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- Background: Gongronema latifolium (G. latifolium) Benth. leaves are traditionally used to treat diabetes mellitus (DM) and other diseases in Nigeria and West Africa. This study was performed to evaluate the neuroprotective effect of aqueous extract of G. latifolium leaf against DM. Antidiabetic activity of G. latifolium extracts (6.36, 12.72 and 25.44 mg kg−1, i.p.) was determined in alloxan-induced diabetic rats. Fasting blood glucose level and oxidative stress markers catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and nitric oxide (NO) levels were measured. Cognitive biomarkers acetylcholinesterase (AChE), butyrylcholinesterase (BChE), dopamine (DOPA), serotonin, epinephrine and norepinephrine and cyclooxygenase (COX-2) were measured in the brain of controls and of G. latifolium-treated diabetic rats. Results: Administration of G. latifolium leaf extract to diabetic rats significantly restored the alterations in the levels of fasting blood glucose (FBG). The MDA and NO levels were significantly reduced with an improvement in CAT, SOD, and GPx activity in the kidneys and brains of diabetic rats treated with G. latifolium. Gongronema latifolium also significantly decreased the levels of AChE, BChE, DOPA, serotonin, epinephrine, and nor-epinephrine in diabetic rats. G. latifolium effectively ameliorated COX-2 in diabetic rats. Conclusion: This study showed that leaf extract of G. latifolium improved antioxidant defense against oxidative stress. It displays a neuroprotective effect resulting in the modulation of brain neurotransmitters, which could be considered as a promising treatment therapy.
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- This research evaluates the hepatoprotective and haematoprotective abilities of the extract of Gongronema latifolium leaves in diabetic rats. Forty animals were induced intraperitoneal using alloxan of 150 mg/kg body weight. The Wistar rats were thereafter divided as follows: normal control, diabetic untreated control, diabetic rats received 5 mg/kg body weight of metformin, and diabetic rats received three ethnobotanical doses (6.36, 12.72, and 25.44 mg/kg body weight) of aqueous extract of G. latifolium leaves (AEGLL). On the 14th day of the experiment, the rats were relinquished, and various hepatoprotective and haematoprotective biomarkers were assessed. Diabetic rats administered AGELL demonstrated normoglycaemia, reduced inflammatory levels as well as activities of transaminases. Also, diabetic animals that received AGELL show a substantial increase in protein, albumin, and hematological parameters determined when linked to diabetic control rats. Hence, three ethnobotanical doses revealed the hepatoprotective and haematoprotective nature of this plant.
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- Orexinergic system dysfunction is the fundamental basis for several neurological illnesses like narcolepsy, insomnia, and drug dependency, yet none of the existing medications are subtype receptor specific. This study examines 124 chemicals from neem to determine if they can be utilised as specific orexinergic receptor modulators using advanced computational methods. The methodology includes detailed clustering, pharmacophoric interaction, pharmacokinetic, statistical, and clustering analyses. Molecular property profiling indicated the majority of the compounds exhibit excellent drug-like qualities (MW 350-450 Da, LogP 0-2), while principal component analysis captured 100% structural variability between two components (92.5% and 7.5%, respectively). Molecular docking simulations indicated selective binding to the 6V9S receptor (-11.3 to -4 kcal/mol) over 4S0V (-9.7 to -4 kcal/mol). Lead compounds Neem_PDB_10257 (Tirucallol) (-11.3 kcal/mol) and Neem_PDB_12072821 ([(5 R,7 R,8 R,9 R,10 R,13S,17 R) -17-(2-methoxy-5-oxo-4,4,8,10,13-pentamethyl-3-oxo-5,6,7,9,11,12,16,17-octahydrocyclopenta[a]phenanthren-7-yl] acetate) were particularly 6V9S selective (>2 kcal/mol difference), whereas Neem_PDB_10160319 ((4S,4aS,5S,10S,13S,14S,17-4,4,10,13,14-pentam -1, 2, 3, 5, 6, 7, 11, 12, 15, 17-decahydrocyclopenta[a]phenanthren-16-one) was most sensitive towards 4S0V. Two top-ranked compound families were discovered by hierarchical cluster analysis with a distance requirement of 35 units, and receptor-specific dendrograms revealed distinctive subcluster branching patterns (4S0V: 5.5 and 6.7 unit subclusters; 6V9S: 7.1 and 7.2 unit subclusters). Interaction pattern (heatmap analysis) identified major interaction hotspots, including TYR348, TRP120, PHE227, and HIS350. Neem_PDB_163184214 (Meliatetraolenone) specifically targeted ASN318 in 6V9S, while Neem_PDB_54580354 (7-Benzoylnimbocinol) favored interaction with GLN134 in 4S0V (>90 interactions). These findings dispute the "one-pharmacophore" theory for orexinergic modulators, showing that intentional functionalization of NEM templates can deliver subtype-selective treatments with maximal sleep-wake modulation and low off-target effects.
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