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植物化学物质作为 NF-κB 的抑制剂用于治疗老年痴呆症。

Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer's disease.

机构信息

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.

出版信息

Pharmacol Res. 2018 Mar;129:262-273. doi: 10.1016/j.phrs.2017.11.030. Epub 2017 Nov 24.

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia. The exact pathophysiology of this disease remains incompletely understood and safe and effective therapies are required. AD is highly correlated with neuroinflammation and oxidative stress in brain causing neuronal loss. Nuclear factor of activated B-cells (NF-κB) is involved in physiological inflammatory processes and thus representing a promising target for inflammation-based AD therapy. Phytochemicals are able to interfere with the NF-κB pathway. They inhibit the phosphorylation or the ubiquitination of signaling molecules, and thus, inhibit the degradation of IκB. The translocation of NF-κB to the nucleus and subsequent transcription of pro-inflammatory cytokines are inhibited by the actions of phytochemicals. Additionally, natural compounds preventing the interaction of NF-κB can block NF-κB's transcriptional activity by inhibiting its binding to target DNA. Many polyphenols including curcumin, resveratrol, pterostilbene, punicalagin, macranthoin G, salidroside, 4-O-methylhonokiol, lycopene, genistein, obovatol and gallic acid were reported as potent NF-κB inhibitors for AD treatment. Several alkaloids such as galantamine, glaucocalyxin B, tetrandrine, berberine, oridonin, anatabine have been shown anti-inflammatory effects in AD models in vitro as well as in vivo. Besides, vitamins, tanshinone IIA, artemisinin, dihydroasparagusic acid, geniposide, xanthoceraside, l-theranine, 1,8-cineole and paeoniflorin were described as promising NF-κB inhibitors. In conclusion, natural products from plants represent interesting candidates for AD treatment. They may qualify as promising compounds for the development of derivatives providing enhanced pharmacological features.

摘要

阿尔茨海默病(AD)是最常见的痴呆症形式。这种疾病的确切病理生理学仍不完全了解,需要安全有效的治疗方法。AD 与大脑中的神经炎症和氧化应激高度相关,导致神经元丢失。激活 B 细胞的核因子(NF-κB)参与生理炎症过程,因此是基于炎症的 AD 治疗的有前途的靶标。植物化学物质能够干扰 NF-κB 途径。它们抑制信号分子的磷酸化或泛素化,从而抑制 IκB 的降解。NF-κB 向核内易位以及随后的促炎细胞因子转录被植物化学物质的作用所抑制。此外,防止 NF-κB 相互作用的天然化合物可以通过抑制其与靶 DNA 的结合来阻断 NF-κB 的转录活性。许多多酚类化合物,包括姜黄素、白藜芦醇、紫檀芪、鞣花酸、大蓟苷 G、红景天苷、4-O-甲基 honokiol、番茄红素、染料木黄酮、obovatol 和没食子酸,被报道为治疗 AD 的有效 NF-κB 抑制剂。几种生物碱,如加兰他敏、glaucocalyxin B、汉防己甲素、小檗碱、冬凌草甲素、梓醇、梓醇苷、藜芦碱、1,8-桉树脑和芍药苷,已被证明在 AD 模型中具有抗炎作用,无论是在体外还是体内。此外,维生素、丹参酮 IIA、青蒿素、二氢天门冬氨酸、栀子苷、梓糖苷、l-茶氨酸、1,8-桉树脑和芍药苷被描述为有前途的 NF-κB 抑制剂。总之,植物来源的天然产物是治疗 AD 的有前途的候选药物。它们可能有资格成为开发具有增强药理特性的衍生物的有前途的化合物。

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