ABSTRACT
Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides (1-18) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1, 5, 6, 11, 12, 15, and 17 significantly reduced the release rate of β-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin (5) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin (5) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin (5) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin (5), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin (5) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.
Subject(s)
Animals , Mice , Glucosides , Mice, Inbred BALB C , Molecular Docking Simulation , Monoterpenes , Paeonia , Plant RootsABSTRACT
AIM: To observe the efficacy of Huangdanyishen Capsule (HDC)(Radix Astragali, Radix Salviae Miltiorr hizae) on renal lesions in diabetic nephropathy(DN) rat induced by Streptozocin(STZ). METHODS: The murine model with DN induced by STZ was made from Wistar rats with insulin resistance after being fed with feedingstuff of hypersugar, hyperlipid, hypercholesterol. These rats were randomly divided into five groups, and all rats were successively administrated corresponding drugs for 10 weeks. The general state and blood sugar were observed during the period. Serum urea nitrogen and creatinine content, the excretory rate of urinary micro-protein and renal pathological features were determined after 10 weeks. RESULTS: HDC could obviously ameliorate psychic status and renal function of rats with diabetes mellitus Ⅱ, and increase DN rats' weight. HDC could reduce the content of DN rats' serum urea. nitrogen and creatinine and urinary micro-protein. The ultramicropathologic histopathologic results indicated that the glomerular basement membrane thickening, synapse displaying foul-up and amalgamation, and mitochondrial swelling were alleviated to a certain extent in HDC groups. The content of murine blood sugar in HDC groups was significantly lower than those in model group. CONCLUSION: HDC has an obvious effect on Ⅱ DN treatment and decrease the content of blood sugar at the same time.