Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis

Hongwei Han; Wenxue Sun; Lu Feng; Zhongling Wen; Minkai Yang; Yingying Ma; Jiangyan Fu; Xiaopeng Ma; Xinhong Xu; Zhaoyue Wang; Tongming Yin; Xiao-Ming Wang; Gui-Hua Lu; Jin-Liang Qi; Hongyan Lin; Yonghua Yang

doi:10.7717/peerj.10675

Differential relieving effects of shikonin and its derivatives on inflammation and mucosal barrier damage caused by ulcerative colitis

PeerJ. 2021 Jan 7:9:e10675. doi: 10.7717/peerj.10675. eCollection 2021.

Authors

Hongwei Han^#^{1

2}, Wenxue Sun^#^{1

2}, Lu Feng^{1

2}, Zhongling Wen^{1

2}, Minkai Yang^{1

2}, Yingying Ma^{1

2}, Jiangyan Fu^{1

2}, Xiaopeng Ma^{1

2}, Xinhong Xu^{1

2}, Zhaoyue Wang^{1

2}, Tongming Yin², Xiao-Ming Wang^{1

2}, Gui-Hua Lu^{1

3}, Jin-Liang Qi^{1

2}, Hongyan Lin^{1

2}, Yonghua Yang^{1

2}

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, China.
² Co-Innovation Center for Sustainable Forestry in Southern China, MOE Key Laboratory of Forest Genetics and Biotechnology, Nanjing Forestry University, Nanjing, China.
³ School of Life Sciences, Huaiyin Normal University, Huaian, China.

^# Contributed equally.

Abstract

Background: Ulcerative colitis (UC) is one of the most challenging human diseases. Natural shikonin (SK) and its derivatives (with have higher accumulation) isolated from the root of Lithospermum erythrorhizon have numerous beneficial effects, such as wound healing and anti-inflammatory activities. Some researchers have reported that hydroxynaphthoquinone mixture (HM) and SK attenuate the acute UC induced by dextran sulfate sodium (DSS). However, no existing study has systemically investigated the effectiveness of SK and other hydroxynaphthoquinone natural derivative monomers on UC.

Methods: In this study, mice were treated with SK and its derivatives (25 mg/kg) and mesalazine (200 mg/kg) after DSS administration daily for one week. Disease progression was monitored daily by observing the changes in clinical signs and body weight.

Results: Intragastric administration natural single naphthoquinone attenuated the malignant symptoms induced by DSS. SK or its derivatives remarkably suppressed the serum levels of pro-inflammatory cytokines while increasing the inflammatory cytokine interleukin (IL)-10 . Additionally, both SK and alkanin restrained the activities of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) in serum and colonic tissues. SK and its derivatives inhibited the activation of nucleotide binding oligomerization domain-like receptors (NLRP3) inflammasome and NF-κB signaling pathway, thereby relieving the DSS-induced disruption of epithelial tight junction (TJ) in colonic tissues.

Conclusions: Our findings shed more lights on the pharmacological efficacy of SK and its derivatives in UC against inflammation and mucosal barrier damage.

Keywords: Anti-inflammatory; Epithelial tight junction; Hydroxynaphthoquinone; Shikonin and its derivatives; Ulcerative colitis.

Grants and funding

This research was supported by the National Natural Science Foundation of China (NSFC) (U1903201, 21702100, 31771413, 31670298, 21907051), the Program for Changjiang Scholars and Innovative Research Team in University (IRT_14R27), the Natural Science Foundation of Jiangsu Bureau of Science and Technology (BK20191254), and the Fundamental Research Funds for the Central Universities (020814380002, 020814380057). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.