Neuroprotective Effect of Aurantio-Obtusin, a Putative Vasopressin V1A Receptor Antagonist, on Transient Forebrain Ischemia Mice Model.
Traditional Chinese medicines (TCMs) have been a rich source of novel drug discovery, and Cassia seed is one of the common TCMs with numerous biological effects. Based on the existing reports on neuroprotection by Cassia seed extract, the present study aims to search possible pharmacological targets behind the neuroprotective effects of the Cassia seeds by evaluating the functional effect of specific Cassia compounds on various G-protein-coupled receptors. Among the four test compounds (cassiaside, rubrofusarin gentiobioside, aurantio-obtusin, and 2-hydroxyemodin 1-methylether), only aurantio-obtusin demonstrated a specific V1AR antagonist effect (71.80 ± 6.0% inhibition at 100 µM) and yielded an IC50 value of 67.70 ± 2.41 μM. A molecular docking study predicted an additional interaction of the hydroxyl group at C6 and a methoxy group at C7 of aurantio-obtusin with the Ser341 residue as functional for the observed antagonist effect. In the transient brain ischemia/reperfusion injury C57BL/6 mice model, aurantio-obtusin attenuated the latency time that was reduced in the bilateral common carotid artery occlusion (BCCAO) groups. Likewise, compared to neuronal damage in the BCCAO groups, treatment with aurantio-obtusin (10 mg/kg, p.o.) significantly reduced the severity of damage in medial cornu ammonis 1 (mCA1), dorsal CA1, and cortex regions. Overall, the findings of this study highlight V1AR as a possible target of aurantio-obtusin for neuroprotection.
['Paudel|Pradeep|P|0000-0001-8482-1129', 'Kim|Dong Hyun|DH|', 'Jeon|Jieun|J|', 'Park|Se Eun|SE|', 'Seong|Su Hui|SH|0000-0002-2683-7373', 'Jung|Hyun Ah|HA|', 'Choi|Jae Sue|JS|0000-0001-9034-8868']
D000818:Animals D000880:Anthraquinones D065092:Antidiuretic Hormone Receptor Antagonists D016893:Carotid Stenosis D002366:Cassia D002867:Chromones D004642:Emodin D004986:Ether D005960:Glucosides D020128:Inhibitory Concentration 50 D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D062105:Molecular Docking Simulation D018696:Neuroprotective Agents D016548:Prosencephalon D017483:Receptors, Vasopressin D012639:Seeds
aurantio-obtusin antagonist cassia molecular docking vasopressin receptor