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Purpose: Drug-induced liver injury (DILI) is the most common cause of acute liver failure. The aim of this study was to investigate the molecular mechanisms by which Ganoderma lucidum mushroom (GLM) may ameliorate cisplatin (CP)-induced hepatotoxicity theoretically and experimentally. Materials and Methods: Thirty-six male Sprague-Dawley (SD) rats were divided into six groups, two of them are normal and Ganoderma lucidum control groups. Liver injury was induced by a single dose of CP (12 mg/kg i.p) in four groups, one of them is CP control group. Besides cisplatin injection in day 1, rats in groups (4-6) were subjected to GLM (500 mg/kg/day) either every other day or daily oral dose or via i.p injection for 10 consecutive days. Results: In this study, GLM supplementation caused significant reduction of elevated highmobility group box-1 (HMGB-1) with a concurrent decline in TNF-α and upregulation of IL-10 compared to the CP group (P<0.05). The histopathological and fibrosis evaluation significantly confirmed the improvement upon simultaneous treatment with GLM. Moreover, immunohistochemical examination also confirmed the recovery following GLM treatment indicated by downregulation of NF-κB, p53 and caspase-3 along with upsurge of B-cell lymphoma 2 (Bcl-2) expression (P<0.05). GLM treatment significantly decreased serum levels of hepatic injury markers; ALT, AST, T. bilirubin as well as oxidative stress markers; MDA and H 2 O 2 with a concomitant increase in hepatic GSH and SOD. Also, the performed docking simulation of ganoderic acid exhibited good fitting and binding with HMGB-1 through hydrogen bond formation with conservative amino acids which gives a strong evidence for its hepatoprotective effect and may interpret the effect of Ganoderma lucidum. Conclusion: GLM attenuated hepatic injury through downregulation of HMGB-1/NF-kB and caspase-3 resulted in modulation of the induced oxidative stress and the subsequent cross-talk between the inflammatory and apoptotic cascade indicating its promising role in DILI.

Three new series of 2‐phenyl benzimidazole‐based derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activity against breast cancer (MCF‐7) cell lines. Three compounds 8, 9, and 15 showed high cytotoxic activities, with IC50 values of 3.37, 6.30, and 5.84 μM, respectively, while they showed comparable cytotoxicity to the standard drug doxorubicin against human normal cells, including nontumorigenic breast epithelial cell line (MCF‐10F), skin fibroblast cell line (BJ), and lung fibroblast cell line (MRC‐5). Six of the synthesized compounds were screened against vascular endothelial growth factor receptor 2 (VEGFR‐2) where compounds 8, 9, 12, and 15 exhibited an outstanding potency in comparison with sorafenib, with IC50 values of 6.7–8.9 nM. Molecular docking study assessed the good binding patterns of the most potent compounds with the reported conserved amino acids of VEGFR‐2 active site.

Liver fibrosis is a significant health problem that can cause serious illness and death. Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamide induced liver fibrosis in rats through the modulation of toll like receptor 4/nuclear factor kappa B signaling pathway. Both concomitant and late taurine treatment (100 mg/kg, IP, daily) significantly reduced the rise in serum ALT and AST activities and significantly reversed the decrease in serum albumin and total protein. These results were confirmed by histopathological examinations and immunehistochemical inspection of α-SMA, caspase-3 and NF-κB. The antioxidant potential of taurine was verified by a marked increase of GSH content and a reduction of MDA level in liver tissue. The anti-fibrotic effects of taurine were evaluated by investigating the expression of TLR4, NF-κB. The protein levels of IL-6, LPS, MyD88, MD2, CD14, TGF-β1 and TNF-α were determined. Docking studies were carried out to understand how taurine interacts inside TLR4-MD2 complex and it showed good binding with the hydrophobic binding site of MD2. We concluded that the anti-fibrotic effect of taurine was attributable to the modulation of the TLR4/NF-κB signaling.