Pterostilbene as a Therapeutic Alternative for Central Nervous System Disorders: A Review of the Current Status and Perspectives

Abstract

Neurological disorders are diverse, have complex causes, and often result in disability; yet, effective treatments remain scarce. The resveratrol derivative pterostilbene possesses numerous physiological activities that hold promise as a novel therapy for the central nervous system (CNS) disorders. This review aimed to summarize the protective mechanisms of pterostilbene in in vitro and in vivo models of CNS disorders and the pharmacokinetics and safety to assess its possible effects on CNS disorders. Available evidence supports the protective effects of pterostilbene in CNS disorders involving mechanisms such as antioxidant and antiinflammatory activity, regulation of lipid metabolism and vascular smooth muscle cell proliferation, improvement of synaptic function and neurogenesis, induction of glioma cell cycle arrest, and inhibition of glioma cell migration and invasion. Studies have identified possible molecular targets and pathways for the protective actions of pterostilbene in CNS disorders including the AMPK/ STAT3, Akt, NF-κB, MAPK, and ERK signaling pathways. The possible pharmacological effects and molecular pathways of pterostilbene in CNS disorders are critically discussed in this review. Future studies should aim to increase our understanding of pterostilbene in animal models and humans to further evaluate its role in CNS disorders and the detailed mechanisms.

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

“…The results show that resveratrol could delay articular cartilage degeneration by balancing HIF-1α and HIF-2α expressions and promoting chondrocyte autophagy, thereby regulating AMPK/mTOR signaling pathway . Similarly to our study, resveratrol was also reported to induce an inadequate assembly of ASC on the mitochondria and inhibit NF-κB responses, leading to the inactivation of NLRP3 inflammasome. − However, the low bioavailability and rapid metabolization made the clinical application of these natural compounds ineffective. ,, PT, a dimethyl ether analog of resveratrol, shows better health effects due to its two dimethyl groups, which increase its bioavailability and result in a longer half-life in vivo . , In particular, several studies suggested that increasing the water solubility of PT significantly improves its oral absorption, thereby promoting the research on the production of highly water-soluble PT-modified compounds and increasing the research potential of PT. − Our previous study demonstrated that PT could significantly attenuate renal fibrosis by downregulating NLRP3 inflammasome activation . Similar to the results in this study, PT affected the regulation of the NLRP3 inflammasome by reducing the expression of TGF-β-induced NLRP3.…”