Areej Mohammad Al-Taweel1, Mohammad Raish2, Shagufta Perveen1, Ghada Ahmed Fawzy3, Ajaz Ahmad4, Mushtaq Ahmad Ansari5, Shahid Mudassar6, Majid Ahmad Ganaie7. 1. Department of Pharmacognosy, College of Pharmacy, King Saud University. P. O. Box 22452, Riyadh 11495, Kingdom of Saudi Arabia. 2. Department of Pharmaceutics, College of Pharmacy, King Saud University. P. O. Box 22452, Riyadh 11495, Kingdom of Saudi Arabia. Electronic address: mraish@ksu.edu.sa. 3. Department of Pharmacognosy, College of Pharmacy, King Saud University. P. O. Box 22452, Riyadh 11495, Kingdom of Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. 4. Department of Clinical Pharmacy, College of Pharmacy, King Saud University. P. O. Box 22452, Riyadh 11495, Kingdom of Saudi Arabia. 5. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University. P. O. Box 22452, Riyadh 11495, Kingdom of Saudi Arabia. 6. Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. 7. Department of Pharmacology, College of Pharmacy, Prince Sattam bin Abdulaziz University, AlKharj, Saudi Arabia.
Abstract
BACKGROUND: Nepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent. PURPOSE: This study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats. DESIGN/ METHODS: Cardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues. RESULTS: To the best of our knowledge, this is the first study to report the isolation of nine secondary metabolites from this plant: 1α-hydroxy-7α,14α,18-triacetoxy-isopimara-8,15-diene (1), β-sitosterol (2), lupeol (3), ursolic acid (4), 2,3-dihydroxy ursolic acid (5), caffeic acid (6), methyl rosmarinate (7), rosmarinic acid (8), and an irridoid glucoside 8-epi-7-deoxyloganic acid (9). To explain the mechanisms underlying the cardioprotective effect of NDEE, we evaluated the redox-sensitivity of NDEE in ISP-induced cardiac injury. The oral administration of NDEE (50 and 100 mg/kg b.w) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH, and NO) and myocyte injury marker enzymes and inhibited lipid peroxidation (MDA, MPO). Moreover, NDEE downregulated the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-10) and apoptotic markers (caspase-3 and Bax) and upregulated the anti-apoptotic protein Bcl2. Furthermore, NDEE pretreatment significantly downregulated cardiac NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity. Histological data showed that NDEE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the architecture of cardiomyocytes. CONCLUSION: NDEE demonstrated strong antioxidant, cardioprotective, anti-inflammatory, and anti-apoptotic potential against myocardial damage. This further endorses the use of N. deflersiana in Yemeni folk medicine against cardiovascular diseases.
BACKGROUND:Nepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent. PURPOSE: This study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats. DESIGN/ METHODS: Cardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues. RESULTS: To the best of our knowledge, this is the first study to report the isolation of nine secondary metabolites from this plant: 1α-hydroxy-7α,14α,18-triacetoxy-isopimara-8,15-diene (1), β-sitosterol (2), lupeol (3), ursolic acid (4), 2,3-dihydroxy ursolic acid (5), caffeic acid (6), methyl rosmarinate (7), rosmarinic acid (8), and an irridoid glucoside 8-epi-7-deoxyloganic acid (9). To explain the mechanisms underlying the cardioprotective effect of NDEE, we evaluated the redox-sensitivity of NDEE in ISP-induced cardiac injury. The oral administration of NDEE (50 and 100 mg/kg b.w) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH, and NO) and myocyte injury marker enzymes and inhibited lipid peroxidation (MDA, MPO). Moreover, NDEE downregulated the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-10) and apoptotic markers (caspase-3 and Bax) and upregulated the anti-apoptotic protein Bcl2. Furthermore, NDEE pretreatment significantly downregulated cardiac NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity. Histological data showed that NDEE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the architecture of cardiomyocytes. CONCLUSION:NDEE demonstrated strong antioxidant, cardioprotective, anti-inflammatory, and anti-apoptotic potential against myocardial damage. This further endorses the use of N. deflersiana in Yemeni folk medicine against cardiovascular diseases.
Authors: Raha Orfali; Nasir Ali Siddiqui; Perwez Alam; Tawfeq Abdullah Alhowiriny; Areej Mohammad Al-Taweel; Sami Al-Yahya; Najwa Mohammed Majrashi; Rashad Mehmood; Shabana Iqrar Khan; Shagufta Perveen Journal: Evid Based Complement Alternat Med Date: 2018-09-13 Impact factor: 2.629