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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (6): 619-625.doi: 10.3736/jcim20110607

• Original Experimental Research • Previous Articles     Next Articles

Identification of antiplatelet and acetylcholinesterase inhibitory constituents in betel nut

Nabeel Ghayur Muhammad1,2,Faraz Kazim Syed1,Rasheed Huma3,Khalid Asaad3,4,Iqbal Jumani Maliha1,Iqbal Choudhary Muhammad3,Hassan Gilani Anwarul1()   

  1. 1. Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan
    2. Department of Medicine, St. Joseph’s Healthcare Hamilton，McMaster University, Hamilton, Canada
    3. Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi, Pakistan
    4. Medicinal and Aromatic Plants Research Institute, National Center for Research, Khartoum, Sudan
  • Received:2010-12-23 Accepted:2011-03-01 Online:2011-06-20 Published:2018-10-17
  • Contact: Hassan Gilani Anwarul E-mail:anwar.gilani@aku.edu
  • Supported by:
    This study was supported by the grants from the Pakistan Science Foundation and the Higher Education Commission of Pakistan

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Objective: To investigate the possible mechanism and the compound(s) responsible for the antiplatelet and acetylcholinesterase (AChE) inhibitory effects of Areca catechu crude extract (Ac.Cr).
Methods: Aqueous-methanol (70%) was used for extraction of plant material (betel nut). Antiplatelet activity was measured in human platelet-rich plasma by using a Lumi-aggregometer while anti-AChE activity was measured spectrophotometrically in vitro. In an attempt to find the responsible compound(s) in betel nut for antiplatelet and anti-AChE activities, different commercially available betel nut compounds were tested.
Results: Ac.Cr inhibited platelet aggregation induced by arachidonic acid (AA), adenosine diphosphate (ADP), platelet-activating factor (PAF), epinephrine and Ca 2+-ionophore. Ac.Cr was the most potent in inhibiting ADP- and Ca 2+-ionophore-induced aggregation. In the AChE assay, Ac.Cr showed significant AChE inhibitory activity with almost complete inhibition of the enzyme. Out of the tested compounds, none of the compounds in betel nut showed any antiplatelet effect except for catechin that was the most potent against epinephrine-induced aggregation. Catechin was significantly less potent than Ac.Cr, indicating a presence of additional compound(s) with antiplatelet activity. For the AChE inhibitory effect, only tannic acid, gallic acid, diosgenin and isoguvacine were found to be active, whereby tannic acid was more potent than Ac.Cr.
Conclusion: This study shows the possible antiplatelet and AChE inhibitory potential of betel nut while further studies are needed to confirm and identify more compounds in betel nut for these actions.

Key words: Areca catechu, plant extracts, platelet aggregation inhibitors, cholinesterase inhibitors, catechin, tannic acid

Figure 1

Effects of betel nut crude and pure compounds on human platelet aggregation Concentration-response curves show the inhibitory effect of (A) betel nut 70% aqueous-methanolic extract and (B) (+)-catechin, against platelet aggregation induced by agonists such as arachidonic acid (AA, 1.7 mmol/L), adenosine diphosphate (ADP, 4.3 μmol/L), platelet-activating factor (PAF, 8 nmol/L), epinephrine (20 μmol/L) and Ca2+-ionophore (10 μmol/L) in human venous blood. The symbols represent x±sx from 4 to 6 determinations and expressed as a percentage of agonist-induced aggregation."

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[1] Chu NS . Effects of betel chewing on the central and autonomic nervous systems[J]. J Biomed Sci, 2001,8(3):229-236
doi: 10.1007/BF02256596
[2] Gilani AH, Ghayur MN. The betel nut chewing culture. In: Gottschalk-Batshkus CE, Green JC. Ethnotherapies in the cycle of life: fading, being and becoming[M]. Munich: BOD-Books on Demand/Ethnomed Institut für Ethnomedizin e.V, 2005: 287-294
[3] Kusomoto IT, Nakabayashi T, Kida H, Miyashiro H, Hattori M, Namba T, Shimotohna K . Screening of various plant extracts used in ayurvedic medicine for inhibitory effects on human immunodeficiency virus type 1(HIV-1) protease[J]. Phytother Res, 1995,9(3):180-184
doi: 10.1002/(ISSN)1099-1573
[4] Chempakam B . Hypoglycemic activity of arecoline in betel nut Areca catechu L[J]. Indian J Exp Biol, 1993,31(5):474-475
pmid: 8359856
[5] Ohsugi M, Fan W, Hase K, Xiong Q, Tezuka Y, Komatsu K, Namba T, Saitoh T, Tazawa K, Kadota S . Active-oxygen scavenging activity of traditional nourishing-tonic herbal medicines and active constituents of Rhodiola sacra[J]. J Ethnopharmacol, 1999,67(1):111-119
doi: 10.1016/S0378-8741(98)00245-1
[6] Iwamoto M, Matsuo T, Uchino K, Tonosaki Y, Fukuchi A . New 5’-nucleotidase inhibitors, NPF-86ⅠA, NPF-86ⅠB, NPF-86ⅡA, and NPF-86ⅡB from Areca catechu; PartⅡ. Anti-tumor effects[J]. Planta Med, 1988,54(5):422-425
doi: 10.1055/s-2006-962488
[7] Sullivan RJ, Allen JS, Otto C, Tiobech J, Nero K . Effects of chewing betel nut(Areca catechu) on the symptoms of people with schizophrenia in Palau, Micronesia[J]. Br J Psychiatry, 2000,177(2):174-178
doi: 10.1192/bjp.177.2.174
[8] Inokuchi J, Okabe H, Yamauchi T, Nagamatsu A, Nonaka G, Nishioka I . Antihypertensive substance in seeds of Areca catechu L[J]. Life Sci, 1986,38(15):1375-1382
doi: 10.1016/0024-3205(86)90470-4
[9] Gilani AH, Ghayur MN, Saify ZS, Ahmed SP, Choudhary MI, Khalid A . Presence of cholinomimetic and acetylcholinesterase inhibitory constituents in betel nut[J]. Life Sci, 2004,75(20):2377-2389
doi: 10.1016/j.lfs.2004.03.035 pmid: 15350815
[10] Gilani AH, Ghayur MN, Houghton PJ, Jabeen Q, Kazim SF, Jumani MI, Saeed SA . Studies on the hypotensive, cardio-suppressant, vasodilator and antiplatelet activities of betel nut crude extract and its constituents[J]. Int J Pharmacol, 2006,2(1):33-41
doi: 10.3923/ijp.2006.33.41
[11] Ghayur MN, Gilani AH . Cardio-selective inhibitory effect of the betel nut extract: possible explanation[J]. Pharmazie, 2007,62(1):67-71
doi: 10.1691/ph2007.1.6583 pmid: 17294817
[12] Bhandare AM, Kshirsagar AD, Vyawahare NS, Hadambar AA . Potential analgesic, anti-inflammatory and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut[J]. Food Chem Toxicol, 2010,48(12):3412-3417
doi: 10.1016/j.fct.2010.09.013
[13] Pithayanukul P, Nithitanakool S, Bavovada R . Hepatoprotective potential of extracts from seeds of Areca catechu and nutgalls of Quercus infectoria[J]. Molecules, 2009,14(12):4987-5000
doi: 10.3390/molecules14124987
[14] Moutasim KA, Jenei V, Sapienza K, Marsh D, Weinreb PH, Violette SM, Lewis MP, Marshall JF, Fortune F, Tilakaratne WM, Hart IR, Thomas GJ . Betel-derived alkaloid up-regulates keratinocyte alphavbeta6 integrin expression and promotes oral submucous fibrosis[J]. J Pathol, 2011,223(3):366-377
doi: 10.1002/path.2786
[15] Al-Swiahb JN, Chen CH, Chuang HC, Fang FM, Tasi HT, Chien CY . Clinical, pathological and molecular determinants in squamous cell carcinoma of the oral cavity[J]. Future Oncol, 2010,6(5):837-850
doi: 10.2217/fon.10.35 pmid: 20465394
[16] IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. IARC monographs on the evaluation of carcinogenic risk of chemicals to humans, volume 37. Tobacco habits other than smoking; betel-quid and areca-nut chewing; and some related nitrosamines . Summaries of data reported and evaluations. Lyon: World Health Organization, International Agency for Research on Cancer. 1985.
doi: 10.1136/jcp.33.1.98-b pmid: 6998267
[17] IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. IARC monographs on the evaluation of carcinogenic risk of chemicals to humans, volume 85. Betel-quid and areca-nut chewing and some areca-nut-derived nitrosamines. Summaries of data reported and evaluations. Lyon: World Health Organization, International Agency for Research onCancer. 2004
doi: 10.1136/jcp.33.1.98-b pmid: 6998267
[18] Sharan RN . Association of betel nut with carcinogenesis[J]. Cancer J, 1996,9(1):13-19
[19] Warnakulasuriya S, Trivedy C, Peters TJ . Areca nut use: an independent risk factor for oral cancer[J]. BMJ, 2002,324(7341):799-800
doi: 10.1136/bmj.324.7341.799 pmid: 1122751
[20] Trivedy CR, Craig G, Warnakulasuriya S . The oral health consequences of chewing areca nut[J]. Addict Biol, 2002,7(1):115-125
doi: 10.1080/13556210120091482 pmid: 11900631
[21] Sharan RN, Choudhury Y. Betel nut and susceptibility to cancer. In: Sharan RN, Choudhury Y. Environmental factors, genes and the development of human cancers[M]. New York: Springer, 2010: 401-428
[22] Bhat SJ, Blank MD, Balster RL, Nichter M, Nichter M . Areca nut dependence among chewers in a South Indian community who do not also use tobacco[J]. Addiction, 2010,105(7):1303-1310
doi: 10.1111/j.1360-0443.2010.02952.x pmid: 3143027
[23] Shrestha J, Shanbhag T, Shenoy S, Amuthan A, Prabhu K, Sharma S, Banerjee S, Kafle S . Antiovulatory and abortifacient effects of Areca catechu(betel nut) in female rats[J]. Indian J Pharmacol, 2010,42(5):306-311
doi: 10.4103/0253-7613.70350 pmid: 21206624
[24] Nadkarni KM. Dr. K. M . Nadkarni’s Indian materia medica[M]. Bombay: Popular Prakashan, 1976
[25] Lin SK, Chang YJ, Ryu SJ, Chu NS . Cerebral hemodynamic responses to betel chewing: a Doppler study[J]. Clin Neuropharmacol, 2002,25(5):244-250
doi: 10.1097/00002826-200209000-00003 pmid: 12410054
[26] Maiese K, Holloway HH, Larson DM, Soncrant TT . Effect of acute and chronic arecoline treatment on cerebral metabolism and blood flow in the conscious rat[J]. Brain Res, 1994,641(1):65-75
doi: 10.1016/0006-8993(94)91816-3
[27] Shah BH, Rasheed H, Rahman IH, Shariff AH, Khan FL, Rahman HB, Hanif S, Saeed SA . Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine[J]. Exp Mol Med, 2001,33(4):226-233
doi: 10.1038/emm.2001.37
[28] Ghayur MN, Gilani AH, Rasheed H, Khan A, Iqbal Z, Ismail M, Saeed SA, Janssen LJ . Cardiovascular and airway relaxant activities of peony root extract[J]. Can J Physiol Pharmacol, 2008,86(11):793-803
doi: 10.1139/Y08-084 pmid: 19011675
[29] Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM . A new and rapid colorimetric determination of acetylcholinesterase activity[J]. Biochem Pharmacol, 1961,7:88-95
doi: 10.1016/0006-2952(61)90145-9
[30] Jeng JH, Chen SY, Liao CH, Tung YY, Lin BR, Hahn LJ, Chang MC . Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase[J]. Free Radic Biol Med, 2002,32(9):860-871
doi: 10.1016/S0891-5849(02)00749-9
[31] Ghayur MN, Gilani AH . Species differences in the prokinetic effects of ginger[J]. Int J Food Sci Nutr, 2006,57(1-2):65-73
doi: 10.1080/09637480600656074 pmid: 16849115
[32] Ghayur MN, Gilani AH, Houghton PJ . Species differences in the gut stimulatory effects of radish seeds[J]. J Pharm Pharmacol, 2005,57(11):1493-1502
doi: 10.1211/jpp.57.11.0016 pmid: 16259783
[33] Tazawa R, Green ED, Ohashi K, Wu KK, Wang LH . Characterization of the complete genomic structure of human thromboxane synthase gene and functional analysis of its promoter[J]. Arch Biochem Biophys, 1996,334(2):349-356
doi: 10.1006/abbi.1996.0464
[34] Saeed SA, Connor JD, Rasheed H, Gilani AH, Lodhi S, Ali SS, Rashid S, Khan E, Shah BH . Wortmannin inhibits platelet aggregation produced by interaction of gamma-aminobutyric acid and the calcium tonophore, A23187[J]. Res Commun Mol Pathol Pharmacol, 2001,109(1-2):87-94
[35] Kimura Y, Okuda H . Effects of α- and β-adrenergic antagonist on epinephrine-induced aggregation and intracellular free calcium concentration in human platelets[J]. Biochem Biophys Res Commun, 1994,202(2):1069-1075
doi: 10.1006/bbrc.1994.2037
[36] Lages B, Weiss HJ . Enhanced increases in cytosolic Ca2+ in ADP-stimulated platelets from patients with δ-storage pool deficiency — a possible indicator of interactions between granule-bound ADP and the membrane ADP receptor[J]. Thromb Haemost, 1997,77(2):376-382
doi: 10.1055/s-0038-1655971
[37] Gilani AH, Rahman AU . Trends in ethnopharmacology[J]. J Ethnopharmacol, 2005,100(1-2):43-49
doi: 10.1016/j.jep.2005.06.001
[38] Ghayur MN, Khan H, Gilani AH . Antispasmodic, bronchodilator and vasodilator activities of(+)-catechin, a naturally occurring flavonoid[J]. Arch Pharm Res, 2007,30(8):970-975
doi: 10.1007/BF02993965
[39] Guh JY, Chen HC, Tsai JF, Chuang LY . Betel-quid use is associated with heart disease in women[J]. Am J Clin Nutr, 2007,85(5):1229-1235
doi: 10.1186/1476-511X-6-14 pmid: 17490957
[40] Lin WY, Chiu TY, Lee LT, Lin CC, Huang CY, Huang KC . Betel nut chewing is associated with increased risk of cardiovascular disease and all-cause mortality in Taiwanese men[J]. Am J Clin Nutr, 2008,87(5):1204-1211
doi: 10.1093/ajcn/87.5.1204
[41] Yen AM, Chen LS, Chiu YH, Boucher BJ, Chen TH . A prospective community-population-registry based cohort study of the association between betel-quid chewing and cardiovascular disease in men in Taiwan(KCIS no. 19)[J]. Am J Clin Nutr, 2008,87(1):70-78
doi: 10.1093/ajcn/87.1.70
[42] Bullock R . New drugs for Alzheimer’s disease and other dementias[J]. Br J Psychiatry, 2002,180:135-139
doi: 10.1192/bjp.180.2.135 pmid: 11823323
[43] Palmer AM . Pharmacotherapy for Alzheimer’s disease: progress and prospects[J]. Trends Pharmacol Sci, 2002,23(9):426 433
doi: 10.1016/S0165-6147(02)02056-4 pmid: 12237155
[44] Soncrant TT, Raffaele KC, Asthana S, Berardi A, Morris PP, Haxby JV . Memory improvement without toxicity during chronic, low dose intravenous arecoline in Alzheimer’s disease[J]. Psychopharmacology (Berl), 1993,112(4):421-427
doi: 10.1007/BF02244889
[45] Rupniak NM, Steventon MJ, Field MJ, Jennings CA, Iversen SD . Comparison of the effects of four cholinomimetic agents on cognition in primates following disruption by scopolamine or by lists of objects[J]. Psychopharmacology (Berl), 1989,99(2):189-195
doi: 10.1007/BF00442806
[46] Shih YT, Chen PS, Wu CH, Tseng YT, Wu YC, Lo YC . Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system[J]. Free Radic Biol Med, 2010,49(10):1471-1479
doi: 10.1016/j.freeradbiomed.2010.07.017
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