Gynura segetum induces hepatic sinusoidal obstruction syndrome in mice by impairing autophagy

Abstract

Purpose: To investigate the underlying mechanism of hepatic sinusoidal obstruction syndrome (HSOS) induced by Gynura segetum by measuring autophagy in mouse models. Methods: The model group was administered G. segetum (30 g/kg/d) by gavage, while the normal control group was administered an equal volume of saline daily for five weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic histopathological examinations, and Masson staining were performed to evaluate liver injury. Liver intercellular adhesion molecule-1 (ICAM-1) and P-selectin were evaluated by immunohistochemistry. Hepatocellular apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Protein expression levels of autophagy markers were measured using Western blot analysis. Results: Gynura segetum was found to significantly induce liver injury compared with control mice, as evidenced by the increase of serum transaminases, a decrease in triglyceride levels, and histopathological changes in mice. Gynura segetum remarkably induced hepatocellular apoptosis and upregulated the expressions of ICAM-1 and P-selectin and also downregulated the protein expression levels of LC3, Atg12 and cytoplasmic polyadenylation element binding protein. Conclusion: Our results suggested that G. segetum induced liver injury with HSOS, and it was partly due to its ability to impair the autophagy pathway.

Effects of bicyclol on hepatic sinusoidal obstruction syndrome induced by Gynura segetum

“… 33 Several drugs or chemicals may cause direct and predictable liver injury, accompanied by hepatocyte apoptosis, which is also involved in Gynura segetum . 14 , 33 , 34 , 35 , 36 , 37 Consistent results in the current study showed that Gynura segetum significantly increases TUNEL‐positive cells and upregulates the expression of apoptosis‐executing protein Caspase‐3 compared to the control. Interestingly, the expression of apoptosis suppressor protein Bcl‐2 was dramatically upregulated.…”

“…Consequently, a novel therapeutic approach for targeting autophagy is emerging for liver diseases 44 . Our previous study recently reported that autophagy was impaired in response to Gynura segetum ‐induced HSOS in mice 14 . The finding was further extended by the present results showing that the levels of Atg12 and LC3‐II/LC3‐I proteins were markedly downregulated in HSOS mice, while that of Bcl‐2, a blocker of autophagy occurrence, was dramatically upregulated 45 .…”

“…[8][9][10][11][12][13] Our previous study reported that hepatocyte necrosis and autophagy occur in HSOS induced by Gynura segetum, while bicyclol has hepatoprotective and ameliorative effects on autophagy. 14 Taken together, bicyclol exerts hepatoprotective effects on various types of liver diseases via multipath signaling pathways, and may be used in the symptomatic treatment of HSOS induced by Gynura segetum; however, its effect related to HSOS or Gynura segetum has not been reported.…”

“…This function is mediated by multiple mechanisms including antioxidant action, regulation of cytokine secretion, bidirectional regulation of expression of CYP450 , inhibition of apoptosis and induction of cellular autophagy 8–13 . Our previous study reported that hepatocyte necrosis and autophagy occur in HSOS induced by Gynura segetum , while bicyclol has hepatoprotective and ameliorative effects on autophagy 14 . Taken together, bicyclol exerts hepatoprotective effects on various types of liver diseases via multipath signaling pathways, and may be used in the symptomatic treatment of HSOS induced by Gynura segetum ; however, its effect related to HSOS or Gynura segetum has not been reported.…”

Investigation of Gynura segetum root extract (GSrE) induced hepatotoxicity based on metabolomic signatures and microbial community profiling in rats

“…After 1 week of adaptive feeding, animals were randomly divided into 3 groups: the blank group (B, n = 16); the low dose group (L, n = 16); and the high dose group (H, n = 16). The high-dose group and the low-dose group were given 15 and 7.5 g/(kg * d) of GSrE water decoction for 21 days, respectively (Zhang et al, 2022a ). The clinical equivalent dose of 7.5 g/kg in rats is 500 g in humans (Song et al, 2011 ).…”