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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).

Gao X.,U.S. Center 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.

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.

Zhejiang Conba Pharmaceutical Co. | Date: 2002-11-05


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.

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