Plant-Based Antioxidants for Prevention and Treatment of Neurodegenerative Diseases: Phytotherapeutic Potential of Laurus nobilis, Aronia melanocarpa, and Celastrol

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TL;DR

This narrative review examines the neuroprotective potential of three plant-based antioxidants—Laurus nobilis (bay laurel), Aronia melanocarpa (black chokeberry), and celastrol (from Tripterygium wilfordii)—for the prevention and treatment of neurodegenerative diseases (NDDs). The authors summarize preclinical evidence showing these agents reduce oxidative stress and neuroinflammation through mechanisms including Nrf2 activation, NF-κB suppression, and heat shock protein induction, with some studies demonstrating anti-acetylcholinesterase and anti-aggregation effects relevant to Alzheimer's and Parkinson's diseases. The review concludes that despite promising in vitro and in vivo results, further clinical research is needed to establish efficacy, optimal dosing, and bioavailability for these phytotherapeutics in NDDs.

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**Background:** Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), are characterized by progressive neuronal loss and lack curative treatments. Oxidative stress (OS)—an imbalance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant defenses—is increasingly recognized as a central pathogenic mechanism. The brain is especially vulnerable due to high oxygen consumption, abundant polyunsaturated fatty acids, and relatively weak antioxidant systems. OS damages lipids, proteins, and DNA, promotes protein aggregation (Aβ, tau, α-synuclein), triggers mitochondrial dysfunction, and fuels neuroinflammation via microglial activation and NF-κB signaling. Plant-derived antioxidants offer a promising therapeutic strategy by modulating these pathways. This review focuses on three understudied plant-based products: Laurus nobilis leaf extracts, Aronia melanocarpa (black chokeberry) extracts, and celastrol (a pentacyclic nortriterpenquinone from Tripterygium wilfordii and T. regelii).

**Methods:** This is a narrative review summarizing preclinical (in vitro and in vivo) studies on the neuroprotective, antioxidant, and anti-inflammatory effects of L. nobilis, A. melanocarpa, and celastrol. The authors synthesized findings from published literature on chemical composition, mechanisms of action, and experimental models of NDDs. No systematic search strategy or inclusion/exclusion criteria are reported.

**Key Results:** For L. nobilis, the essential oil (LNEO) and its major constituent 1,8-cineole (eucalyptol) demonstrated anti-acetylcholinesterase (AChE) activity, with the water extract achieving 90.72% AChE inhibition. LNEO showed IC50 values >400 µg/mL against SH-SY5Y neuroblastoma cells (not cytotoxic per National Cancer Institute criteria). Spirafolide and reynosin (sesquiterpene lactones) reduced dopamine-induced ROS production and apoptosis in SH-SY5Y cells; the hexane fraction had an IC50 of 3.0 µg/mL for dopamine-induced apoptosis. Reynosin protected against 6-OHDA-induced TH-positive neuronal loss in rats. Lindoldhamine inhibited ASIC1a channels by 98.1%, 93.7%, and 69.3% at pH 6.9, 6.7, and 6.5, respectively. Polyphenol-enriched leaf extracts showed cytoprotective effects against H2O2 and Aβ(25-35) in neuronal cell lines.

For A. melanocarpa, aronia extracts increased SOD, CAT, and GPx enzyme activities and upregulated heat shock protein gene expression. Anthocyanins reduced NO generation, TNF-α and IL-2 production, and suppressed NF-κB, iNOS, and COX-2. In scopolamine-induced memory impairment in mice, aronia extract attenuated learning deficits and decreased hippocampal AChE while increasing BDNF and p-CREB expression. In aged rats (24 months), aronia juice for 105 days increased hippocampal AChE activity and nerve fiber density. Protocatechuic acid (PCA), a major anthocyanin metabolite, inhibited Aβ and α-synuclein fibril formation and destabilized preformed fibrils. In a randomized controlled trial of healthy overweight middle-aged individuals, 24 weeks of aronia extract supplementation showed positive effects on cognitive performance and blood pressure.

For celastrol, neuroprotective mechanisms include inhibition of NF-κB, COX-2, and GSK-3β; induction of HSP27, HSP40, and HSP70 via HSF1 nuclear translocation; reduction of Aβ production by suppressing BACE-1; and promotion of autophagy via TFEB activation to degrade tau aggregates. In PD models, celastrol prevented dopaminergic neuron loss, increased HSP70, and improved motor deficits via the Nrf2-NLRP3-caspase-1 pathway. In SOD1 transgenic ALS mice, celastrol arrested spinal cord neuron loss and decreased TNF-α and iNOS. In cerebral ischemia models, celastrol reduced infarct volume and neuroinflammation via HMGB1/NF-κB suppression and IL-33/ST2-mediated M2 microglial polarization.

**Clinical Implications:** Despite extensive preclinical evidence, no clinical trials have yet validated the neuroprotective effects of L. nobilis or celastrol in NDD patients. Two clinical studies on L. nobilis are registered but results are not available. One human trial with A. melanocarpa showed cognitive benefits in at-risk individuals. Major limitations include poor bioavailability of polyphenols (especially anthocyanins), lack of standardized dosing, insufficient blood-brain barrier penetration data, and absence of long-term safety profiles. The authors call for further research on nanoformulation and prodrug strategies to improve bioavailability, and emphasize the need for rigorous clinical trials to translate these promising preclinical findings into clinical practice.