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Codonopis bulleynana Forest ex Diels (cbFeD) effectively attenuates hepatic fibrosis in CCl4-induced fibrotic mice model - 19/12/20

Doi : 10.1016/j.biopha.2020.110960 
Xiang Li a, b, c, Yue Xing e, Dechang Mao e, Lu Ying g, Yunqi Luan f, Mei Xu e, Hongmin Wang e, Chunyan Li e, Yanmei Li e, Shuangqing Zheng h, Zhipeng Li h, Junbo Hu c, Zhuoya Li a, Huaning Wang b, ⁎ , Yunpeng Luan d, i, ⁎
a Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 
b Department of Pi-wei Disease, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming 650021, China 
c Department of Gastrointestinal Surgery Center and Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China 
d Key Laboratory for Forest Resources Conservation and Utilization in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China 
e Department of Life Technology Teaching and Research, School of Life Science, Southwest Forestry University, Kunming 650224, China 
f Faculty of Soil Science, Department of Geography and Ecology Lomonosov Moscow State University, Russia 
g Yunnan Yisheng Pharmaceutical Co., Ltd., Kunming 650000, China 
h KPC Pharmaceuticals, Inc, Kunming 650106, China 
i Southwest China Eco-development Academy, Southwest Forestry University, Kunming 650224, China 

⁎Corresponding author at: Southwest China Eco-development Academy, Southwest Forestry University, Kunming 650224, ChinaSouthwest China Eco-development Academy, Southwest Forestry UniversityKunming650224China⁎⁎Corresponding author at: Department of Pi-wei disease, The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming 650021, China.Department of Pi-wei diseaseThe First Affiliated Hospital of Yunnan University of Traditional Chinese MedicineKunming650021China

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Highlights

•
Water extract from cbFeD contains hundreds of chemicals which enriched in organic acid and its derivatives, flavone, amino acid derivatives, nucleotide and its derivatives, carbohydrates etc.
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Water extract of cbFeD showed hepatoprotective activities and attenuated liver fibrogenesis against carbon tetrachloride (CCl4)-induced chronic liver injury.
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cbFeD suppressed the intrahepatic recruitment of inflammatory cells and inhibited the activation of hepatic stellate cells (HSCs).

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Abstract

The root of Codonopis bulleynana Forest ex Diels (cbFeD), a tonic food widely used in Yunnan Province of China, was found to have a wide range of pharmacological effects. The present study was designed to investigate the anti-fibrotic effect of water extracts of cbFeD in chronic liver injury mice model induced by carbon tetrachloride (CCl4) and to explore its underlying mechanisms. Phytochemical analysis revealed multiple components were present in the water extract of cbFeD and the compounds were mostly enriched in organic acid and its derivatives, flavone, amino acid derivatives, nucleotide and its derivatives, carbohydrates etc. Treatment with cbFeD significantly attenuated liver injury and fibrosis in CCl4-administered mice evidenced by improved liver histology, ameliorated apoptosis of hepatocytes, and decreased transaminase levels in the serum. Decreased activities of superoxide dismutase (SOD) and catalase (CAT) were markedly reversed upon treatment with cbFeD while levels of malondialdehyde (MDA) and glutathione (GSH) were significantly restored towards normal values. cbFeD also suppressed intrahepatic inflammatory cell infiltration and Kupffer cell activation. Furthermore, our study revealed an inhibitory effect of cbFeD on hepatic stellate cells (HSCs) activation both in vitro and in vivo. In conclusion, cbFeD could exert a protective role against liver fibrosis in mice model induced by CCl4 that is comparable to the positive control silymarin and might be developed into a promising anti-fibrotic drug.

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Abbreviations : NASH, ECM, HSC, α-SMA, PPAR-γ, ASH, cbFeD, TCM, CCl4, HPF, HRP, TUNEL, ALT, AST, SEM, TIC, RT, ROS

Keywords : Codonopis bulleynana Forest ex Diels, Liver injury, Fibrogenesis, Inflammation, Hepatic stellate cell


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© 2020  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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