Polysaccharide from Atractylodes macrocephala Koidz. ameliorates DSS-induced colitis in mice by regulating the Th17/Treg cell balance

Abstract

Atractylodes macrocephala Koidz. is one of the most frequently used traditional Chinese medicines for the treatment of ulcerative colitis (UC). The beneficial effect of polysaccharide from Atractylodes macrocephala Koidz. (PAMK) on UC has been reported, while the underlying mechanism and target remain unclear. In this study, we systematically investigated the therapeutic effect and the underlying mechanism of PAMK in UC based on a mouse model of dextran sodium sulfate (DSS)-induced colitis. PAMK treatment (100 mg/kg, 200 mg/kg and 400 mg/kg) significantly ameliorated DSS-induced colitis, manifested as a reduction in weight loss, disease activity index (DAI), colon shortening, spleen index and histological score. Moreover, PAMK treatment inhibited inflammation and improved the integrity of the intestinal barrier in colitis mice. Mechanistically, microarray analysis determined the critical role of the immunoregulatory effect of PAMK in alleviating UC. Flow cytometry analysis further demonstrated that PAMK treatment regulated the balance between T helper (Th) 17 and regulatory T (Treg) cells in the mesenteric lymph nodes (MLN) and spleen in mice with colitis. In addition, PAMK treatment downregulated the expression of IL-6 and suppressed the phosphorylation of STAT3. Together, these data revealed that PAMK treatment alleviated DSS-induced colitis by regulating the Th17/Treg cell balance, which may be dependent on the inhibition of the IL-6/STAT3 signaling pathway. Our study is the first to elucidate that the underlying mechanism by which PAMK treatment alleviates DSS-induced colitis is associated with an improved the Th17/Treg cell balance. Collectively, the study provides evidence for the potential of PAMK to treat UC.

Mechanisms of Atractylodes macrocephala Koidz. on therapy to diarrheal disease: A systematical review and meta-analysis of preclinical evidence

“…Sensitivity Analysis. After excluding the study conducted by Yang [19], we observed heterogeneity in the spleen index during this meta-analysis. Upon thorough review and comparison with other studies analyzing the spleen index, we found a notable distinction between Yang's study and the others, primarily regarding the age of the mice used.…”

“…( 2) Anti-inflammation: Excessive production and abnormal activation of inflammatory factors can result in an inflammatory response in the intestinal mucosa, leading to impaired barrier function and an imbalance in fluid secretion and absorption, ultimately causing diarrhea [28]. AMK has the potential to alleviate intestinal mucosal inflammation by inhibiting the activation of Drp1 and NLRP3 inflammasomes [17], suppressing NF-κB and STAT3 signaling [19,25], modulating the MAPK/NF-κB pathway [22], activating PPARα [23], reducing the secretion of pro-inflammatory factors such as IL-1β, IL-6, IL-17, and TNF-α, and enhancing the secretion of IL-10. (3) Anti-oxidation: Antioxidation is a factor that helps prevent the worsening of diarrhea [29].…”

“…Finally, 23 papers were included for meta-analysis. [16,[17][18][19][20][21][22][23][24][25][26]. The results based on the above search strategy are shown in Fig.…”

“…After individually excluding studies, we identified Yang [19] as the source of heterogeneity. After excluding this study, the results showed statistical significance, with a significant heterogeneity of the spleen index (I 2 = 62%).…”

Polysaccharide from Atractylodes macrocephala Koidz Binding with Zinc Oxide Nanoparticles as a Novel Mucosal Immune Adjuvant for H9N2 Inactivated Vaccine

“…Atractylodes macrocephala Koidz (AM) is an important traditional Chinese medicine. The polysaccharide from AM (AMP), as one of the main active components, has antiinflammatory [9], antioxidant [10] and immunomodulatory activities [11]. Concurrently, zinc oxide nanoparticles (ZnONPs) exhibit immunomodulatory properties, capable of activating dendritic cells, leading to the production of cytokines such as IL-6 and TNF-α [12].…”