Beneficial effects of aqueous extract of stem bark of Terminalia arjuna (Roxb.), An ayurvedic drug in experimental pulmonary hypertension
The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right v...
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| Published in | Journal of ethnopharmacology Vol. 197; no. NA; pp. 184 - 194 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Ireland
Elsevier B.V
02.02.2017
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| Online Access | Get full text |
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| Abstract | The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects.
Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH.
The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated.
The study was approved by Institutional Animal Ethics Committe.
Male Wistar rats (150–200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively.
MCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil.
Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening.
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| AbstractList | The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH.ETHNOPHARMACOLOGICAL RELEVANCEThe stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH.The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated.AIM OF THE STUDYThe effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated.The study was approved by Institutional Animal Ethics Committe. Male Wistar rats (150-200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively.MATERIALS AND METHODSThe study was approved by Institutional Animal Ethics Committe. Male Wistar rats (150-200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively.MCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil.RESULTSMCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil.Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening.CONCLUSIONSAqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening. The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects.Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH.The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated.The study was approved by Institutional Animal Ethics Committe.Male Wistar rats (150–200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively.MCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil.Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening. The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH. The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated. The study was approved by Institutional Animal Ethics Committe. Male Wistar rats (150–200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively. MCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil. Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening. [Display omitted] The stem bark of Terminalia arjuna (Roxb.) is widely used in Ayurveda in various cardiovascular diseases. Many animal and clinical studies have validated its anti-ischemic, antihypertensive, antihypertrophic and antioxidant effects. Pulmonary hypertension (PH) is a fatal disease which causes right ventricular hypertrophy and right heart failure. Pulmonary vascular smooth muscle hypertrophy and increased oxidative stress are major pathological features of PH. As available limited therapeutic options fail to reduce the mortality associated with PH, alternative areas of therapy are worth exploring for potential drugs, which might be beneficial in PH. The effect of a standardised aqueous extract of the stem bark of Terminalia arjuna (Roxb.) in preventing monocrotaline (MCT)-induced PH in rat was investigated. The study was approved by Institutional Animal Ethics Committe. Male Wistar rats (150-200g) were randomly distributed into five groups; Control, MCT (50mg/kg subcutaneously once), sildenafil (175µg/kg/day three days after MCT for 25 days), and Arjuna extract (TA125 and TA250 mg/kg/day orally after MCT for 25 days). PH was confirmed by right ventricular weight to left ventricular plus septum weight (Fulton index), right ventricular systolic pressure (RVSP), echocardiography, percentage medial wall thickness of pulmonary arteries (%MWT). Oxidative stress in lung was assessed by super oxide dismutase (SOD), catalase, reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). The protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-1) in lung and gene expression of Bcl2 and Bax in heart were analyzed by Western blot and RT PCR respectively. MCT caused right ventricular hypertrophy (0.58±0.05 vs 0.31±0.05; P<0.001 vs. control) and increase in RVSP (33.5±1.5 vs 22.3±4.7mm of Hg; P<0.001). Both sildenafil and Arjuna prevented hypertrophy and RVSP. Pulmonary artery acceleration time to ejection time ratio in echocardiography was decreased in PH rats (0.49±0.05 vs 0.32±0.06; P<0.001) which was prevented by sildenafil (0.44±0.06; P<0.01) and TA250 (0.45±0.06; P<0.01). % MWT of pulmonary arteries was increased in PH and was prevented by TA250. Increase in TBARS (132.7±18.4 vs 18.8±1.6nmol/mg protein; P<0.001) and decrease in SOD (58.4±14.1 vs 117.4±26.9U/mg protein; P<0.001) and catalase (0.30±0.05 vs 0.75±0.31U/mg protein; P<0.001) were observed in lung tissue of PH rats, which were prevented by sildenafil and both the doses of Arjuna extract. Protein expression of NOX1 was significantly increased in lung and gene expression of Bcl2/Bax ratio was significantly decreased in right ventricle in MCT-induced PH, both were significantly prevented by Arjuna and sildenafil. Aqueous extract of Terminalia arjuna prevented MCT-induced pulmonary hypertension which may be attributed to its antioxidant as well as its effects on pulmonary arteriolar wall thickening. |
| Author | Arava, Sudheer Banerjee, Sanjay K. Prabhakar, Pankaj Maulik, Subir Kumar Mohammed, Soheb A. Seth, Sandeep Ray, Ruma Meghwani, Himanshu Hote, Milind P. |
| Author_xml | – sequence: 1 givenname: Himanshu surname: Meghwani fullname: Meghwani, Himanshu organization: Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India – sequence: 2 givenname: Pankaj surname: Prabhakar fullname: Prabhakar, Pankaj organization: Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India – sequence: 3 givenname: Soheb A. surname: Mohammed fullname: Mohammed, Soheb A. organization: Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana 121001, India – sequence: 4 givenname: Sandeep surname: Seth fullname: Seth, Sandeep organization: Department of Cardiology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India – sequence: 5 givenname: Milind P. surname: Hote fullname: Hote, Milind P. organization: Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India – sequence: 6 givenname: Sanjay K. surname: Banerjee fullname: Banerjee, Sanjay K. organization: Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana 121001, India – sequence: 7 givenname: Sudheer surname: Arava fullname: Arava, Sudheer organization: Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India – sequence: 8 givenname: Ruma surname: Ray fullname: Ray, Ruma organization: Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India – sequence: 9 givenname: Subir Kumar surname: Maulik fullname: Maulik, Subir Kumar email: skmaulik@gmail.com organization: Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27401289$$D View this record in MEDLINE/PubMed |
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| Keywords | PAAT RVeDP Ayurveda RVH Cardiovascular Monocrotaline IVS RVSP LVEF NaOH LV LW HCl NADH RT-PCR Terminalia arjuna GSH SS SOD TBARS MWT SDS–PAGE Antioxidant PVDF TA Pulmonary hypertension ET AoD RVoTD PH NOX1 MCT |
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| Title | Beneficial effects of aqueous extract of stem bark of Terminalia arjuna (Roxb.), An ayurvedic drug in experimental pulmonary hypertension |
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