Diallyl trisulfide plays an antifibrotic role by inhibiting the expression of Bcl‐2 in hepatic stellate cells

Abstract

Hepatic fibrosis is an important early stage in the evolution of liver cirrhosis, and specific medicine and therapeutic measures are unavailable to date. Hepatic stellate cells (HSCs) are the main cells involved in the formation of hepatic fibrosis, and induction of the apoptosis of HSCs is an important strategy for the treatment of hepatic fibrosis. Diallyl trisulfide (DATS) is a natural product and is the main active ingredient in garlic. However, the exact molecular mechanisms underlying HSC apoptosis induced by DATS are not well understood. This study aimed to analyze the efficiency and mechanism of DATS in hepatic fibrosis. Different concentrations (25, 50, 100, and 200 μM) of DATS were used to treat HSCs. Changes in cell morphology and formation of apoptotic bodies were observed under an inverted microscope and an electric microscope. Bcl‐2 signaling involving Bax, Caspase‐3, Caspase‐6, Caspase‐8, Caspase‐9, p53, Apaf‐1, and Cyto‐c in fibrosis were examined, which is a critical step in the evaluation of antihepatic fibrosis agents. We also evaluated the effect of DATS on the cellular morphology of HSCs and apoptosis‐related factors under different Bcl‐2 expression states. Our results suggest that DATS regulates hepatic fibrosis by blocking the Bcl‐2 signaling pathway and upregulating the Bax/Bcl‐2 ratio.

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

“…Inducing autophagy and natural killer cell-mediated killing effect [228] Galangin Inducing HSCs Apoptosis via the PI3K/Akt, Bax/ Bcl-2, and Wnt/beta-Catenin Pathway in LX-2 Cells Liquiritigeni (LQ) Targeting the miR-181b/PTEN axis [230] NPLC0393 Targeting the TGF-β 1/NDRG2/MAPK signaling axis [231] Hemistepsin A Inhibiting NF-κB/Akt-dependent signaling pathway [232] Tetrandrine Inhibiting NF-κB/Akt-dependent signaling pathway Blocking PI3K/Akt/mTOR and NF-κB signaling pathways [224] Small Astragaloside IV [224] Diallyl trisulfide (DATS) Blocking PI3K/Akt/mTOR and NF-κB signal; Inhibiting the expression of Bcl-2 in HSCs; Regulating JNK/c-JUN signal [233] Platycodin D [234] Sweroside FXR-miR-29a signal [235] Dehydromevalonolactone Repressing activation of NLRP3 inflammasome.…”

“…(8) Inhibiting HSC activation on the basis of preventing PI3K/Akt/mTOR and NF-κB signal pathways: Tormentic acid [279] , Astragaloside IV [252] , Inonotsuoxide B [207] . ( 9) Anti-fibrotic effect by inhibiting Bcl-2 expression in HSCs: Diallyl trisulfide (DATS) [233] . (10) Attenuates LF and HSC activation by modulating the JNK/c-JUN signaling pathway: Platycodin D [280] .…”