Abstract
Jakyakgamcho-Tang (JGT) is a traditional medicine used to treat muscular tension, spasm, and pain. Several studies have reported its clinical use as an anti-inflammatory and in gynaecological treatment. This study aimed to compare the anti-inflammatory effects of JGT according to extraction solvent, water (JGTW) and 30% EtOH (JGTE) on lipopolysaccharide (LPS)—stimulated macrophages and in mice with monosodium urate (MSU)—induced gouty arthritis. We evaluated the production of inflammatory mediators and cytokines and the expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. We also examined oedema, pain, and inflammation in MSU-induced mice by measuring affected hind paw swelling, weight-bearing, pro-inflammatory cytokines levels, and myeloperoxidase (MPO) activity. In LPS-stimulated RAW264.7 cells, JGTW and JGTE significantly decreased prostaglandin (PG) E2(PGE2) production via suppressing COX-2 expression and cytokines interleukin-1β and interleukin-6. Only JGTE reduced the production of NO and cytokines and the mRNA levels of iNOS and cytokines. In MSU-induced mice, JGTE and JGTW efficiently decreased paw swelling and attenuated joint pain. JGTE (200 and 300 mg/kg) effectively suppressed inflammation by downregulating pro-inflammatory cytokines (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) and MPO activity, which were only slightly reduced by JGTW. Our data demonstrate the anti-inflammatory activity of JGT in macrophage and gouty arthritis animal models and show that JGTE is more effective than JGTW at lower concentrations.
Highlights
Jakyakgamcho-Tang (JGT; Shakuyaku-kanzo-to in Japanese; Shaoyao-gancao-tang in Chinese) is a traditional herbal medicine composed of Paeonia lactiflora Pall. (Paeoniae Radix) and Glycyrrhiza uralensis Fisch (Glycyrrhizae Radix et Rhizoma)
We have previously reported that the major constituents in JGT are oxypaeoniflorin, paeoniflorin, pentagalloylglucose, benzoyl paeoniflorin, liquiritin apioside, liquiritin, isoliquiritin, apioside, liquiritigenin, and glycyrrhizin, and that the relative amounts of JGT components are approximately 19–53% higher in the 30% ethanol extract than in the water extract
Macrophages activated by a variety of inflammatory mediators, such as nitric oxide (NO), prostaglandin (PG) E2, cyclooxygenase-2 (COX-2), inducible expression of nitric oxide synthase, 5-lipoxygenase (5-LOX), tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, contribute to the pathogenesis of inflammatory diseases
Summary
Jakyakgamcho-Tang (JGT; Shakuyaku-kanzo-to in Japanese; Shaoyao-gancao-tang in Chinese) is a traditional herbal medicine composed of Paeonia lactiflora Pall. (Paeoniae Radix) and Glycyrrhiza uralensis Fisch (Glycyrrhizae Radix et Rhizoma). Other applications of JGT, such as gynaecological therapeutics and anti-inflammatory treatment, are emerging as new areas in its clinical use [6]. The medicinal properties of JGT have been reported in several studies, the impact of the extraction solvent on the anti-inflammatory action of JGT in lipopolysaccharide (LPS)-stimulated macrophages and monosodium urate (MSU)-induced gouty arthritis models has not been investigated yet. LPS-induced RAW 264.7 macrophages are a widely used model to study inflammatory responses in vitro [8]. Macrophages activated by a variety of inflammatory mediators, such as nitric oxide (NO), prostaglandin (PG) E2, cyclooxygenase-2 (COX-2), inducible expression of nitric oxide synthase (iNOS), 5-lipoxygenase (5-LOX), tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, contribute to the pathogenesis of inflammatory diseases. Inhibiting the production of these pro-inflammatory mediators could be a highly efficient tool for blocking the development and progression of inflammatory diseases [9]
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