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KMID : 0363620210420040010
Journal of Korean Oriental Medicine
2021 Volume.42 No. 4 p.10 ~ p.24
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 Hye-Kyung

Jin Seong-Eun
Seo Chang-Seob
Shin Hyeun-Kyoo
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 ¥ìg/mL. YST inhibited the activity of uridine diphosphate- glucuronosyltransterase (UGT) 1A4 with an IC50 value of 49.35 ¥ìg/mL. The activities of cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP3A4, and UGT1A1 were inhibited by PJS (IC50 < 100 ¥ìg/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.
KEYWORD
Yongdamsagan-tang, Paljung-san, Benign prostatic hyperplasia, Anti-inflammation, Drug metabolizing enzymes
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