Phytoconstituents of Datura metel extract improved motor coordination in haloperidol-induced cataleptic mice: Dual-target molecular docking and behavioural studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a prominent health challenge characterized by complex aetiology and limited therapeutic breakthroughs. Datura metel (DM) is a medicinal plant containing active phytoconstituents with neuropharmacological potentials. In traditional medicine, it exerts anticholinergic, anti-inflammatory and antioxidant effects, and protection from organophosphate poisoning inclusively involved in the pharmacotherapy of PD. Its other PD-related medicinal potency includes treatment of motor sickness and bradycardia. However, the exact mechanisms of anti-PD effects of its phytoconstituents remain underexplored. MATERIALS AND METHODS: In this study, methanolic extract of DM was evaluated for anti-PD behavioural effects in vivo haloperidol-induced cataleptic mice. The GC-MS-identified phytochemicals were studied for one-drug-multi-target inhibitory mechanisms against some key targets for PD treatment, alpha-synuclein (ASN) and dopa decarboxylase (DDC) using molecular docking. RESULTS: and discussion: Chronic administration of 50, 100 and 200 mg/kg of DM extract improved the 14-s latency time induced by haloperidol to 54, 54 and 57 s respectively, whereas levodopa (30 mg/kg) produced 47 s in rotarod tests. Similarly, the descending times for haloperidol-induced cataleptic mice were significantly reduced from 110 s to 17.7, 17.7 and 12.5 s by the respective chronic doses of DM extract, whereas levodopa-administered mice spent 17.5 s descending the same 30 cm pole. The interesting motor coordination enhancements are suggestively due to synergistic inhibition of ASN and DCC by the phytoconstituents of DM, especially, atropine and scopolamine. From the docking analysis, the two phytochemicals interacted more potently with the active therapeutic sites of the dual targets than levodopa and carbidopa. CONCLUSION: Methanolic extract of DM contains active phytochemicals for multi-target-directed antiparkinsonian mechanisms amenable for further studies.

Nutritional and Pharmaceutical Applications of Under-Explored Knottin Peptide-Rich Phytomedicines.

Phytomedicines reportedly rich in cystine knot peptides (Knottins) are found in several global diets, food/herbal supplements and functional foods. However, their knottin peptide content has largely been unexplored, notably for their emerging dual potentials at both the food and medicine space. The nutritional roles, biological targets and mechanism(s) of activity of these knotted peptides are largely unknown. Meanwhile, knottins have recently been unveiled as emerging peptide therapeutics and nutraceuticals of primary choice due to their broad spectrum of bioactivity, hyper stability, selective toxicity, impressive selectivity for biomolecular targets, and their bioengineering applications. In addition to their potential dietary benefits, some knottins have displayed desirable limited toxicity to human erythrocytes. In an effort to appraise what has been accomplished, unveil knowledge gaps and explore the future prospects of knottins, an elaborate review of the nutritional and pharmaceutical application of phytomedicines rich in knottins was carried out. Herein, we provide comprehensive data on common dietary and therapeutic knottins, the majority of which are poorly investigated in many food-grade phytomedicines used in different cultures and localities. Findings from this review should stimulate scientific interest to unveil novel dietary knottins and knottin-rich nutraceutical peptide drug candidates/leads with potential for future clinical application.