title: Glycyrrhizin Attenuates Proinflammatory Cytokines through a Peroxisome Proliferator-Activated Receptor-γ-Dependent Mechanism and Experimental Vasospasm in a Rat Model.
abstract: The peroxisome proliferator-activated receptor (PPAR) is downregulated in the cortex of experimental subarachnoid hemorrhage (SAH) animals. This study is to examine the effect of glycyrrhizin on the alternation of PPARs and proinflammatory cytokines in a rodent SAH model. CSF cytokines were evaluated by RT-PCR. Basilar arteries (BAs) were harvested to examine PPARs (RT-PCR and Western blot), and a morphological examination was conducted. Deformed endothelium and tortuous elastic lamina were observed in the BAs of the SAH groups, but they were absent in the glycyrrhizin groups or the healthy controls. The PPAR-γ and -δ protein levels were reduced in the SAH groups (p < 0.01). Glycyrrhizin significantly increased the expressed PPAR-γ protein and mRNA (preconditioning) and PPAR-δ mRNA (both treatment and preconditioning), which corresponded to the reduced IL-1β and TNF-α levels. The administration of a PPAR-γ inhibitor, BADGE, halted the reduction of IL-1β and TNF-α in the glycyrrhizin groups. Conclusively, glycyrrhizin exerts anti-inflammatory effects on SAH-induced vasospasm and attenuates the expression of PPARs, especially PPAR-γ, which corresponds to the severity of SAH-related inflammation. These findings also offer credit to the antivasospastic effect of glycyrrhizin and its vasculoprotective effect in animals subjected to SAH.
authors.affiliation: Department of Surgery, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Chih-Zen
authors.initials: CZ
authors.lastname: Chang
authors.forename: Shu-Chuan
authors.initials: SC
authors.lastname: Wu
authors.forename: Aij-Lie
authors.initials: AL
authors.lastname: Kwan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001488:Basilar Artery / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000134:cerebrospinal fluid / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation; D007260:Infusion Pumps; D008297:Male; D047494:PPAR delta / Q000096:biosynthesis / Q000235:genetics; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008517:Phytotherapy; D011292:Premedication; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016037:Single-Blind Method; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D047494:PPAR delta; D047495:PPAR gamma; D012333:RNA, Messenger; D019695:Glycyrrhizic Acid