Efficacy of medicinal herbs in the management of depression prodromal to dementia: A translational study from murine models to humans

Abstract

Depression is a prodromal sign of dementia and may worsen with metabolic disorders like diabetes mellitus. The present study was done to evaluate efficacy of saffron (Saf) and chamomile (Cham) against diabetes associated depression and memory impairment in murine model and through clinical trial in human volunteers visiting psychiatry clinics at the Aga Khan University Hospital, Karachi, Pakistan. In murine study, 50 old diabetic albino wistar rats divided into 5 groups as healthy control (HC), diabetic control (DC), Saf water decoction (WD) 10mg/kg, Cham water decoction (CWD) 30mg/kg and Saf+Cham WD 5mg/kg+15mg/kg for two weeks. The behavioral analysis was done through forced swim (FST) and novel object recognition tests (NOR). Afterwards, animals were sacrificed for blood and brain samples collection. In second phase, 100 depressed patients were given Saf+Cham tea (20mg+1mg) as an adjuvant therapy for depression, assessed through PHQ9 scale. in animals, treatment of Saf and Cham significantly reduced glucose (F4, 45 =9.847, p<0.05) and cholesterol levels (F4, 45 = 20.595, p<0.05). likewise, neurotransmitters dopamine (F4, 45 = 189.593, p<0.05) and acetylcholine (F4, 45 = 69995.098, p<0.05) were also increased along with enhancement in brain derived neurotrophic factor (BDNF) in the hippocampus (F4, 45 = 116.200; p<0.05) with improved FST (F4, 45 = 24.612, p<0.05) and NOR performance (F4, 45 = 55.718, p<0.05). The clinical trial also revealed significant improvement in PHQ 9 scale (F3, 80 = 20.036, p<0.05) with maintenance of normoglycemia (F3, 80 = 10.07, p<0.05) and cholesterol (F3, 80 = 8.89, p<0.05) of test volunteers. The study was validated through animals showing saffron and chamomile augment BDNF level and neurotransmitters with alleviation of metabolic alterations by regulating glucose and lipid metabolism. The clinical trial also showed strong modulating effects of herbal tea on metabolic profile with alleviation of depression a prodromal sign of dementia.