title: Stimulatory effect of allantoin on imidazoline I₁ receptors in animal and cell line.
abstract: Allantoin is known as the agonist of imidazoline receptor, especially the I₂ subtype. Effect of allantoin on imidazoline I₁ receptor (I₁R) relating to reduction of blood pressure and its merit in steatosis are still obscure. Also, farnesoid X receptor (FXR) plays an important role in lipid homeostasis related to I₁R activation. Thus, we administered allantoin into high fat diet (HFD)-fed mice showing hypertriglyceridemia and hypercholesterolemia. Allantoin significantly improved hyperlipidemia in HFD mice after 4 weeks of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I₁R activation, attenuated the action of allantoin. In addition, in cultured HepG2 cells, allantoin increased the expression of farnesoid X receptor (FXR). The allantoin-induced FXR expression was blocked by efaroxan. Similar changes were observed in the expressions of FXR-targeted genes. Otherwise, allantoin also lowered systolic blood pressure (SBP) in HFD mice that can be blocked by efaroxan. Taken together, allantoin has an ability to activate I₁R for improvement of metabolic disorders.
authors.affiliation: The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Yanchao, Kaohsiung City, Taiwan.
authors.forename: T T
authors.initials: TT
authors.lastname: Yang
authors.forename: N H
authors.initials: NH
authors.lastname: Chiu
authors.forename: H H
authors.initials: HH
authors.lastname: Chung
authors.forename: C T
authors.initials: CT
authors.lastname: Hsu
authors.forename: W J
authors.initials: WJ
authors.lastname: Lee
authors.forename: J-T
authors.initials: JT
authors.lastname: Cheng
mesh_terms: D000481:Allantoin / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000924:Anticholesteremic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001572:Benzofurans / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control; D056945:Hep G2 Cells; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000960:Hypolipidemic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000481:Allantoin; D000924:Anticholesteremic Agents; D000959:Antihypertensive Agents; D001572:Benzofurans; D000960:Hypolipidemic Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; D000099150:Receptor, Farnesoid X-Activated; C573412:LDLR protein, human; C410887:imidazoline I1 receptors; C062597:efaroxan