Planta Med 2014; 80(17): 1569-1579
DOI: 10.1055/s-0034-1383121
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Attenuation of Cisplatin-Induced Emetogenesis by Standardized Bacopa monnieri Extracts in the Pigeon: Behavioral and Neurochemical Correlations

Ihsan Ullah
1   Department of Pharmacy, University of Swabi, Swabi, Pakistan
2   Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
,
Fazal Subhan
2   Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
,
John A. Rudd
3   School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong SAR, China
,
Khalid Rauf
4   Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan
,
Javaid Alam
2   Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
,
Muhammad Shahid
2   Department of Pharmacy, University of Peshawar, Peshawar, Pakistan
,
Robert D. E. Sewell
5   Welsh School of Pharmacy, Cardiff University, Cardiff, UK
› Author Affiliations
Further Information

Publication History

received 19 June 2014
revised 17 August 2014

accepted 27 August 2014

Publication Date:
08 October 2014 (online)

Abstract

Nausea and vomiting are the most distressing and common side effects of cancer chemotherapy which often result in patient noncompliance. In the present study, standardized methanolic and n-butanolic fractions of Bacopa monnieri were evaluated against cisplatin-induced emesis in the pigeon in relation to their activity on central and intestinal neurotransmitters levels. Cisplatin (7.0 mg/kg, i. v.) induced reproducible emesis without lethality in healthy pigeons. The methanolic (10–40 mg/kg) and the bacoside-rich n-butanolic fractions of B. monnieri (5–20 mg/kg), as well as the antioxidant N-(2-mercaptopropionyl) glycine (10 mg/kg), attenuated cisplatin-induced emesis by 66.3 % (p < 0.05), 71.6 % (p < 0.001), and 76.5 % (p < 0.001), respectively, where the standard antiemetic metoclopramide (30 mg/kg) produced a 48.9 % reduction (p < 0.01). The methanolic and n-butanolic fractions of B. monnieri at all of the doses tested significantly reduced the serotonin concentration (p < 0.001) in the brain stem and intestine 3 h after cisplatin administration, while at the 18th h, B. monnieri treatments attenuated not only the dopamine upsurge in the area postrema and brain stem (p < 0.05–0.001), but also the intestinal 5-HT concentration (p < 0.01–0.001). B. monnieri treatments alone did not alter the basal neurotransmitters or their metabolites in the brain areas and intestine. The prolonged suppressive effect of B. monnieri treatments on the behavioral signs of cisplatin-induced emesis, the subsequent supportive neural evidence, and the safety and tolerability profile suggest that B. monnieri methanolic and bacoside-rich n-butanolic fractions might be a valuable adjunct in the treatment of emetogenic chemotherapy, and this warrants further study in other models of emesis.

Supporting Information

 
  • References

  • 1 Topal A, Kaya M, Gül N. Ondansetron and granisetron in prophylaxis of nausea and emesis induced by cisplatin in dogs. Acta Vet Brno 2005; 74: 111-116
  • 2 Glaus A, Knipping C, Morant R, Böhme C, Lebert B, Beldermann F, Glawogger B, Ortega PF, Hüsler A, Deuson R. Chemotherapy-induced nausea and vomiting in routine practice: a European perspective. Support Care Cancer 2004; 12: 708-715
  • 3 Naylor R, Rudd J. Mechanisms of chemotherapy/radiotherapy-induced emesis in animal models. Oncology 1996; 53: 8-17
  • 4 Sharma S, Kochupillai V, Gupta S, Seth S, Gupta Y. Antiemetic efficacy of ginger (Zingiber officinale) against cisplatin-induced emesis in dogs. J Ethnopharmacol 1997; 57: 93-96
  • 5 Cubeddu L. Mechanisms by which cancer chemotherapeutic drugs induce emesis. Semin Oncol 1992; 19: 2-13
  • 6 Rossel R, Moreno I, Abed A. Delayed emesis after cisplatin treatment: incidence, source and management. In: Diaz-Rubio E, Martin M, editors Antiemetic therapy: current status and future prospects. Madrid: Creaciones Elba, SA; 1992: 202-209
  • 7 Molassiotis A, Brearley SG, Stamataki Z. Use of antiemetics in the management of chemotherapy-related nausea and vomiting in current UK practice. Support Care Cancer 2011; 19: 949-956
  • 8 Sodhi A, Gupta P. Increased release of hydrogen peroxide (H2O2) and superoxide anion (O 2) by murine macrophages in vitro after cisplatin treatment. Int J Immunopharmacol 1985; 8: 709-714
  • 9 Sangeetha P, Das U, Koratkar R, Suryaprabha P. Increase in free radical generation and lipid peroxidation following chemotherapy in patients with cancer. Free Radic Biol Med 1990; 8: 15-19
  • 10 Torii Y, Mutoh M, Saito H, Matsuki N. Involvement of free radicals in cisplatin-induced emesis in Suncus murinus . Eur J Pharmacol 1993; 248: 131-135
  • 11 Matsuki N, Torii Y, Saito H. Effects of iron and deferoxamine on cisplatin-induced emesis: further evidence for the role of free radicals. Eur J Pharmacol 1993; 248: 329-331
  • 12 Minami M, Endo T, Hirafuji M, Hamaue N, Liu Y, Hiroshige T, Nemoto M, Saito H, Yoshioka M. Pharmacological aspects of anticancer drug-induced emesis with emphasis on serotonin release and vagal nerve activity. Pharmacol Ther 2003; 99: 149-165
  • 13 Gupta Y, Sharma S. Antiemetic activity of antioxidants against cisplatin-induced emesis in dogs. Environ Toxicol Pharmacol 1996; 1: 179-184
  • 14 Lucot JB. Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat. Pharmacol Biochem Behav 1989; 32: 207-210
  • 15 Yamakuni H, Nakayama H, Matsui S, Imazumi K, Matsuo M, Mutoh S. Inhibitory effect of zacopride on cisplatin-induced delayed emesis in ferrets. J Pharmacol Sci 2006; 101: 99-102
  • 16 Tanihata S, Oda S, Kakuta S, Uchiyama T. Antiemetic effect of a tachykinin NK1 receptor antagonist GR205171 on cisplatin-induced early and delayed emesis in the pigeon. Eur J Pharmacol 2003; 461: 197-206
  • 17 Ray AP, Chebolu S, Darmani NA. Receptor-selective agonists induce emesis and Fos expression in the brain and enteric nervous system of the least shrew (Cryptotis parva). Pharmacol Biochem Behav 2009; 94: 211-218
  • 18 Darmani NA, Johnson JC. Central and peripheral mechanisms contribute to the antiemetic actions of delta-9-tetrahydrocannabinol against 5-hydroxytryptophan-induced emesis. Eur J Pharmacol 2004; 488: 201-212
  • 19 Darmani N, Zhao W, Ahmad B. The role of D2 and D3 dopamine receptors in the mediation of emesis in Cryptotis parva (the least shrew). J Neural Transm 1999; 106: 1045-1061
  • 20 Darmani NA, Crim JL. Delta-9-tetrahydrocannabinol differentially suppresses emesis versus enhanced locomotor activity produced by chemically diverse dopamine D2/D3 receptor agonists in the least shrew (Cryptotis parva). Pharmacol Biochem Behav 2005; 80: 35-44
  • 21 Osinski MA, Uchic ME, Seifert T, Shaughnessy TK, Miller LN, Nakane M, Cox BF, Brioni JD, Moreland RB. Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets. Pharmacol Biochem Behav 2005; 81: 211-219
  • 22 Saito R, Takano Y, Kamiya HO. Roles of substance P and NK1 receptor in the brainstem in the development of emesis. J Pharmacol Sci 2003; 91: 87-94
  • 23 Le Moine C, Bloch B. D1 and D2 dopamine receptor gene expression in the rat striatum: sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAs in distinct neuronal populations of the dorsal and ventral striatum. J Comp Neurol 1995; 355: 418-426
  • 24 Higgins G, Kilpatrick G, Bunce K, Jones B, Tyers M. 5-HT3 receptor antagonists injected into the area postrema inhibit cisplatin-induced emesis in the ferret. Br J Pharmacol 1989; 97: 247-255
  • 25 Du Sert NP, Rudd J, Apfel C, Andrews P. Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists. Cancer Chemother Pharmacol 2011; 67: 667-686
  • 26 Grélot L, Dapzol J, Estève E, Frugière A, Bianchi AL, Sheldrick RL, Gardner CJ, Ward P. Potent inhibition of both the acute and delayed emetic responses to cisplatin in piglets treated with GR205171, a novel highly selective tachykinin NK1 receptor antagonist. Br J Pharmacol 1998; 124: 1643-1650
  • 27 Kim DY, Camilleri M. Serotonin: a mediator of the brain–gut connection. Am J Gastroenterol 2000; 95: 2698-2709
  • 28 Minami M, Endo T, Hamaue N, Hirafuji M. Serotonin and anticancer drug-induced emesis. Yakugaku Zasshi 2004; 124: 491-507
  • 29 Grunberg SM, Koeller JM. Palonosetron: a unique 5-HT3-receptor antagonist for the prevention of chemotherapy-induced emesis. Expert Opin Pharmacother 2003; 4: 2297-2303
  • 30 Cubeddu L, OʼConnor D, Hoffmann I, Parmer R. Plasma chromogranin A marks emesis and serotonin release associated with dacarbazine and nitrogen mustard but not with cyclophosphamide-based chemotherapies. Br J Cancer 1995; 72: 1033-1038
  • 31 Veyrat-Follet C, Farinotti R, Palmer JL. Physiology of chemotherapy-induced emesis and antiemetic therapy. Drugs 1997; 53: 206-234
  • 32 Qureshi R, Bhatti G. Taxonomy of Scrophulariaceae from Nara desert, Pakistan. Pak J Bot 2008; 40: 973-978
  • 33 Gohil KJ, Patel JA. A review on Bacopa monnieri: Current research and future prospects. Int J Green Pharm 2010; 4: 1-9
  • 34 Russo A, Borrelli F. Bacopa monnieri, a reputed nootropic plant: an overview. Phytomedicine 2005; 12: 305-317
  • 35 Dar A, Channa S. Calcium antagonistic activity of Bacopa monnieri on vascular and intestinal smooth muscles of rabbit and guinea-pig. J Ethnopharmacol 1999; 66: 167-174
  • 36 Sumathi T, Veluchamy G. Inhibitory effect of Bacopa monnieri on morphine induced pharmacological effects in mice. Nat Prod Sci 2007; 13: 46-53
  • 37 Bhattacharya S, Bhattacharya A, Kumar A, Ghosal S. Antioxidant activity of Bacopa monnieri in rat frontal cortex, striatum and hippocampus. Phytother Res 2000; 14: 174-179
  • 38 Jyoti A, Sethi P, Sharma D. Bacopa monnieri prevents from aluminium neurotoxicity in the cerebral cortex of rat brain. J Ethnopharmacol 2007; 111: 56-62
  • 39 Jyoti A, Sharma D. Neuroprotective role of Bacopa monnieri extract against aluminium-induced oxidative stress in the hippocampus of rat brain. Neurotoxicology 2006; 27: 451-457
  • 40 Kharbangar A, Khynriam D, Prasad S. Effect of cisplatin on mitochondrial protein, glutathione, and succinate dehydrogenase in Dalton lymphoma-bearing mice. Cell Biol Toxicol 2000; 16: 363-373
  • 41 Santos N, Catao C, Martins N, Curti C, Bianchi M, Santos A. Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Arch Toxicol 2007; 81: 495-504
  • 42 Deepak M, Sangli G, Arun P, Amit A. Quantitative determination of the major saponin mixture bacoside A in Bacopa monnieri by HPLC. Phytochem Anal 2005; 16: 24-29
  • 43 Rauf K, Subhan F, Abbas M, Ul Haq I, Ali G, Ayaz M. Effect of acute and sub chronic use of Bacopa monnieri on dopamine and serotonin turnover in mice whole brain. Afr J Pharm Pharmacol 2012; 6: 2767-2774
  • 44 Rauf K, Subhan F, Abbas M, Badshah A, Ullah I, Ullah S. Effect of bacopasides on acquisition and expression of morphine tolerance. Phytomedicine 2011; 18: 836-842
  • 45 Hildebrand F, Paas E. Pharmacological studies on glycoside mixture from Boviea volubilis . Naunyn Schmiedebergs Arch Exp Pathol Pharmakol 1953; 220: 492-499
  • 46 Hanzlik P, Wood D. The mechanism of digitalis-emesis in pigeons. J Pharmacol Exp Ther 1929; 37: 67-100
  • 47 Gupta G, Dhawan B. Blockade of reserpine emesis in pigeons. Arch Int Pharmacodyn Ther 1960; 128: 481-490
  • 48 Hudzik TJ. Sigma ligand-induced emesis in the pigeon. Pharmacol Biochem Behav 1992; 41: 215-217
  • 49 Wolff MC, Leander JD. Effects of a 5-HT1A receptor agonist on acute and delayed cyclophosphamide-induced vomiting. Eur J Pharmacol 1997; 340: 217-220
  • 50 Navarra P, Martire M, del Carmine R, Pozzoli G, Preziosi P. A dual effect of some 5-HT3 receptor antagonists on cisplatin-induced emesis in the pigeon. Toxicol Lett 1992; 64: 745-749
  • 51 Ullah I, Subhan F, Rauf K, Badshah A, Ali G. Role of gastrointestinal motility/gastric emptying in cisplatin-induced vomiting in pigeon. Afr J Pharm Pharmacol 2012; 6: 2592-2599
  • 52 Wolff MC, Leander JD. Comparison of the antiemetic effects of a 5-HT1A agonist, LY228729, and 5-HT3 antagonists in the pigeon. Pharmacol Biochem Behav 1995; 52: 571-575
  • 53 Tanihata S, Oda S, Nakai S, Uchiyama T. Antiemetic effect of dexamethasone on cisplatin-induced early and delayed emesis in the pigeon. Eur J Pharmacol 2004; 484: 311-321
  • 54 Tanihata S, Igarashi H, Suzuki M, Uchiyama T. Cisplatin-induced early and delayed emesis in the pigeon. Br J Pharmacol 2000; 130: 132-138
  • 55 Fukui H, Yamamoto M. Methotrexate produces delayed emesis in dogs: a potential model of delayed emesis induced by chemotherapy. Eur J Pharmacol 1999; 372: 261-267
  • 56 Rudd J, Naylor R. Effects of 5-HT3 receptor antagonists on models of acute and delayed emesis induced by cisplatin in the ferret. Neuropharmacology 1994; 33: 1607-1608
  • 57 Johnston KD, Lu Z, Rudd JA. Looking beyond 5-HT3 receptors: a review of the wider role of serotonin in the pharmacology of nausea and vomiting. Eur J Pharmacol 2014; 722: 13-25
  • 58 Zhang F, Wang L, Yang ZH, Liu ZT, Yue W. Value of mink vomit model in study of anti-emetic drugs. World J Gastroenterol 2006; 12: 1300
  • 59 Coronas R, Pitarch L, Mallol J. Blockade of reserpine emesis in pigeons by metoclopramide. Eur J Pharmacol 1975; 32: 380-382
  • 60 DʼSouza P, Deepak M, Rani P, Kadamboor S, Mathew A, Chandrashekar AP, Agarwal A. Brine shrimp lethality assay of Bacopa monnieri . Phytother Res 2002; 16: 197-198
  • 61 Shinomol GK. Bacopa monnieri modulates endogenous cytoplasmic and mitochondrial oxidative markers in prepubertal mice brain. Phytomedicine 2011; 18: 317-326
  • 62 Deepak M, Amit A. ‘Bacoside B’ – the need remains for establishing identity. Fitoterapia 2013; 87: 7-10
  • 63 Singh H, Dhawan B. Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monnieri Linn. (Brahmi). Indian J Pharmacol 1997; 29: 359
  • 64 Sheikh N, Ahmad A, Siripurapu KB, Kuchibhotla VK, Singh S, Palit G. Effect of Bacopa monnieri on stress induced changes in plasma corticosterone and brain monoamines in rats. J Ethnopharmacol 2007; 111: 671-676
  • 65 Das A, Shanker G, Nath C, Pal R, Singh S, Singh HK. A comparative study in rodents of standardized extracts of Bacopa monnieri and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacol Biochem Behav 2002; 73: 893-900
  • 66 Mathew J, Paul J, Nandhu M, Paulose C. Increased excitability and metabolism in pilocarpine induced epileptic rats: Effect of Bacopa monnieri . Fitoterapia 2010; 81: 546-551
  • 67 Khan R, Krishnakumar A, Paulose C. Decreased glutamate receptor binding and NMDA R1 gene expression in hippocampus of pilocarpine-induced epileptic rats: neuroprotective role of Bacopa monnieri extract. Epilepsy Behav 2008; 12: 54-60
  • 68 Ghosh T, Kumar Maity T, Das M, Bose A, Kumar Dash D. In vitro antioxidant and hepatoprotective activity of ethanolic extract of Bacopa monnieri Linn. aerial parts. Iran J Pharmacol Ther 2007; 6: 77-85
  • 69 Minami M, Endo T, Nemoto M, Hamaue N, Hirafuji M, Monma Y, Yajima T, Yoshioka M, Saito H. How do toxic emetic stimuli cause 5-HT release in the gut and brain?. In: Raynold D, Andrews P, Davis CJ, editors Serotonin and the scientific basis of anti-emetic therapy. Oxford: Oxford Clinical Communications; 1995: 68-76
  • 70 Kwiatkowska M, Parker LA, Burton P, Mechoulam R. A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology 2004; 174: 254-259
  • 71 Himmi T, Perrin J, El Ouazzani T, Orsini JC. Neuronal responses to cannabinoid receptor ligands in the solitary tract nucleus. Eur J Pharmacol 1998; 359: 49-54
  • 72 Laporte A, Koscielniak T, Ponchant M, Verge D, Hamon M, Gozlan H. Quantitative autoradiographic mapping of 5-HT3 receptors in the rat CNS using [125I]iodo-zacopride and [3H]zacopride as radioligands. Synapse 1992; 10: 271-281
  • 73 Percie du Sert N, Rudd JA, Moss R, Andrews PL. The delayed phase of cisplatin-induced emesis is mediated by the area postrema and not the abdominal visceral innervation in the ferret. Neurosci Lett 2009; 465: 16-20
  • 74 Yoshikawa T, Yoshida N, Hosoki K. Involvement of dopamine D3 receptors in the area postrema in R (+)-7-OH-DPAT-induced emesis in the ferret. Eur J Pharmacol 1996; 301: 143-149
  • 75 Miller AD, Leslie RA. The area postrema and vomiting. Front Neuroendocrinol 1994; 15: 301-320
  • 76 King GL. Animal models in the study of vomiting. Can J Physiol Pharmacol 1990; 68: 260-268
  • 77 Nakayama H, Yamakuni H, Higaki M, Ishikawa H, Imazumi K, Matsuo M, Mutoh S. Antiemetic activity of FK1052, a 5-HT3-and 5-HT4-receptor antagonist, in Suncus murinus and ferrets. J Pharmacol Sci 2005; 98: 396-403
  • 78 Diemunsch P, Grélot L. Potential of substance P antagonists as antiemetics. Drugs 2000; 60: 533-546
  • 79 Darmani N, Janoyan J, Kumar N, Crim J. Behaviorally active doses of the CB1 receptor antagonist SR 141716A increase brain serotonin and dopamine levels and turnover. Pharmacol Biochem Behav 2003; 75: 777-787
  • 80 Rauf K, Subhan F, Abbas G, Ali G, Abid SMA, Arshad U, Sharif MJH. Bacopa monnieri inhibits locomotor hyperactivity induced by morphine without altering noradrenaline. Pharmacologyonline 2013; 1: 172-181
  • 81 Rauf K, Subhan F, Sewell RDE. A bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover. Phytother Res 2011; 26: 758-763
  • 82 Qian QH, Yue W, Wang YX, Yang ZH, Liu ZT, Chen WH. Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks. Arch Pharm Res 2009; 32: 565-573
  • 83 Darmani NA, Crim JL, Janoyan JJ, Abad J, Ramirez J. A re-evaluation of the neurotransmitter basis of chemotherapy-induced immediate and delayed vomiting: evidence from the least shrew. Brain Res 2009; 1248: 40-58
  • 84 Vohora S, Khanna T, Athar M, Ahmad B. Analgesic activity of bacosine, a new triterpene isolated from Bacopa monnieri . Fitoterapia 1997; 68: 361-365
  • 85 Subhan F, Abbas M, Rauf K, Arfan M, Sewell RD, Ali G. The role of opioidergic mechanism in the activity of Bacopa monnieri extract against tonic and acute phasic pain modalities. Pharmacologyonline 2010; 3: 903-914
  • 86 Charmandari E, Tsigos C, Chrousos G. Endocrinology of the stress response. Annu Rev Physiol 2005; 67: 259-284
  • 87 Kahol AP, Singh T, Tandon S, Gupta MM, Khanuja SPS. Process for the preparation of a extract rich in bacosides from the herb Bacopa monnieri. US Patent 6833143 B; 2004.
  • 88 Okunlola A, Adewoyin BA, Odeku OA. Evaluation of pharmaceutical and microbial qualities of some herbal medicinal products in south western Nigeria. Trop J Pharm Res 2007; 6: 661-670
  • 89 Nayak B, Pereira LMP. Catharanthus roseus flower extract has wound-healing activity in Sprague Dawley rats. BMC Complement Altern Med 2006; 6: 41
  • 90 Sofowora A. Research on medicinal plants and traditional medicine in Africa. J Altern Complem Med 1996; 2: 365-372
  • 91 Oyedapo O, Sab F, Olagunju J. Bioactivity of fresh leaves of Lantana camara . Biomed Lett 1999; 59: 175-183
  • 92 Preziosi P, DʼAmato M, Del Carmine R, Martire M, Pozzoli G, Navarra P. The effects of 5-HT3 receptor antagonists on cisplatin-induced emesis in the pigeon. Eur J Pharmacol 1992; 221: 343-350
  • 93 Karten HJ, Hodos W. A stereotaxic atlas of the brain of the pigeon: Columba livia . Baltimore: Johns Hopkins University Press; 1967
  • 94 Duvernoy HM, Risold PY. The circumventricular organs: an atlas of comparative anatomy and vascularization. Brain Res Rev 2007; 56: 119-147