Gynostemma pentaphyllum promotes skeletal muscle recovery via its inhibition of PXR-IL-6 expression

Abstract

Backgroundour recent discovery based on pharmacological experiment indicated that Gynostemma pentaphyllum (Gyp), an ingredient of Yinlan capsule can significanly accelerate the recovery of skeletal muscle for strain injury; and such effect was found to be based on inhibition of PXR-IL-6 expression. Purposeto validate and investigate the PXR-IL-6 induced skeletal muscle recovery of Gyp, as well as its material basis by identification and determination of the herb's main active compounds both in-vitro and in-vivo. Methodsweight-drop model rats were used for evaluation of the recovery effect induced by Gyp, the animals were treated by orally administrating aqueous-ethanol (50:50. v/v) extract of Gyp in different dosages, and the results were compared with positive control (Celecoxib); a network pharmacology research was carried out to the main active target (s) of Gyp on strain injury recovery; Then, blood was taken from all experiment groups to test their values of PXR (by PCR) and IL-6 (by ELISA) expression, and statistically evaluated for the purpose of investigating Gyp's influence on PXR-IL-6 expression. At the meantime, Gyp extract was analyzed by a UPLC-TOF-MS method to identify its components; monomer solutions were prepared according to the results, and all found compounds were tested for their PXR-IL-6 regulation activities; those passing cyto-biological evaluation were introduced as indexes for content determination, and the pharmacokinetic analysis in the subsequent step; finally, the components with good regulatory effect, suitable herb and serum concentration, along with good pharmacokinetic profiles were recognized as active components, which comprise the material basis of Gyp's acceleration of strain injury recovery. ResultsGyp significantly promotes skeletal muscle recovery in all doses (p<0.05, compared with model), among which, the medium and high dosages (875, 1750mg.kg−1) had no obvious difference with positive control (p>0.05); the network pharmacological investigation indicated that PXR-IL-6 pathway was Gyp's main active one; In terms of PXR-IL-6 expression, Gyp effectively up-regulates the former and down-regulates the latter, which was comparable to that of the positive control; the UPLC-TOF-MS identification found 10 compounds, namely Rutin, Narcissoside, Quercetin, Isoquercitrin, Isorhamnetin, Linoleic acid, Kaempferol, GypenosideA, Gypenoside XVII and Gypenoside LXXIV, all of them except Rutin had obvious regulatory effect on PXR-IL-6 expression, and the trend of such regulation was in line with the herb extract; content determination and pharmacokinetic research showed that 5 of the 9 compounds had both suitable concentration in the extract and the serum, with good pharmacokinetic profiles, except quercetin and Isorhamnetin. ConclusionGyp effectively promotes skeletal muscle recovery via its activation of PXR and suppression of IL-6; such activity based on PXR-IL-6 regulatory components found in Gyp, its suggested that those active compounds be recognized as material basis explaining Gyp's therapeutic effect.