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Wang C.-P.,Nanjing University | Wang Y.,Nanjing University | Wang Y.,Fred Hutchinson Cancer Research Center | Wang X.,Nanjing University | And 4 more authors.
Planta Medica | Year: 2011

Mulberroside A is a major stilbene glycoside of Morus alba L. (Moraceae), which is effectively used for the treatment of hyperuricemia and gout in traditional Chinese medicine. We examined whether mulberroside A had effects on renal urate underexcretion and dysfunction in oxonate-induced hyperuricemic mice and investigated the potential uricosuric and nephroprotective mechanisms involved. Mulberroside A at 10, 20, and 40 mg/kg decreased serum uric acid levels and increased urinary urate excretion and fractional excretion of uric acid in hyperuricemic mice. Simultaneously, it reduced serum levels of creatinine and urea nitrogen (10-40 mg/kg), urinary N-acetyl - D-glucosaminidase activity (10-40 mg/kg), microglobulin (10-40 mg/kg) and albumin (20-40 mg/kg), and increased creatinine clearance (10-40 mg/kg) in hyperuricemic mice. Furthermore, mulberroside A downregulated mRNA and protein levels of renal glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1), and upregulated mRNA and protein levels of renal organic anion transporter 1 (mOAT1) and organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1, and mOCTN2) in hyperuricemic mice. This is the first study demonstrating that mulberroside A exhibits uricosuric and nephroprotective effects mediated in part by cooperative attenuation of the expression alterations of renal organic ion transporters in hyperuricemic mice. These data suggest that mulberroside A may be a new drug candidate for the treatment of hyperuricemia with renal dysfunction. © Georg Thieme Verlag KG Stuttgart · New York.


PubMed | Centers for Disease Control and Prevention, Hangzhou Normal University, Zhejiang CONBA Pharmaceutical Co. and Zhejiang University
Type: Journal Article | Journal: PloS one | Year: 2016

Previously, we have shown that paraspeckle protein 1 (PSPC1), a protein component of paraspeckles that was involved in cisplatin-induced DNA damage response (DDR), probably functions at the G1/S checkpoint. In the current study, we further examined the role of PSPC1 in another DNA-damaging agent, methyl methanesulfonate (MMS)-induced DDR, in particular, focusing on MMS-induced apoptosis in HeLa cells. First, it was found that MMS treatment induced the expression of PSPC1. While MMS treatment alone can induce apoptosis, depletion of PSPC1 expression using siRNA significantly increased the level of apoptosis following MMS exposure. In contrast, overexpressing PSPC1 decreased the number of apoptotic cells. Interestingly, morphological observation revealed that many of the MMS-treated PSPC1-knockdown cells contained two or more nuclei, indicating the occurrence of mitotic catastrophe. Cell cycle analysis further showed that depletion of PSPC1 caused more cells entering the G2/M phase, a prerequisite of mitosis catastrophe. On the other hand, over-expressing PSPC1 led to more cells accumulating in the G1/S phase. Taken together, these observations suggest an important role for PSPC1 in MMS-induced DDR, and in particular, depletion of PSPC1 can enhance MMS-induced apoptosis through mitotic catastrophe.


Gao X.,Centers for Disease Control and Prevention | Gao X.,Zhejiang University | Zhang G.,Zhejiang University | Shan S.,Zhejiang University | And 8 more authors.
PLoS ONE | Year: 2016

Previously, we have shown that paraspeckle protein 1 (PSPC1), a protein component of paraspeckles that was involved in cisplatin-induced DNA damage response (DDR), probably functions at the G1/S checkpoint. In the current study, we further examined the role of PSPC1 in another DNA-damaging agent, methyl methanesulfonate (MMS)-induced DDR, in particular, focusing on MMS-induced apoptosis in HeLa cells. First, it was found that MMS treatment induced the expression of PSPC1. While MMS treatment alone can induce apoptosis, depletion of PSPC1 expression using siRNA significantly increased the level of apoptosis following MMS exposure. In contrast, overexpressing PSPC1 decreased the number of apoptotic cells. Interestingly, morphological observation revealed that many of the MMS-treated PSPC1-knockdown cells contained two or more nuclei, indicating the occurrence of mitotic catastrophe. Cell cycle analysis further showed that depletion of PSPC1 caused more cells entering the G2/M phase, a prerequisite of mitosis catastrophe. On the other hand, over-expressing PSPC1 led to more cells accumulating in the G1/S phase. Taken together, these observations suggest an important role for PSPC1 in MMSinduced DDR, and in particular, depletion of PSPC1 can enhance MMS-induced apoptosis through mitotic catastrophe. © 2016 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Zhang J.-S.,Zhejiang Conba Pharmaceutical Co. | Wu T.,Hangzhou Addisun Medicine Co. | Tang Q.-J.,Zhejiang Chinese Medical University | Gao J.-L.,Zhejiang Chinese Medical University | And 2 more authors.
Chinese Traditional and Herbal Drugs | Year: 2014

Objective: To study the protection of extract from Phyllanthus emblica (EPE) on focal cerebral ischemia-reperfusion injury in rats and its mechanism. Methods: Male SD rats were divided into six groups such as Sham, model, Ginkgo biloba extract (100 mg/kg, positive control), low-, mid-, and high-dose (crude drug 6.0, 3.0, and 1.5 g/kg) EPE groups. The rats in the treatment groups were ig administered once daily for 10 d. On day 10 the focal cerebral ischemia-reperfusion rat model was established using middle cerebral artery occlusion method. After the model establishment, the neurological function scores were observed, the infarct size was measured by TTC staining, and the contents of SOD, MDA, NO, IL-1β, IL-6, iNOS, and NF-κB in brain tissue were measured. Results: Compared with the model group, EPE could significantly reduce the neurological function scores (P < 0.05), decrease the cerebral infarct size (P < 0.05), increase the activity of SOD (P < 0.05), and reduce the contents of MDA, NO, IL-1β, IL-6, iNOS, and NF-κB (P < 0.05) in brain tissue. Conclusion: EPE has the significant protection on cerebral ischemia-reperfusion injury in rats due to increasing the anti-oxidant activity and inhibiting the inflammatory reaction. ©, 2014, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.


Liu Z.,Zhejiang University | Liu Z.,Zhejiang Conba Pharmaceutical Co. | Wang R.,Zhejiang Conba Pharmaceutical Co. | Wang R.,Zhejiang Chinese Medical University | And 5 more authors.
Zhongguo Zhongyao Zazhi | Year: 2012

Objective: To study the water-soluble non-alkaloid chemical constituents of Corydalis yanhusuo. Method: The 80% alcohol extracts of C. yanhusuo passed through DA201 macroporous resin. Eluted fractions were collected and passed though 732 # cation exchange resin. Water eluate was collected, dried and derived with trimethylsilane. Gas Chromatography/Mass Spectrometry and NIST 2005 library were adopted for MS/MS mass spectrogram to infer the compound structure. Result: Sixteen compounds were tentatively identified from about fifty peaks detected by GC-MS and identified as hydroxyl and carboxyl polar compounds. Conclusion: These sixteen compounds were found for the first time in C. yanhusuo. The results provide scientific basis for in-depth development of C. yanhusuo.


PubMed | University of Miami, Zhejiang University of Technology and Zhejiang CONBA Pharmaceutical Co.
Type: | Journal: International journal of analytical chemistry | Year: 2015

More and more saffron has been cultivated in China because of the increasing saffron demand, but no paper has studied the influence of drying methods on the quality of Chinese saffron. In this paper, three different dehydration treatments applied in actual production were evaluated: dehydration with electric oven, vacuum oven, and microwave. We determined that the highest quality of saffron will be obtained when fresh saffron is treated at higher temperatures (no more than 70C) for a long time by electric oven drying and vacuum oven drying. In microwave drying, treatments at lower microwave power and longer time benefit the quality of saffron. In addition, the influence of the drying method on antioxidants in saffron is discussed. The correlation between individual saffron profiles and the antioxidant value was estimated by spectrum-effect relationships analysis.


PubMed | Hubei University for Nationalities, Zhejiang University of Technology and Zhejiang CONBA Pharmaceutical Co.
Type: Journal Article | Journal: Chemistry & biodiversity | Year: 2015

Two new triterpenoids, 30-hydroxylup-20(29)-ene 3-caffeate (1) and 24-nor-friedelan-6,10-dihydroxy-1,2-dioxo-4,7-dien-29-oic acid (2), together with eight known compounds 3-10, were isolated from the roots of Celastrus stylosus. The structures of these compounds were elucidated on the basis of spectroscopic analyses. To the best of our knowledge, this represents the first study on the chemical constituents of C. stylosus. The antiproliferative activities of the triterpenoids against six human cancer cell lines (PANC-1, A549, PC-3, HepG2, SGC-7901, and HCCLM3) were evaluated. Compounds 3, 4, and 10 exhibited comparable activities against PC-3 and HCCLM3 cell lines as the positive control taxol.


PubMed | Nanjing University and Zhejiang CONBA Pharmaceutical Co.
Type: | Journal: Journal of ethnopharmacology | Year: 2015

Wuling San, a famous prescription in Chinese medicine, is composed of Polyporus, Poria, Alismatis rhizoma, Cinnamomi cortex and Atractylodis macrocephalae rhizoma, and promotes kidney function and diuresis. The main purpose of this study was to investigate its renal protective effect in high fructose-induced hyperuricemic mice.ICR mice were fed with 30% fructose in drinking water for 6 weeks to induce hyperuricemia and renal dysfunction. Then mice were orally administrated for other 6 weeks with Wuling San (987, 1316, 1755 and 2340mg/kg), allopurinol (5mg/kg) and water daily, respectively. Serum and urine levels of uric acid, creatinine and blood urea nitrogen (BUN) were measured. Hematoxylin and eosin staining was used to assess renal histological changes. Renal interleukin (IL)-1 concentrations were measured using ELISA kit. Renal protein levels of organic ion transporters, as well as toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling and pyrin domain containing 3 (NLRP3) inflammasome were determined by Western blot assay.Wuling San significantly decreased serum uric acid, creatinine and BUN levels, increased fractional excretion of uric acid (FEUA) in fructose-fed mice. It restored fructose-induced dysregulation of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), ATP-binding cassette subfamily G member 2 (ABCG2) and organic anion transporter 1 (OAT1), as well as organic cation transporter 1 (OCT1) and OCT2 in mice. Wuling San obviously alleviated infiltration of inflammation cells in kidney glomerulus of fructose-fed mice. Moreover, Wuling San suppressed the activation of TLR4/ MyD88 signaling to inhibit nuclear factor B (NF-B) signaling and mitogen-activated protein kinases (MAPKs) activation in fructose-fed mice. Additionally, Wuling San decreased NLRP3 inflammasome activation and IL-1 secretion in the kidney of fructose-fed mice.Wuling San exerts renal protective effect by modulating renal organic ion transporters in fructose-induced hyperuricemic mice. The molecular mechanism of its action may be associated with the suppression of TLR4/MyD88 signaling and NLRP3 inflammasome activation to reduce IL-1 production in high fructose-induced hyperuricemic mice.


Chen Z.,Zhejiang University | Tu M.,Zhejiang University | Sun S.,Zhejiang University | Kong S.,Zhejiang University | And 5 more authors.
Drug Metabolism and Pharmacokinetics | Year: 2012

Summary: Luteolin (3',4',5,7-tetrahydroxyflavone) and apigenin (4',5,7-trihydroxyflavone) are two common flavones and major bioactive components in Flos Chrysanthemi extract (FCE). Although FCE contains approximately equal amounts of luteolin (6.5%, w/w) and apigenin (5.4%, w/w), luteolin showed a much lower exposure than apigenin when FCE was orally administered to rats. The aim of the present study is to elucidate the mechanisms that caused the pharmacokinetic difference between luteolin and apigenin in rats. The results of an in situ rat intestinal single-pass perfusion model showed that the permeability of luteolin (k a, 7.96 × 10 -2 min -1 and P eff, 4.87 × 10 -3 cm/min) was about 50% that of apigenin (k a, 18.5 × 10 -2 min -1 and P eff, 10.8 × 10 -3 cm/min), which agreed with the observation that oral bioavailability of luteolin (30.4%) from FCE was significantly lower than that of apigenin (51.1%). On the other hand, luteolin was much more unstable than apigenin during the incubation with primary rat hepatocytes, and methylated metabolites of luteolin were detected after incubation. In addition, further metabolism of methylated luteolin also contributed to the faster elimination of luteolin. In conclusion, luteolin and apigenin are very similar in structure, however, one-hydroxyl difference gives them different characteristics in absorption and metabolism, which results in much lower exposure of luteolin than apigenin when FCE is orally administered to rats. © 2012 by the Japanese Society for the Study of Xenobiotics (JSSX).


Yao J.-B.,Zhejiang CONBA Pharmaceutical Co. | Yao J.-B.,Zhejiang Provincial Key Laboratory of Chinese Materia Medica Pharmacecutical Technology | Jin H.-H.,Zhejiang CONBA Pharmaceutical Co. | Jin H.-H.,Zhejiang Provincial Key Laboratory of Chinese Materia Medica Pharmacecutical Technology | And 4 more authors.
Chinese Traditional and Herbal Drugs | Year: 2015

Objective: To establish the method for the specific chromatograms analysis of Crocus sativus, so as to distinguish the active constituents between saffron and gardenia. Methods: HPLC with ZorBax XDB-C18 column was used, the mobile phase was a linear gradient of methanol containing 0.5% acetic acid and water containing 0.5% acetic acid in 45 min, the detection wavelength was set at 254 nm and the flow-rate was 1.0 mL/min. Results: Multi batches of samples were analyzed to establish the specific chromatograms. Eight marked peaks were separated. The methodological evaluation showed that the method had a good repeatability. The active constituents between saffron and gardenia could be significantly distinguished by this method. Conclusion: The method is simple, rapid, and accurate with good reproducibility and can be used for the quality control and identification of C. sativus. ©, 2015, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.

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