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The beneficial effects of curcumin in cirrhotic rats with portal hypertension.
Biosci Rep. 2017 Dec 22; 37(6)BR

Abstract

In liver cirrhosis with portal hypertension, the uneven distribution of vasoactive substances leads to increased intrahepatic vascular resistance and splanchnic vasodilatation. Angiogenesis also induces increased portal inflow and portosystemic collaterals. The collaterals may induce lethal complications such as gastroesophageal variceal hemorrhage, but the therapeutic effect of vasoconstrictors is still suboptimal due to poor collateral vasoresponsivenss. Curcumin has aroused much attention for its antifibrosis, vasoactive, and anti-angiogenesis actions. However, whether it affects the aforementioned aspects is unknown. Liver cirrhosis was induced by common bile duct ligation (CBDL) in Sprague-Dawley rats. Sham-operated rats were controls. CBDL and sham rats were randomly allocated to receive curcumin (600 mg/kg per day) or vehicle since the 15th day after BDL. On the 29th day, portal hypertension related parameters were surveyed. Portosystemic collateral in situ perfusion was performed to evaluate vascular activity. Chronic curcumin treatment decreased portal pressure (PP), cardiac index (CI) and increased systemic vascular resistance (SVR) in cirrhotic rats. In splanchnic system, curcumin decreased superior mesenteric artery (SMA) flow and increased SMA resistance. Mesenteric angiogenesis was attenuated by curcumin. Acute administration of curcumin significantly induced splanchnic vasoconstriction. The mesenteric protein expressions of p-endothelial nitric oxide synthase (eNOS), cyclooxygenase (COX) 2 (COX2), vascular endothelial growth factor (VEGF), p-VEGF receptor 2 (VEGFR2), and p-Erk were down-regulated. In collateral system, curcumin decreased portosystemic shunting and induced vasoconstriction. In conclusion, chronic curcumin administration in cirrhotic rats ameliorated portal hypertension related hemodynamic derangements and portosystemic collaterals. Curcumin also attenuated splanchnic hyperdynamic circulation by inducing vasoconstriction through inhibition of eNOS activation and by decreasing mesenteric angiogenesis via VEGF pathway blockade.

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Authors+Show Affiliations

Hsu SJ
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Lee JY
Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Lin TY
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Hsieh YH
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Huang HC
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan hchuang2@vghtpe.gov.tw hchuang2@gmail.com fylee@vghtpe.gov.tw. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Lee FY
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan hchuang2@vghtpe.gov.tw hchuang2@gmail.com fylee@vghtpe.gov.tw. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Lin HC
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Hou MC
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.
Lee SD
Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan hchuang2@vghtpe.gov.tw hchuang2@gmail.com fylee@vghtpe.gov.tw. Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.

MeSH

AnimalsCurcuminCyclooxygenase 2Disease Models, AnimalGene Expression RegulationHumansHypertension, PortalLiverLiver CirrhosisMesenteric Artery, SuperiorNeovascularization, PathologicNitric Oxide Synthase Type IIIRatsSplanchnic CirculationVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Vascular ResistanceVasoconstriction

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29162665

Citation

Hsu, Shao-Jung, et al. "The Beneficial Effects of Curcumin in Cirrhotic Rats With Portal Hypertension." Bioscience Reports, vol. 37, no. 6, 2017.
Hsu SJ, Lee JY, Lin TY, et al. The beneficial effects of curcumin in cirrhotic rats with portal hypertension. Biosci Rep. 2017;37(6).
Hsu, S. J., Lee, J. Y., Lin, T. Y., Hsieh, Y. H., Huang, H. C., Lee, F. Y., Lin, H. C., Hou, M. C., & Lee, S. D. (2017). The beneficial effects of curcumin in cirrhotic rats with portal hypertension. Bioscience Reports, 37(6). https://doi.org/10.1042/BSR20171015
Hsu SJ, et al. The Beneficial Effects of Curcumin in Cirrhotic Rats With Portal Hypertension. Biosci Rep. 2017 Dec 22;37(6) PubMed PMID: 29162665.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The beneficial effects of curcumin in cirrhotic rats with portal hypertension. AU - Hsu,Shao-Jung, AU - Lee,Jing-Yi, AU - Lin,Te-Yueh, AU - Hsieh,Yu-Hsin, AU - Huang,Hui-Chun, AU - Lee,Fa-Yauh, AU - Lin,Han-Chieh, AU - Hou,Ming-Chih, AU - Lee,Shou-Dong, Y1 - 2017/12/15/ PY - 2017/02/06/received PY - 2017/12/11/revised PY - 2017/11/14/accepted PY - 2017/11/23/pubmed PY - 2018/8/16/medline PY - 2017/11/23/entrez KW - angiogenesis KW - curcumin KW - liver cirrhosis KW - portal hypertension KW - portosystemic collaterals JF - Bioscience reports JO - Biosci Rep VL - 37 IS - 6 N2 - In liver cirrhosis with portal hypertension, the uneven distribution of vasoactive substances leads to increased intrahepatic vascular resistance and splanchnic vasodilatation. Angiogenesis also induces increased portal inflow and portosystemic collaterals. The collaterals may induce lethal complications such as gastroesophageal variceal hemorrhage, but the therapeutic effect of vasoconstrictors is still suboptimal due to poor collateral vasoresponsivenss. Curcumin has aroused much attention for its antifibrosis, vasoactive, and anti-angiogenesis actions. However, whether it affects the aforementioned aspects is unknown. Liver cirrhosis was induced by common bile duct ligation (CBDL) in Sprague-Dawley rats. Sham-operated rats were controls. CBDL and sham rats were randomly allocated to receive curcumin (600 mg/kg per day) or vehicle since the 15th day after BDL. On the 29th day, portal hypertension related parameters were surveyed. Portosystemic collateral in situ perfusion was performed to evaluate vascular activity. Chronic curcumin treatment decreased portal pressure (PP), cardiac index (CI) and increased systemic vascular resistance (SVR) in cirrhotic rats. In splanchnic system, curcumin decreased superior mesenteric artery (SMA) flow and increased SMA resistance. Mesenteric angiogenesis was attenuated by curcumin. Acute administration of curcumin significantly induced splanchnic vasoconstriction. The mesenteric protein expressions of p-endothelial nitric oxide synthase (eNOS), cyclooxygenase (COX) 2 (COX2), vascular endothelial growth factor (VEGF), p-VEGF receptor 2 (VEGFR2), and p-Erk were down-regulated. In collateral system, curcumin decreased portosystemic shunting and induced vasoconstriction. In conclusion, chronic curcumin administration in cirrhotic rats ameliorated portal hypertension related hemodynamic derangements and portosystemic collaterals. Curcumin also attenuated splanchnic hyperdynamic circulation by inducing vasoconstriction through inhibition of eNOS activation and by decreasing mesenteric angiogenesis via VEGF pathway blockade. SN - 1573-4935 UR - https://www.unboundmedicine.com/medline/citation/29162665/The_beneficial_effects_of_curcumin_in_cirrhotic_rats_with_portal_hypertension_ DB - PRIME DP - Unbound Medicine ER -