Neuroprotective Potential of Betulin and Its Drug Formulation with Cyclodextrin—In Vitro Assessment
Open Access
- 11 June 2025
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 26 (12) , 5605
Abstract
Central nervous system disorders, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, are associated with complex pathophysiological mechanisms involving oxidative stress, inflammation, and protein misfolding. According to the literature, betulin, a natural compound derived from the bark of birch trees, demonstrates promising neuroprotective effects. This study investigates the neuroprotective potential of betulin and its complex with cyclodextrin, referred to as Betula Forte, using an in vitro model of differentiated SH-SY5Y neuroblastoma cells. Specifically, the study explores the antioxidant and antiapoptotic properties of these compounds under oxidative stress induced by hydrogen peroxide (H2O2). Our results indicated that Betula Forte exhibited lower cytotoxicity compared to betulin alone. Both substances enhanced cell viability in pre-incubation and co-incubation models, with Betula Forte showing superior efficacy under severe oxidative stress. Additionally, both substances exhibited protective effects against H2O2-induced oxidative stress and apoptosis, as evidenced by reduced levels of reactive oxygen species (ROS) and a lower number of apoptotic cells compared with the H2O2-treated cells. These findings suggest that Betula Forte, due to lower cytotoxicity, may offer a more effective neuroprotective strategy than betulin alone, highlighting its potential as a therapeutic agent for neurodegenerative diseases.Keywords
This publication has 34 references indexed in Scilit:
- The potential role of nitric oxide in the anticonvulsant effects of betulin in pentylenetetrazole (PTZ)-induced seizures in miceIBRO Neuroscience Reports, 2024
- Betulinic acid in the treatment of breast cancer: Application and mechanism progressFitoterapia, 2023
- Betulinic acid in the treatment of tumour diseases: Application and research progressBiomedicine & Pharmacotherapy, 2021
- Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration modelsEuropean Journal of Medicinal Chemistry, 2021
- Delivering Crocetin across the Blood-Brain Barrier by Using γ-Cyclodextrin to Treat Alzheimer’s DiseaseScientific Reports, 2020
- Betulin and its derivatives as novel compounds with different pharmacological effectsBiotechnology Advances, 2020
- DJ-1/PARK7 inhibits high glucose-induced oxidative stress to prevent retinal pericyte apoptosis via the PI3K/AKT/mTOR signaling pathwayExperimental Eye Research, 2019
- Cytoprotective mechanisms of DJ-1 against oxidative stress through modulating ERK1/2 and ASK1 signal transductionRedox Biology, 2018
- Protective effect of betulin on cognitive decline in streptozotocin (STZ)-induced diabetic ratsNeuroToxicology, 2016
- The attenuating effect of memantine on staurosporine-, salsolinol- and doxorubicin-induced apoptosis in human neuroblastoma SH-SY5Y cellsNeurochemistry International, 2008