Role of gambogenic acid in regulating PI3K/Akt/NF-kβ signaling pathways in rat model of acute hepatotoxicity

Abstract

The purpose of this study is to investigate the protective effect of gambogenic acid (GA) in acetaminophen (APAP)-induced hepatotoxicity in rat models. GA (10 mg/kg) was administered intraperitoneal (i.p.) to rats for 7 consecutive days followed by APAP (500 mg/kg) single dose (i.p.) on the final day after GA administration. The levels of MDA, GSH, SOD, CAT, GPx, GST, ALP, AST, ALT, proinflammatory cytokines (TNF-α, IL-1β, IL-6), apoptosis markers (caspase-3 and -9, Bax, Bcl-2), 4-hydroxynonenal (4-HNE), and prostaglandin E2 (PGE2) were evaluated. Results exhibited protective effects of GA by inhibiting inflammation, preventing oxidative stress and apoptosis in APAP-induced liver. Histopathological changes caused by APAP were attenuated, protein expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) were upregulated, and nuclear factor–kappa β (NF-kβ) was downregulated by GA. In summary, GA significantly exerted anti-inflammatory and antiapoptotic effects against APAP-induced hepatotoxicity potentially through regulation of PI3K/Akt and NF-kβ signaling pathways.

The Protective Effect and Mechanism of a Phytochemical Extract from the Wild Vegetable Shutou (Crateva unilocularis Buch.) against Acetaminophen-Induced Liver Injury in Mice

“…APAP-induced cell death is caused by massive mitochondrial dysfunction and damage to the nuclear DNA [ 55 ]. The PI3K/Akt signaling pathway is a crucial point for hepatoprotection via inhibiting apoptosis under oxidative stress and inflammatory conditions [ 24 ]. PI3K is an intracellular phosphatidylinositol kinase, and Akt is one of its key downstream effectors.…”

“…As a member of the Bcl-2 family, Bax can interact with and inactivate Bcl-2 to enhance apoptosis [ 23 ]. Ding et al showed that the natural active ingredient gambogenic acid can exhibit antiapoptotic activity by activating the signaling pathway of PI3K/Akt [ 24 ].…”

Structural diversity and biological activities of caged Garcinia xanthones: recent updates

“…Downregulation of its associated downstream molecules, that is, c-Myc and p-Akt, has been observed. Furthermore, gambogenic acid exerts anti-inflammatory and antiapoptotic effects against in vivo acute hepatotoxicity by regulating the PI3K/Akt and NF-κB signaling pathways [125]. Its inhibitory effect on NF-κB signaling has also been found to suppress growth and metastasis of bladder cancer cells [126].…”

Determination and tissue distribution comparisons of five xanthones after orally administering crude and processed gamboge

“…Therefore, it is necessary to study this pair of isomers separately. GNA, differing from GA in having an open pyran ring, exhibits anticancer activity in colorectal cancer (Zhao et al, 2020), hepatocellular carcinoma (Yu, Zhao, Wang, et al, 2016), glioblastoma (Chen et al, 2012) and lung adenocarcinoma (Huang et al, 2019; Xu et al, 2018), besides cytotoxicity and anti‐inflammatory activity (Ding et al, 2021; Tao et al, 2009; Yu, Zhao, Zhang, et al, 2016). Related studies have proved that β ‐MA and IGNA also possess potential anticancer and antibacterial effects (Li et al, 2015; Reutrakul et al, 2007; Zhao et al, 2017).…”