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Wang Y, An J, Zhou J, Chang L, Zhang Q, Peng F. Hydroxysafflor yellow A: a natural pigment with potential anticancer therapeutic effect. Front Pharmacol 2025; 15:1495393. [PMID: 39877386 PMCID: PMC11772350 DOI: 10.3389/fphar.2024.1495393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 12/23/2024] [Indexed: 01/31/2025] Open
Abstract
Hydroxysafflor yellow A (HSYA), a natural pigment with a chalcone structure extracted from Carthamus tinctorius L. (Safflower), has been widely proven to have good efficacy on cardiovascular diseases, atherosclerosis, cancer, and diabetes. However, no study has reported on the anticancer mechanisms of Hydroxysafflor yellow A (HSYA), a principal bioactive compound in safflower. This review discusses recent developments in the physicochemical properties and sources, pharmacological effects and mechanisms, pharmacokinetic progress, and safety of HSYA, focusing on the involvement of HSYA in the regulation of related pathways and mechanisms of apoptosis, autophagy, and the tumor immune microenvironment in a variety of cancers. This can serve as a theoretical basis for further research and development of HSYA, with insights into the mechanisms of anticancer signaling pathways.
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Affiliation(s)
- Yuhan Wang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Department of Pharmacy, West China Hospital, Chengdu, China
| | - Junsha An
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Department of Pharmacy, West China Hospital, Chengdu, China
| | - Jianbo Zhou
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Department of Pharmacy, West China Hospital, Chengdu, China
| | - Liming Chang
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Department of Pharmacy, West China Hospital, Chengdu, China
| | - Quan Zhang
- Sichuan Province College Key Laboratory of Structure-Specific Small Molecule Drugs, School of Pharmacy, Chengdu Medical College, Institute of Materia Medica, Chengdu, China
- Development and Regeneration Key Lab of Sichuan Province, Department of Pathology, Chengdu Medical College, Chengdu, China
- Development and Regeneration Key Lab of Sichuan Province, Department of Anatomy and Histology and Embryology, Chengdu Medical College, Chengdu, China
| | - Fu Peng
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Department of Pharmacy, West China Hospital, Chengdu, China
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Xu TT, Deng YY, Yu XY, Li M, Fu YY. Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential. Acta Pharmacol Sin 2025; 46:8-32. [PMID: 39090393 PMCID: PMC11697321 DOI: 10.1038/s41401-024-01356-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 07/04/2024] [Indexed: 08/04/2024]
Abstract
Non-communicable diseases (NCDs) are defined as a kind of diseases closely related to bad behaviors and lifestyles, e.g., cardiovascular diseases, cancer, and diabetes. Driven by population growth and aging, NCDs have become the biggest disease burden in the world, and it is urgent to prevent and control these chronic diseases. Autophagy is an evolutionarily conserved process that degrade cellular senescent or malfunctioning organelles in lysosomes. Mounting evidence has demonstrated a major role of autophagy in the pathogenesis of cardiovascular diseases, cancer, and other major human diseases, suggesting that autophagy could be a candidate therapeutic target for NCDs. Natural products/phytochemicals are important resources for drugs against a wide variety of diseases. Recently, compounds from natural plants, such as resveratrol, curcumin, and ursolic acid, have been recognized as promising autophagy modulators. In this review, we address recent advances and the current status of the development of natural autophagy modulators in NCDs and provide an update of the latest in vitro and in vivo experiments that pave the way to clinical studies. Specifically, we focus on the relationship between natural autophagy modulators and NCDs, with an intent to identify natural autophagy modulators with therapeutic potential.
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Affiliation(s)
- Ting-Ting Xu
- NMPA Key Laboratory for Clinical Research and Evaluation of Drug for Thoracic Diseases, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China
| | - Ying-Yi Deng
- NMPA Key Laboratory for Clinical Research and Evaluation of Drug for Thoracic Diseases, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China
| | - Xi-Yong Yu
- NMPA Key Laboratory for Clinical Research and Evaluation of Drug for Thoracic Diseases, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
| | - Min Li
- School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-Sen University, Guangzhou, 510006, China.
| | - Yuan-Yuan Fu
- NMPA Key Laboratory for Clinical Research and Evaluation of Drug for Thoracic Diseases, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
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Cao Z, Tian K, Ran Y, Zhou H, Zhou L, Ding Y, Tang X. Beclin-1: a therapeutic target at the intersection of autophagy, immunotherapy, and cancer treatment. Front Immunol 2024; 15:1506426. [PMID: 39650649 PMCID: PMC11621085 DOI: 10.3389/fimmu.2024.1506426] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 11/01/2024] [Indexed: 12/11/2024] Open
Abstract
The significant identification of Beclin-1's function in regulating autophagy flow signified a significant progression in our understanding of cellular operations. Beclin-1 acts as a scaffold for forming the PI3KC3 complex, controlling autophagy and cellular trafficking processes in a complicated way. This intricate protein has garnered considerable attention due to its substantial impact on the development of tumors. Strong evidence indicates Beclin-1 plays a critical role in controlling autophagy in various human cancer types and its intricate connection with apoptosis and ferroptosis. The potential of Beclin-1 as a viable target for cancer therapy is highlighted by its associations with key autophagy regulators such as AMPK, mTOR, and ATGs. Beclin-1 controls the growth and dissemination of tumors by autophagy. It also affects how tumors react to therapies such as chemotherapy and radiation therapy. The role of Beclin-1 in autophagy can influence apoptosis, depending on whether it supports cell survival or leads to cell death. Beclin-1 plays a crucial role in ferroptosis by increasing ATG5 levels, which in turn promotes autophagy-triggered ferroptosis. Finally, we analyzed the possible function of Beclin-1 in tumor immunology and drug sensitivity in cancers. In general, Beclin-1 has a significant impact on regulating autophagy, offering various potentials for medical intervention and altering our understanding of cancer biology.
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Affiliation(s)
- Zhumin Cao
- Department of Hepatobiliary Surgery, The Seventh People’s Hospital of Chongqing, Chongqing, China
| | - Ke Tian
- Department of Hepatobiliary Surgery, The Seventh People’s Hospital of Chongqing, Chongqing, China
| | - Yincheng Ran
- Department of Hepatobiliary Surgery, The Seventh People’s Hospital of Chongqing, Chongqing, China
| | - Haonan Zhou
- Department of Hepatobiliary Surgery, The Seventh People’s Hospital of Chongqing, Chongqing, China
| | - Lei Zhou
- Department of Hepatobiliary Surgery, The Seventh People’s Hospital of Chongqing, Chongqing, China
| | - Yana Ding
- Department of Hepatobiliary Surgery, District Traditional Chinese Medicine Hospital, Chongqing, China
| | - Xiaowei Tang
- Department of Hepatobiliary Surgery, District Traditional Chinese Medicine Hospital, Chongqing, China
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Cheng H, Yang C, Ge P, Liu Y, Zafar MM, Hu B, Zhang T, Luo Z, Lu S, Zhou Q, Jaleel A, Ren M. Genetic diversity, clinical uses, and phytochemical and pharmacological properties of safflower ( Carthamus tinctorius L.): an important medicinal plant. Front Pharmacol 2024; 15:1374680. [PMID: 38799156 PMCID: PMC11127628 DOI: 10.3389/fphar.2024.1374680] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 04/22/2024] [Indexed: 05/29/2024] Open
Abstract
Safflower (Carthamus tinctorius L.), a member of the Asteraceae family, is widely used in traditional herbal medicine. This review summarized agronomic conditions, genetic diversity, clinical application, and phytochemicals and pharmacological properties of safflower. The genetic diversity of the plant is rich. Abundant in secondary metabolites like flavonoids, phenols, alkaloids, polysaccharides, fatty acids, polyacetylene, and other bioactive components, the medicinal plant is effective for treating cardiovascular diseases, neurodegenerative diseases, and respiratory diseases. Especially, Hydroxysafflor yellow A (HYSA) has a variety of pharmacological effects. In terms of treatment and prevention of some space sickness in space travel, safflower could be a potential therapeutic agent. Further studies are still required to support the development of safflower in medicine. Our review indicates that safflower is an important medicinal plant and research prospects regarding safflower are very broad and worthy of further investigation.
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Affiliation(s)
- Hao Cheng
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science and Technology Center, Chengdu, China
| | - Chenglong Yang
- School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Pengliang Ge
- College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Yi Liu
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science and Technology Center, Chengdu, China
| | - Muhammad Mubashar Zafar
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science and Technology Center, Chengdu, China
| | - Beibei Hu
- School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
| | - Tong Zhang
- Chengdu Florascape Technology Service Center, Chengdu, China
| | - Zengchun Luo
- Chengdu Florascape Technology Service Center, Chengdu, China
| | - Siyu Lu
- Chengdu Florascape Technology Service Center, Chengdu, China
| | - Qin Zhou
- Chengdu Florascape Technology Service Center, Chengdu, China
| | - Abdul Jaleel
- Department of Integrative Agriculture, College of Agriculture and Veterinary Medicine, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Maozhi Ren
- Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu National Agricultural Science and Technology Center, Chengdu, China
- School of Agricultural Sciences, Zhengzhou University, Zhengzhou, China
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Islam MR, Rauf A, Alash S, Fakir MNH, Thufa GK, Sowa MS, Mukherjee D, Kumar H, Hussain MS, Aljohani ASM, Imran M, Al Abdulmonem W, Thiruvengadam R, Thiruvengadam M. A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways. Med Oncol 2024; 41:134. [PMID: 38703282 DOI: 10.1007/s12032-024-02333-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 02/13/2024] [Indexed: 05/06/2024]
Abstract
Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.
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Affiliation(s)
- Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23561, Khyber Pakhtunkhwa, Pakistan.
| | - Shopnil Alash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Md Naeem Hossain Fakir
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Gazi Kaifeara Thufa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Mahbuba Sharmin Sowa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Dattatreya Mukherjee
- Raiganj Government Medical College and Hospital, Pranabananda Sarani, Raiganj, 733134, West Bengal, India
| | - Harendra Kumar
- Dow University of Health Sciences, Mission Rd, New Labour Colony Nanakwara, Karachi, 74200, Sindh, Pakistan
| | - Md Sadique Hussain
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, 302017, Rajasthan, India
| | - Abdullah S M Aljohani
- Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Muhammad Imran
- Chemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, 61413, Abha, Saudi Arabia
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Rekha Thiruvengadam
- Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical & Technical Sciences (SIMATS), Saveetha University, Chennai, 600077, Tamil Nadu, India.
| | - Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, 05029, South Korea
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Batudeligen, Han Z, Chen H, Narisu, Xu Y, Anda, Han G. Luteolin Alleviates Liver Fibrosis in Rat Hepatic Stellate Cell HSC-T6: A Proteomic Analysis. Drug Des Devel Ther 2023; 17:1819-1829. [PMID: 37360572 PMCID: PMC10285022 DOI: 10.2147/dddt.s402864] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 05/23/2023] [Indexed: 12/31/2023] Open
Abstract
BACKGROUND Traditional Chinese medicine (TCM) with single or compound materials is an effective cure for liver fibrosis. Hepatic stellate cells (HSCs) play a key role in liver fibrosis pathology and have become a novel drug target for this condition. METHODS CCK-8 assay was used to determine the cytotoxicity of four components, SYPA, HSYPA, Apigenin, and Luteolin, from Deduhonghua-7 powder on HSC-T6 cells. Transforming Growth Factor β 1 (TGFβ1)-induced fibrotic cell model and CCI4-induced fibrotic rat model were constructed, the expression of fibrosis-related genes, the pathological changes and serum biochemical markers were evaluated. Proteomic analysis was performed to determine the mechanism by which luteolin attenuated liver fibrosis, which were further confirmed by Western blot. RESULTS Luteolin attenuates liver fibrosis in HSC-T6 cells and luteolin decreases the liver fibrosis index level in vivo. A total of 5000 differentially expressed proteins (DEPs) were obtained using proteomic analysis. KEGG analysis found that DEPs were concentrated in various metabolic pathways, including DNA replication and repair and lysosomal signaling. GO analysis showed that molecular functions included the activity and binding of various enzymes, related cellular components included the extracellular space, lysosomal lumen, mitochondrial matrix, and nucleus, and biological processes included collagen organization and biosynthesis and the positive regulation of cell migration. Western blot results showed that CCR1, CD59, and NAGA were downregulated in TGFβ1 treatment, while upregulated both in Lut2 and Lut10 treatment. Meanwhile, eight proteins, ITIH3, MKI67, KIF23, DNMT1, P4HA3, CCDC80, APOB, FBLN2, that were upregulated in TGFβ1 treatment, while downregulated both in Lut2 and Lut10 treatment. CONCLUSION Luteolin was shown to have a strong protective effect on liver fibrosis. CCR1, CD59, and NAGA may promote liver fibrosis while ITIH3, MKI67, KIF23, DNMT1, P4HA3, CCDC80, APOB, and FBLN2 may facilitate protection against fibrosis.
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Affiliation(s)
- Batudeligen
- Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao City, Inner Mongolia, People’s Republic of China
| | - Zhiqiang Han
- Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao City, Inner Mongolia, People’s Republic of China
| | - Hongmei Chen
- Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao City, Inner Mongolia, People’s Republic of China
| | - Narisu
- Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao City, Inner Mongolia, People’s Republic of China
| | - Yanhua Xu
- Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao City, Inner Mongolia, People’s Republic of China
| | - Anda
- Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao City, Inner Mongolia, People’s Republic of China
| | - Gegentaoli Han
- Institute of Clinical Pharmacology of Traditional Mongolian Medicine, Affiliated Hospital of Inner Mongolia Minzu University, Tongliao City, Inner Mongolia, People’s Republic of China
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Alharbi KS, Almalki WH, Albratty M, Meraya AM, Najmi A, Vyas G, Singh SK, Dua K, Gupta G. The therapeutic role of nutraceuticals targeting the Nrf2/HO-1 signaling pathway in liver cancer. J Food Biochem 2022; 46:e14357. [PMID: 35945911 DOI: 10.1111/jfbc.14357] [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] [Received: 05/26/2022] [Revised: 07/01/2022] [Accepted: 07/19/2022] [Indexed: 11/28/2022]
Abstract
Liver cancer (L.C.) is the most common cause of cancer death in the United States and the fifth most common globally. The overexpression of nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) caused by oxidative stress has been associated with tumor growth, aggressiveness, treatment resistance, and poor prognosis. Nutraceuticals that inhibit Nrf2/HO-1 signaling may become the most effective strategy to treat liver cancer. Phytochemicals found in fruits and vegetables, also known as nutraceuticals, tend to emerge as chemopreventive agents, with the added benefit of low toxicity and high nutritional values. This paper reviews the present scientific knowledge of the Nrf2/HO-1 signaling as a possible target molecule for chemotherapeutic agents, its basic control mechanisms, and Nrf2/HO-1 inducers produced from natural products that might be employed as cancer chemopreventive drugs. The growing interest in the contribution of the Nrf2/ARE/HO-1 signaling in the development of liver cancer and the Use of nutraceuticals to treat liver cancer by targeting Nrf2/ARE/HO-1. PRACTICAL APPLICATIONS: An increase in Nrf2 expression indicates that Nrf2 is the most important player in liver cancer. Cancer patients are more resistant to chemotherapy because of this erroneous Nrf2 signaling. Furthermore, an increasing body of evidence indicates that activation of the Nrf2/HO-1 pathway results in the production of phase II detoxifying and antioxidant enzymes, which serve a defense purpose in cells. As a consequence, treating liver cancer. This master regulator may be a possibility. Nutraceuticals that reduce Nrf2/HO-1 signaling may be the most effective strategy for preventing liver cancer. The methods of action of numerous natural substances are examined in this article.
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Affiliation(s)
- Khalid Saad Alharbi
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Mohammed Albratty
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Abdulkarim M Meraya
- Pharmacy Practice Research Unit, Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Asim Najmi
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Govind Vyas
- R&D, Quality and Regulatory Compliance, Invahealth Inc., Cranbury, New Jersey, USA
| | - Sachin Kumar Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.,Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, New South Wales, Australia
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, New South Wales, Australia.,Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, New South Wales, Australia
| | - Gaurav Gupta
- Department of Pharmacology, School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India.,Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.,Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
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Michalkova R, Kello M, Kudlickova Z, Gazdova M, Mirossay L, Mojzisova G, Mojzis J. Programmed Cell Death Alterations Mediated by Synthetic Indole Chalcone Resulted in Cell Cycle Arrest, DNA Damage, Apoptosis and Signaling Pathway Modulations in Breast Cancer Model. Pharmaceutics 2022; 14:503. [PMID: 35335879 PMCID: PMC8953149 DOI: 10.3390/pharmaceutics14030503] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 02/18/2022] [Accepted: 02/22/2022] [Indexed: 11/28/2022] Open
Abstract
Although new chemotherapy significantly increased the survival of breast cancer (BC) patients, the use of these drugs is often associated with serious toxicity. The discovery of novel anticancer agents for BC therapy is expected. This study was conducted to explore the antiproliferative effect of newly synthesized indole chalcone derivative ZK-CH-11d on human BC cell lines. MTT screening, flow cytometry, Western blot, and fluorescence microscopy were used to evaluate the mode of cell death. ZK-CH-11d significantly suppressed the proliferation of BC cells with minimal effect against non-cancer cells. This effect was associated with cell cycle arrest at the G2/M phase and apoptosis induction. Apoptosis was associated with cytochrome c release, increased activity of caspase 3 and caspase 7, PARP cleavage, reduced mitochondrial membrane potential, and activation of the DNA damage response system. Furthermore, our study demonstrated that ZK-CH-11d increased the AMPK phosphorylation with simultaneous inhibition of the PI3K/Akt/mTOR pathway indicating autophagy initiation. However, chloroquine, an autophagy inhibitor, significantly potentiated the cytotoxic effect of ZK-CH-11d in MDA-MB-231 cells indicating that autophagy is not principally involved in the antiproliferative effect of ZK-CH-11d. Taking together the results from our experiments, we assume that autophagy was activated as a defense mechanism in treated cells trying to escape from chalcone-induced harmful effects.
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Affiliation(s)
- Radka Michalkova
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia; (R.M.); (M.G.); (L.M.)
| | - Martin Kello
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia; (R.M.); (M.G.); (L.M.)
| | - Zuzana Kudlickova
- NMR Laboratory, Institute of Chemistry, Faculty of Science, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia;
| | - Maria Gazdova
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia; (R.M.); (M.G.); (L.M.)
| | - Ladislav Mirossay
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia; (R.M.); (M.G.); (L.M.)
| | - Gabriela Mojzisova
- Department of Experimental Medicine, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia;
| | - Jan Mojzis
- Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Kosice, Slovakia; (R.M.); (M.G.); (L.M.)
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9
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Bao X, Chen L, Liu Y, Sheng H, Wang K, Luo Y, Qin T, Liu Y, Qiu Y. Treatment of Liver Cancer: Role of the Traditional Mongolian Medicine. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:6535977. [PMID: 35198036 PMCID: PMC8860509 DOI: 10.1155/2022/6535977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 01/19/2022] [Indexed: 11/18/2022]
Abstract
Liver cancer is an extraordinarily heterogeneous malignancy with relatively high mortality and increasing incidence rate among the so far identified cancers. Improvements in liver cancer therapy have been made in the past decades, but therapeutics against liver cancer are still limited. Traditional Mongolian Medicine, formed and developed by the Mongolian people to maintain health in the medical practice of fighting against diseases, has been recognized as one of the key components of the world healthcare system. Traditional Mongolian Medicine has been used to treat various malignancies, including liver cancer, for a long time in Asia and its advantages have become more and more apparent. Herein, this review made a comprehensive summary of Traditional Mongolian Medicine, including the ideas in the liver cancer treatment, sources of medicines or prescriptions, traditional applications, modern pharmacological research, chemical structure and mechanisms of several monomer compounds isolated from Traditional Mongolian Medicine, with a view to finding promising drugs against liver cancer and expanding the clinical application of Traditional Mongolian Medicine in liver cancer therapy.
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Affiliation(s)
- Xiaomei Bao
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- School of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Lu Chen
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yiman Liu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Hua Sheng
- School of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Kailong Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yanming Luo
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Tongling Qin
- School of Pharmacy, Tianjin Medical University, Tianjin, China
| | - Ying Liu
- School of Pharmacy, Tianjin Medical University, Tianjin, China
| | - Yuling Qiu
- School of Pharmacy, Tianjin Medical University, Tianjin, China
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Huo C, Wang L, Wang Q, Yang Y, Chen B. Hydroxysafflor Yellow A inhibits the viability and migration of vascular smooth muscle cells induced by serum from rats with chronic renal failure via inactivation of the PI3K/Akt signaling pathway. Exp Ther Med 2021; 22:850. [PMID: 34149896 PMCID: PMC8210222 DOI: 10.3892/etm.2021.10282] [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: 10/30/2020] [Accepted: 05/19/2021] [Indexed: 12/15/2022] Open
Abstract
It has been reported that the viability and migration of vascular smooth muscle cells contributes to arteriovenous fistula stenosis. Hydroxysafflor Yellow A (HSYA) has been demonstrated to inhibit the viability and migration of VSMCs by regulating Akt signaling. The present study aimed to investigate the role of HSYA on the viability and migration of human umbilical vein smooth muscle cells (HUVSMCs) following stimulation using serum from rats with chronic renal failure (CRF), and to determine the effects of HSYA on PI3K/Akt signaling. Wistar rats were randomly divided into two groups, control and CRF groups. Serum from each group was collected to stimulate the HUVSMCs. Cell Counting Kit-8 and wound healing assays were performed to assess cell viability and migration, respectively. Flow cytometry analysis was performed to assess apoptosis, and western blot analysis was performed to detect protein expression levels of PI3K and Akt. Nitric oxide (NO) production was measured using the Nitrate/Nitrite assay kit. The results demonstrated that serum from CRF rats significantly enhanced cell viability, migration and apoptosis, the effects of which were reversed following treatment with HSYA. In addition, CRF serum decreased NO and endothelial NO synthase expression, whilst increasing the protein expression levels of PI3K and phosphorylated-Akt in HUVSMCs. Notably, treatment with HSYA markedly restored NO production and inactivated the PI3K/Akt signaling pathway. Furthermore, the PI3K/Akt inhibitor, AMG511, exerted similar effects to HSYA. Taken together, the results of the present study suggest that HSYA suppresses cell viability and migration in the presence of CRF serum by inactivating the PI3K/Akt signaling pathway.
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Affiliation(s)
- Changliang Huo
- Department of Nephrology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu 222000, P.R. China
| | - Li Wang
- Department of Nephrology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu 222000, P.R. China
| | - Qiuli Wang
- Department of Nephrology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu 222000, P.R. China
| | - Yanbo Yang
- Department of Nephrology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu 222000, P.R. China
| | - Bo Chen
- Department of Nephrology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang, Jiangsu 222000, P.R. China
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Michalkova R, Mirossay L, Gazdova M, Kello M, Mojzis J. Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones. Cancers (Basel) 2021; 13:cancers13112730. [PMID: 34073042 PMCID: PMC8198114 DOI: 10.3390/cancers13112730] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/20/2021] [Accepted: 05/27/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Despite the important progress in cancer treatment in the past decades, the mortality rates in some types of cancer have not significantly decreased. Therefore, the search for novel anticancer drugs has become a topic of great interest. Chalcones, precursors of flavonoid synthesis in plants, have been documented as natural compounds with pleiotropic biological effects including antiproliferative/anticancer activity. This article focuses on the knowledge on molecular mechanisms of antiproliferative action of chalcones and draws attention to this group of natural compounds that may be of importance in the treatment of cancer disease. Abstract Although great progress has been made in the treatment of cancer, the search for new promising molecules with antitumor activity is still one of the greatest challenges in the fight against cancer due to the increasing number of new cases each year. Chalcones (1,3-diphenyl-2-propen-1-one), the precursors of flavonoid synthesis in higher plants, possess a wide spectrum of biological activities including antimicrobial, anti-inflammatory, antioxidant, and anticancer. A plethora of molecular mechanisms of action have been documented, including induction of apoptosis, autophagy, or other types of cell death, cell cycle changes, and modulation of several signaling pathways associated with cell survival or death. In addition, blockade of several steps of angiogenesis and proteasome inhibition has also been documented. This review summarizes the basic molecular mechanisms related to the antiproliferative effects of chalcones, focusing on research articles from the years January 2015–February 2021.
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Bioactive Substances in Safflower Flowers and Their Applicability in Medicine and Health-Promoting Foods. INTERNATIONAL JOURNAL OF FOOD SCIENCE 2021; 2021:6657639. [PMID: 34136564 PMCID: PMC8175185 DOI: 10.1155/2021/6657639] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 04/15/2021] [Accepted: 05/05/2021] [Indexed: 12/17/2022]
Abstract
Safflower flowers (Carthamus tinctorius) contain many natural substances with a wide range of economic uses. The most famous dye isolated from flower petals is hydroxysafflor A (HSYA), which has antibacterial, anti-inflammatory, and antioxidant properties. This review is aimed at updating the state of knowledge about their applicability in oncology, pulmonology, cardiology, gynecology, dermatology, gastrology, immunology, and suitability in the treatment of obesity and diabetes and its consequences with information published mainly in 2018-2020. They were also effective in treating obesity and diabetes and its consequences. The issues related to the possibilities of using HSYA in the production of health-promoting food were also analyzed.
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Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer. Biomolecules 2021; 11:biom11020135. [PMID: 33494431 PMCID: PMC7911475 DOI: 10.3390/biom11020135] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 01/11/2021] [Accepted: 01/18/2021] [Indexed: 12/13/2022] Open
Abstract
Autophagy, which is a conserved biological process and essential mechanism in maintaining homeostasis and metabolic balance, enables cells to degrade cytoplasmic constituents through lysosomes, recycle nutrients, and survive during starvation. Autophagy exerts an anticarcinogenic role in normal cells and inhibits the malignant transformation of cells. On the other hand, aberrations in autophagy are involved in gene derangements, cell metabolism, the process of tumor immune surveillance, invasion and metastasis, and tumor drug-resistance. Therefore, autophagy-targeted drugs may function as anti-tumor agents. Accumulating evidence suggests that flavonoids have anticarcinogenic properties, including those relating to cellular proliferation inhibition, the induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, the impairment of cell migration, invasion, tumor angiogenesis, and the reduction of multidrug resistance in tumor cells. Flavonoids, which are a group of natural polyphenolic compounds characterized by multiple targets that participate in multiple pathways, have been widely studied in different models for autophagy modulation. However, flavonoid-induced autophagy commonly interacts with other mechanisms, comprehensively influencing the anticancer effect. Accordingly, targeted autophagy may become the core mechanism of flavonoids in the treatment of tumors. This paper reviews the flavonoid-induced autophagy of tumor cells and their interaction with other mechanisms, so as to provide a comprehensive and in-depth account on how flavonoids exert tumor-suppressive effects through autophagy.
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Zhao F, Wang P, Jiao Y, Zhang X, Chen D, Xu H. Hydroxysafflor Yellow A: A Systematical Review on Botanical Resources, Physicochemical Properties, Drug Delivery System, Pharmacokinetics, and Pharmacological Effects. Front Pharmacol 2020; 11:579332. [PMID: 33536906 PMCID: PMC7849182 DOI: 10.3389/fphar.2020.579332] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 10/23/2020] [Indexed: 12/14/2022] Open
Abstract
Hydroxysafflower yellow A (HSYA), as a principal natural ingredient extracted from safflower (Carthamus tinctorius L.), has significant pharmacological activities, such as antioxidant, anti-inflammatory, anticoagulant, and anticancer effects. However, chemical instability and low bioavailability have been severely hampering the clinical applications of HSYA during the treatment of cardiovascular and cerebrovascular disease. Therefore, this present review systematically summarized the materials about HSYA, including acquisition methods, extraction and detection methods, pharmacokinetics, pharmacological effects and molecular mechanism, especially focus on the possible causes and resolutions about the chemical instability and low bioavailability of HSYA, in order to provide relatively comprehensive basic data for the related research of HSYA.
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Affiliation(s)
- Feng Zhao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Ping Wang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuanyuan Jiao
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaoxiao Zhang
- Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
- Postdoctoral Management Office, China Academy of Chinese Medical Sciences, Beijing, China
- China Association of Chinese Medicine, Beijing, China
| | - Daquan Chen
- School of Pharmacy, Yantai University, Yantai, China
| | - Haiyu Xu
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
- Shaanxi Institute of International Trade and Commerce, Xianyang, China
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