1. Academic Validation
  2. Ameliorative Effect of Structurally Divergent Oleanane Triterpenoid, 3-Epifriedelinol from Ipomoea batatas against BPA-Induced Gonadotoxicity by Targeting PARP and NF-κB Signaling in Rats

Ameliorative Effect of Structurally Divergent Oleanane Triterpenoid, 3-Epifriedelinol from Ipomoea batatas against BPA-Induced Gonadotoxicity by Targeting PARP and NF-κB Signaling in Rats

  • Molecules. 2022 Dec 29;28(1):290. doi: 10.3390/molecules28010290.
Muhammad Majid 1 Anam Farhan 2 Muhammad Waleed Baig 3 Muhammad Tariq Khan 4 Yousaf Kamal 1 Syed Shams Ul Hassan 5 Simona Bungau 6 Ihsan-Ul Haq 3
Affiliations

Affiliations

  • 1 Faculty of Pharmacy, Hamdard University, Islamabad 45550, Pakistan.
  • 2 Department of Biology, School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan.
  • 3 Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
  • 4 Faculty of Pharmacy, Capital University of Science and Technology, Islamabad 44000, Pakistan.
  • 5 Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 6 Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania.
Abstract

The Pentacyclic Triterpenoids (PTs) of plant origin are reputed to restrain prostate Cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with Bax, −8.1 Kcal/mol (Bcl-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3−50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated Bax and P53 and decreased Bcl-2 and NF-κB expression, thereby triggering Apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or Adjuvant therapy against PCa and toxins-induced gonadotoxicity.

Keywords

Ipomoea; aerial part; antiproliferative; apoptosis; inflammation; pentacyclic triterpenoids; prostate; sweet potato.

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