Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Abstract

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

Porphyromonas gingivalis and Lactobacillus rhamnosus GG regulate the Th17/Treg balance in colitis via TLR4 and TLR2

“…Consequently, how microbes communicate with hosts in the development of local and distant inflammation has recently become a hot spot in the study of pathogenesis. 2 Herein, we show that CD4 + T helper (Th) cells play a pivotal role in maintaining immune homeostasis in this process, among which the balance between proinflammatory CD4 + IL-17 + Th17 cells and immunosuppressive CD4 + CD25 + Foxp3 + T regulatory (Treg) cells is proven to be the cornerstone. Th17 cells exhibit dual characteristics in the pathogenesis of colitis.…”

“…As microbial imbalance is an initiating factor for these diseases, their progression is primarily regulated by the interactions between microorganisms and host immune responses. Consequently, how microbes communicate with hosts in the development of local and distant inflammation has recently become a hot spot in the study of pathogenesis 2 . Herein, we show that CD4 + T helper (Th) cells play a pivotal role in maintaining immune homeostasis in this process, among which the balance between proinflammatory CD4 + IL‐17 + Th17 cells and immunosuppressive CD4 + CD25 + Foxp3 + T regulatory (Treg) cells is proven to be the cornerstone.…”

Decursinol Angelate Mitigates Sepsis Induced by Methicillin-Resistant Staphylococcus aureus Infection by Modulating the Inflammatory Responses of Macrophages

“…DA was also found to suppress the induction of IL-1β, IL-6, and iNOS in RAW264.7 and HL-60 cells activated with LPS and phorbol-12-myristate-13-acetate, respectively [14]. In addition, we previously reported the anti-inflammatory effect of DA on T cells, in which DA suppressed type 17 helper T-cell responses and ameliorated colitis in a mouse model [8]. However, the biological impact of decursin and DA was unclear on the functional activities of primary macrophages and/or macrophage-associated inflammatory diseases.…”

“…The roots of the plant are regarded as the so-called 'female ginseng' due to a beneficial effect on gynecologic health. Bioactive ingredients of the roots have been studied, in order to evaluate their potential to improve many disease conditions, including inflammatory diseases and cancer [7,8]. Pyranocoumarins, decursin, and its structural isomer decursinol angelate (DA) are the most abundant compounds of the ethanol extracts of A. gigas and are reported to have anti-inflammatory activities in several cancer cell lines [9,10].…”

Heme Oxygenase-1 in Gastrointestinal Tract Health and Disease

“…In this sense, several studies have claimed how artemisinin derivatives ameliorate IBM via decreasing pro-inflammatory cytokines, inhibiting NF-κB, promoting Th cell apoptosis and increasing Treg cells, through HO-1 upregulation, and so promoting an anti-inflammatory state [148,149]. Similar effects over the regulation of Th/Treg balance, mediated by HO-1 induction, have been observed after the administration of others plant extracts from oriental medicine, such as Atractylodes macrocephala and Taraxacum herba [150], and Angelica gigas [151,152]. Oligonol, a polyphenol derived from the Chinese lychee fruit, ameliorates colitis in DSS-induced colitis model, but, interestingly, Oligonol prevents IBD relapse better than sulfasalazine [153].…”