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Vasodilatory Effects of Combined Traditional Chinese Medicinal Herbs in Optimized Ratio

Loh YC, Tan CS, Ch'ng YS, Ahmad M, Asmawi MZ, Yam MF

J Med Food, 2017 Mar;20(3):265-278.
PMID: 28296594 DOI: 10.1089/jmf.2016.3836

Recently, a new syndromic disease combination theory of traditional Chinese medicine (TCM) for hypertensive treatment has been introduced. In the wake of this new concept, a new science-based TCM formula that counteracts various syndromes is needed. The objective of this study was to develop such a formula. Five of the most clinically prescribed TCM herbs that work on different syndromes, namely Gastrodia elata, Uncaria rhynchophylla, Pueraria thomsonii, Panax notoginseng, and Alisma orientale, were selected for this study. The fingerprints of these five herbs were analyzed by tri-step Fourier transform infrared spectroscopy. Three different solvents, 95% ethanol, 50% ethanol, and distilled water, were used for the maceration of the herbs and their vasodilatory effects were studied using in vitro precontracted aortic ring model. Among these, the 50% ethanolic extracts of G. elata (GE50) and A. orientale (AO50), and 95% ethanolic extracts of U. rhynchophylla (UR95), P. thomsonii (PT95), and P. notoginseng (PN95) were found to be the most effective for eliciting vasodilation. Thus, these five extracts were used for orthogonal stimulus-response compatibility group studies by using L25 (5(5)) formula. The best combination ratio for GE50, UR95, PT95, PN95, and AO50, which was assigned as Formula 1 (F1), was found at EC0, EC25, EC20, EC20, and EC10, respectively. The vasodilatory effect of the extracts prepared from different extraction methods using F1 ratio was also studied. From the results, the EC50 and Rmax of total 50% ethanolic extract of five herbs using F1 ratio (F1-2) were 0.028 ± 0.005 mg/mL and 101.71% ± 3.64%, with better values than F1 (0.104 ± 0.014 mg/mL and 97.80% ± 3.12%, respectively). In conclusion, the optimum ratio and appropriate extraction method (F1-2) for the new TCM formula were revealed.
Synergistic antidiabetic activity of Vernonia amygdalina and Azadirachta indica: Biochemical effects and possible mechanism

Atangwho IJ, Ebong PE, Eyong EU, Asmawi MZ, Ahmad M

J Ethnopharmacol, 2016 12 04;193:725.
PMID: 27720513 DOI: 10.1016/j.jep.2016.09.057
Fulltext Correction to: Standardized extract of Ficus deltoidea stimulates insulin secretion and blocks hepatic glucose production by regulating the expression of glucose-metabolic genes in streptozitocin-induced diabetic rats

Farsi E, Ahmad M, Hor SY, Khadeer Ahamed MB, Yam MF, Khoo BY, et al.

BMC Complement Altern Med, 2018 09 27;18(1):262.
PMID: 30261874 DOI: 10.1186/s12906-018-2333-3

After the publication of this article [1] it came to our attention that one author, Boon Yin Khoo, was erroneously omitted from the authorship list.
Identification of green energy ranunculaceous flora of district Chitral, Northern Pakistan using pollen features through scanning electron microscopy

Ahmad M, Zafar M, Sultana S, Ahmad M, Abbas Q, Ayoub M, et al.

Microsc Res Tech, 2018 Sep;81(9):1004-1016.
PMID: 30303585 DOI: 10.1002/jemt.23066

Pollen micro-morphological features have proven to be helpful for the plant taxonomists in the identification and classification of plants. The utilization of this plantmayhelpfulin the areas of lignocellulosic conversion to biofuels and diversify application toward biomass. The current study was planned with the aim to evaluate the pollen features of complex Ranunculaceous flora of District Chitral, Northern Pakistan using both scanning electron microscopy (SEM) and Light Microscope (LM) for their taxonomic importance. Pollens of 18 Ranunculaceous species belonging to 6 genera were collected from different localities of the research area. SEM and LM were used to examine both qualitative and quantitative micro-morphological features. Sculptring of the sexine include; Scabrate, psilate, echinate, verrucate, perforate gemmate, and reticulate and so forth. Shape of the pollens was sub-spheroidal, spheroidal, prolate, subprolate and oblate and so forth. Type of pollen was ranged from mono to tricolpate and tricolporate. Quantitative characters include length/width of the pollen, colpus, exine thickness, and P/E ratio. Based on these micro-morphological features a taxonomic key was prepared for the fast and correct identification. RESEARCH HIGHLIGHT: Study of the pollen micro-morphological features of Ranunculaceous species by SEM and LM. Analysing both qualitative and quantitative characters of the pollens. Preparation of taxonomic key based on micro-morphological features for the correct and fast identification.
Role of trees in climate change and their authentication through scanning electron microscopy

Arshad S, Ahmad M, Saboor A, Ibrahim FH, Mustafa MRU, Zafar M, et al.

Microsc Res Tech, 2019 Feb;82(2):92-100.
PMID: 30511479 DOI: 10.1002/jemt.23106

Climate change is the most realistic theory of this era. Sudden and drastic changes are happening on the earth and the survival of mankind is becoming questionable in the future. The plants play the key role in controlling the climate change. The study emphasizes on role of trees in the cop up or damaging the climate of this earth, whether they are medicinal trees or economically important trees. Due to the overgrazing and intense deforestation the climate is being affected hazardously. The global warming phenomenon is occurring due to the less availability of trees and more carbon dioxide in the atmosphere. In total 20 plants were collected from across the Pakistan on the basis of their abundance and their key roles. Out of which seeds of eight plants were scanned through scanning electron microscope for correct authentication and importance of these medicinally important trees in mitigating the climate change. RESEARCH HIGHLIGHTS: The role of forest sector in the climate's change mitigation. Medicinally and economically important tree species across Pakistan. By using SEM, Ultra seed sculpturing features as an authentication tool. To formulate some policies to stop or control deforestation.
Fulltext Exploring Culture, Religiosity and Spirituality Influence on Antihypertensive Medication Adherence Among Specialised Population: A Qualitative Ethnographic Approach

Abdul Wahab NA, Makmor Bakry M, Ahmad M, Mohamad Noor Z, Mhd Ali A

Patient Prefer Adherence, 2021;15:2249-2265.
PMID: 34675490 DOI: 10.2147/PPA.S319469

Background: Hypertension is one of the major risk factors of stroke and leading risk factors for global death. Inadequate control of blood pressure due to medication non-adherence remains a challenge and identifying the underlying causes will provide useful information to formulate suitable interventions.
Purpose: This study aimed to explore the roles of culture, religiosity, and spirituality on adherence to anti-hypertensive medications.
Methodology: A semi-structured qualitative interview was used to explore promoters and barriers to medication adherence among hypertensive individuals residing in urban and rural areas of Perak State, West Malaysia. Study participants were individuals who are able to comprehend either in Malay or English, above 18 years old and on antihypertensive medications. Interview transcriptions from 23 participants were coded inductively and analyzed thematically. Codes generated were verified by three co-investigators who were not involved in transcribing process. The codes were matched with quotations and categorized using three levels of themes named as organizing, classifying and general themes.
Results: Cultural aspects categorized as societal and communication norms were related to non-adherence. The societal norms related to ignorance, belief in testimony and anything "natural is safe" affected medication adherence negatively. Communication norms manifested as superficiality, indirectness and non-confrontational were also linked to medication non-adherence. Internal and organizational religiosity was linked to increased motivation to take medication. In contrast, religious misconception about healing and treatment contributed towards medication non-adherence. The role of spirituality remains unclear and seemed to be understood as related to religiosity.
Conclusion: Culture and religiosity (C/R) are highly regarded in many societies and shaped people's health belief and behaviour. Identifying the elements and mechanism through which C/R impacted adherence would be useful to provide essential information for linking adherence assessment to the interventions that specifically address causes of medication non-adherence.
Fulltext Report: antioxidant and nutraceutical value of wild medicinal Rubus berries

Ahmad M, Masood S, Sultana S, Hadda TB, Bader A, Zafar M

Pak J Pharm Sci, 2015 Jan;28(1):241-7.
PMID: 25553701

Nutritional quality and antioxidant capacity of three edible wild berries (Rubus ellipticus Smith, Rubus niveus Thunb, Rubus ulmifolius L.) from Lesser Himalayan Range (LHR) were evaluated. Their edible portion was assayed for moisture, fats, ash, carbohydrates, proteins, fibers, essential minerals (Ca, P, Mg, K, Na, Cl, S, Mn, Zn, Fe, Cu, Se, Co, Ni) and DPPH free radical scavenging activity was applied to determine the antioxidant potential. The fruit of Rubus ulmifolius L. (blackberry) possessed the highest values of energy (403.29 Kcal), total protein (6.56g/100 g), Nitrogen (N) content (1500mg/100g), K (860.17mg/100g), Ca (620.56mg/100g), Zn (17.509mg/100g) and the strongest antioxidant activity (98.89% inhibition). While the raspberries (Rubus ellipticus Smith, Rubus niveus Thunb.) exhibited more significant contents of dietary fiber (5.90g/100g), carbohydrates (86.4 g/100 g) and Fe (4.249mg/100g). Significant variation was observed among the tested samples in all the investigated features. The combination of bio elements and active antioxidants clearly showed the applicability of these berries as a nutraceutical supplement.
Fulltext Combined 3D-QSAR, molecular docking and dynamics simulations studies to model and design TTK inhibitors

Ashraf N, Asari A, Yousaf N, Ahmad M, Ahmed M, Faisal A, et al.

Front Chem, 2022;10:1003816.
PMID: 36405310 DOI: 10.3389/fchem.2022.1003816

Tyrosine threonine kinase (TTK) is the key component of the spindle assembly checkpoint (SAC) that ensures correct attachment of chromosomes to the mitotic spindle and thereby their precise segregation into daughter cells by phosphorylating specific substrate proteins. The overexpression of TTK has been associated with various human malignancies, including breast, colorectal and thyroid carcinomas. TTK has been validated as a target for drug development, and several TTK inhibitors have been discovered. In this study, ligand and structure-based alignment as well as various partial charge models were used to perform 3D-QSAR modelling on 1H-Pyrrolo[3,2-c] pyridine core containing reported inhibitors of TTK protein using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches to design better active compounds. Different statistical methods i.e., correlation coefficient of non-cross validation (r2), correlation coefficient of leave-one-out cross-validation (q2), Fisher's test (F) and bootstrapping were used to validate the developed models. Out of several charge models and alignment-based approaches, Merck Molecular Force Field (MMFF94) charges using structure-based alignment yielded highly predictive CoMFA (q2 = 0.583, Predr2 = 0.751) and CoMSIA (q2 = 0.690, Predr2 = 0.767) models. The models exhibited that electrostatic, steric, HBA, HBD, and hydrophobic fields play a key role in structure activity relationship of these compounds. Using the contour maps information of the best predictive model, new compounds were designed and docked at the TTK active site to predict their plausible binding modes. The structural stability of the TTK complexes with new compounds was confirmed using MD simulations. The simulation studies revealed that all compounds formed stable complexes. Similarly, MM/PBSA method based free energy calculations showed that these compounds bind with reasonably good affinity to the TTK protein. Overall molecular modelling results suggest that newly designed compounds can act as lead compounds for the optimization of TTK inhibitors.
Synthesis and α-glucosidase inhibition studies of norfloxacin-acetanilide hybrids

Walayat K, Ahmad M, Ali Ashfaq U, Ali Khan Z, Sultan S

Pak J Pharm Sci, 2021 Sep;34(5(Supplementary)):1909-1915.
PMID: 34836859

α-Glucosidase inhibitors occupy a prominent position among the various treatments of type-2 diabetes mellitus (DM2). In this study, a series of new norfloxacin-acetanilide hybrid molecules were synthesized and screened for α-glucosidase inhibition activity. The synthetic methodology involves the synthesis of a series of α-bromoacetanilides by condensing bromoacetyl bromide with various substituted anilines. These α-bromoacetanilides were coupled with norfloxacin in DMF to get the titled hybrids. The structure elucidation of synthesized compounds were characterized by 1H NMR, 13C NMR and LC-MS. Finally, the compounds were screened for their α-glucosidase inhibition activity using acarbose as a reference drug (IC50 =58 μM). Among the tested compounds, 3i and 3j displayed potent α-glucosidase inhibition activity with IC50 values of 7.81±0.038 and 5.55±0.012 μM respectively. In-addition, 3m, 3f and 3k were demonstrated moderate alpha-glucosidase inhibition activities with IC50 values of 52.905±0.041, 23.79± 0.087 and 23.06±0.026 μM respectively. The structure-activity relationship was established with the help of molecular docking by using Molecular Operating Environment software (MOE 2014).
Factors associated with severe envenomation of snakebite cases at emergency department, Hospital Sultan Abdul Halim, Kedah, Malaysia

Mhd Nizar MNF, Rahman A, Baharuddin KA, Ahmad MZ, Mohamed Ismail M

Med J Malaysia, 2022 Jan;77(1):20-25.
PMID: 35086990

INTRODUCTION: Snakebite envenomation is a medical emergency and cases continue to be encountered in Malaysian hospitals. This study aims to determine the prevalence of snakebite presentations and the associated factors with severe envenomation of snakebite in Sungai Petani, Kedah, Malaysia.
MATERIALS AND METHODS: This was a retrospective, crosssectional study involving snakebite patients presented at the Emergency Department (ED), Hospital Sultan Abdul Halim (HSAH), Kedah from 1 July 2015 to 30 June 2019. The cases were extracted from the computerized system and the case records of patients were retrieved from the Medical Record Unit. Patients that met the study criteria were included and their sociodemographic features, clinical presentations including use of anti-venom were collected. Logistic regression analysis was performed to determine the factors associated with severe envenomation.
RESULTS: A total of 220 snakebite cases with the mean age of patients was 39.66 (SD±21.79) years old. Majority of them were Malay and males. 41.4% of snakebite cases occurred in late evenings and the mean time-lapsed to arrive at HSAH was 108.6 minutes. 81.4% of snakebite cases occurred while engaging in outdoor activities and 43.6% of the snakebite cases involved work-related incidents. 58.2% of the patients were bitten in the lower limb. 78.6% of patients were bitten by the identified snake species, predominantly from Viperidae family. The prevalence of severe envenomation was 50.9%. Malay ethnicity (adj. OR =2.549, 95% CI =1.277,5.089), bite to the upper limb (adj. OR =2.125, 95% CI =1.192, 3.790), and bite by snakes from Viperidae family (adj. OR =3.017, 95% CI =1.613, 5.642) were found to have significant associations with severe envenomation of snakebite.
CONCLUSION: The prevalence of severe envenomation was more than 50% of snakebite cases. Malay ethnicity, upper limb snake bites, and snakebite from a Viperidae family had a higher chance of severe envenomation.
Fulltext An Intelligent Proposed Model for Task Offloading in Fog-Cloud Collaboration Using Logistics Regression

Bukhari MM, Ghazal TM, Abbas S, Khan MA, Farooq U, Wahbah H, et al.

Comput Intell Neurosci, 2022;2022:3606068.
PMID: 35126487 DOI: 10.1155/2022/3606068

Smart applications and intelligent systems are being developed that are self-reliant, adaptive, and knowledge-based in nature. Emergency and disaster management, aerospace, healthcare, IoT, and mobile applications, among them, revolutionize the world of computing. Applications with a large number of growing devices have transformed the current design of centralized cloud impractical. Despite the use of 5G technology, delay-sensitive applications and cloud cannot go parallel due to exceeding threshold values of certain parameters like latency, bandwidth, response time, etc. Middleware proves to be a better solution to cope up with these issues while satisfying the high requirements task offloading standards. Fog computing is recommended middleware in this research article in view of the fact that it provides the services to the edge of the network; delay-sensitive applications can be entertained effectively. On the contrary, fog nodes contain a limited set of resources that may not process all tasks, especially of computation-intensive applications. Additionally, fog is not the replacement of the cloud, rather supplement to the cloud, both behave like counterparts and offer their services correspondingly to compliance the task needs but fog computing has relatively closer proximity to the devices comparatively cloud. The problem arises when a decision needs to take what is to be offloaded: data, computation, or application, and more specifically where to offload: either fog or cloud and how much to offload. Fog-cloud collaboration is stochastic in terms of task-related attributes like task size, duration, arrival rate, and required resources. Dynamic task offloading becomes crucial in order to utilize the resources at fog and cloud to improve QoS. Since this formation of task offloading policy is a bit complex in nature, this problem is addressed in the research article and proposes an intelligent task offloading model. Simulation results demonstrate the authenticity of the proposed logistic regression model acquiring 86% accuracy compared to other algorithms and confidence in the predictive task offloading policy by making sure process consistency and reliability.
Fulltext Vasorelaxant properties of Vernonia amygdalina ethanol extract and its possible mechanism

Ch'ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, et al.

Pharm Biol, 2017 Dec;55(1):2083-2094.
PMID: 28832263 DOI: 10.1080/13880209.2017.1357735

CONTEXT: Vernonia amygdalina Del. (VA) (Asteraceae) is commonly used to treat hypertension in Malaysia.
OBJECTIVE: This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint.
MATERIALS AND METHODS: Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0.01-2.55 mg/mL at 20-min intervals) were evaluated on aortic rings isolated from Sprague Dawley rats in the presence of antagonists.
RESULTS: The tri-step FTIR spectroscopy showed that VAE contains alkaloids, flavonoids, and saponins. VAE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC50 of 0.057 ± 0.006 and 0.430 ± 0.196 mg/mL, respectively. In the presence of Nω-nitro-l-arginine methyl ester (EC50 0.971 ± 0.459 mg/mL), methylene blue (EC50 1.203 ± 0.426 mg/mL), indomethacin (EC50 2.128 ± 1.218 mg/mL), atropine (EC50 0.470 ± 0.325 mg/mL), and propranolol (EC50 0.314 ± 0.032 mg/mL), relaxation stimulated by VAE was significantly reduced. VAE acted on potassium channels, with its vasorelaxation effects significantly reduced by tetraethylammonium, 4-aminopyridine, barium chloride, and glibenclamide (EC50 0.548 ± 0.184, 0.158 ± 0.012, 0.847 ± 0.342, and 0.304 ± 0.075 mg/mL, respectively). VAE was also found to be active in reducing Ca2+ released from the sarcoplasmic reticulum and blocking calcium channels.
CONCLUSIONS: The vasorelaxation effect of VAE involves upregulation of NO/cGMP and PGI2 signalling pathways, and modulation of calcium/potassium channels, and muscarinic and β2-adrenergic receptor levels.
Overview of Signaling Mechanism Pathways Employed by BPAid in Vasodilatory Activity

Loh YC, Tan CS, Ch'ng YS, Ahmad M, Ng CH, Yam MF

J Med Food, 2017 Dec;20(12):1201-1213.
PMID: 28953423 DOI: 10.1089/jmf.2017.3958

Hypertension, one of the famous "silent killers" that can attack people at any age, is a current hot topic among scientists due to multiple syndromic behavior and concomitant diseases. The new scientific-based Traditional Chinese Medicine (TCM) formulation approach was used in a previous study by combining five TCM herbs, including Gastrodia elata Bl., Uncaria rhynchophylla (Miq.) Miq. ex Havil., Pueraria thomsonii Benth., Panax notoginseng (Burk.) F.H. Chen, and Alisma orientalis (Sam.) Juzep in optimized ratio (named BPAid). The objective of the present study was to evaluate the mechanism pathways employed by BPAid for vasodilatory effect with the use of an in vitro isolated aortic rings assay. Interestingly, all the mechanisms investigated were involved in the BPAid's vasodilation activity in which the majority contributed through the nitric oxide/soluble guanylyl cyclase/cyclic guanosine monophosphate (NO/sGC/cGMP) pathways, followed by prostacyclin (PGI2), β2-adrenergic, and M3-receptors pathways. Furthermore, the BPAid appeared to manage vascular tone by regulating action potential through potassium and both voltage-operated calcium channel and inositol triphosphate receptor (IP3R) pathways. The results obtained has confirmed the expected outcome that the benefits of TCM herbs in BPAid can meet the criteria of counteracting multiple signaling mechanism pathways involved in the etiology of hypertension. In addition to this study, the fingerprints and chemical properties of BPAid was identified by using tri-step Fourier transform infrared spectroscopy and compared with its derivatives. The results obtained suggested that the majority of the vasodilatory effects exerted by BPAid were attributed to the presence of saponins and aromatic ring-containing vasoactive compounds.
Mechanisms of Action of Uncaria rhynchophylla Ethanolic Extract for Its Vasodilatory Effects

Loh YC, Ch'ng YS, Tan CS, Ahmad M, Asmawi MZ, Yam MF

J Med Food, 2017 Sep;20(9):895-911.
PMID: 28771084 DOI: 10.1089/jmf.2016.3804

Uncaria rhynchophylla is one of the major components included in Traditional Chinese Medicine prescriptions for hypertensive treatment. Previous studies have suggested that U. rhynchophylla might contain vasodilation-mediating active compounds, especially indole alkaloids. Hence, this study was carried out to determine the vasodilatory effects of U. rhynchophylla, which was extracted by different solvents. The most effective extract was then further studied for its signaling mechanism pathways. The authenticity of U. rhynchophylla was assured by using modernized tri-step Fourier transform infrared (FTIR), including conventional 1D FTIR, second derivative scanning combined with 2D-correlated IR spectroscopy. Results obtained proved that the fingerprint of U. rhynchophylla used was identical to the atlas. Isolated aortic rings from male Sprague-Dawley rats were preconstricted with phenylephrine (PE) followed by cumulative addition of U. rhynchophylla extracts. The signaling mechanism pathways were studied by incubation with different receptor antagonists before the PE precontraction. In conclusion, the 95% ethanolic U. rhynchophylla extract (GT100) was found to be most effective with an EC50 value of 0.028 ± 0.002 mg/mL and an Rmax value of 101.30% ± 2.82%. The signaling mechanism pathways employed for exerting its vasodilatory effects included nitric oxide/soluble guanylyl cylcase/cyclic guanosine monophosphate (NO/sGC/cGMP) and PGI2 (endothelium-derived relaxing factors), G protein-coupled M3- and β2 receptors, regulation of membrane potential through voltage-operated calcium channel, intracellular Ca2+ released from inositol triphosphate receptor (IP3R), and all potassium channels except the Kca channel.
Anti-hypertensive and vasodilatory effects of amended Banxia Baizhu Tianma Tang

Tan CS, Loh YC, Ng CH, Ch'ng YS, Asmawi MZ, Ahmad M, et al.

Biomed Pharmacother, 2018 Jan;97:985-994.
PMID: 29136777 DOI: 10.1016/j.biopha.2017.11.021

Although Banxia Baizhu Tianma Tang (BBT) has been long administered for hypertensive treatment in Traditional Chinese Medicine (TCM), the ratio of the herbal components that makes up the formulation has not been optimized with respect to the anti-hypertensive effect that it inherently possesses. A newly amended BBT (ABBT) formulation was developed using the evidence-based approach of orthogonal stimulus-response compatibility model. The ABBT showed enhanced therapeutic effect while maintaining its traditional theoretical approach rooted in TCM. This study was designed to investigate the possible mechanism of actions involved in the vasodilatory activity of ABBT-50 by evaluating its vasodilative effect on isolated Sprague Dawley rats in the presence of absence of various antagonists. When pre-contracted with phenylephrine, relaxation was observed in endothelium intact (EC50=0.027±0.003mg/ml, Rmax=109.8±2.12%) and denuded aortic rings (EC50=0.409±0.073mg/ml, Rmax=63.15±1.78%), as well as in endothelium intact aortic rings pre-contracted with potassium chloride (EC50=32.7±12.16mg/ml, Rmax=34.02±3.82%). Significant decrease in the vasodilative effect of ABBT-50 was observed in the presence of Nω-nitro-l-arginine methyl ester (EC50=0.12±0.021mg/ml, Rmax=75.33±3.28%), 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (EC50=0.463±0.18mg/ml, Rmax=54.48±2.02%), methylene blue (EC50=0.19±0.037mg/ml, Rmax=83.69±3.19%), indomethacin (EC50=0.313±0.046mg/ml, Rmax=71.33±4.12%), atropine (EC50=0.146±0.013mg/ml, Rmax=77.2±3.41%), and 4-aminopyridine (EC50=0.045±0.008mg/ml, Rmax=95.55±2.36%). ABBT-50 was also suppressing Ca2+ release from sarcoplasmic reticulum and inhibiting calcium channels. Vasodilatory effects of ABBT-50 are mediated through NO/sGC/cGMP cascade and PGI2, followed by muscarinic pathways and calcium channels.
Synthesis, monoamine oxidase inhibition activity and molecular docking studies of novel 4-hydroxy-N'-[benzylidene or 1-phenylethylidene]-2-H/methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides

Saddique FA, Zaib S, Jalil S, Aslam S, Ahmad M, Sultan S, et al.

Eur J Med Chem, 2018 Jan 01;143:1373-1386.
PMID: 29126721 DOI: 10.1016/j.ejmech.2017.10.036

Three series of 4-hydroxy-N'-[benzylidene/1-phenylethylidene]-2-H/methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides (9-11)a-l were synthesized and unraveled to be highly potent dual inhibitors of monoamine oxidases (MAO-A and MAO-B). All the examined compounds demonstrated IC50 values in lower micro-molar range for both MAO-A as well as MAO-B. The most active MAO-A inhibitor was 4-hydroxy-N'-(1-phenylethylidene)-2H-benzo[e][1,2]thiazine-3-carbohydrazide 1,1-dioxide (9i) with an IC50 value of 0.11 ± 0.005 μM, whereas, methyl 4-hydroxy-2H-benzo[e][1,2]thiazine-3-carboxylate 1,1-dioxide (3) was the most active MAO-B inhibitor with an IC50 value of 0.21 ± 0.01 μM. Enzyme kinetics studies revealed that the most potent compounds inhibited both MAO enzymes (A & B) in a competitive fashion. Molecular docking studies were also performed to obtain an intuitive picture of inhibition potential for potent inhibitors. The high potency of these compounds is optimally combined with highly favorable ADME profile with predicted good oral bioavailability.
Vasodilation and Antihypertensive Activities of Swietenia macrophylla (Mahogany) Seed Extract

Ch'ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, et al.

J Med Food, 2018 Mar;21(3):289-301.
PMID: 29420109 DOI: 10.1089/jmf.2017.4008

The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists. The pharmacological effect of SM50 was investigated by oral administration of spontaneously hypertensive rats (SHRs) with three different doses of SM50 (1000, 500, and 250 mg/kg/day) for 4 weeks and their systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured weekly using tail-cuff method. The tri-step FTIR macro-fingerprint of SM50 showed that SM50 contains stachyose, flavonoids, limonoids, and ester, which may contribute to its vasorelaxant effect. The results showed that the vasorelaxant activity of SM50 was mostly attributed to channel-linked receptors pathways through the blockage of voltage-operated calcium channels (VOCC). SM50 also acts as both potassium channels opener and inositol triphosphate receptor (IP3R) inhibitor, followed by β2-adrenergic pathway, and ultimately mediated through the nitric oxide/soluble guanylyl cyclase/cyclic 3',5'-guanosine monophosphate (NO/sGC/cGMP) signaling pathways. The treatment of SM50 also significantly decreased the SBP and DBP in SHRs. In conclusion, the antihypertensive mechanism of SM50 was mediated by VOCC, K+ channels, IP3R, G-protein-coupled β2-adrenergic receptor, and followed by NO/sGC/cGMP signaling mechanism pathways in descending order. The data suggested that SM50 has the potential to be used as a herbal medicament to treat hypertension.
Life Review Intervention: A Systematic Review of Its Feasibility Among Persons With Cancer

Ng JK, Subramaniam P, Ismail F, Ahmad M, Shamsudin NL

J Pain Symptom Manage, 2022 Nov;64(5):e235-e249.
PMID: 35931402 DOI: 10.1016/j.jpainsymman.2022.07.016

CONTEXT: Life Review Intervention (LRI) has started to shift in emphasis of focus onto persons with cancer and its effectiveness in improving their psychological well-being. The process has now begin integrating into healthcare settings as a complementary treatment for this population.
OBJECTIVES: The current systematic review aims to synthesize existing feasibility studies on LRI among persons with cancer.
METHODS: A literature search was conducted from the databases PubMed, ScienceDirect, PsychArticles, Scopus, Psychology and Behavioral Science Collection, Cochrane, EBSCO, and other methods. Eligible articles were selected based on the predetermined inclusion criteria and data extraction revolved around the study design, intervention procedure, and feasibility and psychological outcome measures.
RESULTS: The search yielded 8,627 articles, to which respondents simultaneously receiving other forms of psychological interventions were excluded. Eight were selected for evaluation. Four were integrated interventions while the remaining were conducted with the standard intervention. The sample size range from 5 to 90 persons with cancer. All reviewed articles reported optimum feasibility, as presented by recruitment capability, participant retention rate, acceptability and satisfaction, intervention implementation, and evaluation of intervention outcome measures. However, a majority of psychological outcome measures indicated no statistical significance.
CONCLUSION: LRI is feasible to be implemented among persons with cancer, given the high acceptability and availability of resources for its implementation. The present review highlighted the preliminary knowledge on the feasibility of the intervention.
Fulltext Modified matrix solid phase dispersion-HPLC method for determination of pesticide residue in vegetables and their impact on human health: A risk assessment

Mujahid M, Latif S, Ahmed M, Shehzadi W, Imran M, Ahmad M, et al.

Front Chem, 2022;10:1084350.
PMID: 36569961 DOI: 10.3389/fchem.2022.1084350

The use of pesticides is unavoidable in agricultural practices. This class of chemicals is highly toxic for the environment as well as for humans. The present work was carried out to assess the presence of some pesticides (diafenthiuron, lufenuron, azoxystrobin, difenoconazole, and chlorothalonil) residues in five of the very commonly used vegetables (eggplant, capsicum, apple gourd, cauliflower, and sponge gourd). Matrix solid phase dispersion (MSPD) technique was used to extract the pesticides and subsequently their quantification was performed through high performance liquid chromatography (HPLC) coupled to ultraviolet-visible (UV-Vis) detector. The elution was accomplished at wavelength of 254 nm by injecting 20 µL of standards or samples into chromatographic system. The mobile phase consisted of acetonitrile and water (80:20 v/v), where the flow rate was adjusted at 1.0 ml/min. The linearity was good (R 2 ≥ 0.994) over a concentration range from 20 to 100 μg/ml for the investigated pesticides. The low detection limits showed a quite appreciable potential of the method to detect (1.12-1.61 μg/L) and quantify (3.73-5.36 μg/ml) the pesticides under study. The accuracy was demonstrated in terms of percent recovery which ranged between 88.5% and 116.9% for all the pesticides under investigation. These results justify the suitability of the technique for the intended purpose. The concentration of difenoconazole in apple gourd (20.97 mg/kg), cauliflower (10.28 mg/kg), and sponge gourd (40.32 mg/kg) whereas diafenthiuron in cauliflower (0.66 mg/kg) exceeded the maximum residue level (MRLs) as defined by Food and Agriculture Organization of the United Nations and the World Health Organization (FAO/WHO). Target hazard quotient (THQ) values of difenoconazole and diafenthiuron (except for adults) were more than one which indicates the significant effect on human health on consumption of apple gourd, cauliflower, and sponge gourd.
Photocatalytic degradation of methyl orange from wastewater using a newly developed Fe-Cu-Zn-ZSM-5 catalyst

Ahmad M, Aziz ARA, Mazari SA, Baloch AG, Nizamuddin S

Environ Sci Pollut Res Int, 2020 Jul;27(21):26239-26248.
PMID: 32358758 DOI: 10.1007/s11356-020-08940-9

Photo-Fenton oxidation is one of the most promising processes to remove recalcitrant contaminants from industrial wastewater. In this study, we developed a novel heterogeneous catalyst to enhance photo-Fenton oxidation. Multi-composition (Fe-Cu-Zn) on aluminosilicate zeolite (ZSM-5) was prepared using a chemical process. Subsequently, the synthesized catalyst was characterized by using X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), high-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray (spectroscopy) (EDX), and Brunauer-Emmett-Teller (BET). Activity of the synthesized catalyst is analysed to degrade an azo dye, methyl orange. Taguchi method is used to optimize color removal and total carbon content (TOC) removal. The dye completely degraded, and 76% of TOC removal was obtained at optimized process conditions. The amount of catalyst required for the desired degradation of dye significantly reduced up to 92% and 30% compared to conventional homogenous and heterogeneous Fenton oxidation processes, respectively.

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