In vitro Anti-Inflammatory and Anti-Oxidative Stress Activities of Kushenol C Isolated from the Roots of Sophora flavescens.

Byoung Ok Cho,Ji-Su Kim,Hyun Ju Kang,Seon Il Jang,Jang Hoon Kim,Denis Nchang Che,Jae Young Shin

doi:10.3390/molecules25081768

Byoung Ok Cho, Ji-Su Kim + Show 5 more

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https://doi.org/10.3390/molecules25081768

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Abstract

Kushenol C (KC) is a prenylated flavonoid isolated from the roots of Sophora flavescens aiton. Little is known about its anti-inflammatory and anti-oxidative stress activities. Here, we investigated the anti-inflammatory and anti-oxidative stress effects of KC in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The results demonstrated that KC dose-dependently suppressed the production of inflammatory mediators, including NO, PGE2, IL-6, IL1β, MCP-1, and IFN-β in LPS-stimulated RAW264.7 macrophages. The study demonstrated that the inhibition of STAT1, STAT6, and NF-κB activations by KC might have been responsible for the inhibition of NO, PGE2, IL-6, IL1β, MCP-1, and IFN-β in the LPS-stimulated RAW264.7 macrophages. KC also upregulated the expression of HO-1 and its activities in the LPS-stimulated RAW264.7 macrophages. The upregulation of Nrf2 transcription activities by KC in the LPS-stimulated RAW264.7 macrophages was demonstrated to be responsible for the upregulation of HO-1 expression and its activity in LPS-stimulated RAW264.7 macrophages. In HaCaT cells, KC prevented DNA damage and cell death by upregulating the endogenous antioxidant defense system involving glutathione, superoxide dismutase, and catalase, which prevented reactive oxygen species production from tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The upregulated activation of Nrf2 and Akt in the PI3K-Akt signaling pathway by KC was demonstrated to be responsible for the anti-oxidative stress activity of KC in HaCaT cells. Collectively, the study suggests that KC can be further investigated as a potential anti-inflammatory candidate for the treatment of inflammatory diseases.

Highlights

The roots of Sophora flavescens aiton have been used in Chinese traditional medicine as an analgesic, antipyretic, and anthelmintic, and for the treatment of gastrointestinal hemorrhage, diarrhea, and eczema [1]
We found that cells treated with only LPS had significantly raised NO production, while cells pretreated with 50 or 100 μM of Kushenol C (KC) before administration of LPS showed a significant and dose-dependent decrease in NO production when compared to the LPS only-treated cells (Figure 1C)
The results demonstrated that cells treated with 1 μg/mL of LPS only significantly raised the levels of prostaglandin E2 (PGE2), IL-6, IL-1β, IFN-β, and MCP-1 concentrations in the cell culture media, when compared to the untreated cells (Figure 2)

Summary

Introduction

The roots of Sophora flavescens aiton have been used in Chinese traditional medicine as an analgesic, antipyretic, and anthelmintic, and for the treatment of gastrointestinal hemorrhage, diarrhea, and eczema [1]. This prompted the isolation and identification of active compounds of S. flavescens. Many prenylated flavonoids with significant biological activities have been identified in S. flavescens. Despite the well-studied biological activities of S. flavescens and its compounds, very little is known about the anti-oxidant and anti-inflammatory activities of the individual active compounds in different cells of the body. The anti-inflammatory activities of the crude extracts of S. flavescens have been described [5,6,7,8]

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