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CLINICAL RESEARCH
Curcumin ameliorates ulcerative colitis via inhibiting STAT3-mediated angiogenesis
1
Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Jiangsu, China
2
Clinical Medical College of Nanjing University of Chinese Medicine, Jiangsu, China
3
Yancheng Clinical College of Xuzhou Medical University, Jiangsu, China
Submission date: 2025-08-01
Final revision date: 2025-11-26
Acceptance date: 2025-12-13
Online publication date: 2025-12-30
Corresponding author
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Ulcerative colitis (UC) is a chronic and persistent inflammatory bowel disease with limited clinical treatment options and significant therapeutic challenges. This study aimed to evaluate whether the therapeutic effect of curcumin against ulcerative colitis is positively correlated with its inhibition of angiogenesis and to elucidate the underlying angiogenesis-related molecular mechanism.
Material and methods:
A multi-database analysis was performed to predict the possible targets involved in curcumin inhibition of UC. Tube formation and aortic ring assays were used to evaluate angiogenesis in vitro. A dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model was used to evaluate curcumin’s effect on UC.
Results:
We first employed a comprehensive multi-database analysis to identify overlapping targets connecting curcumin, ulcerative colitis, and angiogenesis, leading to the identification of signal transducer and activator of transcription 3 (STAT3) as a potential mediator of this process. In vitro experimental results demonstrated that curcumin significantly inhibited tube formation in human umbilical vein endothelial cells (HUVEC) and suppressed endothelial sprouting in rat aortic rings. Furthermore, curcumin downregulated the expression of vascular endothelial growth factor (VEGF) in HUVEC cells and concurrently inhibited the expression of phosphorylated JAK2 and phosphorylated STAT3 (Y705). Notably, the addition of VEGF partially reversed curcumin’s inhibitory effects on p-JAK2 and p-STAT3. In vivo studies using a DSS-induced mouse model of ulcerative colitis revealed that curcumin ameliorated DSS-induced colon shortening and various disease symptoms. It also suppressed serum levels of TNF- and IL-6 and inhibited the expression of STAT3 and VEGF in colonic tissues.
Conclusions:
Curcumin ameliorates ulcerative colitis through inhibition of the VEGF-mediated JAK2/STAT3 signaling pathway. These findings position curcumin as a potential clinical candidate drug for the treatment of ulcerative colitis.
Ulcerative colitis (UC) is a chronic and persistent inflammatory bowel disease with limited clinical treatment options and significant therapeutic challenges. This study aimed to evaluate whether the therapeutic effect of curcumin against ulcerative colitis is positively correlated with its inhibition of angiogenesis and to elucidate the underlying angiogenesis-related molecular mechanism.
Material and methods:
A multi-database analysis was performed to predict the possible targets involved in curcumin inhibition of UC. Tube formation and aortic ring assays were used to evaluate angiogenesis in vitro. A dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model was used to evaluate curcumin’s effect on UC.
Results:
We first employed a comprehensive multi-database analysis to identify overlapping targets connecting curcumin, ulcerative colitis, and angiogenesis, leading to the identification of signal transducer and activator of transcription 3 (STAT3) as a potential mediator of this process. In vitro experimental results demonstrated that curcumin significantly inhibited tube formation in human umbilical vein endothelial cells (HUVEC) and suppressed endothelial sprouting in rat aortic rings. Furthermore, curcumin downregulated the expression of vascular endothelial growth factor (VEGF) in HUVEC cells and concurrently inhibited the expression of phosphorylated JAK2 and phosphorylated STAT3 (Y705). Notably, the addition of VEGF partially reversed curcumin’s inhibitory effects on p-JAK2 and p-STAT3. In vivo studies using a DSS-induced mouse model of ulcerative colitis revealed that curcumin ameliorated DSS-induced colon shortening and various disease symptoms. It also suppressed serum levels of TNF- and IL-6 and inhibited the expression of STAT3 and VEGF in colonic tissues.
Conclusions:
Curcumin ameliorates ulcerative colitis through inhibition of the VEGF-mediated JAK2/STAT3 signaling pathway. These findings position curcumin as a potential clinical candidate drug for the treatment of ulcerative colitis.
REFERENCES (38)
1.
Berre CL, Honap S, Peyrin-Biroulet L. Ulcerative colitis. Lancet 2023; 402: 571-84.
2.
Wangchuk P, Yeshi K, Loukas A. Ulcerative colitis: clinical biomarkers, therapeutic targets, and emerging treatments. Trends Pharmacol Sci 2024; 45: 892-903.
3.
Du L, Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterol Clin North Am 2020; 49: 643-54.
4.
Jeong JH, Ojha U, Lee YM. Pathological angiogenesis and inflammation in tissues. Arch Pharmacal Res 2021; 44: 1-15.
5.
Szade A, Grochot-Przeczek A, Florczyk U, Jozkowicz A, Dulak J. Cellular and molecular mechanisms of inflammation-induced angiogenesis. IUBMB Life 2015; 67: 145-59.
6.
Liang Y, Li Y, Lee C, Yu Z, Chen C, Liang C. Ulcerative colitis: molecular insights and intervention therapy. Mol Biomed 2024; 5: 42.
7.
Stavsky J, Maitra R. The synergistic role of diet and exercise in the prevention, pathogenesis, and management of ulcerative colitis: an underlying metabolic mechanism. Nutr Metab Insights 2019; 12: 1178638819834526.
8.
Ismail AMA, Morsy MM. Effect of baduanjin exercise on lipid profile, blood pressure, and thyroid-stimulating hormone in elderly with subclinical hypothyroidism and mild cognitive impairment: a randomized-controlled trial in women. Geriatr Nurs 2025; 64: 103434.
9.
Kotha RR, Luthria DL. Curcumin: biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules 2019; 24: 2930.
10.
Weng W, Goel A. Curcumin and colorectal cancer: an update and current perspective on this natural medicine. Semin Cancer Biol 2022; 80: 73-86.
11.
Peng Y, Ao M, Dong B, et al. Anti-inflammatory effects of curcumin in the inflammatory diseases: status, limitations and countermeasures. Drug Des Dev Ther 2021; 15: 4503-25.
12.
Talpan D, Salla S, Seidelmann N, Walter P, Fuest M. Antifibrotic effects of caffeine, curcumin and pirfenidone in primary human keratocytes. Int J Mol Sci 2023; 24: 1461.
13.
Wang Y, Tang Q, Duan P, Yang L. Curcumin as a therapeutic agent for blocking NF-B activation in ulcerative colitis. Immunopharmacol Immunotoxicol 2018; 40: 476-82.
14.
Afrin R, Arumugam S, Rahman A, et al. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-B translocation. Int Immunopharmacol 2017; 44: 174-82.
15.
Guo J, Zhang YY, Sun M, Xu LF. Therapeutic potential of curcumin in a rat model of dextran sulfate sodium-induced ulcerative colitis by regulating the balance of treg/Th17 cells. Inflammation 2022; 45: 2163-71.
16.
Wang Z, Zheng J, Yang S, et al. Curcumin prevents the arsenic-induced neuroimmune injury through JAK2/STAT3 pathway. Chin J Cell Mol Immunol 2024; 40: 1067-74.
17.
Zhang X, Zhang H, Wang J, et al. Curcumin attenuates ulcerative colitis via regulation of sphingosine kinases 1/NF-B signaling pathway. Biofactors 2025; 51: e70001.
18.
Yang M, Wang J, Yang C, Han H, Rong W, Zhang G. Oral administration of curcumin attenuates visceral hyperalgesia through inhibiting phosphorylation of TRPV1 in rat model of ulcerative colitis. Mol Pain 2017; 13: 1744806917726416.
19.
Rogers NM, Kireta S, Coates PTH. Curcumin induces maturation-arrested dendritic cells that expand regulatory T cells in vitro and in vivo. Clin Exp Immunol 2010; 162: 460-73.
20.
Lugano R, Ramachandran M, Dimberg A. Tumor angiogenesis: causes, consequences, challenges and opportunities. Cell Mol Life Sci 2020; 77: 1745-70.
21.
Otrock ZK, Mahfouz RAR, Makarem JA, Shamseddine AI. Understanding the biology of angiogenesis: review of the most important molecular mechanisms. Blood Cells Mol Dis 2007; 39: 212-20.
22.
Lopes-Coelho F, Martins F, Pereira SA, Serpa J. Anti-angiogenic therapy: current challenges and future perspectives. Int J Mol Sci 2021; 22: 3765.
23.
Li Z, Zeng L, Huang W, Zhang X, Zhang L, Xie Q. Angiogenic factors and inflammatory bowel diseases. Biomedicines 2025; 13: 1154.
24.
Zhang L, Wei W, Ai X, et al. Extracellular vesicles from hypoxia-preconditioned microglia promote angiogenesis and repress apoptosis in stroke mice via the TGF-/Smad2/3 pathway. Cell Death Dis 2021; 12: 1068.
25.
Aplin AC, Nicosia RF. The rat aortic ring model of angiogenesis. Methods Mol Biol 2015; 1214: 255-64.
26.
Hao L, Alkry LT, Alattar A, et al. Ibrutinib attenuated DSS-induced ulcerative colitis, oxidative stress, and the inflammatory cascade by modulating the PI3K/akt and JNK/NF-B pathways. Arch Med Sci 2022; 18: 805-15.
27.
Kou H, Huang L, Jin M, He Q, Zhang R, Ma J. Effect of curcumin on rheumatoid arthritis: a systematic review and meta-analysis. Front Immunol 2023; 14: 1121655.
28.
Ahmad A, Nawaz MI. Molecular mechanism of VEGF and its role in pathological angiogenesis. J Cell Biochem 2022; 123: 1938-65.
29.
Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol 2018; 15: 325-40.
30.
Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity 2019; 51: 27-41.
31.
Scaldaferri F, Vetrano S, Sans M, et al. VEGF-a links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology 2009; 136: 585-95.
32.
Hu C, Wu Z, Huang Z, et al. Nox2 impairs VEGF-a-induced angiogenesis in placenta via mitochondrial ROS-STAT3 pathway. Redox Biol 2021; 45: 102051.
33.
Zhu D, Shen Z, Liu J, et al. The ROS-mediated activation of STAT-3/VEGF signaling is involved in the 27-hydroxycholesterol-induced angiogenesis in human breast cancer cells. Toxicol Lett 2016; 264: 79-86.
34.
Wang L, Astone M, Alam SK, et al. Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability. Dis Models Mech 2021; 14: dmm049029.
35.
Hu Y, Zhou N, Zhu Q. Curcumin inhibits proliferation and invasion of papillary thyroid carcinoma cells by inhibiting the JAK2 / STAT3 pathway. J BUON 2021; 26: 1635-41.
36.
Sun Y, Liu L, Wang Y, He A, Hu H, Zhang J, et al. Curcumin inhibits the proliferation and invasion of MG-63 cells through inactivation of the p-JAK2/p-STAT3 pathway. OncoTargets Ther 2019; 12: 2011-21.
37.
Zhu S, Zhang C, Weng Q, Ye B. Curcumin protects against acute renal injury by suppressing JAK2/STAT3 pathway in severe acute pancreatitis in rats. Exp Ther Med 2017; 14: 1669-74.
38.
Jiang Z, Liu L, Su H, et al. Curcumin and analogues in mitigating liver injury and disease consequences: from molecular mechanisms to clinical perspectives. Phytomedicine 2024; 123: 155234.
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| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
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