Inflammatory bowel disease (IBD), denominated by Crohn’s disease (CD) and ulcerative colitis (UC), is an immune-mediated chronic intestinal disorder characterized by rectal bleeding, mucous stool and diarrhea, in which epithelial barrier disruption and mucosal ulceration are associated [
1]. The mainstay therapies for colitis include anti-inflammatory drugs, 5-aminosalicylic acid and glucocorticosteroids, and immunomodulatory agents, azathioprine, mercaptopurines and cyclosporine [
2]. However, these drugs are unsatisfactory as repeated relapses and serious side effects often occur. Indeed, the drug-induced toxicity appears to be a continuous challenge. Over the past decades, though substantial progress has been made to treat this debilitating disease, effective therapies are yet available. Although the exact etiologies of colitis remain unknown, it is generally accepted that IBD is an autoimmune disease with an initial defect in sampling gut luminal antigens, or a mucosal susceptibility that leads to the activation of immune responses. In consequence, the overproduction of pro-inflammatory mediators from immune cells, such as reactive oxygen species, nitrogen metabolites and pro-inflammatory cytokines, result in mucosal damage and the sustenance of inflammatory responses [
3] [
4]. According to a number of studies, we acknowledged that various kinds of intestinal immune cells play important roles in the initiation of IBD; however, activated CD4+ T helper (Th) cells, explicitly Th1 and Th2, are definitely responsible for the maintenance of the inflammatory condition s of CD and UC [
5]. It is established that CD is generally considered as a Th1 cytokine-mediated disorder whereas UC appears to be likely arisen from Th2-mediated responses. Nevertheless, some other new subsets of Th cells have also been suggested to induce the IBD pathologies [
6]. Upon the intrinsic generation of different inflammatory mediators and their release into the bloodstream, tissue injury and/or epithelial damage are observed as the disrupted mucosal homeostasis, tissue injury and/or epithelial damage are observed as the disrupted mucosal homeostasis in IBD. Among these pro-inflammatory mediators, the pro-inflammatory cytokines, particularly tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-12 and IL-23 are believed to play crucial roles in the pathogenesis of IBD [
7‐
9]. Therefore,the regulation of these cytokines has been proposed as a strategy to treat IBD [
10]. In this regard, anti-inflammatory drugs, aminosalicylates and corticosteroids, and immunosuppressive agents, are considered as the first-line therapies for IBD patients [
11]. As mentioned earlier, undesired side effects are often arisen from these mainstream pharmaceuticals, the recrudescence rates of IBD stay relatively high [
12,
13]. Therefore, the use of complementary and alternative (CAM) approaches has been increasingly appreciated by the sufferers in the management of colitis.
In recent years, traditional Chinese medicine (TCM) has been considered as one of the most popular CAM approaches for IBD patients as the bioactivities of a variety of TCM herbs have been validated by bench-to-bedside studies. Intriguingly, the application of medicinal formulations, which are mixtures of herbs or phytocompounds that influence multiple systems in the body, has been shown with preferential effect over the individual conventional treatment protocols for IBD sufferers indicating that herbal medicine can be a promising alternative approach for the management of colitic conditions [
14], and several medicinal formulas comprising Chinese herbs have been demonstrated effective against IBD [
15].
According to the Chinese medical theory, the symptoms of UC are derived from the imbalance of
Qi accompanied with dampness or cold-dampness in the spleen and intestine. BaiTouWeng decoction (BTWD) is a traditional Chinese herbal recipe for invigorating the intestine and restoring the imbalance of
Qi that has been prescribed in TCM clinics for many years. To the traditional BTWD, we added in the following herbal medicines: HerbaPogostemonis, Herba Centellat and, indigo naturalis, and we named this modified formula Chang-An-Shuan (CAS). In detail, our formula CAS comprises: Pulsatilla chinensisRegel (root of
Pulsatilla Adans, family: Ranunculaceae), Cortex Fraxini (bark of
Fraxinus chinensis Roxb, family: Oleaceae), RhizomaCoptidis (rhizome of
Coptis chinensis Franch, family: Ranunculaceae), HerbaPogostemonis [leaf and stem of
Pogostemon cablin(Blanco) Benth, family: Lamiaceae], Herba Centellat [leaf of
Centella asiatica (L.) Urban, family: Umbelliferae], and indigo naturalis[extractive of
Baphicacanthus cusia (Nees) Bremek, family: Acanthaceae]. Recently, Dai et al. reported that BTWD-based Chinese medicine formula could greatly improve the clinical symptoms of patients with acute period of left hemicolon type-UC [
16]. According to the TCM clinical experience, several ingredients of the CAS formulation are useful for some common gastrointestinal ailments [
17], including nausea, vomiting, diarrhea and abdominal cramps. However,no scientific evidence of efficacy or mechanistic action of CAS on experimental colitis has been provided. Therefore, in this study, we aimed to assess the anti-inflammatory effect of CAS on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, and to elucidate the underlying mechanisms of its in vivo activities.