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Ethnopharmacological relevance Pogostemon cablin (Blanco) Benth is a well-known medicinal herb commonly used in many Asian countries for inflammatory diseases. Pogostone (PO), a natural product isolated from Pogostemon cablin , is known to exert various pharmacological activities. This study aimed to investigate the anti-inflammatory property of PO, to elucidate its mechanism of action, and to evaluate its potential acute toxicity. Materials and methods The in vitro anti-inflammatory activity of PO was assessed using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The protein and mRNA levels of proinflammatory mediators were measured with ELISA and RT-PCR, respectively. Proteins of the NF- κ B and MAPK family were determined by Western blot to investigate the underlying molecular mechanisms. The in vivo anti-inflammatory activity of PO was tested using LPS-induced endotoxic shock in mice. In addition, the median lethal dose (LD 50 ) of PO in mice was tested in an acute toxicity test. Results In vitro, PO significantly inhibited the protein and mRNA expression of proinflammatory mediators including TNF-α, IL-6, IL-1β, NO, and PGE 2 . The action mechanism of the anti-inflammatory activity of PO was partly dependent on inhibition of the activation of NF- κ B and the phosphorylation of JNK and p38 MAPK. In vivo , PO was able to significantly reduce the mortality induced by LPS in mice. Furthermore, PO could markedly suppress the production of the proinflammatory mediators in serum, and attenuate liver and lung injury. The action mechanisms of PO during endotoxic shock may be attributed to down-regulation of the mRNA expression of inflammatory mediators in multiple organs via inhibition of the activation of NF- κ B and the phosphorylation of p38 MAPK. Moreover, the LD 50 of PO in mice was about 163 mg/kg with intravenous administration, which was about 8-fold higher than the dose used in the animal experiment. Conclusions Our findings regarding the anti-inflammatory effect of PO and the underlying molecular mechanisms help justify the use of Pogostemon cablin in Chinese medicine for the treatment of inflammatory diseases. More importantly, the results also render PO a promising anti-inflammatory agent worthy of further development into a pharmaceutical drug for the treatment of septic shock.

Bushen‑Yizhi formula (BSYZ), a traditional Chinese medicine formula consisting of six herbs has been reported to possess a neuroprotective effect. The present study aimed to investigate the effects of BSYZ on learning and memory abilities, as well as oxidative stress and neuronal apoptosis in the hippocampus of scopolamine (SCOP)‑induced senescence in mice, in order to reveal whether BSYZ is a potential therapeutic agent for Alzheimer's disease (AD). A high‑performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of BSYZ. Extracts of BSYZ were orally administered to mice with SCOP‑induced memory impairment for two weeks. The learning and memory abilities were determined by the Morris water maze test. The oxidant stress‑related indices, such as activity of superoxide dismutase (SOD) and levels of glutathione (GSH) and malondialdehyde (MDA) were examined in hippocampus of SCOP‑treated mice. The cell death ratio was assessed by TUNEL staining, while apoptotic‑related proteins including Bcl‑2 and Bax were determined by immuno-fluorescent staining and western blot analysis. Caspase‑3 was determined by western blot analysis. Consequently, a chromatographic condition, which was conducted at 35˚C with a flow rate of 0.8 ml/min on the Gemini C18 column with mobile phase of acetonitrile and water‑phosphoric acid (100:0.1, v/v), was established to yield common fingerprint chromatography under 203 nm with a similarity index of 0.986 within 10 batches of BSYZ samples. BSYZ at a dose of 2.92 g/kg significantly improved the cognitive ability, restored the abnormal activity of SOD and increased the levels of MDA and GSH induced by SCOP. Moreover, the neural apoptosis in the hippocampus of SCOP‑treated mice was reversed by BSYZ by regulating the expression of Bcl‑2, Bax and caspase‑3. The results demonstrated that BSYZ had neuroprotective effects in SCOP‑induced senescence in mice by ameliorating oxidative stress and neuronal apoptosis in the brain, supporting its potential in AD treatment.

In the present study, the inactivation effect of scutellarin (SL) on jack bean urease was investigated to elucidate the inhibitory potency, kinetics and mechanism of inhibition. It was revealed that SL acted as a concentration- and time-dependent inactivator of urease characteristic of slow-binding inhibition with an IC50 of 1.35±0.15 mM. The rapid formation of the initial SL-urease complex with an inhibition constant of Ki=5.37×10(-2) mM was followed by a slow isomerization into the final complex with the overall inhibition constant of Ki*=3.49×10(-3) mM. High effectiveness of thiol protectors, such as L-cysteine (L-cys), 2-mercaptoethanol (2-ME) and dithiothreitol (DTT) significantly slowed down the rate of inactivation, indicating the strategic role of the active site sulfhydryl group in the blocking process. While the insignificant protection by boric acid and fluoride from the inactivation further confirmed that the active site cysteine should be obligatory for urease inhibition, which was also rationalized by the molecular docking study. The inhibition of SL on urease proved to be reversible since SL-blocked urease could be reactivated by DTT application and multidilution. The results obtained indicated that urease inactivation resulted from the reaction between SL and the sulfhydryl group.

Pogostemon cablin (Blanco) Benth. (Lamiaceae), which is named ‘Guang-Huo-Xiang’ in Chinese, has various therapeutic functions to remove dampness, relieve summer-heat and exterior syndrome, stop vomiting, and stimulate appetite. Patchouli oil is the essential oil of Pogostemonis herba. This study is aimed to investigate the antinociceptive and anti-allergy activities of patchouli oil. The antinociceptive activity of patchouli oil (20, 40, and 80 mg/kg) was evaluated using the acetic acid-induced writhing test (NIH mice) and the hot-plate test (NIH mice), and those for anti-allergy activity were tested using Schultz–Dale reaction, the passive cutaneous anaphylaxis (PCA) test, and delayed-type hypersensitivity (DTH) test. All doses of patchouli oil could significantly (p

Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC50of BA against jack-bean urease was2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant ofKi=3.89 × 10−3 mM was followed by a slow isomerization into the final complex with an overall inhibition constant ofKi*=1.47×10-4 mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases.

The present work was designed to evaluate the in vitro and in vivo anti-Candida activity of pogostone (PO), a natural product isolated from Pogostemon cablin (Blanco) Benth. PO showed potent in vitro activity against clinical Candida spp. isolates tested in this study. PO and the reference drug voriconazole (VRC) were equally effective against all the fluconazole-resistant Candida albicans strains, with MIC ranging from 3.1 μg/ml to 50 μg/ml. Besides, PO was fungicidal against all Candida isolates with MFC ranging from 50 μg/ml to 400 μg/ml. By contrast, VRC was fungistatic as it failed to elicit a fungicidal effect against the Candida spp. isolates at the highest tested concentration (400 μg/ml). Furthermore, oral and topical PO administration effectively reduced the fungal load in vagina of vulvovaginal candidiasis mouse models. Topical PO administration (1.0-4.0 mg/kg) demonstrated higher activity against the vulvovaginal candidiasis than VRC (4.0 mg/kg). The pharmacokinetics and safety profile of PO were also investigated. The pharmacokinetics assay revealed that PO was easily absorbed after oral administration in mice, which might account for its in vivo anti-Candida effect. The acute toxicity test showed that the median lethal dose of PO in mice was 355 mg/kg, which was much higher than the daily dose used for the therapeutic experiments. This study demonstrated the potential of PO as a promising candidate for the treatment of Candida infections, particularly for vulvovaginal candidiasis.

Supported by the integrated model of nutrients for the Miyun Reservoir in part I, effects of different control measures were studied on the water quality of the reservoir. Four scenarios were assumed and analyzed. Results of the base case scenario showed that TN concentration of the Miyun Reservoir had highly exceeded the environmental quality standard for surface water, and TP was relatively better. Furthermore, there were many regions that chlorophyll-a concentration exceeded 10 microg/L in the reservoir, and centralized in the reservoir area of Chaohe River. Scenario 1, 2 and 3 investigated effects of different pollution control measures on the water quality of the reservoir. Results showed that the control of nutrient input loads could improve the water quality greatly, especially control of TP loadings would limit algae growth effectively, and regions that chlorophyll-a concentration exceeded 10 microg/L even disappeared. The results indicated that some control measures, such as changing farming style, part treatment on stockbreeding pollution and reducing point source pollutant loadings were very effective and essential to decrease the eutrophic level of the reservoir.

In recent years, the Miyun Reservoir faces severe problems of water quality and quantity due to continuous drought. In order to simulate and predict the eutrophic status of the Miyun Reservoir and its watershed, an integrated model was developed based on GIS and RS technology, which was composed of non-point source (NPS) simulation model, aquatic ecological-hydrodynamic model, and river water quality model. Ecological-hydrodynamic model was developed through coupling water quality analysis simulation program (WASP) with environmental fluid dynamics Code (EFDC). SWAT was selected as NPS simulation model, which could also perform water quality simulation in the river. Then the integrated model was calibrated using Markov Chain Monte Carlo method and verified using observed data. Results indicated that observed water quality data laid around the mode curves of simulation distribution, and which also dropped into the confidence interval on 80 percent credibility of water quality simulation distribution. In conclusion, the results show that the integrated model can meet the need of application.