The protective effects of S14G-humanin (HNG) against mono-sodium urate (MSU) crystals- induced gouty arthritis.
Zhang. Jihui J; Lei. Hongwei H; Li. Xiu X
Key Findings
- S14G‑humanin reduced joint inflammation and pain scores in mice with MSU‑crystal‑induced gout.
- The peptide lowered mitochondrial ROS, NOX‑4, and NLRP3 inflammasome activation in macrophages.
- Its anti‑inflammatory action required SIRT1, as knocking down SIRT1 removed the benefit.
Practical Outcomes
- For biohackers, S14G‑humanin shows promise as a potential anti‑gout agent, but it’s only been proven in animal studies and isn’t commercially available. Until human safety and dosing are established, it’s not ready for self‑experimentation; however, the study highlights SIRT1 activation as a target for future DIY interventions.
Summary
A modified peptide called S14G‑humanin (HNG) was tested in mice with gout‑like arthritis caused by urate crystals. The peptide lowered joint inflammation, pain‑related gait changes, and markers of oxidative stress, working through a pathway involving SIRT1. Its effects were similar to, but a bit weaker than, the standard gout drug colchicine.
Abstract
Gout is a common and complex form of arthritis that has brought great inconveniences to the normal lives of patients. It is reported that oxidative stress and nod-like receptor family protein 3 (NLRP3) inflammasome-mediated inflammatory reactions are involved in the pathogenesis of gout arthritis. S14G-humanin (S14G-HNG) is a modified peptide of HNG with higher inhibitory activity on the accumulation and deposition of Aβ. Recently, S14G-HNG has been reported to exert great anti-inflammatory effects. The present study proposed to explore the possible therapeutic property of S14G-HNG against gout arthritis. An animal model was established by stimulation with mono-sodium urate (MSU) crystals, followed by treatment with colchicine and S14G-HNG, respectively. The elevated Gait score promoted synovitis score and activated myeloperoxidase (MPO) observed in MSU crystals-treated mice were significantly reversed by colchicine and S14G-HNG. Bone marrow-derived macrophages (BMDMs) were isolated from mice and stimulated with MSU crystals, followed by being treated with 25 and 50 μM S14G-HNG. The increased mitochondrial reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, upregulated NADPH oxidase-4 (NOX-4), activated NLRP3 inflammasome, and elevated production of inflammatory factors in MSU crystals-treated BMDMs were dramatically reversed by S14G-HNG, accompanied by the upregulation of sirtuin type-1 (SIRT1). Lastly, the protective effects of S14G-HNG against MSU crystals-induced NLRP3 inflammasome activation were significantly abolished by the knockdown of SIRT1. In conclusion, our data reveal that S14G-HNG could possess potential benefits against MSU crystals-induced gout arthritis, with colchicine displaying a better effect.
Study Information
pubmed
2022
2021-12-29T00:00:00.000Z
10.1080/21655979.2021.2001911
9
38