Serratol, a cembrane diterpene from Boswellia serrata attenuates α-synuclein and fibrillar amyloid-β aggregation in Caenorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Boswellia serrata oleo-gum resin, known as Kundur in Unani medicine, has traditional applications in neurological and cognitive disorders, including Majoon-e-Nisyan and Dawa-ul-Kibreet for Nisyan (amnesia) and Muqawwi-e-Asab (nerve-strengthening) respectively. Serratol is a cembrane diterpene constituent of B. serrata resin, while related frankincense cembranes exhibit neuroactive properties. However, the contribution of serratol to the neurological activities of B. serrata remains poorly explored.

AIM OF THE STUDY: To isolate serratol from B. serrata resin, evaluate its effects on protein-aggregation associated phenotypes in transgenic Caenorhabditis elegans models expressing human α-syn and Aβ1-42, and investigate potential molecular associations.

MATERIALS AND

METHODS

Serratol was isolated from B. serrata resin and evaluated in NL5901 and CL4176 C. elegans models. Network pharmacology, molecular docking and quantitative real-time PCR were used to investigate potential molecular associations.

RESULTS

Serratol reduced α-syn associated fluorescence in NL5901 worms, although no significant improvement was observed in behavioral assays. Network pharmacology identified Alzheimer's disease and Notch signaling related pathways and PSEN1 as a computationally predicted candidate target. In CL4176 worms, serratol reduced ThT-positive, fibrillar Aβ associated fluorescence. Because Aβ1-42 is directly expressed in this model, this phenotype does not provide evidence for altered APP processing or γ-secretase-mediated Aβ production. Molecular docking predicted a possible association of serratol with the catalytic region of human PSEN1 and C. elegans SEL-12, while sel-12 mRNA expression remained unchanged. These computational findings do not establish direct target engagement. In silico ADME analysis showed compliance with several conventional physicochemical filters but a low predicted probability of blood-brain barrier penetration.

CONCLUSION

Serratol modulates protein-aggregation associated phenotypes involving α-syn and fibrillar Aβ1-42 in C. elegans. The findings provide preliminary evidence supporting further investigation of serratol as a natural product scaffold for proteinopathies, while direct aggregation mechanisms, target engagement, functional rescue and CNS exposure remain to be established.