Guizhi Shaoyao Zhimu Decoction ameliorates gouty arthritis in rats via altering gut microbiota and improving metabolic profile.
Phytomedicine : international journal of phytotherapy and phytopharmacology
BACKGROUND:The incidence of gouty arthritis (GA) has gradually increased, and modern drug therapies have obvious side effects. Guizhi Shaoyao Zhimu Decoction (GSZD), a classic prescription in Traditional Chinese Medicine for treating various osteoarthritis, has shown significant advantages in curing GA. PURPOSE:To verify the therapeutic effect of GSZD on GA and investigate its potential pharmacological mechanism via integrated analysis of the gut microbiota and serum metabolites for the first time. METHODS:The chemical composition of GSZD was determined using UPLC-MS. The GA rat model was established by the induction of a high-purine diet combined with local injection. We examined the effects and mechanisms of GSZD after 21 d using enzyme-linked immunosorbent assays, 16S rRNA, and non-targeted metabolomics. Finally, correlation analysis and validation experiment were performed to explore the association among the gut microbiota, serum metabolites, and GA-related clinical indices. RESULTS:In total, 19 compounds were identified as GSZD. High-purine feedstuff with local injection-induced arthroceles were significantly attenuated after GSZD treatment. GSZD improved bone erosion and reduced the serum levels of inflammatory factors (lipopolysaccharide, tumor cell necrosis factor-α, and interleukin) and key indicators of GA (uric acid). 16S rRNA analysis indicated that GSZD-treated GA rats exhibited differences in the composition of the gut microbiota. The abundance of flora involved in uric acid transport, including Lactobacillus, Ruminococcaceae, and Turicibacter, was elevated to various degrees, whereas the abundance of bacteria involved in inflammatory responses, such as Blautia, was markedly reduced after treatment. Moreover, serum metabolite profiles revealed 27 different metabolites associated with the amelioration of GA, which primarily included fatty acids, glycerophospholipids, purine metabolism, amino acids, and bile acids, as well as primary metabolic pathways, such as glycerophospholipid metabolism and alanine. Finally, correlation analysis of the heat maps and validation experiment demonstrated a close relationship among inflammatory cytokines, gut microbial phylotypes, and metabolic parameters. CONCLUSION:This study demonstrated that GSZD could modulate the gut microbiota and serum metabolic homeostasis to treat GA. In addition, the application of gut microbiota and serum metabolomics correlation analyses sheds light on the mechanism of Traditional Chinese Medicine compounds in the treatment of bone diseases.
10.1016/j.phymed.2024.155800
Multimodal smart systems reprogramme macrophages and remove urate to treat gouty arthritis.
Nature nanotechnology
Gouty arthritis is a chronic and progressive disease characterized by high urate levels in the joints and by an inflammatory immune microenvironment. Clinical data indicate that urate reduction therapy or anti-inflammatory therapy alone often fails to deliver satisfactory outcomes. Here we have developed a smart biomimetic nanosystem featuring a 'shell' composed of a fusion membrane derived from M2 macrophages and exosomes, which encapsulates liposomes loaded with a combination of uricase, platinum-in-hyaluronan/polydopamine nanozyme and resveratrol. The nanosystem targets inflamed joints and promotes the accumulation of anti-inflammatory macrophages locally, while the uricase and the nanozyme reduce the levels of urate within the joints. Additionally, site-directed near-infrared irradiation provides localized mild thermotherapy through the action of platinum and polydopamine, initiating heat-induced tissue repair. Combined use of these components synergistically enhances overall outcomes, resulting in faster recovery of the damaged joint tissue.
10.1038/s41565-024-01715-0
Microneedle transdermal drug delivery as a candidate for the treatment of gouty arthritis: Material structure, design strategies and prospects.
Acta biomaterialia
Gouty arthritis (GA) is caused by monosodium urate (MSU) crystals deposition. GA is difficult to cure because of its complex disease mechanism and the tendency to reoccur. GA patients require long-term uric acid-lowering and anti-inflammatory treatments. In the past ten years, as a painless, convenient and well-tolerated new drug transdermal delivery method, microneedles (MNs) administration has been continuously developed, which can realize various drug release modes to deal with various complex diseases. Compared with the traditional administration methods (oral and injection), MNs are more conducive to the long-term independent treatment of GA patients because of their safe, efficient and controllable drug delivery ability. In this review, the pathological mechanism of GA and common therapeutic drugs for GA are summarized. After that, MNs drug delivery mechanisms were summarized: dissolution release mechanism, swelling release mechanism and channel-assisted release mechanism. According to drug delivery patterns of MNs, the mechanisms and applications of rapid-release MNs, long-acting MNs, intelligent-release MNs and multiple-release MNs were reviewed. Additionally, existing problems and future trends of MNs in the treatment of GA were also discussed. STATEMENT OF SIGNIFICANCE: Gout is an arthritis caused by metabolic disease "hyperuricemia". Epidemiological studies show that the number of gouty patients is increasing rapidly worldwide. Due to the complex disease mechanism and recurrent nature of gout, gouty patients require long-term therapy. However, traditional drug delivery modes (oral and injectable) have poor adherence, low drug utilization, and lack of local localized targeting. They may lead to adverse effects such as rashes and gastrointestinal reactions. As a painless, convenient and well-tolerated new drug transdermal delivery method, microneedles have been continuously developed, which can realize various drug release modes to deal with gouty arthritis. In this review, the material structure, design strategy and future outlook of microneedles for treating gouty arthritis will be reviewed.
10.1016/j.actbio.2024.08.032
Unraveling the impact of miRNAs on gouty arthritis: diagnostic significance and therapeutic opportunities.
Naunyn-Schmiedeberg's archives of pharmacology
Gouty arthritis is a prevalent inflammatory illness. Gout attacks begin when there is an imbalance in the body's uric acid metabolism, which leads to urate buildup and the development of the ailment. A family of conserved, short non-coding RNAs known as microRNAs (miRNAs) can regulate post-transcriptional protein synthesis by attaching to the 3' untranslated region (UTR) of messenger RNA (mRNA). An increasing amount of research is pointing to miRNAs as potential players in several inflammatory diseases, including gouty arthritis. miRNAs may influence the progression of the disease by regulating immune function and inflammatory responses. This review mainly focused on miRNAs and how they contribute to gouty arthritis. It also looked at how miRNAs could be used as diagnostic, prognostic, and potential therapeutic targets.
10.1007/s00210-024-03603-9