Alcoholic Extract of Terminalia Arjuna Protects Rabbit Heart against Ischemic-Reperfusion Injury: Role of Antioxidant Enzymes and Heat Shock Protein
The present study was designed to investigate the
cardio protective role of chronic oral administration of alcoholic
extract of Terminalia arjuna in in-vivo ischemic reperfusion injury
and the induction of HSP72. Rabbits, divided into three groups, and
were administered with the alcoholic extract of the bark powder of
Terminalia arjuna (TAAE) by oral gavage [6.75mg/kg: (T1) and
9.75mg/kg: (T2), 6 days /week for 12 weeks]. In open-chest
Ketamine pentobarbitone anaesthetized rabbits, the left anterior
descending coronary artery was occluded for 15 min of ischemia
followed by 60 min of reperfusion. In the vehicle-treated group,
ischemic-reperfusion injury (IRI) was evidenced by depression of
global hemodynamic function (MAP, HR, LVEDP, peak LV (+) & (-
) (dP/dt) along with depletion of HEP compounds. Oxidative stress
in IRI was evidenced by, raised levels of myocardial TBARS and
depletion of endogenous myocardial antioxidants GSH, SOD and
catalase. Western blot analysis showed a single band corresponding
to 72 kDa in homogenates of hearts from rabbits treated with both the
doses. In the alcoholic extract of the bark powder of Terminalia
arjuna treatment groups, both the doses had better recovery of
myocardial hemodynamic function, with significant reduction in
TBARS, and rise in SOD, GSH, catalase were observed. The results
of the present study suggest that the alcoholic extract of the bark
powder of Terminalia arjuna in rabbit induces myocardial HSP 72
and augments myocardial endogenous antioxidants, without causing
any cellular injury and offered better cardioprotection against
oxidative stress associated with myocardial IR injury.
[1] E. Braunwald and R. A. Kloner, "The stunned myocardium prolonged
post ischemic ventricular dysfunction," Circulation., 1982, vol. 66, pp.
1146-1149.
[2] J. L. Park and B. R. Lucchest, "Mechanism of Myocardial
ischemic reperfusion injury," Ann Thorac Surg., 1999,
vol. 68, pp. 1905-1912.
[3] G. Ambrosio, J. T. Flaherty, C. Dullio, I. Tritto, G.
Sanoro, P. P. Ellia, M. Condorelli, and M. Chiariello,
"Oxygen radicals generated at reflow induce peroxidation
of membrane lipids in reperfused hearts," J Clin Invest.,
1991, Vol. 87, pp. 2056-2066.
[4] R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni, E. Pasini and O. Visioli,
"The occurrence of oxidative stress during reperfusion in experimental
animals and men". Cardiovascular Drugs and Therapeutics., 1991,
Vol. 5, pp. 277-288.
[5] J. G. Gross, R. K. Judy, and C. W. David, "Mechanism of post ischemic
contractile dysfunction," Ann Thoracic Surge., 1999, vol. 68, pp. 1898-
1904.
[6] R. Bolli, "The Late Phase of Preconditioning," Circ. Res.,
2000, vol. 87, pp. 972-983.
[7] K. Gauthaman, M. Maulik, R. Kumari, S. C. Manchanda, A. K. Dinda
and S.K. Maulik, "Effect of chronic treatment with bark of Terminalia
arjuna: A study on the isolated ischemic reperfused rat heart," Journal
of Ethnopharmacology., 2001, vol. 75 (2-3), pp. 197-201.
[8] K. Karthikeyan, B. R. Bai, K. Gauthaman, K. S. Sathish and S. N.
Devaraj, "Cardioprotective effect of the alcoholic extract of Terminalia
arjuna bark in an in vivo model of myocardial ischemic reperfusion
injury," Life Sci., 2003, vol. 73(21), pp. 2727-2739.
[9] K. Gauthaman, S. K. Banerjee, A. K. Dinda, C. C. Ghosh and S. K.
Maulik, "Terminalia arjuna (Roxb.) protects rabbit heart against
ischemic-reperfusion injury: role of antioxidant enzymes and heat shock
protein," Journal of Ethnopharmacology., 2005, vol. 96, pp. 403-409.
[10] D. M. Yellon, and D. J. Hausenloy, "Myocardial reperfusion injury," N Engl J
Med., 2007, vol. 357, pp. 1121-1135.
[11] K. Gauthaman, T. S. Mohamed Saleem, V. Ravi and S. Niranjali
Devaraj, "Cardioprotective properties of Methanolic extract of
Terminalia arjuna Linn Bark in an in vitro model of Myocardial
ischemic reperfusion injury in rats," Int. J.Pharmacol.Biol.Sci., vol. 2
(1), 2008, pp. 13-28.
[12] A. A. Knowlton, "The role of heat shock protein in
heart," Journal of Molecular & Cellular cardiology.,
1995, vol. 27, pp. 121-31.
[13] E. K. Hiodromitis, G. K. Karavolias, E. Bofilis, D. M. Yellon and D.T.
Kremastinos, "Enhanced protection of heat shock in myocardial
infarction: inhibition of detrimental effect of systemic hyperthermia,"
Cardiovascular Drugs Therapy., 1999, vol. 13 (3), pp. 223-231.
[14] S. K. Powers, M. Locke and H. A. Demirel, "Exercise, heat shock
proteins, and myocardial protection from I-R injury," Med Sci Sports
Exerc., Mar 2001, vol 33 (3), pp. 386-392.
[15] K. Gauthaman and S. Niranjali Devaraj, "Terminalia arjuna barks
protects rat hearts with induction of the 72 kDa Heat shock protein (HSP
72)," Biomedicine., 2003, (3&4), pp. 26-30.
[16] C. G. Caroline, A. Mohamed and H. Y. Magdi, "Heat stress proteins
and myocardial protection: Experimental model or potential clinical
tool?" The International Journal of Biochemistry and Cell Biology,
1999, vol 31, pp. 559-573.
[17] A. K. Nadkarni, Indian Materia Medica vol.1, Bombay: Popular
Prakashan (Pvt.) Ltd., India. 1976.
[18] A. B. Vaidya, "Terminalia arjuna in cardiovascular therapy," J Assoc
Physicians India ., April 1994 , vol. 42 (4), pp. 281-282.
[19] Y. B. Tripathi, "Terminalia arjuna extract modulates the contraction of
rat aorta induced by KCl and norepinephrine," Phytotherapy Research.,
1993, vol. 7, pp. 320-322.
[20] S. Dwivedi, "Antianginal and cardioprotective effects of Terminalia
arjuna, an indigenous drug, in coronary heart disease," Journal
Association Physician India., 1994, vol. 42 (4), pp. 287-289.
[21] M. Gautham, M. Sunit, and K. D. Dipak, "Evaluation of Antioxidant
Effectiveness of a few selected Vegetables," Enviromental & Nutrional
Interactions., 1997, vol. 1, pp. 287-297.
[22] S. K. Maulik, R. Kumari, M. Maulik., S. C. Manchanda and S. K. Gupta,
"Captopril and its time of administration in myocardial ischemicreperfusion
injury," Pharmacol Res., 2001, vol. 44 (2), pp. 123-127.
[23] W. Lamprecht, F. Stan, H. Weisser, and F. Heinz, "Determination of
creatine phosphate and adenosine triphosphate with creatine kinase,"
In: Methods of Enzymatic Analysis., Bergmayer, H.U. (Ed.). Academic
Press: New York 1974, pp. 1776-1778.
[24] P. Kakkar, B. Das and P. N. Viswanathan, "A modified
spectrophotometric assay of superoxide dismutase" Indian Journal
Biochemistry Biophysics., 1984, vol. 21, pp. 130-132.
[25] H. Aebi, Catalase, In: Bergmeyer HU, editor. Methods of Enzymatic
Analysis. Verlag: Chemic Academic Press Inc., 1974, pp. 673-85.
[26] G. L. Ellman, "Tissue sulphydryl groups," Archive Biochemistry
Biophysics., 1959, vol. 82, pp. 70-77.
[27] H. Okhawa, N. Oohishi and K. Yagi, "Assay for Lipid peroxides in
animal tissues by thiobarbituric acid reaction," Annals of Biochemistry.,
1979, vol. 95, pp. 351-358.
[28] M. M. Hutter, R. E. Sievers, V. Barbose and C.L. Wolfe, "Heat shock
protein induction in rat hearts. A direct correlation between the amount
of heat shock protein induced and the degree of myocardial protection"
Circulation., 1994, vol. 89, pp. 355-360.
[29] M. M. Bradford, "A rapid and sensitive method for the quantitation of
microgram quantities of protein utilizing the principle of protein-dye
binding," Analytical Biochemistry., 1976, vol. 7 (72), pp. 248-254.
[30] V Pathania, N. Syal, M. H. Hundal, and K. L. Khanduja,
"Geriforte stimulates antioxidant defense system," Indian
Journal of Experimental Biology., 1998, vol. 36, pp. 414-
417.
[31] S. K. Banerjee, A. K. Dinda, S. C. Manchanda and S. K. Maulik,
"Chronic garlic administration protects rat heart against oxidative stress
induced by ischemic reperfusion injury," BMC Pharmacology., 2002,
vol. 2 (1), 16.
[32] A. L. Miller, "Botanical influences on cardiovascular disease,"
Alternative Medical Review., 1998, vol. 3 (6), pp. 422-431.
[33] H. Yamasaki, H. Uefuji, and Y. Sakihama, Arch Biochem.
Biophys., 1996; 332(1), 183-186.
[34] J. C. Tilak, T. P. A. Devasagayam, T. Kon, Y. Naito and T. Yoshikawa,
"Protection by an medicinal plant, Terminalia arjuna, and its active
component, Baicalein against superoxide and singlet oxygen," In
International conference on natural products, free radicals and
padioprotectors in health (NFR - 200) and III annual meeting of SFRR -
India., Jan17- 19, 2004, pp. 21-22.
[35] P. K. Singal, A. K. Dhalla, M. Hill, and T. P. Thomas, "Endogenous
antioxidant changes in the myocardium in response to acute and chronic
stress conditions," Molecular cell biochemistry, 1993, vol. 129, pp. 179-
186.
[36] S. D. Seth, M. Maulik, C. K. Katiyar, and S. K. Mauilk, "Role of lipistat
in protection against isoproterenol induced myocardial necrosis in rats:
A biochemical and histopathological study," Indian Journal of
Physiology and Pharmacology., 1998, vol. 42 (1), pp. 101-106.
[37] D. K. Das, and N. Maulik, In "Cell Biology of Trauma", eds. By
Lemasters J.L., Oliver C., Boca Raton CRC press 1995, pp 193-211.
[38] S. E. Steare and D. M. Yellon, "The potential for endogenous
myocardial antioxidant to protect the myocardium against ischemicreperfusion
injury; refreshing the parts exogenous antioxidants can not
reach," J. Mol. Cell. Cardiol., 1995, vol. 27, pp. 65-74.
[1] E. Braunwald and R. A. Kloner, "The stunned myocardium prolonged
post ischemic ventricular dysfunction," Circulation., 1982, vol. 66, pp.
1146-1149.
[2] J. L. Park and B. R. Lucchest, "Mechanism of Myocardial
ischemic reperfusion injury," Ann Thorac Surg., 1999,
vol. 68, pp. 1905-1912.
[3] G. Ambrosio, J. T. Flaherty, C. Dullio, I. Tritto, G.
Sanoro, P. P. Ellia, M. Condorelli, and M. Chiariello,
"Oxygen radicals generated at reflow induce peroxidation
of membrane lipids in reperfused hearts," J Clin Invest.,
1991, Vol. 87, pp. 2056-2066.
[4] R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni, E. Pasini and O. Visioli,
"The occurrence of oxidative stress during reperfusion in experimental
animals and men". Cardiovascular Drugs and Therapeutics., 1991,
Vol. 5, pp. 277-288.
[5] J. G. Gross, R. K. Judy, and C. W. David, "Mechanism of post ischemic
contractile dysfunction," Ann Thoracic Surge., 1999, vol. 68, pp. 1898-
1904.
[6] R. Bolli, "The Late Phase of Preconditioning," Circ. Res.,
2000, vol. 87, pp. 972-983.
[7] K. Gauthaman, M. Maulik, R. Kumari, S. C. Manchanda, A. K. Dinda
and S.K. Maulik, "Effect of chronic treatment with bark of Terminalia
arjuna: A study on the isolated ischemic reperfused rat heart," Journal
of Ethnopharmacology., 2001, vol. 75 (2-3), pp. 197-201.
[8] K. Karthikeyan, B. R. Bai, K. Gauthaman, K. S. Sathish and S. N.
Devaraj, "Cardioprotective effect of the alcoholic extract of Terminalia
arjuna bark in an in vivo model of myocardial ischemic reperfusion
injury," Life Sci., 2003, vol. 73(21), pp. 2727-2739.
[9] K. Gauthaman, S. K. Banerjee, A. K. Dinda, C. C. Ghosh and S. K.
Maulik, "Terminalia arjuna (Roxb.) protects rabbit heart against
ischemic-reperfusion injury: role of antioxidant enzymes and heat shock
protein," Journal of Ethnopharmacology., 2005, vol. 96, pp. 403-409.
[10] D. M. Yellon, and D. J. Hausenloy, "Myocardial reperfusion injury," N Engl J
Med., 2007, vol. 357, pp. 1121-1135.
[11] K. Gauthaman, T. S. Mohamed Saleem, V. Ravi and S. Niranjali
Devaraj, "Cardioprotective properties of Methanolic extract of
Terminalia arjuna Linn Bark in an in vitro model of Myocardial
ischemic reperfusion injury in rats," Int. J.Pharmacol.Biol.Sci., vol. 2
(1), 2008, pp. 13-28.
[12] A. A. Knowlton, "The role of heat shock protein in
heart," Journal of Molecular & Cellular cardiology.,
1995, vol. 27, pp. 121-31.
[13] E. K. Hiodromitis, G. K. Karavolias, E. Bofilis, D. M. Yellon and D.T.
Kremastinos, "Enhanced protection of heat shock in myocardial
infarction: inhibition of detrimental effect of systemic hyperthermia,"
Cardiovascular Drugs Therapy., 1999, vol. 13 (3), pp. 223-231.
[14] S. K. Powers, M. Locke and H. A. Demirel, "Exercise, heat shock
proteins, and myocardial protection from I-R injury," Med Sci Sports
Exerc., Mar 2001, vol 33 (3), pp. 386-392.
[15] K. Gauthaman and S. Niranjali Devaraj, "Terminalia arjuna barks
protects rat hearts with induction of the 72 kDa Heat shock protein (HSP
72)," Biomedicine., 2003, (3&4), pp. 26-30.
[16] C. G. Caroline, A. Mohamed and H. Y. Magdi, "Heat stress proteins
and myocardial protection: Experimental model or potential clinical
tool?" The International Journal of Biochemistry and Cell Biology,
1999, vol 31, pp. 559-573.
[17] A. K. Nadkarni, Indian Materia Medica vol.1, Bombay: Popular
Prakashan (Pvt.) Ltd., India. 1976.
[18] A. B. Vaidya, "Terminalia arjuna in cardiovascular therapy," J Assoc
Physicians India ., April 1994 , vol. 42 (4), pp. 281-282.
[19] Y. B. Tripathi, "Terminalia arjuna extract modulates the contraction of
rat aorta induced by KCl and norepinephrine," Phytotherapy Research.,
1993, vol. 7, pp. 320-322.
[20] S. Dwivedi, "Antianginal and cardioprotective effects of Terminalia
arjuna, an indigenous drug, in coronary heart disease," Journal
Association Physician India., 1994, vol. 42 (4), pp. 287-289.
[21] M. Gautham, M. Sunit, and K. D. Dipak, "Evaluation of Antioxidant
Effectiveness of a few selected Vegetables," Enviromental & Nutrional
Interactions., 1997, vol. 1, pp. 287-297.
[22] S. K. Maulik, R. Kumari, M. Maulik., S. C. Manchanda and S. K. Gupta,
"Captopril and its time of administration in myocardial ischemicreperfusion
injury," Pharmacol Res., 2001, vol. 44 (2), pp. 123-127.
[23] W. Lamprecht, F. Stan, H. Weisser, and F. Heinz, "Determination of
creatine phosphate and adenosine triphosphate with creatine kinase,"
In: Methods of Enzymatic Analysis., Bergmayer, H.U. (Ed.). Academic
Press: New York 1974, pp. 1776-1778.
[24] P. Kakkar, B. Das and P. N. Viswanathan, "A modified
spectrophotometric assay of superoxide dismutase" Indian Journal
Biochemistry Biophysics., 1984, vol. 21, pp. 130-132.
[25] H. Aebi, Catalase, In: Bergmeyer HU, editor. Methods of Enzymatic
Analysis. Verlag: Chemic Academic Press Inc., 1974, pp. 673-85.
[26] G. L. Ellman, "Tissue sulphydryl groups," Archive Biochemistry
Biophysics., 1959, vol. 82, pp. 70-77.
[27] H. Okhawa, N. Oohishi and K. Yagi, "Assay for Lipid peroxides in
animal tissues by thiobarbituric acid reaction," Annals of Biochemistry.,
1979, vol. 95, pp. 351-358.
[28] M. M. Hutter, R. E. Sievers, V. Barbose and C.L. Wolfe, "Heat shock
protein induction in rat hearts. A direct correlation between the amount
of heat shock protein induced and the degree of myocardial protection"
Circulation., 1994, vol. 89, pp. 355-360.
[29] M. M. Bradford, "A rapid and sensitive method for the quantitation of
microgram quantities of protein utilizing the principle of protein-dye
binding," Analytical Biochemistry., 1976, vol. 7 (72), pp. 248-254.
[30] V Pathania, N. Syal, M. H. Hundal, and K. L. Khanduja,
"Geriforte stimulates antioxidant defense system," Indian
Journal of Experimental Biology., 1998, vol. 36, pp. 414-
417.
[31] S. K. Banerjee, A. K. Dinda, S. C. Manchanda and S. K. Maulik,
"Chronic garlic administration protects rat heart against oxidative stress
induced by ischemic reperfusion injury," BMC Pharmacology., 2002,
vol. 2 (1), 16.
[32] A. L. Miller, "Botanical influences on cardiovascular disease,"
Alternative Medical Review., 1998, vol. 3 (6), pp. 422-431.
[33] H. Yamasaki, H. Uefuji, and Y. Sakihama, Arch Biochem.
Biophys., 1996; 332(1), 183-186.
[34] J. C. Tilak, T. P. A. Devasagayam, T. Kon, Y. Naito and T. Yoshikawa,
"Protection by an medicinal plant, Terminalia arjuna, and its active
component, Baicalein against superoxide and singlet oxygen," In
International conference on natural products, free radicals and
padioprotectors in health (NFR - 200) and III annual meeting of SFRR -
India., Jan17- 19, 2004, pp. 21-22.
[35] P. K. Singal, A. K. Dhalla, M. Hill, and T. P. Thomas, "Endogenous
antioxidant changes in the myocardium in response to acute and chronic
stress conditions," Molecular cell biochemistry, 1993, vol. 129, pp. 179-
186.
[36] S. D. Seth, M. Maulik, C. K. Katiyar, and S. K. Mauilk, "Role of lipistat
in protection against isoproterenol induced myocardial necrosis in rats:
A biochemical and histopathological study," Indian Journal of
Physiology and Pharmacology., 1998, vol. 42 (1), pp. 101-106.
[37] D. K. Das, and N. Maulik, In "Cell Biology of Trauma", eds. By
Lemasters J.L., Oliver C., Boca Raton CRC press 1995, pp 193-211.
[38] S. E. Steare and D. M. Yellon, "The potential for endogenous
myocardial antioxidant to protect the myocardium against ischemicreperfusion
injury; refreshing the parts exogenous antioxidants can not
reach," J. Mol. Cell. Cardiol., 1995, vol. 27, pp. 65-74.
@article{"International Journal of Biological, Life and Agricultural Sciences:56143", author = "K. Gauthaman and T.S. Mohamed Saleem and V. Ravi and Sita Sharan Patel and S. Niranjali Devaraj", title = "Alcoholic Extract of Terminalia Arjuna Protects Rabbit Heart against Ischemic-Reperfusion Injury: Role of Antioxidant Enzymes and Heat Shock Protein", abstract = "The present study was designed to investigate the
cardio protective role of chronic oral administration of alcoholic
extract of Terminalia arjuna in in-vivo ischemic reperfusion injury
and the induction of HSP72. Rabbits, divided into three groups, and
were administered with the alcoholic extract of the bark powder of
Terminalia arjuna (TAAE) by oral gavage [6.75mg/kg: (T1) and
9.75mg/kg: (T2), 6 days /week for 12 weeks]. In open-chest
Ketamine pentobarbitone anaesthetized rabbits, the left anterior
descending coronary artery was occluded for 15 min of ischemia
followed by 60 min of reperfusion. In the vehicle-treated group,
ischemic-reperfusion injury (IRI) was evidenced by depression of
global hemodynamic function (MAP, HR, LVEDP, peak LV (+) & (-
) (dP/dt) along with depletion of HEP compounds. Oxidative stress
in IRI was evidenced by, raised levels of myocardial TBARS and
depletion of endogenous myocardial antioxidants GSH, SOD and
catalase. Western blot analysis showed a single band corresponding
to 72 kDa in homogenates of hearts from rabbits treated with both the
doses. In the alcoholic extract of the bark powder of Terminalia
arjuna treatment groups, both the doses had better recovery of
myocardial hemodynamic function, with significant reduction in
TBARS, and rise in SOD, GSH, catalase were observed. The results
of the present study suggest that the alcoholic extract of the bark
powder of Terminalia arjuna in rabbit induces myocardial HSP 72
and augments myocardial endogenous antioxidants, without causing
any cellular injury and offered better cardioprotection against
oxidative stress associated with myocardial IR injury.", keywords = "Antioxidants, HSP72, Ischemic reperfusion injury,Terminalia arjuna.", volume = "2", number = "6", pages = "108-11", }
