Okada Kohki, Matsuo Kano
Department of Medical Technology and Sciences, Faculty of Health Sciences, Kyoto Tachibana University, Kyoto 607-8175, Japan.
Graduate School of Health Sciences, Kyoto Tachibana University, Kyoto 607-8175, Japan.
Biomedicines. 2023 Mar 16;11(3):922. doi: 10.3390/biomedicines11030922.
Ulcerative colitis (UC) is an intractable disease that causes persistent colonic inflammation. Numerous studies have reported that smoking can afford clinical benefits in UC. This study aimed to elucidate whether nicotine, the main component in cigarettes, can exert pharmacological effects against experimental UC. To achieve this objective, we compared the effects of nicotine with those of structural nicotine analogs in a UC rodent model (Slc: Wistar rats, male, 9-week-old, and 220-250 g/rat). Nicotine, or a respective structural analog (nornicotine, cotinine, anabasine, myosmine, and anatabine), was administered intraperitoneally daily to rats ( = 6/group) exhibiting dextran sulfate sodium-induced experimental colitis. Examining the colon tissues of model rats, we compared disease severity, cytokine secretion, and α7 nicotine acetylcholine receptor (nAChR7) expression. We observed that nicotine administration induced weight loss at 2.35% in 10 days. Notably, the reduction in histological severity (score) of UC was more pronounced in rats treated with nicotine (score = 4.83, = 0.042) than in untreated rats (score = 8.17). Nicotine administration increased nAChR7 expression 6.88-fold ( = 0.022) in inflammatory sites of the colon, mainly by suppressing the production of interleukin (IL)-1β and IL-6. Moreover, the secretion of these cytokines was suppressed in lipopolysaccharide-stimulated rat macrophages (MΦ) treated with nicotine. In conclusion, nicotine better alleviates experimental UC than the examined structural analogs by activating nAChR7 expression and suppressing proinflammatory cytokines in MΦ.
溃疡性结肠炎（UC）是一种导致结肠持续炎症的难治性疾病。众多研究报告称，吸烟对UC具有临床益处。本研究旨在阐明香烟中的主要成分尼古丁是否能对实验性UC发挥药理作用。为实现这一目标，我们在UC啮齿动物模型（Slc: Wistar大鼠，雄性，9周龄，220 - 250克/只）中比较了尼古丁与结构类似物的作用。将尼古丁或各自的结构类似物（去甲烟碱、可替宁、新烟草碱、毒藜碱和安纳他宾）每日腹腔注射给表现出葡聚糖硫酸钠诱导的实验性结肠炎的大鼠（每组 = 6只）。通过检查模型大鼠的结肠组织，我们比较了疾病严重程度、细胞因子分泌和α7尼古丁乙酰胆碱受体（nAChR7）表达。我们观察到，给予尼古丁在10天内导致体重减轻2.35%。值得注意的是，尼古丁治疗的大鼠（评分 = 4.83， = 0.042）的UC组织学严重程度（评分）降低比未治疗的大鼠（评分 = 8.17）更明显。给予尼古丁使结肠炎症部位的nAChR7表达增加6.88倍（ = 0.022），主要是通过抑制白细胞介素（IL）-1β和IL-6的产生。此外，在用尼古丁处理的脂多糖刺激的大鼠巨噬细胞（MΦ）中，这些细胞因子的分泌受到抑制。总之，尼古丁通过激活nAChR7表达和抑制MΦ中的促炎细胞因子，比所研究的结构类似物能更好地减轻实验性UC。
