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Song L, Deng Y, Huang J, Zhu X, Zhong Y, Zhong Q, Zhou W, Liu Y, Zhao H, Ge W, Liu D. Effect of curcumin regulated memory Th7 cells in mice with DSS-induced colitis. Int Immunopharmacol 2025; 145:113770. [PMID: 39642569 DOI: 10.1016/j.intimp.2024.113770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 11/03/2024] [Accepted: 11/30/2024] [Indexed: 12/09/2024]
Abstract
Abnormal activation or dysfunction of memory helper T (mTh) cells is closely associated with the development of ulcerative colitis (UC). Curcumin (Cur), the main component of turmeric, plays a critical role in the treatment of UC due to its favorable anti-inflammatory and immunomodulatory bioactivities. However, whether Cur modulates mTh7 cells to alleviate UC is unknown. In the present study, dextran sulphate sodium (DSS) was administered to establish a colitis model in mice. Our current findings indicated that Cur effectively ameliorated the manifestations of colitis in mice, and had a significant effect in reducing disease activity index (DAI), as well as in the colonic weight and the proportion of colonic weight to colonic length. While Cur reduced the pathological injuries of the colon, restore the length of the colon, inhibited the secretion of IL-7 and IL-21, restored the secretion of IL-2, IL-4, and IL-10. Furthermore, Cur had a regulatory effect on mTh7 cells and their subpopulation status. The results of molecular docking simulations and Surface Plasmon Resonance (SPR) indicated that Cur demonstrates strong interaction capabilities with both IL-7 and IL-7R and reduced the expression levels of IL-7/IL-7R mRNA and protein. It is suggested that the alleviation of DSS-induced colitis by Cur may be achieved by reducing the level of mTh7 cells and inhibiting the activation of IL-7/IL-7R signaling.
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Affiliation(s)
- Lizhao Song
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Yifei Deng
- Clinical Medical School, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Jiaqi Huang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Xiyan Zhu
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Youbao Zhong
- Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Qin Zhong
- School of Nursing, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Wen Zhou
- Nanchang Medical College, Nanchang 330052, Jiangxi Province, China
| | - Yali Liu
- Nanchang Medical College, Nanchang 330052, Jiangxi Province, China
| | - Haimei Zhao
- Formula-Pattern Research Center of Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
| | - Wei Ge
- Department of Proctology, Affiliated Hospital of Jiangxi University of Chinese Medicine, 1688 Meiling Road, Nanchang 330004, Jiangxi Province, China.
| | - Duanyong Liu
- School of Nursing, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Formula-Pattern Research Center of Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
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Zhang X, Zhang H, Wang J, Chen Y, Lin J, Wang Q, Wu C, Chen H, Lin Y. Curcumin attenuates ulcerative colitis via regulation of Sphingosine kinases 1/NF-κB signaling pathway. Biofactors 2025; 51:e70001. [PMID: 39832759 DOI: 10.1002/biof.70001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 01/10/2025] [Indexed: 01/22/2025]
Abstract
Curcumin, a compound from Curcuma longa L., has significant anti-inflammatory properties. However, the mechanisms underlying its anti-inflammatory activity in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) remain inadequately understood. This study aimed to further elucidate the molecular mechanisms of curcumin DSS-induced UC mice. Our data showed that curcumin alleviated DSS-induced colitis by reducing intestinal damage and inflammation, increasing goblet cells in colon tissues. Enzyme-linked immunosorbent assay revealed that curcumin reduced the expression of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1β, and interleukin-8) in serum and myeloperoxidase in colon tissues. A comprehensive analysis integrating network pharmacology and RNA sequencing (RNA-seq) revealed significant enrichment of the nuclear factor kappa B (NF-κB) signaling pathways. Notably, RNA-seq analysis demonstrated that curcumin significantly downregulated the mRNA expression of sphingosine kinase 1 (SphK1). Furthermore, molecular docking analysis showed that curcumin can bind to SphK1 and NF-κB. Additionally, curcumin was found to inhibit the activation of the SphK1/NF-κB signaling pathway in DSS-induced UC colon tissue. This study addresses pharmacologic and mechanistic perspectives of curcumin that ameliorates DSS-induced UC and inflammatory response.
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Affiliation(s)
- Xiuli Zhang
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Hao Zhang
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Jingting Wang
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Yangyi Chen
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Jiumao Lin
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Qingshui Wang
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Cheng Wu
- Basic Medical Experimental Teaching Center, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China
| | - Hui Chen
- Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Yao Lin
- College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
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Gao F, Deng S, Liu Y, Wu P, Huang L, Zhu F, Wei C, Yuan Y, Gui Y, Tian Y, Fan H, Wu H. Compound sophora decoction alleviates ulcerative colitis by regulating macrophage polarization through cGAS inhibition: network pharmacology and experimental validation. Aging (Albany NY) 2024; 16:6921-6936. [PMID: 38613801 PMCID: PMC11087132 DOI: 10.18632/aging.205734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Accepted: 03/18/2024] [Indexed: 04/15/2024]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a refractory disease with complex pathogenesis, and its pathogenesis is not clear. The present study aimed to investigate the potential target and related mechanism of Compound Sophora Decoction (CSD) in treating UC. METHODS A network pharmacology approach predicted the components and targets of CSD to treat UC, and cell and animal experiments confirmed the findings of the approach and a new target for CSD treatment of UC. RESULTS A total of 155 potential targets were identified for CSD treatment of UC, with some related to macrophage polarization, such as nitric oxide synthase (NOS2), also known as inducible nitric oxide synthase (iNOS). GO and KEGG enrichment analysis indicated that oxidative stress response and multiple inflammatory signaling pathways such as TNF-α may play a significant role. In vitro experiments revealed that Interferon-stimulated DNA (ISD) interference can cause polarization imbalances in Raw 264.7 and bone marrow-derived macrophages (BMDMs). Flow cytometry demonstrated that polarization of macrophages in the intestine, spleen, and lymph nodes in vivo was also unbalanced after dextran sulfate sodium (DSS) modeling with pathological intestinal injury. Both in vitro and in vivo studies indicated that after inducing inflammation, the levels of macrophage polarization-related markers (iNOS and Arg1) and inflammation-related factors (CCL17, IL10, TNF-α, and CXCL10) changed, accompanied by increased expression of cGAS. However, CSD treatment based on inflammation can inhibit the expression of cGAS protein and mRNA, lower the level of inflammatory factors, promote the expression of anti-inflammatory factors, and regulate macrophage polarization. CONCLUSION We concluded that CSD alleviated DSS-induced UC by inhibiting cGAS, thus regulating macrophage polarization.
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Affiliation(s)
- Fei Gao
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Shuangjiao Deng
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yujin Liu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Pengcheng Wu
- Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Lifen Huang
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Feng Zhu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Chunzhu Wei
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yuyi Yuan
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yang Gui
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yushi Tian
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Heng Fan
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Hui Wu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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Ananthakrishnan AN. Is it Time for the Alternative to Move to the Mainstream? Clin Gastroenterol Hepatol 2024; 22:235-236. [PMID: 37453593 DOI: 10.1016/j.cgh.2023.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 07/05/2023] [Indexed: 07/18/2023]
Affiliation(s)
- Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
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Ben-Horin S, Salomon N, Karampekos G, Viazis N, Lahat A, Ungar B, Eliakim R, Kuperstein R, Kriger-Sharabi O, Reiss-Mintz H, Yanai H, Dotan I, Zittan E, Maharshak N, Hirsch A, Weitman M, Mantzaris GJ, Kopylov U. Curcumin-QingDai Combination for Patients With Active Ulcerative Colitis: A Randomized, Double-Blinded, Placebo-Controlled Trial. Clin Gastroenterol Hepatol 2024; 22:347-356.e6. [PMID: 37302449 DOI: 10.1016/j.cgh.2023.05.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/13/2023]
Abstract
BACKGROUND & AIMS We evaluated the efficacy of herbal combination of curcumin-QingDai (CurQD) in active ulcerative colitis (UC). METHODS Part I was an open-label trial of CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index score of 5 or higher and a Mayo endoscopic subscore of 2 or higher. Part II was a placebo-controlled trial conducted in Israel and Greece, randomizing active UC patients at a 2:1 ratio to enteric-coated CurQD 3 g/d or placebo for 8 weeks. The co-primary outcome was clinical response (reduction in the Simple Clinical Colitis Activity Index of ≥3 points) and an objective response (Mayo endoscopic subscore improvement of ≥1 or a 50% fecal calprotectin reduction). Responding patients continued either maintenance curcumin or placebo alone for an additional 8 weeks. Aryl-hydrocarbon receptor activation was assessed by cytochrome P450 1A1 (CYP1A1) mucosal expression. RESULTS In part I, 7 of 10 patients responded and 3 of 10 achieved clinical remission. Of 42 patients in part II, the week 8 co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (P = .033). Clinical response was observed in 85.7% vs 30.7% (P < .001), clinical remission in 14 of 28 (50%) vs 1 of 13 (8%; P = .01), a 50% calprotectin reduction in 46.4% vs 15.4% (P = .08), and endoscopic improvement in 75% vs 20% (P = .036) in the CurQD and placebo groups, respectively. Adverse events were comparable between groups. By week 16, curcumin-maintained clinical response, clinical remission, and clinical biomarker response rates were 93%, 80%, and 40%, respectively. CurQD uniquely up-regulated mucosal CYP1A1 expression, which was not observed among patients receiving placebo, mesalamine, or biologics. CONCLUSIONS In this placebo-controlled trial, CurQD was effective for inducing response and remission in active UC patients. The aryl-hydrocarbon receptor pathway may merit further study as a potential UC treatment target. CLINICALTRIALS gov ID: NCT03720002.
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Affiliation(s)
- Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel; School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
| | - Nir Salomon
- Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel.
| | - Georgios Karampekos
- Department of Gastroenterology, Evangelismos-Polykliniki General Hospital of Athens, Athens, Greece
| | - Nikos Viazis
- Department of Gastroenterology, Evangelismos-Polykliniki General Hospital of Athens, Athens, Greece
| | - Adi Lahat
- Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel; School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Bella Ungar
- Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel; School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel; School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Rafael Kuperstein
- School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Leviev Heart Center, Sheba Medical Center, Ramat-Gan, Israel
| | | | - Hilla Reiss-Mintz
- Gastroenterology Department, Mayanei HaYeshua Medical Center, Bnei Brak, Israel
| | - Henit Yanai
- School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Iris Dotan
- School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Eran Zittan
- Department of Gastroenterology and Liver Diseases, Emek Medical Center, Afula, Israel; The Rappaport Faculty of Medicine Technion, Israel Institute of Technology, Haifa, Israel
| | - Nitsan Maharshak
- School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Gastroenterology, Tel Aviv Medical Center, Tel-Aviv, Israel
| | - Ayal Hirsch
- School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Gastroenterology, Tel Aviv Medical Center, Tel-Aviv, Israel
| | - Michal Weitman
- MS Unit, Chemistry Department, Bar llan University, Ramat-Gan, Israel
| | - Gerassimos J Mantzaris
- Department of Gastroenterology, Evangelismos-Polykliniki General Hospital of Athens, Athens, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel; School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Zheng LX, Guo KE, Huang JQ, Liu MH, Deng BL, Liu DY, Zhou BG, Zhou W, Zhong YB, Zhao HM. Curcumin alleviated dextran sulfate sodium-induced colitis by recovering memory Th/Tfh subset balance. World J Gastroenterol 2023; 29:5226-5239. [PMID: 37901446 PMCID: PMC10600958 DOI: 10.3748/wjg.v29.i36.5226] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 08/26/2023] [Accepted: 09/07/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND Restoration of immune homeostasis by targeting the balance between memory T helper (mTh) cells and memory follicular T helper (mTfh) cells is a potential therapeutic strategy against ulcerative colitis (UC). Because of its anti-inflammatory and immunomodulatory properties, curcumin (Cur) is a promising drug for UC treatment. However, fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis. AIM To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium (DSS) in mice by regulating the mTh and mTfh immune homeostasis. METHODS Balb/c mice were administered 3% and 2% DSS to establish the UC model and treated with Cur (200 mg/kg/d) by gavage on days 11-17. On the 18th d, all mice were anesthetized and euthanized, and the colonic length, colonic weight, and colonic weight index were evaluated. Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining. Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry. Western blotting was performed to detect SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in colon tissues. RESULTS Cur effectively mitigates DSS-induced colitis, facilitates the restoration of mouse weight and colonic length, and diminishes the colonic weight and colonic weight index. Simultaneously, it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane. While the percentage of Th1, mTh1, Th7, mTh7, Th17, mTh17, Tfh1, mTfh1, Tfh7, mTfh7, Tfh17, and mTfh17 cells decreased after Cur treatment of the mice for 7 d, and the frequency of mTh10, Th10, mTfh10, and Tfh10 cells in the mouse spleen increased. Further studies revealed that Cur administration prominently decreased the SOCS-1, SOCS-3, STAT3, p-STAT3, JAK1, p-JAK1, and NF-κB p65 protein expression levels in the colon tissue. CONCLUSION Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage, potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.
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Affiliation(s)
- Lin-Xin Zheng
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Kai-En Guo
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Jia-Qi Huang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Miao-Hua Liu
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Bai-Ling Deng
- College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Duan-Yong Liu
- Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Bu-Gao Zhou
- Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Wen Zhou
- Nanchang Medical College, Nanchang 330052, Jiangxi Province, China
| | - You-Bao Zhong
- Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Hai-Mei Zhao
- College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
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Yanai H, Salomon N, Lahat A, Ungar B, Eliakim R, Kriger-Sharabi O, Reiss-Mintz H, Koslowsky B, Shitrit ABG, Tamir-Degabli N, Dotan I, Zittan E, Maharshak N, Hirsch A, Ben-Horin S, Kopylov U. Real-world experience with Curcumin-QingDai combination for patients with active ulcerative colitis: A retrospective multicentre cohort study. Aliment Pharmacol Ther 2023; 58:175-181. [PMID: 37157131 DOI: 10.1111/apt.17538] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/06/2023] [Accepted: 04/19/2023] [Indexed: 05/10/2023]
Abstract
BACKGROUND Curcumin and QingDai (QD, Indigo) have been shown to be effective for treating active ulcerative colitis (UC). AIM To evaluate the real-world experience with the Curcumin-QingDai (CurQD) herbal combination to induce remission in active UC. METHODS A retrospec-tive multicentre adult cohort study from five tertiary academic centres (2018-2022). Active UC was defined as a Simple Clinical Colitis Activity Index (SCCAI) ≥ 3. Patients were induced by CurQD. The primary outcome was clinical remission at weeks 8-12, defined as SCCAI ≤2 and a decrease ≥3 points from baseline. Secondary outcomes were clinical response (SCCAI decrease ≥3 points), corticosteroid-free remission, faecal calprotectin (FC) response (reduction ≥50%), FC normalisation (FC ≤100 μg/g for patients with FC ≥300 μg/g at baseline), and safety. All outcomes were analysed for patients who were maintaining stable treatment. RESULTS Eighty-eight patients were included; 50% were biologics/small molecules experienced, and 36.5% received ≥2 biologics/small molecules. Clinical remission was achieved in 41 (46.5%), and clinical response in 53 (60.2%). Median SCCAI decreased from 7 (IQR:5-9) to 2 (IQR:1-3); p < 0.0001. Of the 26 patients on corticosteroids at baseline, seven achieved corticosteroid-free remission. Among 43 biologics/small molecules experienced patients, clinical remission was achieved in 39.5% and clinical response in 58.1%. FC normalisation and response were achieved in 17/29 and 27/33, respectively. Median FC decreased from 1000 μg/g (IQR:392-2772) at baseline to 75 μg/g (IQR:12-136) at the end of inductions (n = 30 patients with paired samples); p < 0.0001. No overt safety signals emerged. CONCLUSION In this real-world cohort, CurQD effectively induced clinical and biomarker remission in patients with active UC, including patients who were biologics/small molecules experienced.
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Affiliation(s)
- Henit Yanai
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Nir Salomon
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Adi Lahat
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Bella Ungar
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Rami Eliakim
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | | | - Hilla Reiss-Mintz
- Department of Gastroenterology, Mayanei HaYeshua Medical Center, Bnei Brak, Israel
| | - Benjamin Koslowsky
- Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Ariella Bar-Gil Shitrit
- Digestive Diseases Institute, Shaare Zedek Medical Center, Jerusalem, Israel
- Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Natalie Tamir-Degabli
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Internal Medicine E, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Eran Zittan
- Department of Gastroenterology and Liver Diseases, Emek Medical Center, Afula, Israel
- The Rappaport Faculty of Medicine Technion-Israel Institute of Technology, Haifa, Israel
| | - Nitsan Maharshak
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Gastroenterology, Tel Aviv Medical Center, Tel-Aviv, Israel
| | - Ayal Hirsch
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Gastroenterology, Tel Aviv Medical Center, Tel-Aviv, Israel
| | - Shomron Ben-Horin
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Uri Kopylov
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
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Alhalabi M. Ustekinumab for steroid-refractory pancolitis in a biologically naive child: A case report and literature review. Medicine (Baltimore) 2023; 102:e33061. [PMID: 36862878 PMCID: PMC9981362 DOI: 10.1097/md.0000000000033061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
Ustekinumab is not recommended for the treatment of children with inflammatory bowel disease, but its off-label use is increasing despite a lack of pediatric pharmacokinetic data. The purpose of this review is to evaluate the therapeutic effects of Ustekinumab on children with inflammatory bowel disease and to recommend the best treatment regimen. Ustekinumab was the first biological treatment for a 10-year-old Syrian boy with steroid-refractory pancolitis who weighed 34 kg. A 260 mg/kg (~6 mg/kg) intravenous dose was followed by 90 mg of subcutaneous Ustekinumab at week 8 (induction). The patient was supposed to receive the first maintenance dose after twelve weeks, but after ten weeks, he developed acute severe ulcerative colitis which was managed according to treatment guidelines, except receiving 90 mg of subcutaneous Ustekinumab when he was discharged. The maintenance dose of 90 mg subcutaneous Ustekinumab was intensified to every 8 weeks. Throughout the treatment period, he achieved and maintained clinical remission. In pediatric inflammatory bowel disease, a dose of intravenous ~6 mg/kg of Ustekinumab is a common induction regimen, while children weighing < 40 kg may require a dose of 9 mg/kg. For maintenance, children may require 90 mg of subcutaneous Ustekinumab every 8 weeks. The outcome of this case report is interesting with improved clinical remission and highlighting the expansion of clinical trials on Ustekinumab for children.
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Affiliation(s)
- Marouf Alhalabi
- Syrian Board in Gastroenterology, a Gastroenterologist at the Gastroenterology Department of Damascus Hospital, Damascus, Syria
- * Correspondence: Marouf Alhalabi, Syrian Board in Gastroenterology, a Gastroenterologist at the Gastroenterology Department of Damascus Hospital, Almujtahed Street, Damascus, Syria (e-mail: )
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Old but Fancy: Curcumin in Ulcerative Colitis-Current Overview. Nutrients 2022; 14:nu14245249. [PMID: 36558408 PMCID: PMC9781182 DOI: 10.3390/nu14245249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/06/2022] [Accepted: 12/07/2022] [Indexed: 12/13/2022] Open
Abstract
Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD). It is a chronic autoimmune inflammation of unclear etiology affecting the colon and rectum, characterized by unpredictable exacerbation and remission phases. Conventional treatment options for UC include mesalamine, glucocorticoids, immunosuppressants, and biologics. The management of UC is challenging, and other therapeutic options are constantly being sought. In recent years more attention is being paid to curcumin, a main active polyphenol found in the turmeric root, which has numerous beneficial effects in the human body, including anti-inflammatory, anticarcinogenic, and antioxidative properties targeting several cellular pathways and making an impact on intestinal microbiota. This review will summarize the current knowledge on the role of curcumin in the UC therapy.
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Yang Z, Lin S, Feng W, Liu Y, Song Z, Pan G, Zhang Y, Dai X, Ding X, Chen L, Wang Y. A potential therapeutic target in traditional Chinese medicine for ulcerative colitis: Macrophage polarization. Front Pharmacol 2022; 13:999179. [PMID: 36147340 PMCID: PMC9486102 DOI: 10.3389/fphar.2022.999179] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 08/12/2022] [Indexed: 11/13/2022] Open
Abstract
Intestinal macrophages are the main participants of intestinal immune homeostasis and intestinal inflammation. Under different environmental stimuli, intestinal macrophages can be polarized into classical activated pro-inflammatory phenotype (M1) and alternative activated anti-inflammatory phenotype (M2). Its different polarization state is the “guide” to promoting the development and regression of inflammation. Under normal circumstances, intestinal macrophages can protect the intestine from inflammatory damage. However, under the influence of some genetic and environmental factors, the polarization imbalance of intestinal M1/M2 macrophages will lead to the imbalance in the regulation of intestinal inflammation and transform the physiological inflammatory response into pathological intestinal injury. In UC patients, the disorder of intestinal inflammation is closely related to the imbalance of intestinal M1/M2 macrophage polarization. Therefore, restoring the balance of M1/M2 macrophage polarization may be a potentially valuable therapeutic strategy for UC. Evidence has shown that traditional Chinese medicine (TCM) has positive therapeutic effects on UC by restoring the balance of M1/M2 macrophage polarization. This review summarizes the clinical evidence of TCM for UC, the vital role of macrophage polarization in the pathophysiology of UC, and the potential mechanism of TCM regulating macrophage polarization in the treatment of UC. We hope this review may provide some new enlightenment for the clinical treatment, fundamental research, and research and development of new Chinese medicine of UC.
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Affiliation(s)
- Zhihua Yang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shanshan Lin
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wanying Feng
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yangxi Liu
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Zhihui Song
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Guiyun Pan
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuhang Zhang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiangdong Dai
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xinya Ding
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lu Chen
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Lu Chen, ; Yi Wang,
| | - Yi Wang
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- *Correspondence: Lu Chen, ; Yi Wang,
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Caban M, Lewandowska U. Polyphenols and the potential mechanisms of their therapeutic benefits against inflammatory bowel diseases. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Zhang X, Deng J, Tang Y, Guan X, Chen X, Fan J. Zingiberaceae plants/curcumin consumption and multiple health outcomes: An umbrella review of systematic reviews and meta-analyses of randomized controlled trials in humans. Phytother Res 2022; 36:3080-3101. [PMID: 35623903 DOI: 10.1002/ptr.7500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 02/17/2022] [Accepted: 05/06/2022] [Indexed: 01/10/2023]
Abstract
This umbrella review is to recapitulate and grade the available evidence of associations between consumption of Zingiberaceae plants/curcumin (Cur) and multiple health-related outcomes. This study included 161 meta-analyses of randomized controlled trials in 76 articles with 67 unique health outcomes. Data on heterogeneity and publication bias are considered to assess the quality of evidence. Based on the different impact of Zingiberaceae plants/Cur on human health, the advantages outweigh the disadvantages. Zingiberaceae plants/Cur can mainly improve metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and some chronic inflammatory diseases, likewise, obviously relief the pain of osteoarthritis and related diseases. Ginger supplements have been shown to improve vomiting during pregnancy and to relieve nausea and vomiting caused by chemotherapy and surgery. The surgery is any type of surgery, including laparoscopic surgery, gynecological surgery and mixed surgery. Beneficial associations were found with Cur intervention in gastrointestinal, neurological and oral diseases. Zingiberaceae plants/Cur are generally safe and favorable for multiple health outcomes in humans. High-quality research is further needed to prove the observed associations.
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Affiliation(s)
- Xiaofeng Zhang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Jinlan Deng
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Yujun Tang
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xiaoxian Guan
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xiaoli Chen
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Jianming Fan
- Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, China
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Rahiman N, Markina YV, Kesharwani P, Johnston TP, Sahebkar A. Curcumin-based nanotechnology approaches and therapeutics in restoration of autoimmune diseases. J Control Release 2022; 348:264-286. [PMID: 35649486 DOI: 10.1016/j.jconrel.2022.05.046] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 05/24/2022] [Accepted: 05/26/2022] [Indexed: 12/15/2022]
Abstract
Autoimmune diseases usually arise as a result of an aberrant immune system attack on normal tissues of the body, which leads to a cascade of inflammatory reactions. The immune system employs different types of protective and anti-inflammatory cells for the regulation of this process. Curcumin is a known natural anti-inflammatory agent that inhibits pathological autoimmune processes by regulating inflammatory cytokines and their associated signaling pathways in immune cells. Due to the unstable nature of curcumin and its susceptibility to either degradation, or metabolism into other chemical entities (i.e., metabolites), encapsulation of this agent into various nanocarriers would appear to be an appropriate strategy for attaining greater beneficial effects from curcumin as it pertains to immunomodulation. Many studies have focused on the design and development of curcumin nanodelivery systems (micelles, dendrimers, and diverse nanocarriers) and are summarized in this review in order to obtain greater insight into novel drug delivery systems for curcumin and their suitability for the management of autoimmune diseases.
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Affiliation(s)
- Niloufar Rahiman
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad, Iran
| | - Yuliya V Markina
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Avtsyn Research Institute of Human Morphology of FSBI "Petrovsky National Research Center of Surgery", 3 Tsyurupy Str., 117418, Moscow, Russia
| | - Prashant Kesharwani
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran..
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Shi H, Wang D, Chen W, Li Y, Si G, Yang T. Quality of Evidence Supporting the Role of Supplement Curcumin for the Treatment of Ulcerative Colitis: An Overview of Systematic Reviews. Gastroenterol Res Pract 2022; 2022:3967935. [PMID: 35251163 PMCID: PMC8896949 DOI: 10.1155/2022/3967935] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/07/2022] [Accepted: 02/08/2022] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES Curcumin is a potential complementary treatment for ulcerative colitis (UC). This overview systematically summarizes and evaluates the existing evidence of curcumin in the treatment of UC. METHODS Two researchers searched seven databases for systematic reviews (SRs)/meta-analyses (MAs) which are about randomized controlled trials (RCTs) on curcumin for UC. Two researchers use the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the included SRs/MAs. RESULTS Seven published SRs/MAs were included in our study. According to the results of the AMSTAR-2 assessment, all SRs/MAs are considered to be of very low quality. According to the ROBIS evaluation results, no SR/MA has been assessed as a low risk of bias. According to the results of the PRISMA checklist assessment, no SR/MA has been fully reported on the PRISMA checklist. According to GRADE, a total of 19 outcome indicators extracted from the included SRs/MAs were evaluated. The quality of evidence was 10 moderate, 6 low, and 3 very low. CONCLUSIONS Curcumin may be an effective and safe complementary treatment for UC. However, further standard and comprehensive SRs/MAs and RCTs are needed to provide an evidence-based medical rationale for this.
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Affiliation(s)
- Hongshuo Shi
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Dan Wang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Wenqiang Chen
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yinghao Li
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Guomin Si
- Department of Traditional Chinese Medicine, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Tiantian Yang
- Department of Traditional Chinese Medicine, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
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15
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Maia PDDS, Baião DDS, Nanini HF, da Silva VPF, Frambach LB, Cabral IM, Pêgo B, Ribeiro BE, Pavão MSG, Paschoalin VMF, de Souza HSP, Pierucci APTR. Bioactive Compounds from Pale Ale Beer Powder Attenuate Experimental Colitis in BALB/c Mice. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27041194. [PMID: 35208981 PMCID: PMC8877795 DOI: 10.3390/molecules27041194] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/02/2022] [Accepted: 02/07/2022] [Indexed: 12/19/2022]
Abstract
Phenolic compounds (PCs) present in foods are associated with a decreased risk of developing inflammatory diseases. The aim of this study was to extract and characterize PCs from craft beer powder and evaluate their potential benefits in an experimental model of inflammatory bowel disease (IBD). PCs were extracted and quantified from pure beer samples. BALB/c mice received either the beer phenolic extract (BPE) or beer powder fortified with phenolic extract (BPFPE) of PCs daily for 20 days by gavage. Colon samples were collected for histopathological and immunohistochemical analyses. Dextran sodium sulfate (DSS)-induced mice lost more weight, had reduced colon length, and developed more inflammatory changes compared with DSS-induced mice treated with either BPE or BPFPE. In addition, in DSS-induced mice, the densities of CD4- and CD11b-positive cells, apoptotic rates, and activation of NF-κB and p-ERK1/2 MAPK intracellular signaling pathways were higher in those treated with BPE and BPFPE than in those not treated. Pretreatment with the phenolic extract and BPFPE remarkably attenuated DSS-induced colitis. The protective effect of PCs supports further investigation and development of therapies for human IBD.
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Affiliation(s)
- Paola D. D. S. Maia
- Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 393, Rio de Janeiro 21941-590, Brazil; (P.D.D.S.M.); (V.P.F.d.S.); (L.B.F.); (I.M.C.); (A.P.T.R.P.)
| | - Diego dos Santos Baião
- Institute of Chemistry, Federal University of Rio de Janeiro, Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, Brazil; (D.d.S.B.); (V.M.F.P.)
| | - Hayandra F. Nanini
- Department of Clinical Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, 11th floor, Rio de Janeiro 21941-617, Brazil; (H.F.N.); (B.P.); (B.E.R.)
| | - Victor Paulo F. da Silva
- Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 393, Rio de Janeiro 21941-590, Brazil; (P.D.D.S.M.); (V.P.F.d.S.); (L.B.F.); (I.M.C.); (A.P.T.R.P.)
| | - Lissa Bantim Frambach
- Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 393, Rio de Janeiro 21941-590, Brazil; (P.D.D.S.M.); (V.P.F.d.S.); (L.B.F.); (I.M.C.); (A.P.T.R.P.)
| | - Iuri Matheus Cabral
- Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 393, Rio de Janeiro 21941-590, Brazil; (P.D.D.S.M.); (V.P.F.d.S.); (L.B.F.); (I.M.C.); (A.P.T.R.P.)
| | - Beatriz Pêgo
- Department of Clinical Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, 11th floor, Rio de Janeiro 21941-617, Brazil; (H.F.N.); (B.P.); (B.E.R.)
| | - Beatriz E. Ribeiro
- Department of Clinical Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, 11th floor, Rio de Janeiro 21941-617, Brazil; (H.F.N.); (B.P.); (B.E.R.)
| | - Mauro Sérgio Gonçalves Pavão
- Institute of Medical Biochemistry, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, 4th floor, Rio de Janeiro 21941-617, Brazil;
| | - Vania M. F. Paschoalin
- Institute of Chemistry, Federal University of Rio de Janeiro, Av. Athos da Silveira Ramos, 149, Rio de Janeiro 21941-909, Brazil; (D.d.S.B.); (V.M.F.P.)
| | - Heitor S. P. de Souza
- Department of Clinical Medicine, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco 255, 11th floor, Rio de Janeiro 21941-617, Brazil; (H.F.N.); (B.P.); (B.E.R.)
- D’Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro 22281-100, Brazil
- Correspondence: ; Tel.: +55-21-3938-2669
| | - Anna Paola T. R. Pierucci
- Basic and Experimental Nutrition Department, Josué de Castro Nutrition Institute, Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 393, Rio de Janeiro 21941-590, Brazil; (P.D.D.S.M.); (V.P.F.d.S.); (L.B.F.); (I.M.C.); (A.P.T.R.P.)
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Sawayama H, Miyamoto Y, Yoshida N, Baba H. Essential updates 2020/2021: Colorectal diseases (benign)—Current topics in the surgical and medical treatment of benign colorectal diseases. Ann Gastroenterol Surg 2022; 6:321-335. [PMID: 35634190 PMCID: PMC9130914 DOI: 10.1002/ags3.12548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 12/27/2021] [Indexed: 11/23/2022] Open
Abstract
The development of new drugs for inflammatory bowel disease (IBD) is remarkable, and treatment strategies using multiple agents and various techniques are required; however, the treatment strategy is likely to be complex. Therefore, appropriate evaluation of traditional surgical treatment strategies and accurate knowledge of the efficacy and limitations of novel treatments are required. Total infectious complications were found to be associated with the use of corticosteroids and anti‐tumor necrosis factor‐α agents, but not with immunomodulators, anti‐integrin agents, and 5‐aminosalicylic acid. Regarding surgical procedures for IBD, conceived anastomosis methods, including Kono‐S for Crohn's disease stenosis, are associated with better outcomes than conventional techniques. Autologous cell transplantation for Crohn's fistulae has been shown to have a favorable outcome. Diverticulitis is increasing and will be treated more frequently in the future. Risk factors for the incidence of diverticulitis and differences in pathogenesis according to right or left side diverticulitis have been reported. Antibiotic therapy may be omitted for uncomplicated diverticulitis. Moreover, regarding surgical procedures, both bowel resection and anastomosis are associated with favorable short‐term outcomes, higher stoma closure rate, and superior medical economy compared to Hartmann's procedure. Risk factors for recurrence after diverticulitis surgery may provide better postoperative follow‐up. In this review, we explore the current topics of colorectal benign diseases, focusing on IBD and diverticulitis, based on clinical trials and meta‐analyses from 2020‐2021. This review consolidates the available knowledge and improves the quality of surgical procedures and perioperative management for IBD and diverticulitis.
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Affiliation(s)
- Hiroshi Sawayama
- Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery Graduate School of Medical Sciences Kumamoto University Kumamoto Japan
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Dibba P, Kothari M, Grosman I. Prebiotics, Probiotics, and Dietary Supplements. NUTRITION, WEIGHT, AND DIGESTIVE HEALTH 2022:169-192. [DOI: 10.1007/978-3-030-94953-2_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Peng Y, Ao M, Dong B, Jiang Y, Yu L, Chen Z, Hu C, Xu R. Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:4503-4525. [PMID: 34754179 PMCID: PMC8572027 DOI: 10.2147/dddt.s327378] [Citation(s) in RCA: 283] [Impact Index Per Article: 70.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 08/30/2021] [Indexed: 01/08/2023]
Abstract
Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.
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Affiliation(s)
- Ying Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Mingyue Ao
- State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Baohua Dong
- State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Yunxiu Jiang
- State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Lingying Yu
- State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Zhimin Chen
- State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Changjiang Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.,Neo-Green Pharmaceutical Co., Ltd., Chengdu, People's Republic of China
| | - Runchun Xu
- State Key Laboratory of Southwestern Chinese Medicine Resources; Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
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Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis. Gastroenterol Res Pract 2021; 2021:5570796. [PMID: 34659400 PMCID: PMC8514927 DOI: 10.1155/2021/5570796] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 09/01/2021] [Accepted: 09/21/2021] [Indexed: 02/06/2023] Open
Abstract
Curcumin is a natural polyphenol and is supposed to possess antioxidant, anti-inflammatory, anticancer, and antiapoptotic properties. Although some studies have reported the therapeutic effects of curcumin on ulcerative colitis (UC), the specific mechanism remains unclear. An in vitro coculture model of Caco-2 and differentiated THP-1 cells was established. After administration of curcumin (10 μM), Western blot analysis was performed to evaluate the protein levels of tight junction (TJ) proteins zonula occludens- (ZO-) 1 and claudin-1. Annexin V-APC/7-AAD assays and flow cytometry were conducted to assess Caco-2 cell apoptosis. The expression levels of oxidative stress and endoplasmic reticulum stress- (ERS-) related molecules were determined by Western blot analysis. Curcumin administration significantly upregulated ZO-1 and claudin-1 protein levels and reduced Caco-2 cell apoptosis. The protein levels of oxidative stress markers inducible nitric oxide synthase (iNOS) and γH2AX and ERS-induced apoptosis-related molecules C/EBP homologous protein (CHOP) and cleaved caspase-12 were significantly downregulated upon curcumin treatment. Furthermore, curcumin administration greatly blocked the protein kinase-like endoplasmic reticulum kinase- (PERK-) eukaryotic translation initiation factor 2α- (eIF2α-) activating transcription factor 4- (ATF4-) CHOP signaling pathway. Curcumin enhanced intestinal epithelial barrier integrity in the in vitro coculture model by upregulating TJ protein expressions and reducing intestinal epithelial cell apoptosis. The potential mechanisms may be suppression of ERS and subsequent apoptosis.
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Colonic macrophage-targeted curcumin nanoparticles alleviate DSS-induced colitis in mice through the NF-kappa B pathway. FOOD BIOSCI 2021. [DOI: 10.1016/j.fbio.2021.101089] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Abdel-Tawab M. Considerations to Be Taken When Carrying Out Medicinal Plant Research-What We Learn from an Insight into the IC 50 Values, Bioavailability and Clinical Efficacy of Exemplary Anti-Inflammatory Herbal Components. Pharmaceuticals (Basel) 2021; 14:437. [PMID: 34066427 PMCID: PMC8148151 DOI: 10.3390/ph14050437] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 04/23/2021] [Accepted: 04/29/2021] [Indexed: 12/11/2022] Open
Abstract
Medicinal plants represent a big reservoir for discovering new drugs against all kinds of diseases including inflammation. In spite the large number of promising anti-inflammatory plant extracts and isolated components, research on medicinal plants proves to be very difficult. Based on that background this review aims to provide a summarized insight into the hitherto known pharmacologically active concentrations, bioavailability, and clinical efficacy of boswellic acids, curcumin, quercetin and resveratrol. These examples have in common that the achieved plasma concentrations were found to be often far below the determined IC50 values in vitro. On the other hand demonstrated therapeutic effects suggest a necessity of rethinking our pharmacokinetic understanding. In this light this review discusses the value of plasma levels as pharmacokinetic surrogates in comparison to the more informative value of tissue concentrations. Furthermore the need for new methodological approaches is addressed like the application of combinatorial approaches for identifying and pharmacokinetic investigations of active multi-components. Also the physiological relevance of exemplary in vitro assays and absorption studies in cell-line based models is discussed. All these topics should be ideally considered to avoid inaccurate predictions for the efficacy of herbal components in vivo and to unlock the "black box" of herbal mixtures.
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Affiliation(s)
- Mona Abdel-Tawab
- Central Laboratory of German Pharmacists, Carl-Mannich-Str. 20, 65760 Eschborn, Germany; ; Tel.: +49-6196-937-955
- Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University, Max-von-Laue-Straße 9, 60438 Frankfurt am Main, Germany
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Hagan M, Hayee BH, Rodriguez-Mateos A. (Poly)phenols in Inflammatory Bowel Disease and Irritable Bowel Syndrome: A Review. Molecules 2021; 26:1843. [PMID: 33805938 PMCID: PMC8036772 DOI: 10.3390/molecules26071843] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 03/22/2021] [Accepted: 03/23/2021] [Indexed: 12/12/2022] Open
Abstract
(Poly)phenols (PPs) may have a therapeutic benefit in gastrointestinal (GI) disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The aim of this review is to summarise the evidence-base in this regard. Observational evidence does not give a clear indication that PP intake has a preventative role for IBD or IBS, while interventional studies suggest these compounds may confer symptomatic and health-related quality of life improvements in known patients. There are inconsistent results for effects on markers of inflammation, but there are promising reports of endoscopic improvement. Work on the effects of PPs on intestinal permeability and oxidative stress is limited and therefore conclusions cannot be formed. Future work on the use of PPs in IBD and IBS will strengthen the understanding of clinical and mechanistic effects.
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Affiliation(s)
- Marilyn Hagan
- Department of Nutrition and Dietetics, Royal Papworth Hospital NHS Foundation Trust, Cambridge CB2 0AY, UK;
| | - Bu' Hussain Hayee
- Department of Gastroenterology, King’s College Hospital NHS Foundation Trust, London SE5 9RS, UK;
| | - Ana Rodriguez-Mateos
- Department of Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, London WC2R 2LS, UK
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23
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Goulart RDA, Barbalho SM, Rubira CJ, Araújo AC, Lima VM, Rogerio Leoni B, Guiguer EL. Curcumin therapy for ulcerative colitis remission: systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol 2020; 14:1171-1179. [PMID: 32772752 DOI: 10.1080/17474124.2020.1808460] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Despite significant advances in the study of Ulcerative colitis (UC) management, up to a third of patients may be refractory to conventional therapy, and specialists have considered natural compounds such as curcumin. AREA COVERED The meta-analyzes found in the literature compare the effects of curcumin used in different administration routes or compare patients in remission with patients with active disease. Due to the biases in these studies, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) that investigated the efficacy of orally administrated curcumin in mild-to-moderate active UC. EXPERT OPINION Curcumin produces relevant anti-inflammatory and antioxidant effects that are crucial in inducing remission in UC patients. Unfortunately, in the treatment of UC, we have not observed studies with standardization of dose and routes of administration. Existing meta-analyses are biased because they compare studies using different administration routes and patients in different stages of the disease. Our meta-analysis is the only one that tried to make a comparison with a few of biases as possible and show that curcumin can help in the induction of remission in UC subjects.
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Affiliation(s)
- Ricardo de Alvares Goulart
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR) , Marília, São Paulo, Brazil
| | - Sandra M Barbalho
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR) , Marília, São Paulo, Brazil.,School of Medicine, University of Marília (UNIMAR) , Marília, São Paulo, Brazil.,Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília , Marília, São Paulo, Brazil
| | - Cláudio José Rubira
- School of Medicine, University of Marília (UNIMAR) , Marília, São Paulo, Brazil
| | - Adriano Cressoni Araújo
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR) , Marília, São Paulo, Brazil.,School of Medicine, University of Marília (UNIMAR) , Marília, São Paulo, Brazil
| | | | - Buchaim Rogerio Leoni
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR) , Marília, São Paulo, Brazil.,Department of Biological Sciences, University of São Paulo (FOB - USP) , Bauru, São Paulo, Brazil
| | - Elen Landgraf Guiguer
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR) , Marília, São Paulo, Brazil.,School of Medicine, University of Marília (UNIMAR) , Marília, São Paulo, Brazil.,Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília , Marília, São Paulo, Brazil
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24
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Goulart RDA, Barbalho SM, Lima VM, Souza GAD, Matias JN, Araújo AC, Rubira CJ, Buchaim RL, Buchaim DV, Carvalho ACAD, Guiguer ÉL. Effects of the Use of Curcumin on Ulcerative Colitis and Crohn's Disease: A Systematic Review. J Med Food 2020; 24:675-685. [PMID: 33155879 DOI: 10.1089/jmf.2020.0129] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is an umbrella term used to describe chronic inflammatory disorders related to a substantial reduction in the quality of life of patients. Some patients with Crohn's disease (CD) and ulcerative colitis (UC) are refractory to conventional therapies, and Curcuma longa derivatives have been considered as adjuvants. Owing to the anti-inflammatory and antioxidant effects, some clinical trials used this plant in the therapeutic approach of IBD, and some meta-analyses evaluated the outcomes found in these studies. Owing to controversial findings, our systematic review aimed to evaluate these studies to show whether C. longa compounds can still be considered in the therapeutic approach of patients with CD and UC. MEDLINE-PubMed, EMBASE, and Cochrane were searched, and Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed. The results of the randomized clinical trials (RCTs) showed promising results with the use of curcumin in the therapeutic approach of both UC and CD patients. Some meta-analyses show controversial results, possibly due to the presence of bias in the included studies. The actions of curcumin are achieved by several mechanisms, such as reducing the expression of interleukin (IL)-1, IL-6, IL-12, and tumor necrosis factor-α. Moreover, it reduces the levels of reactive oxygen species, such as superoxide anions and malondialdehyde. The results of using curcumin in CD and UC patients are challenging to be evaluated because RCTs are variable in the dose and the formulations of curcumin, in the time of treatment, and the route of administration. The number of patients in the samples is also usually small.
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Affiliation(s)
- Ricardo de Alvares Goulart
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Marília, Brazil
| | - Sandra M Barbalho
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Marília, Brazil.,Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, Brazil.,Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília, Marília, Brazil
| | - Vinícius Marinho Lima
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, Brazil
| | - Gabriela Achete de Souza
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, Brazil
| | - Julia Novaes Matias
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, Brazil
| | - Adriano Cressoni Araújo
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Marília, Brazil.,Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, Brazil
| | - Cláudio José Rubira
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, Brazil
| | - Rogério Leone Buchaim
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Marília, Brazil.,University of São Paulo (FOB-USP), Alameda Doutor Octávio Pinheiro Brisolla, Bauru, Brazil
| | - Daniela Vieira Buchaim
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Marília, Brazil.,Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, Brazil.,Medical School, University Center of Adamantina (UniFAI), Adamantina, Brazil
| | | | - Élen Landgraf Guiguer
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Marília, Brazil.,Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, Brazil.,Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília, Marília, Brazil
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25
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Kayal M, Shah S. Ulcerative Colitis: Current and Emerging Treatment Strategies. J Clin Med 2019; 9:jcm9010094. [PMID: 31905945 PMCID: PMC7019865 DOI: 10.3390/jcm9010094] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 12/23/2019] [Accepted: 12/24/2019] [Indexed: 02/07/2023] Open
Abstract
Historically, medical therapy for ulcerative colitis (UC) was limited to corticosteroids. Excitingly, over the past just 1-2 decades, the options for medical therapy have expanded and include biologics and small molecules, with more agents actively being developed. In this article, we review the current and emerging treatment strategies for UC stratified according to disease severity.
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Affiliation(s)
- Maia Kayal
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Shailja Shah
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN 97203, USA
- Correspondence:
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