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