摘要
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 bradykinin(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-HT1 A, 5-HT1 B, and 5-HT1 D 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-HT1 A and 5-HT1 B but not 5-HT1 D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.
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 bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 rain) 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 1NDCA with selective 5-HT1A, 5-HT1B, and 5-HTI D 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 hypera|gesia 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-HTIA and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, 1NDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.
基金
supported by Indus Biotech Private Limited,Pune