Shah MA

References (11)

Title : The curative and mechanistic acumen of curcuminoids formulations against haloperidol induced Parkinson's disease animal model - Saleem_2022_Metab.Brain.Dis_38_1051
Author(s) : Saleem U , Khalid S , Chauhdary Z , Anwar F , Shah MA , Alsharif I , Babalghith AO , Khayat RO , Albalawi AE , Baokbah TAS , Farrukh M , Vargas-De-La-Cruz C , Panichayupakaranant P
Ref : Metabolic Brain Disease , 38 :1051 , 2022
Abstract : 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, 1smg/kg haloperidol daily intraperitoneally, for 3sweeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30smg/kg, L-dopa and carbidopa (100 + 25smg/kg) were orally administered on each day for 3sweeks. 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.
ESTHER : Saleem_2022_Metab.Brain.Dis_38_1051
PubMedSearch : Saleem_2022_Metab.Brain.Dis_38_1051
PubMedID: 36437394

Title : Differential neuroprotective effect of curcuminoid formulations in aluminum chloride-induced Alzheimer's disease - Shabbir_2022_Environ.Sci.Pollut.Res.Int__
Author(s) : Shabbir A , Rehman K , Akash MSH , Akbar M , Chaudhary Z , Panichayupakaranant P , Shah MA
Ref : Environ Sci Pollut Res Int , : , 2022
Abstract : Alzheimer's disease (AD) is a slowly progressive brain degenerative disorder which gradually impairs memory, thinking, and ability to perform easy routine tasks. This degenerative disorder mainly targets the elderly people and has imposed an endemic burden on society. Hence, there is a crucial need to investigate the efficacious herbal pharmacotherapies that can effectively mitigate and prevent the pathological hallmarks of AD. The current study aims to explore the potential efficacy of curcuminoid-rich extract (CRE) and its ternary complex (TC). Experimental rodents were administered with AlCl(3) (300 mg/kg) to induce AD and treated with rivastigmine, curcuminoid crude extract, CRE, and TC orally for three consecutive weeks. Neurobehavioral, biochemical, and histopathological studies were performed from the last week of the study period. The mRNA expression of different pathological biomarkers was estimated by RT-qPCR analysis. The results of the study suggested that CRE and TC significantly improved the behavioral, biochemical parameters and acetylcholinesterase inhibitory activity in treatment groups. Histological analysis was also carried out indicating that the neurodegenerative changes and neuronal loss were stabilized by CRE and TC supplementation. CRE and TC supplementation remarkably downregulated the interleukin-1alpha, tumor necrosis factor-alpha, interleukin-1beta, acetylcholinesterase, and beta-secretase pathological gene expression. Hence, it was concluded that CRE and TC may act as promising candidates in the prevention of AD via numerous underlying signaling pathways.
ESTHER : Shabbir_2022_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Shabbir_2022_Environ.Sci.Pollut.Res.Int__
PubMedID: 35525893

Title : Sarcococca saligna ameliorated D-galactose induced neurodegeneration through repression of neurodegenerative and oxidative stress biomarkers - Saleem_2022_Metab.Brain.Dis_38_717
Author(s) : Saleem U , Chauhdary Z , Islam S , Zafar A , Khayat RO , Althobaiti NA , Shah GM , Alqarni M , Shah MA
Ref : Metabolic Brain Disease , 38 :717 , 2022
Abstract : Sarcococca saligna is a valuable source of bioactive secondary metabolites exhibiting antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities. The study was intended to explore the therapeutic pursuits of S. saligna in amelioration of cognitive and motor dysfunctions induced by D-galactose and linked mechanistic pathways. Alzheimer's disease model was prepared by administration of D-galactose subcutaneous injection100 mg/kg and it was treated with rivastigmine (100 mg/kg, orally) and plant extract for 42 days. Cognitive and motor functions were evaluated by behavioral tasks and oxidative stress biomarkers. Level of acetylcholinesterase, reduced level of glutathione, protein and nitrite level, and brain neurotransmitters were analyzed in brain homogenate. The level of apoptosis regulator Bcl-2, Caspases 3 and heat shock protein HSP-70 in brain homogenates were analyzed by ELISA and colorimetric method, respectively. AChE, IL-1beta, TNF-alpha, IL-1alpha and beta secretase expressions were analyzed by RT-PCR. S. saligna dose dependently suppressed the neurodegenerative effects of D-galactose induced behavioral and biochemical impairments through modulation of antioxidant enzymes and acetylcholinesterase inhibition. S. saligna markedly (P < 0.05) ameliorated the level of brain neurotransmitters, Bcl-2, HSP-70 and Caspases-3 level. S. saligna at 500-1000 mg/kg considerably recovered the mRNA expression of neurodegenerative and neuro-inflammatory biomarkers, also evident from histopathological analysis. These findings suggest that S. saligna could be applicable in cure of Alzheimer's disease.
ESTHER : Saleem_2022_Metab.Brain.Dis_38_717
PubMedSearch : Saleem_2022_Metab.Brain.Dis_38_717
PubMedID: 35881299

Title : Neuroprotective potential of Malva neglecta is mediated via down-regulation of cholinesterase and modulation of oxidative stress markers - Saleem_2021_Metab.Brain.Dis_36_889
Author(s) : Saleem U , Akhtar R , Anwar F , Shah MA , Chaudary Z , Ayaz M , Ahmad B
Ref : Metabolic Brain Disease , 36 :889 , 2021
Abstract : 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 AlCl(3)-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.
ESTHER : Saleem_2021_Metab.Brain.Dis_36_889
PubMedSearch : Saleem_2021_Metab.Brain.Dis_36_889
PubMedID: 33570733

Title : Pharmacological Screening of Viola odorata L. for Memory-Enhancing Effect via Modulation of Oxidative Stress and Inflammatory Biomarkers - Saleem_2021_Front.Pharmacol_12_664832
Author(s) : Saleem U , Hira S , Anwar F , Shah MA , Bashir S , Baty RS , Badr RH , Blundell R , Batiha GE , Ahmad B
Ref : Front Pharmacol , 12 :664832 , 2021
Abstract : Purpose: Alzheimer disease (AD) is a progressive neurodegenerative disorder that is caused by neuroinflammation and oxidative stress. The present study aimed to characterize and then investigate the memory-enhancing potential of Viola odorata methanolic extract in lipopolysaccharide (LPS)-treated mice. Methods: V. odorata characterization was done by using the GCMS technique. Neuroinflammation was induced by the intracerebroventricular administration of LPS at a dose of 12 microg. Animals were divided randomly into six groups (n = 10). Group I was normal control, which was given vehicle. Group II was disease control, which received LPS (12 microg) via the intracerebroventricular route. Group III was standard, which was administered with donepezil (3 microg) orally for 21 days. Groups IV-VI were the treatment groups, which were administered with the extract at 100, 200, and 400 mg/kg dose levels orally respectively for 21 days. Groups III-VI received LPS (12 microg) on the first day along with their treatments. During the treatment, the animals were assessed for memory retention by employing different behavioral paradigms namely elevated plus maze, passive avoidance, foot shock and open field. Various mediators [endogenous antioxidants, neurotransmitters, and acetylcholinesterase (AChE)] involved in the pathogenesis of AD were quantified by using the UV spectrophotometric method. Results: Extract-treated groups showed a remarkable improvement in cognitive impairment in all behavioral paradigms. Oxidative stress biomarkers, that is, superoxide dismutase, catalase, and glutathione were raised dose-dependently in the treatment groups with a dose-dependent decrease in the malonaldehyde and AChE levels in the brains of the treated animals. The treatment groups showed decreased levels of inflammatory biomarkers, that is, tumor necrosis factor-alpha, nuclear factor kappa light-chain enhancer of activated beta-cells, and cyclo-oxygenase, which supports the therapeutic effectiveness of the treatment. Conclusion: Based on behavioral, oxidative stress biomarker, and neuroinflammatory data, it is concluded that V. odorata possesses memory-enhancing activity and may prove a beneficial role in the management of AD.
ESTHER : Saleem_2021_Front.Pharmacol_12_664832
PubMedSearch : Saleem_2021_Front.Pharmacol_12_664832
PubMedID: 34149418

Title : Neuroprotective potential of berberine in modulating Alzheimer's disease via multiple signaling pathways - Akbar_2021_J.Food.Biochem__e13936
Author(s) : Akbar M , Shabbir A , Rehman K , Akash MSH , Shah MA
Ref : J Food Biochem , :e13936 , 2021
Abstract : Berberine is one of the most important quinoline alkaloids, which has shown numerous pharmacological activities. There are pieces of evidence that berberine serves as a promising substance for treating Alzheimer's disease (AD). Recently, numerous studies on animal models have shown the neuroprotective role of berberine. AD is a complex disease having multiple pathological factors. Berberine restrains the deposition of amyloid plaques and neurofibrillary tangles. Substantial studies have demonstrated that berberine may also exhibit the protective effect against the risk factors associated with AD. This review illustrates the role of berberine in neuroinflammation, oxidative stress and its activity against acetylcholinesterase enzyme. It also focuses on the bioavailability and safety of berberine in AD. However, more investigations are required to explore the bioavailability and safety assessment of berberine and its new perspectives in limiting the AD-related pathogenesis and risk factors. PRACTICAL APPLICATIONS: Current therapeutic measures only provide symptomatic relief against AD by slowing memory loss, resolving thinking problems and behavioral issues. In recent past years, many biological actions and potential therapeutic applications have been observed by berberine particularly in neurological diseases. Berberine has been investigated by various researchers for its activity against AD. This review demonstrates a variety of mechanisms by which berberine imparts its neuroprotective roles and provides the possible mechanism of action of berberine by which it prevents the formation of neurofibrillary tangles and disaggregation of amyloid beta plaques in AD. It also focuses that berberine limits the neuroinflammation and oxidative stress in AD. Pre-clinical aspects of berberine against AD are also discussed. Eventually, a prospect is formulated that berberine might be a therapeutically significant agent for treating and preventing AD.
ESTHER : Akbar_2021_J.Food.Biochem__e13936
PubMedSearch : Akbar_2021_J.Food.Biochem__e13936
PubMedID: 34523148

Title : Antiparkinsonian activity of Cucurbita pepo seeds along with possible underlying mechanism - Saleem_2021_Metab.Brain.Dis_36_1231
Author(s) : Saleem U , Shehzad A , Shah S , Raza Z , Shah MA , Bibi S , Chauhdary Z , Ahmad B
Ref : Metabolic Brain Disease , 36 :1231 , 2021
Abstract : Cucurbita pepo is used as a vegetable in Pakistan and its seeds are also rich in tocopherol. Data showed the pivotal role of tocopherol in the treatment of Parkinson's disease (PD). The current study was designed to probe into the antiparkinson activity of methanolic extract of C. pepo (MECP) seeds in the haloperidol-induced Parkinson rat model. Behavioral studies showed improvement in motor functions. The increase in catalase, superoxide dismutase, glutathione levels whereas the decreases in the malondialdehyde and nitrite levels were noted in a dose-dependent manner. Acetylcholine-esterase (AchE) activity was increased. Molecular docking results revealed significant binding interaction of selected phytoconstituents within an active site of target protein AchE (PDB ID: 4EY7). Furthermore, alpha-synuclein was up regulated with down regulation of TNF-alpha and IL-1beta in the qRT-PCR study. Subsequently, ADMET results on the basis of structure to activity predictions in terms of pharmacokinetics and toxicity estimations show that selected phytochemicals exhibited moderately acceptable properties. These properties add knowledge towards the structural features which could improve the bioavailability of selected phytochemicals before moving towards the initial phase of the drug development. Our integrated drug discovery scheme concluded that C. pepo seeds could ameliorate symptoms of PD and may prove a lead remedy for the treatment of PD.
ESTHER : Saleem_2021_Metab.Brain.Dis_36_1231
PubMedSearch : Saleem_2021_Metab.Brain.Dis_36_1231
PubMedID: 33759084

Title : Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential - Javaid_2021_Curr.Pharm.Des_27_3591
Author(s) : Javaid N , Shah MA , Rasul A , Chauhdary Z , Saleem U , Khan H , Ahmed N , Uddin MS , Mathew B , Behl T , Blundell R
Ref : Curr Pharm Des , 27 :3591 , 2021
Abstract : Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead to neuronal cell death. Alzheimer's disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset and gradually worsens. Neuropathology, AD is characterized by the presence of neuroinflammation, mitochondrial dysfunction, increased oxidative stress, decreased antioxidant defense as well as increased acetylcholinesterase activity. Moreover, enhanced expression of amyloid precursor proteins leads to neural apoptosis, which has a vital role in the degeneration of neurons. The inability of commercial therapeutics to treat a single feature of AD pathology leads to the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid; latest studies revealed that ellagic acid can initiate numerous cell signaling transmissions and decrease the progression of neurodegeneration. The neuroprotective effects of ellagic acid to protect the neurons against neurodegenerative events are due to its antioxidant effect, iron chelating, and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mechanism of action of ellagic acid against AD.
ESTHER : Javaid_2021_Curr.Pharm.Des_27_3591
PubMedSearch : Javaid_2021_Curr.Pharm.Des_27_3591
PubMedID: 33183192

Title : TV 3326 for Alzheimer's dementia: a novel multimodal ChE and MAO inhibitors to mitigate Alzheimer's-like neuropathology - Uddin_2020_J.Pharm.Pharmacol__
Author(s) : Uddin S , Kabir T , Rahman M , Mathew B , Shah MA , Ashraf GM
Ref : J Pharm Pharmacol , : , 2020
Abstract : OBJECTIVES: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders and a well-recognized cause of dementia with ageing. In this review, we have represented the ChE and MAO inhibitory potential of TV 3326 against AD based on current scientific evidence. KEY FINDINGS: The aetiology of AD is quite complex and not completely understood. However, it has been observed that AD involves the deposition of abnormal amyloid beta (Abeta), along with hyperphosphorylation of tau, oxidative stress, low acetylcholine (ACh) level and biometal dyshomeostasis. Due to the complex nature of AD aetiology, active research is required in the areas of development of multitarget drugs with 2 or more complementary biological functions, as they might represent significant progress in the AD treatment. Interestingly, it has been found that TV 3326 (i.e. ladostigil) is regarded as a novel therapeutic agent since it has the potential to cause inhibition of monoamine oxidase (MAO) A and B, and acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain. Furthermore, it has the capacity to reverse memory impairments, which further suggests the ability of this drug to elevate cholinergic activity in the brain. SUMMARY: TV 3326 can avert oxidative-nitrative stress and gliosis. It has also been confirmed that TV 3326 contains neuroprotective and anti-apoptotic properties. Therefore, this distinctive combined inhibition of ChE and MAO along with its neuroprotective property makes TV 3326 a useful drug in the treatment of AD.
ESTHER : Uddin_2020_J.Pharm.Pharmacol__
PubMedSearch : Uddin_2020_J.Pharm.Pharmacol__
PubMedID: 32149402

Title : Neuroprotective evaluation of Tribulus terrestris L. in aluminum chloride induced Alzheimer's disease - Chauhdary_2019_Pak.J.Pharm.Sci_32_805
Author(s) : Chauhdary Z , Saleem U , Ahmad B , Shah S , Shah MA
Ref : Pak J Pharm Sci , 32 :805 , 2019
Abstract : Tribulus terrestris (T.T) is enriched with steroidal saponins and flavonoids which have neuroprotective effect. The study was aimed to explore the potential of T.T methanol extract (T.T ME) for anti-Alzheirmer activity along with its safety evaluation. Plant was characterized by physicochemical, phytochemical and GCMS analyses whereas acute oral toxicity (OECD 425) was performed for safety evaluation. AlCl3 induced Alzheimer's disease rat model was used for anti-Alzheirmer activity. T.T ME was given orally at 100, 300 and 1000 mg/kg doses for 21 days and behavioral parameters were observed on 22nd study day. Physicochemical parameters were in permissible limits. GCMS analysis showed eight different compounds and benzene dicarboxylic acid showed maximum % peak area (64.19). No mortality was noted in acute toxicity study. Behavioral studies showed highly significant (p<0.001) improvement in T.T ME treated groups. Antioxidant enzymes and acetylcholinesterase levels were significantly (p<0.05) improved on treatment with T.T ME. Histopathological analysis indicated that neurofibrillary tangles were significantly improved in T.T ME treated groups. Biochemical and behavioral results suggested that T.T contained lead compounds which are effective in the treatment of Alzheimer disease.
ESTHER : Chauhdary_2019_Pak.J.Pharm.Sci_32_805
PubMedSearch : Chauhdary_2019_Pak.J.Pharm.Sci_32_805
PubMedID: 31103976

Title : A large-scale evaluation of pirimiphos-methyl 25\% WP during 1980-1981 for malaria control in Pakistan - Nasir_1982_J.Trop.Med.Hyg_85_239
Author(s) : Nasir SM , Ahmad N , Shah MA , Azam CM
Ref : J Trop Med Hyg , 85 :239 , 1982
Abstract : The emergence of strains of malaria vectors resistant to malathion in an area of Pakistan, and the continuing search for improved methods of control, necessitated the examination of alternative safe insecticides, with improved residual effects, for future use in the Malaria Control Programme in Pakistan. For these reasons, the effectiveness of pirimiphos-methyl, as Actellic 25 WP, was evaluated on a large scale in one sub-sector of Sheikhupura district of Punjab Province near Lahore. Entomological and parasitological evaluations demonstrated that 1 g of pirimiphos-methyl/m2 was as effective as 2 g/m2. Vector mosquito densities were reduced to zero, or almost so, in all areas sprayed with pirimiphos-methyl, and only began to approach vector levels in unsprayed areas after 9-10 months. No new cases of malaria were detected in those areas sprayed with pirimiphos-methyl. Blood cholinesterase determinations after the application of the pirimiphos-methyl spray confirmed the absence of any toxic effect on the spray operators, nor were there any toxic symptoms in the house occupants.
ESTHER : Nasir_1982_J.Trop.Med.Hyg_85_239
PubMedSearch : Nasir_1982_J.Trop.Med.Hyg_85_239
PubMedID: 7154146