Matricaria chamomilla L. leaf and flower extracts improved scopolamine-induced amnesia via regulation of cholinergic dysfunction and brain antioxidant status: An in-vivo and in-silico study

Abstract

Ethnopharmacological relevance: Chamomile (M. Chamomilla L. flowers, Family: Asteraceae) is a notable folk medicine in western Asia and Europe. It has traditionally been used to calm the nerves, induce sleep, and relieve digestive issues like stomach cramps and diarrhea. Nonetheless, studies suggest that its leaf extract also possesses memory-enhancing and antioxidant characteristics.

Aim of the study: The present study aimed to provide evidence showing that the hydroalcoholic extracts of M. Chamomilla L. leaf and flower may regulate memory in a scopolamine-induced amnestic rat model via exerting neuroprotective effects.

Materials and methods: For 21 days, rats were given hydroalcoholic extracts of the leaf and flower extracts (200 and 300 mg/kg per day) orally, while scopolamine hydrobromide (1 mg/kg) was administered intraperitoneally, 30 min before the treatment to cause memory impairment. Initially, the extract's total flavonoid, polyphenolic content, and GC-MS analysis were carried out. The antioxidant and MTT assay testing were also quantified. Passive avoidance, open field, stationary rod, rotarod, and water maze tests were employed for memory and locomotor assessment. In the rat's brain, ACh and AChE activity were assessed along with histopathological changes. The total amount of anti-inflammatory biomarkers in the rat brain and the levels of glutathione peroxidase, C-reactive protein, and superoxide dismutase were measured. And at last, predict the binding affinity of some identified compounds with the AChE receptor by In-silico molecular docking.

Results: Our results showed that M. Chamomilla L. leaf and flower extracts have 60 compounds in the flower extract and 70 compounds in the leaf extract, which significantly restored memory impairment and locomotor activities as compared to the scopolamine group. Treatment with both extracts significantly reversed not only scopolamine-induced changes in the oxidative-antioxidative balance, acetylcholine and acetylcholinesterase activity in the rat's brain (P<0.05). Moreover, we have found that the flower and leaf extract significantly reduced IL-1β and TNF-α expression in the rat's brain and restored scopolamine-induced histopathological distortion. The molecular docking analysis revealed a high probability of AChE inhibition by the identified compounds in the extracts.

Conclusion: Thus, In-silico and In-vivo results suggest that M. Chamomilla L. leaf and flower extracts may be an effective neuropharmacological treatment for memory loss by enhancing the cholinergic system and antioxidant activities.

Keywords: Acetylcholinesterase; Amnesia; Antioxidant; Matricaria Chamomilla L. anti-inflammatory; Neuroinflammation; Scopolamine.