Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) characterized by recurrent nonspecific inflammatory disease of the gastrointestinal tract, commonly manifesting as intestinal bleeding and mucosal erosion [1]. Patients with UC endure a prolonged and relapsing disease course, with severe chronic intestinal inflammation increasing the risk of colonic carcinogenesis [2]. The incidence and prevalence of UC are rising globally, with rates ranging from 200 to 500 cases per 100,000 individuals in Europe, Canada, and the United States [3]. The associated medical costs are estimated to be as high as 12.5 to 29.1 billion euros in Europe and 8.1 to 14.9 billion dollars in the United States [4]. The exact pathogenesis of UC remains unclear, although the most widely accepted hypothesis involves complex interactions between genetic predisposition, environmental factors, obesity, and immune dysregulation [5]. The modern diet, rich in high-calorie, high-fat, and high-sugar foods, along with reduced dietary fiber intake, has contributed to rising obesity rates. Additionally, the pervasive stress and sedentary lifestyle in modern society disrupt the balance of energy intake and expenditure, further exacerbating obesity. Obesity is a known risk factor for many diseases, and the incidence of UC in obese individuals is higher than in the general population [[6], [7], [8]].

Memory T follicular helper cells (mTfh) are a specialized subset of memory T helper cells that play a crucial role in immune memory and antibody-mediated immune responses [9]. mTfh cells persist after the initial immune response and rapidly activate upon re-exposure to the same antigen, supporting B cells in producing high-affinity antibodies [10]. Studies have indicated that a dysfunction in mTfh cell numbers in UC may facilitate the production of autoantibodies by B cells, exacerbating intestinal inflammation [11]. Dysfunction and imbalance of mTh cells and their subsets, including circulating memory follicular helper (cmTfh) cells and effector memory follicular helper (emTfh) cells, disrupt immune homeostasis, thereby precipitating autoimmune diseases, including inflammatory bowel disease (IBD). The generation of mTfh cells is closely associated with Tfh cells. Tfh cells are a novel CD4+ T cell subset primarily responsible for assisting B cells in forming and maintaining germinal centers (GCs), high-affinity antibody secretion, and the formation of plasma cells and memory B cells [12]. Tfh cells develop from the differentiation of CD4+ T cells within GCs and IL-21 to promote self-proliferation and differentiation, highly expressing CXC chemokine receptor 5 (CXCR5), nuclear transcription factor B cell lymphoma 6 (Bcl-6), and B lymphocyte-induced maturation protein 1 (Blimp-1) [13]. Abnormal changes in the number or function of Tfh cells can lead to abnormal GC reactions, characterized by an abundance of plasma cells and memory B cells, as well as a storm of high-affinity antibodies and inflammatory cytokines, resulting in colonic tissue damage and potentially increased cancer risk.

Ginsenoside Rg1 (G-Rg1) is a triterpenoid saponin primarily found in the roots and stems of Panax ginseng and is one of the main active components of the traditional herbal plant [14]. Renowned for its health benefits, ginseng is cherished and used as a health supplement and food additive by people globally, including in Southeast Asia and China, for thousands of years. G-Rg1 is well-known for its diverse pharmacological effects, such as antioxidation [15], anticancer, anti-apoptosis, anti-inflammation [16], and neuroprotection [17]. Studies have demonstrated that ginsenosides, including G-Rg1, have potential therapeutic value for UC by inhibiting inflammatory pathways and restoring intestinal microbial balance [18]. G-Rg1 at a dose of 200 mg/kg can inhibit the release of IL-1β and TNF-α by upregulating NLRP12 for the treatment of colitis in mice [19], while the G-Rg1 alleviates experimental colitis in rats by blocking TLR4/NF-κB signaling pathway [20]. Numerous studies have shown that G-Rg1 can modulate the balance and differentiation of Treg/Th17 cells and Th1/Th2 to treat other diseases [21,22]; however, whether G-Rg1 can regulate mTfh cells through the Bcl-6/Blimp-1 pathway to mitigate UC symptoms in obese individuals remains unclear.Therefore, in this study, we investigated the potential mechanism of G-Rg1 ameliorated UC by observing the activation of Bcl-6/Blimp-1 pathway and the proportions of mTfh cell subsets. We induced UC in obese mice using 2.5% dextran sulfate sodium (DSS) and administered 200 mg/kg of G-Rg1.