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Tribulusterine Containing Tribulus terrestris Extract Exhibited Neuroprotection Through Attenuating Stress Kinases Mediated Inflammatory Mechanism: In Vitro and In Vivo Studies

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Abstract

The present study has been aimed to explore the different secondary messengers of the inflammatory pathway NF-κB, kinases (JNK, P38MAPK, GSK3β/βcatenin), apoptosis pathway (Caspase-3 and AIF), and neuronal survival pathway (BDNF) in order to understand the neuroprotective mechanism of aqueous extract of Tribulus terrestris (AQTT). In primary cortical neurons, the ischemic condition was induced through oxygen–glucose deprivation (OGD). Anti-inflammatory activity of AQTT was evaluated in formalin induced inflammation model and carrageenan-induced paw edema test. The bilateral common carotid artery occlusion model was employed for whole animal studies. Treatment of AQTT (100 mg/kg) significantly reduced the inflammation induced by formalin and carrageenan. The neuroprotective mechanism of AQTT (50 and 100 mg/kg) was assessed by pre- and post-administration. The results indicate down regulation of kinases and NFkB, suggesting possible anti-inflammatory activity of AQTT. Additionally, AQTT down regulated both caspase dependent and independent apoptotic pathways suggesting its possible anti-apoptotic activity. The treatment of AQTT also reduced GSK3β levels and increased p-Ser9 GSK3β levels; stabilizing the unphosphorylated form of β-catenin and its translocation into the nucleus suggesting role of AQTT in neuronal survival and GSK3β mediated anti-inflammatory property. In comparison to pretreatment, post treatment of AQTT had lesser effects indicating tribulusterine standardized AQTT may have prophylactic effect. This study can be concluded with the thesis that AQTT has neuroprotective effect through alternating neuroinflammation, apoptosis, and promoting neuron survival. Being that it produced better effect with pretreatment, exploring this with thrombolytic drugs will be beneficial. For the first time AQTT has been reported for this indication.

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Acknowledgements

This study was financially supported by University of Toledo, OHIO, USA, PSG Sons & Charities, and PSG College of Pharmacy, Coimbatore, India. We are grateful to Dr. Sivaram Hariharan for his helpful grammar corrections on the manuscript. We thank N. Rama Varier of Ayurvedic foundation for providing gift sample of T.terrestris aqueous extract.

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Authors and Affiliations

  1. Department of Pharmacology, PSG College of Pharmacy, Peelamedu, Coimbatore, Tamil Nadu, 641004, India

    R. Ranjithkumar & Muthiah Ramanathan

  2. Department of Medicinal and Biological Chemistry, Frederic and Mary Wolfe Center 292A, University of Toledo, 3000 Arlington Avenue, Toledo, OH, 43614, USA

    Qasim Alhadidi & Zahoor A. Shah

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  1. R. Ranjithkumar
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Correspondence to Muthiah Ramanathan.

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Ranjithkumar, R., Alhadidi, Q., Shah, Z.A. et al. Tribulusterine Containing Tribulus terrestris Extract Exhibited Neuroprotection Through Attenuating Stress Kinases Mediated Inflammatory Mechanism: In Vitro and In Vivo Studies. Neurochem Res 44, 1228–1242 (2019). https://doi.org/10.1007/s11064-019-02768-7

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