Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), constitutes a range of chronic inflammation conditions influencing the gastrointestinal tract (Liu et al., 2023). UC and CD Both share numerous manifestations, including ocular complications, mucocutaneous lesions, hepatobiliary disorders, abdominal pain, diarrhea, arthropathies, and thromboembolic events (Rogler et al., 2021). Globally, approximately 6–8 million individuals are affected by these conditions, with a notable increase in the morbidity of IBD observed in Asia since the turn of the 21st century. As a chronic, progressive, and recurrent gastrointestinal disorder, IBD profoundly impairs patients' quality of life and daily functioning, thereby exacerbating the strain on the burden on healthcare systems (Sheehan et al., 2023).

IBD emerges as a complex interplay of diverse factors that disrupts gut homeostasis. At the core of IBD lies genetic susceptibility, where individuals inherit specific gene mutations or variations that predispose them to developing the disease (Hodson, 2016).

In addition, an aberrant immune response instigates an overactive immune reaction to normal gut flora or dietary antigens, resulting in chronic intestinal inflammation (Dart et al., 2023). Lastly, environmental factors also significantly contribute to the development and progression of IBD. Dietary habits (high in processed foods and low in fiber) and smoking have been linked to increased disease risk. Early-life exposures to infections, antibiotics, and stress can alter gut microbiota composition and immune system maturation, potentially setting the stage for later development of IBD (Lavelle and Sokol, 2020; Lu et al., 2022).

Inflammation is a core pathological feature of IBD, characterized by the body's immune response to abnormal stimuli, including pathogens, damaged cellular components, and imbalances in the gut microbiota (Rugtveit et al., 1997). The inflammatory process in IBD involves aberrant activation of various immune cells and inflammatory mediators. Initially, injured intestinal epithelial cells discharge damage-associated molecular patterns (DAMPs), and they are identified by pattern recognition receptors (PRRs) on immune cells, thereby triggering an inflammatory response (Gong et al., 2020). Subsequently, immune cells, for instance, macrophages and B cells, exhibit aberrant activation, releasing significant amounts of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL 6), monocyte chemotactic protein 1 (MCP-1), and interferon-gamma (IFN-γ), further exacerbating relevant inflammatory response (Yang et al., 2023, Yang et al., 2024, Zhang et al., 2024a, Luo et al., 2024, Zhang et al., 2024b). Therefore, modulating inflammation and the balance of immunity in the gut has become a strategy for treating IBD.

Andrographis paniculata, known as Chuan Xin Lian in Chinese, is a perennial herb belonging to the family Acanthaceae. A. paniculata is used as a potent herb for clearing heat, detoxifying, cooling blood, and reducing swelling, is commonly employed in the treatment of colds, sore throat, dysentery, hepatitis, and other ailments (Chen et al., 2023, Zhang et al., 2023a). Andrographolide (AND) is the major active constituent found in A. paniculata, while andrographolide sodium bisulfite (ASB) is its sulfated metabolite in vivo (Guan et al., 2022, Tang et al., 2024). Recently, some studies have illustrated that AND and ASB display protective effects through the NF-κB pathway in DSS-induced UC mice (Li et al., 2024, Qian et al., 2021, Chunhong et al., 2024). Although they can suppress macrophage proinflammatory polarization in dextran sodium sulfate (DSS)-induced IBD (Guo et al., 2019, Liu et al., 2014, Gao et al., 2020), the underlying mechanism of AND and ASB for treating IBD remains elusive. Therefore, we investigated the protective effects of AND and its metabolite ASB in DSS-induced IBD and explored their potential mechanisms in inflammation and immunity.