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Planta Med 2020; 86(08): 548-555
DOI: 10.1055/a-1144-3663
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antinociceptive Activity of Asiaticoside in Mouse Models of Induced Nociception

Rasyidah Ryta Ayumi
1   Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Wan Mastura Shaik Mossadeq
1   Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Zainul Amiruddin Zakaria
2   Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Muhammad Taher Bakhtiar
3   Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
,
Nadhirah Kamarudin
1   Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Nadia Hisamuddin
1   Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Madihah Talib
1   Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Aina Mardhiah Sabar
3   Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
› Author AffiliationsSupported by: Geran Putra-Inisiatif Putra Siswazah UPM GP-IPS/2016/9472300
Further Information

Publication History

received 28 October 2019
revised 09 March 2020

accepted 17 March 2020

Publication Date:
15 April 2020 (online)

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Erratum: Antinociceptive Activity of Asiaticoside in Mouse Models of Induced NociceptionPlanta Med 2020; 86(08): e6-e6
DOI: 10.1055/a-1170-9487

Abstract

The antinociceptive property of Centella asiatica extracts is known but the analgesic activity of its bioactive constituent asiaticoside has not been reported. We evaluated the antinociceptive activity of orally (p. o.) administered asiaticoside (1, 3, 5, and 10 mg/kg) in mice using the 0.6% acetic acid-induced writhing test, the 2.5% formalin-induced paw licking test, and the hot plate test. The capsaicin- and glutamate-induced paw licking tests were employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Asiaticoside (3, 5, and 10 mg/kg, p. o.) reduced the rate of writhing (p < 0.0001) by 25.3, 47.8, and 53.9%, respectively, and increased the latency period (p < 0.05) on the hot plate at 60 min post-treatment until the end of the experiment. Moreover, asiaticoside (3, 5, and 10 mg/kg, p. o.) shortened the time spent in licking/biting the injected paw (p < 0.0001) in the early phase of the formalin test by 45.7, 51.4, and 52.7%, respectively, and in the late phase (p < 0.01) by 23.6, 40.5, and 50.6%, respectively. Antinociception induced by asiaticoside (10 mg/kg) was not antagonized by naloxone in both the 2.5% formalin-induced nociception and the hot plate test, indicating a nonparticipation of the opioidergic system. Asiaticoside (1, 3, 5, and 10 mg/kg, p. o.) reduced the duration of biting/licking the capsaicin-injected paw (p < 0.0001) by 40.5, 48.2, 59.5, and 63.5%, respectively. Moreover, asiaticoside (5 and 10 mg/kg) shortened the time spent in biting/licking the glutamate-injected paw (p < 0.01) by 29.9 and 48.6%, respectively. Therefore, asiaticoside (5 and 10 mg/kg, p. o.) induces antinociception possibly through the vanilloid and glutamatergic systems.

Key words

Apiaceae - Centella asiatica - asiaticoside - antinociception - mouse

Supporting Information

 

  • References

  • 1 Loeser JD, Treede R. The Kyoto protocol of IASP basic pain terminology. Pain 2008; 137: 473-477
    CrossrefPubMedGoogle Scholar
  • 2 Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res 2003; 110: 255-258
    CrossrefPubMedGoogle Scholar
  • 3 Li D, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ 2003; 327: 1-5
    CrossrefPubMedGoogle Scholar
  • 4 Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000; 321: 1183-1187
    CrossrefPubMedGoogle Scholar
  • 5 Aithal PG, Day CP. The natural history of histologically proved drug induced liver disease. Gut 1999; 44: 731-735
    CrossrefPubMedGoogle Scholar
  • 6 Hawboldt J. Adverse events associated with NSAIDs. US Pharm 2008; 33: 1-9
    PubMedGoogle Scholar
  • 7 Chahl LA. Opioids – mechanisms of action. Aust Prescr 1996; 19: 1-6
    PubMedGoogle Scholar
  • 8 Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glase SE, Vallejo R. Opioid complications and side effects. Pain Physician 2008; 11 (Suppl. 02) S105-S120
    PubMedGoogle Scholar
  • 9 Dumas EO, Pollack GM. Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. AAPS J 2008; 10: 537-551
    CrossrefPubMedGoogle Scholar
  • 10 Savage SR. Long-term opioid therapy: assessment of consequences and risks. J Pain Symptom Manage 1996; 11: 274-286
    CrossrefPubMedGoogle Scholar
  • 11 Hashim P. Centella asiatica in food and beverage applications and its potential antioxidant and neuroprotective effect. Int Food Res J 2011; 18: 1215-1222
    PubMedGoogle Scholar
  • 12 Wijeweera P, Arnason JT, Koszycki D, Merali Z. Evaluation of anxiolytic properties of Gotukola – (Centella asiatica) extracts and asiaticoside in rat behavioral models. Phytomedicine 2006; 13: 668-676
    CrossrefPubMedGoogle Scholar
  • 13 Azis HA, Taher M, Ahmed AS, Sulaiman WMAW, Susanti D, Chowdhury SR, Zakaria ZA. In vitro and in vivo wound healing studies of methanolic fraction of Centella asiatica extract. S Afr J Bot 2017; 108: 163-174
    CrossrefPubMedGoogle Scholar
  • 14 Somchit MN, Sulaiman MR, Zuraini A, Samsuddin L, Somchit N, Israf DA, Moin S. Antinociceptive and anti-inflammatory effects of Centella asiatica . Indian J Pharmacol 2004; 36: 377-380
    PubMedGoogle Scholar
  • 15 Rahman S, Jamal MM, Parvin A, Al-Mamun MM, Islam MR. Antidiabetic activity of Centella asiatica (L.) urbana in alloxan induced type 1 diabetic model rats. J Biosci 2011; 19: 23-27
    PubMedGoogle Scholar
  • 16 Rattanakom S, Yasurin P. Chemical profiling of Centella asiatica under different extraction solvents and its antibacterial activity, antioxidant activity. Orient J Chem 2015; 31: 2453-2459
    CrossrefPubMedGoogle Scholar
  • 17 Nurlaily A, Noor Baitee AR, Musalmah M. Comparative antioxidant and anti-inflammatory activity of different extracts of Centella asiatica (L.) Urban and its active compounds, asiaticoside and madecassoside. Med Health 2012; 7: 62-72
    PubMedGoogle Scholar
  • 18 Huang SS, Chiu CS, Chen HJ, Hou WC, Sheu MJ, Lin YC, Shie PH, Huang GJ. Antinociceptive activities and the mechanisms of anti-inflammation of asiatic acid in mice. Evid Based Complementary Alternat Med 2011; 2011: 895857
    PubMedGoogle Scholar
  • 19 James JT, Dubery IA. Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules 2009; 14: 3922-3941
    CrossrefPubMedGoogle Scholar
  • 20 Cheng CL, Guo JS, Luk J, Koo MWL. The healing effects of Centella extract and asiaticoside on acetic acid induced gastric ulcers in rats. Life Sci 2004; 74: 2237-2249
    CrossrefPubMedGoogle Scholar
  • 21 Liang X, Huang YN, Chen SW, Wang WJ, Xu N, Cui S, Liu XH, Zhang H, Liu YN, Yang M, Dong Y. Antidepressant-like effect of asiaticoside in mice. Pharmacol Biochem Behav 2008; 89: 444-449
    CrossrefPubMedGoogle Scholar
  • 22 Qi F, Yang L, Tian Z, Zhao M, Liu S, An J. Neuroprotective effects of asiaticoside. Neural Regen Res 2014; 9: 1275-1282
    CrossrefPubMedGoogle Scholar
  • 23 Zhang Z, Li X, Li D, Luo M, Li Y, Song L, Jiang X. Asiaticoside ameliorates β-amyloid-induced learning and memory deficits in rats by inhibiting mitochondrial apoptosis and reducing inflammatory factors. Exp Ther Med 2017; 13: 413-420
    CrossrefPubMedGoogle Scholar
  • 24 Al-Saeedi FJ. Study of the cytotoxicity of asiaticoside on rats and tumour cells. BMC Cancer 2014; 14: 1-13
    CrossrefPubMedGoogle Scholar
  • 25 Hou Q, Li M, Lu YH, Liu DH, Li CC. Burn wound healing properties of asiaticoside and madecassoside. Exp Ther Med 2016; 12: 1269-1274
    CrossrefPubMedGoogle Scholar
  • 26 Sampath U, Janardhanam VA, Gopal G. Acute and sub-chronic oral toxicity of asiaticoside to mice. Int J Eng Sci Technol 2012; 4: 4247-4252
    PubMedGoogle Scholar
  • 27 Ming-Tatt L, Khalivulla SI, Akhtar MN, Mohamad AS, Perimal EK, Hanief M, Akira A, Lajis N, Israf DA, Sulaiman MR. Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone on nociception-induced models in mice. Basic Clin Pharmacol Toxicol 2012; 110: 275-282
    CrossrefPubMedGoogle Scholar
  • 28 Bars DL, Gozariu M, Cadden WS. Animal models of nociception. Pharmacol Rev 2001; 53: 597-652
    PubMedGoogle Scholar
  • 29 Khatun A, Imam MZ, Rana MS. Antinociceptive effect of methanol extract of leaves of Persicaria hydropiper in mice. BMC Complement Altern Med 2015; 15: 1-8
    CrossrefPubMedGoogle Scholar
  • 30 Uddin J, Rahman M, Abdullah-Al-Mamun M, Sadik G. Vanda roxburghii: an experimental evaluation of antinociceptive properties of a traditional epiphytic medicinal orchid in animal models. BMC Complement Altern Med 2015; 15: 1-8
    CrossrefPubMedGoogle Scholar
  • 31 Jaios ES, Rahman SA, Ching SM, Kadir AA, Desa MNM, Zakaria ZA. Possible mechanisms of antinociception of methanol extract of Melastoma malabathricum leaves. Braz J Pharmacog 2016; 26: 586-594
    PubMedGoogle Scholar
  • 32 Berkenkopf JW, Weichman BM. Production of prostacyclin in mice following intraperitoneal injection of acetic acid, phenylbenzoquinone and zymosan: Its role in the writhing response. Prostaglandins 1988; 36: 693-709
    CrossrefPubMedGoogle Scholar
  • 33 Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol 1971; 231: 232-235
    PubMedGoogle Scholar
  • 34 Sani MHM, Taher M, Susanti D, Kek TL, Salleh MZ, Zakaria ZA. Mechanisms of α-Mangostin-induced antinociception in a rodent model. Biol Res Nurs 2015; 17: 68-77
    CrossrefPubMedGoogle Scholar
  • 35 Rahim MHA, Zakaria ZA, Mohd Sani MH, Omar MH, Yakob Y, Cheema MS, Ching SM, Ahmad Z, Kadir AA. Methanolic extract of Clinacanthus nutans exerts antinociceptive activity via the opioid/nitric oxide-mediated, but cGMP-independent, pathways. Evid Based Complement Alternat Med 2016; 2016: 1494981
    PubMedGoogle Scholar
  • 36 Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test: characteristic biphasic pain response. Pain 1989; 38: 347-352
    CrossrefPubMedGoogle Scholar
  • 37 Sulaiman MR, Zakaria ZA, Mohamad AS, Ismail M, Hidayat MT, Israf DA, Adilius M. Antinociceptive and anti-inflammatory effects of the ethanol extract of Alpinia conchigera rhizomes in various animal models. Pharm Biol 2010; 48: 861-868
    CrossrefPubMedGoogle Scholar
  • 38 Saha S, Guria T, Singha T, Maity TK. Evaluation of analgesic and anti-inflammatory activity of chloroform and methanol extracts of Centella asiatica Linn. ISRN Pharmacol 2013; 2013: 789613
    PubMedGoogle Scholar
  • 39 Sakurada T, Matsumura T, Moriyama T, Sakurada C, Ueno S, Sakurada S. Differential effects of intraplantar capsazepine and ruthenium red on capsaicin-induced desensitization in mice. Pharmacol Biochem Behav 2003; 75: 115-121
    CrossrefPubMedGoogle Scholar
  • 40 Cortright DN, Szallasi A. Biochemical pharmacology of the vanilloid receptor TRPV1. Eur J Biochem 2004; 271: 1814-1819
    CrossrefPubMedGoogle Scholar
  • 41 Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000; 288: 306-313
    CrossrefPubMedGoogle Scholar
  • 42 Beirith A, Santos ARS, Calixto JB. Mechanisms underlying the nociception and paw oedema caused by injection of glutamate into the mouse paw. Brain Res 2002; 924: 219-228
    CrossrefPubMedGoogle Scholar
  • 43 Zhuo M. Ionotropic glutamate receptors contribute to pain transmission and chronic pain. Neuropharmacology 2017; 112: 228-234
    CrossrefPubMedGoogle Scholar
  • 44 Sani MHM, Zakaria ZA, Balan T, Teh LK, Salleh MZ. Antinociceptive activity of methanol extract of Muntingia calabura leaves and the mechanisms of action involved. Evid Based Complement Alternat Med 2012; 2012: 890361
    PubMedGoogle Scholar
  • 45 Zakaria ZA, Jaios ES, Omar MH, Abd Rahman S, Hamid SSA, Ching SM, Teh LK, Salleh MZ, Deny S, Taher M. Antinociception of petroleum ether fraction derived from crude methanol extract of Melastoma malabathricum leaves and its possible mechanisms of action in animal models. BMC Complement Altern Med 2016; 16: 1-18
    PubMedGoogle Scholar