Insampaedok-San Extract Exerts an Immune-Enhancing Effect through NF-κB p65 Pathway Activation.

Insampaedok-san (IS) has traditionally been prescribed as a medication for cold-related symptoms in Northeast Asia, including Korea and China. In this study, we focused on elucidating the molecular mechanism underlying the immunomodulatory activity of IS water extract (ISE) in macrophages. ISE significantly enhanced the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) by increasing the expression of inducible NO synthase and cyclooxygenase-2 (COX-2) in a dose-dependent manner. ISE, which consists of many herbs, contains a large number of active compounds whose pharmacological targets and mechanisms are complicated. Therefore, network pharmacology analysis was used to predict the potential key components, targets, and mechanisms of ISE as immunomodulators. Subsequently, the network pharmacology results were validated experimentally. Seven key components were identified through HPLC-QTOF-MS. As predicted by the network pharmacology analysis, ISE increased the mRNA expression of Tnf and Il6. Furthermore, ISE increased the phosphorylation, nuclear translocation, and transcriptional activity of the p65 subunit of the nuclear factor-κB (NF-κB) signaling pathway. In contrast, rapamycin, an NF-κB inhibitor, suppressed the ISE-induced mRNA expression of Tnf and Il6. In conclusion, ISE is an immune activator that can elevate the production of NO, PGE2, and proinflammatory cytokines mediated by NF-κB signaling.

Diospyros kaki leaves inhibit HGF/Met signaling-mediated EMT and stemness features in hepatocellular carcinoma.

Persimmon (Diospyros kaki L.f.) trees are widely cultivated for their edible fruits in Asia. D. kaki leaves are abundant in phytochemicals that have numerous medicinal properties. Hepatocyte growth factor (HGF) and its receptor Met lead to poor prognosis via the promotion of metastasis and chemoresistance in hepatocellular carcinoma (HCC). Therefore, inhibitors targeting the HGF/Met pathway are regarded as promising drugs against HCC. Here, we investigated the effects of D. kaki leaves on HGF-induced epithelial-to-mesenchymal transition (EMT) and stemness traits in HCC. The ethanol extract of D. kaki leaves (EEDK) markedly suppressed HGF-mediated cell migration and invasion through upregulation of CDH1 and downregulation of SNAI1, VIM, MMP1, MMP2, and MMP9. Moreover, EEDK increased the cytotoxicity of sorafenib, which was reduced by HGF, and decreased the expression of the stemness markers KRT19 and CD44. Additionally, we found a clear correlation between stemness and EMT markers in HCC patients. Importantly, EEDK reduced Met activity and attenuated HGF-mediated activation of JNK/c-Jun. Our findings provide new evidence that EEDK can ameliorate HCC with poor prognosis and aggressive phenotype by blocking HGF/Met signaling.

Synthesis and biological evaluation of isoliquiritigenin derivatives as a neuroprotective agent against glutamate mediated neurotoxicity in HT22 cells.

Glutamate-induced neurotoxicity is characterized by cellular Ca2+ uptake, which is upstream of reactive oxygen species (ROS)-induced apoptosis signaling and MAPKs activation. In the present study, we synthesized isoliquiritigenin analogs with electron-donating and electron-withdrawing functional groups. These analogs were evaluated for neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells. Among these analogs, compound BS11 was selected as a potent neuroprotective agent. Cellular Ca2+ concentration, ROS level, MAPKs activation and AIF translocation to the nucleus were increased upon treatment with 5 mM glutamate. In contrast, we identified that compound BS11 reduced the cellular Ca2+ concentration and ROS level upon glutamate exposure. Western blot analysis showed that MAPK activation was decreased by treatment with compound BS11. We further identified that cotreatment of compound BS11 and glutamate inhibited translocation of AIF to the nucleus.

Synthesis, Structure Revision, and Cytotoxicity of Nocarbenzoxazole G.

The total synthesis of nocarbenzoxazoles F (1) and G (2), originally obtained from the marine-derived halophilic bacterial strain Nocardiopsis lucentensis DSM 44048, was achieved via a simple and versatile route involving microwave-assisted construction of a benzoxazole skeleton, followed by carbon-carbon bond formation with the corresponding aryl bromides. Unfortunately, the 1H and 13C NMR spectra of natural nocarbenzoxazole G did not agree with those of the synthesized compound. In particular, the spectra of the isolated and synthesized compounds showed considerable differences in the signals from the protons and carbons in the aryl group. The revised structure was validated by the total synthesis of the actual nocarbenzoxazole G (8c) molecule, which is a regioisomer of the compound that was reported earlier as nocarbenzoxazole G. The synthesized derivatives showed specific cytotoxicity to the human cervical carcinoma cell line, HeLa, but did not have any remarkable effect on the other cell lines.

Flavonoids from Lindera glauca Blume as low-density lipoprotein oxidation inhibitors.

In order to identify antioxidant flavonoids from Lindera glauca Blume, we performed phytochemical analysis of L. glauca Blume heartwood and isolated eight flavonoids - lindeglaucol (1), lindeglaucone (2), cilicicone B (3), tamarixetin 3-O-α-L-rhamnoside (4), procyanidin A2 (5), cinnamtannin B1 (6), cinnamtannin D1 (7), and procyanidin A1 (8) - through repeated column chromatography over silica gel (SiO2), octadecyl silica gel (ODS) and Sephadex LH-20. The chemical structures of compounds 1-8 were elucidated from spectroscopic data (NMR, IR and MS). The low-density lipoprotein oxidation inhibitory activities of the isolated compounds were evaluated in vitro by using the thiobarbituric acid reactive substances assay. Compounds 5-8 exhibited high inhibition activity, comparable to the positive control butyl hydroxyl toluene. Compounds 2 and 3 were slightly less active, while 1 and 4 expressed low activity.