Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice.

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

The curative and mechanistic acumen of curcuminoids formulations against haloperidol induced Parkinson's disease animal model.

Parkinson's disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1 mg/kg haloperidol daily intraperitoneally, for 3 weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30 mg/kg, L-dopa and carbidopa (100 + 25 mg/kg) were orally administered on each day for 3 weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies' formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson's disease medications.

Curative potential of Populus ciliata Wall ex. Royle extract against adjuvant-induced arthritis and peripheral neuropathy in Wistar rats.

Populus ciliata (PCCR) is traditionally used to treat muscular swelling, inflammation, pain, and fever. The current study was designed to validate the potential of aqueous ethanolic extract of the plant against inflammation, peripheral neuropathy, and pain in arthritic rats. The PCCR was chemically characterized by gas chromatography-mass spectroscopy and high-performance liquid chromatography. In vitro antioxidant, and in vitro anti-inflammatory assays were carried out on PCCR. For anti-arthritic potential, Wistar rats' rear paws were injected with 0.1 ml Complete Freund's Adjuvant using methotrexate (3 mg/kg/week) as standard control. PCCR at 100, 200, and 400 mg/kg was given orally to arthritic rats for 21 days. The PCCR exhibited significant inhibition of bovine serum albumin denaturation (IC-50: 202.1 µg/ml), egg albumin denaturation (IC-50:553.5 mg/ml) and RBC membrane stabilization (IC-50: 122.5 µg/ml) and antioxidant (IC-50 = 49.43 µg/ml) activities. The PCCR notably decreased the paw diameter and increased body weight of treated arthritic animals as equated to diseased control. The treatment notably (p < 0.05-0.0001) decreased malondialdehyde, and increased superoxide dismutase, reduced glutathione, and catalase in the liver and sciatic nerve homogenate in compared to diseased rats. The PCCR treatment remarkably (p < 0.05-0.0001) regulated the levels of nor-adrenaline and serotonin in sciatic nerve in contrast to diseased rats. Treatment with PCCR improved the motor activity, pain, ligament degeneration, and synovial hyperplasia in arthritic rats. Moreover, PCCR significantly (p < 0.01-0.0001) decreased the IL-6 and TNF-α. It is evident from the current study that PCCR had ameliorated polyarthritis and peripheral neuropathy through reduction of inflammatory markers, and improvement of oxidative stress might be due to presence of phenolic acids, flavonoids, phytosterols, and other fatty acids.

Pterostilbene reduces the progression of atopic dermatitis via modulating inflammatory and oxidative stress biomarkers in mice.

Atopic dermatitis (AD) is one of the most prevalent chronic skin inflammatory disorders requiring continuous treatment and care. Pterostilbene (PTN) belongs to stilbene and is a polyphenolic compound of natural origin. It is similar to resveratrol and has analogous anti-inflammatory, anti-oxidant, and anti-carcinogenic characteristics. This study was intended to evaluate the effect of PTN against atopic dermatitis. The disease was induced by sensitization with 2,4-dinitrochlorobenzene (DNCB) in mice. The standard control group (SCG) received topical 0.1% tacrolimus (TC), whereas three other treatment groups received daily topical PTN at 0.2, 0.6, and 1% w/w for 28 days. Dermatitis scoring, ear thickness, and body weight of animals were weekly determined while other parameters were assessed at the termination of the experiment. PTN reduced the ear weight, skin thickness, and the weight and size of thymus glands and spleen in comparison with diseased animals. PTN also reduced the elevated immunoglobulin E (IgE) level and blood inflammatory cells in diseased mice. The histopathological findings showed a decreased epidermal thickness in PTN-treated groups. Moreover, treatment with PTN improved the amount of oxidative stress markers in the skin of the diseased mice. The expressions of IL-4, IL-6, TNF-α, and NF-κB in the skin of diseased mice were also reduced by PTN. This study concludes that PTN ameliorated the symptoms of atopic dermatitis through the reduction of inflammation, oxidative damage, and inflammatory cytokines in the skin of diseased animals. Therefore, PTN must be further investigated for the treatment of AD complications and other inflammatory skin disorders.

Investigation of anti-Parkinson activity of dicyclomine.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder. The major causative factors that progress the PD are age, genetic abnormalities, environmental factors and degeneration of dopamine neurons in substantia nigra. PD normally exerts a tonic inhibitory effect on striatal cholinergic interneurons. Anticholinergics act by normalizing the disequilibrium between striatal dopamine and acetylcholine-resulted reduction in tremors. OBJECTIVE: This study sought to evaluate the anti-Parkinson potential of dicyclomine in haloperidol (HAL)- and paraquat (PQT)-induced Parkinsonism models in mice. MATERIALS AND METHODS: Sixty albino mice were divided into six groups (n = 10) for each model. Group I: received distilled water 1 mL/kg, Group II: diseased group received HAL (1 mg/kg) for consecutive 21 days and PQT (2 mg/kg) every three days for three weeks, Group III: treated with sinemet (20 mg/kg), Group IV-VI: received 40, 80 and 160 mg/kg dose of dicyclomine, respectively, for consecutive 21 days. The effect of treatments on spontaneous locomotor activity and motor co-ordination was evaluated by using open field, rotarod, actophotometer and light and dark box tests. Cataleptic behavior was estimated by the block method and triple horizontal bar apparatus. Biochemical markers of oxidative stress and levels of neurotransmitters were estimated. RESULTS: Findings from this study showed that dicyclomine at highest dose level of 160 mg/kg prevented HAL- and PQT-induced PD through enhancement of antioxidant defense system. CONCLUSION: The study concluded that dicyclomine could be the potential drug in the management of Parkinsonism.

Pterostilbene improves CFA-induced arthritis and peripheral neuropathy through modulation of oxidative stress, inflammatory cytokines and neurotransmitters in Wistar rats.

Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.

Screening of Synthetic Isoxazolone Derivative Role in Alzheimer's Disease: Computational and Pharmacological Approach.

Alzheimer's disease (AD) is age-dependent neurological disorder with progressive loss of cognition and memory. This multifactorial disease is characterized by intracellular neurofibrillary tangles, beta amyloid plaques, neuroinflammation, and increased oxidative stress. The increased cellular manifestations of these markers play a critical role in neurodegeneration and pathogenesis of AD. Therefore, reducing neurodegeneration by decreasing one or more of these markers may provide a potential therapeutic roadmap for the treatment of AD. AD causes a devastating loss of cognition with no conclusive and effective treatment. Many synthetic compound containing isoxazolone nucleus have been reported as neuroprotective agents. The aim of this study was to explore the anti-Alzheimer's potential of a newly synthesized 3,4,5-trimethoxy isoxazolone derivative (TMI) that attenuated the beta amyloid (Aß1-42) and tau protein levels in streptozotocin (STZ) induced Alzheimer's disease mouse model. Molecular analysis revealed increased beta amyloid (Aß1-42) protein levels, increased tau protein levels, increased cellular oxidative stress and reduced antioxidant enzymes in STZ exposed mice brains. Furthermore, ELISA and PCR were used to validate the expression of Aß1-42. Pre-treatment with TMI significantly improved the memory and cognitive behavior along with ameliorated levels of Aß1-42 proteins. TMI treated mice further showed marked increase in GSH, CAT, SOD levels while decreased levels of acetylcholinesterase inhibitors (AChEI's) and MDA intermediate. The multidimensional nature of isoxazolone derivatives and its versatile affinity towards various targets highpoint its multistep targeting nature. These results indicated the neuroprotective potential of TMI which may be considered for the treatment of neurodegenerative disease specifically in AD.

Drotaverine Inhibitor of PDE4: Reverses the Streptozotocin Induced Alzheimer's Disease in Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with decline in memory and cognitive impairments. Phosphodiesterase IV (PDE4) protein, an intracellular cAMP levels regulator, when inhibited act as potent neuroprotective agents by virtue of ceasing the activity of Pro-inflammatory mediators. The complexity of AD etiology has ever since compelled the researchers to discover multifunctional compounds to combat the AD and neurodegeneration. The aim of this study was to probe into role of drotaverine a PDE4 inhibitor in the management of AD. Albino mice were divided into seven groups (n = 10). Group 1 control group received carboxy methyl cellulose (CMC 1 mL/kg), group II diseased group treated with streptozotocin (STZ 3 mg/kg) by intracerebroventricular (ICV) route, group III administered standard drug Piracetam 200 mg/kg and groups IV-VII were given drotaverine (10, 20, 40, and 80 mg/kg i/p respectively). Groups II-VII were given STZ (3 mg/kg, ICV) on 1st and 3rd day of treatment to induce AD. All the groups were given their respective treatments for 23 days. Improvement in learning and memory was evaluated by using behavioral tests like open field test, elevated plus maze test, Morris water maze test and passive avoidance test. Furthermore, brain levels of biochemical markers of oxidative stress, neurotransmitters, ß-amyloid and tau protein were also measured. Drotaverine showed statistically significant dose dependent improvement in behavioral and biochemical markers of AD: the maximum response was achieved at a dose level of 80 mg/kg. The Study concluded that drotaverine ameliorates cognitive impairment and as well as exhibited modulated the brain levels of neurotransmitters.

Neuroprotective potential of Malva neglecta is mediated via down-regulation of cholinesterase and modulation of oxidative stress markers.

Alzheimer's disease affects daily routine due to loss of memory and decline in cognition. In vitro data showed acetylcholine esterase inhibition activity of Malva neglecta but no in vivo evidence is available. The current study aims to investigate the anti-Alzheimer's activity of Malva neglecta methanolic extract in the AlCl3-induced Alzheimer disease rats' model. Thirty Wistar rats were divided into six groups and respective doses were given orally for 21 days. Behavioural observations were recorded and biochemical analysis was performed on brain homogenate. Improvement in memory and cognition was noted in treated rats as compared to disease control. A dose-dependent decrease (0.530 ± 0.009 at 200 mg/kg, 0.212 ± 0.007 at 400 mg/kg, 0.173 ± 0.005 at 600 mg/kg) in AChE activity was noted in the treatment groups with reference to disease control value (1.572 ± 0.013). This decrease in AChE activity is linked with an increase in acetylcholine in the brain which plays a key role in retaining memory. Oxidative stress biomarkers; GSH (66.77 ± 0.01 at 600 mg/kg), SOD (26.60 ± 0.10 at 600 mg/kg), CAT (21.46 ± 0.01 at 600 mg/kg) levels were increased with a decrease in MDA (103.33 ±0.49 at 600 mg/kg) level in a dose-dependently manner in the treatment groups as compared to disease control respective values. It is concluded that Malva neglecta could ameliorate Alzheimer's symptoms possibly by decreasing AChE activity and oxidative stress.

Exploring the Therapeutic Potentials of Highly Selective Oxygenated Chalcone Based MAO-B Inhibitors in a Haloperidol-Induced Murine Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder of dopaminergic, noradrenergic, and serotonergic systems, in which dopamine, noradrenaline, and serotonin levels are depleted and lead to the development of motor and non-motor symptoms such as tremor, bradykinesia, weight changes, fatigue, depression, and visual hallucinations. Therapeutic strategies place much focus on dopamine replacement and the inhibition of dopamine metabolism. The present study was based on the known abilities of chalcones to act as molecular scaffolds that selectively inhibit MAO-B with the added advantage of binding reversibly. Recently, we synthesized a series of 26 chalcone compounds, amongst which (2E)-1-(2H-1,3-benzodioxol-5-yl)-3-(4-fluorophenyl)prop-2-en-1-one (O10) and (2E)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(4-fluorophenyl)prop-2-en-1-one (O23) most inhibited MAO-B. Hence, the present study was performed to explore the molecular mechanisms responsible for the neuroprotective effect of O10 and O23 at varying doses such as 10, 20, and 30 mg/kg each in a haloperidol-induced murine model of PD. Both compounds were effective (though O23 was the more effective) at ameliorating extrapyramidal and non-motor symptoms in the model and improved locomotory and exploratory behaviors, reduced oxidative stress markers, and enhanced antioxidant marker and neurotransmitter levels. Furthermore, histopathological studies showed O10 and O23 both reduced neurofibrillary tangles and plaques to almost normal control levels.

Anti-urolithiatic activity of Salvia hispanica L. seeds in ethylene glycol induced urolithiasis rat's model.

Urolithiasis is a disorder of kidneys in which stones formation occur due to the excessive deposition of minerals in the urinary tract. It affects 12% of the population worldwide. Salvia hispanica seeds are rich source of quercetin which has preventive role in renal stone formation. The study objective was to explore scientifically the anti-urolithiatic effect of Salvia hispanica seed's methanol extract using in vitro and in vivo urolithiasis models. For in-vitro study nucleation, growth and aggregation assays were performed. In vivo study was performed on rats and they were divided into six groups (n=6). Group-I was given vehicle only. Group-II was disease control, treated with 0.75% EG in drinking water which triggered urolithiasis. Groups-III received cystone (750 mg/kg, orally). Groups IV-VI were treated with extract at 100, 300 and 700 mg/kg doses orally once daily. Groups III-VI additionally received 0.75% EG in drinking water. In vitro study revealed concentration dependent increase in percentage inhibition of crystal's nucleation, growth and aggregation. In vivo study revealed anti-urolithiatic activity by lowering oxalate, calcium, phosphate, sodium and potassium levels in the urine and the serum uric acid, blood urea nitrogen, total proteins and total albumin. Salvia hispanica seeds are good alterative of allopathic anti-urolithiatic drugs to treat urolithiasis.

Pharmacological and toxicological evaluation of two anti-asthmatic polyherbal formulations.

The study aim was to evaluate the toxic potential of two polyherbal formulation i.e. " PH 1 & PH 2" and scientific validation of their anti-asthmatic use. Acute oral toxicity study as per OECD 425 TG was conducted. For validation of anti-asthmatic claim, in vivo assay named Ovalbumin (OVA)-induced murine method in Wistar rats was used. Eosinophils and IgE antibody were quantified post-administration of low and high doses of the formulations. No mortality was observed in acute toxicity study. Elevated levels of alkaline phosphatase and damaged liver structure indicating the hepatotoxicity were more pronounced in PH 2 treated rats. Congestion in kidney tissue and increased urea level were evident of the nephrotoxic nature of PH 2 in animals. Treatment with selected polyherbal products decreased the MDA level while increasing the SOD and GSH levels in lung tissue homogenates. The maximum decrease in IgE load (3.18 ± 0.08 IU/mL) was found in rats treated with 12 mg/kg dose of PH 1 followed by 100 mg/kg dose of PH 2 (3.44 ± 0.06 IU/mL). It was concluded that both polyherbal formulations had anti-asthmatic activities, however, PH 1 exhibited the liver and kidney toxicity and should be cautiously used.

Kaempferol Facilitated Extinction Learning in Contextual Fear Conditioned Rats via Inhibition of Fatty-Acid Amide Hydrolase.

Background: Fear, stress, and anxiety-like behaviors originate from traumatic events in life. Stress response is managed by endocannabinoids in the body by limiting the uncontrolled retrieval of aversive memories. Pharmacotherapy-modulating endocannabinoids, especially anandamide, presents a promising tool for treating anxiety disorders. Here, we investigated the effect of kaempferol, a flavonoid, in the extinction of fear related memories and associated anxiety-like behavior. Methods: The ability of kaempferol to inhibit fatty-acid amide hydrolase (FAAH, the enzyme that catabolizes anandamide) was assessed in vitro using an enzyme-linked immunosorbent assay (ELISA) kit. For animal studies (in vivo), the extinction learning was evaluated using contextual fear conditioning (CFC, a behavioral paradigm based on ability to learn and remember aversive stimuli). Furthermore, an elevated plus-maze (EPM) model was used for measuring anxiety-like behavior, while serum corticosterone served as a biochemical indicator of anxiety. Lastly, the interaction of kaempferol with FAAH enzyme was also assessed in silico (computational study). Results: Our data showed that kaempferol inhibited the FAAH enzyme with an IC50 value of 1 µM. In CFC, it reduced freezing behavior in rats. EPM data demonstrated anxiolytic activity as exhibited by enhanced number of entries and time spent in the open arm. No change in blood corticosterone levels was noted. Our computational study showed that Kaempferol interacted with the catalytic amino acids (SER241, PHE192, PHE381, and THR377) of FAAH enzyme Conclusion: Our study demonstrate that kaempferol facilitated the extinction of aversive memories along with a reduction of anxiety. The effect is mediated through the augmentation of endocannabinoids via the inhibition of FAAH enzyme.

In-silico computational analysis of [6-(2, 3-Dichlorophenyl)-1, 2, 4-Triazine-3, 5-Diamine] metal complexes on voltage gated sodium channel and dihydrofolate reductase enzyme.

Epilepsy is the disease associated with seizures and convulsions. Various antiepileptic drugs have been used widely to treat these disorders. Lamotrigine [6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine] shows certain adverse effects at small doses, to evaluate its efficacy lamotrigine schiff based metal complexes were screened in-silico at voltage gated sodium channel for antiepileptic effect and dihydrofolate reductase enzyme for anticancer activity. Post docking analysis revealed that lamotrigine shows greater antiepileptic effect with its Schiff base complex of tin, with greater binding affinities on voltage gated sodium channel. However, anticancer effect of lamotrigine with its Schiff base silver complex shows highest binding affinity on dihydrofolate reductase enzyme. Study concluded that Schiff base derivative and its metal complexes express significant binding interactions with voltage gated sodium channel and dihydrofolate reductase enzyme.

Chronopharmacology: Appraising the Influence of Biorhythms on the Efficacy and Safety of Antihypertensive Drugs.

This review is dedicated to chronopharmacology and chronotherapeutics of hypertension interventions. The aim of chronopharmacology is to determine the most suitable time for administration of a drug to enhance efficacy and safety, prevent tolerance, and minimize the untoward effects of the given therapy. In other words, chronotherapeutics and chronopharmacology optimize drug therapy through matching the disease rhythms to drug availability. Chronobiological principles to optimize the therapeutic effects of antihypertensive drugs attained significance a few decades ago. Circadian rhythm plays a pivotal role in the regulation of blood pressure and expresses as a contender for application of chronotherapeutics. Changes in the normal circadian rhythmic pattern of blood pressure also foretell the risk for developing cardiovascular events. This review highlights studies conducted on the chronopharmacology of different antihypertensive drug classes and prospective areas of chronotherapy to make it comprehensible for application in clinical practice to achieve optimum control of hypertension.

Systems pharmacology based approach to investigate the in-vivo therapeutic efficacy of Albizia lebbeck (L.) in experimental model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra pars compacta and clinically manifested mainly with motor dysfunctions. Plants are rich source of medicinally important bioactive compounds and inhabitants of underdeveloped countries used plants for treatment of various ailments. Albizia lebbeck has been reported to possess antioxidant and neuroprotective properties that suggest the evaluation of its traditional therapeutic potential in neurodegenerative diseases. The aim of present study was to validate the traditional use of Albizia lebbeck (L.) and delineate its mechanism of action in PD. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD. METHODS: The haloperidol-induced catalepsy was adopted as experimental model of PD for in-vivo studies in wistar albino rats. The systems pharmacology approach was employed to explain the Albizia lebbeck (L.) mechanism of action in PD. RESULTS: In-vivo studies revealed that Albizia lebbeck improved the motor functions and endurance as demonstrated in behavioral studies which were further supported by the rescue of endogenous antioxidant defense and reversal of ultrastructural damages in histological studies. System pharmacology approach identified 25 drug like compounds interacting with 132 targets in a bipartite graph that revealed the synergistic mechanism of action at system level. Kaemferol, phytosterol and okanin were found to be the important compounds nodes with prominent target nodes of TDP1 and MAPT. CONCLUSION: The therapeutic efficiency of Albizia lebbeck in PD was effectively delineated in our experimental and systems pharmacology approach. Moreover, this approach further facilitates the drug discovery from Albizia lebbeck for PD.

Experimental and Computational Studies to Characterize and Evaluate the Therapeutic Effect of Albizia lebbeck (L.) Seeds in Alzheimer's Disease.

Background and Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder that deteriorates daily life due to loss of memory and cognitive impairment. It is believed that oxidative stress and cholinergic deficit are the leading causes of AD. Disease-modifying therapies for the treatment of AD are a challenging task for this century. The search for natural and synthetic agents has attracted the attention of researchers. The objective of this study was a scientific approach to search for most suitable remedy for AD by exploiting the potential of Albizia lebbeck (L.) seeds. Materials and Methods: Hydromethanolic extract of Albizia lebbeck seeds (ALE) was prepared by maceration. The plant was characterized by physico-chemical, phyto-chemical, and high-performance liquid chromatography (HPLC). Thirty-six Wistar albino rats were used in this study and divided into six groups (n = 6). Group I: normal control; Group II: disease control (AlCl3; 100 mg/Kg); Group III: standard control (galantamine; 0.5mg/Kg); Groups IV-VI were treated ALE at 100, 200 and 300 mg/Kg dose levels, respectively. All the treatments were given orally for 21 consecutive days. Y-maze, T-maze, Morris water maze, hole board, and open field behavioral tests were performed to analyze the cognitive impairment. Biochemical, histological, and computational studies were performed to support the results of behavioral tests. Results: HPLC analysis indicated the presence of quercetin, gallic acid, m-coumaric acid, and sinapic acid. ALE significantly improved the memory and cognitive impairments. Endogenous antioxidant stress biomarker levels and histopathological outcomes supported the therapeutic potential of A. lebbeck in AD. Cholinergic deficits were also ameliorated by ALE co-administration, possibly by the inhibition of hyperactive acetylcholinesterase (AChE). Docking studies supported the potential of ALE against AD. Conclusions: The data suggested that ALE has neuroprotective potential that can be exploited for beneficial effects to treat AD.

Lawsonia Inermis Markedly Improves Cognitive Functions in Animal Models and Modulate Oxidative Stress Markers in the Brain.

Background and Objective: Medicinal plants represent an important source of alternative medicine for the management of various diseases. The present study was undertaken to assess the potential of Lawsonia inermis ethanol (Li.Et) and chloroform (Li.Chf) extracts as memory-enhancing agents in experimental animals. Materials and Methods: Li.Et and Li.Chf were phytochemically characterized via gas chromatography-mass spectroscopy (GC-MS). Samples were tested for nootropic potentials at doses of 25, 50, 100, 200 mg/kg (per oral in experimental animals (p.o.)). Swiss albino mice of either sex (n = 210) were divided into 21 × 10 groups for each animal model. Memory-enhancing potentials of the samples were assessed using two methods including "without inducing amnesia" and "induction of amnesia" by administration of diazepam (1 mg/kg, intraperitoneally. Piracetam at 400 mg/kg (i.p.) was used as positive control. Cognitive behavioral models including elevated plus maze (EPM) and the passive shock avoidance (PSA) paradigm were used. Biochemical markers of oxidative stress such as glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) levels were analyzed in the brain tissue of treated mice. Results: In 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals scavenging assay, Li.Et and Li.Chf exhibited 70.98 ± 1.56 and 66.99 ± 1.76% inhibitions respectively at 1.28 mg/mL concentration. GCMS results revealed the presence of important phytochemicals. Both samples (Li.Et and Li.Chf) at 25 mg/kg (p.o.) dose significantly (p < 0.05) improved learning and memory as indicated by decline in transfer latency and increase in step down latency in EPM and PSA models respectively. Li.Et and Li.Chf at 25 mg/kg (p.o.) showed considerable increase in GSH (2.75 ± 0.018 ***), SOD (2.61 ± 0.059 ***) and CAT (2.71 ± 0.049 ***) levels as compared to positive and negative control groups. Conclusions: This study provides the preliminary clue that L. inermis may be a potential source of memory-enhancing and anti-oxidant compounds and thus warrant further studies.

Injectable Chitosan-Methoxy Polyethylene Glycol Hybrid Hydrogel Untangling the Wound Healing Behavior: In Vitro and In Vivo Evaluation.

Wound healing, particularly for difficult-to-treat wounds, presents a serious threat and may lead to complications. Currently available dressings lack mucoadhesion, safety, efficacy, and, most importantly, patient compliance. Herein, we developed a unique, simple, and inexpensive injectable chitosan-methoxy polyethylene glycol (chitosan-mPEG) hybrid hydrogel with tunable physicochemical and mechanical properties for wound healing. The detailed physicochemical and rheological characterization of the chitosan-mPEG hydrogel has revealed chemical interaction between available -NH2 groups of chitosan and -COOH groups of mPEG acid, which, to our perspective, enhanced the mechanical and wound healing properties of hybrid chitosan and mPEG hydrogel compared to solo chitosan or PEG hydrogel. By introducing mPEG, the wound healing ability of hydrogel is synergistically improved due to its antibacterial feature, together with chitosan's innate role in hemostasis and wound closure. The detailed hemostasis and wound closure potential of the chitosan-mPEG hydrogel were investigated in a rat model, which confirmed a significant acceleration in wound healing and ultimately wound closure. In conclusion, the developed chitosan-mPEG hydrogel met all the required specifications and could be developed as a promising material for hemostasis, especially wound management, and as an excellent candidate for wound healing application.

The wound healing potential of Hedychium spicatum Sm. and Zinnia peruviana (L.) ethanolic extracts against excision wound model in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants used for wound healing, are key to unlock the doors for combating the resistance of pathogens by provision of new source of compounds. AIM OF THE STUDY: This study is aimed to evaluate and compare the wound healing properties of ethanolic extract of Hedychium spicatum Sm. rhizome and of Zinnia peruviana's leaves and roots. MATERIALS & METHODS: Albino rats were divided into 10 groups (n = 6), control, positive control, negative control, untreated, Hedychium spicatum Sm. (125 mg/kg), Hedychium spicatum Sm (250 mg/kg), Zinnia peruviana (L.)(Leaves) (125 mg/kg), Zinnia peruviana (L.) (Leaves) (250 mg/kg), Zinnia peruviana (L.)(Roots) (125 mg/kg), Zinnia peruviana (L.)(Roots) (250 mg/kg) respectively. Excision wound of 1.5 cm wound was inflicted on the dorsal side of each rat except control group. 5% CMC gel, fusidic acid and extract gels were applied topically once daily on the wound area which was measured at intervals of 3 days until epithelization and complete wound closure. Different biochemical markers were analyzed in both blood and skin to validate the wound healing potential of these plants. RESULTS: Topical application of an ethanolic extract of Hedychium spicatum Sm. (250 mg/kg) had significant (p ˂ 0.001) rate of wound healing and reduced epithelization period. Marked amelioration of hydroxyproline content, remarkable results on histopathological changes, reduction in oxidative stress was observed with Hedychium spicatum Sm. ethanolic extract at dose level of 250 mg/kg in comparison with untreated group. CONCLUSION: This study concluded that the Hedychium spicatum Sm. rhizome ethanolic extract gel is effective in wound repair and may possess potential for the development of dermatologic preparation for topical diseases.