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Updated: Jul 1, 2025
Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats
Published on: August 1, 2018
Curcumol Attenuates Portal Hypertension and Collateral Shunting Via Inhibition of Extrahepatic Angiogenesis in
Xinyuan Wang1, Juan Li2, Jiao Nong3
1Development of Planning Division, Guangxi University of Chinese Medicine, Nanning, 530000, China.
Insights
Curcumol effectively reduces portal hypertension in liver cirrhosis by inhibiting angiogenesis and the JAK2/STAT3 pathway. This natural compound offers a promising therapeutic approach for managing this severe liver condition.
Area of Science:
- Hepatology
- Vascular Biology
- Pharmacology
Background:
- Liver cirrhosis disrupts hepatic blood flow, increasing portal venous pressure and leading to portal hypertension.
- Portal hypertension triggers collateral formation and severe complications, with extrahepatic angiogenesis playing a key role.
- Curcumol, a sesquiterpenoid from Curcumae Rhizoma, is known to inhibit angiogenesis and alleviate liver fibrosis.
Purpose of the Study:
- To investigate the therapeutic effects of curcumol on extrahepatic angiogenesis and portal hypertension in a rat model of liver cirrhosis.
- To elucidate the underlying molecular mechanisms by which curcumol exerts its protective effects.
Main Methods:
- Liver cirrhosis was induced in Sprague Dawley rats using bile duct ligation (BDL).
- Curcumol (30 mg/kg/d) or vehicle was administered orally starting 15 days post-surgery.
- Effects on portal pressure, splanchnic inflow, liver injury, fibrosis, collateral shunting, and angiogenesis were assessed on day 28.
Main Results:
- Curcumol significantly reduced portal pressure and abnormal splanchnic inflow in cirrhotic rats.
- Curcumol mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting.
- These benefits were linked to curcumol's inhibition of mesenteric angiogenesis and partial reversal of JAK2/STAT3 pathway activation.
Conclusions:
- Curcumol demonstrates significant efficacy in attenuating portal hypertension associated with liver cirrhosis.
- The mechanism involves the suppression of extrahepatic angiogenesis via inhibition of the JAK2/STAT3 signaling pathway.
- Curcumol presents a potential therapeutic agent for managing liver cirrhosis complications by targeting angiogenesis.
Abstract:
Liver cirrhosis can cause disturbances in blood circulation in the liver, resulting in impaired portal blood flow and ultimately increasing portal venous pressure. Portal hypertension induces portal-systemic collateral formation and fatal complications. Extrahepatic angiogenesis plays a crucial role in the development of portal hypertension. Curcumol is a sesquiterpenoid derived from the rhizome of Curcumae Rhizoma and has been confirmed to alleviate liver fibrosis by inhibiting angiogenesis. Therefore, our study was designed to explore the effects of curcumol on extrahepatic angiogenesis and portal hypertension. To induce cirrhosis, Sprague Dawley rats underwent bile duct ligation (BDL) surgery. Rats received oral administration with curcumol (30 mg/kg/d) or vehicle (distilled water) starting on day 15 following surgery, when BDL-induced liver fibrosis had developed. The effect of curcumol was assessed on day 28, which is the typical time of BDL-induced cirrhosis. The results showed that curcumol markedly reduced portal pressure in cirrhotic rats. Curcumol inhibited abnormal splanchnic inflow, mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting in cirrhotic rats. These protective effects were partially attributed to the inhibition on mesenteric angiogenesis by curcumol. Mechanically, curcumol partially reversed the BDL-induced activation of the JAK2/STAT3 signaling pathway in cirrhotic rats. Collectively, curcumol attenuates portal hypertension in liver cirrhosis by suppressing extrahepatic angiogenesis through inhibiting the JAK2/STAT3 signaling pathway.
