The Partial Study On Toxicology And Pharmacodynamics Of APN Soft Capsules And Its Antipyretic Mechanisms

Andrographis Paniculata Nees soft capsules (APN soft capsules) is a pure traditional Chinese drug preparation that developed in Guangzhou university of traditional Chinese medicine recently, was made up of extraction from the plant Andrographis Paniculata. Andrographis Paniculata Nees is one kind of herbal drug for relieving the internal heat of the body, it has the effect of antifebrile, detoxifies, cooling blood and detumescence, so it's used to treat the heat-syndrome of the interior in the differential diagnosis. In the medicinal works "the herbalism of QuanZhou" , there was the record for this medicinal plant that it may lower febrile, detoxify, diminish inflammation and tumefaction, may be used to the throat inflammation, dysentery and high fever. Previous pharmacological research indicated that APN preparation have strong action in antipyretic, antiphlogistic, antibacterial and antiviral. Therefore it' s applied to the fever of cold, acute and chronic pharyngitis, dysentery, endotoxemia in clinic. In this study, we designed the acute toxicity and Pharmacodynamics experiments of APN soft capsules and its antipyretic mechanisms in order to offer pharmacological and experimental basis for its safe and effective use in clinic.There are three parts in the thesis:Part â…  The experiment on acute toxicity of APN soft capsulesWe observed that the maximum tolerance dose(MTD) of APN soft capsules on mice, administered orally, is 110.25(crude drug)/kg, and no acute toxicity reaction has been observed.Part â…¡ The experimental on Pharmacodynamics of APN soft capsules1. The experiment on antipyretic effect of APN soft capsulesIn acute fever model, the dose of 23. 52g/kg and 11.76g/kg of APN soft capsules administered orally showed potent inhibitory effect(p<0.05 or p<0. 01) on LPS-induced rabbit fever, and when compared with same dose of APN tablets (the preparation in pharmacopoeia), there was a remarkable difference within one hour after setting up of fever model. 22. 68g/kg, 11.34g/kg APN soft capsules, administered orally, have a better antipyretic effect in rat baker' s yeast-induced fever(p<0.05 or p<0.01), but there was no remarkable difference compared with same dose APN tablet.2. The experiment on anti-inflammatory effect of APN soft capsulesIn acute inflammatory model, the dose of 11. 34g/kg and5. 67g/kg of APN soft capsules administered orally(three days) could reduce the pedal swelling in rat induced by carrageenin(vs model group p<0. 05), but there was no remarkable difference compared with same dose APN tablet. Moreover, APN soft capsules (16. 38, 8. 19, 4.lOg/kg), administered orally(three days), showed potent inhibitory effect on dimethylbenzene-induced mice auricle edema, and APN soft capsules(8.19,4.10,2.05g/kg) all showed inhibitory effect on acetic acid-induced increased permeability of mice abdominal capillary(vs model group p<0. 05 or p<0. 01).3. The experiment on analgesic effect of APN soft capsules16. 38g/kg, 8.19g/kg, 4. lOg/kg APN soft capsules administered orally, showed no effect on increasing the mice pain threshold of hot-plate test(vs model group p>0.05). Again, APN soft capsules showed no effective antinociception in the acetic acid induced writhing test in mice(vs model group p>0.05). PartHJ The research on antipyretic mechanism of APN soft capsules17.64g/kg APN soft capsules, administered- orally, showed potent inhibitory effects on LPS-induced rabbit fever, and within one hour after setting up of fever model, the AT, thermal response index(TRI) are all less than the model group(p<0.05), but have no remarkable difference with the control group(p>0. 05).Concentration of 5-HT and cAMP in rabbit' s hypothalamus and cerebrospinal fluid (CSF) were measured lh after the fever model. The results indicated that 5-HT content in hypothalamus in APN soft capsules group are...