| This thesis consists of two parts.The first part is about the research of natural products to reverse tumor multidrug resistance in vitro and the mechanism of action of neo-clerodane diterpenoids,jatrophane diterpenoids and lathyris diterpenoids to reverse tumor multidrug resistance.The second part is the research about sedative hypnotic and improving digestion action of the processing Valeriana jatamansion in mice.In the first part of study,the reversal effect of 162 natural products isolated from Scutellaria barbata D.Don,Euphorbia kansui,Tripterygium hypoglaucum(Levl.)Hutch,Valeriana jatamansi Jones,Sophora davidii and Elsholtzia bodinieri Vaniot on the resistance to Adriamycin in HepG2/Adr cells was evaluated 25 compounds,which structural types included neo-clerodane diterpenoids,jatrophane diterpenoids,lathyris diterpenoids and dihydroagarofuran sesquiterpene,were found to have potential activity of overcome MDR.The study on the mechanism of reversing multidrug resistance of neocrotane diterpene compounds 1,2,3,6 isolated from Scutellaria barbata D.Don and lathyris diterpenoids compounds 41 and 42 isolated from Euphorbia neriifolia L were evaluated.The results shows that the compounds above had reversing action when it combined with Adr,with reversal index(RI)values from 14.04 to 39.42.Western blot analysis indicated that p-glycoprotein expression in HepG2/Adr cells was significantly higher than that in sensitive strains,which might be the main factor causing drug resistance.Fluorescence results showed that the compounds significantly promoted the accumulation of Adr in HepG2/Adr cells.However,the compounds did not affect the p-glycoprotein expression.These results indicated that compounds above reversed tumor multidrug resistance by inhibiting the efflux function of P-glycoprotein.The jatrophane diterpenoids compounds 38 and 39 isolated from Kansui were also reversed the resistance of Hep G/Adr cells to Adr.It also proved that compounds 38 and 39 could promote the accumulation of Adr and Rhodamine 123(RHO 123)in HepG2/Adr cells.The further results indicated that compounds did not influence the expression of P-gp neither treated solo nor co-treated with Adr.However,it increases the consumption of ATP,suggesting that it activates p-gp ATPase activity.It shows that compounds 38 and 39 are effective substrates for p-gp.In addition,compounds 38 can also inhibit the production of NO and IL-6 induced by LPS in macrophages,and i NOS expression was also significantly inhibited,but the expression of COX-2 protein was significantly up-regulated.The results show that compound 38 has a regulatory effect on immune cells.The second part is the research about sedative hypnotic and improving digestion action of the processing Valeriana jatamansion in mice.To research the sedative and hypnotic effects of raw Valeriana jatamansi and its processed products in different solvents(water phase and oil phase)with the turn over reflecting method.The results showed that both the raw V.jatamansi and its processed products,in different solvent phases,could improve the sleep rate of mice.In the water phase group,the sleep rate of the processed products increased by 10% compared with the raw ones,while in the oil phase group,the sleep rate of the processed products increased by 20%.Furthermore,both the raw V.jatamansi and its processed products could prolong the sleep time and shorten the sleep latency of mice.The sleeping time increased from 16.10 ± 4.6 min to 25.18 ± 6.25 min(P<0.05)in the water phase group,while in the oil phase group,there was no significant difference in sleeping time between the raw V.jatamansi and its processed products.It can be seen that the different solvent conditions affect the pharmacodynamics of the raw V.jatamansi and its processed products.To study the effects of processing on improving digestive function of Valeriana jatamansi,the gastric residual rate and intestinal propulsion rate in mice of V.jatamansi and its processed products were measured.Nutritive semi-solid paste was used for intragastric administration to observe the change of gastric evacuation and intestinal propulsion.The gastric residual rates of the domperidone group(0.51 ± 0.12),the low-dose(0.52 ± 0.78)and high-dose(0.66 ± 0.12)groups of the processed products decreased significantly compared with the control group(0.91 ± 0.14),and the difference was significant(P<0.05).In addition,all drug-administered groups could promote intestinal propulsion dramatically compared with the control group(0.50 ± 0.13).The effects of both the low(0.92 ± 0.07)and high-dose(0.94 ± 0.07)groups of the processed products were better than those of the domperidone group(0.58 ± 0.08)and Tablet Xiangguo Jianxiao group(0.67 ± 0.15),and the difference was significant(P< 0.05).Therefore,processing plays a key role in promoting the digestion of V.jatamansi. |
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