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.

Elucidation of Phytochemicals Affecting Platelet Responsiveness in Dangguisu-san: Active Ingredient Prediction and Experimental Research Using Network Pharmacology.

Plant-derived phytochemicals are emerging as novel agents for protection against chronic disorders. Dangguisu-san is a herbal prescription to invigorate the blood and relieve pain. Among the numerous active constituents of Dangguisu-san, those expected to be effective at inhibiting platelet aggregation were predicted using a network pharmacological method, and their efficacy was experimentally demonstrated. All four identified chemical components, namely chrysoeriol, apigenin, luteolin, and sappanchalcone, suppressed the aggregation of platelets to a certain extent. However, we report, for the first time, that chrysoeriol acts as a strong inhibitor of platelet aggregation. Although additional in vivo studies are needed, among the complex constituents of herbal medicines, the components that exert an inhibitory effect on platelet aggregation were predicted using a network pharmacological method and experimentally confirmed with human platelets.

Chemical constituents from the stem bark of Albizia julibrissin and their SREBP-1c inhibitory activity.

One new lignan, julibrissinoside II, along with thirteen known compounds, was isolated from the stem bark of Albizia julibrissin. The structure of julibrissinoside II was determined on the basis of extensive spectroscopic methods, including NMR and CD spectroscopic data. The isolated compounds were tested for their SREBP-1c inhibitory activity at different concentrations using mouse hepatocyte AML12 cell lines. Among them, linoleic acid (2) and 3-O-methylfisetin (4) showed significant SREBP-1c inhibitory activity at the concentration of 100 µM.

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.

Mitigation of Gastric Damage Using Cinnamomum cassia Extract: Network Pharmacological Analysis of Active Compounds and Protection Effects in Rats.

Gastritis is a common disease worldwide that is caused by various causes such as eating habits, smoking, severe stress, and heavy drinking, as well as Helicobacter pylori infections and non-steroidal anti-inflammatory drugs. Cinnamomum cassia is a tropical aromatic evergreen tree commonly used as a natural medicine in Asia and as a functional food ingredient. Studies have reported this species' anti-obesity, anti-diabetic, and cardiovascular disease suppression effects. We evaluated the potential effects of C. cassia using non-steroidal anti-inflammatory drugs (NSAIDs), ethanol (EtOH), and ethanol/hydrochloric acid (HCl)-induced gastric mucosal injury models. C. cassia extracts reduced the area of gastric mucosa injury caused by indomethacin, NSAID, EtOH, and EtOH/HCl. We also applied a network pharmacology-based approach to identify the active compounds, potential targets, and pharmacological mechanisms of C. cassia against gastritis. Through a network pharmacology analysis, 10 key components were predicted as anti-gastritis effect-related compounds of C. cassia among 51 expected active compounds. The NF-κB signaling pathway, a widely known inflammatory response mechanism, comprised a major signaling pathway within the network pharmacology analysis. These results suggest that the anti-gastritis activities of C. cassia may be induced via the anti-inflammatory effects of key components, which suppress the inflammation-related genes and signaling pathways identified in this study.

Combined Anti-Adipogenic Effects of Hispidulin and p-Synephrine on 3T3-L1 Adipocytes.

Hispidulin is abundant in Arrabidaea chica, Crossostephium chinense, and Grindelia argentina, among others. p-Synephrine is the main phytochemical constituent of Citrus aurantium. It has been used in combination with various other phytochemicals to determine synergistic effects in studies involving human participants. However, there have been no reports comparing the anti-adipogenic effects of the combination of hispidulin and p-synephrine. The current study explores the anti-adipogenic effects of hispidulin alone and in combination with p-synephrine in a murine preadipocyte cell line, 3T3-L1. Co-treatment resulted in a greater inhibition of the formation of red-labeled lipid droplets than the hispidulin or p-synephrine-alone treatments. Co-treatment with hispidulin and p-synephrine also significantly inhibited adipogenic marker proteins, including Akt, mitogen-activated protein kinases, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, glucocorticoid receptor, and CCAAT/enhancer-binding protein ß. Although further studies are required to assess the effects of each drug on pharmacokinetic parameters, a combination treatment with hispidulin and p-synephrine may be a potential alternative strategy for developing novel anti-obesity drugs.

Fatty Acid Derivatives Isolated from the Oil of Persea americana (Avocado) Protects against Neomycin-Induced Hair Cell Damage.

Avocado oil is beneficial to human health and has been reported to have beneficial effects on sensorineural hearing loss (SNHL). However, the compounds in avocado oil that affect SNHL have not been identified. In this study, we identified 20 compounds from avocado oil, including two new and 18 known fatty acid derivatives, using extensive spectroscopic analysis. The efficacy of the isolated compounds for improving SNHL was investigated in an ototoxic zebrafish model. The two new compounds, namely (2R,4R,6Z)-1,2,4-trihydroxynonadec-6-ene and (2R,4R)-1,2,4-trihydroxyheptadecadi-14,16-ene (compounds 1 and 2), as well as compounds 7, 9, 14, 17 and 19 showed significant improvement in damaged hair cells in toxic zebrafish. These results led to the conclusion that compounds from avocado oil as well as oil itself have a regenerative effect on damaged otic hair cells in ototoxic zebrafish.

Neuraminidase Inhibitors from the Roots of Caragana sinica.

Two new oligostilbenes, caragasinins D and E, along with four known compounds, kobophenol A, α-viniferin, wistin, and 5-hydroxy-2-[(4-hydroxyphenyl)acetyl]-3-methoxybenzoic acid, were isolated from the roots of Caragana sinica. These compounds were spectroscopically analyzed for their structures and configurations and compared with existing data. The configurations of caragasinins D and E were elucidated by 1 H-NMR spectroscopy, CD spectroscopy, and time-dependent density-functional theory simulated ECD spectral data. All six compounds were evaluated for their inhibitory activity against neuraminidase (NA) from Clostridium perfringens. Among the tested compounds, 5-hydroxy-2-[(4-hydroxyphenyl)acetyl]-3-methoxybenzoic acid demonstrated statistically significant NA inhibitory activity, which was comparable to the positive control, mangiferin.

Chemical constituents of leaves of Persea americana (avocado) and their protective effects against neomycin-induced hair cell damage

ABSTRACT Persea americana Mill., Lauraceae, commonly known as the avocado, is native to tropical and subtropical regions, including Brazil. From the leaves of P. americana, one previously undescribed flavonol glycoside (1) together with ten known flavonoids (2-11), four megastigmane glycosides (12-15) and two lignans (16-17) were isolated. Their structures were determined by extensive spectroscopic methods including 1D- and 2D-nuclear magnetic resonance and mass spectrometry data. This is the first investigation that reports megastigmane glycoside and lignan classes within the genus Persea. All the isolated compounds have been assessed through the cell survival of larval zebrafish following neomycin-induced damage and the cell viability of a House Ear Institute-Organ of Corti 1 mouse auditory cell line. Among the tested compounds, juglanin (2) and (+)-lyoniresinol (16) showed significant cell regeneration in neomycin-damaged hair cell without cellular toxicity.

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.