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Zhikang Capsule ameliorates dextran sodium sulfate-induced colitis by inhibition of inflammation, apoptosis, oxidative stress and MyD88-dependent TLR4 signaling pathway.
J Ethnopharmacol. 2016 Nov 04; 192:236-247.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Zhikang Capsule (ZKC) is a traditional Chinese medicine (TCM) modified from classic formulas Qi-Li-San (an ancient formula dating to Qing Dynasty) and Fu-Jin-Sheng-Ji-San (written into The Golden Mirror of Medicine). ZKC contains 14 kinds of materials and has been widely used for the clinical therapy of inflammatory bowel diseases (IBD) for a long time. However, the therapeutic mechanisms of ZKC are still unclear.

AIM OF THE STUDY

To determine the protective effect of ZKC on dextran sodium sulfate (DSS)-induced colitis and explore the underlying mechanisms.

MATERIALS AND METHODS

C57BL/6 mice were fed with 3% DSS in drinking water for one week to induce experimental colitis. They were randomly assigned to six groups according to the treatment conditions. The histological changes of colon tissues were observed by hematoxylin and eosin (H&E) staining. The serum concentration of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-12) and anti-inflammatory mediators (IL-4 and IL-10) was detected by enzyme-linked immune sorbent assays (ELISAs). The production of MPO, SOD, MDA, NO, and caspase-3 was assessed by biochemical assay kits. The expression of iNOS, ICAM-1, and NF-ΚB was evaluated by immunohistochemistry staining. The levels of TLR4, MyD88, and TRAF6 were determined by western blot.

RESULTS

Histologic analysis exhibited that ZKC alleviated the inflammation, loss of goblet cells, and submucosal edema induced by DSS. ZKC significantly suppressed the pro-inflammatory cytokines and promoted the anti-inflammatory mediators. The antioxidation of ZKC was indicated by increased activity of SOD and reduced production of MDA, NO, and iNOS in ZKC-treated mice. Furthermore, ZKC repressed the colonic expression of caspase-3 and the activity of the MyD88-dependent TLR4 signaling pathway.

CONCLUSIONS

This research demonstrated the protective effect of ZKC on DSS-induced colitis. For the first time, we identified four therapeutic mechanisms of ZKC, including effective inhibition of the inflammatory responses, significant alleviation of intestinal epithelium apoptosis, considerable prevention of oxidative stress, and selective down-regulation of the MyD88-dependent TLR4 signaling pathway. With high therapeutic effects and low toxic effects, ZKC exhibits great superiority over western medicines in IBD treatment.

Authors+Show Affiliations

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277Jiefang Road, Wuhan 430022, PR China. Electronic address: LiangFei2016@126.com.Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277Jiefang Road, Wuhan 430022, PR China. Electronic address: xuzou2016@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27452656

Citation

Fei, Liang, and Keshu Xu. "Zhikang Capsule Ameliorates Dextran Sodium Sulfate-induced Colitis By Inhibition of Inflammation, Apoptosis, Oxidative Stress and MyD88-dependent TLR4 Signaling Pathway." Journal of Ethnopharmacology, vol. 192, 2016, pp. 236-247.
Fei L, Xu K. Zhikang Capsule ameliorates dextran sodium sulfate-induced colitis by inhibition of inflammation, apoptosis, oxidative stress and MyD88-dependent TLR4 signaling pathway. J Ethnopharmacol. 2016;192:236-247.
Fei, L., & Xu, K. (2016). Zhikang Capsule ameliorates dextran sodium sulfate-induced colitis by inhibition of inflammation, apoptosis, oxidative stress and MyD88-dependent TLR4 signaling pathway. Journal of Ethnopharmacology, 192, 236-247. https://doi.org/10.1016/j.jep.2016.07.055
Fei L, Xu K. Zhikang Capsule Ameliorates Dextran Sodium Sulfate-induced Colitis By Inhibition of Inflammation, Apoptosis, Oxidative Stress and MyD88-dependent TLR4 Signaling Pathway. J Ethnopharmacol. 2016 Nov 4;192:236-247. PubMed PMID: 27452656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zhikang Capsule ameliorates dextran sodium sulfate-induced colitis by inhibition of inflammation, apoptosis, oxidative stress and MyD88-dependent TLR4 signaling pathway. AU - Fei,Liang, AU - Xu,Keshu, Y1 - 2016/07/21/ PY - 2016/05/20/received PY - 2016/07/17/revised PY - 2016/07/20/accepted PY - 2016/7/28/pubmed PY - 2017/5/16/medline PY - 2016/7/26/entrez KW - Aloe emodin (PubChem CID: 10207) KW - Apoptosis KW - Berberine (PubChem CID: 2353) KW - Chrysophanol (PubChem CID: 10208) KW - Dencichine (PubChem CID: 2360) KW - Emodin (PubChem CID: 3220) KW - Glycyrrhizic acid (PubChem CID: 14982) KW - Imperatorin (PubChem CID: 10212) KW - Inflammation KW - Inflammatory bowel disease KW - Isoimperatorin (PubChem CID: 68081) KW - Oxidative stress KW - Physcion (PubChem CID: 10639) KW - Rhein (PubChem CID: 10168) KW - Toll-like receptor 4 SP - 236 EP - 247 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 192 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Zhikang Capsule (ZKC) is a traditional Chinese medicine (TCM) modified from classic formulas Qi-Li-San (an ancient formula dating to Qing Dynasty) and Fu-Jin-Sheng-Ji-San (written into The Golden Mirror of Medicine). ZKC contains 14 kinds of materials and has been widely used for the clinical therapy of inflammatory bowel diseases (IBD) for a long time. However, the therapeutic mechanisms of ZKC are still unclear. AIM OF THE STUDY: To determine the protective effect of ZKC on dextran sodium sulfate (DSS)-induced colitis and explore the underlying mechanisms. MATERIALS AND METHODS: C57BL/6 mice were fed with 3% DSS in drinking water for one week to induce experimental colitis. They were randomly assigned to six groups according to the treatment conditions. The histological changes of colon tissues were observed by hematoxylin and eosin (H&E) staining. The serum concentration of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-12) and anti-inflammatory mediators (IL-4 and IL-10) was detected by enzyme-linked immune sorbent assays (ELISAs). The production of MPO, SOD, MDA, NO, and caspase-3 was assessed by biochemical assay kits. The expression of iNOS, ICAM-1, and NF-ΚB was evaluated by immunohistochemistry staining. The levels of TLR4, MyD88, and TRAF6 were determined by western blot. RESULTS: Histologic analysis exhibited that ZKC alleviated the inflammation, loss of goblet cells, and submucosal edema induced by DSS. ZKC significantly suppressed the pro-inflammatory cytokines and promoted the anti-inflammatory mediators. The antioxidation of ZKC was indicated by increased activity of SOD and reduced production of MDA, NO, and iNOS in ZKC-treated mice. Furthermore, ZKC repressed the colonic expression of caspase-3 and the activity of the MyD88-dependent TLR4 signaling pathway. CONCLUSIONS: This research demonstrated the protective effect of ZKC on DSS-induced colitis. For the first time, we identified four therapeutic mechanisms of ZKC, including effective inhibition of the inflammatory responses, significant alleviation of intestinal epithelium apoptosis, considerable prevention of oxidative stress, and selective down-regulation of the MyD88-dependent TLR4 signaling pathway. With high therapeutic effects and low toxic effects, ZKC exhibits great superiority over western medicines in IBD treatment. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/27452656/Zhikang_Capsule_ameliorates_dextran_sodium_sulfate_induced_colitis_by_inhibition_of_inflammation_apoptosis_oxidative_stress_and_MyD88_dependent_TLR4_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(16)30481-0 DB - PRIME DP - Unbound Medicine ER -