Identification and mechanistic investigation of ellagitannins from Osbeckia octandra that attenuate liver fibrosis via the TGF-β/SMAD signaling pathway

Author:

Bogahawaththa Sudarma123,Kawamura Tomoaki2,Bandaranayake Udari34,Hirakawa Tomoaki12,Yamada Goki12,Ishino Hana5,Hirohashi Tsuzumi5,Kawaguchi Shin-ichi16,Wijesundera Kavindra K7,Wijayagunawardane Missaka P B3,Ishimaru Kanji5,Kodithuwakku Suranga P38,Tsujita Tadayuki12

Affiliation:

1. The United Graduate School of Agricultural Sciences, Kagoshima University , Kagoshima , 890-0065, Japan

2. Laboratory of Biochemistry, Department of Advanced Lifesciences and Food Chemistry, Faculty of Agriculture, Saga University , Saga , 840-8502, Japan

3. Department of Animal Science, Faculty of Agriculture, University of Peradeniya , Peradeniya , 20400, Sri Lanka

4. Department of Functional Material Science, Graduate School of Science and Engineering, Saitama University , Shimo-Okubo 225, Sakura-ku, Saitama , 338-8570, Japan

5. Department of Biological Resource Sciences, Faculty of Agriculture, Saga University , 1 Honjo, Saga , 840-8502, Japan

6. Center for Education and Research in Agricultural Innovation, Faculty of Agriculture, Saga University , Karatsu, Saga , 847-0021, Japan

7. Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya , Peradeniya , 20400, Sri Lanka

8. ERA Chair COMBIVET, Institute of veterinary Medicine and Animal Science, Estonian University of Life Science , Tartu , 51014, Estonia

Abstract

ABSTRACT Fibrosis is a major problem in chronic liver disease with limited treatment options due to its complex nature. Herbal medicines are often used as an alternative. The aim of this study was to investigate the therapeutic potential of Osbeckia octandra and to identify its active compounds and regulatory pathways. The effects of crude leaf suspension and boiled leaf extract were investigated in an animal model, and the extract was found to be the more effective treatment. Three major bioactive compounds, pedunculagin, casuarinin, and gallic acid, were isolated from the extract using the hepatic stellate cell line, LX-2-based antifibrotic effect evaluation system. The results showed that all these compounds ameliorated LX-2 in fibrotic state. This inhibitory mechanism was confirmed through the TGF-β/SMAD signaling pathway. Collectively, the presence of these compounds in O. octandra suggests its potential as a treatment for liver fibrosis.

Funder

JSPS

Basis for Supporting Innovative Drug Discovery and Life Science Research

Japan Agency for Medical Research and Development

Advanced Research Infrastructure for Materials and Nanotechnology

ARIM

Ministry of Education, Culture, Sports, Science and Technology

University of Peradeniya

Publisher

Oxford University Press (OUP)

Subject

Organic Chemistry,Molecular Biology,Applied Microbiology and Biotechnology,General Medicine,Biochemistry,Analytical Chemistry,Biotechnology

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