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Review
. 2020 Dec 10:11:603476.
doi: 10.3389/fphar.2020.603476. eCollection 2020.

Efficacy and Safety of Sophora flavescens (Kushen) Based Traditional Chinese Medicine in the Treatment of Ulcerative Colitis: Clinical Evidence and Potential Mechanisms

Mingjun Chen  1 , Yuxuan Ding  2 , Zhanqi Tong  1
Affiliations
Free PMC article
Review

Efficacy and Safety of Sophora flavescens (Kushen) Based Traditional Chinese Medicine in the Treatment of Ulcerative Colitis: Clinical Evidence and Potential Mechanisms

Mingjun Chen et al. Front Pharmacol. .
Free PMC article

Abstract

Background: Radix Sophorae flavescentis (Kushen), a Chinese herb, is widely used in the treatment of ulcerative colitis (UC) with damp-heat accumulation syndrome (DHAS) according to traditional Chinese medicine (TCM) theory. Objective: The aim of this study was to illuminate the clinical efficacy and potential mechanisms of Kushen-based TCM formulations in the treatment of UC with DHAS. Materials and Methods: A systematic literature search was performed in the PubMed, EMBASE, Chinese Biomedical Literature database, China National Knowledge Infrastructure database, Chongqing VIP Information database, and Wanfang database for articles published between January 2000 and July 2020 on randomized controlled trials (RCTs) that used Kushen-based TCM formulations in the treatment of UC with DHAS. A network pharmacology approach was conducted to detect the potential pathways of Kushen against UC with DHAS. Results: Eight RCTs with a total of 983 subjects were included in the meta-analysis. Compared with the control subjects (5-aminosalicylic acid therapy), those who received Kushen-based TCM formulations for the treatment of UC showed a significantly higher clinical remission rate (RR = 1.20, 95% CI: [1.04, 1.38], p = 0.02) and lower incidence of adverse events (RR = 0.63, 95% CI [0.39, 1.01], p = 0.06). A component-target-pathway network was constructed, indicating five main components (quercetin, luteolin, matrine, formononetin, and phaseolin), three major targets (Interleukin-6, Myc proto-oncogene protein, and G1/S-specific cyclin-D1) and one key potential therapeutic pathway (PI3K-Akt signaling) of Kushen against UC with DHAS. Conclusion: Kushen-based TCM formulations provide good efficacy and possess great potential in the treatment of UC. Large-scale and high-quality clinical trials and experimental verification should be considered for further confirmation of the efficacy of Kushen-based formulations.

Keywords: Sophora flavescens; damp-heat accumulation syndrome; herbal medicine; meta-analysis; network pharmacology analysis; ulcerative colitis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Clinical evidence and potential mechanism of Kushen for the treatment of (ulcerative colitis) UC with (damp-heat accumulation syndrome) DHAS.
FIGURE 2
FIGURE 2
Flow diagram of the literature screening and study selection.
FIGURE 3
FIGURE 3
Risk of bias summary.
FIGURE 4
FIGURE 4
Forest plot for the meta-analysis of clinical remission rates.
FIGURE 5
FIGURE 5
Forest plot for the meta-analysis of Clinical response rates.
FIGURE 6
FIGURE 6
Forest plot for the meta-analysis of Chinese medical syndrome scores.
FIGURE 7
FIGURE 7
Forest plot for the meta-analysis of Mayo (endoscopy) scores.
FIGURE 8
FIGURE 8
Forest plot for the meta-analysis of adverse drug reaction rates.
FIGURE 9
FIGURE 9
Overlapping targets of Kushen against (ulcerative colitis) UC and (damp-heat accumulation syndrome) DHAS related genes. (A) The number of common sets of targets between Kushen with UC and DHAS related targets were shown in the Venn diagram. There were 99 targets related to Kushen, 378 targets related DHAS, and 1949 targets related to UC. UC-related targets of Kushen shared 63 common targets, and DHAS shared 10 targets simultaneously. (B) The C-T network of Kushen against UC and DHAS-related targets containing 91 nodes and 292 edges. The yellow vees represent components of Kushen, the blue octagons represent the five TCM symptoms of UC with DHAS, the red diamond represents the disease UC, and the green ellipses represent the targets.
FIGURE 10
FIGURE 10
PPI networks of (ulcerative colitis) UC and UC with (damp-heat accumulation syndrome) DHAS related targets. (A) The PPI network of target genes from Kushen against UC with DHAS related targets. (B) The PPI network of target genes from Kushen against UC-related targets. The ellipse nodes represented targets, and the colors of nodes were illustrated from blue to orange in descending order of degree values.
FIGURE 11
FIGURE 11
Components-targets-pathways network of Kushen. The top 20 enriched KEGG pathways of (ulcerative colitis) UC and UC with (damp-heat accumulation syndrome) DHAS were integrally submitted to Cytoscape for Kushen C-T-P network constructions with nine common pathways of UC and DHAS, 11 unique UC-related pathways, and 11 unique DHAS-related pathways. The yellow, pink, and blue vees represent pathways of unique UC-related pathways, common pathways, and unique DHAS-related pathways, respectively. The red, blue, yellow, and green ellipses represent the disease UC, the TCM symptoms of DHAS, components of Kushen, and targets of Kushen, respectively.
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