– 274 – Chinese Journal of Natural Medicines 2015, 13(4): 0274−0282 doi: 10.3724/SP.J.1009.2015.00274 Chinese Journal of Natural Medicines Prophylactic effects of asiaticoside-based standardized extract of Centella asiatica (L.) Urban leaves on experimental migraine: Involvement of 5HT1A/1B receptors Vijeta Bobade 1 , Subhash L. Bodhankar 1* , Urmila Aswar 2 , Vishwaraman Mohan 3 , Prasad Thakurdesai 3 1 Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune-411038, India; 2 Department of Pharmacology, Sinhgad Institute of Pharmacy, Narhe, Pune 411041, India; 3 Indus Biotech Private Limited, 1, Rahul residency, Kondhwa, Pune-411026, India Available online 20 Apr. 2015 [ABSTRACT] The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg −1 , i.p.) and bra- dykinin (BK, 10 µg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg −1 , s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg −1 (oral) and 100 µg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg −1 , 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action. [KEY WORDS] Centella asiatica (L.) Urban; Experimental migraine; Anti-nociception; Serotonin, 5HT1A and 5HT1B receptors [CLC Number] R965 [Document code] A [Article ID] 2095-6975(2015)02-0274-09 Introduction Migraine is a disabling headache characterized by inter- mittent attacks with a number of physiological and emotional stressors associated with pain, tiredness, nausea, vomiting, photophobia, or phonophobia [1] . Migraine is multi-mechanistic disease and associated with a wide array of symptoms in- [Received on] 28-May-2014 [Research funding] This work was supported by Indus Biotech Pri- vate Limited, Pune. [*Corresponding author] Tel: +91-20-24537237 (Ext. 29), Fax: +91-20-25439386, E-mail: sbodhindus@gmail.com All the authors have no conflict of interest to declare. cluding nausea, vomiting, and increased sensitivity to light and sounds. Migraine attacks can be unilateral throbbing headache, worsened by movements and routine daily activi- ties, and lasting from 4 to 72 h. The underlying mechanisms of migraine interspersed with acute symptoms of attack ap- pear to be increasingly complex. An important aspect of mi- graine heterogeneity is comorbidity with other neurological, cardiovascular, and psychiatric diseases [2] . Migraine associ- ated aura is associated with peripheral sensitization is an acute, chemical-induced form of functional plasticity, which con- verts high-threshold nociceptors into low-threshold sensory neurons. This form of sensitization occurs in migraine attacks where the nerve terminals (meningeal nociceptors) of the neurons of the trigeminal ganglion are soaked with the "in- flammatory" soup (prostaglandin E 2 , bradykinin, serotonin,