Neuroprotective properties of Betulin, Betulinic acid, and Ursolic acid as triterpenoids derivatives: a comprehensive review of mechanistic studies

ABSTRACTABSTRACTCognitive deficits are the main outcome of neurological disorders whose occurrence has risen over the past three decades. Although there are some pharmacologic approaches approved for managing neurological disorders, it remains largely ineffective. Hence, exploring novel nature-based nutraceuticals is a pressing need to alleviate the results of neurodegenerative diseases, such as Alzheimer’s disease (AD) and other neurodegenerative disorders. Some triterpenoids and their derivates can be considered potential therapeutics against neurological disorders due to their neuroprotective and cognitive-improving effects. Betulin (B), betulinic acid (BA), and ursolic acid (UA) are pentacyclic triterpenoid compounds with a variety of biological activities, including antioxidative, neuroprotective and anti-inflammatory properties. This review focuses on the therapeutic efficacy and probable molecular mechanisms of triterpenoids in damage prevention to neurons and restoring cognition in neurodegenerative diseases. Considering few studies on this concept, the precise mechanisms that mediate the effect of these compounds in neurodegenerative disorders have remained unknown. The findings can provide sufficient information about the advantages of these compounds against neurodegenerative diseases.KEYWORDS: BetulinBetulinic acidUrsolic acidAlzheimer’s diseaseParkinson’s diseaseIschemiastress oxidativeneuroinflammation AcknowledgmentsThe author is thankful for the Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran, for supporting this study.Disclosure statementNo potential conflict of interest was reported by the author(s).Data availability statementData regarding the present study are available from the corresponding author, upon reasonable request.Additional informationNotes on contributorsMahan FarzanMahan Farzan is a medical student, writes on neuroscience and nutrition, vaccine design and tissue engineering. Among his recent publications are: Role of Antioxidants in Autoimmune Diseases (ISBN: 979-8751126810) and Iranian Future Healthcare Professionals' knowledge and opinions about rare diseases: cross-sectional study (Orphanet Journal of Rare Diseases, 2022).Mahour FarzanMahour Farzan is a medical student, writes on neuroscience and nutrition, vaccine design and tissue engineering. Among his recent publications are: Role of Antioxidants in Autoimmune Diseases (ISBN: 979-8751126810) and Engineering of a core-shell polyvinyl alcohol/gelatin fibrous scaffold for dual delivery of Thymus daenensis essential oil and Glycyrrhiza glabra L. extract as an antibacterial and functional wound dressing (Journal of Drug Delivery Science and Technology, 2023).Mehrdad ShahraniMehrdad Shahrani is a Professor of physiology, writes on neuroscience and nutrition. Among his recent articles are: Coumaric acid ameliorates experimental colitis in rats through attenuation of oxidative stress, inflammatory response and apoptosis (Inflammopharmacology, 2022).Seyedeh Parisa NavabiSeyedeh Parisa Navabi, Assistant Professor of physiology, writes on neuroscience and nutrition. Among his recent articles are: The effects of betulinic acid on neurobehavioral activity, electrophysiology and histological changes in an animal model of the Alzheimer's disease (Behavioural Brain Research, 2018) and Protective Effects of Co-administration of Zinc and Selenium Against Streptozotocin-Induced Alzheimer's Disease: Behavioral, Mitochondrial Oxidative Stress, and GPR39 Expression Alterations in Rats (neurotoxicity research, 2020).Hossien Rajabi VardanjaniHossien Rajabi Vardanjani is an employee and PhD of pharmacology, writes on pharmacology. Among his recent articles is: PMSF Attenuates Morphine Antinociceptive Tolerance and Dependence in Mice: Its Association with the Oxidative Stress Suppression (Iranian Journal of Pharmaceutical Research, 2021).Hossein Amini-KhoeiHossein Amini-Khoei is a professor of pharmacology, writes on neurology, psychiatry and gastroenterology. Among his recent articles are: Anticonvulsant effect of quercetin in pentylenetetrazole (PTZ)-induced seizures in male mice: The role of anti-neuroinflammatory and anti-oxidative stress (International Immunopharmacology, 2023) and Coumaric acid ameliorates experimental colitis in rats through attenuation of oxidative stress, inflammatory response and apoptosis (Inflammopharmacology, 2022).Sahreh ShabaniSahreh Shabani is a Professor of physiology, writes on neuroscience and nutrition. Among his recent articles are: Diosmin is neuroprotective in a rat model of scopolamine-induced cognitive impairment (Biomedicine & Pharmacotherapy, 2018) and Exploring the multifaceted neuroprotective actions of gallic acid: A review (International Journal of Food Properties, 2020).