| Background:The global population is aging,with implication for nearly all sectors of society.The demand for prevention and treatment of aging-related diseases has increased dramatically,therefore research on aging and anti-aging mechanisms has also become increasingly urgent.And the anti-aging effect reaserch of Traditional Chinese Medicine has attracted more and more researchers' attention.Scutellaria baicalensis Georgi,a perennial herb of Labiatae family,is widely distributed in the north of China.As the traditional medicinal part,its root has a long history and a wide range of clinical application.Combined literatures and our previous studies,the extract of Scutellariae Radix and its main components,e.g.baicalein,baicalin,wogonoside and wogonin,all have the anti-aging activity in different aging models.While as the aerial parts,the stem and leaf of Scutellaria baicalensis Georgi grown vigorously,yield high,and some areas still retain the habit of drinking tea from the leaf.Pharmacological studies indicated that the total flavonoids and components like scutellarin may have the potential of anti-aging,which has rarely been reported.Therefore,in order to expand the medicinal resources and increase the added value of Scutellaria baicalensis Georgi,it is of great significance to carry out the comparative studies on the chemical constituents,anti-aging effects and mechanisms of different parts of Scutellaria baicalensis Georgi.Objective: 1.Systematic analyze the chemical constituents and differences of root,stem and leaf of Scutellaria baicalensis Georgi;2.Identify the anti-aging activity and potential mechanism of root,stem and leaf of Scutellaria baicalensis Georgi;3.Screening the possible constituents for anti-aging effect of root,stem and leaf of Scutellaria baicalensis Georgi.Methods: 1.Using LC-MS metabolomics combined with multivariate statistical analysis,analyze the chemical constituents of root,stem and leaf of Scutellaria baicalensis Georgi,and assess the significantly different constituents of them.2.Using D-galactose induced aging rat model,combining weight and appearance of rats,behavior tests,HE staining tissue sections and serum biochemical test,evaluate the anti-aging effects of root,stem and leaf of Scutellaria baicalensis Georgi.3.Explore the abnormal serum metabolism of D-galactose induced aging rats and the possible anti-aging metabolic regulation mechanism of Scutellaria baicalensis Georgi using ~1H-NMR serum metabolomics combined with multivariate statistical analysis.4.Guided by the spectrum-effect correlation theory,Artificial Neural Network and Partial Least Squares Regression were used to correlate the results of Morris water maze with the chemical constituents of root,stem and leaf of Scutellaria baicalensis Georgi for screening the potential pharmacodynamic constituents which may improve the learning and memory abilities of aging rats.At the same time,Artificial Neural Network and Partial Least Squares Regression were also used to correlate the relative contents of serum differential metabolites with the chemical constituents of root,stem and leaf of Scutellaria baicalensis Georgi in order to screen the potential pharmacodynamic constituents which may ameliorate the serum metabolism abnormalities of aging rats.The above results comprehensively represent the potential anti-aging constituents of the root,stem and leaf of Scutellaria baicalensis Georgi.Results: 1.The chemical constituents of root,stem and leaf of Scutellaria baicalensis Georgi were significantly different.Among the significantly different constituents,5,6,7,3',4'-Pentahydroxy flavanone-7-O-glucuronide,carthamidin-7-O-glucuronide,scutellarin,isocarthamidin-7-O-glucuronide,apigenin-7-O-glucuronide were higher in stem and leaf especially in leaf,while baicalin,oroxylin A-7-O-glucuronide,wogonoside,baicalein,norwogonin-7-O-glucuronide,wogonin,skullcapflavon ? were higher in root,and chrysin-7-O-glucuronide was higher in both root and leaf.2.Root,stem and leaf of Scutellaria baicalensis Georgi had the anti-aging effect,which could ameliorate the appearance features of aging rats,improve the learning and memory ability as well as spontaneous activity of aging rats,decrease the liver damage and hippocampal neurons damage in duced by Dgalactose,ameliorate oxidative stress in aging rats by inhibiting the MDA production in serum and increasing the antioxidant enzyme levels.3.Root,stem and leaf of Scutellaria baicalensis Georgi could ameliorate the abnormality of serum metabolism in rats,recall the significantly different metabolites,i.e.isobutyric acid,3-hydroxybutyric acid,lactate,acetone,threonine,leucine,lysine,glycine,glutamate,glutamine,guanidinoacetate,glycerol,regulate D-Glutamine and D-glutamate metabolism,alanine,aspartate and glutamate metabolism,nitrogen metabolism and other key metabolic pathways,in which the regulation of leaf is more comprehensive.4.Through the pectrum-effect correlation analysis,the potential active constituents for the root,stem and leaf of Scutellaria baicalensis Georgi to improve the learning and memory ability of aging rats may be carthamidin-7-O-glucuronide,isocarthamidin-7-O-glucuronide,baicalin,norwogonin-7-Oglucuronide,oroxylin A-7-O-glucuronide,wogonoside,baicalein,wogonin and skullcapflavon ?.The potential active constituents for improving the abnormal serum metabolism of aging rats may be 5,6,7,3',4'-pentahydroxy flavanone-7-O-glucuronide,carthamidin-7-O-glucuronide,isocarthamidin-7-O-glucuronide,scutellarin,baicalin,oroxylin A-7-O-glucuronide,wogonoside,baicalein.Conclusion: 1.The chemical constituents of root,stem and leaf of Scutellaria baicalensis Georgi were significantly different,but they all have the effect of anti-aging,by improving the abnormality of serum metabolism,recalling the different metabolites and metabolic pathways with different degrees.2.5,6,7,3',4'-pentahydroxy flavanone-7-O-glucuronide,carthamidin-7-O-glucuronide,scutellarin,isocarthamidin-7-O-glucuronide,baicalin,norwogonin-7-O-glucuronide,oroxylin A-7-O-glucuronide,wogonoside baicalein,wogonin and skullcapflavon ? may be the potential anti-aging constituents of the root,stem and leaf of Scutellaria baicalensis Georgi. |
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