Analgesic Effect and Action Mechanisms of Wenjing Zhitong Prescription on Primary Dysmenorrhea / 中国实验方剂学杂志

Objective:To evaluate the analgesic effects of Wenjing Zhitong prescription （WZP） and explore its possible analgesic mechanisms so as to provide experimental basis for research and development of new Chinese medicine. Method:Analgesic effects of WZP were evaluated by observing the writhing latency and number in the writhing models which were induced by oxytocin in rats as well as those induced by acetic acid and prostaglandin E₁ （PGE₁）， respectively in mice. Effect of WZP on uterine contraction frequency， amplitude and activity were evaluated by observing the oxytocin-induced contraction of uterine smooth muscle in rats and rabbits <italic>in vivo</italic>. In the oxytocin-induced rat writhing models， the content of prostaglandin F₂<italic>_α</italic>（PGF₂<italic>_α</italic>） and prostaglandin E₂（PGE₂） in rat uterine tissues and the content of beta-endorphins （<italic>β</italic>-EP） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA）. Expression of estrogen receptor （ER） and oxytocin receptor （OTR） in rat uterine were tested by Real-time polymerase chain reaction（Real-time PCR） method to investigate the possible molecular mechanism of WZP for its analgesic effect. Result:Results of analgesic effect showed that in oxytocin-induced rat writhing experiment， the number of writhing responses in both the WZP （1.5，3.0 g·kg^-1） group was lower than than in the model group （<italic>P</italic><0.05）. In acetic acid-induced mice writhing experiment， the latency of writhing response in WZP （6.0 g·kg^-1） group was significantly prolonged as compared with that in model group <italic>（P</italic><0.01）， and the number of writhing response was significantly reduced （<italic>P</italic><0.05）. In PGE₁-induced mice writhing model， the writhing number in WZP （1.5，3.0，6.0 g·kg^-1） groups was significantly lower than that in the model group （<italic>P</italic><0.05，<italic>P</italic><0.01）. Results of effect on uterine smooth muscle demonstrated that WZP （0.38，0.75，1.50 g·kg^-1） could significantly reduce the frequency of uterine smooth muscle contraction in rabbits （<italic>P</italic><0.05，<italic>P</italic><0.01）， WZP （0.75，1.50，3.00 g·kg^-1） could significantly reduce the contractile amplitude and activity of smooth muscle in the uterus of rats （<italic>P</italic><0.05）. Results of molecular mechanisms of analgesic effects showed that the WZP （0.75，1.50，3.00 g·kg^-1） significantly reduced the content of PGF₂<italic>_α</italic> and the ratio of PGF₂<italic>_α</italic> to PGE₂ in the uterine tissue of rats （<italic>P</italic><0.01）. In the WZP （3.00 g·kg^-1） group， the levels of <italic>β</italic>-EP in the serum of rats were significantly increased （<italic>P</italic><0.01）， and the levels of OTR in uterus of rats in the WZP （1.50，3.00 g·kg^-1） group were significantly decreased （<italic>P</italic><0.05）. Conclusion:Pharmacological studies demonstrated potent analgesic effect of WZP， and such analgesic effect were mediated by significantly inhibiting contraction of uterine smooth muscle， decreasing the contents of PGF₂<italic>_α </italic>and ratio of PGF₂<italic>_α</italic>/PGE₂， reducing OTR expression in uterine as well as increasing the amount of <italic>β</italic>-EP in serum.

Comparative Study on Hepatotoxicity of Psoraleae Fructus in Rats and Mice / 中国实验方剂学杂志

Objective:Arrange long-term toxicity experiments by a uniform design method， so as to explore the effect of different extracts of Psoraleae Fructus on liver toxicity in rats and mice， and find the drug factors that cause psoralen liver toxicity. Method:Based on the factors of processing， extraction technology， dosage and treatment course， each experimental group was arranged by uniform design method. A total of 220 SD rats and 220 Kunming mice with half male and half female were divided into normal groups and drug groups 1 to 8. The corresponding drugs （50% alcohol extract of salt Psoraleae Fructus in rats 2.57 g·kg-1， mice 5.14 g·kg-1， 95% alcohol extract of Psoraleae Fructus in rats 0.51 g·kg-1， mice 1.02 g·kg-1， 70% alcohol extract of salt Psoraleae Fructus in rats 1.71 g·kg-1， mice 3.42 g·kg-1， water extract of Psoraleae Fructus in rats 1.03 g·kg-1， mice 2.06 g·kg-1， water extract of salt Psoraleae Fructus in rats 1.03 g·kg-1， mice 2.06 g·kg-1， 70% alcohol extract of Psoraleae Fructus in rats 1.71 g·kg-1， mice 3.42 g·kg-1， 95% alcohol extract of salt Psoraleae Fructus in rats 0.51 g·kg-1， mice 1.02 g·kg-1， 50% alcohol extract of Psoraleae Fructus in rats 2.57 g·kg-1， mice 5.14 g·kg-1） were administered by gavage daily. The body weight and food intake of the rats and mice were measured once a week. After the treatment course， the rats were anesthetized with sodium pentobarbital， and blood was taken from the abdominal aorta， and the mice were sacrificed by removing the eyeballs， and the liver and brain were taken to calculate the organ coefficients. Serum was taken to determine liver function-related indicators， and the liver was taken for histopathological examination by hematoxylin-eosin （HE） staining. Result:The liver visceral-brain ratio of female rats in group 3 were significantly increased （P<0.05）. The liver quality， visceral-body ratio and visceral-brain ratio of male mice in groups 1 to 3 were significantly increased （P<0.05， P<0.01）. Histopathological manifestations in mice were more obvious than those in rats. Histopathology showed hepatocyte hypertrophy in the central area of liver lobules in mice， in particular in group 3. According to the multiple regression equation， there were interactions between extraction technology， processing， dosage and treatment course， and the extraction technology was positively correlated with the pathological score of liver injury. Based on the results of visual analysis and other indicators， it is concluded that the extraction technology factor is most relevant to psoralen liver toxicity of Psoraleae Fructus. Conclusion:Psoraleae Fructus has the hepatotoxicity， which is related to ethanol extraction technology； alcohol extraction is more toxic than water extraction， and 70% ethanol extraction is the most toxic. Besides， there are species differences， with a more significant hepatotoxicity in mice than that in rats.

Effect of Xuesaitong drop pills on experimerntal thrombosis and thrombolysis in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect and the mechanism of Xuesaitong drop pills (total saponins in Radix Notoginseng; XDP) on experimental thrombosis, thrombolysis and blood theology.</p><p><b>METHOD</b>First, the rats were randomly divided into five groups: control, XDP (90, 30, 10 mg x kg(-1)), Xuesaitong tablet (XP) 30 mg x kg(-1). Then the effect of the drugs on thrombus and thrombosis was studied after the ratsthrombosis was induced by the arteriovenous shunt. Second, the rats were randomly divided into seven groups: model, XDP (90, 30, 10 mg x kg(-1)), XT (90, 30 mg x kg(-1)), lumbrukinase capsule. Then the effect of the drugs on thrombus and thrombosis was studied after the rats'thrombosis was induced by the electrical stimulation of common carotid artery. Third, the rats were randomly divided into six groups: control, model, XDP (80, 40 mg x kg(-1)), XT (40, 20 mg x kg(-1)). Then the effect of the drugs on blood circulation promoting was observed after the rats'acute blood stasis induced by adrenalin and icy water.</p><p><b>RESULT</b>XDP 90, 30 mg x kg(-1) could notably lighten the wet-weight and dry-weight of thrombus in the arteriovenous shunt model in rats in a dose-dependent manner (P < 0.01). XDP 90 mg x kg(-1) with intragastric administration for 3 days had the satisfactory effect on thrombolysis after the rat's thrombosis was induced by the electrical stimulation of common carotid artery (P < 0.01). XDP 80, 40 , 20 mg x kg(-1) reduced significantly erythrocyte aggregation (P < 0.01) and decreased the whole blood viscosity at low shear rate (P < 0.05). XDP 80, 40 mg x kg(-1) reduced the whole blood viscosity at high shear rate and plasma viscosity (P < 0.05). XDP 80 mg x kg(-1) decreased the whole blood viscosity at high shear rate (P < 0.05).</p><p><b>CONCLUSION</b>XDP can significantly inhibit the thrombosis and has the satisfactory effect on thrombolysis. One kind of the mechanism is related to the effect on blood rheology.</p>