Elsevier

Journal of Ethnopharmacology

Volume 127, Issue 3, 17 February 2010, Pages 589-595
Journal of Ethnopharmacology

Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora flavescens

https://doi.org/10.1016/j.jep.2009.12.020Get rights and content

Abstract

Ethnopharmacological relevance

The roots of Sophora flavescens have long been used in Chinese medicine for the treatment of fever, inflammatory disorders, ulcers and skin burns. Sophora flavescens contains flavonoids and alkaloids.

Aim of the study

This study was conducted to develop a plant-based anti-inflammatory agent focused on chronic inflammatory disorders. To accomplish this, the alkaloid-free prenylated flavonoid-enriched fraction (PFS) of rhizomes of Sophora flavescens was prepared and its in vitro and in vivo anti-inflammatory activities were then evaluated for the first time.

Materials and methods

The inhibitory activity of PFS on PGE2, NO, IL-6 and TNF-α production of lipopolysaccharide (LPS)-treated RAW 264.7 cells was measured. Additionally, adjuvant-induced arthritis in rats was used as an animal model of chronic inflammation to establish the in vivo anti-inflammatory effects of PFS.

Result

PFS inhibited cyclooxygenase-2 (COX-2)-catalyzed PGE2 and inducible nitric oxide synthase (iNOS)-catalyzed NO production by lipopolysaccharide (LPS)-treated RAW 264.7 cells at 10–50 μg/ml, and these effects primarily occurred via COX-2 inhibition and iNOS down-regulation, respectively. PFS also inhibited IL-6 and TNF-α production. When tested against adjuvant-induced arthritis in rats (chronic inflammation), PFS strongly inhibited arthritic inflammation when administered orally at doses of 10–100 mg/kg/day. In addition, PFS administered orally potently inhibited acetic acid-induced writhing in mice.

Conclusions

Our results suggest that PFS inhibits chronic inflammatory response and the inhibition of proinflammatory molecules such as COX-2, iNOS and IL-6 may contribute, at least in part, to the anti-inflammatory activity in vivo. Overall, these results indicate that PFS from Sophora flavescens may have the potential for treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Graphical abstract

The prenylated favonoid-enriched fraction (PFS) from the roots of Sophera flavescens showed anti-arthritic activity in vivo. PFS contains the following flavonoids.

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Introduction

Numerous molecules are involved in the induction and maintenance of the inflammatory response. In addition to pivotal cytokines such as interleukin-1, -6 and tumor necrosis factor-α (TNF-α), prostaglandins (PG) and nitric oxide (NO) are important chemical mediators of inflammation (Gallin and Snyderman, 1999). PGs are synthesized by cyclooxygenases (COX), which exist as at least two isoforms, COX-1 and the inducible COX-2. NO is synthesized from arginine by nitric oxide synthases, among which the inducible isoform of nitric oxide synthase (iNOS) is primarily responsible for producing large amounts of NO in inflammatory lesions. Therefore, inhibition and/or down-regulation of these proinflammatory molecules may exert anti-inflammatory effects.

The roots of Sophora flavescens (Sophorae radix) have long been used as a traditional Chinese medicine for the treatment of fever, inflammatory disorders, ulcers and skin burns (Bae, 2000). Additionally, one formulation containing Sophorae radix was found to inhibit angiogenesis of collagen-induced arthritis in rats (Li et al., 2003). Moreover, antipruritic effects of Sophora flavescens have been described (Yamaguchi-Miyamoto et al., 2003), and it was recently demonstrated that Sophora flavescens extract inhibited allergic reactions in vitro and in vivo, including passive cutaneous anaphylaxis (Hong et al., 2009). This extract has also been shown to inhibit histamine release and cytokine production in the human mast cell line, probably via inhibition of the nuclear factor-κB (NF-κB) activation pathway. Furthermore, the neuroprotective activity of the alkaloid-free ethyl acetate extract from the same plant material has been reported (Park et al., 2009). However, the detailed anti-inflammatory activity of the roots of Sophora flavescens, especially on chronic inflammation, has not been reported to date. In addition, the cellular action mechanism(s) of Sophora flavescens, including its modulating effect on proinflammatory molecules, have yet to be elucidated.

Among the constituents isolated from the roots of Sophora flavescens, the prenylated flavonoids including sophoraflavanone G, kuraridin and kurarinone were previously found to inhibit eicosanoid producing enzymes such as COX-1, COX-2, 5-lipoxygenase (5-LOX) and 12-LOX (Chi et al., 2001, Kim et al., 2002). Sophoraflavanone G was also shown to exert in vivo anti-inflammatory activity in several animal models via oral and topical treatment. Additionally, kurarinone was reported to inhibit monocyte chemoattractant protein-1-induced chemotaxis (Lee et al., 2005). Taken together, these previous results strongly suggest that the prenylated flavonoid-enriched fraction of this plant material possesses promising anti-inflammatory activity. Therefore, in the present investigation, the alkaloid-free prenylated flavonoid-enriched fraction (PFS) of Sophora flavescens was prepared and its anti-inflammatory activity was evaluated while focusing on joint inflammatory disorder in order to determine if it has the potential for use as a new anti-inflammatory agent.

Section snippets

Chemicals

N-[2-cyclohexyloxy-4-nitrophenyl]methane sulfonamide (NS-398) was obtained from Biomol (Plymouth Meeting). 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine hydrochloride (AMT) was a product of Tocris Cookson Ltd. (UK). Arachidonic acid (AA, 99%), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lipopolysaccharide (LPS, Escherichia coli 0127:B8) and λ-carrageenan (CGN) were purchased from Sigma Chemical Co. (St. Louis, MO). Prednisolone was obtained from Upjohn Co. (Kalamazoo,

Results and discussion

PFS contains various prenylated flavonoids including sophoraflavanone G as the major ingredients, but does not contain alkaloids (Fig. 2). To determine the anti-inflammatory activity of PFS in vitro, the mouse macrophage-like cell line, RAW 264.7, was used. Upon treatment with LPS (1 μg/ml), RAW 264.7 cells induce COX-2 and iNOS to produce increased amounts of PGE2 and NO (Chi et al., 2001). In the present experiment, RAW 264.7 cells produced 114.0 ± 11.2 nM PGE2 and 22.1 ± 0.8 μM NO for 24 h after

Acknowledgements

This study was supported by post-BK21 project from the Ministry of Education (Korea). The authors would like to thank the Pharmaceutical Research Institute (KNU) for the use of bioassay facilities.

References (16)

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