Phytoecdysteroids from Dianthus superbus L.: Structures and anti-neuroinflammatory evaluation.

Six undescribed C27-phytoecdysteroid derivatives, named superecdysones A-F, and ten known analogs were extracted from the whole plant of Dianthus superbus L. Their structures were identified by extensive spectroscopy, mass spectrometric methods, chemical transformations, chiral HPLC analysis, and the single-crystal X-ray diffraction analysis. Superecdysones A and B possess a tetrahydrofuran ring in the side chain and superecdysones C-E are rare phytoecdysones containing a (R)-lactic acid moiety, whereas superecdysone F is an uncommon B-ring-modified ecdysone. Notably, based on the variable temperature (from 333 K to 253 K) NMR experiments of superecdysone C, the missing carbon signals were visible at 253 K and assigned. The neuroinflammatory bioassay of all compounds were evaluated, and 22-acetyl-2-deoxyecdysone, 2-deoxy-20-hydroxyecdysone, 20-hydroxyecdysone, ecdysterone-22-O-benzoate, 20-hydroxyecdysone-20,22-O-R-ethylidene, and acetonide derivative 20-hydroxyecdysterone-20, 22-acetonide significantly suppressed the LPS-induced nitric oxide generation in microglia cells (BV-2), with IC50 values ranging from 6.9 to 23.0 µM. Structure-activity relationships were also discussed. Molecular docking simulations of the active compounds confirmed the possible mechanism of action against neuroinflammations. Furthermore, none compounds showed cytotoxicity against HepG2 and MCF-7. It is the first report about the occurrence and anti-neuroinflammatory activity of the phytoecdysteroids in the genus Dianthus. Our findings demonstrated that ecdysteroids may be used as potential anti-inflammatory drugs.

New cyathane diterpenoids with neurotrophic and anti-neuroinflammatory activity from the bird's nest fungus Cyathus africanus.

Eleven new cyathane diterpenoids, designated cyafricanins A-K (1-11), were isolated from the culture broth of the baisidiomycete Cyathus africanus (Nidulariaceae, Bird's nest fungi). Their structures were elucidated by comprehensive analysis of their NMR and HRESIMS data. Cyafricanins A (1) was found to possess an unusual 3,4-seco­carbon skeleton. All compounds were evaluated for their neurotrophic activity in PC-12 cells and anti-neuroinflammatory activity in BV2 microglia cells. All of the diterpenoids showed nerve growth factor induced neurite outgrowth-promoting activity at concentration of 20 µM. Among them, cyafricanin B (2) and cyafricanin G (7) exhibited promising neurotrophic activity, and cyafricanin A (1) showed strong inhibitory effects on both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, molecular docking studies revealed that cyafricanin A (1) showed strong interactions with the iNOs protein in the active cavity.

Astragalus on the anti-fatigue effect in hypoxic mice.

OBJECTIVE: Astragalus is a traditional Chinese medicine to improve the function of the body. The purpose of this study is to investigate the effect of astragalus on improvement of anti-fatigue capacity in mice under simulated plateau environment. METHODS: Male Kunming mice were randomly divided into the following groups: the control group, astragalus treatment groups in low dosage (LD) (1.0 g/kg·d), mid dosage (MD) (3.0 g/kg·d), and high dosage (HD) (30 g/kg·d). The control group were fed under normoxia environment, and hypoxic mice were fed at a stimulated elevation of 5000 meters. After continuous intragastric administration for 10 days, exhaustive swimming experiment was conducted in the anoxic environment. The swimming time, glucose and lactic acid concentration in blood, glycogen contents in liver, SOD and MDA were determined. RESULTS: Compared with the control group, the swimming time of each astragalus treated group was evidently prolonged (P < 0.05), and the area under the blood lactic acid curve was significantly decreased (P < 0.05). In the high and middle dose of astragalus group, liver glycogen was obviously increased. After exhausted swimming, glycogen contents in blood and SOD were significantly increased, while MDA was evidently reduced (P < 0.05). CONCLUSION: Astragalus can alleviate physical fatigue in mice under simulated plateau environment. It has an obvious anti-fatigue effect and it's worthy of further study.

The antioxidant effects of garlic saponins protect PC12 cells from hypoxia-induced damage.

Hypoxia frequently occurs under several different cellular circumstances. Excess reactive oxygen species that are induced by hypoxia may result in cell injury and dysfunction. Recently, garlic has been found to possess some biological and pharmacological activities. The present study examined the effects of garlic saponins (GSP) on the survival of differentiated PC12 (dPC12) cells and the oxidative-antioxidant system. dPC12 cells were exposed to 2 % O2 in order to establish a neuronal insult model. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction assay and lactate dehydrogenase (LDH) release assay. The expression of selected genes (catalase (CAT), p65 and neuron-specific class III ß-tubulin) was evaluated by real-time PCR and immunoblot assays. CAT activity, malondialdehyde (MDA) and 8-hydroxy-deoxyguanosine (8-OH-dG) concentrations were also determined. The data showed that hypoxia dramatically damaged dPC12 cells, while treatment with approximately 5 × 10- 2-10 ng/ml GSP improved cell viability, decreased LDH leakage and caused the cells to maintain neuronal-like characteristics in hypoxia. The production of MDA and 8-OH-dG was attenuated by GSP. CAT activity in dPC12 cells pretreated with GSP was higher than that of the hypoxic control. Moreover, GSP up-regulated CAT expression and decreased the total protein expression as well as the nuclear expression of p65 in hypoxic cells. These data indicate that GSP has antioxidant properties that can protect dPC12 cells from hypoxia-induced damage, which may be related to the up-regulation of CAT expression and activity as well as a decrease in the expression and nucleus distribution of p65 through effects on redox-sensitive signalling pathways.

Effects of sodium tanshinone II A sulphonate on hypoxic pulmonary hypertension in rats in vivo and on Kv2.1 expression in pulmonary artery smooth muscle cells in vitro.

AIM OF THE STUDY: To investigate the effect of sodium tanshinone IIA sulphonate (STS), a water-soluble derivative of tanshinone II A, on hypoxic pulmonary hypertension (HPH) in rats and its underlying mechanisms. MATERIALS AND METHODS: Rats were exposed to hypoxia for two or three weeks, pretreated with or without STS. We detected mean pulmonary arterial pressure (mPAP), the ratio of right ventricle weight to left ventricle with septum weight [RV/(LV+S)], wall thickness and voltage-activated potassium channel (Kv) 2.1 mRNA level of pulmonary arteries (PAs), respectively, and the in vitro effects of STS on proliferation and Kv2.1 expression of cultured pulmonary smooth muscle cells (PASMCs) from normal rats. Cell proliferation was determined by 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyltetrazoliumbromiede (MTT) assay and direct cell counting. Kv2.1 mRNA and protein level were evaluated by reverse transcription-polymerase chain reaction and Western blot, respectively. RESULTS: Chronic hypoxia increased values of mPAP and RV/(LV+S) and inhibited Kv2.1 mRNA level in PAs. Three weeks' daily STS pretreatment inhibited the hypoxia-induced increased mPAP and RV/(LV+S), pulmonary arterial thickening and up-regulated Kv2.1 mRNA level in PAs. Further study in vitro showed that STS suppressed significantly hypoxia-induced PASMCs proliferation and inhibition of Kv2.1 expression in PASMCs. CONCLUSIONS: STS might play protective effects on HPH through decreasing mPAP, V/(LV+S) and inhibiting structural remodeling in distal PAs. The mechanism of these effects may be attributed to inhibiting PASMCs proliferation and stimulating Kv2.1 expression.

[Hemodynamic effects of aminophylline and nifedipine in patients with high altitude pulmonary edema].

AIM: To evaluate the hemodynamic effects of aminophylline and nifedipine in patients with HAPE. METHODS: 10 patients with HAPE undergone Swan-Ganz catheter. The parameters of hemodynamics and arterial blood gases in HAPE were measured before and after administration of nifedipine 20 mg sublingually and aminophylline 0.25 g intravenously respectively. RESULTS: After administering 0.25 g aminophylline the mPAP and PVR significantly decreased, the cardiac output and the level of PaO2, SaO2 increased obviously, the mSAP, HR did not change so much. After using 20 mg nifedipine, the mPAP, PVR and mSAP also decreased, while the cardiac output, HR and the level of PaO2, SaO2 did not show any changes. CONCLUSION: Both of aminophylline and nifedipine can attenuate pulmonary hypertension in patients with HAPE, but the effect of aminophylline was better than the effect of nifedipine.