Penicacids E-G, three new mycophenolic acid derivatives from the marine-derived fungus Penicillium parvum HDN17-478 / 中国天然药物

Three new mycophenolic acid derivatives, penicacids E-G (1-3), together with three known analogues, mycophenolic acid (4), 4'-hydroxy-mycophenolic acid (5) and mycophenolic methyl ester (6), were isolated from a marine-derived fungus Penicillium parvum HDN17-478 from a South China Sea marine sediment sample. The structures of compounds 1-3 were elucidated by HRMS, NMR, and Mosher's method. Among them, compounds 1 and 2 were the first examples of mycophenolic acid analogs with a double bond at C-3'/C-4' position. The cytotoxicity of 1-6 was evaluated against the HCT-116, BEL-7402, MGC-803, SH-SY5Y, HO-8910 and HL-60 cell lines, and compounds 4 and 6 showed potent cytotoxicity with IC

Simultaneous determination and pharmacokinetics of eight ginsenosides by LC-MS/MS after intravenously infusion of 'SHENMAI' injection in dogs

SHENMAI injection, a prescription comprised of Panax ginseng and Ophiopogon japonicas, is being extensively applied in the field of cardio-protection and immune-modulation in China. Ginsenosides are the main active components in SHENMAI injection. In order to capture and analyze the pharmacokinetic profile of major ginsenosides of SHENMAI injection in Beagle dogs, liquid chromatography equipped with electro-spray ionization and tandem mass spectrometry method was applied in simultaneous determination for protopanaxatriol type ginsenoside [Re, Rf, Rg1], protopanaxadiol type ginsenoside [Rb2, Rb1, Rd, Rc] and oleanolic acid type ginsenoside [Ro]. A C18 column [150 × 2.1mm, 5micro m] and a linear gradient program were used to achieve chromatographic separation, with 0.02% acetic acid solution and acetonitrile. I.S. and ginsenosides were detected by LC-MS/MS in selective reaction mode. Good linearity spanning 5- 1500ng/mL was achieved with the R[2] values higher than 0.99 for all analytes. Limit of quantification of all analytes were 3ng/mL. Intra- and inter-day precisions ranges from 0.47 to15.68 % and accuracies were within the range of 85.27-117.57%. Validated analyzing method was then used in the pharmacokinetic experiment for SMI in dogs. The results showed that the pharmacokinetic profile of protopanaxadiol, protopanaxatriol and oleanolic acid type ginsenoside were significant difference in dogs. Protopanaxadiol type ginsenosides exhibited an extremely higher level of exposure and a much slower elimination process. Whereas protopanaxatriol type ginsenosides were quickly eliminated. We concluded that 20 [S] - protopanaxadiol type ginseno sides could be a potential pharmacokinetic marker of SHENMAI injection

In silico target fishing for the potential bioactive components contained in Huanglian Jiedu Tang (HLJDD) and elucidating molecular mechanisms for the treatment of sepsis / 中国天然药物

The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction (HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2R proteins were established using the homology modelling (HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.

Effect of pulchinenoside on FZD8 expression of adjuvant arthritis rats / 中国中药杂志

To study the effect of pulchinenoside (PULC) on the Frizzled (FZD) expression of adjuvant arthritis ( AA) rats. AA rats were prepared through the toe injection with complete Freund's adjuvant to culture fibroblast-like synoviocytes (FLS). The effect of the oral administration with PULC on the FZD8 expression was detected by the real time qPCR. The effect of FZD8 knockout on the expressions of IL-1, IL-6, IL-8 were detected by MTT and ELISA. The role of miR-375 in the abnomal expression of FZD8 was detected by the real time qPCR. The results showed signfiicant decrease in the FZD8 expression among AA rats, FLS proliferation ater FZD8 knockout and IL-1, IL-6, IL-8 expressions and notable increase in miR-375 expression after the oral administration with PULC. The up-regulated miR-375 expression can inhibit the FZD8 expression. PULC may inhibit the FZD8 expression by up-regulating the miR-375 expression.

Flavonoids of Echinps latifolius suppress Wnt signaling in adjuvant arthritis rats / 中国中药杂志

The role of flavonoids of Echinps latifolius (FELT) in Wnt signaling was investigated in adjuvant arthritis (AA) rats. The therapeutic effects of FELT on AA rats were detected by rat arthritis score and MTT. The effect of FELT gavage treatment on the Wnt signaling key gene β-catenin, C-myc and cyclin D1 in synovium from AA rats was detected by Real-time qPCR, and the effects of FELT gavage treatment on the upstream negative regulation gene SFRP 1,2,4,5 in synovium from AA rats were detected by Real-time qPCR. The results showed that FELT gavage treatment significantly inhibited arthritis score and MTT values in AA rats, significantly inhibited the expression of the Wnt signaling gene β-catenin, C-myc and cyclin D1, significantly up-regulated the expression of the up- stream negative regulation gene SFRP 1,2,4. FELT has a better therapeutic effect for AA rats.

Treatment of rheumatoid arthritis with flavonoids of Echinps latifolius Tausch in rat model / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of Flavonoids extracted from Echinps latifolius Tausch(FELT) on rheumatoid arthritis (RA) in rat model.</p><p><b>METHOD</b>Fifty SD rats were randomly divided into model group, control group, and low, medium, and high-dose FELT groups (n=10 in each group). Complete Freund's adjuvant (0.1 mL) was used to induce RA in rats. FELT in doses of 50 mg/kg, 100 mg/kg, 150 mg/kg was given to rats in low, medium and high-dose FELT groups by gavage, and same volume of PBS was given to rats in control group. The arthritis score and the paw swelling score were measured to evaluate the therapeutic effect of FELT. Real time qPCR was used to detect the mRNA expression of fibronectin and MMP3 in synovial tissue and the mRNA expression of caspase 3, Bcl-2 and Bcl-2 associated X protein (Bax) in fibroblast-like synoviocytes (FLS).</p><p><b>RESULTS</b>The arthritis score and the paw swelling score were significantly decreased in three FELT groups compared to RA model rats (P <0.05). The relative expression levels of FN and MMP3 mRNA in synovium of three FELT-treatment groups were significantly lower than those in model group (1.80, 1.76 and 1.67 vs 2.53; 1.69, 1.46 and 1.45 vs 2.67, respectively, all P <0.05). The relative expression levels of Bax and caspase 3 mRNA in FLSs of three FELT groups were higher than those in model group (0.56, 0.58 and 0.60 vs 0.30; 0.54, 0.56 and 0.59 vs 0.29, respectively, all P <0.05); while the relative expression levels of Bcl-2 mRNA in FELT groups were lower than that in model group (2.20, 2.08 and 2.08 vs 4.04, respectively, P <0.05).</p><p><b>CONCLUSION</b>FELT may inhibit the synovium proliferation in RA model rats through promoting the FLS apoptosis.</p>

Pulchinenoside control MeCP2 expression in FLS from RA model rats / 中国中药杂志

The role of pulchinenoside (PULC) in the regulation of MeCP2 expression was investigated in RA model rats. Adjuvant arthritis rats were used as RA model rats, and fibroblast-like synoviocytes (FLS) from the RA model rats were cultured. The effect of 100 mg x kg(-1) PULC gavage treatment on the MeCP2 expression and the effect of MeCP2 siRNA on the expression of SFRP2 and β-catenin were detected by real time qPCR and Western blotting. The role of PULC in the FLS proliferation was detected by MTT. The results showed that the MeCP2 expression was down-regulated, the SFRP2 expression was up-regulated and the FLS proliferation was inhibited in FLS after therapy. MeCP2 siRNA significantly inhibited the MeCP2 expression, up-regulated the SFRP2 expression and inhibited the β-catenin expression in FLS from RA model rats. PULC may increase the SFRP2 expression, inhibit the Wnt signaling and inhibit the FLS proliferation in FLS from the RA model rats by inhibiting the MeCP2 expression.

Effect of pulchinenoside in regulating FLS SFRP2 expression of RA model rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of pulchinenoside (PULC) in modulating SFRP2 expression in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) model rats.</p><p><b>METHOD</b>The effect of PULC in treating RA rats was evaluated by rat arthritis score and paw swelling score. The inhibitory effect of PULC on FLS proliferation was detected by MTT reagent. The effects of PULC gavage treatment in modulating gene expression of FLS SFRP2, critical gene beta-catenin of Wnt pathway and downstream effector genes C-myc of of Wnt pathway were detected by RT-PCR and Western blotting.</p><p><b>RESULT</b>PULC had a significant effect in treating RA rats and that SFRP2 expression was down-regulated in FLS. After PULC gavage treatment, FLS SFRP2 expression was obviously up-regulated, whereas beta-catenin and C-myc gene expressions were significantly down-regulated.</p><p><b>CONCLUSION</b>PULC can inhibit abnormal proliferation of synovial membrane by modulating Wnt pathway of RA rats.</p>

Effect of cyclovirobuxinum-D on cerebral ischemia-reperfusion injury in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of cyclovirobuxinum-D (CVB-D) on cerebral ischemia-reperfusion injury in rats and explore its mechanisms.</p><p><b>METHOD</b>One hundred and twenty rats were randomly divided into three CVB-D groups (2, 1, 0.5 mg x kg(-1)), Nimodipine group (2 mg x kg(-1)), model group and sham operated group, 20 rats each group. Rat cerebral ischemia-reperfusion injury model was induced by middle cerebral artery occlusion, the nerve injury symptoms was evaluated, the level of SOD and MDA in brain tissue were determined, the concentration of intracellar Ca2+ of brain was measured, and the pathological change of brain was also observed.</p><p><b>RESULT</b>CVB-D could improve the nerve injury symptoms, reduce the infarction area of brain, the concentration of intracellar Ca2+ and the level of MDA, increase the activity of SOD, and decrease the pathological change of brain.</p><p><b>CONCLUSION</b>CVB-D has protective effect on cerebral ischemia-reperfusion injury in rats.</p>

Study on the effect of a community-based early education and service program regarding intelligence development of infants / 中华流行病学杂志

<p><b>UNLABELLED</b>Study on the effect of a community-based early education and service program regarding intelligence</p><p><b>OBJECTIVE</b>To assess the effect on a community-based early education and service programs regarding the development of infants' intelligence.</p><p><b>METHODS</b>A community-based intervention study was carried out among 359 infants and their families. Base-line survey were carried out when infants reached their one month, where after infants and their families in the intervention group received instructions and services focused on baby fostering and intelligence development. When the infants reached their six-months and twelve-months of age, their families were informed to complete the follow-up surveys, using both questionnaire investigation and testing the infants' intelligence quotients. The infants' intelligence quotients were measured by Development Screening Test for children under six. By comparing intelligence quotients of infants in two study groups in the follow-up surveys, this paper evaluated the impacts of community intervention on the infants' intelligence development.</p><p><b>RESULTS</b>During two follow-ups, no statistical difference had been detected between the two groups of infants in term of gender or delivery process. Baseline data showed that infants' mental index (MI) scored 98.26 in the intervention group and 101.79 in the control one, and development quotient (DQ) scored 94.50 and 99.36 in respective groups. Infants' MI score increased 6.07 and 8.86 at the six-month and twelve-month follow-up periods respectively in the intervention group compared during the baseline, higher than the MI increments of the control group at the two follow-up periods (-2.46 and 1.05 respectively). DQ score of infants in the intervention group increased 12.94 and 11.24 respectively in the two follow-up surveys, which were also higher than increments in the control group (-0.18 and 0.34). The group x time effect(interaction effect) of MI and DQ in six-month and twelve-month follow-ups were both significantly higher than that of the baseline level.</p><p><b>CONCLUSION</b>The community-based early education and service programs could effectively improve the infants' intelligence.</p>