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| Effect and mechanism of curcumin and its analogues on inhibiting CCl4 induced hepatic fibrosis in rats |
| WANG Zikai* MAO Yongbin* KONG Li ZHONG Xing SUN Xiaowen WU Dan YUAN Xiaohuan |
| Mudanjiang Medical University, Heilongjiang Province, Mudanjiang 157011, China |
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Abstract Objective To study the effect and mechanism of curcumin and its analogues on CCl4 induced hepatic fibrosis in rats. Methods Forty male Wistar rats were randomly divided into model, normal curcumin, H8 low and high dose groups, with 8 rats in each group according to body weight. The model group, curcumin group and H8 group were intraperitoneally injected with 40% CCl4 olive oil to replicate the liver fibrosis model. After 8 weeks, the curcumin group, H8 low and high dose groups were given the corresponding drugs by gavage, and intraperitoneal injection of 40% CCl4 olive oil once for 4 weeks. After sacrificed the rats, blood biochemical indicators were measured, pathological morphological changes were observed by HE and Masson staining of liver tissue, while Col1, fibronectin (FN), transforming growth factor-β (TGF-β), and α-smooth muscle actin (Α-SMA) mRNA were measured by QPCR. Results The alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum glutamyl transpeptidase (GGT), liver coefficient, Col1, FN, TGF-β, α-SMA mRNA in the model group were significantly higher than those in the control group, and the differences were highly statistically significant (P ＜ 0.01). In the curcumin group, the serum ALT, AST, GGT, liver coefficient, Col1, FN, TGF-β, and α-SMA mRNA in the H8 low and high-dose groups were significantly lower than those in the model group, and the differences were statistically significant (P ＜ 0.05). Conclusion Curcumin and its analogue H8 have therapeutic and protective effects on CCl4 induced liver fibrosis in rats, and H8 has better effects than curcumin.
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[1] Epstein J，Sanderson IR，Macdonald TT. Curcumin as a therapeutic agent：the evidence from in vitro，animal and human studies [J]. Br J Nutr，2010，103（11）：1545-1557.
[2] Joseph AI，Edwards RL，Luis PB，et al. Stability and anti-inflammatory activity of the reduction-resistant curcumin analog，2,6-dimethyl-curcumin [J]. Org Biomol Chem，2018，16（17）：3273-3281.
[3] Rajabi M，Farhadian S，Shareghi B，et al. Noncovalent interactions of bovine trypsin with curcumin and effect on stability，structure，and function [J]. Colloids Surf B Biointerfaces，2019，183：110287.
[4] Rezzani R，Franco C. Curcumin as a Therapeutic Strategy in Liver Diseases [J]. Nutrients，2019，11（10）：pii：E2498.
[5] Mody D，Athamneh AIM，Seleem MN. Curcumin：A natural derivative with antibacterial activity against Clostridium difficile [J]. J Glob Antimicrob Resist，2019，pii：S2213-7165（19）：30259-0.
[6] Aggarwal BB，Gupta SC，Sung B. Curcumin：an orally bioavailable blocker of TNF and otherpro-inflammatory biomarkers [J]. Br J Pharmacol，2013，169（8）：1672-1692.
[7] Yuan X，Li H，Bai H，et al. The 11β-hydroxysteroid dehydrogenase type 1 inhibitor protects against the insulin resistance and hepatic steatosis in db/dbmice [J]. Eur J Pharmacol，2016，788：140-151.
[8] Yuan X，Li H，Bai H，et al. Synthesis of novel curcumin analogues for inhibition of 11β-Hydroxysteroid dehydrogenase type 1 with anti-diabetic properties [J]. Eur J Med Chem，2014，77：223-230.
[9] Gowri Shankar NL，Manavalan R，Venkappayya D，et al. Hepatoprotective and antioxidant effects of Commiphoraberryi（Arn）Engl bark extract against CCl4-induced oxidative damage in rats [J]. Food Chem Toxicol，2008，46（9）：3182-3185.
[10] Weber LW，Boll M，Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes：carbon tetrachloride as a toxicological model [J]. Crit Rev Toxicol，2003，33（2）：105-136.
[11] Jiang Y，Wang C，Li YY，et al. Mistletoe alkaloid fractions alleviates carbon tetrachloride-induced liver fibrosis through inhibition of hepatic stellate cell activation via TGF-β/Smadinterference [J]. J Ethnopharmacol，2014，158：230-238.
[12] Fan J，Chen CJ，Wang YC，et al. Hemodynamic changes in hepatic sinusoids of hepatic steatosis mice [J]. World J Gastroenterol，2019，25（11）：1355-1365.
[13] Ge MX，Liu HT，Zhang N，et al. Costunolide represses hepatic fibrosis through WWP2-mediated Notch3 degradation [J]. Br J Pharmacol，2019，177（6）：1453.
[14] Li L，Li H，Zhang Z，et al. Recombinant truncated TGF-β receptor Ⅱ attenuates carbon tetrachloride-induced epithelial-mesenchymal transition and liver fibrosis in rats [J]. Mol Med Rep，2018，17（1）：315-321.
[15] Han F，Shu J，Wang S，et al. Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro [J]. Stem Cells Int，2019，2019：9019648.
[16] Gertz HJ，Kiefer M. Review about Ginkgo biloba special extract EGb 761（Ginkgo）[J]. Curr Pharm Des，2004，10（3）：261-264.
[17] Ezhilarasan D，Sokal E，Najimi M. Hepatic fibrosis：It is time to go with hepatic stellate cell-specific therapeutic targets [J]. Hepatobiliary Pancreat Dis Int，2018，17（3）：192-197.
[18] Hellerbrand C. Hepatic stellate cells—the pericytes in the liver [J]. Pflugers Arch，2013，465（6）：775-778.
[19] Xu F，Liu C，Zhou D，et al. TGF-β/SMAD Pathway and Its Regulation in Hepatic Fibrosis [J]. J Histochem Cytochem，2016，64（3）：157-167.
[20] Hernández-Aquino E，Muriel P. Beneficial effects of naringenin in liver diseases：Molecular mechanisms [J]. World J Gastroenterol，2018，24（16）：1679-1707. |
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