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Unveiling the Cardioprotective Power: Liquid Chromatography–Mass Spectrometry (LC–MS)-Analyzed Neolamarckia cadamba (Roxb.) Bosser Leaf Ethanolic Extract against Myocardial Infarction in Rats and In Silico Support Analysis

Authors

  • Raghupathi Kumar Department of Pharmacology, Santhiram College of Pharmacy, JNTUA, Nandyal 518112, Andhra Pradesh, India; [email protected] (R.N.K.); [email protected] (P.G.M.)
  • Dsnbk Prasanth Department of Pharmacognosy, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada 520010, Andhra Pradesh, India; [email protected]
  • Praisy Midthuri Department of Pharmacology, Santhiram College of Pharmacy, JNTUA, Nandyal 518112, Andhra Pradesh, India; [email protected] (R.N.K.); [email protected] (P.G.M.)
  • Sheikh Ahmad Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
  • Attuluri Badarinath Department of Pharmaceutics, Santhiram College of Pharmacy, Nandyala 518112, Andhra Pradesh, India; [email protected]
  • Srikanth Karumanchi Department of Pharmaceutical Chemistry, DKSS Institute of Pharmaceutical Science & Research (for Girls), Swami-Chincholi, Bhigwan 413130, Maharashtra, India; [email protected]
  • Ramanjaneyulu Seemaladinne Department of Chemistry and Biochemistry, Lamar University, Beaumont, TX 77705, USA; [email protected]
  • Rahul Nalluri Department of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA; [email protected]
  • Praveen Pasala Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, JNTUA, Anantapuramu 515721, Andhra Pradesh, India

Keywords:

Neolamarckia cadamba, HR-LC–MS, molecular docking, myocardial infarction, oxidative stress, HMG-CoA reductase

Abstract

Neolamarckia cadamba (Roxb.) Bosser, a member of the Rubiaceae family, is a botanical species with recognized therapeutic properties. It is commonly used in traditional medicine to treat cardiac ailments and other disorders. However, the precise active constituents and the potential mechanisms by which they manage cardiovascular disorders remain unclear. Therefore, this study aimed to ascertain the bioactive components and investigate their underlying mechanisms of action. N. cadamba is used to treat cardiovascular disorders using the integrated metabolomic methodology. An HPLC-QTOF-MS/MS analysis determined the potential chemicals in the N. cadamba leaf ethanol extract (NCEE). A thorough investigation of the NCEE samples used in this study led to the identification of 32 phytoconstituents. Of the 32 compounds, 19 obeyed Lipinski’s rule of five (RO5). A molecular docking study directed towards HMG-CoA reductase used 19 molecules. The reference drug atorvastatin indicated a binding energy of −3.9 kcal/mol, while the other substances, Cinchonain Ib and Dukunolide B, revealed binding energies of −5.7 and −5.3 kcal/mol, respectively. Both phytocompounds showed no toxicity and exhibited favorable pharmacokinetic properties. In vivo study results concluded that treatment with NCEE significantly reduced the cardiac myocardial infarction (MI) marker CK-MB and atherogenic risk indices, such as the atherogenic index plasma (AIP), cardiac risk ratio (CRR), and atherogenic coefficient (AC) in isoproterenol-induced MI rats. In MI rats, NCEE therapy significantly improved the antioxidant system of the heart tissue, as evidenced by the increased levels of GSH and SOD, lower levels of the oxidative stress marker MDA, and significantly decreased HMG-CoA activity. Additionally, electrocardiogram (ECG) signals from rats treated with NCEE resembled those treated with traditional atorvastatin to treat myocardial infarction. This study used H&E staining to show that administering NCEE before treatment reduced cardiac myocyte degeneration in rats with myocardial infarction, increased the presence of intact nuclei, and increased myocardial fiber strength. The potential cardioprotective effect observed in myocardial infarction (MI) rats treated with NCEE can be extrapolated from computational data to be caused by Cinchonain Ib. Keywords: Neolamarckia cadamba, HR-LC–MS, molecular docking, myocardial infarction, oxidative stress, HMG-CoA reductase

Author Biographies

Raghupathi Kumar, Department of Pharmacology, Santhiram College of Pharmacy, JNTUA, Nandyal 518112, Andhra Pradesh, India; [email protected] (R.N.K.); [email protected] (P.G.M.)

Methodology

Dsnbk Prasanth, Department of Pharmacognosy, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada 520010, Andhra Pradesh, India; [email protected]

Software

Praisy Midthuri, Department of Pharmacology, Santhiram College of Pharmacy, JNTUA, Nandyal 518112, Andhra Pradesh, India; [email protected] (R.N.K.); [email protected] (P.G.M.)

Methodology

Sheikh Ahmad, Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

Writing – original draft

Attuluri Badarinath, Department of Pharmaceutics, Santhiram College of Pharmacy, Nandyala 518112, Andhra Pradesh, India; [email protected]

Validation, Data curation

Srikanth Karumanchi, Department of Pharmaceutical Chemistry, DKSS Institute of Pharmaceutical Science & Research (for Girls), Swami-Chincholi, Bhigwan 413130, Maharashtra, India; [email protected]

Formal analysis, Writing – original draft

Ramanjaneyulu Seemaladinne, Department of Chemistry and Biochemistry, Lamar University, Beaumont, TX 77705, USA; [email protected]

Writing – original draft

Rahul Nalluri, Department of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA; [email protected]

Writing – review & editing

Praveen Pasala, Department of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, JNTUA, Anantapuramu 515721, Andhra Pradesh, India

Investigation

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