Abstract
Objective Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. Methods An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. Results DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (P < 0.05). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (P < 0.05), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint's synovium (P < 0.05), and the serum levels of IL-1β, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. Conclusion DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint's synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway.
Highlights
Gout is a metabolic disorder that results in hyperuricaemia and the consequent deposition of uric acid crystals in the tissues and joints [1]. e incidence of gout has been increasing for decades [2]
We explored the antigout mechanism of Dendrobium loddigesii extract (DLE) based on its effects on hyperuricaemic mice induced by potassium oxonate (PO) and acute gouty arthritis rats induced by monosodium urate (MSU) crystals. e levels of uric acid and creatinine in the mice were measured to explore the effect of DLE on the treatment of hyperuricaemia
We evaluated the effects of DLE on ankle swelling, protein expression of TLRs/ myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) in the ankle joint’s synovium, and the downstream inflammatory factors IL-1β, IL-6, and tumour necrosis factor-α (TNF-α) in the acute gouty arthritis rats
Summary
Gout is a metabolic disorder that results in hyperuricaemia and the consequent deposition of uric acid crystals in the tissues and joints [1]. e incidence of gout has been increasing for decades [2]. Some studies have demonstrated that acute gouty arthritis is associated with the presence of MSU crystals, which serve as a signal affecting specific immune cells, cytokine production, and effector molecule expression, triggering immune responses [9, 10]. Some inflammatory factors, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α), have been found to play essential roles in the occurrence and development of acute gouty arthritis [11]. Toll-like receptor 4 (TLR4) is a kind of transmembrane
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