Anti-Fibrotic and Anti-Angiogenic Activities of Osbeckia octandra Leaf Extracts in Thioacetamide-Induced Experimental Liver Cirrhosis.

Sudarma Bogahawaththa,Chandana B Herath,Kavindra K Wijesundera,Lalith Jayasinghe,Waruna L Dissanayaka,Jayanthe Rajapakse,Missaka P B Wijayagunawardane,Suranga P Kodithuwakku,Eranga H Siriweera,Tadayuki Tsujita

doi:10.3390/molecules26164836

Abstract

Chronic liver inflammation has become a major global health concern. In the absence of clinical surrogate markers to diagnose inflammatory liver disease, the intervention with effective drugs in modern medicine tends to be late. In Sri Lanka, traditional medical practitioners prescribe herbal preparations from Osbeckia octandra for the prevention and treatment of liver disorders. To test the efficacy of such treatments, we have administered thioacetamide (TAA) to male Wistar rats to induce chronic liver damage (disease control; DC) and examined how various leaf extracts: crude leaf suspension (CLS), boiled leaf extract (BLE), sonicated leaf extract (SLE), methanol leaf extract (MLE) and hexane leaf extract (HLE) of O. octandra ameliorate TAA-induced liver disease. The CLS, BLE and SLE treatments in cirrhotic rats significantly attenuated disease-related changes, such as liver weight and hepato-enzymes. The mRNA levels of Tnf-α were significantly decreased by 3.6, 10 and 3.9 times in CLS, BLE and SLE compared to DC. The same treatments resulted in significantly lower (19.5, 4.2 and 2.4 times) α-Sma levels compared to DC. In addition, Tgf-β1 and Vegf-R2 mRNA expressions were significantly lower with the treatments. Moreover, BLE expressed a strong anti-angiogenic effect. We conclude that CLS, BLE and SLE from O. octandra have potent hepatic anti-fibrotic effects in TAA-induced liver cirrhosis.

Highlights

The liver is an important organ that contributes to the metabolism of carbohydrates, amino acids and lipids
Supporting previously published work [7], histological sections from crude leaf suspension (CLS) and BLE livers showed close to normal cellular architecture, which corroborates with improved liver biochemistry. These findings indicate that crude suspension or boiled leaf extracts of O. octandra could be considered as ideal preparations with the highest hepatoprotective properties
A total of 30 g of freeze-dried powder was mixed with 480 mL of distilled water and boiled for boiled leaf extract (BLE), and the same mixture was sonicated in VWR Ultrasonic cleaner (USC 1700 D, Randor, PA, USA) for 20 min to obtain sonicated leaf extract (SLE)

Summary

Introduction

The liver is an important organ that contributes to the metabolism of carbohydrates, amino acids and lipids. It is involved in the detoxification and elimination of endogenously and exogenously derived toxic substances [1]. Owing to the lack of sensitive surrogate markers to diagnose chronic liver injury, intervention timing tends to be late. This leads to progressive liver damage up to severe liver cirrhosis. Previous work has suggested that natural antioxidants present in the extracts of O. octandra can overcome oxidative damage caused by reactive oxygen species of the injured liver with the arrest of subsequent development of liver fibrosis [8]

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Conclusion