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Anti-inflammatory Effects in LPS-treated RAW 264.7 Cells and the Influences on Drug Metabolizing Enzyme Activities by the Traditional Herbal Formulas, Yongdamsagan-Tang and Paljung-san

  • Ha, Hyekyung (KM Science Research Division, Korea Institute of Oriental Medicine) ;
  • Jin, Seong Eun (KM Science Research Division, Korea Institute of Oriental Medicine) ;
  • Seo, Chang-Seob (KM Science Research Division, Korea Institute of Oriental Medicine) ;
  • Shin, Hyeun-kyoo (KM Science Research Division, Korea Institute of Oriental Medicine)
  • Received : 2021.01.28
  • Accepted : 2021.07.30
  • Published : 2021.12.01

Abstract

Objectives: Yongdamsagan-tang (YST) and Paljung-san (PJS) in traditional medicine and finasteride in modern medicine are used to treat benign prostatic hyperplasia (BPH). In recent, the use of combination herbal remedies with conventional drugs has been increasing. Therefore, we investigated the anti-inflammatory effects of these drugs to treat BPH and the influence of herbal formulas on finasteride metabolism. Methods: The inhibitory effects of the herbal formulas and finasteride on the production of inflammatory mediators and cytokines were determined in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Additionally, the influence of herbal formulas on activities of human drug metabolizing enzymes (DMEs) was assessed using human microsomal enzymes. Results: We observed that YST, PJS and finasteride inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2) and interleukin-6 (IL-6) in RAW 264.7 cells. The half maximal inhibitory concentration (IC50) of YST on PGE2 production was calculated to be below 25 ㎍/mL. YST inhibited the activity of uridine diphosphate-glucuronosyltransterase (UGT) 1A4 with an IC50 value of 49.35 ㎍/mL. The activities of cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP3A4, and UGT1A1 were inhibited by PJS (IC50 < 100 ㎍/mL, each). Although PJS and YST inhibited the activities of CYP3A4 and UGT1A4, respectively, these formulas may not influence the metabolism of finasteride because the IC50 values of herbal formulas on DMEs are too high to affect metabolism. Conclusions: Our results suggest that the combination of finasteride and YST or PJS might not influence their drug metabolism and that the drugs may have synergistic effects against BPH.

Keywords

Acknowledgement

This research was supported by grants of the 'Construction of Scientific Evidence for Herbal Medicine Formulas (K17251)' and 'Construction of Safety and Efficacy for Traditional Herbal Prescriptions of Medicinal Institution (KSN2013310)' projects from the Korea Institute of Oriental Medicine (KIOM), Republic of Korea.

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