Effect of compound sophorae decoction on dextran sodium sulfate (DSS)-induced colitis in mice by regulating Th17/Treg cell balance

Xu, Meng; Duan, Xueyun; Chen, Qian-Yun; Fan, Heng; Hong, Zongchao; Deng, Shuangjiao; Zhang, Nan; Wu, Hui; Dong, Yalan; Liu, Yujin; Zhou, Chengzhi

doi:10.1016/j.biopha.2018.11.087

Cited by 84 publications

(46 citation statements)

References 56 publications

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“…In addition, in a model of colitis, the transplantation of defined microbial flora has been shown to restore the balance of Th17/Tregs (49). Moreover, studies have confirmed that both Compound Sophorae Decoction and Rhubarb Peony Decoction exert protective effects against DSS-induced colitis in mice, and the mechanisms are related to the regulation of the Th17/Treg balance (50,51). Therefore, maintaining the Treg/Th17 balance may provide a treatment strategy for DSS-induced UC.…”

Section: Discussionmentioning

confidence: 94%

Poly(ADP‑ribose) polymerase‑1 inhibitor ameliorates dextran sulfate sodium‑induced colitis in mice by regulating the balance of Th17/Treg cells and inhibiting the NF‑κB signaling pathway

et al. 2020

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Poly(ADP-ribose) polymerase-1 (PARP-1) plays a critical role in inflammatory pathways. The PARP-1 inhibitor, 5-aminoisoquinolinone (5-AIQ), has been demonstrated to exert significant pharmacological effects. The present study aimed to further examine the potential mechanisms of 5-AIQ in a mouse model of dextran sodium sulfate (DSS)-induced colitis. Colitis conditions were assessed by changes in weight, disease activity index, colon length, histopathology and pro-inflammatory mediators. The colonic expression of PARP/NF-κB and STAT3 pathway components was measured by western blot analysis. Flow cytometry was used to analyze the proportion of T helper 17 cells (Th17) and regulatory T cells (Tregs) in the spleen. Western blot analysis and reverse transcription-quantitative PCR were employed to determine the expression of the transcription factors retinoic acid-related orphan receptor and forkhead box protein P3. The results demonstrated that 5-AIQ reduced tissue damage and the inflammatory response in mice with experimental colitis. Moreover, 5-AIQ increased the proportion of Treg cells and decreased the percentage of Th17 cells in the spleen. Furthermore, following 5-AIQ treatment, the main components of the PARP/NF-κB and STAT3 pathways were downregulated. Collectively, these results demonstrate that the PARP-1 inhibitor, 5-AIQ, may suppress intestinal inflammation and protect the colonic mucosa by modulating Treg/Th17 immune balance and inhibiting PARP-1/NF-κB and STAT3 signaling pathways in mice with experimental colitis.

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Section: Discussionmentioning

confidence: 94%

Poly(ADP‑ribose) polymerase‑1 inhibitor ameliorates dextran sulfate sodium‑induced colitis in mice by regulating the balance of Th17/Treg cells and inhibiting the NF‑κB signaling pathway

et al. 2020

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“…When the antioxidant system weakens or oxygen radicals are overproduced, oxygen-free radicals can cause damage to surrounding tissues, denature the protein molecules, inactivate enzymes, and even cause cell-death by promoting inflammatory exudation and edema. Excessive free radicals in the intestinal mucosa of UC patients could covalently combine with the multichain unsaturated fatty acids on the cell membrane, triggering a chain reaction of lipid peroxidation [ 19 , 20 ]. Matrine and oxymatrine can ameliorate the oxidative stress in cells by reducing the absorption of the free fatty acids, enhancing the oxidative utilization of the free fatty acids, enhancing the activity of antioxidant enzymes in cells, and reducing lipid peroxidation [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Analysis of Serum Principal Components Treated with Compound Sophora Decoction and Related Compounds Based on High‐Resolution Mass Spectrometry (HRMS)

Sun

Zhang

Conghui

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. To compare the differences in the serum principal components in ulcerative colitis- (UC-) induced rats, treated with compound Sophora decoction, matrine, oxymatrine monomer mixture, and indirubin monomer, and to provide a modern scientific basis for elucidating the clinical efficacy of compound Sophora decoction for the treatment of UC. Methods. The serum samples of rats from each group were obtained after drug administration, and the serum principal components of each group were analyzed by high-resolution mass spectrometry. Agilent Eclipse XDB C18 chromatographic column (100 mm × 2.1 mm, 3.5 m) was used for separation. The mobile phase was water (A) and methanol (B) (0.1% formic acid) gradient elution, 0–3 min (B: 20%–40%), 3–10 min (B: 40%–54%), 10–25 min (B: 54%), 25–35 min (B: 54%–70%), 35–45 min (B: 70%–80%), 45–50 min (B: 80%), 50–60 min (B: 80%–100%), 70–72 min (B: 100%–20%), and 72–77 min (B: 20%); flow rate, 300 μL/min; column temperature, 40°C; and injection volume, 10 μL. ESI source was selected and scanned in the positive and negative ion modes. The scanning range was 70–1500 m/z; ion-source gas 1 (GS1): 55 psi; ion-source gas 2 (GS2): 60 psi; CUR: 30 psi; ion-source temperature (TEM): 550°C; ion-source voltage (ISVF) : 5500 V/−4500 V; decluster voltage (DP): 100 V; collision energy (CE): 35 V/−35 V; collision energy gain (CES) : 15 V/−15 V; and data acquisition mode: IDA. After the data from each group were imported into MarkView 1.3, the molecular weights and retention times of different substances were obtained and qualitatively analyzed by ChemSpider and PeakView 2.0. Results. In the negative ion mode, 26 differential compounds were identified in the compound Sophora decoction group (FFKST) compared to the model group (M), and 18 differential compounds were identified in the matrine and oxymatrine group (KST) compared to the model group (M). In the positive ion mode, 11 and 7 differential compounds were identified in the compound Sophora decoction group (FFKST) and the matrine and oxymatrine group (KST) compared to the model group (M), respectively. The responses of all compounds in each group were compared with each other. As the different principal component substances in the indirubin group (DYH) displayed little correlation with other groups, the different components in this group were not researched thoroughly. Conclusion. By comparing the differences in the serum principal components from each administration group, we found that the FFKST group exhibited enhanced synthesis of the serum principal components; however, the compound doses of matrine and oxymatrine monomers did not exhibit the same changes in the serum principal components of UC-induced rats. Finally, the traditional Chinese medicine compound is more advantageous than monomers.

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“…Recent advances have subscribed to the belief that continual inflammatory excitation structures a favourable background for UCRCC formation, providing proof that pivotal inflammatory mediators encompassing IL-6, TNF- α , NF- κ B, and IL-17 (also called IL-17A) coupled with Th17 cells are enriched in UC and colorectal cancer [8, 30–34]. Given its remarkable therapeutic capacity of CSD in UC [19, 20], the concept has fueled our hypothesis that CSD may mitigate the progression of UCRCC to a certain degree. Delightedly, in our study, CSD demonstrates an inhibitory effect on the release of these inflammation-related cytokines and secretion of Th17 cells coinciding with reduced occurrence of polyp/tumor and preferable well-being.…”

Section: Discussionmentioning

confidence: 99%

“…Compound sophorae decoction (CSD) is a classical traditional Chinese medicine (TCM) preparation developed from qingre zaoshi liangxue fang (QRZSLXF) [18] has been widely applied in China to medicate UC patients and is clinically efficient [19, 20]. Kushen, videlicet, Sophora flavescens Ait., is the sovereign drug of CSD and is used extensively to treat fibrosis, asthma, inflammatory disorders, ulcers, and solid tumor [19–26].…”

Section: Introductionmentioning

confidence: 99%

Uncovering the Anticancer Mechanism of Compound Sophorae Decoction against Ulcerative Colitis-Related Colorectal Cancer in Mice

Deng

Tang

Duan

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Compound sophorae decoction (CSD), a traditional Chinese medicine (TCM) formula, has been voluminously used in China to deal with ulcerative colitis and gained significant therapeutic effect. Tremendous explorations have unraveled a contributory role of inflammatory bowel disease (IBD) like ulcerative colitis (UC) and Crohn's disease (CD) at the onset of colorectal cancer, scilicet, and colitis-related cancer (CRC). In light of the anti-inflammatory properties of CSD in UC, we appraised its chemoprevention capacity and underlying mechanism in ulcerative colitis-related colorectal cancer (UCRCC), employing a model of azoxymethane (AOM) plus dextran sulfate sodium- (DSS-) induced colorectal cancer (CRC) in C57BL/6 mice. Rapturously, our results illuminated the ameliorative effect of CSD against UCRCC in mice portrayed by lesser polyps or adenomas, attenuated colonic xenograft tumor growth in company with the preferable well-being of mice in contrast to the Model Group. We examined significant downregulation of proinflammatory cytokines such as TNF-α, NF-κB, IL-6, STAT3, and IL-17 after exposure to CSD, with the concomitant repression of inflammation-associated proteins, including COX-2 and iNOS. Independent of this, treatment with CSD declined the proportion of T helper 17 cells (Th17) and protein level of matrix metallopeptidase 9 (MMP-9). Moreover, transmission electron microscopy (TEM) detected observably suppressed mitophagy in mice administered with CSD and that was paralleled by the pro-apoptotic effect as indicated by upregulating caspase-3 together with caspase-9 and deregulating B-cell lymphoma 2 (Bcl-2). In closing, these findings suggest CSD executes the UCRCC-inhibitory activity through counteracting inflammatory responses and rescuing detuning of apoptosis as well as neutralizing overactive mitophagy, concurring to build up an oncosuppressive microenvironment.

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Effect of compound sophorae decoction on dextran sodium sulfate (DSS)-induced colitis in mice by regulating Th17/Treg cell balance

Cited by 84 publications

References 56 publications

Poly(ADP‑ribose) polymerase‑1 inhibitor ameliorates dextran sulfate sodium‑induced colitis in mice by regulating the balance of Th17/Treg cells and inhibiting the NF‑κB signaling pathway

Poly(ADP‑ribose) polymerase‑1 inhibitor ameliorates dextran sulfate sodium‑induced colitis in mice by regulating the balance of Th17/Treg cells and inhibiting the NF‑κB signaling pathway

Differential Analysis of Serum Principal Components Treated with Compound Sophora Decoction and Related Compounds Based on High‐Resolution Mass Spectrometry (HRMS)

Uncovering the Anticancer Mechanism of Compound Sophorae Decoction against Ulcerative Colitis-Related Colorectal Cancer in Mice

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