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We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis. Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+. Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle. These results demonstrated that gomisin D had a significant effect on isoproterenol-induced myocardial injury by inhibiting oxidative stress, calcium overload and improving mitochondrial energy metabolism. [ABSTRACT FROM AUTHOR]

The regulatory effect of luteolin on the progression of Alzheimer's disease (AD) remains unclear from the perspective of apoptosis. The present study aimed to investigate the protective effects of luteolin against Aβ25-35-induced cell apoptosis in pheochromocytoma (PC-12) cells. Aβ25-35 was used to induce an in vitro model of AD. Estradiol was used as a positive control. The PC-12 cells were incubated with luteolin alone or in combination with fulvestrant or U0126. The results showed that luteolin treatment significantly prevents Aβ25-35-induced decrease in cell viability and inhibits Aβ25-35-induced cell apoptosis. After the addition of fulvestrant and U0126, the apoptosis rate of PC-12 cells increased significantly. In addition, luteolin treatment significantly upregulated the expression of Bcl-2 and downregulated the expression of Bax and caspase-3, whereas fulvestrant and U0126 partially reversed the effects of luteolin. Moreover, luteolin treatment upregulated the expression of ERβ and p-ERK1/2, whereas fulvestrant blocked the expression of p-ERK1/2. The study showed that luteolin could activate the ER/ERK/MAPK signalling pathway to protect PC-12 cells against Aβ25-35-induced cell apoptosis via selectively acting on ERβ. Thus, luteolin may be considered as a potential novel therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

Objective: To characterize the molecular mechanism underlying the antineoplastic activity of Celastrus orbiculatus Thunb. extracts (COE). Methods: The human hepatocellular carcinoma HepG2 cells with mammalian target of rapamycin (mTOR) knockdown expressed (HepG2/mTOR) were constructed using molecular biological technology. In vitro, the HepG2/mTOR− cells were treated with COE at various concentrations (10, 20, 40, 80, 160 and 320 µ g/mL). Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. According to the half-maximal inhibitory concentration (IC50) value (140 mg/L), the concentrations of COE in the subsequent experiment was set to alleviate cytotoxicity. The HepG2/mTOR− cells were divided into 5 groups: negative control (untreated), COE treatment groups (40, 80, 120 mg/L COE) and positive control group (cisplatin, DDP, 2 mg/L), respectively. Wild-type HepG2 cells were used as a blank control. The effects of COE on the cell apoptosis were analyzed by flow cytometry and transmission electronic microscopy (TEM), respectively. The protein expression levels of mTOR signal pathways were determined by Western blotting. In vivo, HepG2/mTOR− cells (2 × 106 cell/mice) were subcutaneously injected into the right flank of nude mice. Thirty-six female nude mice were randomly assigned to 6 groups according to body weight (6 mice per group) as follows: solvent vehicle control, Banmao Capsule treated group (BM, 195 mg/kg), Tegafur, Gimeracil and Oteracil Potassium Capsules (10 mg/kg) treated group, and different dosages of COE (10, 20, 40 mg/kg) groups. Tumor growth was monitored and immunohistochemical staining was used to examine the expression of apoptosis-related proteins in tumor tissues. Results: COE inhibited the proliferation significantly in a concentration-dependent manner in HepG2/mTOR− cells (P<0.01). COE significantly induced the apoptosis of HepG2/mTOR− cells (P<0.01), and the apoptotic bodies can be observed under TEM. COE significantly inhibits the proteins expression of mTOR-related signal pathways. In vivo, COE significantly inhibited tumor growth in nude mice (P<0.01). Moreover, the results showed that COE down-regulated the expression of Bcl-2 and Bcl-xL, and up-regulated the levels of Bax and caspase-3 protein (P<0.01). Conclusion: COE was a potential chemotherapeutic drug in HCC treatments via targeting mTOR signal pathway. [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]

Five new sesquiterpenoids named acasenterpene A-E (1–5) were isolated from the fruits of Acanthopanax senticosus. The structures of all compounds were elucidated by extensive spectroscopic data analyses (1D, 2D NMR, and HR-ESI-MS) combined with physico-chemical analysis methods (enzyme hydrolysis, optical rotation, and CD). The cytotoxicity of all compounds in vitro against four human cancer cell lines (MGC-803, Ishikawa, LN-229 and SMMC-7721) were evaluated by CCK-8 assay. Unlabelled Image [ABSTRACT FROM AUTHOR]