Icariin Treatment Improves the Aging Gut Microbiome in Mice

The gut microbiome is important in health and aging. Populations of microbes change with age, favoring harmful inflammatory populations at the expense of populations that generate beneficial metabolites. Restoration of a youthful microbiome via fecal microbiota transplantation has been demonstrated to be beneficial in animal studies. The research community is also evaluating other approaches to at least partially rejuvenate the aged gut microbiome, such as flagellin immunization to provoke the immune system into removing more of the harmful gut microbes. Researchers here provide evidence for treatment with icariin, a plant-derived flavonoid, to favorably adjust the balance of intestinal microbial populations in mice, though it is unclear as to the mechanism of action.

We previously reported the neuroprotective effects of icariin in rat cortical neurons. Here, we present a study on icariin's anti-aging effect in 24-month aged mice by treating them with a single daily dose of 100 mg/kg of icariin for 15 consecutive days. Icariin treatment improved motor coordination and learning skills while lowered oxidative stress biomarkers in the serum, brain, kidney, and liver of the aged mice. In addition, icariin improved the intestinal integrity of the aged mice by upregulating tight junction adhesion molecules and the Paneth cells and goblet cells, along with the reduction of iNOS and pro-inflammatory cytokines (IL-1β, TNF-α, IL-2 and IL-6, and IL-12). Icariin treatments also significantly upregulated aging-related signaling molecules, Sirt 1, Sirt 3 and Sirt 6, Pot1α, BUB1b, FOXO1, Ep300, ANXA3, Calb1, SNAP25, and BDNF in old mice.

Through gut microbiota (GM) analysis, we observed icariin-associated improvements in GM composition of aged mice by reinstating bacteria found in the young mice, while suppressing some bacteria found in the untreated old mice. To clarify whether icariin's anti-aging effect is rooted in the GM, we performed fecal microbiota transfer (FMT) from icariin-treated old mice to the old mice. FMT-recipients exhibited similar improvements in the rotarod score and age-related biomarkers as observed in the icariin-treated old mice. Equal or better improvement on the youth-like features was noticed when aged mice were FMT with feces from young mice. Our study shows that both direct treatments with icariin and fecal transplant from the icariin-treated aged mice produce similar anti-aging phenotypes in the aged mice. We prove that GM plays a pivotal role in the healing abilities of icariin. Icariin has the potentials to be developed as a medicine for the wellness of the aged adults.

Link: https://doi.org/10.1016/j.phrs.2021.105587