| Astragali Radix, as the tranditional tonifying herb, has been recorded as top grade in Shen nong ben caojing. It has Buqi Gubiao effect and been widely used. Chinese materia medica research and literature showed Astragali Radix has obvious antifatigue effect. However, the effect hasn’t been studied systematically in physiological and pathological conditions. Astragalus membranaceus (Fisch.) Bge. var. mongholicus(Bge.) Hsiao (A. monghlicus) has been the main-current commodity in the market and generated two patterns so far. A. monghlicus in the pattern, which is the wild or semi-wild manner and mainly from Hunyuan and Ying county in Shanxi province, has been exported in the international market as the superior present and occupied less production. A. monghlicus in the other pattern, which is the cultivated fast-growing manner and mainly from Gansu and Inner Mongolia provinces, has almost occupied eighty percent of production and been widespread in the Chinese herbal medicine market. The quality of two types of A. monghlicus was mainly evaluated by chemical detection and the reliable result should be biological effect evaluation. However, it hasn’t obtained systematic results that whether they are different in the antifatigue effect.Objectives:The antifatigue mechanism of Astragali Radix could be elucidated and the difference of endogenic metabolites in serum between physiological and pathological conditions could be compared. It can provide a scientific basis for selecting materials in clinic and pharmaceutical companies to compare the antifatigue effect of A. monghlicus from the wild or semi-wild and cultivated fast-growing manners.Methods:(1) Three doses of 1 g/kg,3 g/kg and 6 g/kg were designed to study the antifatigue effect of Astragali Radix in the physiological condition. The exhaustive swimming time of rats was tested after administrated for 21 days, and superoxide dismutase, lactic acid, blood urea nitrogen, creatine kinase in serum and hepatic glycogen in liver were measured. Then serum, urine, muscle and spleen samples were investigated by JH NMR based metabolomic approach. (2) The antifatigue model was duplicated by forced exhaustive swimming plus food intake restriction and three doses of 3 g/kg,6 g/kg and 12 g/kg were designed to study the antifatigue effect of Astragali Radix in the pathological condition. The exhaustive swimming time of rats was tested after administrated for 21 days, and triglyceride, total cholesterol, lactate dehydrogenase, creatine kinase, glucose and blood urea nitrogen were also measured. Changes of endogenic metabolites in serum was analyzed by an 1H NMR based metabolomic approach. (3) The antifatigue effects of A. monghlicus from the wild or semi-wild and cultivated fast-growing patterns were compared at a dose of 6 g/kg. The exhaustive swimming time and biochemical parameters at the last day were determined.Results:(1) The dose of 3 g/kg body weight of Astragali Radix exerted better antifatigue effects on rats in a physiological condition, including the significantly extended exhausive swimming time, promotion of contents of superoxide dismutase and liver glycogen, reduction of creatine kinase level and clearance of lactic acid and urea nitrogen. The metabolic results of middle dose group and the control dose group showed that in the OPLS-DA score plots of serum, urine, muscle and spleen samples, a clear tendency of separation between AM and NS groups could be seen. And 10 metabolites in plasma,15 in urine,15 in muscle and 19 in spleen were involved in energy-related pathways, referring to glucose metabolism, lipid metabolism, amino metabolism as well as nucleic acid metabolism.(2) With regard to rat in pathological condition, the dose of 6 g/kg and 12 g/kg body weight of Astragali Radix both showed good antifatigue effects, involving the significantly extended exhausive swimming time, reduction of contents of creatine kinase, triglyceride, total cholesterol and blood urea nitrogen, promotion of lactate dehydrogenase level and glucose storage. The rats treated by Astragali Radix extracts showed higher levels of glucose, TMAO, glutamine, and lower level of lactic acid, isoleucine, leucine, valine and P-hydroxybutyrate in comparison with control group. Alanine ane creatine were increased in drug-treated groups and decreased in control group. The results also indicated that the rats in drug-treated groups showed higher levels of alanine ane creatine than than those of model group.(3) Astragali Radix (AR) in Shanxi and Gansu provinces could both prolong the exhaustive swimming time, and the quality of AR in Shanxi was slightly better than that in Gansu, but not to a statistical extent. The result of biological parameters showed that both kinds of herbs could decrease the contents of creatine kinase, triglyceride, total cholesterol, and blood urea nitrogen and increase the levels of lactate dehydrogenase and glucose, but there were no significant difference between Shanxi AR and Gansu AR. The metabolomic result showed that both kinds of herbs could increase the levels of alanine, glutamate, creatine and trimethylamine oxide and decrease the levels lactic acid, valine, β-hydroxybutyrate, leucine, isoleucine, glutamine.Conclusion:The antifague effect of Astragali Radix was investigated systematically by 1H NMR based metabolomics in this study. The tranditionally typical index, biochemical parameters and multivariate statistical analysis were applied. The results indicated that oral administration of Astragali Radix at a dose of 3 g/kg body weight showed the antifatigue effect in the physiological condition and at doses of 6 g/kg and 12 g/kg body weight in the pathological condition. The antifatigue effect of A. monghlicus from the wild or semi-wild and cultivated fast-growing patterns were compared in vivo, and the results of the exhaustive swimming time and holistic changes of metabolites showed that there was no significant difference. It isn’t necessary to distinguish them in clinic use. This study could provide an comprehensive idea for studying underlying mechanisms of Chinise herb medicine and its Chinese herbal formulae and evaluating quality of different sources of medicinal materials. |
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