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. 2022 Feb 15:2022:8780514.
doi: 10.1155/2022/8780514. eCollection 2022.

Yiyi Fuzi Baijiang Decoction Alleviates Ulcerative Colitis Partly by Regulating TLR4-Mediated PI3K/Akt and NF- κ B Pathways

Affiliations

Yiyi Fuzi Baijiang Decoction Alleviates Ulcerative Colitis Partly by Regulating TLR4-Mediated PI3K/Akt and NF- κ B Pathways

Liping Chen et al. Evid Based Complement Alternat Med. .

Abstract

Yiyi Fuzi Baijiang Decoction (YFBD), an ancient prescription developed by the ancient Chinese physician, Zhang Zhongjing, has shown remarkable effects in treating ulcerative colitis (UC). However, there are few studies on its mechanism. This study was designed to explore the potential mechanism of YFBD in treating UC. The principal ingredients of YFBD were analyzed using high-performance liquid chromatography (HPLC). Dextran sulfate sodium- (DSS-) induced mice and lipopolysaccharide- (LPS-) stimulated RAW264.7 cells were used in the study. The body weight and disease activity index (DAI) of mice were recorded and analyzed for 10 days. After sacrifice, the colonic tissues were harvested. The colon length was measured, and the histopathological changes were observed by hematoxylin and eosin staining. The levels of inflammatory cytokines in mice colons and RAW246.7 cells were determined by real-time quantitative PCR and immunofluorescence. The effects of YFBD on the TLR4-mediated PI3K/Akt and NF-κB pathways were determined by western blot analysis. HPLC identified five compounds in YFBD: chlorogenic acid, caffeic acid, benzoylmesaconine, benzoyl aconitine, and quercetin. YFBD alleviated weight loss, colon shortening, and colonic histopathological lesion in mice. Meanwhile, it decreased the DAI and histological score of mice with UC. In addition, YFBD remarkably decreased the levels of interleukin- (IL-) 6, IL-1β, and tumor necrosis factor (TNF)-α in the colons of DSS-induced mice and LPS-stimulated RAW246.7 cells. Furthermore, the expression of key proteins in TLR4-mediated PI3K/Akt and NF-κB pathways significantly decreased with YFBD treatment. In conclusion, YFBD had protective effects on mice with UC, which was in part related to its anti-inflammatory effects and downregulation of TLR4-mediated PI3K/Akt and NF-κB pathways.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
YFBD attenuated DSS-induced acute colitis. (a) Animal experiment design (10/group). (b) Changes in body weight. (c) Evaluation of DAI. (d) Representative images of colons. (e) Effect of YFBD on colon length. (f) Photographs of H&E-stained colon sections (magnification: ×100). (g) Assessment of the histological scores. Data are presented as mean ± SEM (n = 8). ∗∗P < 0.01 vs. control; #P < 0.05; ##P < 0.01 vs. DSS.
Figure 2
Figure 2
HPLC analysis of the main chemicals of YFBD recorded at 230 nm. (a) Solution of standards. (b) Solution of YFBD.
Figure 3
Figure 3
YFBD decreased the inflammatory cytokines in colons of mice with DSS-induced colitis. (a) mRNA level of IL-6. (b) mRNA level of IL-1β. (c) mRNA level of TNF-α. (d) Colon sections were stained with DAPI (blue) and IL-6 (green), IL-1β (green), and TNF-α (red) and observed under a fluorescence microscope. Data are presented as mean ± SEM (n = 3). ∗∗P < 0.01 vs. control; #P < 0.05; ##P < 0.01 vs. DSS.
Figure 4
Figure 4
YFBD decreased the mRNA levels of inflammatory cytokines in LPS-induced RAW264.7 macrophages. (a) Effects of YFBD on the viability of RAW 264.7 macrophages. (b) mRNA level of IL-6. (c) mRNA level of IL-1β. (d) mRNA level of TNF-α. Data are presented as mean ± SEM (n = 3). ∗∗P < 0.01 vs. control; #P < 0.05; ##P < 0.01 vs. LPS.
Figure 5
Figure 5
YFBD downregulated TLR4-mediated PI3K/Akt and NF-κB pathways in colons of mice with DSS-induced colitis. (a) Effect of YFBD on the protein expression of TLR4, P-PI3K, and p-Akt. (b–d) Quantification of the ratio of TLR4, P-PI3K, and p-Akt. (e) Effect of YFBD on the degradation of IκBα and phosphorylation of NF-κB/p65. (f, g) Quantification of the ratio of IκBα and phosphorylated NF-κB/p65. Data are presented as mean ± SEM (n = 3). ∗∗P < 0.01 vs. control; #P < 0.05; ##P < 0.01 vs. DSS.
Figure 6
Figure 6
YFBD downregulated the TLR4-mediated PI3K/Akt and NF-κB pathways in LPS-induced RAW264.7 cells. (a) Effect of YFBD on the protein expression of TLR4, P-PI3K, and p-Akt. (b–d) Quantification of the ratio of TLR4, P-PI3K, and p-Akt. (e) Effect of YFBD on the degradation of IκBα and phosphorylation of NF-κB/p65. (f, g) Quantification of the ratio of IκBα and phosphorylated NF-κB/p65. Data are presented as mean ± SEM (n = 3). ∗∗P < 0.01 vs. control; #P < 0.05; ##P < 0.01 vs. LPS.
Figure 7
Figure 7
YFBD inhibited PI3K/Akt and NF-κB pathways in RAW 264.7 cells via downregulating TLR4 expression. (a) RAW 264.7 cells were transfected with TLR4 siRNA or control siRNA for 48 h. (b) Effect of YFBD and TLR4 siRNA on the protein expression of TLR4, P-PI3K, and p-Akt. (c–e) Quantification of the ratio of TLR4, P-PI3K, and p-Akt. (f) Effect of YFBD and TLR4 siRNA on the degradation of IκBα and phosphorylation of NF-κB/p65. (g, h) Quantification of the ratio of IκBα and phosphorylated NF-κB/p65. Data are presented as mean ± SEM (n = 3). ∗∗P < 0.01; P < 0.05.
Figure 8
Figure 8
Schematic illustration depicting the potential pathways associated with the therapeutic effect of YFBD on ulcerative colitis.

References

    1. Molodecky N. A., Soon I. S., Rabi D. M., et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology . 2012;142(1):46–54. doi: 10.1053/j.gastro.2011.10.001. - DOI - PubMed
    1. Selvaratnam S., Gullino S., Shim L., et al. Epidemiology of inflammatory bowel disease in South America: a systematic review. World Journal of Gastroenterology . 2019;25(47):6866–6875. doi: 10.3748/wjg.v25.i47.6866. - DOI - PMC - PubMed
    1. Ananthakrishnan A. N., Kaplan G. G., Ng S. C. Changing global epidemiology of inflammatory bowel diseases: sustaining health care delivery into the 21st century. Clinical Gastroenterology and Hepatology . 2020;18(6):1252–1260. doi: 10.1016/j.cgh.2020.01.028. - DOI - PubMed
    1. Kwak M. S., Cha J. M., Lee H. H., et al. Emerging trends of inflammatory bowel disease in South Korea: a nationwide population‐based study. Journal of Gastroenterology and Hepatology . 2019;34(6):1018–1026. doi: 10.1111/jgh.14542. - DOI - PubMed
    1. Kobayashi T., Siegmund B., Le Berre C., et al. Ulcerative colitis. Nature Reviews Disease Primers . 2020;6(1):p. 74. doi: 10.1038/s41572-020-0205-x. - DOI - PubMed

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