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

• Published in: Molecular neurobiology 2022-09, Vol.59 (9), p.5874-5890
• Main Authors: Shadfar, Sina, Khanal, Shristi, Bohara, Ganesh, Kim, Geumjin, Sadigh-Eteghad, Saeed, Ghavami, Saeid, Choi, Hyukjae, Choi, Dong-Young
• Format: Article
• Language: English
• Subjects: alpha-Synuclein - metabolism; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Animals; Autophagy; Biomedical and Life Sciences; Biomedicine; Boswellia; Boswellia - metabolism; Boswellia serrata; Brain-derived neurotrophic factor; Cell Biology; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons - metabolism; Inflammation; Kinases; Mammals - metabolism; Methanol - metabolism; Methanol - pharmacology; Mice; Natural products; Neostriatum; Neurobiology; Neurodegenerative diseases; Neurology; Neurons; Neuroprotection; Neuroprotective Agents - metabolism; Neuroprotective Agents - pharmacology; Neurosciences; Neurotoxicity; Neurotoxicity Syndromes - metabolism; Parkinson's disease; Phosphorylation; Plant Extracts - metabolism; Plant Extracts - pharmacology; Rapamycin; Rotenone; Rotenone - pharmacology; Signal transduction; Substantia nigra; Synuclein; TOR protein
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-022-02943-y

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.