Pimonrat KetsawatsomkronKenjiro MutaNithi AsavapanumasThittaya Den-udom2026-02-262026-02-26202320262023Thesis (M.Sc. (Translational Medicine))--Mahidol University, 2023https://repository.li.mahidol.ac.th/handle/123456789/115372Capsaicin and dihydrocapsaicin (DHC) are the main pungent capsaicinoids derived from chili peppers. Capsaicin has been previously shown to reduce inflammatory responses and promotes vascular health by increasing nitric oxide (NO) production. Although capsaicin has been extensively studied, the biological activities of DHC in the cardiovascular system remain unclear. In this study, we examined the effects of DHC on TNFα-induced endothelial inflammation by using conventional 2D cultures and human 3D capillaries. Our results showed that DHC significantly reduced TNFα-induced intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, and monocyte adhesion to endothelial cells in 2D endothelial cultures. Moreover, DHC mitigated the production of IL-6 induced by TNFα. Next, we investigated whether DHC elicited the same responses in 3D endothelial cell tubes. We first developed and characterized human capillary in a microfluidic device. Our human 3D capillary exhibited a tubular structure and an impermeable barrier to 70 kDa dextran. Stimulation of TNFα led to vascular leakage, increased monocyte adhesion, and IL-6 production in the 3D capillary. Unlike data from 2D cultures, co-incubation of the microvessel with DHC did not improve TNFα-induced vascular leakage and monocyte adhesion. However, IL-6 production was significantly reduced by DHC in 3D capillary. Here, we reported differential effects of DHC on TNFα-induced inflammation in endothelium between 2D and 3D in vitro models and exemplified the use of an organ-on-a-chip technology to evaluate the pharmacological effects of a natural compound. Implication of thesis: The studies demonstrated the utilization of an organ-on-a-chip technology to evaluate the pharmacological activities of natural compounds. This is beneficial for drug discovery and development.xi, 70 leaves : ill.application/pdfengผลงานนี้เป็นลิขสิทธิ์ของมหาวิทยาลัยมหิดล ขอสงวนไว้สำหรับเพื่อการศึกษาเท่านั้น ต้องอ้างอิงแหล่งที่มา ห้ามดัดแปลงเนื้อหา และห้ามนำไปใช้เพื่อการค้าCapsaicinoids -- Physiological effect.Endothelium -- Inflammation -- Prevention.Monocytes -- Adhesion -- Research.M.Sc. (2023)Translational Medicine (Mahidol University 2023)Master ThesisMahidol University