Pandareesh M D, Mythri R B, Srinivas Bharath M M
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, # 2900, Hosur Road, Bangalore 560029, Karnataka, India; Neurotoxicology Laboratory, Neurobiology Research Center, National Institute of Mental Health and Neurosciences, # 2900, Hosur Road, Bangalore 560029, Karnataka, India.
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, # 2900, Hosur Road, Bangalore 560029, Karnataka, India; Neurotoxicology Laboratory, Neurobiology Research Center, National Institute of Mental Health and Neurosciences, # 2900, Hosur Road, Bangalore 560029, Karnataka, India.
Neurochem Int. 2015 Oct;89:198-208. doi: 10.1016/j.neuint.2015.07.003. Epub 2015 Jul 7.
The anatomical location of the central nervous system (CNS) renders it immunologically and pharmacologically privileged due to the blood brain barrier (BBB). Although this limits the transport of unfavorable molecules to the CNS, the ensuing privilege could be disadvantageous for therapeutic compounds. Hence, the greatest challenge in the pharmacotherapy of CNS diseases is to ensure efficient brain targeting and drug delivery. Research evidences indicate that dietary polyphenols have neuroprotective potential against CNS diseases. However, their selective permeability across BBB, poor absorption, rapid metabolism and systemic elimination limit their bioavailability and therapeutic efficacy. Consequently, the beneficial effects of these orally administered agents in the CNS still remain a subject of debate. This has also limited its clinical application either as independent or adjunctive therapy. Improving the in vivo bioavailability by novel methods could improve the therapeutic feasibility of polyphenols and assist in evolving novel drugs and their derivatives with improved efficacy in vivo. Here we review the mechanistic and pharmacological issues related to the bioavailability of polyphenols with therapeutic implications for CNS diseases. We surmise that improving the bioavailability of polyphenols entails efficient in vivo transport across BBB, biochemical stability, improved half-life and persistent neuroprotection in the CNS.
由于血脑屏障（BBB）的存在，中枢神经系统（CNS）的解剖位置使其在免疫和药理学上具有特权。尽管这限制了不利分子向中枢神经系统的转运，但随之而来的特权可能对治疗性化合物不利。因此，中枢神经系统疾病药物治疗的最大挑战是确保有效的脑靶向和药物递送。研究证据表明，膳食多酚对中枢神经系统疾病具有神经保护潜力。然而，它们穿过血脑屏障的选择性通透性、较差的吸收、快速代谢和全身消除限制了它们的生物利用度和治疗效果。因此，这些口服给药制剂在中枢神经系统中的有益作用仍然存在争议。这也限制了其作为独立治疗或辅助治疗的临床应用。通过新方法提高体内生物利用度可以提高多酚的治疗可行性，并有助于开发在体内具有更高疗效的新型药物及其衍生物。在这里，我们综述了与多酚生物利用度相关的机制和药理学问题，这些问题对中枢神经系统疾病具有治疗意义。我们推测，提高多酚的生物利用度需要在体内有效地穿过血脑屏障、生化稳定性、延长半衰期以及在中枢神经系统中持续发挥神经保护作用。
