Anxiolytic Mechanism(S) and Corticosterone-Attenuating Effect of Hydroalcoholic Leaf Extract of Tapinanthus globiferus Mistletoe Growing on Azadirachta indica Tree

Abstract

Similar pharmacodynamic mechanism(s) often underlie drug actions and toxicities of anxiolytic agents and medicinal extracts. Extracts of Tapinanthus globiferus and related plant species have been reported with anxiolytic activities. But mechanistic evaluations on these plant extracts are few. This study investigated the anxiolytic mechanism(s), including the corticosterone-attenuating effect, of hydroalcoholic Tapinanthus globiferus (HATG) leaf extract harvested from Azadirachta indica host tree in the mouse elevated zero-maze and restraint-induced acute stress paradigms using per cent open segment time (%OST) and brain/plasma corticosterone levels as endpoints, respectively. The results show that anxiolytic activity (%OST) of 150 mg/kg HATG leaf extract was reversed by pretreatment with 5 mg/kg caffeine (HATG alone, 10.90±1.73;HATG+Caffeine, 8.66±1.74), 2 mg/kg methysergide (MTD) (HATG alone, 98.70±14.98; HATG+MTD, 74.20±10.82) and 5 mg yohimbine (HATG alone, 120.10±10.72; HATG+Yohimine, 78.44±13.92) but not by 0.5 m/kg atropine (HATG alone, 104.60±25.31; HATG+Atropine, 105.40±11.85), 0.5 mg/kg flumazenil (HATG alone,80.27±9.69; HATG+Flumazenil, 80.75±10.19), 2 mg/kg cyproheptadine (HATG alone, 88.67±16.44; HATG+Cyproheptadine, 92.11±12.58), 0.2 mg/kg haloperidol (HATG alone, 74.11±17.33; HATG+Haloperidol, 94.00±32.54) and 5 mg/kg naloxone (HATG alone, 94.30±10.84; HATG+Naloxone, 95.30±6.86). The results also indicate HATG leaf extract (at 50, 150, 500 and 1500 mg/kg) caused largely dose-dependent and significant (p<0.05) attenuations in brain/plasma corticosterone levels (5.64±0.66/3.91±0.44,3.78±0.39/3.39±0.38, 4.26±0.34/3.22±0.18 and 2.74±0.51/2.74±0.22), respectively, in extract- compared to distilled water- (5.93±0.60/4.56±0.37) and diazepam-treated (2.34±0.19/2.44±0.29) mice subjected to restraint-induced acute stress. These findings suggest anxiolytic mechanism(s) of the extract may involve its interactions with the adenosine, non-5HT2 serotonin, alpha (α)2 receptors and the hypothalamus-pituitary-adrenal (HPA) axis. This study may constitute the first mechanistic and corticosterone modulation report on the extracts of this parasitic medicinal plant and may benefit from confirmatory radio-labelled binding assays in subsequent studies.