The metabolism of berberine and its contribution to the pharmacological effects

References

• Ahmed T, Gilani AU, Abdollahi M, et al. (2015). Berberine and neurodegeneration: a review of literature. Pharmacol Rep 67:970–979.
   PubMed Web of Science ®Google Scholar
• Balasubramani SP, Goraya GS, Venkatasubramanian P. (2011). Development of ITS sequence-based markers to distinguish Berberis aristata DC. from B. lycium Royle and B. asiatica Roxb. 3 Biotech 1:11–19.
   PubMedGoogle Scholar
• Bao MM, Cao ZF, Yu D, et al. (2012). Columbamine suppresses the proliferation and neovascularization of metastatic osteosarcoma U2OS cells with low cytotoxicity. Toxicol Lett 215:174–180.
   PubMed Web of Science ®Google Scholar
• Brezova V, Dvoranova D, Kost'alova D. (2004). Oxygen activation by photoexcited protoberberinium alkaloids from Mahonia aquifolium. Phytother Res 18:640–646.
   PubMed Web of Science ®Google Scholar
• Caliceti C, Franco P, Spinozzi S, et al. (2016). Berberine: new insights from pharmacological aspects to clinical evidences in the management of metabolic disorders. Curr Med Chem 23:1460–1476.
   PubMed Web of Science ®Google Scholar
• Campisi A, Acquaviva R, Mastrojeni S, et al. (2011). Effect of berberine and Berberis aetnensis C. Presl. alkaloid extract on glutamate-evoked tissue transglutaminase up-regulation in astroglial cell cultures. Phytother Res 25:816–820.
   PubMed Web of Science ®Google Scholar
• Cao SJ, Zhou Y, Xu PX, et al. (2013). Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells. J Ethnopharmacol 149:576–582.
   PubMed Web of Science ®Google Scholar
• Chen G, Lu F, Xu LJ, et al. (2013a). The anti-diabetic effects and pharmacokinetic profiles of berberine in mice treated with Jiao-Tai-Wan and its compatibility. Phytomedicine 20:780–786.
   PubMed Web of Science ®Google Scholar
• Chen HX, Huang JL, Li J. (2010a). Structural elucidation of in vivo and in vitro metabolites of epiberberine in rat and its liver and intestines by liquid chromatography-tandem mass spectrometry. Anal Lett 43:2505–2517.
   Web of Science ®Google Scholar
• Chen HY, Ye XL, Cui XL, et al. (2012). Cytotoxicity and antihyperglycemic effect of minor constituents from Rhizoma Coptis in HepG2 cells. Fitoterapia 83:67–73.
   PubMed Web of Science ®Google Scholar
• Chen JL, Zhang YL, Dong Y, et al. (2013b). Enzyme reaction kinetics, metabolic enzyme phenotype, and metabolites of berberine. Zhong Cao Yao 44:3334–3340.
   Google Scholar
• Chen ML, Xian YF, Ip SP, et al. (2010b). Chemical and biological differentiation of Cortex Phellodendri Chinensis and Cortex Phellodendri Amurensis. Planta Med 76:1530–1535.
   PubMed Web of Science ®Google Scholar
• Chen ZJ, Zheng SR, Li LP, et al. (2014). Metabolism of flavonoids in human: a comprehensive review. Curr Drug Metab 15:48–61.
   PubMed Web of Science ®Google Scholar
• Cheng ML, Liu RJ, Wu Y, et al. (2016). LC-MS/MS determination and urinary excretion study of seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets. J Pharm Biomed Anal 118:89–95.
   PubMed Web of Science ®Google Scholar
• Cho JY, Kim AR, Park MH. (2001). Lignans from the rhizomes of Coptis japonica differentially act as anti-inflammatory principles. Planta Med 67:312–316.
   PubMed Web of Science ®Google Scholar
• Cho YJ. (2011). Anti-inflammatory effect of jatrorhizine form Phellodendron amurense in lipopolysaccharide-stimulated raw 264.7 cells. J Appl Biol Chem 54:114–119.
   Google Scholar
• Cicero AFG, Tartagni E. (2012). Antidiabetic properties of berberine: from cellular pharmacology to clinical effects. Hosp Pract (1995) 40:56–63.
   PubMedGoogle Scholar
• Cui HM, Zhang QY, Wang JL, et al. (2015). Poor permeability and absorption affect the activity of four alkaloids from Coptis. Mol Med Rep 12:7160–7168.
   PubMed Web of Science ®Google Scholar
• Cui HS, Hayasaka S, Zhang XY, et al. (2006). Effect of berberrubine on interleukin-8 and monocyte chemotactic protein-1 expression in human retinal pigment epithelial cell line. Life Sci 79:949–956.
   PubMed Web of Science ®Google Scholar
• Dan Y, Liu YZ, Peng Y, et al. (2011). New collection of crude drugs in Chinese pharmacopoeia 2010 II. Sankezhen (Berberis spp.). Chin Herb Med 3:272–288.
   Google Scholar
• Deng YC, Zhang M, Luo HY. (2012). Identification and antimicrobial activity of two alkaloids from traditional Chinese medicinal plant Tinospora capillipes. Ind Crops Prod 37:298–302.
   Web of Science ®Google Scholar
• Diogo CV, Machado NG, Barbosa IA, et al. (2011). Berberine as a promising safe anti-cancer agent - is there a role for mitochondria? Curr Drug Targets 12:850–859.
   PubMed Web of Science ®Google Scholar
• El-Salam MA, Mekky H, El-Naggar EMB, et al. (2015). Hepatoprotective properties and biotransformation of berberine and berberrubine by cell suspension cultures of Dodonaea viscosa and Ocimum basilicum. S Afr J Bot 97:191–195.
   Web of Science ®Google Scholar
• Feng R, Shou JW, Zhao ZX, et al. (2015). Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep 5:12155–12169.
   PubMed Web of Science ®Google Scholar
• Fu Y, H BR, T Q, et al. (2005). Hypoglycemic activity of Jatrorrhizine. J Huazhong Univ Sci Technol. Med. Sci 25:491–493.
   PubMedGoogle Scholar
• Gambhir S, Vyas D, Hollis M, et al. (2015). Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies. World J Gastroenterol 21:3174–3183.
   PubMed Web of Science ®Google Scholar
• Gilca M, Gaman L, Panait E, et al. (2010). Chelidonium majus-an integrative review: traditional knowledge versus modern findings. Forsch Komplementmed 17:241–248.
   PubMedGoogle Scholar
• Gulfraz M, Mehmood S, Ahmad A, et al. (2008). Comparison of the antidiabetic activity of Berberis lyceum root extract and berberine in alloxan-induced diabetic rats. Phytother Res 22:1208–1212.
   PubMed Web of Science ®Google Scholar
• Guo Y, Li F, Ma X, et al. (2011). CYP2D plays a major role in berberine metabolism in liver of mice and humans. Xenobiotica 41:996–1005.
   PubMed Web of Science ®Google Scholar
• Hambright HG, Batth IS, Xie JP, et al. (2015). Palmatine inhibits growth and invasion in prostate cancer cell: potential role for rpS6/NFκB/FLIP. Mol Carcinog 54:1227–1234.
   PubMed Web of Science ®Google Scholar
• Hamid HA, Yusoff MM, Liu M, et al. (2015). α-Glucosidase and α-amylase inhibitory constituents of Tinospora crispa: Isolation and chemical profile confirmation by ultra-high performance liquid chromatography-quadrupole time-of-flight/mass spectrometry. J Funct Foods 16:74–80.
   Web of Science ®Google Scholar
• Han FM, Zhu MM, Chen HX, et al. (2006). Liquid chromatography-tandem electrospray ionization ion trap mass spectrometric assay for the metabolites of jatrorrhizine in rat urine. Yao Xue Xue Bao 41:846–851.
   PubMedGoogle Scholar
• He JM, Mu Q. (2015). The medicinal uses of the genus Mahonia in traditional Chinese medicine: an ethnopharmacological, phytochemical and pharmacological review. J Ethnopharmacol 175:668–683.
   PubMed Web of Science ®Google Scholar
• He K, Kou SM, Zou ZY, et al. (2016). Hypolipidemic effects of alkaloids from Rhizoma Coptidis in diet-induced hyperlipidemic hamsters. Planta Med 82:1–9.
   PubMed Web of Science ®Google Scholar
• Hua WY, Ding L, Chen Y, et al. (2007). Determination of berberine in human plasma by liquid chromatography-electrospray ionization-mass spectrometry. J Pharm Biomed Anal 44:931–937.
   PubMed Web of Science ®Google Scholar
• Hussain N, Adhikari A, Ahmad MS, et al. (2017). Two new prenylated flavonoids from the roots of Berberis thunbergii DC. Nat Prod Res 31:785–790.
   PubMed Web of Science ®Google Scholar
• Hwang BY, Roberts SK, Chadwick LR, et al. (2003). Antimicrobial constituents from goldenseal (the Rhizomes of Hydrastis canadensis) against selected oral pathogens. Planta Med 69:623–627.
   PubMed Web of Science ®Google Scholar
• Ikekawa T, Ikeda Y. (1982). Antitumor activity of 13-methyl-berberrubine derivatives. J Pharmacobio-dyn 5:469–474.
   PubMedGoogle Scholar
• Jang MH, Kim HY, Kang KS, et al. (2009). Hydroxyl radical scavenging activities of isoquinoline alkaloids isolated from Coptis chinensis. Arch Pharm Res 32:341–345.
   PubMed Web of Science ®Google Scholar
• Ji HF, Shen L. (2011). Berberine: a potential multipotent natural product to combat Alzheimer's disease. Molecules 16:6732–6740.
   PubMed Web of Science ®Google Scholar
• Jiang W, Duan WB, Li S, et al. (2016). Jatrorrhizine protects against okadaic acid induced oxidative toxicity through inhibiting the mitogen-activated protein kinases pathways in HT22 hippocampal neurons. CNS Neurol Disord Drug Targets 14:1334–1342.
   Web of Science ®Google Scholar
• Kaboli PJ, Rahmat A, Ismail P, et al. (2014). Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer. Eur J Pharmacol 740:584–595.
   PubMed Web of Science ®Google Scholar
• Kang MR, Chung IK. (2002). Down-regulation of DNA topoisomerase IIalpha in human colorectal carcinoma cells resistant to a protoberberine alkaloid, berberrubine. Mol Pharmacol 61:879–884.
   PubMed Web of Science ®Google Scholar
• Kheir MM, Wang Y, Hua L, et al. (2010). Acute toxicity of berberine and its correlation with the blood concentration in mice. Food Chem Toxicol 48:1105–1110.
   PubMed Web of Science ®Google Scholar
• Kim SA, Kwon Y, Kim JH, et al. (1998). Induction of topoisomerase II-mediated DNA cleavage by a protoberberine alkaloid, berberrubine. Biochemistry 37:16316–16324.
   PubMed Web of Science ®Google Scholar
• Laamech J, El-Hilaly J, Fetoui H, et al. (2017). Berberis vulgaris L. effects on oxidative stress and liver injury in lead-intoxicated mice. J Complement Integr Med. [Epub ahead of print]. doi:10.1515/jcim-2015-0079
   PubMedGoogle Scholar
• Lan JR, Dong FX, Yan ZY, et al. (2015). Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol 161:69–81.
   PubMed Web of Science ®Google Scholar
• Lau CW, Yao XQ, Chen ZY, et al. (2006). Cardiovascular actions of berberine. Cardiovasc Drug Rev 19:234–244.
   Google Scholar
• Lee HY, He XL, Ahn J. (2010). Enhancement of antimicrobial and antimutagenic activities of Korean barberry (Berberis koreana Palib.) by the combined process of high-pressure extraction with probiotic fermentation. J Sci Food Agric 90:2399–2404.
   PubMed Web of Science ®Google Scholar
• Li M, Xu J, Zhao M, et al. (2014). UPLC-Q-TOFMS/MS analysis of berberine and gut microbiota transformed metabolites. Xinyang Shifan Xue Yuan Xue Bao 27:510–514.
   Google Scholar
• Li Y, Ren G, Wang YX, et al. (2011). Bioactivities of berberine metabolites after transformation through CYP450 isoenzymes. J Transl Med 9:286–298.
   Web of Science ®Google Scholar
• Liu CS, Zheng YR, Zhang YF, et al. (2016). Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia 109:274–282.
   PubMed Web of Science ®Google Scholar
• Liu LH, Chen ZL. (2012). Analysis of four alkaloids of Coptis chinensis in rat plasma by high performance liquid chromatography with electrochemical detection. Anal Chim Acta 737:99–104.
   PubMed Web of Science ®Google Scholar
• Liu RF, Cao ZF, Pan YY, et al. (2013). Jatrorrhizine hydrochloride inhibits the proliferation and neovascularization of C8161 metastatic melanoma cells. Anticancer Drugs 24:667–676.
   PubMed Web of Science ®Google Scholar
• Liu YT, Hao HP, Xie HG, et al. (2010). Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats. Drug Metab Dispos 38:1779–1784.
   PubMed Web of Science ®Google Scholar
• Liu YT, Hao HP, Xie HG, et al. (2009). Oxidative demethylenation and subsequent glucuronidation are the major metabolic pathways of berberine in rats. J Pharm Sci 98:4391–4401.
   PubMed Web of Science ®Google Scholar
• Luo T, Jiang W, Kong Y, et al. (2016). The protective effects of jatrorrhizine on β-amyloid (25-35)-induced neurotoxicity in rat cortical neurons. CNS Neurol Disord Drug Targets 11:1030–1037.
   Google Scholar
• Luo T, Zhang H, Zhang WW, et al. (2011). Neuroprotective effect of jatrorrhizine on hydrogen peroxide-induced cell injury and its potential mechanisms in PC12 cells. Neurosci Lett 498:227–231.
   PubMed Web of Science ®Google Scholar
• Ma CH, Li ZX, Wang LX, et al. (2009). Identification of major alkaloids in rat urine by HPLC/DAD/ESI-MS/MS method following oral administration of Cortex Phellodendri decoction. Helvetica Chimica Acta 92:379–398.
   Web of Science ®Google Scholar
• Ma JY, Feng R, Tan XS, et al. (2013). Excretion of berberine and its metabolites in oral administration in rats. J Pharm Sci 102:4181–4192.
   PubMed Web of Science ®Google Scholar
• Ma Y, Zeng M, Sun RJ, et al. (2014). Disposition of flavonoids impacts their efficacy and safety. Curr Drug Metab 15:841–864.
   PubMed Web of Science ®Google Scholar
• Mishra KP, Sharma N, Soree P, et al. (2016). Hypoxia-induced inflammatory chemokines in subjects with a history of high-altitude pulmonary edema. Indian J Clin Biochem 31:81–86.
   PubMed Web of Science ®Google Scholar
• Mizokami SS, Hohmann MS, Staurengo-Ferrari L, et al. (2016). Pimaradienoic acid inhibits carrageenan-induced inflammatory leukocyte recruitment and edema in mice: inhibition of oxidative stress, nitric oxide and cytokine production. PLoS One 11:1–17.
   Web of Science ®Google Scholar
• Ni WJ, Ding HH, Tang LQ. (2015). Berberine as a promising anti-diabetic nephropathy drug: an analysis of its effects and mechanisms. Eur J Pharmacol 760:103–112.
   PubMed Web of Science ®Google Scholar
• Ning N, He K, Wang YZ, et al. (2015). Hypolipidemic effect and mechanism of palmatine from Coptis chinensis in hamsters fed high-fat diet. Phytother Res 29:668–673.
   PubMed Web of Science ®Google Scholar
• Ortiz LM, Lombardi P, Tillhon M, et al. (2014). Berberine, an epiphany against cancer. Molecules 19:12349–12367.
   PubMed Web of Science ®Google Scholar
• Pan JF, Yu C, Zhu DY, et al. (2002). Identification of three sulfate-conjugated metabolites of berberine chloride in healthy volunteers' urine after oral administration. Acta Pharmaceutica Sin 23:77–82.
   Google Scholar
• Pang B, Zhao LH, Zhou Q, et al. (2015). Application of berberine on treating type 2 diabetes mellitus. Int J Endocrinol 2015:1–13.
   Web of Science ®Google Scholar
• Patel MB, Mishra S. (2011). Hypoglycemic activity of alkaloidal fraction of Tinospora cordifolia. Phytomedicine 18:1045–1052.
   PubMed Web of Science ®Google Scholar
• Potdar D, Hirwani RR, Dhulap S. (2012). Phyto-chemical and pharmacological applications of Berberis aristata. Fitoterapia 83:817–830.
   PubMed Web of Science ®Google Scholar
• Qiang XY, Xu LL, Zhang M, et al. (2016). Demethyleneberberine attenuates non-alcoholic fatty liver disease with activation of AMPK and inhibition of oxidative stress. Biochem Biophys Res Commun 472:603–609.
   PubMed Web of Science ®Google Scholar
• Qiu F, Zhu Z, Kang N, et al. (2008). Isolation and identification of urinary metabolites of berberine in rats and humans. Drug Metab Dispos 36:2159–2165.
   PubMed Web of Science ®Google Scholar
• Rackova L, Majekova M, Kost'alova D, et al. (2004). Antiradical and antioxidant activities of alkaloids isolated from Mahonia aquifolium. Structural aspects. Bioorg Med Chem 12:4709–4715.
   PubMed Web of Science ®Google Scholar
• Sangeetha MK, Priya CD, Vasanthi HR. (2013). Anti-diabetic property of Tinospora cordifolia and its active compound is mediated through the expression of Glut-4 in L6 myotubes. Phytomedicine 20:246–248.
   PubMed Web of Science ®Google Scholar
• Shi R, Zhou H, Ma BL, et al. (2012). Pharmacokinetics and metabolism of jatrorrhizine, a gastric prokinetic drug candidate. Biopharm Drug Dispos 33:135–145.
   PubMed Web of Science ®Google Scholar
• Spinozzi S, Colliva C, Camborata C, et al. (2014). Berberine and its metabolites: relationship between physicochemical properties and plasma levels after administration to human subjects. J Nat Prod 77:766–772.
   PubMed Web of Science ®Google Scholar
• Sun Y, Xun K, Wang Y, et al. (2009). A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs. Anticancer Drugs 20:757–769.
   PubMed Web of Science ®Google Scholar
• Tan XS, Ma JY, Feng R, et al. (2013). Tissue distribution of berberine and its metabolites after oral administration in rats. PLoS One 8:1–9.
   Web of Science ®Google Scholar
• Tang J, Feng YB, Tsao S, et al. (2009). Berberine and Coptidis rhizoma as novel antineoplastic agents: a review of traditional use and biomedical investigations. J Ethnopharmacol 126:5–17.
   PubMed Web of Science ®Google Scholar
• Thomson DM, Winder WW. (2009). AMP-activated protein kinase control of fat metabolism in skeletal muscle. Acta Physiol (Oxf) 196:147–154.
   PubMed Web of Science ®Google Scholar
• Tsai PL, Tsai TH. (2004). Hepatobiliary excretion of berberine. Drug Metab Dispos 32:405–417.
   PubMed Web of Science ®Google Scholar
• Valko M, Leibfritz D, Moncol J, et al. (2007). Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84.
   PubMed Web of Science ®Google Scholar
• Vollekova A, Kost'alova D, Kettmann V, et al. (2003). Antifungal activity of Mahonia aquifolium extract and its major protoberberine alkaloids. Phytother Res 17:834–837.
   PubMed Web of Science ®Google Scholar
• Vrba J, Papouskova B, Pyszkova M, et al. (2015). Metabolism of palmatine by human hepatocytes and recombinant cytochromes P450. J Pharm Biomed Anal 102:193–198.
   PubMed Web of Science ®Google Scholar
• Wang K, Qiu F. (2013). Curcuminoid metabolism and its contribution to the pharmacological effects. Curr Drug Metab 14:791–806.
   PubMed Web of Science ®Google Scholar
• Wang XQ, Wang SH, Ma JS, et al. (2015a). Pharmacokinetics in rats and tissue distribution in mouse of berberrubine by UPLC-MS/MS. J Pharm Biomed Anal 115:368–374.
   PubMed Web of Science ®Google Scholar
• Wang Y, Shou JW, Jiang JD. (2015b). Metabolism of Chinese materia medica in gut microbiota and its biological effects. Chinese Herb Med 7:109–115.
   Google Scholar
• Wang YC, Zhao Z, Yan Y, et al. (2016). Demethyleneberberine protects against hepatic fibrosis in mice by modulating NF-kappaB signaling. Int J Mol Sci 17:1036–1051.
   PubMed Web of Science ®Google Scholar
• Wu H, He K, Wang YZ, et al. (2014). The antihypercholesterolemic effect of jatrorrhizine isolated from Rhizoma Coptidis. Phytomedicine 21:1373–1381.
   PubMed Web of Science ®Google Scholar
• Wu M, Wang J, Liu LT. (2010). Advance of studies on anti-atherosclerosis mechanism of berberine. Chin J Integr Med 16:188–192.
   PubMed Web of Science ®Google Scholar
• Wu Y, Liu RJ, Gu P, et al. (2015). Highly sensitive method for simultaneous determination of nine alkaloids of Shuanghua Baihe tablets in human plasma by LC-MS/MS and its application. J Chromatogr B Analyt Technol Biomed Life Sci 1007:81–92.
   PubMed Web of Science ®Google Scholar
• Xie WD, Gu DY, Li JN, et al. (2011). Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice. PLoS One 6:1–10.
   Web of Science ®Google Scholar
• Yan BQ, Wang DS, Dong SW, et al. (2017). Palmatine inhibits TRIF-dependent NF-kappaB pathway against inflammation induced by LPS in goat endometrial epithelial cells. Int Immunopharmacol 45:194–200.
   PubMed Web of Science ®Google Scholar
• Yan D, Jin C, Xiao XH, et al. (2008). Antimicrobial properties of berberines alkaloids in Coptis chinensis Franch by microcalorimetry. J Biochem Biophys Methods 70:845–849.
   PubMedGoogle Scholar
• Yang N, Sun RB, Chen XL, et al. (2017). In vitro assessment of the glucose-lowering effects of berberrubine-9-O-β-D-glucuronide, an active metabolite of berberrubine. Acta Pharmacol Sin 38:351–361.
   PubMed Web of Science ®Google Scholar
• Yang QC, Wu WH, Han FM, et al. (2009). Identification of in-vivo and in-vitro metabolites of palmatine by liquid chromatography-tandem mass spectrometry. J Pharm Pharmacol 61:647–652.
   PubMed Web of Science ®Google Scholar
• Yang TC, Chao HF, Shi LS, et al. (2014). Alkaloids from Coptis chinensis root promote glucose uptake in C2C12 myotubes. Fitoterapia 93:239–244.
   PubMed Web of Science ®Google Scholar
• Yang YH, Kang N, Xia HJ, et al. (2010). Metabolites of protoberberine alkaloids in human urine following oral administration of Coptidis Rhizoma decoction. Planta Med 76:1859–1863.
   PubMed Web of Science ®Google Scholar
• Ye MZ, Fu S, Pi RB, et al. (2009). Neuropharmacological and pharmacokinetic properties of berberine: a review of recent research. J Pharm Pharmacol 61:831–837.
   PubMed Web of Science ®Google Scholar
• Yin J, Xing HL, Ye JP. (2008). Efficacy of berberine in patients with type 2 diabetes mellitus. Metab. Clin. Exp 57:712–717.
   PubMed Web of Science ®Google Scholar
• Yu C, Zhang H, Pan JF, et al. (2000). Determination and preliminary studies of metabolism of berberine in human urine after oral administration. Chin J Clin Pharmacol 16:36–39.
   Google Scholar
• Yu Y, Yi ZB, Liang YZ. (2007). Main antimicrobial components of Tinospora capillipes, and their mode of action against Staphylococcus aureus. FEBS Lett 581:4179–4183.
   PubMed Web of Science ®Google Scholar
• Zhang PC, Qiang XY, Zhang M, et al. (2014). Demethyleneberberine, a natural mitochondria-targeted antioxidant, inhibits mitochondrial dysfunction, oxidative stress, and steatosis in alcoholic liver disease mouse model. J Pharmacol Exp Ther 352:139–147.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Wu WH, Han FM, et al. (2008). LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine. Biomed Chromatogr 22:1360–1367.
   PubMed Web of Science ®Google Scholar
• Zhou H, Shi R, Ma BL, et al. (2013). CYP450 1A2 and multiple UGT1A isoforms are responsible for jatrorrhizine metabolism in human liver microsomes. Biopharm Drug Dispos 34:176–185.
   PubMed Web of Science ®Google Scholar
• Zhou HY, Eshita MS. (2000). The effect of berberine chloride on experimental colitis in rats in vivo and in vitro. J Pharmacol Exp Ther 294:822–829.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Cao SJ, Wang Y, et al. (2014). Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells. Fitoterapia 92:230–237.
   PubMed Web of Science ®Google Scholar
• Zhu MM, Han FM, Chen HX, et al. (2007). Identification of palmatine and its metabolites in rat urine by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 21:2019–2022.
   PubMed Web of Science ®Google Scholar
• Zuo F, Nakamura N, Akao T, et al. (2006). Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ-free rats determined by liquid chromatography/ion trap mass spectrometry. Drug Metab Dispos 34:2064–2072.
   PubMed Web of Science ®Google Scholar