Methanolic Extract of Boswellia serrata Gum Protects the Nigral Dopaminergic Neurons from Rotenone-Induced Neurotoxicity

Abstract

Boswellia serrata gum is a natural product that showed beneficial effects on neurodegenerative diseases in recent studies. In this study, we investigated the effects of Boswellia serrata resin on rotenone-induced dopaminergic neurotoxicity. Firstly, we attempted to see if the resin can induce AMP-activated protein kinase (AMPK) signaling pathway which has been known to have broad neuroprotective effects. Boswellia increased AMPK phosphorylation and reduced phosphorylation of mammalian target of rapamycin (p-mTOR) and α-synuclein (p-α-synuclein) in the striatum while increased the expression level of Beclin1, a marker for autophagy and brain-derived neurotrophic factor. Next, we examined the neuroprotective effects of the Boswellia extract in the rotenone-injected mice. The results showed that Boswellia evidently attenuated the loss of the nigrostriatal dopaminergic neurons and microglial activation caused by rotenone. Moreover, Boswellia ameliorated rotenone-induced decrease in the striatal dopamine and impairment in motor function. Accumulation of α-synuclein meditated by rotenone was significantly ameliorated by Boswellia. Also, we showed that β-boswellic acid, the active constituents of Boswellia serrata gum, induced AMPK phosphorylation and attenuated α-synuclein phosphorylation in SHSY5 cells. These results suggest that Boswellia protected the dopaminergic neurons from rotenone neurotoxicity via activation of the AMPK pathway which might be associated with attenuation of α-synuclein aggregation and neuroinflammation. Further investigations are warranted to identify specific molecules in Boswellia which are responsible for the neuroprotection.

Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases

“…Various environmental stressors are implicated as risk factors for neurodegenerative diseases, and interestingly they are also involved in aging, oxidative stress and/or DNA damage [230]. Of these, heavy metals (Pb, Cd, As, Hg, Cu, Zn and Fe) and pesticides (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP], paraquat, dieldrin, rotenone [231]) in particular are associated with neurotoxicity and induction of DNA damage via oxidative stress [232].…”

The dual face of microglia (M1/M2) as a potential target in the protective effect of nutraceuticals against neurodegenerative diseases

“…Boswellia enhanced AMPK phosphorylation, decreased p-mTOR and p-α-synuclein in the striatum, and raised the expression of Beclin1 and brain-derived neurotrophic factor. Boswellia reduced dopaminergic neuron loss, microglial activation, and a -synuclein accumulation in ROT-injected rats, increasing striatal dopamine levels and motor performance ( Shadfar et al, 2022 ).…”

From Preclinical to Clinical Evidence: Exploring the Multiple Perspectives and Healing Power of Boswellia Serrata Roxb. Ex Colebr

“…In the brain, other mechanisms underlying the beneficial effects of BAs include a decreased glial cell activation and upregulation of antioxidant proteins, resulting in neuroprotection (21). In a rotenone-induced model of Parkinson's disease, B. serrata extract increased AMPK phosphorylation, reducing p-mTOR and α-synuclein (22). In a streptozotocin-induced model of Alzheimer's disease BAs significantly reduced phosphorylated tau and enhanced reelin expression (23).…”

“…Excess glutamate release is also modulated by AKBA or by B. serrata extract activity against excitotoxicity induced apoptosis (106,107). Notably, the neuroprotective effects of boswellia have also been documented in Parkinson's disease (PD) animal models in which boswellia extracts can alleviate experimental dopaminer-gic neuronal loss, modulate autophagy, reduce oxidative stress and inflammation and reduce α-synuclein accumulation (108,109). Multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) are among the neurodegenerative diseases studied to be positively impacted by B. serrata constituents.…”