Gypenoside inhibits RANKL-induced osteoclastogenesis by regulating NF-κB, AKT, and MAPK signaling pathways.[Pubmed: 29797602]

Gypenoside (GP) is one of the most pharmacologically active components in Gynostemma pentaphyllum and possesses neuroprotective, anticancer, anti-oxidant, anti-inflammatory, anti-diabetic, and anti-osteoarthritis effects. However, the involvement of GP the osteoclast differentiation has not yet been investigated. In the present study, we examined the effect of GP on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Our results demonstrated that GP significantly inhibited the formation of osteoclast, as well as suppressed the expression of osteoclastogenesis-related marker proteins in RANKL-stimulated bone marrow macrophages (BMMs). For molecular mechanisms, GP inhibited RANKL-induced NF-κB and MAPK activation and AKT phosphorylation in BMMs. Collectively, these findings suggest that GP inhibits RANKL-induced osteoclastogenesis via regulating NF-κB, AKT, and MAPK signaling pathways. Therefore, GP may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis.

Ombuoside from Gynostemma pentaphyllum Protects PC12 Cells from L-DOPA-Induced Neurotoxicity.[Pubmed: 29734446]

This study investigated the effects of ombuoside on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced neurotoxicity in PC12 cells. Ombuoside did not affect cell viability at concentrations of up to 50 µM for 24 h, and ombuoside (1, 5, and 10 µM) significantly inhibited L-DOPA-induced (100 and 200 µM) decreases in cell viability. L-DOPA (100 and 200 µM) induced sustained phosphorylation of extracellular signal-regulated kinases (ERK1/2) for 6 h, which were significantly decreased by cotreatments with ombuoside (1, 5, and 10 µM). L-DOPA (100 and 200 µM) alone significantly increased c-Jun N-terminal kinase (JNK1/2) phosphorylation for 6 h and cleaved-caspase-3 expression for 24 h, both of which were partially, but significantly, blocked by ombuoside (1, 5, and 10 µM). In addition, ombuoside (1, 5, and 10 µM) significantly restored the L-DOPA-induced (100 and 200 µM) decrease in superoxide dismutase (SOD) activity for 24 h. Taken together, these findings indicate that ombuoside protects against L-DOPA-induced neurotoxicity by inhibiting L-DOPA-induced increases in sustained ERK1/2 and JNK1/2 phosphorylation and caspase-3 expression and L-DOPA-induced decrease in SOD activity in PC12 cells. Thus, ombuoside might represent a novel neuroprotective agent that warrants further study.

Effects of baicalein on pancreatic cancer stem cells via modulation of sonic Hedgehog pathway.[Pubmed: 29697746]

Recent studies have suggested that sonic Hedgehog (Shh) signaling pathway is aberrantly activated in cancer stem cells (CSCs). A seven-herb Chinese medicinal formula composed of Amorphophallus rivieri Durieu, Oldenlandia diffusa (Wild) Roxb, Scutellaria barbata D. Don, Gynostemma pentaphyllum (Thunb.) Mak and Amomum cardamomum L, i.e. Qingyihuaji (QYHJ) formula, has been shown to inhibit proliferation of pancreatic CSCs by inhibiting Shh signaling pathway and thereby prolong the overall survival of pancreatic cancer patients. Mass spectrometry analysis revealed that baicalein is one of the major compounds of QYHJ formula. The objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms of baicalein involved in pancreatic cancer treatment. We examined the effects of baicalein on pancreatic CSCs both in vivo and in vitro. The results indicated that baicalein attenuated the pluripotency of pancreatic CSCs. Then, we investigated the underlying mechanism and found that nuclear transcription factors, such as Sox-2 and Oct-4 as well as members in Shh signaling pathway, e.g. SHH, SMO, and Gli-2, were downregulated after baicalein treatment. Furthermore, silencing Gli-2 expression by small interfering RNA decreased Sox-2 expression and blocked the inhibitory effects of baicalein, suggesting that the effects of baicalein may be mediated through inhibition of Shh pathway. Our results suggested that baicalein, an active compound in QYHJ formula, could suppress the self-renewal of pancreatic CSCs through inhibition of Shh signaling pathway.

[Effects of flavonoids from Gynostemma pentaphyllum on A549 cells damaged by hydrogen peroxide].[Pubmed: 29676102]

This study focuses on the therapeutical effect of flavonoids from Gynostemma pentaphyllum on human lung carcinoma A549 cells induced by H₂O₂ oxidative stress and its possible mechanisms. The oxidative damage model was established using different concentrations H₂O₂ to induce A549 cell for different hours, and then treated with the flavonoids for 10 hours. The effects of flavonoids from G. pentaphyllum on cell viability of A549 cell damaged by H₂O₂ were detected by MTT assay. The contents of ROS were detected by DCFH-DA fluorescent probe method via flow cytometer. The contents of MDA, SOD and GSH were detected by TBA，NBT and DTNB-linked colorimetry assay, respectively. Expressions levels of Nrf2, NQO1 and HO-1 in A549 cells were evaluated by Western blot. The results showed that the cell activity was decreasing with the rise of H₂O₂ concentration within the range of 200-700 μmol·L⁻¹. The cell viability was 60.4% after treated with 500 μmol·L⁻¹H₂O₂ for 10 h, so it was chosen to be as an oxidant stress model. Compared with normal group，the contents of SOD, GSH and HO-1 expressions were lower after damaged with H₂O₂. On the contrary, the contents of ROS and MDA expressions were increased. Compared with model group, the contents of SOD, GSH and the expressions of Nrf2, NQO1 and HO-1 were increased after treated with flavonoids from G. pentaphyllum. The above results demonstrate that flavonoids from G. pentaphyllum may attenuate the effect of H₂O₂-induced oxidative stress on A549 cell by resisting oxidation. The finding may provide a biological evidence for the application of the G. pentaphyllum to fight the oxidative stress related diseases.

[Comparison of saponins from Gynostemma pentaphyllum leaves prepared by different processing methods].[Pubmed: 29600614]

To investigate the differences of chemical compositions in Gynostemma pentaphyllum leaves prepared by different processing methods. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to compare the chemical compositions between shade-dried processing and drum-dried processing. Forty six gypenosides were identified by control comparison， liquid chromatography-mass spectrometry(LC-MSn) fragmentation information， and literature data. The mass spectral peak area statistics was combined with principal component analysis(PCA)， and the results showed that eight batches of Gynostemma pentaphyllum leaves samples were divided into two groups according to the two different processing methods; ten chemical compositions with significant differences were screened according to mass spectrum information combined with partial least-squares discriminant analysis(PLS-DA). The result showed that most parent nucleus of the gypenosides contained three to four glycosides in drum-dried samples， and one to two glycosides in the shade-dried samples. It was inferred from further MS analysis that desugarization of gypenosides was present to produce secondary glycosides with the effect of glucosidase in the shade-drying， thus resulting in difference in compositions. This study provided data support for harvesting， processing and quality control of Gynostemma pentaphyllum leaves.

The inhibitory effect of gypenoside stereoisomers, gypenoside L and gypenoside LI, isolated from Gynostemma pentaphyllum on the growth of human lung cancer A549 cells.[Pubmed: 29545210]

Gypenosides are major constituents in Gynostemma pentaphyllum (Thunb.) Makino. Previous studies have shown that gypenosides isolated from G. pentaphyllum possess inhibitory effect on the growth of cancer cells, especially A549 cells, with structure-activity relationship (SAR). However, the underlying mechanism of gypenoside-induced A549 cell death remains to be clarified.