Costunolide protects against alcohol‐induced liver injury by regulating gut microbiota, oxidative stress and attenuating inflammation in vivo and in vitro

Abstract

Costunolide (cos) derived from the roots of Dolomiaea souliei (Franch.), which belongs to the Dolomiaea genus in the family Compositae, exert the anti-inebriation effect mainly by inhibiting the absorption of alcohol in the gastrointestinal tract. However, the protective effect of cos against alcohol-induced liver injury (ALI) remains obscure.The present study was aimed to evaluate the hepatoprotective effects of cos (silymarin was used as positive control) against ALI and its potential mechanisms. MTT was used to examine the effect of cos on the cell viability of L-02 cells. Plasma was separated from blood that used to test the levels of TNF-α, IL-6 and IL-12, and LPS while serum separated from blood which used to detect the level of ALT and AST.Liver tissues were obtained for histopathological examination and western blot analysis. Fresh mice feces samples were collected for the detection of bacterial composition. Cos exhibited protective effect against alcoholic-induced liver injury by regulating gut microbiota capacities (higher relative abundance of Firmicutes and Actinobacteria while lower in Bacteroidetes and Proteobacteria), adjusting oxidative stress (reduced the activities of MDA and ROS while promoted SOD, GSH and GSH-PX in L-02 cells) and attenuating inflammation (decreased the levels of ALT, AST, LPS, IL-6, IL-12 and TNF-α) via LPS-TLR4-NF-κB p65 signaling pathway, which might be an active therapeutic agent for treatment of ALI.

Costunolide Protects Myocardial from Ischemia Reperfusion Injury through Nrf2 Activation

“…It has been reported that Cos administration decreased doxorubicin-induced cardiorenal injury by suppressing oxidative stress [31]. In another study, Cos attenuated alcohol-induced liver injury by reducing ROS production [32]. Interestingly, Cos obviously increases the intracellular oxidative stress in human U2OS cells and promotes the generation of ROS in esophageal cancer cells, and eventually induces apoptosis of carcinoma cells [33].…”

Oxybaphus himalaicus Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation

“…RAW264.7 macrophages were seeded into 96-well plates at a density of 5 × 10 3 cells per well and cultured for 24 h. Then, cells were pretreated with OE (80 μg/mL) for 3 h, and LPS (1 μg/mL) was subsequently added and cultured for the indicated time. Immunofluorescence staining was performed as per our previous report [ 12 ]. Images were captured at 400× magnification with confocal mode by Operetta CLS High Content Analysis System (PerkinElmer, Waltham, MA, USA).…”

Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy

“…One of the naturally occurring sesquiterpene lactones is costunolide, which has been extensively investigated for a wide range of biological activities. A study found that costunolide treats ALD by modulating oxidative stress and reducing inflammation in vivo and in vitro , which is inseparable from its impact on the gut microbiota ( 30 ). Coprinus Comatus polysaccharide, a polysaccharide extract of the edible mushroom species Coprinus Comatus, has been shown to exert prebiotic-like effects to increase gut microbiota diversity, which might improve adverse changes in gut microbiota caused by alcohol consumption and delay ALD progression ( 31 ).…”