Caspase-Mediated Anti-Apoptotic Effect of Ginsenoside Rg5, a Main Rare Ginsenoside, on Acetaminophen-Induced Hepatotoxicity in Mice

Abstract

Frequent overdose of acetaminophen (APAP) is one of the most common and important incentives of acute hepatotoxicity. Prior to this work, our research group confirmed that black ginseng (Panax ginseng, BG) showed powerful protective effects on APAP-induced ALI. However, it is not clear which kind of individual ginsenoside from BG plays such a liver protection effect. The objective of the current investigation was to evaluate whether ginsenoside Rg5 (G-Rg5) protected against APAP-induced hepatotoxicity and the involved action mechanisms. Mice were administrated with G-Rg5 at two dosages of 10 or 20 mg/kg for 7 consecutive days. After the last treatment, all of the animals that received a single intraperitoneal injection of APAP (250 mg/kg) showed severe liver toxicity after 24 h, and the liver protection effects of G-Rg5 were examined. The results clearly indicated that pretreatment with G-Rg5 remarkably inhibited the production of serum tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) compared with the APAP group. Meanwhile, G-Rg5 decreased the hepatic malondialdehyde (MDA) content, the protein expression levels of 4-hydroxynonenal (4-HNE) and cytochrome P450 2E1 (CYP2E1) in the liver tissues. G-Rg5 decreased APAP caused the hepatic overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Furthermore, analysis of immunohistochemistry and Western blotting also indicated that G-Rg5 pretreatment inhibited activation of apoptotic pathways mainly via increasing the expression of Bcl-2 protein, decreasing the expression of Bax protein, proliferating cell nuclear antigen (PCNA), cytochrome c, caspase-3, caspase-8, and caspase-9. Liver histopathological observation provided further evidence that pretreatment with G-Rg5 could significantly inhibit hepatocyte necrosis, inflammatory cell infiltration, and apoptosis caused by APAP. In conclusion, the present study clearly demonstrates that G-Rg5 exerts a liver protection effect against APAP-induced acute hepatotoxicity mainly via a caspase-mediated anti-apoptotic effect.

Dietary α-Mangostin Provides Protective Effects against Acetaminophen-Induced Hepatotoxicity in Mice via Akt/mTOR-Mediated Inhibition of Autophagy and Apoptosis

“…In addition, BNIP3 caused apoptosis and promoted Bax/Bad-dependent release of pro-apoptotic mediators [ 39 ]. Present results revealed that APAP injection downregulated Bcl-2 and upregulated Bax, and cleaved caspase 3 protein expression in hepatocytes, which was in line with our previous studies [ 23 ]. Importantly, supplementation of α-MG partially maintained the balance between Bax and Bcl-2, resulting in the prevention of mitochondrial dysfunction caused by APAP.…”

“…For the histology examination, liver samples were fixed immediately with neutral buffered formalin solution. Liver sections (5 μm thickness) were prepared from paraffin-embedded tissue and subjected to H&E staining for further histological analysis under a light microscope (100× and 400×) [ 23 ]. The necrotic degree (as a percentage of the total area) was assessed by the necrotic area, inflammatory cell infiltration degree, and congestion relative to the entire histological sections.…”

Pseudoginsengenin DQ Exhibits Therapeutic Effects in Cisplatin-Induced Acute Kidney Injury via Sirt1/NF-κB and Caspase Signaling Pathway without Compromising Its Antitumor Activity in Mice

“…Under normal circumstances, apoptosis is a permanent and fundamental form of programmed cell death that occurs in multicellular organisms [ 8 ]. Although apoptosis is a regular biological phenomenon, acute cellular injury also can trigger defective apoptosis and further touch off tissue necrosis in CDDP-induced AKI [ 9 ]. It was reported that oxidative stress and inflammation are also leading factors in CDDP-induced nephrotoxicity [ 10 ].…”

Diet induces hepatocyte protection in fatty liver disease via modulation of PTEN signaling (Review)

“…Certain to-date unknown components of rosemary inhibit PTEN expression in K562 myeloid cells (70) and rosemary promotes liver regeneration in an experimental injury model (69). In contrast, levels of PTEN are increased when treated with Ginsenoside, a class of natural steroid glycosides, which exhibit hepatoprotective effects against acute hepatotoxicity in mice (71). Furthermore, certain types of diet rich in fat or carbohydrates contribute to hepatocyte protection (72).…”