Pharmacokinetics-derived absorbed components responsible for Guizhi-Fuling capsule target PI3K/Akt-Erk to exert an anti-dysmenorrhea effect

Jul 10, 2022Journal of ethnopharmacology

Absorbed ingredients from Guizhi-Fuling capsule may reduce menstrual pain by targeting the PI3K/Akt-Erk pathway

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Abstract

The 11 absorbed components from Guizhi-Fuling capsule contributed an average of 113.55% to its anti-dysmenorrhea efficacy.

Pharmacokinetic profiles of herbal components differed between healthy and primary dysmenorrhea rats.
The absorbed components exhibited an anti-primary dysmenorrhea effect by improving various pain-related indexes.
The regulatory mechanism involved the PI3K-Akt/ERK pathway.
Identifying these components may aid in understanding the efficacy of the herbal remedy.

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ETHNOPHARMACOLOGICAL RELEVANCE: Guizhi-Fuling capsule (GZFL), a well-known herbal remedy, has been widely used to treat primary dysmenorrhea (PD). Hence, systematic identifying multiple active ingredients and the involved mechanism is essential and urgently needed for GZFL.

AIM OF THE STUDY: This study was planned to assess the pharmacokinetics of GZFL in rats, and identify whether these GZFL-derived absorbed components (ACs) contribute to the efficacy of source herbs and relevant mechanism.

MATERIALS AND METHODS: The in vivo pharmacokinetic profile of 11 phytochemicals and 13 metabolites in healthy and PD rats were evaluated using liquid chromatography with mass spectrometry (LC-MS/MS). Whereafter, the introduced contribution strategy assessed ACs' effect (doses = their contents in GZFL) in PD rats with the mechanism.

RESULT: The pharmacokinetic profiles of prototypes and metabolites differed in healthy and PD rats. As a main proxy of GZFL, 11ACs exerted an anti-PD effect (improvement of indexes for writhing latency, writhing time, PGF/PGE, TXB/6-keto-PGFand β-EP) by regulating PI3K-Akt/ERK pathway. 2α 2 2 1α

CONCLUSION: As a paradigmatic example, 11ACs contributed an average of 113.55% to GZFL in terms of anti-PD efficacy, providing an approach to rapidly, accurately and consistently identify the bioactive components and their pathway from herbs.

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Pharmacokinetics-derived absorbed components responsible for Guizhi-Fuling capsule target PI3K/Akt-Erk to exert an anti-dysmenorrhea effect

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