors indicated that lncRNAs and target mRNAs were significantly reduced after naringenin treatment in mouse liver AML12 cells and obese mouse. These results suggest that naringenin helps to prevent liver dysfunction through the regulation of lncRNA-mRNA axis to reduce oxidative stress and inflammatory factors.
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16
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Lu R, Yu RJ, Yang C, Wang Q, Xuan Y, Wang Z, He Z, Xu Y, Kou L, Zhao YZ, Yao Q, Xu SH. Evaluation of the hepatoprotective effect of naringenin loaded nanoparticles against acetaminophen overdose toxicity. Drug Deliv 2022; 29:3256-3269. [PMID: 36321805 PMCID: PMC9635473 DOI: 10.1080/10717544.2022.2139431] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Acute liver injury is a common clinical disease, which easily leads to liver failure and endangers life, seriously threatening human health. Naringenin is a natural flavonoid that holds therapeutic potential against various liver injuries; however it has poor water solubility and bioavailability. In this study, we aimed to develop naringenin-loaded bovine serum albumin nanoparticles (NGNPs) and to evaluate their hepatoprotective effect and underlying mechanisms against acetaminophen overdose toxicity. In vitro data indicated that NGNPs significantly increased the drug solubility and also more effectively protected the hepatocyte cells from oxidative damage during hydrogen peroxide exposure or lipopolysaccharide (LPS) stimulation. In vivo results confirmed that NGNPs showed an enhanced accumulation in the liver tissue. In the murine model of acetaminophen-induced hepatotoxicity, NGNPs could effectively alleviate the progression of acute liver injury by reducing drug overdose-induced levels of oxidative stress, inflammation and apoptosis in hepatocytes. In conclusion, NGNPs has strong hepatoprotective effects against acetaminophen induced acute liver injury.
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Affiliation(s)
- Ruijie Lu
- Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China,School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China,The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, China
| | - Run-Jie Yu
- Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China,School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Chunhui Yang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Qian Wang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Yunxia Xuan
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Zeqing Wang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Zhimin He
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Yan Xu
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Longfa Kou
- The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, China
| | - Ying-Zheng Zhao
- Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China,School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Qing Yao
- Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China,School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China,CONTACT Qing Yao Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, University Town, Chashan, Wenzhou 325000, Zhejiang, China
| | - Shi-Hao Xu
- Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China,Shi-Hao Xu Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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17
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Kumar M, Kumar D, Kumar S, Kumar A, Mandal UK. A Recent Review on Bio-availability Enhancement of Poorly Water-soluble Drugs by using Bioenhancer and Nanoparticulate Drug Delivery System. Curr Pharm Des 2022; 28:3212-3224. [PMID: 36281868 DOI: 10.2174/1381612829666221021152354] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 08/17/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND Intravenous route of drug administration has maximum bioavailability, which shows 100% of the drug reaches blood circulation, whereas the oral administration of drugs, are readily undergoing pre-systemic metabolism, which means the poor bioavailability of the drug and limited amount of drug reaches the target site. INTRODUCTION Bioenhancers are substances having medicinal entities which enhance the bioavailability and efficacy of the active constituents of drugs. The enhanced bioavailability of drugs may lead to dose reduction, which may further reduce the cost and undesired side effects associated with the drugs. METHODS The solid lipid nanoparticles (SLNs) loaded with ketoprofen made from carnauba wax and beeswax. It was discovered that when the drug-loaded SLNs were mixed with egg-lecithin and Tween-80, as well as when the total surfactant concentration was increased, the average particle size of the drug-loaded SLNs decreased. RESULTS The drug-loaded nanoparticles, when given in combination with bio-enhancers such as piperine and quercetin, enhanced the drug's effectiveness. The Area Under Curve (AUC) was increased when the drug was coupled with bio-enhancers. Based on the findings, it can be concluded that piperine and quercetin when used with drug-loaded nanoparticles improve their therapeutic effectiveness. CONCLUSION Bioenhancers are crucial to amplifying the bioavailability of many synthetic drugs. These attributes are useful to reduce the dose of drugs and increase the therapeutic efficacy of drugs with poor bioavailability.
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Affiliation(s)
- Mohit Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| | - Devesh Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| | - Sumant Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| | - Akshay Kumar
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
| | - Uttam Kumar Mandal
- Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University (MRSPTU), Bathinda, 151001, Punjab, India
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18
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Sharma S, Hafeez A, Usmani SA. Nanoformulation approaches of naringenin- an updated review on leveraging pharmaceutical and preclinical attributes from the bioactive. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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19
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Islam F, Khadija JF, Islam MR, Shohag S, Mitra S, Alghamdi S, Babalghith AO, Theyab A, Rahman MT, Akter A, Al Mamun A, Alhumaydhi FA, Emran TB. Investigating Polyphenol Nanoformulations for Therapeutic Targets against Diabetes Mellitus. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:5649156. [PMID: 35832521 PMCID: PMC9273389 DOI: 10.1155/2022/5649156] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 06/03/2022] [Indexed: 12/11/2022]
Abstract
Diabetes mellitus (DM) is a fatal metabolic disorder, and its prevalence has escalated in recent decades to a greater extent. Since the incidence and severity of the disease are constantly increasing, plenty of therapeutic approaches are being considered as a promising solution. Many dietary polyphenols have been reported to be effective against diabetes along with its accompanying vascular consequences by targeting multiple therapeutic targets. Additionally, the biocompatibility of these polyphenols raises questions about their use as pharmacological mediators. Nevertheless, the pharmacokinetic and biopharmaceutical properties of these polyphenols limit their clinical benefit as therapeutics. Pharmaceutical industries have attempted to improve compliance and therapeutic effects. However, nanotechnological approaches to overcome the pharmacokinetic and biopharmaceutical barriers associated with polyphenols as antidiabetic medications have been shown to be effective to improve clinical compliance and efficacy. Therefore, this review highlighted a comprehensive and up-to-date assessment of polyphenol nanoformulations in the treatment of diabetes and vascular consequences.
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Affiliation(s)
- Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Jannatul Fardous Khadija
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Md. Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Sheikh Shohag
- Department of Biochemistry and Molecular Biology, Faculty of Life Science, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
| | - Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Saad Alghamdi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ahmad O. Babalghith
- Medical Genetics Department, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Abdulrahman Theyab
- Deputy Manager of Laboratory & Blood Bank, Security Forces Hospital, Makkah, Saudi Arabia
| | | | - Aklima Akter
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Abdullah Al Mamun
- Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Fahad A. Alhumaydhi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
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20
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Ishimoto K, Shimada Y, Ohno A, Otani S, Ago Y, Maeda S, Lin B, Nunomura K, Hino N, Suzuki M, Nakagawa S. Physicochemical and Biochemical Evaluation of Amorphous Solid Dispersion of Naringenin Prepared Using Hot-Melt Extrusion. Front Nutr 2022; 9:850103. [PMID: 35571922 PMCID: PMC9093646 DOI: 10.3389/fnut.2022.850103] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 04/06/2022] [Indexed: 11/17/2022] Open
Abstract
Naringenin (NRG) is a plant-derived flavonoid. Due to its antioxidant, anti-inflammatory, and analgesic activities it is beneficial to human health and is often used as a functional food ingredient; however, it has poor water solubility and low in vivo bioavailability. Therefore, the efficacy of NRG can be improved by enhancing its water solubility to increase gastrointestinal absorption. Conventional methods for the formulation of NRG are very complex and use toxic organic solvents, making them impractical for the production of functional foods. The objective of this study was to develop a safe and effective NRG-based functional food material. Previously, we established a technology to prepare amorphous solid dispersions (SDs) from functional food ingredients with poor water solubility and used hot-melt extrusion technology that is comparatively simple and does not involve the use of organic solvents. In this study, we prepared NRG SD and evaluated them both physicochemically and biochemically. NRG SD had superior water solubility and gastrointestinal absorption relative to native NRG and showed higher analgesic efficacy in rats than crystalline NRG. NRG SD was administered to mice in a mixed diet for 28 days, and organ weights and hematological/clinical biochemical parameters were assessed. NRG SD did not demonstrate severe adverse effects. The results suggest that NRG SD is a safe and highly efficacious formulation that can be used as a functional food material in the future.
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Affiliation(s)
- Kenji Ishimoto
- Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.,Laboratory of Innovative Food Science, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.,Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.,Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
| | - Yukiko Shimada
- Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
| | - Akane Ohno
- Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
| | - Shuichi Otani
- Laboratory of Innovative Food Science, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.,Mitsui Norin Co., Ltd., R&D Group, Shizuoka, Japan
| | - Yukio Ago
- Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.,Department of Cellular and Molecular Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Soya Maeda
- Laboratory of Innovative Food Science, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.,Mitsui Norin Co., Ltd., R&D Group, Shizuoka, Japan
| | - Bangzhong Lin
- Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
| | - Kazuto Nunomura
- Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
| | - Nobumasa Hino
- Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
| | - Masayuki Suzuki
- Laboratory of Innovative Food Science, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.,Mitsui Norin Co., Ltd., R&D Group, Shizuoka, Japan
| | - Shinsaku Nakagawa
- Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.,Laboratory of Innovative Food Science, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.,Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.,Center for Supporting Drug Discovery and Life Science Research, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
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21
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Hao Z, Liang L, Liu H, Yan Y, Zhang Y. Exploring the Extraction Methods of Phenolic Compounds in Daylily ( Hemerocallis citrina Baroni) and Its Antioxidant Activity. Molecules 2022; 27:2964. [PMID: 35566310 PMCID: PMC9101449 DOI: 10.3390/molecules27092964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/29/2022] [Accepted: 05/04/2022] [Indexed: 11/16/2022] Open
Abstract
Daylily is a valuable plant resource with various health benefits. Its main bioactive components are phenolic compounds. In this work, four extraction methods, ultrasonic-assisted water extraction (UW), ultrasonic-assisted ethanol extraction (UE), enzymatic-assisted water extraction (EW), and enzymatic-assisted ethanol extraction (EE), were applied to extract phenolic compounds from daylily. Among the four extracts, the UE extract exhibited the highest total phenolic content (130.05 mg/100 g DW) and the best antioxidant activity. For the UE extract, the DPPH value was 7.75 mg Trolox/g DW, the FRAP value was 14.54 mg Trolox/g DW, and the ABTS value was 15.37 mg Trolox/g DW. A total of 26 phenolic compounds were identified from the four extracts, and the UE extract exhibited a higher abundance range of phenolic compounds than the other three extracts. After multivariate statistical analysis, six differential compounds were selected and quantified, and the UE extract exhibited the highest contents of all six differential compounds. The results provided theoretical support for the extraction of phenolic compounds from daylily and the application of daylily as a functional food.
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Affiliation(s)
| | | | | | - Yi Yan
- Beijing Key Laboratory of Flavor Chemistry, School of Light Industry, Beijing Technology and Business University (BTBU), Beijing 100048, China; (Z.H.); (L.L.); (H.L.); (Y.Z.)
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22
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Mirazimi SMA, Dashti F, Tobeiha M, Shahini A, Jafari R, Khoddami M, Sheida AH, EsnaAshari P, Aflatoonian AH, Elikaii F, Zakeri MS, Hamblin MR, Aghajani M, Bavarsadkarimi M, Mirzaei H. Application of Quercetin in the Treatment of Gastrointestinal Cancers. Front Pharmacol 2022; 13:860209. [PMID: 35462903 PMCID: PMC9019477 DOI: 10.3389/fphar.2022.860209] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 03/02/2022] [Indexed: 02/06/2023] Open
Abstract
Many cellular signaling pathways contribute to the regulation of cell proliferation, division, motility, and apoptosis. Deregulation of these pathways contributes to tumor cell initiation and tumor progression. Lately, significant attention has been focused on the use of natural products as a promising strategy in cancer treatment. Quercetin is a natural flavonol compound widely present in commonly consumed foods. Quercetin has shown significant inhibitory effects on tumor progression via various mechanisms of action. These include stimulating cell cycle arrest or/and apoptosis as well as its antioxidant properties. Herein, we summarize the therapeutic effects of quercetin in gastrointestinal cancers (pancreatic, gastric, colorectal, esophageal, hepatocellular, and oral).
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Affiliation(s)
| | - Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Tobeiha
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Shahini
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Raha Jafari
- Department of Medicine, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran
| | - Mehrad Khoddami
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Amir Hossein Sheida
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Parastoo EsnaAshari
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Amir Hossein Aflatoonian
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Fateme Elikaii
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Melika Sadat Zakeri
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Mohammad Aghajani
- Infectious Disease Research Center, School of Nursing and Midwifery, Kashan University of Medical Sciences, Kashan, Iran
| | - Minoodokht Bavarsadkarimi
- Clinical Research Development Center, Mahdiyeh Educational Hospital, Shahid Beheshti 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
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23
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Naeini F, Namkhah Z, Tutunchi H, Rezayat SM, Mansouri S, Yaseri M, Hosseinzadeh-Attar MJ. Effects of naringenin supplementation on cardiovascular risk factors in overweight/obese patients with nonalcoholic fatty liver disease: a pilot double-blind, placebo-controlled, randomized clinical trial. Eur J Gastroenterol Hepatol 2022; 34:345-353. [PMID: 34860705 DOI: 10.1097/meg.0000000000002323] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVE Although several experimental models have suggested promising pharmacological effects of naringenin in the management of obesity and its related disorders, the effects of naringenin supplementation on cardiovascular disorders as one of the main complications of nonalcoholic fatty liver disease (NAFLD) are yet to be examined in humans. METHODS In this double-blind, placebo-controlled, randomized clinical trial, 44 overweight/obese patients with NAFLD were equally allocated into either naringenin or placebo group for 4 weeks. Cardiovascular risk factors including atherogenic factors, hematological indices, obesity-related parameters, blood pressure, and heart rate were assessed pre- and postintervention. RESULTS The atherogenic index of plasma value, serum non-HDL-C levels as well as total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C, low-density lipoprotein cholesterol/HDL-C, and non-HDL-C/HDL-C ratios were significantly reduced in the intervention group, compared to the placebo group post intervention (P < 0.05). Moreover, there was a significant reduction in BMI and visceral fat level in the intervention group when compared with the placebo group (P = 0.001 and P = 0.039, respectively). Furthermore, naringenin supplementation could marginally reduce systolic blood pressure (P = 0.055). Mean corpuscular hemoglobin increased significantly in the naringenin group compared to the placebo group at the endpoint (P = 0.023). Supplementation with naringenin also resulted in a marginally significant increase in the mean corpuscular hemoglobin concentration when compared with the placebo group (P = 0.050). There were no significant between-group differences for other study outcomes post intervention. CONCLUSION In conclusion, these data indicate that naringenin supplementation may be a promising treatment strategy for cardiovascular complications among NAFLD patients. However, further trials are warranted.
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Affiliation(s)
- Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran
| | - Zahra Namkhah
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran
| | - Helda Tutunchi
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz
| | - Seyed Mahdi Rezayat
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran
| | - Siavash Mansouri
- National Iranian Oil Company (NIOC) Health and Family Research Center, Tehran
| | - Mehdi Yaseri
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Yazdani F, Shareghi B, Farhadian S, Momeni L. Structural insights into the binding behavior of flavonoids naringenin with Human Serum Albumin. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2021.118431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Recent Advancement in Chitosan-Based Nanoparticles for Improved Oral Bioavailability and Bioactivity of Phytochemicals: Challenges and Perspectives. Polymers (Basel) 2021; 13:polym13224036. [PMID: 34833334 PMCID: PMC8617804 DOI: 10.3390/polym13224036] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/06/2021] [Accepted: 11/10/2021] [Indexed: 12/15/2022] Open
Abstract
The excellent therapeutic potential of a variety of phytochemicals in different diseases has been proven by extensive studies throughout history. However, most phytochemicals are characterized by a high molecular weight, poor aqueous solubility, limited gastrointestinal permeability, extensive pre-systemic metabolism, and poor stability in the harsh gastrointestinal milieu. Therefore, loading of these phytochemicals in biodegradable and biocompatible nanoparticles (NPs) might be an effective approach to improve their bioactivity. Different nanocarrier systems have been developed in recent decades to deliver phytochemicals. Among them, NPs based on chitosan (CS) (CS-NPs), a mucoadhesive, non-toxic, and biodegradable polysaccharide, are considered the best nanoplatform for the oral delivery of phytochemicals. This review highlights the oral delivery of natural products, i.e., phytochemicals, encapsulated in NPs prepared from a natural polymer, i.e., CS, for improved bioavailability and bioactivity. The unique properties of CS for oral delivery such as its mucoadhesiveness, non-toxicity, excellent stability in the harsh environment of the GIT, good solubility in slightly acidic and alkaline conditions, and ability to enhance intestinal permeability are discussed first, and then the outcomes of various phytochemical-loaded CS-NPs after oral administration are discussed in detail. Furthermore, different challenges associated with the oral delivery of phytochemicals with CS-NPs and future directions are also discussed.
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Namkhah Z, Naeini F, Mahdi Rezayat S, Mansouri S, Javad Hosseinzadeh-Attar M. Does naringenin supplementation improve lipid profile, severity of hepatic steatosis and probability of liver fibrosis in overweight/obese patients with NAFLD? A randomised, double-blind, placebo-controlled, clinical trial. Int J Clin Pract 2021; 75:e14852. [PMID: 34516703 DOI: 10.1111/ijcp.14852] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 08/01/2021] [Accepted: 09/10/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Naringenin has been reported to have some promising pharmacological effects on the management of obesity and related metabolic complications including non-alcoholic fatty liver disease (NAFLD). Therefore, the present clinical trial study was done to assess the effects of naringenin supplementation on lipid profile, aminotransferase levels, severity of steatosis, as well as probability of fibrosis in overweight/obese patients with NAFLD. MATERIALS AND METHODS This placebo-controlled, parallel randomised, double-blind clinical trial study was conducted on 44 eligible overweight/obese patients with NAFLD (naringenin-treated group (n = 22), control group (n = 22)) referred to the national Iranian oil company (NIOC) Central Hospital, Tehran City, Tehran Province, Iran. Participants were randomly assigned to receive naringenin capsules (100 mg) and identical placebo capsules twice a day, before lunch and dinner, for 4 weeks. The primary outcomes were improvement of liver steatosis and NAFLD fibrosis score (NFS), and secondary outcomes included changes in levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lipid profile. RESULTS Naringenin consumption significantly reduced percentages of NAFLD grades (P < .001), as well as, serum levels of triglyceride (TG) (P < .001), total cholesterol (TC) (P = .01), and low-density lipoprotein (LDL) (P = .02) and increased serum level of high-density lipoprotein (HDL) (P = .02) compared with the control group. Even after adjusting for the confounders, the results were significant. However, there were no significant changes in AST, ALT and NFS. CONCLUSION Our findings revealed that daily intake of 200 mg of naringenin for 4 weeks had beneficial effects on lipid profile and percentages of NAFLD grades as an indicator for the severity of hepatic steatosis. Although, NFS values and serum levels of aminotransferase enzymes including AST and ALT did not remarkably change.
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Affiliation(s)
- Zahra Namkhah
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
| | - Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
| | - Seyed Mahdi Rezayat
- Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Siavash Mansouri
- National Iranian Oil Company (NIOC) Health and Family Research Center, Tehran, Iran
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Akamo AJ, Akinloye DI, Ugbaja RN, Adeleye OO, Dosumu OA, Eteng OE, Antiya MC, Amah G, Ajayi OA, Faseun SO. Naringin prevents cyclophosphamide-induced erythrocytotoxicity in rats by abrogating oxidative stress. Toxicol Rep 2021; 8:1803-1813. [PMID: 34760624 PMCID: PMC8567332 DOI: 10.1016/j.toxrep.2021.10.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 09/30/2021] [Accepted: 10/24/2021] [Indexed: 01/02/2023] Open
Abstract
Earlier reports have shown that Cyclophosphamide (CYCP), an anti-malignant drug, elicited cytotoxicity; and that naringin has several beneficial potentials against oxidative stress and dyslipidaemias. We investigated the influence of naringin on free radical scavenging, cellular integrity, cellular ATP, antioxidants, oxidative stress, and lipid profiles in the CYCP-induced erythrocytotoxicity rat model. Rats were pretreated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) naringin before single CYCP (200 mg/kg, i.p.) administration. Afterwards, the rats were sacrificed. Naringin concentrations required for 50 % scavenging hydrogen peroxide and nitric oxide radical were 0.27 mg/mL and 0.28 mg/mL, respectively. Naringin pretreatment significantly (p < 0.05) protected erythrocytes plasma membrane architecture and integrity by abolishing CYCP-induced decrease in the activity of erythrocyte LDH (a marker of ATP). Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-induced decreases in the erythrocytes glutathione levels, activities of glutathione-S-transferase, catalase, glutathione peroxidase, and glutathione reductase; attenuated CYCP-mediated increases in erythrocytes levels of malondialdehyde, nitric oxide, and major lipids (cholesterol, triacylglycerol, phospholipids, and non-esterified fatty acids). Taken together, different acute pretreatment doses of naringin might avert CYCP-mediated erythrocytes dysfunctions via its antioxidant, free-radical scavenging, and anti-dyslipidaemia properties.
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Key Words
- AP-1, activator protein 1
- ATP, adenosine triphosphate
- Antioxidants
- BHT, butylated hydroxytoluene
- C31H28N2Na4O13S, xylenol tetrasodium
- C5FeN6Na2O, sodium nitroprusside
- CAT, catalase
- CDNB, 1-chloro-2,4-dinitrobenzene
- CYCP, cyclophosphamide
- Cu(NO3)2.3H2O, copper II nitrate
- Cyclophosphamide
- DNA, deoxyribonucleic acid
- DTNB, 5,5ˈ-dithiobis(2-nitrobenzoic acid)
- Erythrocytotoxicity
- FeSO4.7H2O, Iron (II) sulfate heptahydrate
- G6PDH, glucose-6-phosphate dehydrogenase
- GSH, reduced glutathione
- GSPx, glutathione peroxidase
- GSR, glutathione reductase
- GSSG, oxidized glutathione
- GST, glutathione-S-transferase
- H2O2, hydrogen peroxide
- H3PO3, phosphoric acid
- HO•, hydroxyl radical
- HSCs, hepatic stellate cells
- K2HPO4, dipotassium hydrogen phosphate
- KCl, potassium chloride
- LDH, lactate dehydrogenase
- Lipid profile
- MAPKs, mitogen-activated protein kinases
- MDA, malondialdehyde
- MMP, matrix metalloprotease
- NAD+, nicotinamide adenine dinucleotide
- NADH, nicotinamide adenine dinucleotide reduced
- NADPH, nicotinamide adenine dinucleotide phosphate reduced
- NF-κB, nuclear factor kappa B
- NH4OH, ammonium hydroxide
- NO, nitric oxide
- NO2−, nitrite
- NO3−, nitrate
- NOAEL, no-observed-adverse-effect level
- Na2HPO4, disodium hydrogen phosphate
- NaH2PO4, sodium dihydrogen phosphate
- Naringin
- Nrf2, nuclear factor-erythroid factor 2-related factor 2
- O2HbFe2+, oxyhemoglobin
- O2•–, superoxide radical
- OONO−, peroxynitrite radical
- Oxidative stress
- PBS, phosphate-buffered saline
- PUFA, Polyunsaturated fatty acids
- R-Smad, Smad activated receptor
- RNS, reactive nitrogen species
- ROS, reactive oxygen species
- SOD, superoxide dismutase
- TBA, 2-thiobarbituric acid
- TBARS, thiobarbituric acid reactive substances
- TGF-β, transforming growth factor-β
- TLR, toll-like receptor
- TROOH, total hydroperoxide
- VLDL, very low density lipoprotein
- eNOS, endothelial nitric oxide synthase
- i.p., intraperitoneally
- mRNA, messenger ribonucleic acid
- metHb, methemoglobin
- α-SMA, alpha smooth muscle actin
- •NO, nitric oxide radical
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Affiliation(s)
- Adio J. Akamo
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Dorcas I. Akinloye
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Regina N. Ugbaja
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Oluwagbemiga O. Adeleye
- Department of Animal Production and Health, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Oluwatosin A. Dosumu
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Ofem E. Eteng
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Moses C. Antiya
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Gogonte Amah
- Department of Biochemistry, Benjamin Carson (SRN) School of Medicine, Babcock University, Ilisan, Ogun State, Nigeria
| | - Oluwafunke A. Ajayi
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Samuel O. Faseun
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
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Maurya P, Pandey P, Singh S, Sonkar A, Singh S, Saraf S. Appraisal of Felodipine nanocrystals for solubility enhancement and pharmacodynamic parameters on cadmium chloride induced hypertension in rats. Curr Drug Deliv 2021; 19:625-634. [PMID: 34325637 DOI: 10.2174/1567201818666210729104351] [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: 01/13/2021] [Revised: 07/05/2021] [Accepted: 07/06/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND AND OBJECTIVE Felodipine (FDP), an antihypertensive drug possesses low water solubility and extensive first-pass metabolism leading to poor bioavailability. This impelled us to improve its solubility, bioavailability, and pharmacodynamic properties through the nanocrystal (NC) approach. METHODS FDP-NC were prepared with Poloxamer F125 (PXM) by the antisolvent precipitation method. The experimental setup aimed at fine-tuning polymer concentration, the proportion of antisolvent to solvent, and the duration of ultrasonication for NC formulation. RESULTS Optimized formulation was characterized for particle size, solubility, and PDI. Particle reduction of 74.96 times was achieved with a 9X solubility enhancement as equated to pure FDP. The morphology of NC was found to be crystalline through scanning electron microscopy observation. The formation of the crystal lattice in FDP-NC was further substantiated by the XRD and DSC results. Lowering of the heat of fusion of FDP-NC is a clear indication of size reduction. The stability studies showed no substantial change in physical parameters of the FDP-NC as assessed by particle size, zeta potential, and drug content. CONCLUSION The crystalline nature and improved solubility of FDP-NC improve the dissolution profile and pharmacodynamic data. The stability study data ensures that FDP-NC can be safely stored at 25℃. It is revealed that FDP-NC had a better release profile and improved pharmacodynamic effects as evident from better control over heart rate than FDP.
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Affiliation(s)
- Priyanka Maurya
- Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, U.P., India
| | - Pawan Pandey
- Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, U.P., India
| | - Samipta Singh
- Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, U.P., India
| | - Alka Sonkar
- Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, U.P., India
| | - Sonali Singh
- Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, U.P., India
| | - Shubhini Saraf
- Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, U.P., India
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Akamo AJ, Rotimi SO, Akinloye DI, Ugbaja RN, Adeleye OO, Dosumu OA, Eteng OE, Amah G, Obijeku A, Cole OE. Naringin prevents cyclophosphamide-induced hepatotoxicity in rats by attenuating oxidative stress, fibrosis, and inflammation. Food Chem Toxicol 2021; 153:112266. [PMID: 33992719 DOI: 10.1016/j.fct.2021.112266] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 05/09/2021] [Accepted: 05/11/2021] [Indexed: 02/06/2023]
Abstract
Cyclophosphamide (CYCP), a synthetic alkylating antineoplastic, disrupts both cancerous and non-cancerous cells to cause cancer regression and multi organotoxicity respectively. CYCP-induced hepatotoxicity is rare but possible. Evidence has shown that naringin has several beneficial potentials against oxidative stress, inflammation, and fibrosis. This study examined the chemoprotective potentials of naringin on exited radical scavenging, hepatic integrity, oxidative stress, fibrosis, and inflammation in CYCP-mediated hepatotoxicity. Rats were pre-treated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) of naringin before single CYCP (200 mg/kg, i.p.) administration. Subsequently, the rats were euthanized; blood and liver were removed, and assessed for serum and hepatic enzymes, oxidative stress, inflammation, and gene expression dynamics. Naringin concentrations required for 50% scavenging hydroxyl radical and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) radical cation were 0.32 mg/mL and 0.39 mg/mL, respectively. Pretreatment with naringin significantly (p < 0.05) abolish CYCP-induced changes in the activities of serum and hepatic ALT, AST, GGT, ALP, and LDH. Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-mediated increases in hepatic levels of malondialdehyde, hydroperoxide, and nitric oxide; reverse CYCP-induced decreases in the hepatic glutathione levels, activities of catalase, glutathione peroxidase, and glutathione reductase; and also attenuated CYCP-induced upregulation of expression of hepatic chemokine (C-C motif) ligand 2 (CCL2), interferon alpha1 (IFN-α1), interleukine-1β, interleukine-1 receptor, and transforming growth factor beta 1 (TGF-β1). Taken together, different doses of naringin can prevent CYCP-induced oxidants generation, hepatocytes dysfunctions, oxidative stress as well as inflammatory perturbations in rats when pre-administered for as few as 14 days.
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Affiliation(s)
- Adio J Akamo
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria.
| | - Solomon O Rotimi
- Biochemistry Unit and Molecular Biology Research Laboratory, Department of Biological Sciences, Covenant University, Ota, Ogun State, Nigeria
| | - Dorcas I Akinloye
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Regina N Ugbaja
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Oluwagbemiga O Adeleye
- Department of Animal Production and Health, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Oluwatosin A Dosumu
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Ofem E Eteng
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Gogonte Amah
- Department of Biochemistry, Benjamin Carson (SRN) School of Medicine, Babcock University, Ilisan, Ogun State, Nigeria
| | - Augustine Obijeku
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
| | - Oluwatosin E Cole
- Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
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De S, Gopikrishna A, Keerthana V, Girigoswami A, Girigoswami K. An Overview of Nanoformulated Nutraceuticals and their Therapeutic Approaches. CURRENT NUTRITION & FOOD SCIENCE 2021. [DOI: 10.2174/1573401316999200901120458] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background:
Economic development and vast changes in food habits have accelerated
the consumption of junk foods, which are the leading causes of several disorders that turn the majority
of the people to use various herbal formulations or drugs for preventing various lifestyle diseases.
Nutraceuticals are the borderline apparatus between nutrients and drugs that provide supplementation
of the particular nutrient with a favorable health effect.
Objective:
Various nutraceutical compounds like vitamins, spices, polyphenols, prebiotics, and probiotics
in the form of powders, tablets, and capsules are currently marketed globally. Among them,
previous literature have reported that polyphenols are the most promising compounds that have
been proven to treat various chronic diseases like cancer, hypertension, diabetes mellitus (DM), osteoporosis,
osteoarthritis, dyslipidemia, multiple sclerosis, congenital anomalies, Alzheimer’s disease,
etc. It is warranted to discuss the benefits of nanoformulations of nutraceuticals.
Methods:
We have searched PubMed using the keywords nutraceuticals, nanoformulations, therapeutic
approaches, bionanotechnology, and therapeutics. The relevant papers and classical papers
in this field were selected to write this review.
Results and Discussion:
The different classifications of nutraceuticals were described in this review.
The comparison between the different categories of nutraceuticals with their nanoformulated
forms was made, explaining the benefits of nanoformulations regarding stability, bioavailability,
enhanced anti-oxidant properties, etc. A glimpse of the drawbacks of nanoformulations was also included.
Conclusion:
The current review highlights an overview of various nanoformulated nutraceuticals
and their approach towards the treatment of multiple diseases.
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Affiliation(s)
- Shaoli De
- Department of Medical Bionanotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chettinad Health City, Kelambakkam, Chennai-603103, India
| | - Agraharam Gopikrishna
- Department of Medical Bionanotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chettinad Health City, Kelambakkam, Chennai-603103, India
| | - Vedhantham Keerthana
- Department of Medical Bionanotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chettinad Health City, Kelambakkam, Chennai-603103, India
| | - Agnishwar Girigoswami
- Department of Medical Bionanotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chettinad Health City, Kelambakkam, Chennai-603103, India
| | - Koyeli Girigoswami
- Department of Medical Bionanotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chettinad Health City, Kelambakkam, Chennai-603103, India
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El-Saad AMA, Abdel-Wahab WM. Naringenin Attenuates Toxicity and Oxidative Stress Induced by Lambda-cyhalothrin in Liver of Male Rats. Pak J Biol Sci 2021; 23:510-517. [PMID: 32363836 DOI: 10.3923/pjbs.2020.510.517] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVES Extensive use of Lambda-cyhalothrin (LTC), a synthetic pyrethroid insecticide, has been associated with serious health problems to the non-target organisms including mammals. The present study investigated the protective effect of naringenin (NGN), an antioxidant flavonoid, against the toxicity induced LTC in the liver of male rats. MATERIALS AND METHODS Five groups of rats were assigned as follows; control group, LTC group (6.12 mg kg-1, 1/10 LD50), LTC-NGN group (6.12 mg kg-1 LTC and 50 mg kg-1 NGN), NGN-LTC group (50 mg kg-1 NGN and 6.12 mg kg-1 LTC) and NGN group (50 mg kg-1). Doses were administrated orally for 21 consecutive days. RESULTS Administration of LTC induced liver damage as indicated by the increase in the activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase and in the level of total bilirubin in serum. LTC also induced a significant elevation in the levels of serum total lipids, total cholesterol, triglycerides and low-density lipoproteins while high-density lipoproteins decreased. Furthermore, LTC significantly disturbed the oxidant/antioxidant balance in the liver as shown by the elevation in lipid peroxidation, lipid hydroperoxides, protein carbonyl content and conjugated dienes with a concomitant inhibition in the major antioxidants such as reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase. Both post-treatment and pre-treatment with NGN significantly modulated the LTC-induced hepatotoxicity and oxidative stress in rat's liver and pretreatment was found to be more effective in improving most of the studied parameters in both serum and liver tissue. CONCLUSION NGN could be used as a safe dietary supplement to protect against the toxicity and oxidative stress associated with the use of LTC.
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Gaur PK. Nanosuspension of flavonoid-rich fraction from Psidium guajava Linn for improved type 2-diabetes potential. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102358] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Zhang M, Zhu S, Yang W, Huang Q, Ho CT. The biological fate and bioefficacy of citrus flavonoids: bioavailability, biotransformation, and delivery systems. Food Funct 2021; 12:3307-3323. [PMID: 33735339 DOI: 10.1039/d0fo03403g] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Citrus fruits are among the most popularly consumed fruits worldwide, including oranges, grapefruits, pomelos and lemons. Citrus flavonoids such as hesperidin, naringin and nobiletin have shown an array of health benefits in cell, animal and clinical studies, including antioxidative, anti-inflammatory, neuroprotective, anticancer, and anti-obesity activities. Citrus flavonoids have limited bioavailability after oral administration, leaving the major part unabsorbed and persisted in the colon. Recent studies have highlighted the important role of the gut microbiota and in vivo biotransformation on the bioactivity of citrus flavonoids. This article discusses the biological fate of citrus flavonoids from the viewpoint of their absorption, distribution, metabolism and excretion in vivo. Many delivery systems have been designed to enhance the oral bioavailability of citrus flavonoids, such as emulsions, self-emulsifying systems, nanoparticles and solid dispersions. The ultimate goal of these delivery systems is to enhance the bioefficacy of citrus flavonoids. Several studies have found that the increased bioavailability leads to enhanced bioefficacy of citrus flavonoids in specific animal models. Regarding the complex dynamics of citrus flavonoids and gut microbiota, the bioavailability-bioactivity relationship is an interesting but under-discussed area. Comprehensively understanding the biological fate and bioefficacy of citrus flavonoids would be helpful to develop functional foods with better health benefits.
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Affiliation(s)
- Man Zhang
- Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick 08901, New Jersey, USA.
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Naringenin Nano-Delivery Systems and Their Therapeutic Applications. Pharmaceutics 2021; 13:pharmaceutics13020291. [PMID: 33672366 PMCID: PMC7926828 DOI: 10.3390/pharmaceutics13020291] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/10/2021] [Accepted: 02/19/2021] [Indexed: 12/18/2022] Open
Abstract
Naringenin (NRG) is a polyphenolic phytochemical belonging to the class of flavanones and is widely distributed in citrus fruits and some other fruits such as bergamot, tomatoes, cocoa, and cherries. NRG presents several interesting pharmacological properties, such as anti-cancer, anti-oxidant, and anti-inflammatory activities. However, the therapeutic potential of NRG is hampered due to its hydrophobic nature, which leads to poor bioavailability. Here, we review a wide range of nanocarriers that have been used as delivery systems for NRG, including polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanosuspensions, and nanoemulsions. These nanomedicine formulations of NRG have been applied as a potential treatment for several diseases, using a wide range of in vitro, ex vivo, and in vivo models and different routes of administration. From this review, it can be concluded that NRG is a potential therapeutic option for the treatment of various diseases such as cancer, neurological disorders, liver diseases, ocular disorders, inflammatory diseases, skin diseases, and diabetes when formulated in the appropriate nanocarriers.
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Murti Y, Semwal BC, Goyal A, Mishra P. Naringenin Scaffold as a Template for Drug Designing. CURRENT TRADITIONAL MEDICINE 2021. [DOI: 10.2174/2215083805666190617144652] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Natural products provide cornucopia of heterocyclic systems. The nucleus of 2-
phenyl chromane is one of the important and well-known heterocycles found in the natural
products. Naringenin, a plant-derived flavanone (2-phenyl chroman-4-one) belongs to the family
of flavanoids. It possesses diverse biologic activities such as antidiabetic, antiatherogenic,
antidepressant, antiandrogenic, antiestrogenic, immunomodulatory, antitumor, antimicrobial,
anti-inflammatory, antiviral, hypolipidemic, antihypertensive, antioxidant, neuroprotective,
anti-obesity, anti-Alzheimer, and memory enhancer activity. It has the potential to be used as
an active pharmacophore. There have been reports of a number of molecular mechanisms
underlying their beneficial activities. With emerging interest in traditional medicine and
exploiting their potential based on a variety of health care systems, naringenin literature was
thought to be explored. Further, this review aims to provide a new era of flavonoid-based
therapeutic agents with new insights into naringenin and its derivatives as a lead compound
in drug design.
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Affiliation(s)
- Yogesh Murti
- Institute of Pharmaceutical Research, GLA University, Mathura N.H.#2, Mathura-Delhi Road, P.O. Chaumuhan, Mathura-281 406, India
| | - Bhupesh Chander Semwal
- Institute of Pharmaceutical Research, GLA University, Mathura N.H.#2, Mathura-Delhi Road, P.O. Chaumuhan, Mathura-281 406, India
| | - Ahsas Goyal
- Institute of Pharmaceutical Research, GLA University, Mathura N.H.#2, Mathura-Delhi Road, P.O. Chaumuhan, Mathura-281 406, India
| | - Pradeep Mishra
- Institute of Pharmaceutical Research, GLA University, Mathura N.H.#2, Mathura-Delhi Road, P.O. Chaumuhan, Mathura-281 406, India
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Hermawan A, Ikawati M, Jenie RI, Khumaira A, Putri H, Nurhayati IP, Angraini SM, Muflikhasari HA. Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies. Saudi Pharm J 2021; 29:12-26. [PMID: 33603536 PMCID: PMC7873751 DOI: 10.1016/j.jsps.2020.12.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Accepted: 12/03/2020] [Indexed: 12/15/2022] Open
Abstract
Cancer therapy is a strategic measure in inhibiting breast cancer stem cell (BCSC) pathways. Naringenin, a citrus flavonoid, was found to increase breast cancer cells' sensitivity to chemotherapeutic agents. Bioinformatics study and 3D tumorsphere in vitro modeling in breast cancer (mammosphere) were used in this study, which aims to explore the potential therapeutic targets of naringenin (PTTNs) in inhibiting BCSCs. Bioinformatic analyses identified direct target proteins (DTPs), indirect target proteins (ITPs), naringenin-mediated proteins (NMPs), BCSC regulatory genes, and PTTNs. The PTTNs were further analyzed for gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction (PPI) networks, and hub protein selection. Mammospheres were cultured in serum-free media. The effects of naringenin were measured by MTT-based cytotoxicity, mammosphere forming potential (MFP), colony formation, scratch wound-healing assay, and flow cytometry-based cell cycle analyses and apoptosis assays. Gene expression analysis was performed using real-time quantitative polymerase chain reaction (q-RT PCR). Bioinformatics analysis revealed p53 and estrogen receptor alpha (ERα) as PTTNs, and KEGG pathway enrichment analysis revealed that TGF-ß and Wnt/ß-catenin pathways are regulated by PTTNs. Naringenin demonstrated cytotoxicity and inhibited mammosphere and colony formation, migration, and epithelial to mesenchymal transition in the mammosphere. The mRNA of tumor suppressors P53 and ERα were downregulated in the mammosphere, but were significantly upregulated upon naringenin treatment. By modulating the P53 and ERα mRNA, naringenin has the potential of inhibiting BCSCs. Further studies on the molecular mechanism and formulation of naringenin in BCSCs would be beneficial for its development as a BCSC-targeting drug.
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Key Words
- BCSCs, Breast cancer stem cells
- Bioinformatics
- Breast cancer stem cells
- CSC, Cancer stem cell
- DAVID, Database for Annotation, Visualization, and Integrated Discovery
- DTPs, Direct target proteins
- DXR, Doxorubicin
- EGF, Epidermal growth factor
- EMT, Epithelial to mesenchymal transition
- ERα
- FITC, fluorescein isothiocyanate
- GO, Gene ontology
- ITPs, Indirect target proteins
- KEGG, Kyoto Encyclopedia of Genes and Genomes
- MET, Metformin
- MFP, Mammosphere forming potential
- NAR, Naringenin
- NMPs, Naringenin-mediated proteins
- Naringenin
- P53
- PE, phycoerythrin
- PPI, Protein-protein interaction
- PTTN, Potential target of naringenin in inhibition of BCSCs
- ROS, Reactive oxygen species
- Targeted therapy
- q-RT PCR, Quantitative real-time polymerase chain reaction
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Affiliation(s)
- Adam Hermawan
- Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia
| | - Muthi Ikawati
- Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia
| | - Riris Istighfari Jenie
- Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia
| | - Annisa Khumaira
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia
| | - Herwandhani Putri
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia
| | - Ika Putri Nurhayati
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia
| | - Sonia Meta Angraini
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia
| | - Haruma Anggraini Muflikhasari
- Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia
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Multi-Therapeutic Potential of Naringenin (4',5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms. PLANTS 2020; 9:plants9121784. [PMID: 33339267 PMCID: PMC7766900 DOI: 10.3390/plants9121784] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 11/26/2020] [Accepted: 11/26/2020] [Indexed: 12/12/2022]
Abstract
Extensive research has been carried out during the last few decades, providing a detailed account of thousands of discovered phytochemicals and their biological activities that have the potential to be exploited for a wide variety of medicinal purposes. These phytochemicals, which are pharmacologically important for clinical use, primarily consist of polyphenols, followed by terpenoids and alkaloids. There are numerous published reports indicating the primary role of phytochemicals proven to possess therapeutic potential against several diseases. However, not all phytochemicals possess significant medicinal properties, and only some of them exhibit viable biological effects. Naringenin, a flavanone found in citrus fruits, is known to improve immunity, repair DNA damage, and scavenge free radicals. Despite the very low bioavailability of naringenin, it is known to exhibit various promising biological properties of medicinal importance, including anti-inflammatory and antioxidant activities. This review focuses on the various aspects related to naringenin, particularly its physicochemical, pharmacokinetic, and pharmacodynamic properties. Furthermore, various pharmacological activities of naringenin, such as anticancer, antidiabetic, hepatoprotective, neuroprotective, cardioprotective, nephroprotective, and gastroprotective effects, have been discussed along with their mechanisms of action.
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Jin Y, Wang H, Yi K, Lv S, Hu H, Li M, Tao Y. Applications of Nanobiomaterials in the Therapy and Imaging of Acute Liver Failure. NANO-MICRO LETTERS 2020; 13:25. [PMID: 34138224 PMCID: PMC8187515 DOI: 10.1007/s40820-020-00550-x] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 10/22/2020] [Indexed: 05/02/2023]
Abstract
This review focuses on the therapeutic mechanisms, targeting strategies of various nanomaterials in acute liver failure, and recent advances of diverse nanomaterials for acute liver failure therapy, diagnosis, and imaging. This review provides an outlook on the applications of nanomaterials, especially on the new horizons in acute liver failure therapy, and inspires broader interests across various disciplines. Acute liver failure (ALF), a fatal clinical disease featured with overwhelming hepatocyte necrosis, is a grand challenge in global health. However, a satisfactory therapeutic option for curing ALF is still absent, other than liver transplantation. Nanobiomaterials are currently being developed for the diagnosis and treatment of ALF. The liver can sequester most of nanoparticles from blood circulation, which becomes an intrinsic superiority for nanobiomaterials targeting hepatic diseases. Nanobiomaterials can enhance the bioavailability of free drugs, thereby significantly improving the therapeutic effects in ALF. Nanobiomaterials can also increase the liver accumulation of therapeutic agents and enable more effective targeting of the liver or specific liver cells. In addition, stimuli-responsive, optical, or magnetic nanomaterials exhibit great potential in the therapeutical, diagnostic, and imaging applications in ALF. Therefore, therapeutic agents in combination with nanobiomaterials increase the specificity of ALF therapy, diminish adverse systemic effects, and offer a multifunctional theranostic platform. Nanobiomaterial holds excellent significance and prospects in ALF theranostics. In this review, we summarize the therapeutic mechanisms and targeting strategies of various nanobiomaterials in ALF. We highlight recent developments of diverse nanomedicines for ALF therapy, diagnosis, and imaging. Furthermore, the challenges and future perspectives in the theranostics of ALF are also discussed.
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Affiliation(s)
- Yuanyuan Jin
- Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People's Republic of China
| | - Haixia Wang
- Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People's Republic of China
| | - Ke Yi
- Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People's Republic of China
| | - Shixian Lv
- Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA
| | - Hanze Hu
- Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA
| | - Mingqiang Li
- Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People's Republic of China.
| | - Yu Tao
- Laboratory of Biomaterials and Translational Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People's Republic of China.
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Ebrahimi MH, Samadian H, Davani ST, Kolarijani NR, Mogharabian N, Salami MS, Salehi M. Peripheral nerve regeneration in rats by chitosan/alginate hydrogel composited with Berberine and Naringin nanoparticles: in vitro and in vivo study. J Mol Liq 2020. [DOI: 10.1016/j.molliq.2020.114226] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Heidary Moghaddam R, Samimi Z, Moradi SZ, Little PJ, Xu S, Farzaei MH. Naringenin and naringin in cardiovascular disease prevention: A preclinical review. Eur J Pharmacol 2020; 887:173535. [DOI: 10.1016/j.ejphar.2020.173535] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/26/2020] [Accepted: 09/03/2020] [Indexed: 12/27/2022]
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Kumar N, Jose J. Current developments in the nanomediated delivery of photoprotective phytochemicals. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:38446-38471. [PMID: 32761528 DOI: 10.1007/s11356-020-10100-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 07/10/2020] [Indexed: 06/11/2023]
Abstract
Natural products have been used to protect the skin from harmful UV radiation for decades. Due to the ecotoxicological implications of synthetic sunscreen exposure in aquatic ecosystems, there is a greater need to explore alternative sources of UV filters. Recent research has focused on discovering novel UV absorbing photoprotective molecules from nature. In response to the excessive damage caused by UVB rays, plants induce the production of high concentrations of phytoprotective secondary metabolites and anti-oxidative enzymes. Despite promising UV absorbing and photoprotective properties, plant secondary metabolites have been underutilized in topical delivery due to low solubility and high instability. Numerous phytochemicals have been effectively nanosized, incorporated in formulations, and studied for their sustained effects in photoprotection. The present review outlines recent developments in nanosizing and delivering photoprotective crude plant extract and phytochemicals from a phytochemical perspective. We searched for articles using keywords: "UV damage," "skin photoprotection," "photodamage," and "nano delivery" in varied combinations. We identified and reviewed literature from 43 original research articles exploring nanosized phytochemicals and crude plant extracts with photoprotective activity. Nanosized phytochemicals retained higher amounts of bioactive compounds in the skin and acted as depots for their sustained release. Novel approaches in nanosizing considerably improved the photostability, efficacy, and water resistance of plant secondary metabolites. We further discuss the need for broad-spectrum sunscreen products, potential challenges, and future growth in this area.
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Affiliation(s)
- Nimmy Kumar
- Department of Pharmacognosy, NITTE Gulabi Shetty Memorial Institute of Pharmaceutical Sciences, NITTE Deemed-to-be University, 575018, Mangalore, India
| | - Jobin Jose
- Department of Pharmaceutics, NITTE Gulabi Shetty Memorial Institute of Pharmaceutical Sciences, NITTE Deemed-to-be University, Mangalore, 575018, India.
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Mehdipour M, Daghigh Kia H, Najafi A, Mohammadi H, Álvarez-Rodriguez M. Effect of crocin and naringenin supplementation in cryopreservation medium on post-thaw rooster sperm quality and expression of apoptosis associated genes. PLoS One 2020; 15:e0241105. [PMID: 33119667 PMCID: PMC7595379 DOI: 10.1371/journal.pone.0241105] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 10/09/2020] [Indexed: 12/26/2022] Open
Abstract
The aim of our study was to examine the effects of crocin (0.5 (C0.5), 1 (C1) and 1.5 (C1.5) mM) and naringenin (50 (N50), 100 (N100) and 150 (N150) μM) in cryopreservation extender for freezing rooster semen. Sperm motility, viability, abnormalities, membrane functionality, active mitochondria, apoptosis status, lipid peroxidation (LP), GPX, SOD, TAC, the mRNA expression of pro-apoptotic (CASPASE 3) and anti-apoptotic (Bcl-2) genes, fertile eggs, hatched eggs and hatching rate were investigated following freeze-thawing. C1 and N100 resulted in higher (P < 0.05) total motility and progressive motility in comparison to the control group. The C1 and N100 groups improved viability, membrane functionality and reduced lipid peroxidation. We found higher values for active mitochondria with C1 and N100 compared to control group. The C1 and N100 groups showed lower percentages of early apoptosis when compared with control group. Also, C1 and N100 had higher TAC, compared to the control group. The mRNA expressions of BCL-2 in the C1 and N100 groups were significantly higher than that of other treatments. The expression of CASPASES 3 was significantly reduced in C1 and N100 group (P < 0.05) when compared to control group. Significantly higher percentages of fertile eggs, hatched eggs and hatching rate were observed in C1 and N100 compared to the control group. In conclusion, crocin at 1 mM and naringenin at 100 μM seem to improve the post-thawing rooster semen quality, fertility and could protect the sperm by reducing the pro-apoptotic (CASPASE 3) and increasing anti-apoptotic (Bcl-2) genes.
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Affiliation(s)
- Mahdieh Mehdipour
- Department of Animal Science, College of Agriculture, University of Tabriz, Tabriz, Iran
| | - Hossein Daghigh Kia
- Department of Animal Science, College of Agriculture, University of Tabriz, Tabriz, Iran
- * E-mail: ,
| | - Abouzar Najafi
- Department of Animal and Poultry Science, College of Aburaihan, University of Tehran, Tehran, Iran
| | - Hossein Mohammadi
- Department of Animal Science, College of Agriculture, University of Tabriz, Tabriz, Iran
| | - Manuel Álvarez-Rodriguez
- Department of Biomedical & Clinical Sciences (BKV), BKH/Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden
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A Comprehensive Review of Natural Products against Liver Fibrosis: Flavonoids, Quinones, Lignans, Phenols, and Acids. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:7171498. [PMID: 33082829 PMCID: PMC7556091 DOI: 10.1155/2020/7171498] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 07/23/2020] [Accepted: 07/25/2020] [Indexed: 12/18/2022]
Abstract
Liver fibrosis resulting from continuous long-term hepatic damage represents a heavy burden worldwide. Liver fibrosis is recognized as a complicated pathogenic mechanism with extracellular matrix (ECM) accumulation and hepatic stellate cell (HSC) activation. A series of drugs demonstrate significant antifibrotic activity in vitro and in vivo. No specific agents with ideally clinical efficacy for liver fibrosis treatment have been developed. In this review, we summarized the antifibrotic effects and molecular mechanisms of 29 kinds of common natural products. The mechanism of these compounds is correlated with anti-inflammatory, antiapoptotic, and antifibrotic activities. Moreover, parenchymal hepatic cell survival, HSC deactivation, and ECM degradation by interfering with multiple targets and signaling pathways are also involved in the antifibrotic effects of these compounds. However, there remain two bottlenecks for clinical breakthroughs. The low bioavailability of natural products should be improved, and the combined application of two or more compounds should be investigated for more prominent pharmacological effects. In summary, exploration on natural products against liver fibrosis is becoming increasingly extensive. Therefore, natural products are potential resources for the development of agents to treat liver fibrosis.
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Mohammed SAA, Khan RA, El-Readi MZ, Emwas AH, Sioud S, Poulson BG, Jaremko M, Eldeeb HM, Al-Omar MS, Mohammed HA. Suaeda vermiculata Aqueous-Ethanolic Extract-Based Mitigation of CCl 4-Induced Hepatotoxicity in Rats, and HepG-2 and HepG-2/ADR Cell-Lines-Based Cytotoxicity Evaluations. PLANTS 2020; 9:plants9101291. [PMID: 33003604 PMCID: PMC7601535 DOI: 10.3390/plants9101291] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 09/22/2020] [Accepted: 09/22/2020] [Indexed: 12/16/2022]
Abstract
Suaeda vermiculata, an edible halophytic plant, used by desert nomads to treat jaundice, was investigated for its hepatoprotective bioactivity and safety profile on its mother liquor aqueous-ethanolic extract. Upon LC-MS (Liquid Chromatography-Mass Spectrometry) analysis, the presence of several constituents including three major flavonoids, namely quercetin, quercetin-3-O-rutinoside, and kaempferol-O-(acetyl)-hexoside-pentoside were confirmed. The aqueous-ethanolic extract, rich in antioxidants, quenched the DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, and also showed noticeable levels of radical scavenging capacity in ABTS (2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) assay. For the hepatoprotective activity confirmation, the male rat groups were fed daily, for 7 days (n = 8/group, p.o.), either carboxyl methylcellulose (CMC) 0.5%, silymarin 200 mg/kg, the aqueous-ethanolic extract of the plant Suaeda vermiculata (100, 250, and 500 mg/kg extract), or quercetin (100 mg/kg) alone, and on day 7 of the administrations, all the animal groups, excluding a naïve (250 mg/kg aqueous-ethanolic extract-fed), and an intact animal group were induced hepatotoxicity by intraperitoneally administering carbon tetrachloride (CCl4). All the animals were sacrificed after 24 h, and aspartate transaminase and alanine transaminase serum levels were observed, which were noted to be significantly decreased for the aqueous-ethanolic extract, silymarin, and quercetin-fed groups in comparison to the CMC-fed group (p < 0.0001). No noticeable adverse effects were observed on the liver, kidney, or heart's functions of the naïve (250 mg/kg) group. The aqueous-ethanolic extract was found to be safe in the acute toxicity (5 g/kg) test and showed hepatoprotection and safety at higher doses. Further upon, the cytotoxicity testings in HepG-2 and HepG-2/ADR (Adriamycin resistant) cell-lines were also investigated, and the IC50 values were recorded at 56.19±2.55 µg/mL, and 78.40±0.32 µg/mL (p < 0.001, Relative Resistance RR 1.39), respectively, while the doxorubicin (Adriamycin) IC50 values were found to be 1.3±0.064, and 4.77±1.05 µg/mL (p < 0.001, RR 3.67), respectively. The HepG-2/ADR cell-lines when tested in a combination of the aqueous-ethanolic extract with doxorubicin, a significant reversal in the doxorubicin's IC50 value by 2.77 folds (p < 0.001, CI = 0.56) was noted as compared to the cytotoxicity test where the extract was absent. The mode of action for the reversal was determined to be synergistic in nature indicating the role of the aqueous-ethanolic extract.
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Affiliation(s)
- Salman A. A. Mohammed
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia;
- Correspondence: (S.A.A.M.); (R.A.K.); (H.A.M.); Tel.: +966-(0)530309899 (S.A.A.M.); +966-(0)508384296 (R.A.K.); +966-(0)566176074 (H.A.M.)
| | - Riaz A. Khan
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia;
- Correspondence: (S.A.A.M.); (R.A.K.); (H.A.M.); Tel.: +966-(0)530309899 (S.A.A.M.); +966-(0)508384296 (R.A.K.); +966-(0)566176074 (H.A.M.)
| | - Mahmoud Z. El-Readi
- Department of Clinical Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
- Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
| | - Abdul-Hamid Emwas
- King Abdullah University of Science and Technology (KAUST), Core Labs, Thuwal 23955-6900, Saudi Arabia; (A.-H.E.); (S.S.)
| | - Salim Sioud
- King Abdullah University of Science and Technology (KAUST), Core Labs, Thuwal 23955-6900, Saudi Arabia; (A.-H.E.); (S.S.)
| | - Benjamin G. Poulson
- King Abdullah University of Science and Technology (KAUST), Biological and Environmental Sciences and Engineering Division (BESE), Thuwal, 23955-6900, Saudi Arabia; (B.G.P); (M.J.)
| | - Mariusz Jaremko
- King Abdullah University of Science and Technology (KAUST), Biological and Environmental Sciences and Engineering Division (BESE), Thuwal, 23955-6900, Saudi Arabia; (B.G.P); (M.J.)
| | - Hussein M. Eldeeb
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia;
- Department of Biochemistry, Faculty of Medicine, Al-Azhar University, Assiut, 71524, Egypt
| | - Mohsen S. Al-Omar
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia;
- Medicinal Chemistry and Pharmacognosy Department, Faculty of Pharmacy, JUST, Irbid 22110, Jordan
| | - Hamdoon A. Mohammed
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia;
- Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Cairo, 11371, Egypt
- Correspondence: (S.A.A.M.); (R.A.K.); (H.A.M.); Tel.: +966-(0)530309899 (S.A.A.M.); +966-(0)508384296 (R.A.K.); +966-(0)566176074 (H.A.M.)
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Yang F, Hu S, Sheng X, Liu Y. Naringenin loaded multifunctional nanoparticles to enhance the chemotherapeutic efficacy in hepatic fibrosis. Biomed Microdevices 2020; 22:68. [PMID: 32955605 DOI: 10.1007/s10544-020-00524-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2020] [Indexed: 10/23/2022]
Abstract
Naringenin is highly potent dietary phenolic compound (Flavonoids) found as a major bioactive in citrus fruits. The low solubility of Naringenin, decreases its availability at the site of action by hindering solubility and transportation across the biological membrane. Naringenin loaded nanoparticles enhance the solubility and drug availability at site of action. Naringenin solid lipid nanoparticles were prepared by emulsification and homogenization method using GMO (glycerylmonooleate) and TPGS (Tocopheryl polyethylene glycol succinate) as co-stabilizer. Physico-chemical characterization confirmed the particles were of nanometer size, smooth and spherical morphology. The FTIR and DSC studies conforms that drug and polymers are compatible. The in-vitro study shows prolong and sustained release of Naringenin upto 90 Hrs. In-vivo studies conforms the prolonged and efficient treatment of Hepatic fibrosis. The liver enzymes and pro inflammatory cytokines in blood got significantly reversed with the rats exposed to Naringenin nanoparticle indicating reduced liver damage and fibrosis. Nanoformulation enhances the bioavailability of Naringenin and liver specific delivery of the same, which up-regulates MMP-2 hepatic proteins resulting in reduced liver fibrosis.
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Affiliation(s)
- Fan Yang
- Department of Clinical Nutrition, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China
| | - Shenghe Hu
- Department of Clinical Laboratory, Affiliated Hospital of Dali University, Dali, 671000, China
| | - Xun Sheng
- School of Stomatology, Kunming Medical University, Kunming, 650032, Yunnan Province, China
| | - Yu Liu
- Department of Pharmacy, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, 650032, Yunnan Province, China.
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Naeini F, Namkhah Z, Ostadrahimi A, Tutunchi H, Hosseinzadeh-Attar MJ. A Comprehensive Systematic Review of the Effects of Naringenin, a Citrus-Derived Flavonoid, on Risk Factors for Nonalcoholic Fatty Liver Disease. Adv Nutr 2020; 12:413-428. [PMID: 32879962 PMCID: PMC8009752 DOI: 10.1093/advances/nmaa106] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 06/08/2020] [Accepted: 08/06/2020] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of liver dysfunction worldwide. Recently, some natural compounds have attracted growing interest in the treatment of NAFLD. In this context, most attention has been paid to natural products derived from fruits, vegetables, and medicinal herbs. Naringenin, a natural flavanone, has been revealed to have pharmacological effects in the treatment of obesity and associated metabolic disorders such as NAFLD. The aim of this study was to examine the therapeutic effects of naringenin and its possible mechanisms of action in the management of NAFLD and related risk factors. The current systematic review was performed according to the guidelines of the 2015 PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statements. We searched PubMed/Medline, Science Direct, Scopus, ProQuest, and Google Scholar databases up until February 2020. Of 1217 full-text articles assessed, 36 studies met the inclusion criteria. The evidence reviewed in the present study indicates that naringenin modulates several biological processes related to NAFLD including energy balance, lipid and glucose metabolism, inflammation, and oxidative stress by different mechanisms. Overall, the favorable effects of naringenin along with its more potency and efficacy, compared with other antioxidants, indicate that naringenin may be a promising therapeutic approach for the management of NAFLD and associated complications. However, due to the lack of clinical trials, future robust human randomized clinical trials that address the effects of naringenin on NAFLD and other liver-related diseases are crucial. Further careful human pharmacokinetic studies are also needed to establish dosage ranges, as well as addressing preliminary safety and tolerability of naringenin, before proceeding to larger-scale endpoint trials.
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Affiliation(s)
- Fatemeh Naeini
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
| | - Zahra Namkhah
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Science, Tehran, Iran
| | - Alireza Ostadrahimi
- Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Li D, Song Y, Wang Y, Guo Y, Zhang Z, Yang G, Wang G, Xu C. Nos2 deficiency enhances carbon tetrachloride-induced liver injury in aged mice. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2020; 23:600-605. [PMID: 32742597 PMCID: PMC7374991 DOI: 10.22038/ijbms.2020.39528.9380] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Objective(s): As a multifunctional molecule, NO has different effects on liver injury. The present work aimed to investigate the effects of Nos2 knockout (KO) on acute liver injury in aged mice treated with carbon tetrachloride (CCl4). Materials and Methods: The acute liver injury model was produced by CCl4 at 10 ml/kg body weight in 24-month-old Nos2 KO mice and wild type (WT) mice groups. The histological changes, transaminase and glutathione (GSH) contents, and the expressions of liver function genes superoxide dismutase (SOD2) and butyrylcholinesterase (BCHE), as well as apoptosis- and inflammation-associated genes were detected at 0, 6, 16, 20, 28, and 48 hr, respectively. Results: Compared with WT aged mice, there are more fat droplets in liver tissues of Nos2 KO aged mice, and the serum levels of ALT and AST were elevated in the KO group; in addition, there was a decrease in the expression of SOD2 and BCHE and GSH content at multiple time-points. Furthermore, the expression of apoptosis protein CASPASE-3 was elevated from 20 to 48 hr, the same as CASPASE-9 at 28 and 48 hr and pro-apoptotic protein BAX at 6 and 28 hr, while the expression of apoptosis inhibitory protein BCL2 declined at 6 and 28 hr; at the same time the mRNA expressions of genes related to inflammation were increased at different extents in liver extracts of Nos2 KO aged mice. Conclusion: Nos2 KO exacerbated liver injury probably by elevated oxidative stress, apoptosis and inflammation response in CCl4-induced aged mice liver intoxication model.
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Affiliation(s)
- Deming Li
- State Key Laboratory Cell Differentiation and Regulation, Xinxiang, Henan, China.,Henan International Joint Laboratory of Pulmonary Fibrosis.,Henan center for outstanding overseas scientists of pulmonary fibrosis, Xinxiang, Henan, China.,College of Life Science, Xinxiang, Henan, China.,Institute of Biomedical Science, Xinxiang, Henan, China.,Overseas Expertise Introduction Center for Discipline Innovation of Pulmonary Fibrosis (111 Project), Henan Normal University, Xinxiang, Henan, China
| | - Yaping Song
- State Key Laboratory Cell Differentiation and Regulation, Xinxiang, Henan, China.,Henan International Joint Laboratory of Pulmonary Fibrosis.,Henan center for outstanding overseas scientists of pulmonary fibrosis, Xinxiang, Henan, China.,College of Life Science, Xinxiang, Henan, China.,Institute of Biomedical Science, Xinxiang, Henan, China.,Overseas Expertise Introduction Center for Discipline Innovation of Pulmonary Fibrosis (111 Project), Henan Normal University, Xinxiang, Henan, China
| | - Yahao Wang
- State Key Laboratory Cell Differentiation and Regulation, Xinxiang, Henan, China.,Henan International Joint Laboratory of Pulmonary Fibrosis.,Henan center for outstanding overseas scientists of pulmonary fibrosis, Xinxiang, Henan, China.,College of Life Science, Xinxiang, Henan, China.,Institute of Biomedical Science, Xinxiang, Henan, China.,Overseas Expertise Introduction Center for Discipline Innovation of Pulmonary Fibrosis (111 Project), Henan Normal University, Xinxiang, Henan, China
| | - Yuedong Guo
- State Key Laboratory Cell Differentiation and Regulation, Xinxiang, Henan, China.,Henan International Joint Laboratory of Pulmonary Fibrosis.,Henan center for outstanding overseas scientists of pulmonary fibrosis, Xinxiang, Henan, China.,College of Life Science, Xinxiang, Henan, China.,Institute of Biomedical Science, Xinxiang, Henan, China.,Overseas Expertise Introduction Center for Discipline Innovation of Pulmonary Fibrosis (111 Project), Henan Normal University, Xinxiang, Henan, China
| | - Zhaoke Zhang
- State Key Laboratory Cell Differentiation and Regulation, Xinxiang, Henan, China.,Henan International Joint Laboratory of Pulmonary Fibrosis.,Henan center for outstanding overseas scientists of pulmonary fibrosis, Xinxiang, Henan, China.,College of Life Science, Xinxiang, Henan, China.,Institute of Biomedical Science, Xinxiang, Henan, China.,Overseas Expertise Introduction Center for Discipline Innovation of Pulmonary Fibrosis (111 Project), Henan Normal University, Xinxiang, Henan, China
| | - Ganggang Yang
- State Key Laboratory Cell Differentiation and Regulation, Xinxiang, Henan, China.,Henan International Joint Laboratory of Pulmonary Fibrosis.,Henan center for outstanding overseas scientists of pulmonary fibrosis, Xinxiang, Henan, China.,College of Life Science, Xinxiang, Henan, China.,Institute of Biomedical Science, Xinxiang, Henan, China.,Overseas Expertise Introduction Center for Discipline Innovation of Pulmonary Fibrosis (111 Project), Henan Normal University, Xinxiang, Henan, China
| | - Gaiping Wang
- State Key Laboratory Cell Differentiation and Regulation, Xinxiang, Henan, China.,Henan International Joint Laboratory of Pulmonary Fibrosis.,Henan center for outstanding overseas scientists of pulmonary fibrosis, Xinxiang, Henan, China.,College of Life Science, Xinxiang, Henan, China.,Institute of Biomedical Science, Xinxiang, Henan, China.,Overseas Expertise Introduction Center for Discipline Innovation of Pulmonary Fibrosis (111 Project), Henan Normal University, Xinxiang, Henan, China
| | - Cunshuan Xu
- State Key Laboratory Cell Differentiation and Regulation, Xinxiang, Henan, China.,Henan International Joint Laboratory of Pulmonary Fibrosis.,Henan center for outstanding overseas scientists of pulmonary fibrosis, Xinxiang, Henan, China.,College of Life Science, Xinxiang, Henan, China.,Institute of Biomedical Science, Xinxiang, Henan, China.,Overseas Expertise Introduction Center for Discipline Innovation of Pulmonary Fibrosis (111 Project), Henan Normal University, Xinxiang, Henan, China
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Md S, Alhakamy NA, Akhter S, Awan ZAY, Aldawsari HM, Alharbi WS, Haque A, Choudhury H, Sivakumar PM. Development of Polymer and Surfactant Based Naringenin Nanosuspension for Improvement of Stability, Antioxidant, and Antitumour Activity. J CHEM-NY 2020; 2020:1-10. [DOI: 10.1155/2020/3489393] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2025] Open
Abstract
Nanosuspensions are widely reported to enhance the solubility of poorly soluble drugs. In addition to enhancement in solubility, improvement of stability and therapeutic efficacy would be an added advantage. In the present study, premilling and subsequent high-pressure homogenization were carried out to produce naringenin nanosuspension. Hydroxypropyl methylcellulose and sodium dodecyl sulfate were evaluated for their performance as stabilizers under various homogenization cycles. The prepared nanosuspensions were studied for average particle size and size distribution, zeta potential, solubility, drug release, antioxidant activity, and in vitro antitumor activity. It was observed that both hydroxypropyl methylcellulose-stabilized nanosuspension and sodium dodecyl sulfate-stabilized nanosuspension produced an enhancement in physical stability, antioxidant potential, and in vitro cytotoxicity compared with naringenin. Furthermore, hydroxypropyl methylcellulose-stabilized nanosuspension was found to be better than sodium dodecyl sulfate-stabilized nanosuspension in terms of particle size and size distribution, storage stability, and drug release. This study showed that nanosuspension formulations could be a potential strategy for improving dissolution and antitumor activity of naringenin.
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Affiliation(s)
- Shadab Md
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
- Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nabil A. Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
- Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sohail Akhter
- Department of New Product Development, Combination Product & Devices, Global R&D, Teva Pharmaceuticals, Runcorn, UK
| | - Zuhier A. Y. Awan
- Department of Medicine and Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Hibah M. Aldawsari
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
- Center of Excellence for Drug Research & Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Waleed S. Alharbi
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Anzarul Haque
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj, Saudi Arabia
| | - Hira Choudhury
- Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Jalan Jalil Perkasa, Bukit Jalil, Kuala Lumpur 57000, Malaysia
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Naringin nano-ethosomal novel sunscreen creams: Development and performance evaluation. Colloids Surf B Biointerfaces 2020; 193:111122. [PMID: 32498002 DOI: 10.1016/j.colsurfb.2020.111122] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 12/24/2019] [Accepted: 05/07/2020] [Indexed: 02/06/2023]
Abstract
Long term exposure of skin to UV rays produces detrimental effects such as premature skin-ageing and skin cancer. Although, zinc oxide (ZnO) and titanium dioxide (TiO2) are good sunscreen agents, they do not provide highly efficient UV radiation protection and antioxidant and anti-aging effects. The present study was aimed at developing and characterizing ethosomes loaded with naringin and then to incorporate them into sunscreen creams containing nano-ZnO and -TiO2 to achieve adequate skin penetration and skin retention so as to scavenge the free radicals by virtue of naringin's antioxidant property. Ethosomes were prepared and optimized with respect to concentrations of ethanol and cholesterol, time of sonication, drug and lipid ratio and amount of drug. The ethosomes were evaluated for size, zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency and surface morphology. Ethosomal sunscreen creams were evaluated for physicochemical tests, spreadability, antioxidant, cytotoxicity and skin permeation studies. Optimized ethosomal formulation exhibited average vesicle size, PDI, ZP and drug encapsulation efficiency of 142.5 ± 5.6 nm, 0.199 ± 0.007, -72.5 ± 2.9 mV and 33.79 ± 1.35%, respectively. Naringin ethosomes showed enhanced retention in the skin (403.44 ± 15.33 μg/cm2) compared to naringin suspension (202.81 ± 9.45 μg/cm2). The optimized sunscreen cream exhibited SPF of 21.21 ± 0.62 with negligible permeation of naringin across the skin. Ethosomes showed pronounced skin permeation for naringin and optimized cream containing naringin ethosomes along with nano- ZnO and TiO2 showed good skin retention for naringin.
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