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1.
J Diabetes Metab Disord ; 22(2): 1817, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37969921

ABSTRACT

[This retracts the article DOI: 10.1007/s40200-021-00749-8.].

2.
Pharmacol Rep ; 75(6): 1454-1473, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37926795

ABSTRACT

Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A2 (SvPLA2) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA2 catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom's adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA2 toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A2, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA2, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA2 effect.


Subject(s)
Snake Bites , Snake Venoms , Animals , Sheep , Humans , Horses , Snake Venoms/therapeutic use , Acetates/therapeutic use , Snake Bites/drug therapy , Snake Bites/metabolism , Phospholipases A2/metabolism , Phospholipases A2/therapeutic use , Inflammation
3.
J Biophotonics ; 16(8): e202300012, 2023 08.
Article in English | MEDLINE | ID: mdl-37074708

ABSTRACT

The loss and progressive dysfunction of neurons are hallmarks of neurodegenerative diseases. The aim of the current study is to explore the effects of photobiomodulation at 460-660 nm (100-1000 lux units) on the progression of scopolamine-induced cognitive dysfunctions in Wistar male rats. Photobiomodulation (PBM) is defined as "the use of monochromatic or quasi-monochromatic light from a low-power laser or light-emitting diode (LED) source to modify or modulate biological functions." Neuroprotective activity was assessed by in vivo models such as the Morris water maze, the elevated plus maze (EPM), and the T-maze. After using scopolamine (1 mg/kg/day) as a dementia induction model for 21 days, the induction was primarily due to impairments in cholinergic transmission, oxidative stress, and inflammation. The in vitro determinations, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), Interleukin 1 beta (IL-1ß), and alkaline phosphatase (ALP), were assessed biochemicals and biomarkers. The structural and morphological integrity of the cortex and hippocampus was investigated through histopathology. In vivo studies of exteroceptive behavior models such as the Morris water maze, the EPM, and the T-maze revealed that administration of scopolamine resulted in enhanced escape latency time (ELT), transfer latency (TL), and decreased percentage alternation, respectively. The levels of AChE, BChE, reduced, GSH, SOD, TNF-α, IL-1ß and ALP were increased, while MDA level was decreased. In contrast to normal and control groups with treatment groups, histopathology of the cortex and hippocampus examination revealed the maintenance of structural integrity and densities of CA1 and CA3 neuronal cells. However, network pharmacology predicted Ca+2 modulation of various pathways, among the treatments with red LED light showed highly significant amelioration compared with normal and control groups. Photobiomodulation by hormesis, chromophores in cells, and tissues excitation can influence neuroprotective effect mainly by scavenging of ROS, variation in the level of GSH MDA and SOD mitochondrial electron transfer, the improved abscopal effects on improved in gut microbiome by resembles the of fecal ALP level correlation of intestinal microbiome, cholinergic neurotransmissions, anti-inflammatory, and antioxidant activities.


Subject(s)
Neurodegenerative Diseases , Neuroprotective Agents , Rats , Male , Animals , Scopolamine/adverse effects , Neuroprotective Agents/pharmacology , Neuroprotective Agents/metabolism , Neuroprotective Agents/therapeutic use , Acetylcholinesterase/metabolism , Acetylcholinesterase/pharmacology , Acetylcholinesterase/therapeutic use , Hormesis , Butyrylcholinesterase/metabolism , Butyrylcholinesterase/pharmacology , Butyrylcholinesterase/therapeutic use , Tumor Necrosis Factor-alpha/pharmacology , Rats, Wistar , Maze Learning , Memory Disorders/drug therapy , Memory Disorders/chemically induced , Memory Disorders/metabolism , Oxidative Stress , Cholinergic Agents/metabolism , Cholinergic Agents/pharmacology , Cholinergic Agents/therapeutic use , Superoxide Dismutase/metabolism , Superoxide Dismutase/pharmacology , Superoxide Dismutase/therapeutic use , Hippocampus/metabolism
4.
Metab Brain Dis ; 37(2): 411-426, 2022 02.
Article in English | MEDLINE | ID: mdl-35023027

ABSTRACT

Parkinsonism is a neurodegenerative disease, mainly imbalance in dopamine and acetylcholine neurotransimitter in mid brain, which manifestation of dysfunctions of extrapyramidal like akinesia, tremor, rigidity and catalepsy etc., even cognitive and memory loss. The current study is framed to evaluate the effect of Vitex negundo (VNL) leaf extract in Haloperidol induced PD in rats. In vitro studies of antioxidant capacity were checked via DPPH and NO assays and identified its Acetylcholinesterase (AChE) inhibitory activity. Secondly the In vivo study of anti-PD activity in Haloperidol induced in rats were evaluated by Rotarod, morris water maze (MWM), cooks pole climb (CPC), actophotometer, novel object recognition (NOR), and T-maze were utilized to assess extrapyramidal, cognitive and memory function. Thirdly, changes in biomarker level viz. (AChE), butyrylcholinesterase. (BChE) in hippocampus and cortex, reduced glutathione (GSH), malondialdehyde (MDA), total protein (TP), superoxide dismutase (SOD), catalase (CAT), and dopamine level in the whole brain were measured. Finally, histopathology of hippocampus and cortex was examined at 40x magnification to access restoring integrity and maintaining the architecture of neuronal cell in the treatment group compared to control group and L-DOPA as a standard treatment group. V. negundo showed potent antioxidant potency on scavenging of DPPH (IC50 84.81 µg/ml) and NO (IC50 133.20 µg/ml) and possess AChE inhibitory potency (IC50 114.35 µg/ml) by in vitro studies. The Rotarod, MWM, CPC, Actophotometer, NOR, T-maze demonstrated that Haloperidol group administration declines performance time, ELT, TL and decreases locomotion, cognitive and memory respectively. The treatment of VNL 100, 200, and 400 mg/kg p.o. significantly (p < 0.05 to p < 0.0001) reversed. Whole brain AChE, BChE, and MDA level were significantly raised and GSH, TP, SOD, CAT and Dopamine were significantly declined in Haloperidol treated group rats, especially V. negundo 400 mg/kg p.o. highly significantly ameliorate the Haloperidol group altered pathological changes through the restoration of the cholinergic function, enhancing the antioxidant defense and by increasing the dopaminergic function. The current study provides validation of V. negundo for its anti-PD activity and could be a valuable source for the treatment of PD in future.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Vitex , Acetylcholinesterase , Animals , Butyrylcholinesterase/pharmacology , Haloperidol/pharmacology , Neuroprotection , Oxidative Stress , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats
5.
J Diabetes Metab Disord ; 20(1): 329-340, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34178841

ABSTRACT

OBJECTIVE: The present study investigates the anti-obesity activity of Luffa cylindrica in progesterone induced obesity model. METHOD: Swiss albino mice were grouped into 7 (n = 6). Obesity was induced by administration of progesterone (10 mg/kg s.c.) for 28 days. Normal group received ad libitum and water. Disease control, positive control and treatment groups received progesterone (10 mg/kg s.c.). Further positive control group received Orlistat (10 mg/kg p.o). Treatment groups received hydro-alcoholic and fractionation extract of Luffa cylindrica at doses 400, 200, 100 mg/kg b.w. Food and water intake were recorded daily, Body weight, BMI and blood glucose were checked weekly. On completion of the study, animals were sacrificed and blood serum being utilized to accesses in vitro to estimate the various biochemical parameters. Serotonin levels and antioxidant biomarkers were also estimated. Histopathology of liver and adipose tissue was studied. RESULT: After the 28 days of treatment with plant extract and fraction, it was observed to improve the progestrogen-induced obesity by improving BMI, body weight, brain serotionin, locomotor activity, blood glucose level, anti-oxidant biomarkers, and lipid profile. CONCLUSION: After assimilating the In vivo and in vitro studies Luffa cylindrical extract highlighted the antilipidemic, anti-hyperglycaemic, antioxidant potential in hormone-induced obesity.

6.
Int J Biol Macromol ; 57: 238-44, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23511060

ABSTRACT

We investigated the lipid lowering ability of simvastatin loaded gellan gum-carrageenan composite polyspheres, which were prepared by ionotropic gelation/covalent crosslinking method. The surface morphology revealed that the polyspheres have rough and dense surface. The drug entrapment efficiency of the polyspheres prepared by ionic crosslinking was higher than those prepared by dual crosslinking. The in vitro drug release study indicated that the ionically crosslinked polyspheres discharged the drug quickly whereas, dual crosslinked polyspheres extended the drug release for longer period. The hypolipidemic activity performed on Wistar rats indicated that the polyspheres have effectively reduced the elevated total serum cholesterol and triglycerides.


Subject(s)
Carrageenan , Delayed-Action Preparations , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Polysaccharides, Bacterial , Simvastatin , Animals , Carrageenan/chemistry , Carrageenan/pharmacokinetics , Carrageenan/pharmacology , Cholesterol/blood , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/pharmacokinetics , Polysaccharides, Bacterial/pharmacology , Rats , Rats, Wistar , Simvastatin/chemistry , Simvastatin/pharmacokinetics , Simvastatin/pharmacology , Triglycerides/blood
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