Hyperoside as a Potential Natural Product Targeting Oxidative Stress in Liver Diseases
Abstract
1. Introduction
2. Methods
3. Phytochemistry of Hyperoside
4. Pharmacological Effects of Hyperoside in Liver Diseases
4.1. Hepatoprotective Effects
4.2. Antiviral Effects
4.3. Antisteatotic Effects
4.4. Anti-Inflammatory Effects
4.5. Antifibrotic Effects
4.6. Anticancer Effects
5. Safety of Hyperoside
6. Discussion
7. Conclusions
Funding
Data Availability Statement
Conflicts of Interest
References
- Moon, A.M.; Singal, A.G.; Tapper, E.B. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin. Gastroenterol. Hepatol. 2020, 18, 2650–2666. [Google Scholar] [CrossRef] [PubMed]
- Asrani, S.K.; Larson, J.J.; Yawn, B.; Therneau, T.M.; Kim, W.R. Underestimation of liver-related mortality in the United States. Gastroenterology 2013, 145, 375–382. [Google Scholar] [CrossRef] [PubMed]
- Oztumer, C.A.; Chaudhry, R.M.; Alrubaiy, L. Association between behavioural risk factors for chronic liver disease and transient elastography measurements across the UK: A cross-sectional study. BMJ Open Gastroenterol. 2020, 7, e000524. [Google Scholar] [CrossRef] [PubMed]
- Lin, C.; Huang, X.; Liu, H.; Wang, Y. Interactions of hepatitis B virus infection with nonalcoholic fatty liver disease: Possible mechanisms and clinical impact. Dig. Dis. Sci. 2015, 60, 3513–3524. [Google Scholar] [CrossRef]
- Younossi, Z.; Henry, L. Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology 2016, 150, 1778–1785. [Google Scholar] [CrossRef]
- Singal, A.K.; Jampana, S.C.; Weinman, S.A. Antioxidants as therapeutic agents for liver disease. Liver Int. 2011, 31, 1432–1448. [Google Scholar] [CrossRef]
- Ma, Y.; Lee, G.; Heo, S.Y.; Roh, Y.S. Oxidative stress is a key modulator in the development of nonalcoholic fatty liver disease. Antioxidants 2021, 11, 91. [Google Scholar] [CrossRef]
- Cederbaum, A.I.; Lu, Y.; Wu, D. Role of oxidative stress in alcohol-induced liver injury. Arch. Toxicol. 2009, 83, 519–548. [Google Scholar] [CrossRef]
- Villanueva-Paz, M.; Morán, L.; López-Alcántara, N.; Freixo, C.; Andrade, R.J.; Lucena, M.I.; Cubero, F.J. Oxidative stress in drug-induced liver injury (DILI): From mechanisms to biomarkers for use in clinical practice. Antioxidants 2021, 10, 390. [Google Scholar] [CrossRef]
- Li, S.; Tan, H.Y.; Wang, N.; Zhang, Z.J.; Lao, L.; Wong, C.W.; Feng, Y. The role of oxidative stress and antioxidants in liver diseases. Int. J. Mol. Sci. 2015, 16, 26087–26124. [Google Scholar] [CrossRef]
- Yuan, W.; Wang, J.; An, X.; Dai, M.; Jiang, Z.; Zhang, L.; Yu, S.; Huang, X. UPLC-MS/MS Method for the Determination of Hyperoside and Application to Pharmacokinetics Study in Rat After Different Administration Routes. Chromatographia 2021, 84, 249–256. [Google Scholar] [CrossRef] [PubMed]
- Pei, J.; Chen, A.; Zhao, L.; Cao, F.; Ding, G.; Xiao, W. One-pot synthesis of hyperoside by a three-enzyme cascade using a UDP-galactose regeneration system. J. Agric. Food Chem. 2017, 65, 6042–6048. [Google Scholar] [CrossRef] [PubMed]
- Falco, M.R.; de Vries, J.X. Isolation of hyperoside (quercetin-3-D-galactoside) from the flowers of acacia melanoxylon. Naturwissenschaften 1964, 51, 462–463. [Google Scholar] [CrossRef]
- Wang, Q.; Wei, H.C.; Zhou, S.J.; Li, Y.; Zheng, T.T.; Zhou, C.Z.; Wan, X.H. Hyperoside: A review on its sources, biological activities, and molecular mechanism. Phytother. Res. 2022, 36, 2779–2802. [Google Scholar] [CrossRef] [PubMed]
- Fu, T.; Wang, L.; Jin, X.; Sui, H.; Liu, Z.; Jin, Y. Hyperoside induces both autophagy and apoptosis in non-small cell lung cancer cells in vitro. Acta Pharmacol. Sin. 2016, 37, 505–518. [Google Scholar] [CrossRef]
- Xiao, R.; Xiang, A.L.; Pang, H.B.; Liu, K.Q. Hyperoside protects against hypoxia/reoxygenation induced injury in cardiomyocytes by suppressing the Bnip3 expression. Gene 2017, 629, 86–91. [Google Scholar] [CrossRef]
- Zhang, Y.; Yu, X.; Wang, M.; Ding, Y.; Guo, H.; Liu, J.; Cheng, Y. Hyperoside from Z. bungeanum leaves restores insulin secretion and mitochondrial function by regulating pancreatic cellular redox status in diabetic mice. Free Radic. Biol Med. 2021, 162, 412–422. [Google Scholar] [CrossRef]
- De Bruyn, F.; Van Brempt, M.; Maertens, J.; Van Bellegem, W.; Duchi, D.; De Mey, M. Metabolic engineering of Escherichia coli into a versatile glycosylation platform: Production of bio-active quercetin glycosides. Microb. Cell Fact. 2015, 14, 138. [Google Scholar] [CrossRef]
- Chen, H.; Jiang, F.; Ding, X.; Liu, D.; Li, M. Optimization of extraction technology for hyperoside, isoquercitrin, quercetin in Abelmoschus manihot (L.) Medic.by response surface method. Sci. Technol. Food Ind. 2015, 24, 216–221. [Google Scholar]
- Qiu, Y.; Wang, M.Z. Isolation and Identification of Hyperoside in Abelmoschus manihot Flower. Adv. Mat. Res. 2013, 781, 880–883. [Google Scholar] [CrossRef]
- He, F.; Li, D.; Wang, D.; Deng, M. Extraction and purification of Quercitrin, Hyperoside, Rutin, and Afzelin from Zanthoxylum Bungeanum maxim leaves using an aqueous two-phase system. J. Food Sci. 2016, 81, C1593–C1602. [Google Scholar] [CrossRef]
- Mapoung, S.; Umsumarng, S.; Semmarath, W.; Arjsri, P.; Srisawad, K.; Thippraphan, P.; Yodkeeree, S.; Dejkriengkraikul, P. Photoprotective Effects of a Hyperoside-Enriched Fraction Prepared from Houttuynia cordata Thunb. on Ultraviolet B-Induced Skin Aging in Human Fibroblasts through the MAPK Signaling Pathway. Plants 2021, 10, 2628. [Google Scholar] [CrossRef] [PubMed]
- Çιrak, C.; Radušienė, J.; Janulis, V.; Ivanauskas, L. Secondary metabolites in Hypericum perfoliatum: Variation among plant parts and phenological stages. Bot. Helv. 2007, 117, 29–36. [Google Scholar] [CrossRef]
- Camas, N.; Radusiene, J.; Stanius, Z.; Caliskan, O.; Cirak, C. Secondary Metabolites of Hypericum leptophyllum Hochst., an Endemic Turkish Species. Sci. World J. 2012, 2012, 501027. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Liu, J.; Zhang, Z.; Yang, L.; Fan, Y.; Liu, Y. Molecular structure and spectral characteristics of hyperoside and analysis of its molecular imprinting adsorption properties based on density functional theory. J. Mol. Graph. 2019, 88, 228–236. [Google Scholar] [CrossRef]
- Saçıcı, E.; Yesilada, E. Development of new and validated HPTLC methods for the qualitative and quantitative analysis of hyperforin, hypericin and hyperoside contents in Hypericum species. Phytochem. Anal. 2022, 33, 355–364. [Google Scholar] [CrossRef]
- Guo, A.; Huanng, Z.; Liu, C. Pharmacokinetic study on hyperoside in Beagle’s dogs. Chin. Herb. Med. 2012, 4, 213–217. [Google Scholar]
- Chang, Q.; Zuo, Z.; Chow, M.S.; Ho, W.K. Difference in absorption of the two structurally similar flavonoid glycosides, hyperoside and isoquercitrin, in rats. Eur. J. Pharm. Biopharm. 2005, 59, 549–555. [Google Scholar] [CrossRef]
- Zhang, X.; Su, J.; Wang, X.; Wang, X.; Liu, R.; Fu, X.; Li, Y.; Xue, J.; Li, X.; Zhang, R. Preparation and Properties of Cyclodextrin Inclusion Complexes of Hyperoside. Molecules 2022, 27, 2761. [Google Scholar] [CrossRef]
- Corless, J.K.; Middleton, H.M. Normal liver function: A basis for understanding hepatic disease. Arch. Intern. Med. 1983, 143, 2291–2294. [Google Scholar] [CrossRef]
- Jaeschke, H.; Gores, G.J.; Cederbaum, A.I.; Hinson, J.A.; Pessayre, D.; Lemasters, J.J. Mechanisms of hepatotoxicity. Toxicol. Sci. 2002, 65, 166–176. [Google Scholar] [CrossRef] [PubMed]
- Dash, R.P.; Kala, M.; Nivsarkar, M.; Babu, R.J. Implication of formulation strategies on the bioavailability of selected plant-derived hepatoprotectants. Crit. Rev. Ther. Drug Carr. Syst. 2017, 34, 489–526. [Google Scholar] [CrossRef] [PubMed]
- Ram, V.J.; Goel, A. Past and present scenario of hepatoprotectants. Curr. Med. Chem. 1999, 6, 217–254. [Google Scholar] [CrossRef]
- Choi, J.H.; Kim, D.W.; Yun, N.; Choi, J.S.; Islam, M.N.; Kim, Y.S.; Lee, S.M. Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice. J. Nat. Prod. 2011, 74, 1055–1060. [Google Scholar] [CrossRef] [PubMed]
- Zou, L.; Chen, S.; Li, L.; Wu, T. The protective effect of hyperoside on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2. Exp. Toxicol. Pathol. 2017, 69, 451–460. [Google Scholar] [CrossRef] [PubMed]
- Xing, H.; Fu, R.; Cheng, C.; Cai, Y.; Wang, X.; Deng, D.; Gong, X.; Chen, J. Hyperoside protected against oxidative stress-induced liver injury via the PHLPP2-AKT-GSK-3β signaling pathway in vivo and in vitro. Front. Pharmacol. 2020, 11, 1065. [Google Scholar] [CrossRef]
- Cai, Y.; Li, B.; Peng, D.; Wang, X.; Li, P.; Huang, M.; Xing, H.; Chen, J. Crm1-Dependent Nuclear Export of Bach1 is Involved in the Protective Effect of Hyperoside on Oxidative Damage in Hepatocytes and CCl4-induced Acute Liver Injury. J. Inflamm. Res. 2021, 14, 551–565. [Google Scholar] [CrossRef]
- Huang, C.; Yang, Y.; Li, W.X.; Wu, X.Q.; Li, X.F.; Ma, T.T.; Zhang, L.; Meng, X.M.; Li, J. Hyperin attenuates inflammation by activating PPAR-γ in mice with acute liver injury (ALI) and LPS-induced RAW264.7 cells. Int. Immunopharmacol. 2015, 29, 440–447. [Google Scholar] [CrossRef]
- Qiao, J.; Wang, B.; Li, Y.; Bai, M.; Miao, M. Protective effects of hyperoside on acute alcohol-inducing liver injury in mice. Zhongguo Zhong Yao Za Zhi 2017, 33, 30–33. [Google Scholar]
- Huang, M.; Chen, J.; Hu, X.; Xia, P.; Cai, Y.; Wang, Q. Effect of hyperin on acute liver injury in rats against oxidative stress-induced by CCl4. Jujie Shushuxue Za Zhi 2013, 6, 588–590. [Google Scholar]
- Mun, S.; Ryu, H.; Choi, J. Inhibition effects of Zanthoxylum schinifolium and its active principle on lipid peroxidation and liver damage in carbon tetrachloride-treated mice. J. Korean Soc. Food Sci. Nutr. 1997, 26, 943–951. [Google Scholar]
- Ito, M.; Shimura, H.; Watanabe, N.; Tamai, M.; Hanada, K.; Takahashi, A.; Tanaka, Y.; Arai, I.; Zhang, P.L.; Rao, C. Hepatorotective Compounds from Canarium album and Euphorbia nematocypha. Chem. Pharm. Bull. 1990, 38, 2201–2203. [Google Scholar]
- Xing, H.Y.; Cai, Y.Q.; Wang, X.F.; Wang, L.L.; Li, P.; Wang, G.Y.; Chen, J.H. The cytoprotective effect of hyperoside against oxidative stress is mediated by the Nrf2-ARE signaling pathway through GSK-3β inactivation. PLoS ONE 2015, 10, e0145183. [Google Scholar] [CrossRef]
- Choi, S.J.; Tai, B.H.; Cuong, N.M.; Kim, Y.H.; Jang, H.D. Antioxidative and anti-inflammatory effect of quercetin and its glycosides isolated from mampat (Cratoxylum formosum). Food Sci. Biotechnol. 2012, 21, 587–595. [Google Scholar] [CrossRef]
- Abd Rashid, N.; Abd Halim, S.A.S.; Teoh, S.L.; Budin, S.B.; Hussan, F.; Ridzuan, N.R.A.; Jalil, N.A.A. The role of natural antioxidants in cisplatin-induced hepatotoxicity. Biomed. Pharmacother. 2021, 144, 112328. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.S.; Buters, J.T.; Pineau, T.; Fernandez-Salguero, P.; Gonzalez, F.J. Role of CYP2E1 in the Hepatotoxicity of Acetaminophen. J. Biol. Chem. 1996, 271, 12063–12067. [Google Scholar] [CrossRef] [PubMed]
- Liou, G.G.; Hsieh, C.C.; Lee, Y.J.; Li, P.H.; Tsai, M.S.; Li, C.T.; Wang, S.H. N-Acetyl cysteine overdose inducing hepatic steatosis and systemic inflammation in both propacetamol-induced hepatotoxic and normal mice. Antioxidants 2021, 10, 442. [Google Scholar] [CrossRef] [PubMed]
- Niu, C.; Ma, M.; Han, X.; Wang, Z.; Li, H. Hyperin protects against cisplatin-induced liver injury in mice. Acta Cir. Bras. 2017, 32, 633–640. [Google Scholar] [CrossRef]
- Jiang, Z.; Wang, J.; Liu, C.; Wang, X.; Pan, J. Hyperoside alleviated N-acetyl-para-amino-phenol-induced acute hepatic injury via Nrf2 activation. Int. J. Clin. Exp. Pathol. 2019, 12, 64–76. [Google Scholar]
- Xie, W.; Jiang, Z.; Wang, J.; Zhang, X.; Melzig, M.F. Protective effect of hyperoside against acetaminophen (APAP) induced liver injury through enhancement of APAP clearance. Chem.-Biol. Interact. 2016, 246, 11–19. [Google Scholar] [CrossRef]
- Hu, C.; Chen, Y.; Cao, Y.; Jia, Y.; Zhang, J. Metabolomics analysis reveals the protective effect of quercetin-3-O-galactoside (Hyperoside) on liver injury in mice induced by acetaminophen. J. Food Biochem. 2020, 44, e13420. [Google Scholar] [CrossRef] [PubMed]
- An, R.B.; Kim, H.C.; Tian, Y.H.; Kim, Y.C. Free radical scavenging and hepatoprotective constituents from the leaves of Juglans sinensis. Arch. Pharm. Res. 2005, 28, 529–533. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Wang, M.; Dong, H.; Yu, X.; Zhang, J. Anti-hypoglycemic and hepatocyte-protective effects of hyperoside from Zanthoxylum bungeanum leaves in mice with high-carbohydrate/high-fat diet and alloxan-induced diabetes. Int. J. Mol. Med. 2018, 41, 77–86. [Google Scholar] [CrossRef] [PubMed]
- Wu, L.; Yang, X.; Huang, Z.; Liu, H.; Wu, G. In vivo and in vitro antiviral activity of hyperoside extracted from Abelmoschus manihot (L) medik. Acta Pharmacol. Sin. 2007, 28, 404–409. [Google Scholar] [CrossRef]
- Guo, X.; Zhu, C.; Liu, X.; Ge, Y.; Jiang, X.; Zhao, W. Hyperoside protects against heart failure-induced liver fibrosis in rats. Acta Histochem. 2019, 121, 804–811. [Google Scholar] [CrossRef]
- Shen, D.; Hou, J.; Yuan, F. Hyperoside suppresses injury in Mycoplasma pneumoniae pneumonia mice. Chin. J. Pathol. 2017, 12, 884–889. [Google Scholar]
- Shi, Y.; Qiu, X.; Dai, M.; Zhang, X.; Jin, G. Hyperoside attenuates hepatic ischemia-reperfusion injury by suppressing oxidative stress and inhibiting apoptosis in rats. Transplant. Proc. 2019, 51, 2051–2059. [Google Scholar] [CrossRef]
- Lu, X.; Huang, Z.; Yang, X.; Wang, H.; Geng, M.; Li, Z. Liver protective effects of hyperin on duck hepatitis B virus infection. Zhongguo Zhong Yao Za Zhi 2007, 23, 10–12. [Google Scholar]
- Guo, X.; Qu, F.; Xin, Y.; Wang, J.; Li, H.; Ma, A.; Zhao, W. Effect and mechanism of hyperin on liver fibrosis in rats with heart failure. Shandong Yi Yao 2021, 61, 40–45. [Google Scholar]
- Abdelhameed, R.F.; Ibrahim, A.K.; Elfaky, M.A.; Habib, E.S.; Mahamed, M.I.; Mehanna, E.T.; Darwish, K.M.; Khodeer, D.M.; Ahmed, S.A.; Elhady, S.S. Antioxidant and Anti-Inflammatory Activity of Cynanchum acutum L. Isolated Flavonoids Using Experimentally Induced Type 2 Diabetes Mellitus: Biological and In Silico Investigation for NF-κB Pathway/miR-146a Expression Modulation. Antioxidants 2021, 10, 1713. [Google Scholar] [CrossRef]
- Guan, X.; Zhao, W.; Min, D.; Liu, C.; Shang, Y.; Hu, L. Protective effect of hyperoside on non-alcoholic fatty liver disease in ApoE-/- mice induced by high-fat diet. Drug Eval. Res. 2022, 45, 281–286. [Google Scholar]
- Huang, K.; Gen, M.; Wang, J.; Huang, Z.; Yang, X.; Chen, H. Protective Effect of Hyperin on Immunological Liver Injury in Mice. Zhongguo Shiyan Fangjixue Zazhi 2015, 21, 137–141. [Google Scholar]
- Xiong, Q.; Fan, W.; Tezuka, Y.; Adnyana, I.K.; Stampoulis, P.; Hattori, M.; Namba, T.; Kadota, S. Hepatoprotective effect of Apocynum venetum and its active constituents. Planta Med. 2000, 66, 127–133. [Google Scholar] [CrossRef] [PubMed]
- Saravanan, S.; Velu, V.; Nandakumar, S.; Madhavan, V.; Shanmugasundaram, U.; Murugavel, K.G.; Balakrishnan, P.; Kumarasamy, N.; Solomon, S.; Thyagarajan, S.P. Hepatitis B virus and hepatitis C virus dual infection among patients with chronic liver disease. J. Microbiol. Immunol. Infect. 2009, 42, 122–128. [Google Scholar] [PubMed]
- Goyal, A.; Murray, J.M. The impact of vaccination and antiviral therapy on hepatitis B and hepatitis D epidemiology. PLoS ONE 2014, 9, e110143. [Google Scholar] [CrossRef] [PubMed]
- Geng, M.; Wang, J.H.; Chen, H.Y.; Yang, X.B.; Huang, Z.M. Effects of hyperin on the cccDNA of duck hepatitis B virus and its immunological regulation. Yao Xue Xue Bao 2009, 44, 1440–1444. [Google Scholar]
- Shen, B.; Wu, N.; Shen, C.; Zhang, F.; Wu, Y.; Xu, P.; Zhang, L.; Wu, W.; Lu, Y.; Han, J. Hyperoside nanocrystals for HBV treatment: Process optimization, in vitro and in vivo evaluation. Drug Dev. Ind. Pharm. 2016, 42, 1772–1781. [Google Scholar] [CrossRef]
- Schreiner, S.; Nassal, M. A role for the host DNA damage response in hepatitis B virus cccDNA formation—and beyond? Viruses 2017, 9, 125. [Google Scholar] [CrossRef]
- Rehman, S.; Ashfaq, U.A.; Ijaz, B.; Riazuddin, S. Anti-hepatitis C virus activity and synergistic effect of Nymphaea alba extracts and bioactive constituents in liver infected cells. Microb. Pathog. 2018, 121, 198–209. [Google Scholar] [CrossRef]
- Nguyen, P.; Leray, V.; Diez, M.; Serisier, S.; Bloc’h, J.L.; Siliart, B.; Dumon, H. Liver lipid metabolism. J. Anim. Physiol. Anim. Nutr. 2008, 92, 272–283. [Google Scholar] [CrossRef]
- Ding, W.X.; Yang, L. Alcohol and drug-induced liver injury: Metabolism, mechanisms, pathogenesis and potential therapies. Liver Res. 2019, 3, 129–131. [Google Scholar] [CrossRef] [PubMed]
- Farrell, G.C.; Larter, C.Z. Nonalcoholic fatty liver disease: From steatosis to cirrhosis. Hepatology 2006, 43, S99–S112. [Google Scholar] [CrossRef] [PubMed]
- Lian, C.Y.; Zhai, Z.Z.; Li, Z.F.; Wang, L. High fat diet-triggered non-alcoholic fatty liver disease: A review of proposed mechanisms. Chem.-Biol. Interact. 2020, 330, 109199. [Google Scholar] [CrossRef] [PubMed]
- Sun, B.; Zhang, R.; Liang, Z.; Fan, A.; Kang, D. Hyperoside attenuates non-alcoholic fatty liver disease through targeting Nr4A1 in macrophages. Int. Immunopharmacol. 2021, 94, 107438. [Google Scholar] [CrossRef]
- Duan, J.Y.; Chen, W.; Zhao, Y.Q.; He, L.L.; Li, E.C.; Bai, Z.H.; Wang, Y.J.; Zhang, C.P. Flavonoids from Hypericum patulum enhance glucose consumption and attenuate lipid accumulation in HepG2 cells. J. Food Biochem. 2021, 45, e13898. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.; Sheng, F.; Zou, L.; Xiao, J.; Li, P. Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism. J. Adv. Res. 2021, 34, 109–122. [Google Scholar] [CrossRef]
- Robinson, M.W.; Harmon, C.; O’Farrelly, C. Liver immunology and its role in inflammation and homeostasis. Cell. Mol. Immunol. 2016, 13, 267–276. [Google Scholar] [CrossRef]
- Szabo, G.; Csak, T. Inflammasomes in liver diseases. J. Hepatol. 2012, 57, 642–654. [Google Scholar] [CrossRef]
- Tilg, H.; Kaser, A.; Moschen, A.R. How to modulate inflammatory cytokines in liver diseases. Liver Int. 2006, 26, 1029–1039. [Google Scholar] [CrossRef]
- Petrescu, A.D.; DeMorrow, S. Interleukin-24 therapy-a potential new strategy against liver fibrosis. EBioMedicine 2021, 65, 103245. [Google Scholar] [CrossRef]
- Hernandez-Gea, V.; Friedman, S.L. Pathogenesis of liver fibrosis. Annu. Rev. Pathol. 2011, 6, 425–456. [Google Scholar] [CrossRef] [PubMed]
- Pinzani, M.; Rombouts, K.; Colagrande, S. Fibrosis in chronic liver diseases: Diagnosis and management. J. Hepatol. 2005, 42, S22–S36. [Google Scholar] [CrossRef]
- Singh, S.; Fujii, L.L.; Murad, M.H.; Wang, Z.; Asrani, S.K.; Ehman, R.L.; Kamath, P.S.; Talwalkar, J.A. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: A systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 2013, 11, 1573–1584. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Li, J.; Zhou, Q.; Zhang, D.; Bi, Q.; Wu, Y.; Huang, W. Liver stiffness measurement predicted liver-related events and all-cause mortality: A systematic review and nonlinear dose-response meta-analysis. Hepatol. Commun. 2018, 2, 467–476. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Yue, Z.; Guo, M.; Fang, L.; Bai, L.; Li, X.; Tao, Y.; Wang, S.; Liu, Q.; Zhi, D. Dietary flavonoid hyperoside induces apoptosis of activated human LX-2 hepatic stellate cell by suppressing canonical NF-κB signaling. Biomed. Res. Int. 2016, 2016, 1068528. [Google Scholar] [CrossRef] [PubMed]
- Fabregat, I.; Moreno-Càceres, J.; Sánchez, A.; Dooley, S.; Dewidar, B.; Giannelli, G.; Ten Dijke, P.; Consortium, I.L. TGF-β signalling and liver disease. FEBS J. 2016, 283, 2219–2232. [Google Scholar] [CrossRef]
- Severi, T.; Van Malenstein, H.; Verslype, C.; Van Pelt, J.F. Tumor initiation and progression in hepatocellular carcinoma: Risk factors, classification, and therapeutic targets. Acta Pharmacol. Sin. 2010, 31, 1409–1420. [Google Scholar] [CrossRef]
- EASL. EASL clinical practice guidelines: Management of hepatocellular carcinoma. J. Hepatol. 2018, 69, 182–236. [Google Scholar] [CrossRef]
- Mittal, S.; El-Serag, H.B. Epidemiology of HCC: Consider the Population. J. Clin. Gastroenterol. 2013, 47, S2–S6. [Google Scholar] [CrossRef]
- Amarapurkar, D. Asia-Pacific working party on prevention of hepatocellular carcinoma. Application of surveillance programs for hepatocellular carcinoma in the Asia-Pacific Region. J. Gastroenterol. Hepatol. 2009, 24, 955–961. [Google Scholar] [CrossRef]
- Wei, S.; Sun, Y.; Wang, L.; Zhang, T.; Hu, W.; Bao, W.; Mao, L.; Chen, J.; Li, H.; Wen, Y. Hyperoside suppresses BMP-7-dependent PI3K/AKT pathway in human hepatocellular carcinoma cells. Ann. Transl. Med. 2021, 9, 1233. [Google Scholar] [CrossRef] [PubMed]
- Jiang, S.; Xiong, H.; Wu, H.; Wen, J.; Liang, L. Regulatory effect of hyperoside on proliferation and apoptosis of hepatic carcinoma cell HepG2 via mitochondrial P53/Caspase signaling pathway. Chin. J. Immunol. 2018, 34, 1832–1836. [Google Scholar]
- Sattler, F.R.; Paolucci, S.; Kreider, J.W.; Ladda, R.L. A human hepatoma cell line (PLC/PRF/5) produces lung metastases and secretes HBsAg in nude mice. Eur. J. Cancer Clin. Oncol. 1982, 18, 381–389. [Google Scholar] [CrossRef]
- Han, J.; Meng, J.; Chen, S.; Wang, X.; Yin, S.; Zhang, Q.; Liu, H.; Qin, R.; Li, Z.; Zhong, W. YY1 complex promotes quaking expression via super-enhancer binding during EMT of hepatocellular carcinoma. Cancer Res. 2019, 79, 1451–1464. [Google Scholar] [CrossRef]
- Xu, S.; Chen, S.; Xia, W.; Sui, H.; Fu, X. Hyperoside: A Review of Its Structure, Synthesis, Pharmacology, Pharmacokinetics and Toxicity. Molecules 2022, 27, 3009. [Google Scholar] [CrossRef] [PubMed]
- Ai, G.; Huang, Z.; Wang, D.; Zhang, H. Acute toxicity and genotoxicity evaluation of hyperoside extracted from Abelmoschus manihot (L.) Medic. J. Chin. Pharm. Sci. 2012, 21, 477. [Google Scholar] [CrossRef]
- Ai, G.; Huang, Z.; Wang, D.; Zhang, H. Toxicity of hyperoside after long-term oral administration in Sistar rats. Chin. J. New Drugs 2012, 21, 2811–2816. [Google Scholar]
- Ai, G.; Wang, D.; Huang, Z.; Zhang, H. Long-term toxicity of hyperoside in Beagle dogs. Chin. J. New Drugs 2015, 24, 1641–1647. [Google Scholar]
- Liu, B.; Tu, Y.; He, W.; Liu, Y.; Wu, W.; Fang, Q.; Tang, H.; Tang, R.; Wan, Z.; Sun, W.; et al. Hyperoside attenuates renal aging and injury induced by D-galactose via inhibiting AMPK-ULK1 signaling-mediated autophagy. Aging 2018, 10, 4197–4212. [Google Scholar] [CrossRef]
- Zhou, J.; Zhang, S.; Sun, X.; Lou, Y.; Yu, J. Hyperoside protects HK-2 cells against high glucose-induced apoptosis and inflammation via the miR-499a-5p/NRIP1 pathway. Pathol. Oncol. Res. 2021, 27, 629829. [Google Scholar] [CrossRef]
- Ai, G.; Huang, Z.; Wang, D.; Liu, Z. Study on toxicity of hyperoside in rat embryo-fetal development. Zhongguo Zhong Yao Za Zhi 2012, 37, 2452–2455. [Google Scholar] [PubMed]
- Wei, A.; Song, Y.; Ni, T.; Xiao, H.; Wan, Y.; Ren, X.; Li, H.; Xu, G. Hyperoside attenuates pregnancy loss through activating autophagy and suppressing inflammation in a rat model. Life Sci. 2020, 254, 117735. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.W.; Zhu, Z.Q.; Hu, T.X.; Zhu, D.Y. Structure-activity relationship of natural flavonoids in hydroxyl radical-scavenging effects. Acta Pharmacol. Sin. 2002, 23, 667–672. [Google Scholar] [PubMed]
- Jang, E.; Kim, B.J.; Lee, K.T.; Inn, K.S.; Lee, J.H. A survey of therapeutic effects of Artemisia capillaris in liver diseases. Evid. Based Complement. Alternat. Med. 2015, 2015, 728137. [Google Scholar] [CrossRef] [PubMed]
- Hyogo, H.; Yamagishi, S. Advanced glycation end products (AGEs) and their involvement in liver disease. Curr. Pharm. Des. 2008, 14, 969–972. [Google Scholar] [CrossRef]
- Zhang, Z.; Sethiel, M.S.; Shen, W.; Liao, S.; Zou, Y. Hyperoside downregulates the receptor for advanced glycation end products (RAGE) and promotes proliferation in ECV304 cells via the c-Jun N-terminal kinases (JNK) pathway following stimulation by advanced glycation end-products in vitro. Int. J. Mol. Sci. 2013, 14, 22697–22707. [Google Scholar] [CrossRef] [PubMed]
- Zhou, L.; An, X.F.; Teng, S.C.; Liu, J.S.; Shang, W.B.; Zhang, A.H.; Yuan, Y.G.; Yu, J.Y. Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy. J. Med. Food 2012, 15, 461–468. [Google Scholar] [CrossRef]
Hyperoside/Source | Experimental Model | Dose | Results/Molecular Mechanisms | References |
---|---|---|---|---|
Hyp/Artemisia capillaris | CCl4-induced liver injury in mice | 50, 100, 200 mg/kg | ↓serum AST, ALT ↓centrizonal necrosis ↓hepatic MDA ↑hepatic GSH ↑hepatic Nrf2 protein ↑hepatic HO-1 mRNA and protein | [34] |
Hyp | CCl4-induced male Kunming mice | 200, 400 mg/kg | ↓serum AST, ALT ↓hepatocellular necrosis ↓hepatic MDA, SOD, GSH-Px ↑hepatic CAT ↑hepatic Nrf2 | [35] |
Hyp | CCl4-induced male Sprague-Dawley rats | 60 mg/kg | ↓serum AST, ALT ↓liver cell edema, nuclear condensation, hepatocellular vacuolization ↓hepatic MDA ↑hepatic SOD ↑hepatic p-AKT, p-GSK-3β ↑hepatic nuclear Nrf2 ↑hepatic HO-1 ↓hepatic p-Fyn ↓hepatic PHLPP2 | [36] |
Hyp | CCl4-induced male BALB/c mice | 50, 100 mg/kg | ↓serum AST, ALT ↓hepatocellular vacuolization ↓hepatic MDA, SOD ↑hepatic GSH | [37] |
Hyp | CCl4-induced C57BL/6J mice | 200 mg/kg | ↓serum AST, ALT ↓hepatocyte destruction ↓hepatic p-p38, p-Erk protein | [38] |
Hyp | CCl4-induced rats | 30, 60 mg/kg | ↓hepatic focal necrosis ↓hepatic MDA ↑hepatic SOD, GSH | [40] |
Hyp/Zanthoxylum schinifolium | CCl4-induced mice | 10, 20 mg/kg | ↓serum AST, ALT ↓hepatic TBARS | [41] |
Hyp/Canarium album and Euphorbia nematocypha | CCl4-induced primary cultured rat hepatocytes | 1, 10 µM | ↓MDA | [42] |
Hyp/Zanthoxylum bungeanum leaves | High-carbohydrate/high-fat diet and alloxan-induced male Kunming mice | 200 mg/kg | ↓hepatic AST, ALT ↑hepatic Na+/K+ ATPase ↓hepatic focal necrosis ↑hepatic SOD, GSH, CAT ↓hepatic MDA ↓hepatic ATF3 ↓hepatic p-p65 ↓hepatic p-p38, p-Erk1/2, p-JNK ↓hepatic Bax ↑hepatic Bcl-2 ↓hepatic caspase 3,9 ↓hepatic cytochrome c | [53] |
Hyp | ApoE−/− mice fed high-fat diet | 200 mg/kg | ↓serum AST, ALT ↓hepatic MDA ↑hepatic SOD, GSH-Px | [61] |
Hyp | Kunming mice given 50% alcohol | 25, 50 mg/kg | ↓serum AST, ALT ↓hepatocellular necrosis and edema ↓hepatic MDA ↑hepatic SOD, GSH | [39] |
Hyp/Abelmoschus manihot | Ducklings inoculated with HBV-DNA | 0.1 g/kg/day | ↓hepatocellular necrosis ↓hepatocellular vacuolation | [54] |
Hyp | Ducklings inoculated with duck HBV DNA | 60 mg/kg | ↓hepatic ALT ↓hepatic cord derangement | [58] |
Hyp | Heart failure-induced liver fibrosis in male Wistar rats | 100, 200 mg/kg | ↓serum AST, ALT ↓serum ALP | [55] |
Hyp | Heart failure-induced liver fibrosis in male Wistar rats | 100, 200 mg/kg | ↓serum AST, ALT ↓hepatic MDA ↑hepatic SOD, GSH-Px | [59] |
Hyp | Diabetes-induced rats | 10 mg/kg | ↓serum AST, ALT | [60] |
Hyp | Pneumonia-induced liver injury in BALB/c mice | 12.5, 50 mg/kg | ↓serum AST, ALT | [56] |
Hyp | Cisplatin-induced liver injury in male ICR mice | 50 mg/kg | ↓serum AST, ALT, GGT ↓hepatocellular vacuolation ↓hepatic MDA ↑hepatic T-AOC, SOD, CAT, GSH, GSH-Px, GST | [48] |
Hyp | H2O2-induced LO2 liver cells | 100 µM | ↑cell survival rate, ↓LDH leakage ↑GSH ↑HO-1 mRNA and protein ↑nuclear Nrf-2 mRNA and protein ↑ARE, p-GSK-3β | [43] |
Hyp | H2O2-induced LO2 liver cells | 100, 200 µM | ↓MDA, ROS ↑HO-1 ↑ARE ↑nuclear Nrf-2 ↓nuclear Bach1 ↑Crm1 ↑Erk1/2 | [37] |
Hyp | H2O2-induced HepG2 cells | 1, 10 µM | ↓ROS | [44] |
Hyp | t-BHP-induced LO2 liver cells | 100 µM | ↑HO-1 ↑nuclear Nrf-2 ↓p-Fyn ↑p- GSK-3β ↑p-Akt ↓PHLPP2 | [36] |
Hyp | Concanavalin A-induced Kunming mice | 25, 50 mg/kg | ↓serum AST, ALT ↓hepatocellular necrosis ↓hepatic MDA ↑hepatic SOD | [62] |
Hyp/Apocynum venetum | D-GalN/TNF-α-induced primary cultured mouse hepatocytes | 20, 40, 80 µM | ↑cell survival rate | [63] |
Hyp/Canarium album and Euphorbia nematocypha | D-GalN-induced primary cultured rat hepatocytes | 3, 10, 30 µM | ↓ALT | [42] |
Hyp | Acetaminophen-induced LO2 liver cells | 10, 20 µM | ↑cell survival rate ↓LDH ↓ALT ↑nuclear Nrf2 ↑HO-1, GCLC, NQO1 | [49] |
Hyp | Acetaminophen-induced male Kunming mice | 100 mg/kg | ↓serum AST, ALT ↓liver congestion, centrilobular necrosis ↑hepatic UGTs ↑hepatic SULTs ↓hepatic CYP2E1 ↑nuclear Nrf-2 mRNA and protein | [50] |
Hyp | Acetaminophen-induced male C57BL/6 mice | 25, 50, 100 mg/kg | ↓serum AST, ALT, ALP ↓hepatic MDA ↑hepatic GSH, SOD, GST, GSH-Px ↑hepatic nuclear Nrf2 ↑hepatic HO-1, GCLC, NQO1 | [49] |
Hyp | Acetaminophen-induced male C57BL/6 mice | 60 mg/kg | ↓serum AST, ALT ↓hepatocellular vacuolation, lintrahepatic hemorrhage, lymphocyte infiltration ↓hepatic ROS, MDA ↑hepatic GSH, GST, GSH-Px ↓hepatic CYP2E1 mRNA and protein | [51] |
Hyp | Hepatic ischemia-reperfusion injury male Wistar rats | 50 mg/kg | ↓serum AST, ALT ↓Suzuki score ↓hepatic MDA ↑hepatic SOD, GSH-Px ↑hepatic HO-1, NQO1 protein ↓apoptotic cells in liver ↑hepatic Bcl-2 protein ↓hepatic Bax, caspase-3 protein | [57] |
Hyperoside/Source | Experimental Model | Dose | Results/Molecular Mechanisms | References |
---|---|---|---|---|
Hyp/Abelmoschus manihot | HepG2.2.15 cells | 0.0125, 0.025, 0.05 g/L | ↓HBsAg ↓HBeAg | [54] |
Hyp/Abelmoschus manihot | Ducklings inoculated with duck HBV DNA | 0.1 g/kg/day | ↓serum HBV DNA | [54] |
Hyp | Duck HBV infection model and normal mouse spleen lymphocyte | 25, 50 mg/kg | ↓serum HBV DNA ↓hepatic cccDNA ↓Th1 cytokine in normal mouse spleen lymphocyte | [66] |
Hyp | Ducklings inoculated with duck HBV DNA | 300 mg/kg | ↓serum HBV DNA ↓rebound of serum HBV DNA compared with lamivudine | [67] |
Hyp | Huh-7 cells transfected with NS3 gene of HCV | Not known | ↓HCV NS3 protease by docking the binding sites of NS3 protein | [69] |
Hyperoside/Source | Experimental Model | Dose | Results/Molecular Mechanisms | References |
---|---|---|---|---|
Hyp | High-fat diet-induced male C57BL/6 mice | 50 mg/kg | ↓liver weight ↓hepatic fat accumulation ↓hepatic TG, TC, NEFA | [74] |
Hyp | Diabetes-induced rats | 10 mg/kg | ↓liver weight ↓hepatic TG, TC ↓hepatic steatosis score | [60] |
Hyp/Hypericum patulum | Oleic acid-treated HepG2 cells | 2.5, 5 µM | ↓fat accumulation ↓TG contents ↓ROS ↑PPARγ | [75] |
Hyp | ApoE-/- mice fed high-fat diet | 200 mg/kg | ↓hepatic fat accumulation ↓hepatic MDA ↑hepatic SOD, GSH-Px | [61] |
Hyp | Wistar male rats fed high-fat diet | 0.6, 1.5 mg/kg | ↓hepatic fat accumulation ↑hepatic CYP7A1, CYP27A1 ↑hepatic FXR, LXRα ↑hepatic ACC, pACC ↓hepatic SREBP1,2 | [76] |
Hyp | Kunming mice given 50% alcohol | 25, 50 mg/kg | ↓ hepatic fat accumulation ↓hepatic MDA ↑hepatic SOD, GSH | [39] |
Hyperoside/Source | Experimental Model | Dose | Results/Molecular Mechanisms | References |
---|---|---|---|---|
Hyp/Artemisia capillaris | CCl4-induced liver injury in mice | 50, 100, 200 mg/kg | ↓Portal inflammation ↓Kupffer cell hyperplasia ↓hepatic iNOS, COX2 mRNA and protein ↑hepatic HO-1 mRNA and protein ↑Nrf2 protein | [34] |
Hyp | CCl4-induced C57BL/6J mice | 200 mg/kg | ↓hepatic TNF-α, IL-6 protein ↓hepatic inflammatory cells infiltrations ↓hepatic p-p38, p-Erk protein | [38] |
Hyp | Concanavalin A-induced Kunming mice | 25, 50 mg/kg | ↓hepatic inflammatory cells infiltrations ↓hepatic MDA ↑hepatic SOD | [62] |
Hyp/Zanthoxylum bungeanum leaves | High-carbohydrate/high-fat diet and alloxan-induced male Kunming mice | 200 mg/kg | ↓hepatic NO, iNOS ↓lymphocytic inflammation ↑hepatic SOD, GSH, CAT ↓hepatic MDA ↓hepatic p-p65 ↓hepatic p-p38, p-Erk1/2, p-JNK ↑hepatic Bcl-2 ↓hepatic Bax, caspase-3,9, cytochrome c | [53] |
Hyp | ApoE-/- mice fed high-fat diet | 200 mg/kg | ↓hepatic inflammatory cells infiltrations ↓hepatic MDA ↑hepatic SOD, GSH-Px | [61] |
Hyp | High-fat diet-induced male C57BL/6 mice | 50 mg/kg | ↓hepatic F4/80 positive areas ↓hepatic TNF-α, IL-1β, IL-6, CCL2, CCL5, iNOS mRNA | [74] |
Hyp | Diabetes-induced rats | 10 mg/kg | ↓hepatic TNF-α protein ↓hepatic NFκB protein ↓hepatic inflammation score | [60] |
Hyp | Kunming mice given 50% alcohol | 25, 50 mg/kg | ↓hepatic inflammatory cells infiltrations ↓hepatic MDA ↑hepatic SOD, GSH | [39] |
Hyperoside/Source | Experimental Model | Dose | Results/Molecular Mechanisms | References |
---|---|---|---|---|
Hyp | LX-2 cells | 2 mM/L | ↓cell proliferation ↑cell apoptosis rate ↑proapoptotic genes (Bcl-Xs, DR4, Fas, FasL) ↓antiapoptotic genes (A20, c-IAP1, Bcl-XL, RIP1) ↓α-SMA, collagen I mRNA and protein ↓intracellular ROS ↓TNF-α-induced NFκB p65 DNA binding (by Hyp 1mM/L) | [85] |
Hyp | CCl4-induced male Kunming mice | 200, 400 mg/kg | ↓serum MAO ↓hepatic MAO ↓fibrosis around central vein ↓hepatic MDA ↑hepatic SOD, GSH-Px, CAT ↑hepatic Nrf2 | [35] |
Hyp | High-fat diet-induced male C57BL/6 mice | 50 mg/kg | ↓hepatic fibrotic area ↓hepatic Col1A1, CTGF, TGF-β mRNA | [74] |
Hyp | Heart failure-induced liver fibrosis in male Wistar rats | 100, 200 mg/kg | ↓hepatic hydroxyproline ↓hepatic fibrosis area ↓hepatic α-SMA, collagen I, CTGF mRNA and protein ↓hepatic MMP2, MMP9 mRNA and protein ↓hepatic TGFβ1, p-Smad 2,3 protein | [55] |
Hyp | Heart failure-induced liver fibrosis in male Wistar rats | 200 mg/kg | ↓hepatic hydroxyproline ↓hepatic TGF-β1, CTGF, TIMP1, MMP1, MMP2, collagen III mRNA and protein ↓hepatic MDA ↑hepatic SOD, GSH-Px | [59] |
Hyp | TGF-β1-induced LX-2 cells | 2 mM | ↓α-SMA mRNA and protein ↓collagen I mRNA and protein ↓p-Smad 2,3 protein | [55] |
Hyperoside/Source | Experimental Model | Dose | Results/Molecular Mechanisms | References |
---|---|---|---|---|
Hyp | PLC-PRF-5 hepatoma cells | 20, 50 µM | ↓cell migration ↓cell invasion ↓quaking ↓circRNAs | [94] |
Hyp | BALB/c mice injected with PLC-PRF-5 cells | 50, 100 mg/kg | ↓tumor growth ↑survival times ↓metastatic lung nodules ↓hepatic quaking ↓hepatic vimentin ↑hepatic E-cadherin | [94] |
Hyp | Insulin-resistant HepG2 cells | 10 µM | ↓cell survival rate | [75] |
Hyp | HepG2 cells | 10, 20, 40, 80 µM | ↓cell survival rate ↓BMP-7 mRNA and protein ↓cyclin-D1 and c-Myc ↑G0/G1 arrest ↓p-AKT, PI3K | [91] |
Hyp | HepG2 cells | 20, 50 nmol/L | ↓cell survival rate ↑nuclear shrinkage ↑cell apoptosis rate ↑p53 protein ↑hepatic caspase-3,9 protein | [92] |
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Jang, E. Hyperoside as a Potential Natural Product Targeting Oxidative Stress in Liver Diseases. Antioxidants 2022, 11, 1437. https://doi.org/10.3390/antiox11081437
Jang E. Hyperoside as a Potential Natural Product Targeting Oxidative Stress in Liver Diseases. Antioxidants. 2022; 11(8):1437. https://doi.org/10.3390/antiox11081437
Chicago/Turabian StyleJang, Eungyeong. 2022. "Hyperoside as a Potential Natural Product Targeting Oxidative Stress in Liver Diseases" Antioxidants 11, no. 8: 1437. https://doi.org/10.3390/antiox11081437
APA StyleJang, E. (2022). Hyperoside as a Potential Natural Product Targeting Oxidative Stress in Liver Diseases. Antioxidants, 11(8), 1437. https://doi.org/10.3390/antiox11081437