Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt, 71524.
Pathology Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
Inflammopharmacology. 2023 Jun;31(3):1449-1464. doi: 10.1007/s10787-023-01164-6. Epub 2023 Mar 1.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative illnesses, and yet, no workable treatments have been discovered to prevent or reverse AD. Curcumin (CUR), the major polyphenolic compound of turmeric (Curcuma longa) rhizomes, and Ginkgo biloba extract (GBE) are natural substances derived from conventional Chinese herbs that have long been shown to provide therapeutic advantages for AD. The uptake of curcumin into the brain is severely restricted by its low ability to cross the blood-brain barrier (BBB). Meanwhile, GBE has been shown to improve BBB permeability. The present study evaluated the neuroprotective effects and pharmacokinetic profile of curcumin and GBE combination to find out whether GBE can enhance curcumin's beneficial effects in AD by raising its brain concentration. Results revealed that CUR + GBE achieved significantly higher levels of curcumin in the brain and plasma after 30 min and 1 h of oral administration, compared to curcumin alone, and this was confirmed by reversed phase high-performance liquid chromatography (RP-HPLC). The effect of combined oral treatment, for 28 successive days, on cognitive function and other AD-like alterations was studied in scopolamine-heavy metal mixtures (SCO + HMM) AD model in rats. The combination reversed at least, partially on the learning and memory impairment induced by SCO + HMM. This was associated with a more pronounced inhibitory effect on acetylcholinesterase (AChE), caspase-3, hippocampal amyloid beta (Aβ1-42), and phosphorylated tau protein (p-tau) count, and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukine-1beta (IL-1β), as compared to the curcumin alone-treated group. Additionally, the combined treatment significantly decreased lipid peroxidation (MDA) and increased levels of reduced glutathione (GSH), when compared with the curcumin alone. These findings support the concept that the combination strategy might be an alternative therapy in the management/prevention of neurological disorders. This study sheds light on a new approach for exploring new phyto-therapies for AD and emphasizes that more research should focus on the synergic effects of herbal drugs in future.
阿尔茨海默病(AD)是最常见的神经退行性疾病之一,但目前尚无可行的治疗方法来预防或逆转 AD。姜黄素(CUR)是姜黄根茎中的主要多酚化合物,银杏叶提取物(GBE)是源自传统中药的天然物质,长期以来一直被证明对 AD 具有治疗优势。由于其穿过血脑屏障(BBB)的能力较低,姜黄素进入大脑的能力受到严重限制。同时,GBE 已被证明可提高 BBB 的通透性。本研究评估了姜黄素和 GBE 联合的神经保护作用和药代动力学特征,以确定 GBE 是否可以通过提高其脑浓度来增强 CUR 在 AD 中的有益作用。结果表明,与单独使用 CUR 相比,CUR+GBE 在口服 30 分钟和 1 小时后,大脑和血浆中的 CUR 水平显著升高,这通过反相高效液相色谱(RP-HPLC)得到证实。在 SCO+HMM AD 模型大鼠中,研究了连续 28 天口服联合治疗对认知功能和其他 AD 样改变的影响。联合治疗至少部分逆转了 SCO+HMM 引起的学习和记忆障碍。这与对乙酰胆碱酯酶(AChE)、半胱氨酸天冬氨酸蛋白酶-3(caspase-3)、海马淀粉样β(Aβ1-42)和磷酸化 tau 蛋白(p-tau)计数以及促炎细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的更明显抑制作用有关,与单独使用 CUR 治疗的组相比。此外,与单独使用 CUR 治疗组相比,联合治疗还显著降低了丙二醛(MDA)的水平并增加了还原型谷胱甘肽(GSH)的水平。这些发现支持这样一种概念,即联合治疗策略可能是管理/预防神经障碍的一种替代疗法。本研究为 AD 的新植物疗法探索提供了新的思路,并强调未来应更多地关注草药药物的协同作用。