Moracin E and M isolated from Morus alba Linné induced the skeletal muscle cell proliferation via PI3K-Akt-mTOR signaling pathway.

Twigs of Morus alba have been used in traditional medicine to treat muscle-related symptoms such as aches, numbness, and stiffness. Despite its clinical use in traditional medicine, its active compounds and mode of action have not yet been investigated. Therefore, we aimed to isolate the compounds from the twigs of M. alba and deduce active compounds, key gene targets, and mechanism of action against sarcopenia using network pharmacology analysis. Using various isolation techniques and spectroscopic methods, 43 phytochemicals, including 3 new flavonoids, were isolated and performed network pharmacology analysis. According to the computational-assistant analysis, 28 compounds, 9 genes, and the PI3K-Akt-mTOR signaling pathway were deduced as expected active compounds (EAC), key targets, and the main signaling pathway. To verify the predicted results, the cell proliferation activities of the EAC were evaluated. Especially, moracin E and M significantly increased by 130% (p < 0.001) and 57% (p < 0.05), respectively, which have more than 2- and 1.5-fold stronger effects compared to the control. Furthermore, both increased the expression level of proteins involved in the PI3K-Akt-mTOR signaling pathway and myogenic proteins, including myogenin and MyoD. This study demonstrated that moracin E and M exhibit cell proliferative effects on skeletal muscle cells through the PI3K-Akt-mTOR signaling pathway.

Brevilin A Isolated from Centipeda minima Induces Apoptosis in Human Gastric Cancer Cells via an Extrinsic Apoptotic Signaling Pathway.

Brevilin A, which has anticancer activities against a range of cancers, is an abundant constituent of the medicinal herb Centipeda minima (L.) A. Braun & Asch, which has also been reported to have anticancer activity against breast cancer cells. However, the anticancer activities of C. minima and brevilin A against human gastric cancer have yet to be reported. In this study, we aimed to evaluate the cytotoxicity and molecular basis underlying the anticancer activities of extracts of C. minima (CMX) and brevilin A against human gastric cancer (AGS) cells. We deduced the potential targets and mechanisms underlying the anticancer activity of brevilin A based on a network pharmacology approach. CCND1, CDK4, and BCL2L1 were identified as the key anticancer genes targeted by brevilin A. Cytotoxicity analyses revealed that CMX and brevilin A reduced the viability of AGS cells to levels below 50% (9.73 ± 1.29 µg/mL and 54.69 ± 1.38 µM, respectively). Furthermore, Hoechst 33342, annexin V, and propidium iodide staining and western blot analyses revealed that CMX and brevilin A promoted a significant induction of apoptotic cell death by upregulating the expression of cleaved caspase-8 and cleaved caspase-3 and reducing the ratio of Bax to Bcl-2, which is partially consistent with the findings of our network pharmacology analysis. Collectively, our observations indicate that CMX and brevilin A are novel sources of herbal medicine with potential utility as effective agents for the treatment of gastric cancer.

Chemical constituents from the fruits of Schisandra sphenanthera and their cytotoxicity activity

Abstract Schisandra sphenanthera Rehder & E.H. Wilson, Schisandraceae, is well known as a type of traditional medicine for the treatment of hepatitis, diarrhea and insomnia in Asia. It was also reported to have antiviral and anti-HIV activities. Using various chromatographic resins and isolation techniques, a new lignan (1), erythro-4-(3,4-dimethoxyphenyl)-4-hydroxy-3-methylbutan-2yl-3,4-dimethoxybenzoate, along with fifteen known compounds, were isolated from fruits of S. sphenanthera. The structures of the compounds were identified by extensive spectroscopic and spectrometric methods including 1D and 2D NMR and MS data. All the isolated compounds were evaluated for their cytotoxicity activity against Hela, HepG2 and HCT-116 cells. Among them, compound schisanlactone C showed significant cytotoxicity activity.

A new naphthoquinone analogue and antiviral constituents from the root of Rhinacanthus nasutus.

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) is known as traditional medicine for the treatment of fungal and herpes virus infections. A new naphthoquinone racemate, rhinacasutone (1) together with seven known compounds, rhinacanthone (2), rhinacanthins C, D, N, Q, and E (3-7), and heliobuphthalmin (8) were isolated from root of R. nasutus. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-, 2D-NMR and MS data. All the isolated compounds were tested for their antiviral activities against PR8, HRV1B, and CVB3-infected vero cells. Compounds 3-6 exhibited significant antiviral activities with the IC50 value ranging from 0.03 to 23.7 µM in all three infections.

Estrogenic activity of constituents from the rhizomes of Rheum undulatum Linné.

Stilbenes have been reported to be phytoestrogen compounds owing to its structural similarity to the estrogenic agent diethylstilbestrol. To find new stilbene-derivative phytoestrogens, isolation of stilbene-rich R. undulatum was performed and led to identify six new compounds (1-5 and 28), one newly determined absolute configurations compound (27) together with 21 previously reported compounds (6-26). The structures of compounds were determined on the basis of extensive spectroscopic methods including 1D and 2D NMR and CD spectra data. All the isolated compounds were tested for their estrogenic activities in HepG2 cells transiently transfected with ERα, ERß and ERE-reporter plasmid. Among them, stilbene-derivatives, piceatannol 3'-O-ß-d-xylopyranoside (12), cis-rhaponticin (16) and rhapontigenin 3'-O-ß-d-glucopyranoside (17), showed the more potent binding affinity for estrogen receptors than 17ß-estrodiol.

Neuraminidase inhibitory activity by compounds isolated from aerial parts of Rhinacanthus nasutus.

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) is known as traditional medicine for the treatment of various diseases, such as cancer, fungal infections, herpes virus infections and several types of skin diseases in South-East Asian countries. In this study, eight compounds 1-8 were isolated from the aerial parts of R. nasutus. The structures of compounds were determined by the spectroscopic methods, including 1D and 2D NMR. The isolated compounds were evaluated for neuraminidase inhibitory activity. Several lignans, 2,3-bis[(4-hydroxy-3,5-dimethoxyphenyl)methyl]-1,4-butanediol (5) and 8,8'-bisdihydrosiringenin glucoside (6), significantly inhibited neuraminidase activity, which was comparable to the positive controls, mangiferin and oseltamivir. In addition, a structure-based virtual screening against neuraminidase using bioactive components was demonstrated.