Shaoyao Gancao Decoction protects against dextran sulfate sodium-induced ulcerative colitis by down-regulating ferroptosis

Abstract

Objectives Shaoyao Gancao Decoction (SGD) is a well-known Chinese herbal prescription used to treat ulcerative colitis (UC). This study was designed to evaluate the effect of SGD in dextran sulfate sodium-induced UC and to reveal the potential mechanism. Methods A UC mouse model was established by the administration of dextran sulfate sodium. The mice were given SGD extract intragastrically for 7 days. Histological pathology, inflammatory factors, and ferroptosis regulators were determined in vivo. In addition, ferroptotic Caco-2 cells were prepared to investigate the underlying mechanism of the effects of SGD. Key findings The results showed that SGD reduced the disease activity index, the level of inflammatory factors, and histological damage in mice with UC. Moreover, SGD down-regulated the level of ferroptosis in cells in colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production, compared with the model group. Correspondingly, similar effects of SGD on ferroptosis were observed in Erastin-treated Caco-2 cells. The results of our in vitro reactive oxygen species assays and the changes in mitochondrial structure observed by scanning electron microscopy also supported these results. Conclusion Taken together, these findings suggest that SGD protected against UC by down-regulating ferroptosis in colonic tissue.

Ferroptosis: a new mechanism of traditional Chinese medicine for treating ulcerative colitis

“…By observing iron levels, GSH content, and mitochondrial morphology, the formula was found to downregulate Fe 2+ levels, reduce iron deposition, GSH consumption and MDA levels. It also lowered ferroptosis levels within the colon tissue, ultimately decreasing inflammation markers and histological damage, effectively treating UC ( Hu et al, 2023 ).…”

“…This is demonstrated in the treatment of UC by the following: a single Chinese herbal medicine may contain multiple metabolites, each with different pathways for treating UC. For example, berberine extracted from Coptis MDA (Hu et al, 2023). In the prevention and treatment of UC, TCM offers clinical advantages over Western medicine, including fewer complications, minimal side effects, and lower recurrence rates (Liu et al, 2022).…”

“…For example, berberine extracted from Coptis chinensis can treat UC by regulating pathways such as NK-κB, PI3K-AKT, MAPK, and Nrf2 ( Wang et al, 2021 ). Chinese herbal medicines can be combined into herbal formulas that interact with each other, such as Shaoyao Gancao Tang involving multiple targets like GSH and MDA ( Hu et al, 2023 ). In the prevention and treatment of UC, TCM offers clinical advantages over Western medicine, including fewer complications, minimal side effects, and lower recurrence rates ( Liu et al, 2022 ).…”