Natural products for the prevention and treatment of cholestasis: A review.
bile acids homeostasis
cholestasis
liver injury
multiple targets
natural products
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
15
09
2019
revised:
26
12
2019
accepted:
13
01
2020
pubmed:
7
2
2020
medline:
1
8
2020
entrez:
7
2
2020
Statut:
ppublish
Résumé
Cholestasis is a common manifestation of decreased bile flow in various liver diseases. It results in fibrosis and even cirrhosis without proper treatment. It is believed that a wide range of factors, including transporter dysfunction, oxidative stress, inflammatory damage, and immune disruption, can cause cholestasis. In recent years, natural products have drawn much attention for specific multiple-target activities in diseases. Many attempts have been made to investigate the anticholestatic effects of natural products with advanced technology. This review summarizes recent studies on the biological activities and mechanisms of recognized compounds for cholestasis treatment. Natural products, including various flavonoids, phenols, acids, quinones, saponins, alkaloids, glycosides, and so on, function as comprehensive regulators via ameliorating oxidative stress, inflammation, and apoptosis, restoring bile acid balance with hepatic transporters, and adjusting immune disruption. Moreover, in this progress, nuclear factor erythroid 2-related factor 2, reactive oxygen species production, heme oxygenase-1, NF-κB, cholesterol 7 alpha-hydroxylase, and farnesoid X receptors are thought as main targets for the activity of natural products. Therefore, this review presents the detailed mechanisms that include multiple targets and diverse signalling pathways. Natural products are the valuable when seeking novel therapeutic agents to treat cholestatic liver diseases.
Substances chimiques
Biological Products
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1291-1309Subventions
Organisme : National Natural Science Foundation of China
ID : 81874365
Organisme : Sichuan Science and Technology Program
ID : 2019YJ0492
Organisme : China Postdoctoral Science Foundation
ID : 2017 M622987
Organisme : Chengdu University of TCM
ID : QNXZ2018025
Informations de copyright
© 2020 John Wiley & Sons, Ltd.
Références
Afonso, M. B., Rodrigues, P. M., Simão, A. L., Ofengeim, D., Carvalho, T., Amaral, J. D., … Rodrigues, C. M. (2016). Activation of necroptosis in human and experimental cholestasis. Cell Death & Disease, 7(9), e2390. https://doi.org/10.1038/cddis.2016.280
Ağır, M. S., & Eraslan, G. (2019). The effect of diosmin against liver damage caused by cadmium in rats. Journal of Food Biochemistry, 43, e12966. https://doi.org/10.1111/jfbc.12966
Akbar, S. (2011). Andrographis paniculata: A review of pharmacological activities and clinical effects. Alternative Medicine Review, 16(1), 66-77.
Akdemir, B., Bahcecioglu, I. H., Tuzcu, M., Tuzcu, M., Orhan, C., Ispiroglu, M., … Sahin, S. (2016). Effect of lycopene and genistein on hepatic inflammation and fibrosis in thioacetamide induced liver injury in rats. British Journal of Medicine & Medical Research, 18(6), 1-11. https://doi.org/10.9734/BJMMR/2016/27654
Alagawany, M., Abd El-Hack, M. E., Farag, M. R., Gopi, M., Karthik, K., Malik, Y. S., & Dhama, K. (2017). Rosmarinic acid: Modes of action, medicinal values and health benefits. Animal Health Research Reviews, 18(2), 167-176. https://doi.org/10.1017/S1466252317000081
Ali, F. E. M., Azouz, A. A., Bakr, A. G., Abo-Youssef, A. M., & Hemeida, R. A. M. (2018). Hepatoprotective effects of diosmin and/or sildenafil against cholestatic liver cirrhosis: The role of Keap-1/Nrf-2 and P38-MAPK/NF-κB/iNOS signaling pathway. Food and Chemical Toxicology, 120, 294-304. https://doi.org/10.1016/j.fct.2018.07.027
Ali, F. E. M., Bakr, A. G., Abo-Youssef, A. M., Azouz, A. A., & Hemeida, R. A. M. (2018). Targeting Keap-1/Nrf-2 pathway and cytoglobin as a potential protective mechanism of diosmin and pentoxifylline against cholestatic liver cirrhosis. Life Sciences, 207, 50-60. https://doi.org/10.1016/j.lfs.2018.05.048
Alves, R. R., & Rosa, I. M. (2007). Biodiversity, traditional medicine and public health: Where do they meet? Journal of Ethnobiology and Ethnomedicine, 3, 14. https://doi.org/10.1186/1746-4269-3-14
Ara, C., Kirimlioglu, H., Karabulut, A. B., Coban, S., Ay, S., Harputluoglu, M., … Yilmaz, S. (2005). Protective effect of resveratrol against oxidative stress in cholestasis. The Journal of Surgical Research, 127(2), 112-117. https://doi.org/10.1016/j.jss.2005.01.024
Barta, A., Janega, P., Babál, P., Murár, E., Cebová, M., & Pechánová, O. (2015). The effect of curcumin on liver fibrosis in the rat model of microsurgical cholestasis. Food & Function, 6(7), 2187-2193. https://doi.org/10.1039/c5fo00176e
Beuers, U., Trauner, M., Jansen, P., & Poupon, R. (2015). New paradigms in the treatment of hepatic cholestasis: From UDCA to FXR, PXR and beyond. Journal of Hepatology, 62(1 Suppl), S25-S37. https://doi.org/10.1016/j.jhep.2015.02.023
Bu, P., Le, Y., Zhang, Y., Zhang, Y., & Cheng, X. (2017). Berberine-induced inactivation of signal transducer and activator of transcription 5 Signaling promotes male-specific expression of a bile acid uptake transporter. Journal of Biological Chemistry, 292(11), 4602-4613. https://doi.org/10.1074/jbc.M116.757567
Chai, J., Du, X., Chen, S., Feng, X., Cheng, Y., Zhang, L., … Chen, W. (2015). Oral administration of oleanolic acid, isolated from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats. International Journal of Clinical and Experimental Medicine, 8(2), 1691-1702.
Chan, C. C., Cheng, L. Y., Lin, C. L., Huang, Y. H., Lin, H. C., & Lee, F. Y. (2001). The protective role of natural phytoalexin resveratrol on inflammation, fibrosis and regeneration in cholestatic liver injury. Molecular Nutrition & Food Research, 55(12), 1841-1849. https://doi.org/10.1002/mnfr.201100374
Chedea, V. S., Vicaş, S. I., Sticozzi, C., Pessina, F., Frosini, M., Maioli, E., & Valacchi, G. (2017). Resveratrol: from diet to topical usage. Food & Function, 8(11), 3879-3892. https://doi.org/10.1039/c7fo01086a
Chen, H., Gao, X., Zhao, W., Yu, H., Wang, N., & Mi, S. (2019). Effect of geniposidic acid on SHP-LRH-1 signaling pathway in cholestasis rats. Zhong Nan Da Xue Xue Bao. Yi Xue Ban, 44(6), 605-613. https://doi.org/10.11817/j.issn.1672-7347.2019.06.001
Chen, H., Huang, X., Min, J., Li, W., Zhang, R., Zhao, W., … Zhu, C. (2016). Geniposidic acid protected against ANIT-induced hepatotoxity and acute intrahepatic cholestasis, due to Fxr-mediated regulation of Bsep and Mrp2. Journal of Ethnopharmacology, 179, 197-207. https://doi.org/10.1016/j.jep.2015.12.033
Chen, H., Li, J., Hu, L., Zhao, W., Yu, H., Liu, H. Z., & Ma, S. T. (2019). Effect of geniposidic acid on hepato-enteric circulation in cholestasis rats through Sirt1-FXR signaling pathway. China Journal of Chinese Materia Medica, 44(4), 787-795. https://doi.org/10.19540/j.cnki.cjcmm.20181204.013
Chen, P., Chen, Y., Wang, Y., Cai, S., Deng, L., Liu, J., & Zhang, H. (2016). Comparative evaluation of hepatoprotective activities of geniposide, crocins and crocetin by CCl4-induced liver injury in mice. Biomolecules & Therapeutics (Seoul), 24(2), 156-162. https://doi.org/10.4062/biomolther.2015.094
Chen, P., Li, J., Fan, X., Zeng, H., Deng, R., Li, D., … Bi, H. (2015). Oleanolic acid attenuates obstructive cholestasis in bile duct-ligated mice, possibly via activation of NRF2-MRPs and FXR antagonism. European Journal of Pharmacology, 765, 131-139. https://doi.org/10.1016/j.ejphar.2015.08.029
Chen, P., Zeng, H., Wang, Y., Fan, X., Xu, C., Deng, R., … Huang, M. (2014). Low dose of oleanolic acid protects against lithocholic acid-induced cholestasis in mice: Potential involvement of nuclear factor-E2-related factor 2-mediated upregulation of multidrug resistance-associated proteins. Drug Metabolism and Disposition, 42(5), 844-852. https://doi.org/10.1124/dmd.113.056549
Chen, Z., Hu, L., Lu, M., & Shen, Z. (2016). Resveratrol reduces matrix metalloproteinases and alleviates intrahepatic cholestasis of pregnancy in rats. Canadian Journal of Physiology and Pharmacology, 94(4), 402-407. https://doi.org/10.1139/cjpp-2015-0454
Chen, Z., Ma, X., Zhao, Y., Wang, J., Zhang, Y., Li, J., … Xiao, X. (2015). Yinchenhao decoction in the treatment of cholestasis: A systematic review and meta-analysis. Journal of Ethnopharmacology, 168, 208-216. https://doi.org/10.1016/j.jep.2015.03.058
Chen, Z., Ma, X., Zhu, Y., Zhao, Y., Wang, J., Li, R., … Xiao, X. (2015). Paeoniflorin ameliorates ANIT-induced cholestasis by activating Nrf2 through an PI3K/Akt-dependent pathway in rats. Phytotherapy Research, 29(11), 1768-1775. https://doi.org/10.1002/ptr.5431
Chen, Z., Zhu, Y., Zhao, Y., Ma, X., Niu, M., Wang, J., … Xiao, X. (2016). Serum Metabolomic profiling in a rat model reveals protective function of paeoniflorin against ANIT induced cholestasis. Phytotherapy Research, 30(4), 654-662. https://doi.org/10.1002/ptr.5575
Cheng, F., Liu, C., Jiang, J., Lu, W., Li, W., Liu, G., … Tang, Y. (2012). Prediction of drug-target interactions and drug repositioning via network-based inference. PLoS Computational Biology, 8(5), e1002503. https://doi.org/10.1371/journal.pcbi.1002503
Crocenzi, F. A., Basiglio, C. L., Pérez, L. M., Portesio, M. S., Pozzi, E. J., & Roma, M. G. (2005). Silibinin prevents cholestasis-associated retrieval of the bile salt export pump, Bsep, in isolated rat hepatocyte couplets: Possible involvement of cAMP. Biochemical Pharmacology, 69(7), 1113-1120. https://doi.org/10.1016/j.bcp.2005.01.009
Crocenzi, F. A., Sánchez Pozzi, E. J., Pellegrino, J. M., Favre, C. O., Rodríguez Garay, E. A., Mottino, A. D., … Roma, M. G. (2001). Beneficial effects of silymarin on estrogen-induced cholestasis in the rat: A study in vivo and in isolated hepatocyte couplets. Hepatology, 34(2), 329-339. https://doi.org/10.1053/jhep.2001.26520
Crocenzi, F. A., Sánchez Pozzi, E. J., Pellegrino, J. M., Rodríguez Garay, E. A., Mottino, A. D., & Roma, M. G. (2003). Preventive effect of silymarin against taurolithocholate-induced cholestasis in the rat. Biochemical Pharmacology, 66(2), 355-364. https://doi.org/10.1016/S0006-2952(03)00253-3
Deters, M., Klabunde, T., Meyer, H., Resch, K., & Kaever, V. (2003). Effects of curcumin on cyclosporine-induced cholestasis and hypercholesterolemia and on cyclosporine metabolism in the rat. Planta Medica, 69(4), 337-343. https://doi.org/10.1055/s-2003-38870
Ding, L., Zhang, B., Li, J., Yang, L., & Wang, Z. (2018). Beneficial effect of resveratrol on α-naphthyl isothiocyanate-induced cholestasis via regulation of the FXR pathway. Molecular Medicine Reports, 17(1), 1863-1872. https://doi.org/10.3892/mmr.2017.8051
Ding, Y., Xiong, X. L., Zhou, L. S., Yan, S. Q., Qin, H., Li, H. R., … Zhao, L. (2016). Preliminary study on Emodin alleviating alpha-naphthylisothiocyanate-induced intrahepatic cholestasis by regulation of liver farnesoid X receptor pathway. International Journal of Immunopathology and Pharmacology, 29(4), 805-811. https://doi.org/10.1177/0394632016672218
Ding, Y., Xu, F., Xiong, X. L., & Ling, H. R. (2014). Effect of emodin on expression of farnesoid X receptor in rats with acute cholestatic hepatitis. Chinese Journal of Contemporary Pediatrics, 16(4), 424-429.
Ding, Y., Zhao, L., Mei, H., Zhang, S. L., Huang, Z. H., Duan, Y. Y., & Ye, P. (2008). Exploration of emodin to treat alpha-naphthylisothiocyanate-induced cholestatic hepatitis via anti-inflammatory pathway. European Journal of Pharmacology, 590(1-3), 377-386. https://doi.org/10.1016/j.ejphar.2008.06.044
El-Hawary, S. S., Ali, Z. Y., & Younis, I. Y. (2019). Hepatoprotective potential of standardized Ficus species in intrahepatic cholestasis rat model: Involvement of nuclear factor-κB, and Farnesoid X receptor signaling pathways. Journal of Ethnopharmacology, 231, 262-274. https://doi.org/10.1016/j.jep.2018.11.026
Eraslan, G., Sarıca, Z. S., Bayram, L. Ç., Tekeli, M. Y., Kanbur, M., & Karabacak, M. (2017). The effects of diosmin on aflatoxin-induced liver and kidney damage. Environmental Science and Pollution Research International, 24(36), 27931-27941. https://doi.org/10.1007/s11356-017-0232-7
Fahmy, S. R. (2015). Anti-fibrotic effect of Holothuria arenicola extract against bile duct ligation in rats. BMC Complementary and Alternative Medicine, 15, 14. https://doi.org/10.1186/s12906-015-0533-7
Feng, X. C., Du, X., Chen, S., Yue, D., Cheng, Y., Zhang, L., … Chai, J. (2015). Swertianlarin, isolated from Swertia mussotii Franch, increases detoxification enzymes and efflux transporters expression in rats. International Journal of Clinical and Experimental Pathology, 8(1), 184-195.
Gai, Q. Y., Jiao, J., Luo, M., Wang, W., Zhao, C. J., … Ma, W. (2016). UV elicitation for promoting astragaloside production in Astragalus membranaceus hairy root cultures with transcriptional expression of biosynthetic genes. Industrial Crops and Products, 84, 350-357. https://doi.org/10.1016/j.indcrop.2016.02.010
Ganai, A. A., & Husain, M. (2017). Genistein attenuates D-GalN induced liver fibrosis/chronic liver damage in rats by blocking the TGF-β/Smad signaling pathways. Chemico-Biological Interactions, 2017(261), 80-85. https://doi.org/10.1016/j.cbi.2016.11.022
Ganai, A. A., Khan, A. A., Malik, Z. A., & Farooqi, H. (2015). Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating d-Galactosamine induced fulminant hepatic failure in Wistar rats. Toxicology and Applied Pharmacology, 283(2), 139-146. https://doi.org/10.1016/j.taap.2015.01.012
Goh, K. I., Cusick, M. E., Valle, D., Childs, B., Vidal, M., & Barabási, A. L. (2007). The human disease network. Proceedings of the National Academy of Sciences of the United States of America, 104(21), 8685-8690. https://doi.org/10.1073/pnas.0701361104
Goldstein, J., & Levy, C. (2018). Novel and emerging therapies for cholestatic liver diseases. Liver International, 38(9), 1520-1535. https://doi.org/10.1111/liv.13880
Gumpricht, E., Dahl, R., Devereaux, M. W., & Sokol, R. J. (2005). Licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes. The Journal of Biological Chemistry, 280(11), 10556-10563. https://doi.org/10.1074/jbc.M411673200
Guo, Z. (2017). The modification of natural products for medical use. Acta Pharmaceutica Sinica B, 7(2), 119-136. https://doi.org/10.1016/j.apsb.2016.06.003
Han, H., Xu, L., Xiong, K., Zhang, T., & Wang, Z. (2018). Exploration of hepatoprotective effect of gentiopicroside on alpha-naphthylisothiocyanate-induced cholestatic liver injury in rats by comprehensive proteomic and metabolomic signatures. Cellular Physiology and Biochemistry, 49(4), 1304-1319. https://doi.org/10.1159/000493409
Hashem, R. M., Hassanin, K. M., Rashed, L. A., Mahmoud, M. O., & Hassan, M. G. (2016). Effect of silibinin and vitamin E on the ASK1-p38 MAPK pathway in d-galactosamine/lipopolysaccharide induced hepatotoxicity. Experimental Biology and Medicine (Maywood, N.J.), 241(11), 1250-1257. https://doi.org/10.1177/1535370216636719
He, C. S., Yue, H. Y., Xu, J., Xue, F., Liu, J., Li, Y. Y., & Jing, H. E. (2012). Protective effects of capillary artemisia polysaccharide on oxidative injury to the liver in rats with obstructive jaundice. Experimental and Therapeutic Medicine, 4(4), 645-648. https://doi.org/10.3892/etm.2012.666
He, P., Wu, Y., Shun, J., Liang, Y., Cheng, M., & Wang, Y. (2017). Baicalin ameliorates liver injury induced by chronic plus binge ethanol feeding by modulating oxidative stress and inflammation via CYP2E1 and NRF2 in mice. Oxidative Medicine and Cellular Longevity, 2017, 4820414. https://doi.org/10.1155/2017/4820414
Hirsova, P., Karlasova, G., Dolezelova, E., Cermanova, J., Zagorova, M., Kadova, Z., … Micuda, S. (2013). Cholestatic effect of epigallocatechin gallate in rats is mediated via decreased expression of Mrp2. Toxicology, 303, 9-15. https://doi.org/10.1016/j.tox.2012.10.018
Hsu, Y. C., Chiu, Y. T., Lee, C. Y., Wu, C. F., & Huang, Y. T. (2006). Anti-fibrotic effects of tetrandrine on bile-duct ligated rats. Canadian Journal of Physiology and Pharmacology, 84(10), 967-976. https://doi.org/10.1139/y06-050
Hussein, M. A. (2013). Prophylactic effect of resveratrol against ethinylestradiol-induced liver cholestasis. Journal of Medicinal Food, 16(3), 246-254. https://doi.org/10.1089/jmf.2012.0183
Kabirifar, R., Ghoreshi, Z. A., Safari, F., Karimollah, A., Moradi, A., & Eskandari-Nasab, E. (2017). Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats. Hepatobiliary & Pancreatic Diseases International, 16(1), 88-95. https://doi.org/10.1016/S1499-3872(16)60164-9
Khamphaya, T., Chansela, P., Piyachaturawat, P., Suksamrarn, A., Nathanson, M. H., & Weerachayaphorn, J. (2016). Effects of andrographolide on intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats. European Journal of Pharmacology, 789, 254-264. https://doi.org/10.1016/j.ejphar.2016.07.032
Khan, A. D., & Singh, L. (2016). Various techniques of bioavailability enhancement: A review. Journal of Drug Delivery and Therapeutics, 6(3), 34-41. https://doi.org/10.22270/jddt.v6i3.1228
Kibble, M., Saarinen, N., Tang, J., Wennerberg, K., Mäkelä, S., & Aittokallio, T. (2015). Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products. Natural Product Reports, 32(8), 1249-1266. https://doi.org/10.1039/c5np00005j
Kirimlioglu, V., Ara, C., Yilmaz, M., Ozgor, D., Isik, B., Sogutlu, G., … Yologlu, S. (2006). Resveratrol, a red wine constituent polyphenol, protects gastric tissue against the oxidative stress in cholestatic rats. Digestive Diseases and Sciences, 51(2), 298-302. https://doi.org/10.1007/s10620-006-3128-9
Kumar, A., Ekavali, C. K., Mukherjee, M., Pottabathini, R., & Dhull, D. K. (2015). Current knowledge and pharmacological profile of berberine: An update. European Journal of Pharmacology, 761, 288-297. https://doi.org/10.1016/j.ejphar.2015.05.068
Kumar, V., & Van Staden, J. (2016). A review of Swertia chirayita (Gentianaceae) as a traditional medicinal plant. Frontiers in Pharmacology, 6, 308. https://doi.org/10.3389/fphar.2015.00308
Lee, T. Y., Chen, F. Y., Chang, H. H., & Lin, H. C. (2009). The effect of capillarisin on glycochenodeoxycholic acid-induced apoptosis and heme oxygenase-1 in rat primary hepatocytes. Molecular and Cellular Biochemistry, 325(1-2), 53-59. https://doi.org/10.1007/s11010-008-0019-8
Lee, T. Y., Lee, K. C., & Chang, H. H. (2010). Modulation of the cannabinoid receptors by andrographolide attenuates hepatic apoptosis following bile duct ligation in rats with fibrosis. Apoptosis, 15(8), 904-914. https://doi.org/10.1007/s10495-010-0502-z
Liang, W., Chen, W., Wu, L., Li, S., Qi, Q., Cui, Y., … Zhang, L. (2017). Quality evaluation and chemical markers screening of Salvia miltiorrhiza Bge.(Danshen) based on HPLC fingerprints and HPLC-MSn coupled with chemometrics. Molecules, 22(3), E478. https://doi.org/10.3390/molecules22030478
Liang, W., Zhang, D., Kang, J., Meng, X., Yang, J., Yang, L., … Gou, X. (2018). Protective effects of rutin on liver injury in type 2 diabetic db/db mice. Biomedicine & Pharmacotherapy, 107, 721-728. https://doi.org/10.1016/j.biopha.2018.08.046
Limem-Ben, A. I., Boubaker, J., Ben, S. M., Skandrani, I., Bhouri, W., Neffati, A., … Chekir-Ghedira, L. (2009). Phytochemistry and biological activities of Phlomis species. Journal of Ethnopharmacology, 125(2), 183-202. https://doi.org/10.1016/j.jep.2009.06.022
Lin, S. Y., Wang, Y. Y., Chen, W. Y., Chuang, Y. H., Pan, P. H., & Chen, C. J. (2014). Beneficial effect of quercetin on cholestatic liver injury. The Journal of Nutritional Biochemistry, 25(11), 1183-1195. https://doi.org/10.1016/j.jnutbio.2014.06.003
Lin, S. Y., Wang, Y. Y., Chen, W. Y., Liao, S. L., Chou, S. T., Yang, C. P., & Chen, C. J. (2017). Hepatoprotective activities of rosmarinic acid against extrahepatic cholestasis in rats. Food Chem Toxicol, 108(Pt A), 214-223. https://doi.org/10.1016/j.fct.2017.08.005
Lin, T. K., Huang, L. T., Huang, Y. H., Tiao, M. M., Tang, K. S., & Liou, C. W. (2012). The effect of the red wine polyphenol resveratrol on a rat model of biliary obstructed cholestasis: Involvement of anti-apoptotic signalling, mitochondrial biogenesis and the induction of autophagy. Apoptosis, 17(8), 871-879. https://doi.org/10.1007/s10495-012-0732-3
Liu, D., Wu, T., Zhang, C. L., Xu, Y. J., Chang, M. J., Li, X. P., & Cai, H. J. (2014). Beneficial effect of calculus Bovis Sativus on 17α-ethynylestradiol-induced cholestasis in the rat. Life Sciences, 113(1-2), 22-30. https://doi.org/10.1016/j.lfs.2014.07.024
Liu, H., Chen, Y. F., Li, F., & Zhang, H. Y. (2013). Fructus gardenia (Gardenia jasminoides J. Ellis) phytochemistry, pharmacology of cardiovascular, and safety with the perspective of new drugs development. Journal of Asian Natural Products Research, 15(1), 94-110. https://doi.org/10.1080/10286020.2012.723203
Liu, J., Lu, Y. F., Zhang, Y., Wu, K. C., Fan, F., & Klaassen, C. D. (2013). Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice. Toxicology and Applied Pharmacology, 272(3), 816-824. https://doi.org/10.1016/j.taap.2013.08.003
Liu, J., Wu, Q., Lu, Y. F., & Pi, J. (2008). New insights into generalized hepatoprotective effects of oleanolic acid: Key roles of metallothionein and Nrf2 induction. Biochemical Pharmacology, 76(7), 922-928. https://doi.org/10.1016/j.bcp.2008.07.021
Liu, Q., Pan, R., Ding, L., Zhang, F., Hu, L., … Dou, X. (2017). Rutin exhibits hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipid-induced oxidative. International Immunopharmacology, 49, 132-141. https://doi.org/10.1016/j.intimp.2017.05.026
Lu, Y. F., Wan, X. L., Xu, Y., & Liu, J. (2013). Repeated oral administration of oleanolic acid produces cholestatic liver injury in mice. Molecules, 18(3), 3060-3071. https://doi.org/10.3390/molecules18033060
Ma, X., Zhao, Y. L., Zhu, Y., Chen, Z., Wang, J. B., Li, R. Y., … Xiao, X. H. (2015). Paeonia lactiflora pall. Protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway. Drug Design, Development and Therapy, 9, 5061-5074. https://doi.org/10.2147/DDDT.S90030
Malik, E. M., & Müller, C. E. (2016). Anthraquinones as pharmacological tools and drugs. Medicinal Research Reviews, 36(4), 705-748. https://doi.org/10.1002/med.21391
Mazzanti, G., Menniti-Ippolito, F., Moro, P. A., Cassetti, F., Raschetti, R., Santuccio, C., & Mastrangelo, S. (2009). Hepatotoxicity from green tea: A review of the literature and two unpublished cases. European Journal of Clinical Pharmacology, 65(4), 331-341. https://doi.org/10.1007/s00228-008-0610-7
Min, J., Chen, H., Gong, Z., Liu, X., Wu, T., Li, W., … Wang, N. (2018). Pharmacokinetic and pharmacodynamic properties of rosmarinic acid in rat cholestatic liver injury. Molecules, 23(9), E2287. https://doi.org/10.3390/molecules23092287
Moussa, C., Hebron, M., Huang, X., Ahn, J., Rissman, R. A., Aisen, P. S., & Turner, R. S. (2017). Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease. Journal of Neuroinflammation, 14(1), 1. https://doi.org/10.1186/s12974-016-0779-0
Naveed, M., Hejazi, V., Abbas, M., Kamboh, A. A., Khan, G. J., Shumzaid, M., … Xiao-Hui, Z. (2018). Chlorogenic acid (CGA): A pharmacological review and call for further research. Biomedicine & Pharmacotherapy, 2018(97), 67-74. https://doi.org/10.1016/j.biopha.2017.10.064
Nishio, T., Hu, R., Koyama, Y., Liang, S., Rosenthal, S. B., Yamamoto, G., … Kisseleva, T. (2019). Activated hepatic stellate cells and portal fibroblasts contribute to cholestatic liver fibrosis in MDR2 knockout mice. Journal of Hepatology, 71(3), 573-585. https://doi.org/10.1016/j.jhep.2019.04.012
Pan, P. H., Lin, S. Y., Wang, Y. Y., Chen, W. Y., Chuang, Y. H., Wu, C. C., & Chen, C. J. (2014). Protective effects of rutin on liver injury induced by biliary obstruction in rats. Free Radical Biology & Medicine, 73, 106-116. https://doi.org/10.1016/j.freeradbiomed.2014.05.001
Park, E. J., Zhao, Y. Z., Kim, Y. C., & Sohn, D. H. (2007). PF2401-SF, standardized fraction of Salvia miltiorrhiza and its constituents, tanshinone I, tanshinone IIA, and cryptotanshinone, protect primary cultured rat hepatocytes from bile acid-induced apoptosis by inhibiting JNK phosphorylation. Food and Chemical Toxicology, 45(10), 1891-1898. https://doi.org/10.1016/j.fct.2007.04.005
Park, P. H., Nan, J. X., Park, E. J., Kang, H. C., Kim, J. Y., Ko, G., & Sohn, D. H. (2000). Effect of tetrandrine on experimental hepatic fibrosis induced by bile duct ligation and scission in rats. Pharmacology & Toxicology, 87(6), 261-268. https://doi.org/10.1034/j.1600-0773.2000.pto870604.x
Paula, F. T., Frauches, P. Q., Pedebos, C., Berger, M., Gnoatto, S. C., Gossmann, G., … Graebin, C. S. (2013). Improving the thrombin inhibitory activity of glycyrrhizin, a triterpenic saponin, through a molecular simplification of the carbohydrate moiety. Chemical Biology & Drug Design, 82(6), 756-760. https://doi.org/10.1111/cbdd.12204
Peres, W., Tuñón, M. J., Collado, P. S., Herrmann, S., Marroni, N., & González-Gallego, J. (2000). The flavonoid quercetin ameliorates liver damage in rats with biliary obstruction. Journal of Hepatology, 33(5), 742-750. https://doi.org/10.1016/S0168-8278(00)80305-0
Salas, A. L., Ocampo, G., Fariña, G. G., Reyes-Esparza, J., & Rodríguez-Fragoso, L. (2007). Genistein decreases liver fibrosis and cholestasis induced by prolonged biliary obstruction in the rat. Annals of Hepatology, 6(1), 41-47.
Samur, S., Klebanoff, M., Banken, R., Pratt, D. S., Chapman, R., Ollendorf, D. A., … Chhatwal, J. (2017). Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis. Hepatology, 65(3), 920-928. https://doi.org/10.1002/hep.28932
Santana, D. G., Santos, C. A., Santos, A. D., Nogueira, P. C., Thomazzi, S. M., Estevam, C. S., … Camargo, E. A. (2012). Beneficial effects of the ethanol extract of Caesalpinia pyramidalis on the inflammatory response and abdominal hyperalgesia in rats with acute pancreatitis. Journal of Ethnopharmacology, 142(2), 445-455. https://doi.org/10.1016/j.jep.2012.05.015
Serviddio, G., Bellanti, F., Stanca, E., Lunetti, P., Blonda, M., Tamborra, R., … Giudetti, A. M. (2014). Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis. Free Radical Biology & Medicine, 73, 117-126. https://doi.org/10.1016/j.freeradbiomed.2014.05.002
Shen, K., Feng, X., Pan, H., Zhang, F., Xie, H., & Zheng, S. (2017). Baicalin ameliorates experimental liver cholestasis in mice by modulation of oxidative stress, inflammation, and NRF2 transcription factor. Oxidative Medicine and Cellular Longevity, 2017, 6169128. https://doi.org/10.1155/2017/6169128
Shen, K., Feng, X., Su, R., Xie, H., Zhou, L., & Zheng, S. (2015). Epigallocatechin 3-gallate ameliorates bile duct ligation induced liver injury in mice by modulation of mitochondrial oxidative stress and inflammation. PLoS One, 10(5), e0126278. https://doi.org/10.1371/journal.pone.0126278
Shi, L., Hao, Z., Zhang, S., Wei, M., Lu, B., Wang, Z., & Ji, L. (2018). Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC. Biochemical Pharmacology, 150, 9-23. https://doi.org/10.1016/j.bcp.2018.01.026
Stieger, B., & Mahdi, Z. M. (2017). Model systems for studying the role of canalicular efflux transporters in drug-induced cholestatic liver disease. Journal of Pharmaceutical Sciences, 106(9), 2295-2301. https://doi.org/10.1016/j.xphs.2017.03.023
Sun, Y. F., & Wink, M. (2014). Tetrandrine and fangchinoline, bisbenzylisoquinoline alkaloids from Stephania tetrandra can reverse multidrug resistance by inhibiting P-glycoprotein activity in. Phytomedicine, 21(8-9), 1110-1119. https://doi.org/10.1016/j.phymed.2014.04.029
Swinney, D. C. (2013). Phenotypic vs. target-based drug discovery for first-in-class medicines. Clinical Pharmacology and Therapeutics, 93(4), 299-301. https://doi.org/10.1038/clpt.2012.236
Tan, Z., Liu, A., Luo, M., Yin, X., Song, D., Dai, M., … Chen, B. (2016). Geniposide inhibits alpha-naphthylisothiocyanate-induced intrahepatic cholestasis: The downregulation of STAT3 and NF[formula: See text]B signaling plays an important role. The American Journal of Chinese Medicine, 44(4), 721-736. https://doi.org/10.1142/S0192415X16500397
Tan, Z., Luo, M., Yang, J., Cheng, Y., Huang, J., Lu, C., … Guo, B. (2016). Chlorogenic acid inhibits cholestatic liver injury induced by α-naphthylisothiocyanate: Involvement of STAT3 and NFκB signalling regulation. The Journal of Pharmacy and Pharmacology, 68(9), 1203-1213. https://doi.org/10.1111/jphp.12592
Tang, X., Yang, Q., Yang, F., Gong, J., Han, H., Yang, L., & Wang, Z. (2016). Target profiling analyses of bile acids in the evaluation of hepatoprotective effect of gentiopicroside on ANIT-induced cholestatic liver injury in mice. Journal of Ethnopharmacology, 194, 63-71. https://doi.org/10.1016/j.jep.2016.08.049
Tian, C., Zhang, T., Wang, L., Shan, Q., & Jiang, L. (2014). The hepatoprotective effect and chemical constituents of total iridoids and xanthones extracted from Swertia mussotii Franch. Journal of Ethnopharmacology, 154(1), 259-266. https://doi.org/10.1016/j.jep.2014.04.018
Tokaç, M., Taner, G., Aydın, S., Ozkardeş, A. B., Dündar, H. Z., Taşlıpınar, M. Y., … Basaran, N. (2013). Protective effects of curcumin against oxidative stress parameters and DNA damage in the livers and kidneys of rats with biliary obstruction. Food and Chemical Toxicology, 61, 28-35. https://doi.org/10.1016/j.fct.2013.01.015
Vieira, E. K., Bona, S., Di Naso, F. C., Porawski, M., Tieppo, J., & Marroni, N. P. (2011). Quercetin treatment ameliorates systemic oxidative stress in cirrhotic rats. ISRN Gastroenterol, 2011, 604071. https://doi.org/10.5402/2011/604071
Wang, L., Cao, F., Zhu, L. L., Liu, P., Shang, Y. R., Liu, W. H., … Wang, Z. Y. (2019). Andrographolide impairs alpha-naphthylisothiocyanate-induced cholestatic liver injury in vivo. Journal of Natural Medicines, 73(2), 388-396. https://doi.org/10.1007/s11418-018-01275-3
Wang, L., Huang, Q. H., Li, Y. X., Huang, Y. F., Xie, J. H., Xu, L. Q., … Chen, J. N. (2018). Protective effects of silymarin on triptolide-induced acute hepatotoxicity in rats. Molecular Medicine Reports, 17(1), 789-800. https://doi.org/10.3892/mmr.2017.7958
Wang, L., Wu, G., Wu, F., Jiang, N., & Lin, Y. (2017). Geniposide attenuates ANIT-induced cholestasis through regulation of transporters and enzymes involved in bile acids homeostasis in rats. Journal of Ethnopharmacology, 196, 178-185. https://doi.org/10.1016/j.jep.2016.12.022
Wang, T., Zhou, Z. X., Sun, L. X., Li, X., Xu, Z. M., Chen, M., … Zhang, L. Y. (2014). Resveratrol effectively attenuates α-naphthyl- isothiocyanate-induced acute cholestasis and liver injury through choleretic and anti-inflammatory mechanisms. Acta Pharmacologica Sinica, 35(12), 1527-1536. https://doi.org/10.1038/aps.2014.119
Wang, W., Chen, J., Mao, J., Li, H., Wang, M., Zhang, H., … Chen, W. (2018). Genistein. Ameliorates non-alcoholic fatty liver disease by targeting the thromboxane A2 pathway. Journal of Agricultural and Food Chemistry, 66(23), 5853-5859. https://doi.org/10.9734/BJMMR/2016/27654
Wang, X., Han, L., Bi, Y., Li, C., Gao, X., Fan, G., & Zhang, Y. (2019). Paradoxical effects of emodin on ANIT-induced intrahepatic cholestasis and herb-induced hepatotoxicity in mice. Toxicological Sciences, 168(1), 264-278. https://doi.org/10.1093/toxsci/kfy295
Wang, Y., Jiang, Y., Fan, X., Tan, H., Zeng, H., Wang, Y., … Bi, H. (2015). Hepato-protective effect of resveratrol against acetaminophen-induced liver injury is associated with inhibition of CYP-mediated bioactivation and regulation of SIRT1-p53 signaling pathways. Toxicology Letters, 236(2), 82-89. https://doi.org/10.1016/j.toxlet.2015.05.001
Wang, Y., Zhao, H., Li, X., Wang, Q., Yan, M., Zhang, H., … Li, P. (2019). Formononetin alleviates hepatic steatosis by facilitating TFEB-mediated lysosome biogenesis and lipophagy. The Journal of Nutritional Biochemistry, 73, 108214. https://doi.org/10.1016/j.jnutbio.2019.07.005
Wang, Y. G., Zhou, J. M., Ma, Z. C., Li, H., Liang, Q. D., Tan, H. L., … Gao, Y. (2012). Pregnane X receptor mediated-transcription regulation of CYP3A by glycyrrhizin: A possible mechanism for its hepatoprotective property against lithocholic acid-induced injury. Chemico-Biological Interactions, 200(1), 11-20. https://doi.org/10.1016/j.cbi.2012.08.023
Woolbright, B. L., & Jaeschke, H. (2016). Therapeutic targets for cholestatic liver injury. Expert Opinion on Therapeutic Targets, 20(4), 463-475. https://doi.org/10.1517/14728222.2016.1103735
Woźniak, D., Lamer-Zarawska, E., & Matkowski, A. (2004). Antimutagenic and antiradical properties of flavones from the roots of Scutellaria baicalensis georgi. Nahrung, 48(1), 9-12. https://doi.org/10.1002/food.200200230
Wu, D., Bao, C., Li, L., Fu, M., Wang, D., Xie, J., & Gong, X. (2015). Chlorogenic acid protects against cholestatic liver injury in rats. Journal of Pharmacological Sciences, 129(3), 177-182. https://doi.org/10.1016/j.jphs.2015.10.005
Wu, S. Y., Cui, S. C., Wang, L., Zhang, Y. T., Yan, X. X., Lu, H. L., … Gong, L. K. (2018). 18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway. Acta Pharmacologica Sinica, 39(12), 1865-1873. https://doi.org/10.1038/s41401-018-0110-y
Wu, T., Chang, M. J., Xu, Y. J., Li, X. P., Du, G., & Liu, D. (2013). Protective effect of calculus Bovis Sativus on intrahepatic cholestasis in rats induced by α-Naphthylisothiocyanate. The American Journal of Chinese Medicine, 41(6), 1393-1405. https://doi.org/10.1142/S0192415X13500936
Wu, T., Zhang, Q., Li, J., Chen, H., Wu, J., & Song, H. (2016). Up-regulation of BSEP and MRP2 by Calculus Bovis administration in 17α-ethynylestradiol-induced cholestasis: Involvement of PI3K/Akt signaling pathway. Journal of Ethnopharmacology, 190, 22-32. https://doi.org/10.1016/j.jep.2016.05.056
Xiang, D., Yang, J., Liu, Y., He, W., Zhang, S., Li, X., … Liu, D. (2019). Calculus Bovis Sativus improves bile acid homeostasis via Farnesoid X receptor-mediated Signaling in rats with estrogen-induced cholestasis. Frontiers in Pharmacology, 10, 48. https://doi.org/10.3389/fphar.2019.00048
Xiong, X. L., Ding, Y., Chen, Z. L., Wang, Y., Liu, P., Qin, H., … Zhao, L. (2019). Emodin rescues intrahepatic cholestasis via stimulating FXR/BSEP pathway in promoting the Canalicular export of accumulated bile. Frontiers in Pharmacology, 10, 522. https://doi.org/10.3389/fphar.2019.00522
Yang, F., Tang, X., Ding, L., Zhou, Y., Yang, Q., Gong, J., … Yang, L. (2016). Curcumin protects ANIT-induced cholestasis through signaling pathway of FXR-regulated bile acid and inflammation. Scientific Reports, 6, 33052. https://doi.org/10.1038/srep33052
Yang, F., Xu, Y., Xiong, A., He, Y., Yang, L., Wan, Y. J., & Wang, Z. (2012). Evaluation of the protective effect of Rhei radix et Rhizoma against α-naphthylisothiocyanate induced liver injury based on metabolic profile of bile acids. Journal of Ethnopharmacology, 144(3), 599-604. https://doi.org/10.1016/j.jep.2012.09.049
Yang, Q. L., Yang, F., Gong, J. T., Tang, X. W., Wang, G. Y., Wang, Z. T., & Yang, L. (2016). Sweroside ameliorates α-naphthylisothiocyanate-induced cholestatic liver injury in mice by regulating bile acids and suppressing pro-inflammatory responses. Acta Pharmacologica Sinica, 37(9), 1218-1228. https://doi.org/10.1038/aps.2016.86
Yang, S., Wei, L., Xia, R., Liu, L., Chen, Y., Zhang, W., … Ma, C. (2019). Formononetin ameliorates cholestasis by regulating hepatic SIRT1 and PPARa. Biochemical and Biophysical Research Communications, 512(4), 770-778. https://doi.org/10.1016/j.bbrc.2019.03.131
Yang, T., Khan, G. J., Wu, Z., Wang, X., Zhang, L., & Jiang, Z. (2019). Bile acid homeostasis paradigm and its connotation with cholestatic liver diseases. Drug Discovery Today, 24(1), 112-128. https://doi.org/10.1016/j.drudis.2018.09.007
Yao, J., Zhi, M., & Minhu, C. (2011). Lipid hepatoprotective effect of silibinin on fat-induced nonalcoholic fatty liver rat model. Brazilian Journal of Medical and Biological Research, 44(7), 652-659. https://doi.org/10.1590/s0100-879x2011007500083
Yi, Y. X., Ding, Y., Zhang, Y., Ma, N. H., Shi, F., Kang, P., … Zhang, T. (2018). Yinchenhao decoction ameliorates alpha-naphthylisothiocyanate induced intrahepatic cholestasis in rats by regulating phase II metabolic enzymes and transporters. Front Pharmacol, 9, 510. https://doi.org/10.3389/fphar.2018.00510
Yildirim, M. A., Goh, K. I., Cusick, M. E., Barabási, A. L., & Vidal, M. (2007). Drug-target network. Nature Biotechnology, 25(10), 1119-1126.
Yongping, M., Zhang, X., Xuewei, L., Fan, W., Chen, J., Zhang, H., … Liu, P. (2015). Astragaloside prevents BDL-induced liver fibrosis through inhibition of notch signaling activation. Journal of Ethnopharmacology, 169, 200-209. https://doi.org/10.1016/j.jep.2015.04.015
Yu, D. K., Zhang, C. X., Zhao, S. S., Zhang, S. H., Zhang, H., Cai, S. Y., … He, H. W. (2015). The anti-fibrotic effects of epigallocatechin-3-gallate in bile duct-ligated cholestatic rats and human hepatic stellate LX-2 cells are mediated by the PI3K/Akt/Smad pathway. Acta Pharmacologica Sinica, 36(4), 473-482. https://doi.org/10.1038/aps.2014.155
Yuan, H., Ma, Q., Ye, L., & Piao, G. (2016). The traditional medicine and modern medicine from natural products. Molecules, 21(5), E559. https://doi.org/10.3390/molecules21050559
Zhai, D., Zhao, Y., Chen, X., Guo, J., He, H., Yu, Q., … Wang, J. (2007). Protective effect of glycyrrhizin, glycyrrhetic acid and matrine on acute cholestasis induced by alpha-naphthyl isothiocyanate in rats. Planta Medica, 73(2), 128-133. https://doi.org/10.1055/s-2006-957067
Zhang, C. L., Xu, Y. J., Xiang, D., Yang, J. Y., Lei, K., & Liu, D. (2018). Pharmacokinetic characteristics of baicalin in rats with 17a-ethynylestradiol-induced intrahepatic cholestasis. Current Medical Science, 38(1), 167-173. https://doi.org/10.1007/s11596-018-1861-x
Zhang, G., Zhou, Y., Rao, Z., Qin, H., Wei, Y., Ren, J., … Wu, X. (2015). Effect of Yin-Zhi-Huang on up-regulation of Oatp2, Ntcp, and Mrp2 proteins in estrogen-induced rat cholestasis. Pharmaceutical Biology, 53(3), 319-325. https://doi.org/10.3109/13880209.2014.918156
Zhang, L., Cheng, Y., Du, X., Chen, S., Feng, X., Gao, Y., … Chai, J. (2015). Swertianlarin, an herbal agent derived from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in common bile duct-ligated rats. Evid Based Complement Alternat Med, 2015(2015), 948376. https://doi.org/10.1155/2015/948376
Zhang, M., & Xu, M. (2017). Epigallocatechin-3-gallate ameliorates intrahepatic cholestasis of pregnancy by inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9. Fundamental & Clinical Pharmacology, 31(5), 526-533. https://doi.org/10.1111/fcp.12294
Zhang, X., Ma, Z., Liang, Q., Tang, X., Hu, D., Liu, C., … Gao, Y. (2015). Tanshinone IIA exerts protective effects in a LCA-induced cholestatic liver model associated with participation of pregnane X receptor. Journal of Ethnopharmacology, 164, 357-367. https://doi.org/10.1016/j.jep.2015.01.047
Zhao, Y., He, X., Ma, X., Wen, J., Li, P., Wang, J., … Xiao, X. (2017). Paeoniflorin ameliorates cholestasis via regulating hepatic transporters and suppressing inflammation in ANIT-fed rats. Biomedicine & Pharmacotherapy, 89, 61-68. https://doi.org/10.1016/j.biopha.2017.02.025
Zhao, Y., Zhou, G., Wang, J., Jia, L., Zhang, P., Li, R., … Xiao, X. (2013). Paeoniflorin protects against ANIT-induced cholestasis by ameliorating oxidative stress in rats. Food and Chemical Toxicology, 58, 242-248. https://doi.org/10.1016/j.fct.2013.04.030
Zhao, Y. L., Wang, J. B., Zhou, G. D., Shan, L. M., & Xiao, X. H. (2009). Investigations of free anthraquinones from rhubarb against α-naphthylisothiocyanate-induced cholestatic liver injury in rats. Basic & Clinical Pharmacology & Toxicology, 104(6), 463-469. https://doi.org/10.1111/j.1742-7843.2009.00389.x
Zhao, Z. W., Chang, J. C., Lin, L. W., Tsai, F. H., Chang, H. C., & Wu, C. R. (2018). Comparison of the hepatoprotective effects of four endemic cirsium species extracts from Taiwan on CCl₄-induced acute liver damage in C57BL/6 mice. International Journal of Molecular Sciences, 19(5), E1329. https://doi.org/10.3390/ijms19051329
Zhou, H. Q., Liu, W., Wang, J., Huang, Y. Q., Li, P. Y., Zhu, Y., … Zhao, Y. L. (2017). Paeoniflorin attenuates ANIT-induced cholestasis by inhibiting apoptosis in vivo via mitochondria-dependent pathway. Biomedicine & Pharmacotherapy, 89, 696-704. https://doi.org/10.1016/j.biopha.2017.02.084
Zhou, X., Menche, J., Barabási, A. L., & Sharma, A. (2014). Human symptoms-disease network. Nature Communications, 5, 4212. https://doi.org/10.1038/ncomms5212
Zhu, L., Wang, L., Cao, F., Liu, P., Bao, H., Yan, Y., … Gong, P. (2018). Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxity and cholestasis in bile duct ligation rats: Involvement of SIRT1-mediated deacetylation of FXR and PGC-1α. Journal of Hepato-Biliary-Pancreatic Sciences, 25(3), 195-205. https://doi.org/10.1002/jhbp.537
Zordoky, B. N., Robertson, I. M., & Dyck, J. R. (2015). Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases. Biochimica et Biophysica Acta, 1852(6), 1155-1177. https://doi.org/10.1016/j.bbadis.2014.10.016