A bitter herbal medicine Gentiana scabra root extract stimulates glucagon-like peptide-1 secretion and regulates blood glucose in db/db mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana scabra root extract (GS) is frequently prescribed as an internal remedy in traditional Korean medicine for treatment of diabetes mellitus. GS contains bitter iridoid glycosides including loganic acid, gentiopicrin, trifloroside, and rindoside. We previously reported that the intestinal bitter taste sensation stimulates GLP-1 secretion, and thereupon hypothesized that the blood glucose regulatory effect of GS is due to its GLP-1 secreting effect in enteroendocrine L cells. MATERIALS AND METHOD: We studied GLP-1 secreting effect of GS treatment and its cellular downstream mechanism in human enteroendocrine NCI-H716 cells using the G protein-coupled receptor (GPCR) pathway inhibitors. Intracellular calcium assay also demonstrated the signal transduction pathway stimulated by the GS treatment. Using db/db mice, we performed oral glucose tolerance test (OGTT) to examine the blood glucose lowering effect of GS administration. We also collected the mouse plasma during the OGTT to measure the GLP-1 and insulin levels. RESULT: We demonstrated dose-dependent GLP-1 secreting effect of GS on the NCI-H716 cells. The GLP-1 secreting effect of GS is mediated by the G protein ßγ-subunit and inositol triphosphate. Using db/db mice, we found that the effect of GS on lowering blood glucose is due to its GLP-1 secretion, and consequential insulinotropic effect. The chemical fingerprint of GS was obtained through a direct analysis in realtime mass spectrometry (DART-MS) and high-performance liquid chromatography (HPLC)/MS. Through the GLP-1 secretion study, we found that loganic acid, an iridoid glycoside, contributes to the GLP-1 secreting effect of GS. CONCLUSION: The findings of this study highlight the potential of exploiting the antidiabetic effect of GS on type 2 diabetes mellitus patients.

Effects of the inhaled treatment of liriope radix on an asthmatic mouse model.

As a treatment for allergic asthma, inhaled treatments such as bronchodilators that contain ß2-agonists have an immediate effect, which attenuates airway obstructions and decreases airway hypersensitivity. However, bronchodilators only perform on a one off basis, but not consistently. Asthma is defined as a chronic inflammatory disease of the airways accompanying the overproduction of mucus, airway wall remodeling, bronchial hyperreactivity and airway obstruction. Liriope platyphylla radix extract (LPP), a traditional Korean medicine, has been thoroughly studied and found to be an effective anti-inflammatory medicine. Here, we demonstrate that an inhaled treatment of LPP can attenuate airway hyperresponsiveness (AHR) in an ovalbumin-induced asthmatic mouse model, compared to the saline-treated group (p < 0.01). Moreover, LPP decreases inflammatory cytokine levels, such as eotaxin (p < 0.05), IL-5 (p < 0.05), IL-13 (p < 0.001), RANTES (p < 0.01), and TNF-α (p < 0.05) in the bronchoalveolar lavage (BAL) fluid of asthmatic mice. A histopathological study was carried out to determine the effects of LPP inhalation on mice lung tissue. We performed UPLC/ESI-QTOF-MS, LC/MS, and GC/MS analyses to analyze the chemical constituents of LPP, finding that these are ophiopogonin D, spicatoside A, spicatoside B, benzyl alcohol, and 5-hydroxymethylfurfural. This study demonstrates the effect of an inhaled LPP treatment both on airway AHR and on the inflammatory response in an asthmatic mouse model. Hence, LPP holds significant promise as a nasal inhalant for the treatment of asthmatic airway disease.

Anti-lipoapoptotic effect of Artemisia capillaris extract on free fatty acids-induced HepG2 cells.

BACKGROUND: Artemisia capillaris (AC) has been recognized as one of the promising candidates for hepatoprotective, hypoglycemic, hypolipidemic, antiobesitic and anti-inflammatory therapeutic effectiveness. This study evaluated the inherent mechanism and anti-apoptotic activity of 30% ethanol extract of AC (AC extract) 100 µg/ml on free fatty acids (FFAs)-induced HepG2 cellular steatosis and lipoapoptosis. METHODS: Hepatic steatosis was induced by culturing HepG2 cells with a FFAs mixture (oleic and palmitic acid at the proportion of 2:1) for 24 h, thus ultimately giving rise to lipoapoptosis. Cell viability and lipid accumulation were detected by MTT assay and Oil Red O staining method respectively and Caspase-3, -9, Bax, Bcl-2, p-JNK and PUMA were measured for lipoapoptosis after 24 hours. RESULTS: AC extract significantly improved the FFAs-induced steatosis without cytotoxicity and Caspase-3, -9, Bax and Bcl-2 were modulated profitably to HepG2 cells after AC treatment. In addition, AC extract inhibited the activation of c-Jun NH2 terminal kinase (JNK) and PUMA, which mechanism is related to non-alcoholic steatohepatitis (NASH). CONCLUSIONS: Combined together, AC extract exerted an obvious hypolipidemic and anti-apoptotic effect, indicating that AC extract might have potential therapeutic herb against NASH.

Hexane Fractions of Bupleurum falcatum L. Stimulates Glucagon-Like Peptide-1 Secretion through G ß Î³ -Mediated Pathway.

Bupleurum falcatum L. has been used traditionally as a medicinal herb in Korean medicine. The hexane fraction of BF (HFBF), which was profiled with Direct Analysis in Real Time-Mass Spectrometry (DART-MS), activates the secretion of glucagon-like peptide-1 (GLP-1) in NCI-H716 cells significantly. We performed a microarray analysis and GLP-1 ELISA assay, as well as calcium imaging experiments with inhibitors, to investigate the mechanism of action of the HFBF. Through the microarray analysis, it was found that the ITPR2 gene that encodes the inositol 1,4,5-trisphosphate (IP3) receptor is up-regulated and the HFBF induces cell depolarization by inhibiting the voltage-gated channel expression in NCI-H716 cells. In addition, we found that the intracellular calcium in NCI-H716 cells, with Gallein, U73122, and 2APB as inhibitors, was decreased. These results suggest that the HFBF activates the GLP-1 secretion through the G ßγ pathways in the enteroendocrine L cells after treatment with the HFBF.

The multi-targeted effects of Chrysanthemum herb extract against Escherichia coli O157:H7.

The Chrysanthemum lavandulifolium extract, which includes chrysoeriol, sudachitin, and acacetin, has excellent antibiotic effects on Escherichia coli O157:H7 (E. coli O157). A notable point is that the antibiotic targets of the herb extract are similar to the targets of commonly used antibiotic drugs, including bacterial cell wall biosynthesis, bacterial protein synthesis, and bacterial DNA replication and repair. In addition, the herbal antibiotic inhibits the etiological factors that contribute to the pathogenic property. The herbal sample was extracted and fractionated and then inoculated through a disk diffusion method to confirm its antibiotic effect against E. coli O157. Total RNA was isolated from the affected bacterial cells, and its expression level was analyzed through a microarray analysis. To confirm the accuracy of the microarray data, a real-time PCR was performed. Three active compounds, chrysoeriol, sudachitin, and acacetin, were identified with a high-performance liquid chromatography-electrospray ionization/mass spectrometry chromatogram, and the disk diffusion study confirmed that chrysoeriol and sudachitin contribute to the antibiotic properties of the herb extract. The results demonstrate that the multi-target efficacy of the herbal sample may indicate the potential for the development of more effective and safer drugs that will act as substitutes for existing antibiotics.