Haibo He

Protective effects of total flavonoids from Epimedium on the male mouse reproductive system against cyclophosphamide-induced oxidative injury by up-regulating the expressions of SOD3 and GPX1.

Total flavonoids of Epimedium (TFE) is the main active composition of Epimedium that has been used to treat male reproductive problems. The present aim was to investigate the protective effects of TFE on male mice reproductive system against cyclophosphamide (CP)‐induced oxidative injury. The animals were treated with CP to make testicular injury model and the protective effects of TFE were observed. In the CP‐treated group, testicular and epididymal weights, sperm count and motility significantly decreased relative to the control group (P < 0.05 and P < 0.01, respectively). Compared with the CP‐treated group, TFE (200 and 400 mg/kg) treated mice increased testicular weights by 21.6% and 28.4% (P < 0.05), sperm counts by 81.7% and 148.3% (P < 0.01) and sperm motility by 47.2% and 61.3% (P < 0.01). Meanwhile, the CP‐treated group showed enhancement of lipid peroxidation leading to testicular reproductive toxicity. TFE restored these oxidative damages by up‐regulating the expression of antioxidant enzymes, especially SOD3 and GPX1. TUNEL assay and histopathological observations provided supportive evidence for above results, and when the dose of TFE increased, the aforesaid improvement became more and more strong. These results demonstrated that TFE exerted beneficially protective effects on the structural and functional damage of male mice reproductive system and reduced apoptosis in spermatogenic cells by inhibiting CP‐induced oxidative stress. Copyright

Protective effect of saponins extract from Panax japonicus on myocardial infarction: involvement of NF-κB, Sirt1 and mitogen-activated protein kinase signalling pathways and inhibition of inflammation.

Inflammation is widely acknowledged to increase morbidity and mortality in myocardial infarction (MI), and the ideal therapeutic methods should be aimed at the inflammation reaction triggers. The aim was to evaluate the protective effect of saponins extracted from Panax japonicus (SPJ) on MI, and based on these results investigate the possible involvement mechanism of the nuclear factor‐kappa B (NF‐κB), sirtuin1 (SIRT1) and mitogen‐activated protein kinases (MAPKs) signalling pathways.

Protective effect of tomatine against hydrogen peroxide‐induced neurotoxicity in neuroblastoma (SH‐SY5Y) cells

Reactive oxygen species can induce cell apoptosis, and oxidative stress has been implicated in a variety of neurodegenerative disorders. Tomatine, which is a naturally occurring steroidal glycoalkaloid isolated from Solanum cathayanum, has shown potent anti‐oxidant properties.

The H+K+-ATPase inhibitory activities of Trametenolic acid B from Trametes lactinea (Berk.) Pat, and its effects on gastric cancer cells

Trametenolic acid B (TAB), the bioactive component in the Trametes lactinea (Berk.) Pat, was reported to possess cytotoxic activities and thrombin inhibiting effects. This study was performed to investigate the effects of TAB on H(+)/K(+)-ATPase and gastric cancer. The H(+)/K(+)-ATPase inhibitory activity was determined by gastric parietal cells. Compared to the normal control group, TAB (10, 20, 40 and 80 μg/mL) inhibited the H(+)/K(+)-ATPase activity by 15.97, 16.96, 24.86 and 16.25%, respectively. In the study, 36 Kunming mice were randomly divided into six groups: control, model, TAB-L (TAB, 5 mg/kg/day, i.g.), TAB-M (TAB, 20 mg/kg/day, i.g.), TAB-H (TAB, 40 mg/kg/day, i.g.) and omeprazole (OL, 10 mg/kg/day, i.g.). All mice except the control group were administrated with anhydrous alcohol (5.0 mL/kg, i.g.) for induced gastric-ulcer 1h after the 5th day. At the same time, the control mice were given the same volume of physiological saline. After 4h, TAB was evaluated for H(+)/K(+)-ATPase inhibitory activities of ulcerative gaster, gastric ulcer index and ulcer inhibition. In vitro, the anti-proliferation effect of TAB to gastric cancer cell (HGC-27) in acid environment was detected by MTT, and the apoptosis morphological changes were also observed by Hoechst 33258 dye assay. The results indicated that TAB inhibited moderately H(+)/K(+)-ATPase activity in vitro. Compared to the model group, TAB showed anti-ulcer effects in gastric tissue with the dosages of 20 and 5 mg/kg in vivo. Apart from that, TAB could selectively inhibit gastric cancer cell viability and reduce cell apoptosis against HGC-27 cells at low doses in acid environment.

Trametenolic Acid B Reverses Multidrug Resistance in Breast Cancer Cells Through Regulating the Expression Level of P‐Glycoprotein

Trametenolic acid B (TAB) is the main active composition of Trametes lactinea (Berk.) Pat which possesses anti‐tumor activities. There was no report its antitumor effect through regulating P‐glycoprotein (P‐gp) so far, due to P‐gp over expression is one of the most important mechanisms contributing to the multiple drug resistance phenotype. The present aim was to investigate the effects of TAB on P‐gp in multidrug‐resistant cells; Paclitaxel‐resistant cell line MDA‐MB‐231/Taxol was established by stepwise exposure for 10 months. MDA‐MB‐231 cells and MDA‐MB‐231/Taxol cells were treated with TAB, and their growth was evaluated using MTT assays. Paclitaxel accumulation in the cells was analyzed by high performance liquid chromatogram (HPLC). The activity of P‐gp was detected by intracellular accumulation of rhodamine123 (Rho123), and the protein expression of P‐gp was evaluated using western blot. Results indicated that the IC50 of MDA‐MB‐231/Taxol to paclitaxel (Taxol) was 33 times higher than that of nature MDA‐MB‐231. TAB increased the intracellular concentration of Taxol and inhibited the activity of P‐gp and suppressed the expression of P‐gp in MDA‐MB‐231/Taxol cells. Our present results showed that TAB could reverse Taxol resistance in MDA‐MB‐231/Taxol cells, mainly inhibiting the activity of P‐gp and down‐regulating the expression level of P‐gp, and then enhancing the accumulation of chemotherapy agents.

Effect of Culture Conditions on Metabolite Production of Xylaria sp.

Seeking a strategy for triggering the cryptic natural product biosynthesis to yield novel compounds in the plant-associated fungus Xylaria sp., the effect of culture conditions on metabolite production was investigated. A shift in the production of five known cytochalasin-type analogues 1–5 to six new α-pyrone derivatives, xylapyrones A–F (compounds 6–11), from a solid to a liquid medium was observed. These compounds were identified by analysis of 1D and 2D NMR and HRMS data. Compounds 1–3 showed moderate cytotoxicity against HepG2 and Caski cancer cell lines with IC50 values ranging from 25 to 63 μM and compounds 4–11 were found to be inactive, with IC50 values >100 μM.

Cytotoxic tremulanes and 5,6-secotremulanes, four new sesquiterpenoids from a plant-associated fungus X1-2.

Abstract Two new tremulanes and two new 5,6-secotremulanes, davotremulanes A-D 1–4, along with four known compounds 5–8, were isolated from the culture extract of X1-2, an unidentified plant-associated fungus, which was isolated from the endangered plant, Davidia involucrate Baill. in Shennongjia District. The structures of new compounds 1–4 were established on the basis of extensive spectroscopic analysis. Compounds 1–8 were evaluated for cytotoxic activity to four cancer cell lines, and compounds 1, 2 and 5 displayed selectively moderate activities to A549 cell line with IC50 at 15.3, 25.2, 35.2 μg/mL.

Two new steroidal glycosides with unique structural feature of 14α-hydroxy-5β-steroids from Reineckia carnea

Two new steroidal glycosides (1-2) were isolated from the roots of Reineckia carnea, together with three known compounds (3-5). Their structures were determined on the basis of chemical methods and spectral data. Compounds 1-2 were the unique steroidal glycosides possessing structural feature of 14α-hydroxy-5β-steroids, and compounds 4-5 were isolated from R. carnea for the first time. The isolated compounds (1-5) were tested in vitro for their cytotoxic activities against the A549, HepG 2 and Caski cancer cell lines. Among them, the compounds 2 and 3 showed cytotoxicity against Caski cancer cell line with IC50 values of 34.4 and 3.7μM, respectively.

A Steroidal Saponin RCE-4 Inhibits Lipopolysaccharide-Stimulated Inflammatory Responses via Blocking PI3K/Akt-Mediated Nf-κB Activation in RAW264.7 Cells

Steroidal saponin: (1β,3β,5β,25S)-spirostan-1,3-diol1-[α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranoside] (RCE-4) is the most abundant and bioactive members in Reineckia carnea, has been reported to possess antiinflammatory activity, but the underlying mechanisms remain largely unknown. The present aim was to study expression of inflammatory cytokines, on the basis of this investigation, the possible mechanism of RCE-4 was elucidated. In the present study, we found that the concentrations of TNF-α, IL-1β and IL-6 released from LPS-stimulated RAW264.7cells significantly increased compared to control (P<0.01, respectively). After pretreatment with RCE-4, the TNF-α, IL-1β and IL-6 levels significantly decreased compared with the LPS group (P<0.05, P<0.01, respectively). Further studies indicated that RCE-4 significantly suppressed Akt phosphorylation and NF-қB activation, and with the dose of RCE-4 increasing; their improvement became more and more strong. Our results showed that RCE-4 inhibited LPS-stimiulated TNF-α, IL-1β, IL-6 productions through the blockage of PI3K/Akt-mediated NF-κB activation. Our findings might provide a molecular basis for the ability of RCE-4 serving as a promising candidate for treating various inflammatory diseases.

Fluorescent labeling of oleanolic acid using ‘click’ chemistry

Abstract The natural product oleanolic acid (OA) was functionalized and labeled with the non-aggregated fluorescent dye BOPIM (boron 2-(2′-pyridyl)imidazole complex) using ‘click’ chemistry, yielding a highly fluorescent probe. The pharmacological activity of the probe is comparable to that of unmodified OA, making it suitable for studying the therapeutic mechanisms of OA derivatives in vitro.