[Establishment of an EMEET strategy based on dissection of analgesic ingredients from Syringa pinnatifolia]

This study investigated the analgesic material basis of Syringa pinnatifolia(SP), a Mongolian folk herb medicine traditionally used for pain relief. Through systematic pharmacological evaluation by three classical pain models, acetic acid-induced writhing, formalin test, and hot plate assay, with the dose-equivalent conversions, the analgesic effects of total extract, fractions, subfractions, and isolated compounds were evaluated. The results showed that a key fraction(A), composed of lignans with high polarity, including(-)-secoisolariciresinol(K), alashanols F and G, and pinnatifolin A, exhibited a dose-dependent analgesic effect at 5-20 mg·kg~(-1), equivalent to the efficacy of total extract T, fraction M, and subfraction Ⅱ. However, subfractions M_1, Ⅱ_1, Ⅱ_3, and D_3 containing terpenoids and lignans with low polarity showed no analgesic activity. Further exploration suggested that the pain-relieving mechanism of A was related to the inhibition of NF-κB and MAPK signaling pathways. On basis of these findings abovementioned, an equal mass for equivalent effect transmission(EMEET) strategy for TCM pharmacological substance research was proposed, which emphasized four principles: selection of animal models based on traditional efficacy, dosage conversion based on that in clinical practice, equivalent pharmacological effect transmission based on in vivo evaluation, and in vivo validation by major isolates or its combination at the natural ratio. Eventually, the pharmacological and inactive substances were clarified. In conclusion, the present study not only dissected the primary analgesic material basis and mechanism of SP for the first time but also established a new strategy for pharmacological substance research, hopefully to bring a reference and inspiration in this field.