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Antiparkinsonian activity of Cucurbita pepo seeds along with possible underlying mechanism

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Abstract

Cucurbita pepo is used as a vegetable in Pakistan and its seeds are also rich in tocopherol. Data showed the pivotal role of tocopherol in the treatment of Parkinson’s disease (PD). The current study was designed to probe into the antiparkinson activity of methanolic extract of C. pepo (MECP) seeds in the haloperidol-induced Parkinson rat model. Behavioral studies showed improvement in motor functions. The increase in catalase, superoxide dismutase, glutathione levels whereas the decreases in the malondialdehyde and nitrite levels were noted in a dose-dependent manner. Acetylcholine-esterase (AchE) activity was increased. Molecular docking results revealed significant binding interaction of selected phytoconstituents within an active site of target protein AchE (PDB ID: 4EY7). Furthermore, α-synuclein was up regulated with down regulation of TNF-α and IL-1β in the qRT-PCR study. Subsequently, ADMET results on the basis of structure to activity predictions in terms of pharmacokinetics and toxicity estimations show that selected phytochemicals exhibited moderately acceptable properties. These properties add knowledge towards the structural features which could improve the bioavailability of selected phytochemicals before moving towards the initial phase of the drug development. Our integrated drug discovery scheme concluded that C. pepo seeds could ameliorate symptoms of PD and may prove a lead remedy for the treatment of PD.

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Acknowledgements

Authors are thankful to Riphah Institute of Pharmaceutical Sciences for providing laboratory facilities to complete biochemical analysis.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan

    Uzma Saleem, Aisha Shehzad, Zohaib Raza & Zunera Chauhdary

  2. Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan

    Shahid Shah

  3. Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan

    Muhammad Ajmal Shah

  4. Yunnan Herbal Laboratory, School of Ecology and Environmental Sciences, Yunnan University, Kunming, 650091, Yunnan, China

    Shabana Bibi

  5. The International Joint Research Center for Sustainable Utilization of Cordyceps Bioresouces in China and Southeast Asia, Yunnan University, Kunming, 650091, Yunnan, China

    Shabana Bibi

  6. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, 54000, Pakistan

    Bashir Ahmad

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  1. Uzma Saleem
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  2. Aisha Shehzad
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Contributions

US, MAS and BA conceived and designed the research. AS and ZC performed the experimental work. SS did qRT-PCR and ZR performed docking study. SB performed the pharmacokinetic and toxicity estimations, US, MAS, SB and BA reviewed and drafted the final manuscript.

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Correspondence to Uzma Saleem or Muhammad Ajmal Shah.

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Saleem, U., Shehzad, A., Shah, S. et al. Antiparkinsonian activity of Cucurbita pepo seeds along with possible underlying mechanism. Metab Brain Dis 36, 1231–1251 (2021). https://doi.org/10.1007/s11011-021-00707-6

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