In vitro anti-inflammatory activity screening in LPS intoxicated Raw 264.7 murine macrophage cell line showed tribulusterine/perlolyrine had its activity by down regulating inflammatory mediators such as iNOS, COX2, TNFα and IL1β
• Screening of aqueous extract of Tribulus terrestris has shown neuroprotective activity by regulating the GSK-3β pathway protein level and elevating β-catenin and S9-phospho GSK-3β protein level. It also stabilizes GSK-3 β / β-catenin pathway, maintains GSK-3β in inactive state, prevents dephosphorylation thereby reduces β-catenin degradation and
mediates its translocation resulting in neuroprotection.
• Docking studies revealed tribulusterine / perlolyrine can be a possible prototype from natural source Tribulus terrestris.
• Tribulusterine / perlolyrine protected oxygen glucose deprived reperfusion injured differentiated SHSY5Y cells which is revealed by cell viability studies.
• The molecular pathway through which tribulusterine/perlolyrine exhibits it neuroprotection is by down regulating both caspase dependent and independent pathway by inhibiting stress kinasess.
• Five novel leads have been identified through pharmacophore based structure search which can be explored further for their neuroprotective activity.
The study can be concluded that tribulusterine/perlolyrine exhibits it neuroprotection by down regulating both caspase dependent and independent pathway by inhibiting stress kinases. Further it possesses anti inflammatory activity so it can be efficacious in ischemia condition because stroke pathology involves neuro inflammation as a major cascade for disease prognosis.
IMPACT OF STUDY:
Treatment of neurodegenerative disease such as stroke is a major challenge for the physicians. Neuroprotective effects of voltage dependent calcium channel blockers, NMDA antagonists and radical scavengers were found to be effective in experimental models of cerebral ischemia. The outcome of these drugs as therapeutic regimen is still beyond reach. Medicinal plants have been historically known a rich source for successful lead identification, and always signify an important pool for the discovery of new pharmacological hits as on date. Tribulusterine/perlolyrine, a possible prototype exhibited it neuroprotection is by down regulating both caspase dependent and independent pathway by inhibiting stress kinasess. Five novel leads have been identified from natural source which can be potential candidates as novel anti- inflammatory and neuroprotective agents. In revelation of the increasing cost of development of new drugs, alternative approaches like development from herbal extracts could be beneficial
