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

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.

Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

“…Our results suggested that phaseolin (1) reduced NO synthesis and iNOS expression, (2) suppressed pro-inflammatory mediators and increased anti-inflammatory mediators, (3) inhibited cell-to-ECM adhesion through Ninj1 downregulation, (4) reduced cell migration, and MMP expression, and (5) reduced nuclear NF-κB translocation. The inhibitory effect of phaseolin on IL-6 expression was consistent with Chen’s expectations through a network pharmacology analysis [ 6 ].…”

“…Recently, it has been reported that Kushen (Radix Sophorae flavescentis ), which is a promising herbal medicine against inflammation, contains phaseolin as one of the bioactive ingredients [ 36 ]. In addition, Chen et al predicted that phaseolin is as a major bioactive ingredient responsible for the anti-inflammatory activity represented by Kushen based on a component–target–pathway network [ 6 ]. However, the mechanisms underlying the anti-inflammatory effects of Kushen and the biological relevance of its component phaseolin against inflammation are largely unknown.…”

“…In Chinese traditional medicine, Kushen (Radix Sophorae flavescentis ) has long been used for the prevention and/or treatment of various diseases such as ulcerative colitis [ 6 ] and pruritus [ 7 ]. In addition, Kushen has been widely used as an alternative treatment for cancer, and its components have demonstrated anti-tumorigenic effects against prostatic [ 8 ], gastric [ 9 ], and esophageal [ 10 ] cancer cell lines.…”

“…However, the active components responsible for the anti-inflammatory effects of Kushen against ulcerative colitis or pruritus remain unclear. Recently, Chen et al constructed a component–target–pathway network and tentatively identified five bioactive constituents (phaseolin, formononetin, matrine, luteolin, and quercetin) that were responsible for the anti-inflammatory effects of S. flavescentis [ 6 ]. Therefore, it is necessary to determine whether each of these five components represents anti-inflammatory activity and which mechanisms are involved.…”

Kurarinone Attenuates Collagen-Induced Arthritis in Mice by Inhibiting Th1/Th17 Cell Responses and Oxidative Stress

“…Kuraninone is a natural flavonone purified from Sophora flavescens Aiton, one of the traditional Chinese medicinal herbs. Sophora flavescens is known to have anti-inflammatory effects [ 20 ] and is used to treat inflammatory diseases such as ulcerative colitis [ 21 ], Behcet syndrome [ 22 ], arthritis [ 23 ], pulmonary fibrosis [ 24 ], asthma [ 25 ], and influenza infection [ 24 ]. Other studies have also reported anti-inflammatory effects of kuraninone through its potent inhibition of cyclooxygenase (COX)-1 [ 26 ].…”