Studies On Isolated Guinea-Pig Tracheal Smooth Muscle And Toxic Effects Of Aster Tataricus L.f.

Aster tataricus L. f. is the dried root or rhizome of Asteraceae perennial herb Aster, which is spicy, bitter, warm, and belongs to lung meridian, with the function of moistening lung for arresting cough, resolving phlegm and relieving asthma, for example, Aster tataricus L. f. act its pharmacologic effects as main drug in Chinese herbal compound like Ziwan San, Ziwan Wan, Ziwan Qi Wei Tang. To furtherly study the safe clinical dose of Aster tataricus L. f. and the principle of its effective constituent relieving asthma, this paper studied the acute and subchronic toxicity of 75% alcohol extract and different-polarity extracts of Aster tataricus L. f., and explored the effects of their contraction of guinea-pig tracheal smooth muscle in vitro. Providing a scientific basis for safety of Aster tataricus L. f. on anti-asthma effect. The results were as the following:1. Results of acute toxicity study: the LD50 of 75% alcohol extract was 15.74 g·（kg·bw）-1, its confidence interval was13.995¹7.698 g·（kg·bw）-1.2. Results of subchronic toxicity: The SD rats were oral administrated at dose of 0.34 g·kg-1 body weight continuously 28 d and 91 d. In the 28-d study, compared with control group, WBC decreased（P < 0.05）in ethyl acetate group, n-butyl alcohol group, the lower aqueous phases group in male rats, and decreased in petroleum ether group and ethyl acetate group, n-butyl alcohol group in females; LDH（P < 0.05）were observed increased in female rats in ethyl acetate group（P < 0.05）; Slight congestion and necrosis were showed in liver in petroleum ether group and ethyl acetate group. There was no significant change on other indices. In 91-d test, significant sporadic differences were seen in body weight gains during test groups; The MCHC decreased significantly in females in petroleum ether group, n-butyl alcohol group and the remaining lower aqueous phases group; there were differently increases in ALT、AST、CK、LDL-C、HLD-C、TC、LDH、T-BIL compared to the control group, and only the ALP（P < 0.05）significantly decreased in petroleum ether group and 75% alcohol group; Sporadic lesions, slight congestion and hepatic cord disorders were observed in liver in petroleum ether group and ethyl acetate group, In addition, signs of swelling and dissolution of the cardiac muscle fibres were observed in myocardial cells in petroleum ether group, but there was no significant difference in other organs compared to control ones. And other indices like relative organ weights, urine indices, liver antioxidases, quantitative measurements of inflammation cytokines in petroleum ether group and ethyl acetate group were observed no significant changes.3. Results of contraction of tracheal smooth muscle: 75% alcohol extract and its ethyl acetate extract, n-butyl alcohol extract, the lower aqueous phases possessed dual-direction regulation effects on the contraction of guinea-pig tracheal smooth muscle in vitro, the petroleum ether extract could relax the contractions. They were all expressed concentration-dependent manner, made the cumulative concentration-response curve of His, Ach, CaCl₂ non-parallelled rightward moved and declined of maximal responses. Extracts of Aster tataricus L. f. could restrain the constriction caused by Ca2+ release and influx in cells, but low concentration of 75% alcohol extract and n-butyl alcohol extract, the lower aqueous phases only restrained the constriction caused by Ca2+ influx.At the dose of 0.34 g·（kg·bw）-1, there were some liver toxicity in petroleum ether, ethyl acetate group rats when administrated 28 d and 91 d. And n-butyl alcohol extract could cause slight hepatotoxic effects, petroleum ether extract produces mild myocardial injury when the rats administrated 91 d. The phenomenon showed long-term intake the extracts of Aster tataricus L. f. might result in toxic effect on rats. A certain concentration of 75% alcohol extract and its different-polarity extracts of Aster tataricus L. f. all showed relaxant effect on isolated guinea-pig tracheal smooth muscle, and the principles maybe in relation to the inhibition of extracellular Ca2+ flow by M-receptor, histamine receptor, blocking Ca²⁺ passage.