Flavonoid-enriched extract from Millettia speciosa Champ prevents obesity by regulating thermogenesis and lipid metabolism in high-fat diet-induced obese C57BL/6 mice.

Millettia speciosa (M. speciosa) Champ is a medicinal and edible plant. The roots are rich in flavonoids, which possess multiple biological activities, including lipid-lowering effects. This study aimed to explore the effect of flavonoid-enriched extract from M. speciosa (FMS) on obesity. The UPLC-Q-TOF-MS analysis and chromatographic analysis were adopted to identify flavonoid compounds in FMS. Male C57BL/6J mice were fed with a high-fat diet for 3 months and were then treated with FMS (50 or 100 mg/kg/d) or Orlistat (10 mg kg-1 d-1) for another 8 weeks. A total of 35 flavonoids were identified in the extract of M. speciosa root. FMS reduced body weight gain, liver weight gain, white adipose tissue, lipid accumulation, and blood glucose. The levels of TG, ALT, AST, and inflammatory-related adipokines (TNF-α and IL-6) in serum were also reduced by FMS. In addition, FMS promoted thermogenesis in brown adipose tissue and induced the activation of lipolysis, fatty acid oxidation, and oxidative phosphorylation in white adipose tissues. In summary, long-term administration of FMS could ameliorate high-fat diet-induced obesity by stimulating adipose thermogenesis and lipid metabolism.

A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice.

Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy. Superoxide dismutase (SOD) is a potential therapy for mucositis but efficient product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion. Multi-modified Stable Anti-Oxidant Enzymes® (MS-AOE®) is a new recombinant SOD with better resistance to pepsin and trypsin. We referred it as MS-SOD to distinguish from other SODs. In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms. An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU (50 mg/kg every day, ip). MS-SOD (800 IU/10 g, ig) was given once daily for 9 days. 5-FU caused severe mucositis with intestinal morphological damage, bodyweight loss and diarrhea; MS-SOD significantly decreased the severity. 5-FU markedly increased reactive oxygen species (ROS) and inflammatory cytokines in the intestine which were ameliorated by MS-SOD. Furthermore, MS-SOD modified intestinal microbes, particularly reduced Verrucomicrobia, compared with the 5-FU group. In Caco2 cells, MS-SOD (250-1000 U/mL) dose-dependently decreased tBHP-induced ROS generation. In RAW264.7 cells, MS-SOD (500 U/mL) had no effect on LPS-induced inflammatory cytokines, but inhibited iNOS expression. These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury, thus play an indirect role in anti-inflammatory and barrier protein protection. In conclusion, MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation, and influencing microbes. MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic.

[Present situation and development strategy of Alpinia oxyphylla].

Alpinia oxyphylla is mainly produced in Hainan,and also one of the four famous traditional Chinese medicines in South China with increasing importance in traditional Chinese medicine industry. Field surveys and literatures show that A. oxyphylla has widely used as a medicinal and edible plant,it is an important raw material for many Chinese patent medicines,health products and food,with a long history of artificial cultivation and application. The future development is prospected on health market. But A. oxyphylla industry has faced a lot of problems,including unreasonable planting layout,lack of good varieties,imperfect seed breeding system,low level of standardization,inconsistent quality of medicinal materials,low level of industry,and so on. The suggestions for sustainable development are listed below.First,it is essential to strengthen the research on the basis and application technology of A. oxyphylla,speed up the selection and breeding of improved varieties,and popularize standardized cultivation techniques. Secondly,it is important to strengthen the research on quality standards,improve the quality evaluation system of medicinal materials. Thirdly,it is necessary to take full advantage of the functional components to develop functional products with Hainan characteristics,find out the unique product characteristics of A. oxyphylla,build a famous brand and improve the product competitiveness in the market. It is also important to strengthen policy support and industrial supervision,promote the healthy and rapid development of A. oxyphylla industry.

Different structures of berberine and five other protoberberine alkaloids that affect P-glycoprotein-mediated efflux capacity.

Berberine, berberrubine, thalifendine, demethyleneberberine, jatrorrhizine, and columbamine are six natural protoberberine alkaloid (PA) compounds that display extensive pharmacological properties and share the same protoberberine molecular skeleton with only slight substitution differences. The oral delivery of most PAs is hindered by their poor bioavailability, which is largely caused by P-glycoprotein (P-gp)-mediated drug efflux. Meanwhile, P-gp undergoes large-scale conformational changes (from an inward-facing to an outward-facing state) when transporting substrates, and these changes might strongly affect the P-gp-binding specificity. To confirm whether these six compounds are substrates of P-gp, to investigate the differences in efflux capacity caused by their trivial structural differences and to reveal the key to increasing their binding affinity to P-gp, we conducted a series of in vivo, in vitro, and in silico assays. Here, we first confirmed that all six compounds were substrates of P-gp by comparing the drug concentrations in wild-type and P-gp-knockout mice in vivo. The efflux capacity (net efflux) ranked as berberrubine > berberine > columbamine ~ jatrorrhizine > thalifendine > demethyleneberberine based on in vitro transport studies in Caco-2 monolayers. Using molecular dynamics simulation and molecular docking techniques, we determined the transport pathways of the six compounds and their binding affinities to P-gp. The results suggested that at the early binding stage, different hydrophobic and electrostatic interactions collectively differentiate the binding affinities of the compounds to P-gp, whereas electrostatic interactions are the main determinant at the late release stage. In addition to hydrophobic interactions, hydrogen bonds play an important role in discriminating the binding affinities.

18ß-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway.

Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18ß-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect. According to the results, 18b-GA markedly attenuated ANIT-induced liver injury as indicated the hepatic plasma chemistry index and histopathology examination. In addition, the expression levels of nuclear factors, including Sirt1, FXR and Nrf2, and their target efflux transporters in the liver, which mainly mediate bile acid homeostasis in hepatocytes, significantly increased. Furthermore, we first revealed that 18b-GA treatment significantly activated FXR, and which can be significantly reduced by EX-527 (a potent and selective Sirt1 inhibitor), indicating that 18b-GA activates FXR through Sirt1. Taken together, 18b-GA confers hepatoprotection against ANIT-induced cholestasis by activating FXR through Sirt1, which promotes gene expression of the efflux transporter, and consequently attenuates dysregulation of bile acid homeostasis in hepatocyte compartments.

Spatiotemporal distribution of nitrogen and phosphorus in alpine lakes in the Sanjiangyuan Region of the Tibetan Plateau.

To provide a theoretical basis for alpine source lake protection, ten samples were taken from each lake annually from 2012 to 2015. Each year, the various species of nitrogen and phosphorus nutrients were measured. The average contents of nitrate nitrogen, ammonia nitrogen, nitrite nitrogen, total phosphorus, and total nitrogen in the four lakes are 0.195-0.0 mg/L, 0.038-0.143 mg/L, 0.004-0.168 mg/L, 0.006-0.740 mg/L, and 0.050-0.547 mg/L, respectively. The total phosphorus contents in Eling Lake, Longbao Lake and Sea Star were higher than Class I water quality standards, and the total nitrogen contents in Eling Lake, Sea Star and Zhaling Lake were higher than Class I water quality standards as well. The concentration contour maps of the nitrate nitrogen, ammonia nitrogen, nitrite nitrogen, total phosphorus and total nitrogen showed that the indicators of the four lakes in the east, the west, and the center of the lake did not have the same trend. From 2012 to 2015, each of the measured nutrients showed a rising trend year by year. The four lakes are polluted by both endogenous and exogenous pollution, and it is necessary to limit the exogenous pollution and protect the alpine lakes immediately.

[Liposoluble constituents from the flowers of Calotropis gigantea and their antimicrobial activities].

OBJECTIVE: To study the liposoluble constituents from the flowers of Calotropis gigantea and their antimicrobial activities. METHODS: The liposoluble constituents from the flowers of Calotropis gigantea were analyzed by GC-MS and their relative contents were determined by area normalization. Their antimicrobial activities against 2 pathogens were tested by agar disc diffusion method. RESULTS: 31 compounds were separated and identified, amounting to 85.14% of the total constituents. The liposoluble constituents from the flowers of Calotropis gigantea exhibited weak antimicrobial activities against Staphylococcus aureus and Canidia albicans. CONCLUSION: The research result provides scientific foundation for exploitation and utilization of Calotropis gigantea.

[Study on the chemical constituents in the fruit of Harrisonia perforata].

OBJECTIVE: To study the chemical constituents in the fruit of Harrisonia perforata. METHODS: The chemical constituents were isolated and purified by means of chromatographic techniques and their structures were elucidated by analysis of spectroscopic data and physicochemical properties. RESULTS: Eight compounds were isolated and identified as caryolane-1,9beta-diol (1), gallic acid (2), 4-O-ethylgallic acid (3), syringic acid ethyl ester (4), protocatechuic acid (5), stigmasterol (6), beta-daucoster (7), beta-sitosterol (8). CONCLUSION: Compounds 1, 3 - 5 and 7 are isolated from this plant for the first time. Compounds 1, 3 and 4 are isolated from this genus for the first time.

Clinical and immunologic results of local hyperthermia at 44 °C for extensive genital warts in patients with diabetes mellitus.

BACKGROUND: Genital warts are more extensive and difficult to treat in patients with diabetes mellitus due to defective immune responses. PURPOSE: Our aim was to confirm the suitability of local hyperthermia for the treatment of genital warts in patients with diabetes mellitus and to investigate the immune cells in lesional areas at different time intervals after treatment. METHODS: We treated three diabetic patients with extensive genital warts by local hyperthermia at 44 °C for 30 min a day for 3 consecutive days plus 2 additional days 1 week later, then once a week till there showed signs of clinical clearance. Immunohistochemical profile was described on serial biopsies from a patient with confluent plaques. RESULTS: The warty lesions in the patients resolved in 6, 4 and 9 weeks, respectively. Immunohistochemical staining in the regressing warts revealed abundant infiltrating CD4+ T and CD8+ T lymphocytes (P < 0.01), as well as macrophages and CD1a+ dendritic cells. CONCLUSIONS: This preliminary study suggested that local hyperthermia was a safe and effective single modality in the treatment of genital warts in diabetic patients and could induce a rapid immune response in lesional skin.

Highly diastereoselective switchable enantioselective Mannich reaction of glycine derivatives with imines.

Tuning of diastereoselectivity was realized in the Mannich reaction of glycine derivatives with aromatic and aliphatic N-Ts imines using CuClO4-FcPHOX ligand 4b and 4f having an MeO group at the 4-position and F atom at the 3,5-position of the phenyl ring on the P-atom respectively as catalyst, providing either anti- or syn-alpha,beta-diamino acid derivatives in high yields and in high diastereo- and enantioselectivities.

Palladium-catalyzed enantioselective ring opening of oxabicyclic alkenes with organozinc halides.

Palladium-catalyzed asymmetric ring opening of oxabenzonorbornadienes with readily available organozinc halides under mild conditions in the presence of (S)-Pr(i)-PHOX produces the corresponding 1,2-dihydronaphth-1-ols in good yield and high enantioselectivity. [reaction: see text]