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Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1.
J Ethnopharmacol 2010; 127(3):606-13JE

Abstract

AIM OF THE STUDY

To investigate the effect of Fraxinus rhynchophylla ethanol extract (FR(EtOH)) on liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats.

MATERIALS AND METHODS

Rat hepatic fibrosis was induced by oral administration of CCl(4). Sixty SD rats were divided randomly into 6 groups: control, CCl(4) group, silymarin group and three FR(EtOH)-treated groups. Except for the rats in control group, all rats were administered orally with CCl(4) (20%, 0.2 mL/100g body weight) twice a week for 8 weeks. Rats in FR(EtOH) groups were treated daily with FR(EtOH) (0.1, 0.5 and 1.0 g/kg, p.o.) throughout the whole experimental period. Liver function parameters (such as activities of serum GOT and GPT levels), activities of liver anti-oxidant enzymes (such as catalase, SOD, GPx) and expressions of uPA, tPA, MMP-2, MMP-9 and TIMP-1, -2, -3, -4 in the liver fibrosis pathway were detected.

RESULTS

The results showed that FR(EtOH) (0.1, 0.5 and 1.0 g/kg BW) significantly reduced the elevated activities of sGOT and sGPT caused by CCl(4). FR(EtOH) (0.1 and 0.5 g/kg BW) and significantly increased the activities of GSH-Px. The histopathological study showed that FR(EtOH) (0.1 and 0.5 g/kg BW) reduced the incidence of liver lesions, including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization hepatic necrosis and fibrous connective tissue proliferated induced by CCl(4) in rats. In our study it was showed that CCl(4)-treated group significantly increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FR(EtOH) (0.1 and 0.5 g/kg BW) could inhibit the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. Finally, the amount of esculetin in the FR(EtOH) was 33.54 mg/g extract.

CONCLUSIONS

Oral administration of FR(EtOH) significantly reduces CCl(4)-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular fibrosis by its free radical scavenging ability. FR(EtOH) down-regulated the expressions of uPA, MMP-2 and MMP-9 in CCl(4)-induced liver fibrosis in rats.

Authors+Show Affiliations

Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University, Taichung, Taiwan, ROC. whpeng@mail.cmu.edu.twNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20035854

Citation

Peng, Wen-Huang, et al. "Fraxinus Rhynchophylla Ethanol Extract Attenuates Carbon Tetrachloride-induced Liver Fibrosis in Rats Via Down-regulating the Expressions of uPA, MMP-2, MMP-9 and TIMP-1." Journal of Ethnopharmacology, vol. 127, no. 3, 2010, pp. 606-13.
Peng WH, Tien YC, Huang CY, et al. Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1. J Ethnopharmacol. 2010;127(3):606-13.
Peng, W. H., Tien, Y. C., Huang, C. Y., Huang, T. H., Liao, J. C., Kuo, C. L., & Lin, Y. C. (2010). Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1. Journal of Ethnopharmacology, 127(3), pp. 606-13. doi:10.1016/j.jep.2009.12.016.
Peng WH, et al. Fraxinus Rhynchophylla Ethanol Extract Attenuates Carbon Tetrachloride-induced Liver Fibrosis in Rats Via Down-regulating the Expressions of uPA, MMP-2, MMP-9 and TIMP-1. J Ethnopharmacol. 2010 Feb 17;127(3):606-13. PubMed PMID: 20035854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1. AU - Peng,Wen-Huang, AU - Tien,Yun-Chen, AU - Huang,Chih-Yang, AU - Huang,Tai-Hung, AU - Liao,Jung-Chun, AU - Kuo,Chao-Lin, AU - Lin,Ying-Chih, Y1 - 2009/12/24/ PY - 2009/09/02/received PY - 2009/12/01/revised PY - 2009/12/05/accepted PY - 2009/12/29/entrez PY - 2009/12/29/pubmed PY - 2010/8/7/medline SP - 606 EP - 13 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 127 IS - 3 N2 - AIM OF THE STUDY: To investigate the effect of Fraxinus rhynchophylla ethanol extract (FR(EtOH)) on liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats. MATERIALS AND METHODS: Rat hepatic fibrosis was induced by oral administration of CCl(4). Sixty SD rats were divided randomly into 6 groups: control, CCl(4) group, silymarin group and three FR(EtOH)-treated groups. Except for the rats in control group, all rats were administered orally with CCl(4) (20%, 0.2 mL/100g body weight) twice a week for 8 weeks. Rats in FR(EtOH) groups were treated daily with FR(EtOH) (0.1, 0.5 and 1.0 g/kg, p.o.) throughout the whole experimental period. Liver function parameters (such as activities of serum GOT and GPT levels), activities of liver anti-oxidant enzymes (such as catalase, SOD, GPx) and expressions of uPA, tPA, MMP-2, MMP-9 and TIMP-1, -2, -3, -4 in the liver fibrosis pathway were detected. RESULTS: The results showed that FR(EtOH) (0.1, 0.5 and 1.0 g/kg BW) significantly reduced the elevated activities of sGOT and sGPT caused by CCl(4). FR(EtOH) (0.1 and 0.5 g/kg BW) and significantly increased the activities of GSH-Px. The histopathological study showed that FR(EtOH) (0.1 and 0.5 g/kg BW) reduced the incidence of liver lesions, including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization hepatic necrosis and fibrous connective tissue proliferated induced by CCl(4) in rats. In our study it was showed that CCl(4)-treated group significantly increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FR(EtOH) (0.1 and 0.5 g/kg BW) could inhibit the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. Finally, the amount of esculetin in the FR(EtOH) was 33.54 mg/g extract. CONCLUSIONS: Oral administration of FR(EtOH) significantly reduces CCl(4)-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular fibrosis by its free radical scavenging ability. FR(EtOH) down-regulated the expressions of uPA, MMP-2 and MMP-9 in CCl(4)-induced liver fibrosis in rats. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/20035854/Fraxinus_rhynchophylla_ethanol_extract_attenuates_carbon_tetrachloride_induced_liver_fibrosis_in_rats_via_down_regulating_the_expressions_of_uPA_MMP_2_MMP_9_and_TIMP_1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(09)00756-9 DB - PRIME DP - Unbound Medicine ER -