Aurantiamide

Aurantiamide is a non-covalent, orally active, blood-brain-permeable GRPR selective antagonist with anti-inflammatory and neuroprotective effects. Aurantiamide reduces inflammation and oxidative stress in renal tissue by inhibiting GRPR-mediated renal necrosis pathways (such as RIPK3/MLKL signaling) and NF-κB inflammatory pathways, exerting anti-acute kidney injury and endothelial function activities. Aurantiamide also inhibits the M1 polarization of microglia and inhibits NLRP3 activation, thereby improving AD mouse models. Aurantiamide has in vivo inhibitory efficacy in acute kidney injury models such as ischemia/reperfusion, sepsis, and hypertension models^{[1][2][3][4][5]}. In Vitro:Aurantiamide (25, 50, 100 μM; 12 h) significantly reduces the protein and mRNA expression of the renal injury marker KIM1 in the human renal proximal tubular epithelial cell (HK-2) hypoxia/reoxygenation and LPS (1 mg/mL) stimulation model, inhibits the phosphorylation of proteins related to the RIPK3/MLKL necrosis pathway and NF-κB inflammatory pathway, and alleviates cell damage and inflammatory response^[1].
Aurantiamide (10, 20 μM; 24 h) inhibits LPS and IFN-γ-induced BV2 activation and M1 polarization in mouse BV2 cells, inhibited the activation of NLRP3, and thus exerted anti-CNS inflammatory activity^[2].
Aurantiamide promotes M2 polarization of microglia and improves cognitive ability of Alzheimer's disease mice^[3].
Aurantiamide (3 μM; 18 h) significantly upregulates the mRNA and protein expression of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs), promotes the production of nitric oxide (NO), and has no significant toxic effect on cell viability^[4].
In Vivo:Aurantiamide (2.5, 5, 10 mg/kg; oral gavage; 3 times, 24 hours apart) improves cognitive impairment in C57BL/6 mice after ischemia/reperfusion (I/R) and cecal ligation and puncture (CLP) in a dose-dependent manner, and inhibits microglial polarization and NLRP3 activation^[2].
Aurantiamide (0.5 mg/kg; intraperitoneal injection; once a day, 5 days a week; 4 weeks) significantly reduces mean arterial blood pressure, improves endothelium-dependent vasodilation, upregulates aortic endothelial nitric oxide synthase (eNOS) protein expression and promotes nitric oxide (NO) production in the two-kidney-one-clip (2K-1C) renovascular hypertension model in Sprague-Dawley rats^[4].
The metabolic characteristics of Aurantiamide (0.1 mg/kg; oral gavage; single dose) and Aurantiamide acetate (HY-N2905) (0.2 mg/kg; oral gavage; single dose) in rats shows that they have the characteristics of rapid diffusion, wide distribution, and can pass through the blood-brain barrier, with a peak time of 0.5 h. In addition, the decline rate of aurantiamide acetate is faster than that of aurantiamide^[5].