Planta Med 2014; 80(07): 525-532
DOI: 10.1055/s-0034-1368426
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

The Effect of Leonurus cardiaca Herb Extract and Some of its Flavonoids on Mitochondrial Oxidative Phosphorylation in the Heart

Jurga Bernatoniene
1   Department of Drug Technology and Social Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Dalia M. Kopustinskiene
1   Department of Drug Technology and Social Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
2   Laboratory of Biochemistry, Neuroscience Institute of Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Valdas Jakstas
3   Department of Pharmacognosy, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Daiva Majiene
1   Department of Drug Technology and Social Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
2   Laboratory of Biochemistry, Neuroscience Institute of Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Rasa Baniene
2   Laboratory of Biochemistry, Neuroscience Institute of Lithuanian University of Health Sciences, Kaunas, Lithuania
4   Department of Biochemistry, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Lolita Kuršvietiene
4   Department of Biochemistry, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Ruta Masteikova
5   University of Veterinary and Pharmaceutical Sciences Brno, Faculty of Pharmacy, Department of Pharmaceutics, Brno, Czech Republic
,
Arunas Savickas
1   Department of Drug Technology and Social Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Adolfas Toleikis
2   Laboratory of Biochemistry, Neuroscience Institute of Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Sonata Trumbeckaite
2   Laboratory of Biochemistry, Neuroscience Institute of Lithuanian University of Health Sciences, Kaunas, Lithuania
3   Department of Pharmacognosy, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
› Author Affiliations
Further Information

Publication History

received 15 November 2013
revised 13 March 2014

accepted 24 March 2014

Publication Date:
19 May 2014 (online)

Abstract

Motherwort (Leonurus cardiaca) possesses antibacterial, antioxidant, anti-inflammatory, and analgesic activities, and is used as a complementary remedy to improve heart function and blood circulation. Since cardiovascular diseases are often associated with an alteration of mitochondria, the main producers of ATP in cardiac muscle cells, the aim of our work was to determine bioactive constituents present in motherwort aerial parts extract in ethanol and investigate their effects on the functions of cardiac mitochondria. Quantitative determination of polyphenols in L. cardiaca herb extract was performed by HPLC. Mitochondrial respiration rates were evaluated using a Clark-type oxygen electrode. Mitochondrial ROS generation was determined fluorimetrically with Amplex Red and horseradish peroxidase. The results showed that constituents (chlorogenic acid, orientin, quercetin, hyperoside, and rutin) of L. cardiaca herb extract uncouple (by 20–90 %) mitochondrial oxidation from phosphorylation, partially inhibit (by ~ 40 %) the mitochondrial respiratory chain in cases of pyruvate and malate as well as succinate oxidation, and effectively attenuate the generation of free radicals in mitochondria. Since partial uncoupling of mitochondria, respiratory inhibition, and decreased ROS production are proposed as possible mechanisms of cardioprotection, our results imply that L. cardiaca herb extract could be a useful remedy to protect cardiac muscles from the effects of pathogenic processes.

Supporting Information

 
  • References

  • 1 Jassem W, Fuggle SV, Rela M, Koo DD, Heaton ND. The role of mitochondria in ischemia/reperfusion injury. Transplantation 2002; 73: 493-499
  • 2 Wattanapitayakul SK, Bauer JA. Oxidative pathways in cardiovascular disease: roles, mechanisms, and therapeutic implications. Pharmacol Ther 2001; 89: 187-206
  • 3 Zhu YZ, Huang SH, Tan BK, Sun J, Whiteman M, Zhu YC. Antioxidants in Chinese herbal medicines: a biochemical perspective. Nat Prod Rep 2004; 21: 478-489
  • 4 Wojtyniak K, Szymanski M, Matlawska I. Leonurus cardiaca L. (motherwort): a review of its phytochemistry and pharmacology. Phytother Res 2013; 27: 1115-1120
  • 5 Ali MS, Ibrahim SA, Jalil S, Choudhary MI. Ursolic acid: a potent inhibitor of superoxides produced in the cellular system. Phytother Res 2007; 21: 558-561
  • 6 Duskova J, Dusek J. [Leonurus cardiaca in vitro]. Ceska Slov Farm 2004; 53: 39-41
  • 7 Sun J, Huang SH, Zhu YC, Whiteman M, Wang MJ, Tan BK, Zhu YZ. Anti-oxidative stress effects of Herba leonuri on ischemic rat hearts. Life Sci 2005; 76: 3043-3056
  • 8 Ng TB, Liu F, Lu Y, Cheng CH, Wang Z. Antioxidant activity of compounds from the medicinal herb Aster tataricus . Comp Biochem Physiol C Toxicol Pharmacol 2003; 136: 109-115
  • 9 Mercer LD, Kelly BL, Horne MK, Beart PM. Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. Biochem Pharmacol 2005; 69: 339-345
  • 10 Trumbeckaite S, Bernatoniene J, Majiene D, Jakstas V, Savickas A, Toleikis A. The effect of flavonoids on rat heart mitochondrial function. Biomed Pharmacother 2006; 60: 245-248
  • 11 Shikov AN, Pozharitskaya ON, Makarov VG, Demchenko DV, Shikh EV. Effect of Leonurus cardiaca oil extract in patients with arterial hypertension accompanied by anxiety and sleep disorders. Phytother Res 2011; 25: 540-543
  • 12 Matkowski A, Piotrowska M. Antioxidant and free radical scavenging activities of some medicinal plants from the Lamiaceae. Fitoterapia 2006; 77: 346-353
  • 13 Masteikova R, Muselik J, Bernatoniene J, Majiene D, Savickas A, Malinauskas F, Bernatoniene R, Peciura R, Chalupova Z, Dvorackova K. [Antioxidant activity of tinctures prepared from hawthorn fruits and motherwort herb]. Ceska Slov Farm 2008; 57: 35-38
  • 14 Bernatoniene J, Kucinskaite A, Masteikova R, Kalveniene Z, Kasparaviciene G, Savickas A. The comparison of anti-oxidative kinetics in vitro of the fluid extract from maidenhair tree, motherwort and hawthorn. Acta Pol Pharm 2009; 66: 415-421
  • 15 Liobikas J, Majiene D, Trumbeckaite S, Kursvietiene L, Masteikova R, Kopustinskiene DM, Savickas A, Bernatoniene J. Uncoupling and antioxidant effects of ursolic acid in isolated rat heart mitochondria. J Nat Prod 2011; 74: 1640-1644
  • 16 Di Lisa F, Kaludercic N, Carpi A, Menabo R, Giorgio M. Mitochondrial pathways for ROS formation and myocardial injury: the relevance of p 66(Shc) and monoamine oxidase. Basic Res Cardiol 2009; 104: 131-139
  • 17 Korshunov SS, Skulachev VP, Starkov AA. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 1997; 416: 15-18
  • 18 Skulachev VP. Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms. Mol Aspects Med 1999; 20: 139-184
  • 19 Groen AK, Wanders RJ, Westerhoff HV, van der Meer R, Tager JM. Quantification of the contribution of various steps to the control of mitochondrial respiration. J Biol Chem 1982; 257: 2754-2757
  • 20 Hafner RP, Brown GC, Brand MD. Analysis of the control of respiration rate, phosphorylation rate, proton leak rate and protonmotive force in isolated mitochondria using the ʼtop-downʼ approach of metabolic control theory. Eur J Biochem 1990; 188: 313-319
  • 21 Hollman PC, Bijsman MN, van Gameren Y, Cnossen EP, de Vries JH, Katan MB. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 1999; 31: 569-573
  • 22 Olthof MR, Hollman PC, Vree TB, Katan MB. Bioavailabilities of quercetin-3-glucoside and quercetin-4′-glucoside do not differ in humans. J Nutr 2000; 130: 1200-1203
  • 23 Erlund I, Kosonen T, Alfthan G, Maenpaa J, Perttunen K, Kenraali J, Parantainen J, Aro A. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur J Clin Pharmacol 2000; 56: 545-553
  • 24 Nohl H. Generation of superoxide radicals as byproduct of cellular respiration. Ann Biol Clin (Paris) 1994; 52: 199-204
  • 25 Boveris A, Cadenas E, Stoppani AO. Role of ubiquinone in the mitochondrial generation of hydrogen peroxide. Biochem J 1976; 156: 435-444
  • 26 Hansford RG, Hogue BA, Mildaziene V. Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age. J Bioenerg Biomembr 1997; 29: 89-95
  • 27 Barja G. Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg Biomembr 1999; 31: 347-366
  • 28 Brand MD. Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 2000; 35: 811-820
  • 29 Minners J, van den Bos EJ, Yellon DM, Schwalb H, Opie LH, Sack MN. Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection. Cardiovasc Res 2000; 47: 68-73
  • 30 Minners J, Lacerda L, McCarthy J, Meiring JJ, Yellon DM, Sack MN. Ischemic and pharmacological preconditioning in Girardi cells and C2C12 myotubes induce mitochondrial uncoupling. Circ Res 2001; 89: 787-792
  • 31 Minners J, Lacerda L, Yellon DM, Opie LH, McLeod CJ, Sack MN. Diazoxide-induced respiratory inhibit. Mol Cell Biochem 2007; 294: 11-18
  • 32 Skulachev VP. Uncoupling: new approaches to an old problem of bioenergetics. Biochim Biophys Acta 1998; 1363: 100-124
  • 33 Brown GC. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J 1992; 284: 1-13
  • 34 Borutaite V, Mildaziene V, Brown GC, Brand MD. Control and kinetic analysis of ischemia-damaged heart mitochondria: which parts of the oxidative phosphorylation system are affected by ischemia?. Biochim Biophys Acta 1995; 1272: 154-158
  • 35 Chen Q, Camara AK, Stowe DF, Hoppel CL, Lesnefsky EJ. Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion. Am J Physiol Cell Physiol 2007; 292: C137-C147
  • 36 Lesnefsky EJ, Chen Q, Moghaddas S, Hassan MO, Tandler B, Hoppel CL. Blockade of electron transport during ischemia protects cardiac mitochondria. J Biol Chem 2004; 279: 47961-47967
  • 37 Chen Q, Hoppel CL, Lesnefsky EJ. Blockade of electron transport before cardiac ischemia with the reversible inhibitor amobarbital protects rat heart mitochondria. J Pharmacol Exp Ther 2006; 316: 200-207
  • 38 Aldakkak M, Stowe DF, Chen Q, Lesnefsky EJ, Camara AK. Inhibited mitochondrial respiration by amobarbital during cardiac ischaemia improves redox state and reduces matrix Ca2+ overload and ROS release. Cardiovasc Res 2008; 77: 406-415
  • 39 Stewart S, Lesnefsky EJ, Chen Q. Reversible blockade of electron transport with amobarbital at the onset of reperfusion attenuates cardiac injury. Transl Res 2009; 153: 224-231
  • 40 Shiva S, Sack MN, Greer JJ, Duranski M, Ringwood LA, Burwell L, Wang X, MacArthur PH, Shoja A, Raghavachari N, Calvert JW, Brookes PS, Lefer DJ, Gladwin MT. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med 2007; 204: 2089-2102
  • 41 Nadtochiy SM, Burwell LS, Brookes PS. Cardioprotection and mitochondrial S-nitrosation: effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia-reperfusion injury. J Mol Cell Cardiol 2007; 42: 812-825
  • 42 Chen Q, Yin G, Stewart S, Hu Y, Lesnefsky EJ. Isolating the segment of the mitochondrial electron transport chain responsible for mitochondrial damage during cardiac ischemia. Biochem Biophys Res Commun 2010; 397: 656-660
  • 43 Grisham MB. Methods to detect hydrogen peroxide in living cells: Possibilities and pitfalls. Comp Biochem Physiol A Mol Integr Physiol 2013; 165: 429-438
  • 44 Forman HJ. Use and abuse of exogenous H2O2 in studies of signal transduction. Free Radic Biol Med 2007; 42: 926-932
  • 45 Stone JR, Yang S. Hydrogen peroxide: a signaling messenger. Antioxid Redox Signal 2006; 8: 243-270
  • 46 Chakraborti T, Ghosh SK, Michael JR, Batabyal SK, Chakraborti S. Targets of oxidative stress in cardiovascular system. Mol Cell Biochem 1998; 187: 1-10
  • 47 Bernatoniene J, Bernatoniene R, Jakstas V, Malinauskas F, Brusokas V. [Production technology and analysis of blood circulation improving tincture]. Medicina (Kaunas) 2003; 39 (Suppl. 02) 76-79