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Background: Xanthomicrol is one of the methoxylated flavones and a promising cancer chemopreventive agent, but its anti-migration and anti-invasion ability on human hepatocellular carcinoma (HCC) remains unknown. Objectives: This study aims to explore Xanthomicrol's effects on migration and invasion ability of the human HCC Huh7 cell line. Methods: Viability of Huh7 cells was measured by cell counting kit-8 (CCK8) assay. Cell apoptosis was assayed with flow cytometry analysis. The ability of migration and invasion of Huh7 cells was then detected through Transwell assays. Epithelial–mesenchymal transition (EMT)-related proteins were also detected through Western blot. Key findings: Xanthomicrol inhibits the migration and invasion of Huh7 cells. The overexpression of Μu-opioid receptor (MOR) increases Huh7 cells' proliferation and enhances migration and invasion ability, while xanthomicrol treatment decreases the expression of MOR. Moreover, xanthomicrol can reverse migration, invasion and EMT-related protein expression by overexpressed MOR. Conclusions: These results suggest that xanthomicrol is a potential MOR antagonist, and it possesses potent anti-migration and anti-invasion ability on Huh7 cells. [ABSTRACT FROM AUTHOR]

Objectives: Eurycoma longifolia Jack (Simaroubaceae) is commonly distributed in the Southeast Asia and Indo China, which has been shown to possess antianxiety, antibacterial, anticancer, antifungal, anti‐inflammatory, antimalarial and antioxidant biological activities. 14,15β‐dihydroxyklaineanone is a diterpene isolated from E. longifolia Jack, which is cytotoxic against human lung cancer and human breast cancer cell lines. However, the effects and underlying mechanisms of 14,15β‐dihydroxyklaineanone on hepatocellular carcinoma remain unknown. Methods: Cell viability assay and colony formation assay were used to measure HepG2 cell proliferation. Flow cytometry was used to analyse cell cycle and apoptosis. Wound‐healing assay and transwell assay were used to observe cells migration. RNA sequencing and the enrichment of differentially expressed genes (DEGs) in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to find and determine underlying pathways. Key findings: We found that 14,15β‐dihydroxyklaineanone inhibited the growth and migration of HepG2 cells but did not induce cell apoptosis. 14,15β‐dihydroxyklaineanone induced S cell cycle arrest by downregulating the expression levels of cyclin A, p‐CDK2, cyclin B1, p21, E2F‐1 and PCNA. In addition, RNA sequencing showed that 14,15β‐dihydroxyklaineanone regulated MAPK pathway by increasing the expression levels of phosphor‐p38. Downregulating of p38 via both p38 inhibitor (SB203580) and p38‐siRNA could antagonize the inhibition of cell proliferation and migration and reverse the changes in p‐p38, E‐cadherin, N‐cadherin and PCNA expression induced by 14,15β‐dihydroxyklaineanone treatment. Conclusions: 14,15β‐dihydroxyklaineanone inhibited cell proliferation and migration through regulating p38 MAPK pathway in HCC cells. [ABSTRACT FROM AUTHOR]

Context: Docosahexaenoic acid (DHA) is one of the critical fatty acids for optimal health, which affect the expression of nerve growth factor and brain-derived neurotrophic factor in brain. Objective: This study investigates whether DHA supplementation affects lipid peroxidation and activates the glial-derived neurotrophic factor (GDNF)-mitogen-activated protein kinase pathway (MAPK pathway) in hippocampus of natural aged rat. Materials and methods: Rats were randomly divided into four groups; DHA was orally administered at 80 and 160 mg/kg/day to 24-month female rats for 50 days. The antioxidant parameters and GDNF-GDNF family receptor α-1 (GFRα1)-tyrosine-protein kinase receptor (RET)-MAPK-cyclic AMP response element-binding protein (CERB) pathway were assayed in natural aged rat's hippocampus. Results and discussion: The results demonstrated that DHA supplementation significantly increased the activities of superoxide dismutase (SOD) by 37.39 and 57.69%, glutathione peroxidase (GSH-Px) by 27.62 and 32.57% decreased TBARS level by 28.49 and 49.05%, respectively, but did not significantly affect catalase (CAT), in hippocampus, when compared with the aged group. DHA supplementation in diet resulted in an increase of DHA level in hippocampus. Furthermore, we found that DHA supplementation markedly increased the levels of GDNF and GFRα1 and the phosphorylation of RET, and led to the activation of the MAPK pathway in hippocampus tissue. Conclusion: DHA supplementation can change fatty acids composition, improve antioxidant parameters and activate the GDNF-MAPK pathway in natural aged rat's hippocampus. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The first synthesis of Steroidal Pyridine Derivatives. • New protein-molecular docking target-BIR domain of survivin protein. • Prediction of compound activity by molecular docking software(MOE) • In vitro activity assay screened two compounds 2f and 2p with excellent antitumor activity. Abstract With steroid as a carrier nucleus and introducing a pyridine heterocycle as a pharmacophore on the D ring, a series of steroidal pyridine derivatives were designed and studied for their antitumor activity by molecular docking software. The compounds were synthesized as small molecule inhibitors and studied as anticancer agents. The synthesis of the analogs was performed in a one-pot multi-component reaction and the corresponding compounds were screened in vitro for their antitumor activity. Four adherently growing cancer cell lines were used and arranged before dosing. Among all compounds screened for their antitumor activity, compounds 2f and 2p were found to be the most active. Here, the most obvious changes in the morphology of the treated cells could be observed. [ABSTRACT FROM AUTHOR]

• Free energy of the solution of RIN and IRN was calculated. • Theoretical and experimental spectrums were compared. • The intermolecular interaction modes of RIN and IRN were analyzed. • The possible action sites with iNOS were analyzed. The active components of Gou-teng are indole alkaloids, mainly rhynchophylline (RIN) and isorhynchophylline (IRN). The geometric structures of RIN and IRN were optimized using B3LYP-D3(BJ)/6-311G(2d,p), and the molecular structures of the isomers were compared. Free energy of the solution of RIN and IRN in nine different solutions was calculated. The free energy levels of the solution of RIN and IRN in methanol solution were the lowest. The gap of HOMO-LUMO for RIN was lower than that of IRN. The UV–vis spectrum in the methanol solution and the IR spectra of RIN and IRN were recorded and compared with the results obtained using four different DFT methods. Eight possible intermolecular interaction modes of RIN and IRN were analyzed, and binding energy was calculated using B3LYP-D3(BJ)/def2-TZVP. Numbers 3 and 8 were the optimal interaction modes between RIN and IRN homologous molecules in the methanol solution. The possible action sites of RIN and IRN on nitric oxide and enzymes were analyzed by molecular docking and molecular dynamics, respectively, to reveal their pharmacological effects. RIN and IRN had certain stimulation effects on target proteins, and the effect of IRN was slightly stronger than that of RIN. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth leading killer of female cancer patients worldwide. Each year more than half a million women are diagnosed with cervical cancer and the disease results in over 300, 000 deaths. α-Cyperone is known as the principal active ingredient in the Cyperus rotundus (Family: Cyperaceae). However, the effects of α-Cyperone on cancers, especially on cervical cancer, are yet to be explored. In the present study, the underlying mechanism of the anti-tumor activity of α-Cyperone against HeLa cells was investigated. The results showed that α-Cyperone inhibited proliferation and induced apoptosis in HeLa cells. Mechanistically, α-Cyperone promoted HeLa cells apoptosis via a mitochondrial apoptotic pathway, which was proved by increased level of intracellular reactive oxygen species (ROS) and upregulated expression of cytochrome c, cleaved caspase-3, PARP, and Bax. Further RNA-sequencing revealed α-Cyperone inhibited the activation of PI3K/Akt/mTOR signaling pathway in HeLa cells, which confirmed by PI3K inhibitor and agonist. The PI3K inhibitor (LY294002) synergized with α-Cyperone in arresting the growth of HeLa cells, whereas the PI3K agonist (IGF-1) abrogated such an effect. Interestingly, the expression of PD-L1 was attenuated by both α-Cyperone and LY294002, while the supplement of IGF-1 rescued the low expression of PD-L1. In conclusion, our results reveal that the inhibitory effect of α-Cyperone on HeLa cell growth is triggered via the ROS-mediated PI3K/Akt/mTOR signaling pathway and closely related to a decline in the PD-L1 expression. Mechanism of α-Cyperone for the anti-cancer effects on HeLa cells. Image 1 [ABSTRACT FROM AUTHOR]