Can Glycyrrhiza glabra L. reduce delirium after coronary artery bypass graft surgery?

Hadi Darvishi Khezri, MSc Thalassemia Research Center Hemoglobinopathy Institute, Booali Sina Hospital Pasdaran Boulevard, Sari, Iran [email protected] © 2014 S. Karger AG, Freiburg 1661–4119/14/0216–0418$39.50/0 Coronary artery bypass graft (CABG) surgery is one of the most commonly performed invasive procedures worldwide [1, 2]. Since the introduction of cardiopulmonary bypass (CPB), the neurological consequence of CABG surgery has been an important subject [2]. Delirium is a major problem after CABG surgery with the approximate reported incidence rate of 20–80% [2]. This complication is associated with increased mortality, longer hospital stay, increased hospital costs, and long-term care [2–4]. Regarding the high incidence of delirium in patients undergoing CABG surgery, prophylactic treatment is preferable. Hence, pharmacological neuroprotective strategies have been developed for these patients [3, 4]. A meta-analysis indicated that preoperative low-dose and shortterm administration of haloperidol or risperidone may modestly reduce delirium occurrence in high-risk patients that need intensive care unit (ICU) [4]. Other clinical trials have not reported any decreases in the incidence rate of delirium in patients receiving pharmacologic prophylactic (haloperidol, donepezil [5], citicoline [6], and rivastigmine) [7–9]. Acute inflammation and reduced serotonin neurotransmitter are the most important causes of delirium in these patients [10, 11]. In a meta-analysis, Peng et al. [12] showed the role of peripheral inflammatory markers, such as interleukin-6 and S-100 , in postoperative delirium [13]. Although some studies indicated that use of compounds with brain protective activities (such as propofol, aprotininand lidocaine) can prevent delirium after CABG surgery, no sufficient evidence was presented to make a change in standard clinical practice. Licorice (G. glabra, species: Leguminosae) is a worldwide popular herbal medicine. Just 3 out of the numerous species of licorice are usually used as commercial drugs, including G. glabra, Glycyrrhiza echinata L., and Glycyrrhiza uralensis Fisch. In traditional medicine, the roots and rhizomes (underground stems) of licorice are currently used as therapeutic compounds in many Asian and European countries. Licorice mainly consists of a mixture of glycyrrhizinic acid, glycyrrhizic acid, glycyrrhizin, isoflavones, isoliquiritigenin, hispaglabridin B, paratocarpin B, and glabiridin. Furthermore, this plant has been used as antidote and demulcent, expectorant, antioxidant, antiulcer, laxative, antipyretic, antimicrobial, and antiinflammation agent [14]. Glabridin, a major active flavonoid in licorice, has anti-atherosclerotic, anti-inflammatory, antinephritis, radical scavenging activities and antidepressant-like effects [15]. Moreover, this compound has been reported to be useful for renovascular and cardiovascular diseases [16]. Ojha et al. [16] evaluated the cardioprotective effect of licorice against ischemia-reperfusion injury induced by ligation of left anterior descending coronary artery in rats. Their results confirmed the cardioprotective activity of licorice by alleviating oxidative stress in myocardial ischemia-reperfusion injury [16]. Safe brain-protective agents, such as licorice, could be utilized to reduce the neuroinflammation and delirium caused by CPB in these patients. Muralidharan et al. [14] investigated the cerebroprotective effect of 250 and 500 mg/kg of licorice roots in hypoxic rats and indicated that licorice has a cerebro-