Protective Effects of Three Flavonoids from Dendrobium huoshanense Flowers on Alcohol‐Induced Hepatocyte Injury via Activating Nrf2 and Inhibiting NF‐κB Pathways

Dendrobium huoshanense flowers have been widely used for liver protection in China. This work was aimed to discover the natural products with activity of mitigating alcoholic hepatocyte injury from Dendrobium huoshanense flowers via bioactivity‐guided isolation, and to clarify the underlying mechanisms of these natural products. As a result, three flavonoids, 3′‐O‐methylquercetin‐3‐O‐β‐D‐galactopyranoside (1), 3′‐O‐methylquercetin‐3‐O‐β‐D‐glucopyranoside (2) and quercetin‐3‐O‐β‐D‐glucopyranoside (3), were firstly isolated from D. huoshanense flowers. Results exhibited that flavonoids 1–3 could enhance the cell viability, decrease the expression of ALT and AST, inhibit the cell apoptosis, alleviate the oxidative stress, and mitigate the inflammatory response of alcohol‐induced L02 cells. Mechanism study exhibited that flavonoids 1–3 could increase the expression of Nrf2 as well as its downstream antioxidation genes of alcohol‐induced L02 cells, while ML‐385 (Nrf2 inhibitor) could abolish the inhibitory effects of 1–3 on alcohol‐induced hepatocyte injury. Flavonoids 1–3 could also reduce the phosphorylation levels of IκBα and NF‐κB p65 of alcohol‐induced L02 cells, while SC75741 (NF‐κB inhibitor) could not enhance the inhibitory effects of 1–3 on alcohol‐induced L02 cells injury. The data above indicated that flavonoids 1–3 could inhibit alcohol‐induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF‐κB pathways.

[1]  Wenjing Xu,et al.  Astragaloside IV inhibits hepatocellular carcinoma by continually suppressing the development of fibrosis and regulating pSmad3C/3L and Nrf2/HO-1 pathways. , 2021, Journal of ethnopharmacology.

[2]  Xianjing Hu,et al.  Protection of Ficus pandurata Hance against acute alcohol-induced liver damage in mice via suppressing oxidative stress, inflammation, and apoptosis. , 2021, Journal of ethnopharmacology.

[3]  Lianghui Zhan,et al.  Dendrobium officinale polysaccharides protected against ethanol-induced acute liver injury in vivo and in vitro via the TLR4/NF-κB signaling pathway. , 2020, Cytokine.

[4]  Y. Shangguan,et al.  Rosmarinic acid alleviates ethanol-induced lipid accumulation by repressing fatty acid biosynthesis. , 2020, Food & function.

[5]  X. Lai,et al.  Vitexin protects against ethanol-induced liver injury through Sirt1/p53 signaling pathway. , 2020, European journal of pharmacology.

[6]  J. Wan,et al.  A combination of Pueraria lobata and Silybum marianum protects against alcoholic liver disease in mice. , 2019, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[7]  Feng Zhang,et al.  Oroxylin A prevents alcohol-induced hepatic steatosis through inhibition of hypoxia inducible factor 1alpha. , 2018, Chemico-biological interactions.

[8]  I. Ionkova,et al.  In vitro/in vivo antioxidant and hepatoprotective potential of defatted extract and flavonoids isolated from Astragalus spruneri Boiss. (Fabaceae). , 2018, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[9]  Meilin Xie,et al.  Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression. , 2017, Chemico-biological interactions.

[10]  G. Addolorato,et al.  Treatment of alcohol use disorders in patients with alcoholic liver disease. , 2016, Journal of hepatology.

[11]  Jian-ping Luo,et al.  Polysaccharide of Dendrobium huoshanense activates macrophages via toll-like receptor 4-mediated signaling pathways. , 2016, Carbohydrate polymers.

[12]  Alexandre Louvet,et al.  Alcoholic liver disease: mechanisms of injury and targeted treatment , 2015, Nature Reviews Gastroenterology &Hepatology.

[13]  G. Nardone,et al.  Alcoholic disease: liver and beyond. , 2014, World journal of gastroenterology.

[14]  N. Nieto,et al.  CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver disease. , 2013, Journal of hepatology.

[15]  M. Karin,et al.  NF-κB and STAT3 – key players in liver inflammation and cancer , 2011, Cell Research.

[16]  T. Lawrence.  The nuclear factor NF-kappaB pathway in inflammation. , 2009, Cold Spring Harbor perspectives in biology.

[17]  Defeng Wu,et al.  Role of oxidative stress in alcohol-induced liver injury , 2009, Archives of Toxicology.

[18]  C. B. Pickett,et al.  The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress* , 2009, Journal of Biological Chemistry.

[19]  A. Cederbaum,et al.  Alcohol and oxidative liver injury , 2006, Hepatology.

[20]  J. Wee,et al.  Isolation and Characterization of Antioxidative Compounds from the Aerial Parts of Angelica keiskei , 2005 .

[21]  D. Brenner,et al.  NF-kappaB activation in Kupffer cells after partial hepatectomy. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[22]  Chi-Tang Ho,et al.  Antioxidative phenolic compounds isolated from almond skins (Prunus amygdalus Batsch). , 2002, Journal of agricultural and food chemistry.