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Ginseng (Panax ginseng C. A. Meyer) is a precious traditional Chinese medicine with multiple pharmacological effects. Ginsenoside Rg1 is a main active ingredient extracted from ginseng, which is known for its age-delaying and antioxidant effects. Increasing evidence indicates that Rg1 exhibits anti-inflammatory properties in numerous diseases and may ameliorate oxidative damage and inflammation in many chronic liver diseases. Chronic inflammatory injury in liver cells is an important pathological basis of many liver diseases. However, its mechanism remains unclear and therapeutic strategies to prevent its development need to be further explored. Thus, our study is to delve the protective effect and mechanism of Rg1 against chronic hepatic inflammatory injuries induced by lipopolysaccharide (LPS). The chronic liver damage model in mice was build up by injecting intraperitoneally with LPS (200 μg/kg) for 21 days. Serum liver function indicators and levels of IL-1β, IL-6 and TNF-α were examined by using corresponding Kits. Hematoxylin and Eosin (H&E), Periodic acid-Schiff (PAS), and Masson stains were utilized to visualize hepatic histopathological damage, glycogen deposition, and liver fibrosis. The nuclear import of p-Nrf2 and the generation of Col4 in the liver were detected by IF, while IHC was employed to detect the expressions of NLRP3 and AIM2 in the hepatic. The Western blot and q-PCR were used to survey the expressions of proteins and mRNAs of fibrosis and apoptosis, and the expressions of Keap1, p-Nrf2 and NLRP3, NLRP1, AIM2 inflammasome-related proteins in mouse liver. The cell viability of human hepatocellular carcinoma cells (HepG2) was detected by Cell Counting Kit-8 to select the action concentration of LPS, and intracellular ROS generation was detected using a kit. The expressions of Nuclear Nrf2, HO-1, NQO1 and NLRP3, NLRP1, and AIM2 inflammasome-related proteins in HepG2 cells were detected by Western blot. Finally, the feasibility of the molecular interlinking between Rg1 and Nrf2 was demonstrated by molecular docking. Rg1 treatment for 21 days decreased the levels of ALT, AST, and inflammatory factors of serum IL-1β, IL-6 and TNF-α in mice induced by LPS. Pathological results indicated that Rg1 treatment obviously alleviated hepatocellular injury and apoptosis, inflammatory cell infiltration and liver fibrosis in LPS stimulated mice. Rg1 promoted Keap1 degradation and enhanced the expressions of p-Nrf2, HO-1 and decreased the levels of NLRP1, NLRP3, AIM2, cleaved caspase-1, IL-1β and IL-6 in livers caused by LPS. Furthermore, Rg1 effectively suppressed the rise of ROS in HepG2 cells induced by LPS, whereas inhibition of Nrf2 reversed the role of Rg1 in reducing the production of ROS and NLRP3, NLRP1, and AIM2 expressions in LPS-stimulated HepG2 cells. Finally, the molecular docking illustrated that Rg1 exhibits a strong affinity towards Nrf2. The findings indicate that Rg1 significantly ameliorates chronic liver damage and fibrosis induced by LPS. The mechanism may be mediated through promoting the dissociation of Nrf2 from Keap1 and then activating Nrf2 signaling and further inhibiting NLRP3, NLRP1, and AIM2 inflammasomes in liver cells. [Display omitted] • Rg1 treatment attenuates LPS-induced chronic liver injury and alleviates fibrosis. • Rg1 treatment attenuates LPS-induced ROS accumulation and hepatocyte inflammation. • Rg1 treatment alleviates LPS-induced chronic liver injury by activating Nrf2 signaling. • Rg1 treatment inhibits LPS-induced hepatocyte NLRP3, NLRP1, and AIM2 inflammasomes. [ABSTRACT FROM AUTHOR]

Clinacanthus nutans (Burm. f.) Lindau, a traditional herb renowned for its anti-tumor, antioxidant, and anti-inflammatory properties, has garnered considerable attention. Although its hepatoprotective effects have been described, there is still limited knowledge of its treatment of acute liver injury (ALI), and its mechanisms remain unclear. To assess the efficacy of Clinacanthus nutans in ALI and to identify the most effective fractions and their underlying mechanism of action. Bioinformatics was employed to explore the underlying anti-hepatic injury mechanisms and active compounds of Clinacanthus nutans. The binding ability of schaftoside, a potential active ingredient in Clinacanthus nutans , to the core target nuclear factor E2-related factor 2 (Nrf2) was further determined by molecular docking. The role of schaftoside in improving histological abnormalities in the liver was observed by H&E and Masson's staining in an ALI model induced by CCl 4. Serum and liver biochemical parameters were measured using AST, ALT and hydroxyproline kits. An Fe2+ kit, transmission electron microscopy, western blotting, RT-qPCR, and DCFH-DA were used to measure whether schaftoside reduces ferroptosis-induced ALI. Subsequently, specific siRNA knockdown of Nrf2 in AML12 cells was performed to further elucidate the mechanism by which schaftoside attenuates ferroptosis-induced ALI. Bioinformatics analysis and molecular docking showed that schaftoside is the principal compound from Clinacanthus nutans. Schaftoside was shown to diminish oxidative stress levels, attenuate liver fibrosis, and forestall ferroptosis. Deeper investigations revealed that schaftoside amplified Nrf2 expression and triggered the Nrf2/GPX4 pathway, thereby reversing mitochondrial aberrations triggered by lipid peroxidation, GPX4 depletion, and ferroptosis. The lead compound schaftoside counters ferroptosis through the Nrf2/GPX4 axis, providing insights into a novel molecular mechanism for treating ALI, thereby presenting an innovative therapeutic strategy for ferroptosis-induced ALI. [Display omitted] • Network pharmacology studies have demonstrated the hepatoprotective effects of schaftoside in Clinacanthus nutans. • Ferroptosis is responsible for CCl 4 -induced acute liver injury. • Schaftoside alleviates CCl 4 -induced ferroptosis in acute liver injury. • Schaftoside inhibits ferroptosis via the Nrf2-GPX4 pathway to protect against acute liver injury. [ABSTRACT FROM AUTHOR]

The root of Croton crassifolius has been used as a traditional Chinese medicine (TCM), called Radix Croton Crassifolius, and commonly known as "Ji Gu Xiang" in Chinese. Its medicinal value has been recorded in several medical books or handbooks, such as "Sheng Cao Yao Xing Bei Yao", "Ben Cao Qiu Yuan" and "Zhong Hua Ben Cao". It has been traditional employed for treating sore throat, stomach-ache, rheumatism and cancer. At present, there are limited studies on the evaluation of low-polarity extracts of roots in C. crassifolius. Consequently, the aim of this study was to evaluate the antitumor effect of the low-polarity extract of C. crassifolius root. Extracts were obtained by supercritical fluid extraction. The extracts were tested for antitumor effects in vitro on several cancer cell lines. A CCK-8 kit was used for further analysis of cell viability. A flow cytometer and propidium iodide staining were used to evaluate the cell cycle and apoptosis. Hoechst staining, JC-1 staining and the fluorescence probe DCFH-DA were used to evaluate apoptotic cells. Molecular mechanisms of action were analyzed by quantitative RT‒PCR and Western blotting. Immunohistochemistry was used for the evaluation of xenograft tumors in male BALB/c mice. Finally, molecular docking was employed to predict the bond between the desired bioactive compound and molecular targets. Eleven diterpenoids were isolated from low-polarity C. crassifolius root extracts. Among the compounds, chettaphanin II showed the strongest activity (IC 50 = 8.58 μM) against A549 cells. Evaluation of cell viability and the cell cycle showed that Chettaphanin II reduced A549 cell proliferation and induced G2/M-phase arrest. Chttaphanin II significantly induced apoptosis in A549 cells, which was related to the level of apoptosis-related proteins. The growth of tumor tissue was significantly inhibited by chettaphanin II in experiments performed on naked mice. The antitumor mechanism of chettaphanin II is that it can obstruct the mTOR/PI3K/Akt signaling pathway in A549 cells. Molecular docking established that chettaphanin II could bind to the active sites of Bcl-2 and Bax. Taken together, the natural diterpenoid chettaphanin II was identified as the major antitumor active component, and its potential for developing anticancer therapies was demonstrated for the first time by antiproliferation evaluation in vitro and in vivo. [Display omitted] • Eleven diterpenoids were obtained from the SFE extract of C. crassifolius roots. • Chettaphanin II showed the strongest antitumor activity against A549 cells. • Chettaphanin II inhibited A549 cell proliferation and arrested cells in G2/M-phase. • Chettaphanin II induced A549 cell apoptosis by inhibiting PI3K/AKT/mTOR pathway. • Chettaphanin II significantly inhibited the growth of tumor tissue in nude mice. [ABSTRACT FROM AUTHOR]