Abstract
Inflammatory bowel disease (IBD) is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis. Because IBD is difficult to heal and easily relapses, it could worsen patient quality of life and increase economic burdens. Curcumin (CUR) is a bioactive component derived from the rhizome of turmeric (Curcuma longa). Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules. However, due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability, it is important to select appropriate pharmaceutical preparations.
Keywords: Curcumin, Inflammatory bowel disease, Bioavailability, Nanotherapeutics,
Core Tip: Curcumin (CUR) can efficiently decrease the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules. It is a new area of research that may be promising in the future to treat patients with inflammatory bowel disease, especially in patients with ulcerative colitis. How to improve the bioavailability of CUR in vivo was also discussed.
TO THE EDITOR
With great interest, we have read the article by Zheng et al[1], who found that curcumin (CUR) regulated mTh/mTfh cell homeostasis by inhibiting the c-Jun amino-terminal kinases (JAK) 1/STAT3/SOCS signaling pathway, thus alleviating dextran sulfate sodium (DSS) induced pathological injury in the colon. Various studies have shown that CUR can also efficiently decrease the activity of proinflammatory cytokines by communicating with other transcription factors and signaling molecules. For example, CUR inhibits the activation of transcription factors, multiple protein kinases, and antiapoptotic proteins and modulates various inflammatory cytokines by suppressing the inflammatory transcription factor nuclear factor-κB[2]. Khan et al[3] reported the inhibitory effects of CUR on JNKs, extracellular-signal-regulated kinases, and stress-activated protein kinases. These inhibitory effects involve decreasing the expression and release of proinflammatory mediators, such as tumor necrosis factor (TNF)-α and adhesion molecules. Current research indicates that CUR has high medicinal value, including anti-inflammatory, antioxidant, antitumor, antiapoptotic, antifibrotic, immunoregulatory and other effects, and can be used to treat a variety of diseases[4].
Although CUR has few adverse effects and is highly safe for use, it still has several disadvantages. CUR is hardly soluble in water solution due to its lipophilic properties and low bioavailability after oral administration[5]. Therefore, it is particularly important to choose a combination of CUR and other treatments or a modified CUR formula to treat ulcerative colitis (UC). First, Xu et al’s evaluation of the in vivo therapeutic effects on DSS-induced UC in mice revealed that dexamethasone (DEX)-loaded hydroxyethyl starch-CUR nanoparticles could enhance the efficacy of free DEX and significantly alleviate the lesions caused by UC[6]. Second, A nanocarrier of CUR coated with tannic acid and genipin crosslinked human serum albumin was prepared into CUR nanoparticles by Luo et al[7]. The synthetic nanoparticles prolonged the colonic adhesion of CUR and improved its absorption in Caco-2 cells. In addition, a study demonstrated that oral administration of turmeric-derived nanoparticles containing a specific preparation could ameliorate colitis in mice and accelerate colitis resolution by regulating the expression of proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-1β, and the antioxidant gene HO-1[8].
Notably, CUR nanomaterials have been tested not only in preclinical animal models but also in human clinical trials for the treatment of various diseases[9]. Further clinical studies on the possible benefits and associated risks of CUR nano preparations in patients with IBD are also warranted in the future[10].
Footnotes
Conflict-of-interest statement: There are no conflicts of interest to report.
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Peer-review started: October 6, 2023
First decision: December 6, 2023
Article in press: January 4, 2024
Specialty type: Gastroenterology and hepatology
Country/Territory of origin: China
Peer-review report’s scientific quality classification
Grade A (Excellent): 0
Grade B (Very good): B
Grade C (Good): C
Grade D (Fair): 0
Grade E (Poor): 0
P-Reviewer: Kamada K, Japan; Sassaki LY, Brazil S-Editor: Qu XL L-Editor: A P-Editor: Qu XL
Contributor Information
Zi-Wen Meng, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China.
Bing Chang, Department of Gastroenterology, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Li-Xuan Sang, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China. sanglixuan2008@163.com.
References
- 1.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. doi: 10.3748/wjg.v29.i36.5226. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Buhrmann C, Brockmueller A, Mueller AL, Shayan P, Shakibaei M. Curcumin Attenuates Environment-Derived Osteoarthritis by Sox9/NF-kB Signaling Axis. Int J Mol Sci. 2021;22 doi: 10.3390/ijms22147645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Khan H, Sureda A, Belwal T, Çetinkaya S, Süntar İ, Tejada S, Devkota HP, Ullah H, Aschner M. Polyphenols in the treatment of autoimmune diseases. Autoimmun Rev. 2019;18:647–657. doi: 10.1016/j.autrev.2019.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Salehi B, Stojanović-Radić Z, Matejić J, Sharifi-Rad M, Anil Kumar NV, Martins N, Sharifi-Rad J. The therapeutic potential of curcumin: A review of clinical trials. Eur J Med Chem. 2019;163:527–545. doi: 10.1016/j.ejmech.2018.12.016. [DOI] [PubMed] [Google Scholar]
- 5.Lin Y, Liu H, Bu L, Chen C, Ye X. Review of the Effects and Mechanism of Curcumin in the Treatment of Inflammatory Bowel Disease. Front Pharmacol. 2022;13:908077. doi: 10.3389/fphar.2022.908077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Xu C, Chen S, Chen C, Ming Y, Du J, Mu J, Luo F, Huang D, Wang N, Lin Z, Weng Z. Colon-targeted oral nanoparticles based on ROS-scavenging hydroxyethyl starch-curcumin conjugates for efficient inflammatory bowel disease therapy. Int J Pharm. 2022;623:121884. doi: 10.1016/j.ijpharm.2022.121884. [DOI] [PubMed] [Google Scholar]
- 7.Luo R, Lin M, Zhang C, Shi J, Zhang S, Chen Q, Hu Y, Zhang M, Zhang J, Gao F. Genipin-crosslinked human serum albumin coating using a tannic acid layer for enhanced oral administration of curcumin in the treatment of ulcerative colitis. Food Chem. 2020;330:127241. doi: 10.1016/j.foodchem.2020.127241. [DOI] [PubMed] [Google Scholar]
- 8.Liu C, Yan X, Zhang Y, Yang M, Ma Y, Xu Q, Tu K, Zhang M. Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy. J Nanobiotechnology. 2022;20:206. doi: 10.1186/s12951-022-01421-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Ma Z, Wang N, He H, Tang X. Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application. J Control Release. 2019;316:359–380. doi: 10.1016/j.jconrel.2019.10.053. [DOI] [PubMed] [Google Scholar]
- 10.Karthikeyan A, Young KN, Moniruzzaman M, Beyene AM, Do K, Kalaiselvi S, Min T. Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook. Pharmaceutics. 2021;13 doi: 10.3390/pharmaceutics13040484. [DOI] [PMC free article] [PubMed] [Google Scholar]
