Department of Biochemistry, School of Life Sciences, Federal University of Technology, P.M.B. 704, Akure, 340001, Nigeria.
Inflammopharmacology. 2022 Dec;30(6):2447-2476. doi: 10.1007/s10787-022-01006-x. Epub 2022 Jun 5.
This study investigated the modulatory effects of alkaloid extracts of Cannabis sativa (CSAE), Datura stramonium (DSAE), Nicotiana tabacum (NTAE) and male Carica papaya (CMAE) on neurotransmitter, neurotrophic and neuro-inflammatory systems linked to anxiety and depression. Male Wistar rats were orally administered the alkaloid extracts in doses of 5, 50, 500, and 2000 mg/kg for 90 days. On day 91, neurobehavioural studies were evaluated, rats were sacrificed, brain hippocampus removed and tissue homogenate prepared. Biochemical, cytokine and neurotransmitter metabolisms were estimated in the hippocampus. Expressions of genes linked to anxiety and depression were evaluated by RT-qPCR. Results showed CSAE, NTAE and CMAE act as anxiolytic and antidepressant agents by depleting TNF-α, IL-1β and reactive oxygen species concentrations, and monoamine oxidase, angiotensin 1-converting enzyme and acetylcholinesterase activities while elevating IL-10 and dopamine concentrations and glutamate dehydrogenase activity at doses of 5, 50 and 500. Same doses of CSAE, NTAE and CMAE also depleted the gene expressions of GSK3β, JNK, NF-ĸB, and Nesfatin-1 while increasing expressions of CREB, BDNF, serotonin and Nrf2. However, administration of DSAE and 2000 mg/kg CSAE, NTAE and CMAE had adverse modulatory effects on the neurochemical concentrations and activities as well as the gene expressions of the evaluated neurotransmitter, neurotrophic and inflammatory systems. In conclusion, the study established the sub-chronic instrumentalization potential of CSAE, CMAE, and NTAE for anxiolytic and anti-depressive moods, though their use may be associated with dependence and addiction, which may result in more detrimental effects than any therapeutic potential they may proffer.
本研究调查了大麻（CSA）、曼陀罗（DSA）、烟草（NTA）和木瓜（CMA）生物碱提取物对与焦虑和抑郁相关的神经递质、神经营养和神经炎症系统的调节作用。雄性 Wistar 大鼠经口给予不同剂量（5、50、500 和 2000 mg/kg）的生物碱提取物 90 天。第 91 天，进行神经行为学研究，处死大鼠，取出海马组织并制备组织匀浆。在海马中估计生物化学、细胞因子和神经递质代谢物。通过 RT-qPCR 评估与焦虑和抑郁相关的基因表达。结果表明，CSA、NTA 和 CMA 在 5、50 和 500 剂量下通过耗竭 TNF-α、IL-1β 和活性氧浓度以及单胺氧化酶、血管紧张素 1 转换酶和乙酰胆碱酯酶活性，同时升高 IL-10 和多巴胺浓度和谷氨酸脱氢酶活性，起到抗焦虑和抗抑郁作用。相同剂量的 CSA、NTA 和 CMA 还耗竭了 GSK3β、JNK、NF-ĸB 和 Nesfatin-1 的基因表达，同时增加了 CREB、BDNF、血清素和 Nrf2 的表达。然而，DSA 和 2000 mg/kg CSA、NTA 和 CMA 的给药对所评估的神经递质、神经营养和炎症系统的神经化学浓度和活性以及基因表达具有不利的调节作用。总之，该研究确立了 CSA、CMAE 和 NTAE 作为抗焦虑和抗抑郁情绪的亚慢性仪器化潜力，尽管它们的使用可能与依赖和成瘾有关，这可能导致比它们提供的任何治疗潜力更大的有害影响。
