Compounds that delay aging might also postpone age-related diseases and extend healthspan in humans. Icariin is a flavonol extracted from several plant species of the Epimedium family. The icariin and its metabolic derivatives have been shown to exert wide protective effects in age-related diseases. However, whether icariin and its derivatives have the potency of delaying aging remains unclear. Here, we report that icariin and its derivative icariside II extend C. elegans lifespan. Using HPLC, we found high level of icariside II in the animals treated with icariin, suggesting icariside II is the bioactive form in vivo of icariin. Icariside II also increased the thermo and oxidative stress tolerance, slowed locomotion decline in late adulthood and delayed the onset of paralysis mediated by polyQ and Aβ_1–42 proteotoxicity. The lifespan extension effect of icariside II is dependent on the insulin/IGF-1 signaling (IIS) since the daf-16(mu86) and daf-2(e1370) failed to show any lifespan extension upon icariside II treatment. Consistently, icariside II treatment upregulates the expression of DAF-16 targets in the wild-type. Moreover, our data suggests that the heat shock transcription factor HSF-1 has a role in icariside II-dependent lifespan extension further implicating the IIS pathway. In conclusion, we demonstrate a novel natural compound, icariside II as the bioactive form of icariin, extends the healthspan via IIS pathway in C. elegans.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint destruction, synovitis, and pannus formation. Gut microbiota dysbiosis may exert direct pathogenic effects on gut homeostasis. It may trigger the host’s innate immune system and activate the “gut–joint axis”, which exacerbates the RA. However, although the importance of the gut microbiota in the development and progression of RA is widely recognized, the mechanisms regulating the interactions between the gut microbiota and the host immune system remain incompletely defined. In this review, we discuss the role of gut microbiota-derived biological mediators, such as short-chain fatty acids, bile acids, and tryptophan metabolites, in maintaining intestinal barrier integrity, immune balance and bone destruction in RA patients as the bridge of the gut–joint axis.

Iguratimod (IGU) is a novel small-molecule anti-rheumatic drug with remarkable effectiveness and good safety for the treatment of active rheumatoid arthritis. Its mechanism of action is related to its ability to act simultaneously on T and B lymphocytes. IGU can effectively inhibit expression of various inflammatory factors, inhibit B cells from producing immunoglobulins and autoantibodies, downregulate T-cell-mediated cellular immunity, accelerate bone formation, and exert some activity against anti-pulmonary fibrosis. In recent years, IGU has been gradually applied to the treatment of a variety of rheumatic diseases, such as Sjögren's syndrome, ankylosing spondylitis and systemic lupus erythematosus. This article reviews the mechanism of action and clinical research status of IGU, and provides reference for future research on its mechanism of action and clinical application.

Icariin has a variety of biological activities, such as lipid-lowering effects, and has attracted widespread attention in recent years. However, it is not clear whether lipid-lowering effect is that multiple metabolites or a particular component plays a major role. It is known that icariin has a variety of metabolites in the body, including icariside I, icariside II, icaritin, desmethylicaritin, and other metabolites. Many of these studies have shown that the metabolites of icariin have a lipid-lowering effect. This paper focuses on the lipid-regulating effects of icariin and its metabolites in vitro and in vivo, and highlights the mechanisms involved. Icariin may have potential in the development of therapeutic strategies to regulate lipid metabolism.

A liquid chromatography coupled with mass spectrometry (LC/MS) based metabonomics approach was applied to characterize the aging of rats, and the anti-aging effect of total flavones of Epimedium (TFE), a traditional Chinese medicine, has also been investigated. Serum samples collected from 4, 10, 18 and 24 month-old rats and TFE-administered rats have been profiled by LC/MS. Thirty age-related endogenous metabolites were discovered by partial least squares (PLS) and Hotelling’s T² control chart, among which 25 metabolites were structurally identified by MSⁿ analysis and ten of them were further confirmed via authentic chemicals. All important age-related metabolites, such as unsaturated fatty acids, saturated fatty acids, nucleotides, carnosine, ergothioneine and amino acids, displayed age-related changes, and most of them were reset to a younger level after TFE administration. This study indicated that aging could be characterized by changes of lipid metabolisms and accumulation of free radicals. The anti-aging effects of TFE might due to the intervention on lipid metabolism and its property of anti-oxidation.