Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, South Dakota State University, Brookings, SD 57007, USA.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Cells. 2024 Jun 1;13(11):957. doi: 10.3390/cells13110957.
Inflammatory bowel disease (IBD) is a chronic gut disorder that also elevates the risk of colorectal cancer (CRC). The global incidence and severity of IBD are rising, yet existing therapies often lead to severe side effects. Curcumin offers potent anti-inflammatory and chemotherapeutic properties. However, its clinical translation is hindered by rapid metabolism, as well as poor water solubility and stability, which limits its bioavailability. To address these challenges, we developed OC-S, a water-soluble and colon-targeted curcumin formulation that protects against colitis in mice. The current study advances OC-S as a dietary supplement by establishing its stability and compatibility with various commercial dietary products. Further, OC-S exhibited specific binding to inflamed colon tissue, potentially aiding in targeted drug retention at the inflammation site in colitis with diarrhea symptoms. We further investigated its efficacy in vivo and in vitro using a murine model of colitis and tumoroids from APC mice. OC-S significantly reduced colitis severity and pro-inflammatory cytokine expression compared with curcumin, even at very low doses (5 mg/kg/day). It also demonstrated higher anti-proliferative activity in CRC cells and colon cancer tumoroids vs. curcumin. Overall, this study demonstrated that OC-S effectively targets and retains water-soluble curcumin at the inflamed colon sites, while showing promise in addressing both colitis and colorectal cancer, which potentially paves the way for OC-S to advance into clinical development as a dietary product for both IBD and CRC.
炎症性肠病（IBD）是一种慢性肠道疾病，也会增加结直肠癌（CRC）的风险。IBD 的全球发病率和严重程度正在上升，但现有的治疗方法往往会导致严重的副作用。姜黄素具有强大的抗炎和化疗特性。然而，其临床转化受到快速代谢、较差的水溶性和稳定性的限制，从而限制了其生物利用度。为了解决这些挑战，我们开发了 OC-S，这是一种水溶性和结肠靶向的姜黄素制剂，可预防小鼠结肠炎。本研究通过确定 OC-S 的稳定性及其与各种商业饮食产品的兼容性，将其作为膳食补充剂进行了推进。此外，OC-S 表现出与发炎结肠组织的特异性结合，这可能有助于在伴有腹泻症状的结肠炎中靶向保留在炎症部位的药物。我们进一步使用结肠炎小鼠模型和 APC 小鼠的肿瘤球体在体内和体外研究了其功效。与姜黄素相比，OC-S 可显著降低结肠炎的严重程度和促炎细胞因子的表达，甚至在非常低的剂量（5mg/kg/天）下也是如此。它还显示出对 CRC 细胞和结肠癌肿瘤球体的更高的抗增殖活性。总的来说，这项研究表明，OC-S 可以有效地靶向和保留在发炎的结肠部位的水溶性姜黄素，同时在治疗结肠炎和结直肠癌方面显示出希望，这可能为 OC-S 作为 IBD 和 CRC 的膳食产品进入临床开发铺平道路。
