Pain and depression are often co-existing pathological states that promote mutual severity resulting in limited efficacy of current treatment strategies. Thus, there is a need to develop an efficacious alternate treatment regimen for pain-depression dyad. Skimmetin and osthole are molecules of natural origin that have been explored for an anti-hyperglycemic, anti-bacterial, anti-fungal, and anti-diabetic activities in preclinical studies. in animal models. The current study has been designed to explore the beneficial effect of skimmetin/osthole in reserpine-induced pain-depression dyad in mice. Female Swiss albino mice (n = 6) were challenged with reserpine (0.5 mg/kg s.c.) for the first 3 days to induce a pain-depression dyad-like state. Skimmetin (10 mg/kg i.p.) and osthole (10 mg/kg i.p.) were administered for 5 days consecutively, starting from the first day of study. Reserpine treatment significantly reduced the pain threshold in the pressure application measurement (PAM) and electronic von frey (eVF) test. In forced swim test (FST) and Morris water maze (MWM) test mice displayed an increased immobility time and latency to reach platform respectively. Biochemical results showed an increased level of TNF-α, IL-1β, TBARS, glutamate, and reduced level of GSH, norepinephrine, and serotonin in the reserpine treated group. Reserpine treatment also increased brain MAO-A activity. Skimmetin/osthole treatment was found to attenuate the behavioral and biochemical alterations induced by reserpine. The results of the current investigation delineated that skimmetin/osthole may exert anti-nociceptive, anti-depressant, and improved cognition via inhibiting inflammatory and oxidative stress-mediated neurotransmitter dysregulation.

疼痛和抑郁通常是共存的病理状态，会促进相互严重程度，导致当前治疗策略的疗效有限。因此，需要为疼痛抑郁症开发一种有效的替代治疗方案。Skimmetin 和蛇床子素是天然来源的分子，已在临床前研究中探索其抗高血糖、抗菌、抗真菌和抗糖尿病活性。在动物模型中。目前的研究旨在探索脱脂甲醚/蛇床子素在利血平诱导的小鼠疼痛抑郁二元组中的有益作用。雌性瑞士白化小鼠 ( n = 6) 在前 3 天内用利血平 (0.5 mg/kg sc) 激发以诱导疼痛抑郁二重体样状态。从研究的第一天开始，连续施用 5 天脱脂甲酰胺 (10 mg/kg ip) 和蛇床子素 (10 mg/kg ip)。利血平治疗显着降低了压力应用测量 (PAM) 和电子冯弗雷 (eVF) 测试中的疼痛阈值。在强迫游泳测试 (FST) 和莫里斯水迷宫 (MWM) 测试中，小鼠分别显示出增加的不动时间和到达平台的潜伏期。生化结果显示，利血平治疗组 TNF-α、IL-1β、TBARS、谷氨酸水平升高，谷胱甘肽、去甲肾上腺素和血清素水平降低。利血平治疗也增加了脑 MAO-A 活性。发现脱脂蛋白/蛇床子素治疗可减弱利血平引起的行为和生化改变。目前的调查结果表明，脱脂甲醚/蛇床子素可能通过抑制炎症和氧化应激介导的神经递质失调来发挥抗伤害性、抗抑郁和改善认知的作用。