Therapeutic potential of Polygala saponins in neurological diseases

Background: There are many types of neurological diseases with complex etiologies. At present, most clinical drugs can only relieve symptoms but cannot cure these diseases. Radix Polygalae, a famous traditional Chinese medicine from the root of plants of the genus Polygala, has the traditional effect of treating insomnia, forgetfulness, and palpitation and improving intelligence and other symptoms of neurological diseases. Saponins are important bioactive components of plants of the genus Polygala and exhibit neuroprotective effects. Purpose: This review aimed to summarize the traditional use of Polygala species and discuss the latest phytochemical, pharmacological, and toxicological findings, mainly with regard to Polygala saponins in the treatment of neurological disorders. Methods: Literature was searched and collected using databases, including PubMed, Science Direct, CNKI, and Google Scholar. The search terms used included "Polygala", "saponins", "neurological diseases", "Alzheimer's disease", "toxicity", etc., and combinations of these keywords. A total of 1202 papers were retrieved until August 2022, and we included 135 of these papers on traditional uses, phytochemistry, pharmacology, toxicology and other fields. Results: This literature review mainly reports on the traditional use of the Polygala genus and prescriptions containing Radix Polygalae in neurological diseases. Phytochemical studies have shown that plants of the genus Polygala mainly include saponins, flavonoids, oligosaccharide esters, alkaloids, coumarins, lignans, flavonoids, etc. Among them, saponins are the majority. Modern pharmacological studies have shown that Polygala saponins have neuroprotective effects on a variety of neurological diseases. Its mechanism of action involves autophagic degradation of misfolded proteins, anti-inflammatory, anti-apoptotic, antioxidative stress and so on. Toxicological studies have shown that Polygala saponins trigger gastrointestinal toxicity, and honey processing and glycosyl disruption of Polygala saponins can effectively ameliorate its gastrointestinal side effect. Conclusion: Polygala saponins are the major bioactive components in plants of the genus Polygala that exhibit therapeutic potential in various neurological diseases. This review provides directions for the future study of Polygala saponins and references for the clinical use of prescriptions containing Radix Polygalae for the treatment of neurological diseases.