Phytochemicals targeting lncRNAs: A novel direction for neuroprotection in neurological disorders

Neurological disorders with various etiologies impacting the nervous system are prevalent in clinical practice. Long non-coding RNA (lncRNA) molecules are functional RNA molecules exceeding 200 nucleotides in length that do not encode proteins, but participate in essential activities. Research indicates that lncRNAs may contribute to the pathogenesis of neurological disorders, and may be potential targets for their treatment. Phytochemicals in traditional Chinese herbal medicine (CHM) have been found to exert neuroprotective effects by targeting lncRNAs and regulating gene expression and various signaling pathways. We aim to establish the development status and neuroprotective mechanism of phytochemicals that target lncRNAs through a thorough literature review. A total of 369 articles were retrieved through manual and electronic searches of PubMed, Web of Science, Scopus and CNKI databases from inception to September 2022. The search utilized combinations of natural products, lncRNAs, neurological disorders, and neuroprotective effects as keywords. The included studies, a total of 31 preclinical trials, were critically reviewed to present the current situation and the progress in phytochemical-targeted lncRNAs in neuroprotection. Phytochemicals have demonstrated neuroprotective effects in preclinical studies of various neurological disorders by regulating lncRNAs. These disorders include arteriosclerotic ischemia-reperfusion injury, ischemic/hemorrhagic stroke, Alzheimer's disease, Parkinson's disease, glioma, peripheral nerve injury, post-stroke depression, and depression. Several phytochemicals exert neuroprotective roles through mechanisms such as anti-inflammatory, antioxidant, anti-apoptosis, autophagy regulation, and antagonism of Aβ-induced neurotoxicity. Some phytochemicals targeted lncRNAs and served a neuroprotective role by regulating microRNA and mRNA expression. The emergence of lncRNAs as pathological regulators provides a novel direction for the study of phytochemicals in CHM. Elucidating the mechanism of phytochemicals regulating lncRNAs will help to identify new therapeutic targets and promote their application in precision medicine.