Publications by authors named "Malik Hassan Mehmood"

41 Publications

Knowledge, Attitude, Practice, Behavior and Risk Perception of COVID-19 Pandemic among University Students of Pakistan.

Disaster Med Public Health Prep 2022 Jan 10:1-12. Epub 2022 Jan 10.

Faculty of Pharmacy and Faculty of Medicine & Allied Health Sciences, The Islamia University of Bahawalpur, 63100, Bahawalpur, Punjab, Pakistan.

Objective: Coronavirus disease 2019 (COVID-19) pandemic has substantially affected students around the globe due to the closure of educational institutes. However, student involvements and contributions are important in combating the disease for this reason current study was designed to assess the knowledge-attitude-practice (KAP), preventive behavior, and risk perception among university students.

Methods: A cross-sectional survey-based study was conducted among university students of Punjab, Pakistan from April 1st to June 30th, 2020. The 68 items questionnaire was used to evaluated responses using statistical approaches (student's t-test, regression-analysis and co-relation analysis) by considering p-value <0.05 statistically significant.

Results: A total of 503 university students (medical and non-medical) were selected with the majority of participants were females (83%) and 64.5% were of age ranged from 16 to 21 years old. The participants (80%) reported good disease knowledge with a mean score of 12.06 ± 1.75 (p<0.05), which substantially higher among medical students. Most of the respondents (72%) believed that COVID-19 will be effectively controlled through precautionary measures. In correlation subgroup analysis, a significant relationship (p=0.025) between knowledge and positive attitude were indicated. Fear and knowledge of COVID-19 emerged as strong predictors (p<0.001) of preventive behaviors towards disease.

Conclusion: This study demonstrated satisfactory knowledge, positive attitudes, and suitable practices among students towards COVID-19. University students can be involved in public education to aid the health authorities in achieving the targets of educational campaigns with maximum population coverage.
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http://dx.doi.org/10.1017/dmp.2022.1DOI Listing
January 2022

Pharmacological evaluation of Vitis vinifera and Zingiber zerumbet on electrocardiographic, biochemical alterations and antioxidant status in isoproterenol-induced myocardial infarction in rats.

Pak J Pharm Sci 2021 Sep;34(5(Supplementary)):1929-1937

Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan.

The Vitis vinifera (VV) and Zingiber zerumbet (ZZ) are popular functional foods which are used for the treatment of cardiovascular ailments. These possess antiproliferative, antiplatelet and antioxidant effects. The current study has been designed to ascertain their effectiveness against Isoproterenol (ISO)-induced myocardial infarction (MI). Chronic administration of VV and ZZ was accessed for its cardio-protective effect in ISO-induced MI rats. Male albino rats were treated with VV (250 mg/kg, p.o.), ZZ (200 mg/kg, p.o.) and its combination (Vitis vinifera + Zingiber zerumbet) VZ for 30 days prior to ISO administration (85 mg/kg, S/C). Electrocardiography (ECG) and Blood Pressure (BP) were measured using PowerLab data acquisition system. Biochemical serum markers, tissue histopathology and HPLC finger printing were performed. The VV, ZZ and its combination VZ showed significant protective effects on ST segment elevation, cardiac biomarkers; Troponin I (Trop I), creatine kinase-MB (CK-MB), alanine transaminase (ALT), aspartate amino transferase (AST), lactate dehydrogenase (LDH), enhanced the cardiac antioxidant defense system, restored the hematological (WBCs, RBCs, Platelets) & coagulation parameters and improved the lipid profile and histopathological alterations such as tissue necrosis, infiltration and edema which were observed only in ISO administered rats. These results indicate that V. vinifera and Z. zerumbet possess cardio protective effects possibly mediated through maintenance of endogenous antioxidant levels, cardiac biomarkers and lipid parameters.
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September 2021

Ziziphus Oxyphylla hydro-methanolic extract ameliorates hypertension in L-NAME induced hypertensive rats through NO/cGMP pathway and suppression of oxidative stress related inflammatory biomarkers.

J Ethnopharmacol 2022 Mar 11;285:114825. Epub 2021 Nov 11.

Department of Physiology, Faculty of Life Sciences, Government College University, Faisalabad, Pakistan. Electronic address:

Ethnopharmacological Relevance: Ziziphus Oxyphylla belongs to family Ziziphus and has been used traditionally in hypertension. It is enriched with quercetin and kaempferol derivatives, catechin and cyclopeptide alkaloids.

Aim: The current research evaluates the antihypertensive potential of aqueous methanolic extract of Z. oxyphylla (AMEZO) in NG-nitro-L-arginine methyl ester (LNAME) induced hypertension in rats.

Material And Methodology: Phytochemical analysis of AMEZO was carried out using high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS/MS). Antihypertensive activities of AMEZO (200 and 400 mg/kg) and Kaempferol were assessed in L-NAME (185 μmol/kg, intraperitoneal) injected hypertensive rats. In normotensive rats, blood pressure was assessed using Power Lab data system. Serum and tissue samples were preserved for estimation of nitric oxide (NO), Cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), tumor necrosis factor (TNF- α) and oxidative stress markers respectively. mRNA levels of eNOS, ACE, COX-2 and NF-kB genes were assessed through qPCR.

Results: The HPLC and ESI-MS/MS identified kaempferol, quercetin, catechin, ceanothic acid, zizybernalic acid and oxyphylline F. Chronic administration of AMEZO and kaempferol in L-NAME induced hypertensive rats significantly (p < 0.001) reduced systolic, diastolic and mean blood pressure. AMEZO and kaempferol caused meaningfully improved (p < 0.001) serum NO and cGMP levels. AMEZO administration also noticeably decrease the elevated IL-6 and TNF- α concentration in hypertensive animals. Administration of AMEZO and kaempferol also improved oxidative stress markers (MDA, CAT, SOD, GSH). The antihypertensive activity of AMEZO also resulted in upregulation of eNOS and downregulation of ACE.

Conclusion: These data depict that AMEZO and kaempferol showed antihypertensive activity in LNAME induced hypertensive rats possibly mediated through improvement in NO and cGMP levels, modulation of mRNA expression of eNOS, ACE, COX-2 and NF-kB and suppression of oxidative stress related inflammatory markers, proposing a defensive role in cardiovascular diseases.
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http://dx.doi.org/10.1016/j.jep.2021.114825DOI Listing
March 2022

Pharmacological evaluation of , and in hypertension through in-vivo and in vitro-assays.

Heliyon 2021 Oct 30;7(10):e08094. Epub 2021 Sep 30.

College of Pharmacy, Department of Pharmacology, University of Sargodha, Pakistan.

Objective: This study determines the efficacy and probable underlying mode of action to the folk usage of and in hypertension.

Methods: The aqueous-methanol extracts of (EH.Cr) (FI.Cr) and (CD.Cr) were tested for antihypertensive effects in rats using and blood pressure measuring apparatus. assays were carried out using isolated rat aortae using PowerLab station.

Results: EH.Cr, FI.Cr and CD.Cr at 500 mg/kg (orally) caused a fall in the mean systolic blood pressure in arsenic-induced hypertensive and normotensive rats, similar to nifedipine. In rat aortae, EH.Cr, CD.Cr and FI.Cr reversed low (20 mM), high (80 mM) K and phenylephrine (P.E)-driven contractions, while partially inhibited high K contractions. In the presence of TEA, remained unable to relax low K contractions. EH.Cr and CD.Cr moved Ca concentrations response curves to the right, like nifedipine. All fractions of EH.Cr and CD.Cr except aqueous, pet-ether and chloroform fractions of FI.Cr displayed Ca antagonistic activity. FI.Cr, its ethyl acetate and aqueous fraction exhibited TEA-sensitive potassium channel activation. On baseline tension, test materials also produced phentolamine-sensitive vasospasm.

Conclusion: , and possess antihypertensive activity in arsenic-induced hypertensive rats possibly mediated endothelium-dependent vasorelaxation. In normotensive rats, and showed antihypertensive activities through endothelium-dependent and Ca antagonistic pathways, while exhibited potassium channel activation and Ca antagonistic like effects in its vasorelaxation. Additional weaker vasospastic effects were derived through α-adrenergic like pathways.
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http://dx.doi.org/10.1016/j.heliyon.2021.e08094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529515PMC
October 2021

Chemical characterisation and appraisal of antidiabetic potential of Terminalia citrina extract in streptozotocin induced hyperglycaemia in Wistar rats.

Arch Physiol Biochem 2021 Aug 17:1-14. Epub 2021 Aug 17.

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.

The current research was aimed to evaluate the antidiabetic activity of methanolic extract (TCME) by streptozotocin-induced diabetes in male Wistar rats. TCME exhibited better antioxidant and alpha-amylase inhibitory activity as compared to other tested extracts. TCME at 250, 500, and 750 mg/kg showed notable ( < .05) antidiabetic potential by lowering fasting blood glucose level, restoring lipid level, serum amylase, HbA1c, kidney, and liver function tests as coevidenced from histological findings of the liver, pancreas, and kidney. TCME remarkably reinstated the antioxidant enzymatic activities (CAT: 0.181 ± 0.011 IU/mg protein, SOD: 21.45 ± 1.53 IU/mg protein) and reduced lipid peroxidation level (40.60 ± 2.41 µM/mg protein) in the liver and kidney tissue of diabetic rats at 750 mg/kg dose. The acute and subacute oral toxicity study of TCME exhibited no clinical toxicity signs and mortality. Its GC-MS spectrum unveiled the existence of 10-octadecenoic acid and other compounds which might have contributed to antidiabetic potential.
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http://dx.doi.org/10.1080/13813455.2021.1963783DOI Listing
August 2021

Hydroethanolic Hance Ameliorates Hypertension and Causes Diuresis in Obesogenic Feed-Fed Rat Model.

Front Pharmacol 2021 9;12:670433. Epub 2021 Jul 9.

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University of Faisalabad, Faisalabad, Pakistan.

Hance () has been used widely in traditional Chinese and Ayurvedic medicines. Its folkloric uses include relieving stomach ache, treating cold, improving the circulatory system, and reducing swelling. Its effectiveness and mechanism of antihypertension in obesity-induced hypertensive rats have not been studied yet as per our knowledge. This study has been designed to provide evidence of underlying mechanisms to the medicinal use of as a cardiotonic using an obesity-induced hypertension model in rats. Chronic administration of caused a marked reduction in the body weight gain and Lee index of rats compared to the obesogenic diet-fed rats. Its administration also caused attenuation in blood pressure (systolic, diastolic, and mean), serum total cholesterol, triglyceride, and leptin, while an increase in serum HDL and adiponectin levels was noticed. The catalase and superoxide dismutase enzymatic activities were found to be remarkable in the serum of -treated animal groups. showed mild to moderate diuretic, hepatoprotective, and reno-protective effects. treated group showed less mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase while the mRNA expression of peroxisome proliferator-activated receptor and mRNA expression of cholesterol 7 alpha-hydroxylase were raised in comparison to the hypertensive group of rats evaluated by quantitative real-time polymerase chain reaction. These findings show that possesses antihypertensive and diuretic activities, thus providing a rationale to the medicinal use of in cardiovascular ailments.
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http://dx.doi.org/10.3389/fphar.2021.670433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299705PMC
July 2021

In Vitro Antioxidant Activities and the Therapeutic Potential of Some Newly Synthesized Chalcones Against 4-Acetaminophenol Induced Hepatotoxicity in Rats.

Dose Response 2021 Jan-Mar;19(1):1559325821996955. Epub 2021 Mar 15.

Department of Allied Health Sciences, Sargodha Medical College, University of Sargodha, Sargodha, Pakistan.

The lack of safety and efficacy of existing hepatoprotective agents urge the need to explore novel hepatoprotective agents. The research work was planned to study the therapeutic potential of some newly synthesized chalcones against 4-acetaminophenol induced hepatotoxicity in rats. Male albino rats (N = 30) were divided into 6 groups of 5 animals each i.e. group I; Toxic control (4-acetaminophenol), group II; normal control (Normal saline), group III; Positive control (silymarin; 50 mg/kg bw) and groups IV-VI (test groups) treated with 3 chalcone analogues i-e 3a, 3f & 3 g (100, 150, 150 mg/kg bw, respectively). All the study group animals were administered with 4-acetaminophenol to induce hepatotoxicity except normal control. Following hepatotoxicity induction, test group animals were administered with selected doses of test compounds and toxic group animals left untreated. Liver enzymes including ALT, AST, ALP and serum bilirubin were determined photometrically. Antioxidant activities of test compounds were also determined. Histopathological examination of liver biopsies was also carried out through H & E staining. The test chalcones (, & ) significantly decreased the levels of liver enzymes and serum bilirubin toward normal and the pattern of results in the test group animals were comparable to silymarin administered animals indicating the hepatoprotective potential of test compounds. Moreover, the test chalcones (, & ) antagonized the effect of 4-acetaminophenol and thus, raised the catalase (CAT) and superoxide dismutase (SOD) while decreased the malondialdehyde (MDA) in experimental animals. The test chalcones (, & ) on histological examination of liver showed improvement of tissue morphology. The study concluded that the tested compounds have antioxidant potential and may act as hepatoprotective agent. However, in-depth studies are required to validate their safety and to elucidate the exact mechanism of action.
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http://dx.doi.org/10.1177/1559325821996955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968038PMC
March 2021

A flavonoid driven phyto-pharmacological effects of Capparis decidua Edgew. in rodents.

Pak J Pharm Sci 2020 Jan;33(1(Supplementary)):333-342

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan.

This study elicits the underlying mechanism(s) of Capparis decidua when used for different gut disorders. HPLC chromatogram of C. decidua extract (CD.Cr) and its respective fractions showed a variety of phytochemicals of which, kaempferol being in a high proportion. In mice, CD.Cr at doses of 70 and 150 mg/kg enhanced the wet feces output to 33 and 44% respectively as compared to carbachol (47.6%), while doses of 500 and 700 mg/kg, presented 41 and 70% safety against castor oil-driven diarrhea, respectively. Its flavonoid constituent, kaempferol at doses of (50 and 100 mg/kg) produced 51.7 and 82% safety when compared to nifedipine which provided 95% safety at dose of 40 mg/kg against castor oil-driven diarrhea like loperamide. In isolated jejunum preparations, C. decidua extract and its respective fractions (except pet-ether) produced atropine-sensitive inhibitory effects, whereas kaempferol and nifedipine showed atropine insensitive effects. Against high K-induced contractions, C. decidua's fractions and kaempferol both exhibited a concentration-related non-specific inhibition while displacing the Ca -CRCs to right-ward with suppression in maximal response like nifedipine. In isolated rat ileal preparations, CD.Cr and respective fractions elicited atropine-sensitive gut excitatory responses. In summary, this article reports C. decidua's laxative effect through cholinergic receptor activation as well as its antidiarrheal effects, where its flavonoid constituent kaempferol produces Ca antagonist like activity, thus justifying C. decidua folk use in constipation and diarrhea.
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January 2020

The use of Euphorbia hirta L. (Euphorbiaceae) in diarrhea and constipation involves calcium antagonism and cholinergic mechanisms.

BMC Complement Med Ther 2020 Jan 16;20(1):14. Epub 2020 Jan 16.

The University of Haripur, Haripur, Khyber Pakhtunkhwa, Pakistan.

Background: Euphorbia hirta (Linn) family Euphorbiaceae has been used in indigenous system of medicine for the treatment of gastrointestinal disorders. This study was designed to determine the pharmacological basis for the medicinal use of E. hirta in diarrhea and constipation.

Methods: The aqueous-methanol extract of whole herb of E. hirta (EH.Cr) and its petroleum ether (Pet.EH), chloroform (CHCl.EH), ethyl acetate (Et.Ac.EH) and aqueous (Aq.EH) fractions were tested in the in-vivo experiments using Balb/c mice, while the in-vitro studies were performed on isolated jejunum and ileum preparations of locally bred rabbit and Sprague Dawley rats, respectively, using PowerLab data system.

Results: Qualitative phytochemical analysis showed the presence of alkaloids, saponins, flavonoids, tannins, phenols, cardiac glycosides, while HPLC of EH.Cr showed quercetin in high proportion. In mice, EH.Cr at the dose of 500 and 1000 mg/kg showed 41 and 70% protection from castor oil-induced diarrhea, respectively, similar to the effect of quercetin and loperamide, while at lower doses (50 and 100 mg/kg), it caused an increase in the fecal output. In loperamide-induced constipated mice, EH.Cr also displayed laxative effect with respective values of 28.6 and 35.3% at 50 and 100 mg/kg. In rabbit jejunum, EH.Cr showed atropine-sensitive inhibitory effect in a concentration-dependent manner, while quercetin and nifedipine exhibited atropine-insensitive effects. Fractions of E. hirta also produced atropine-sensitive inhibitory effects except Pet.EH and CHCl.EH. On high (80 mM) and low (20 mM) K - induced contractions, the crude extract and fractions exhibited a concentration-dependent non-specific inhibition of both spasmogens and displaced concentration-response curves of Ca to the right with suppression of the maximum effect similar to the effect quercetin and nifedipine. Fractions showed wide distribution of spasmolytic and Ca antagonist like effects. In rat ileum, EH.Cr and its fractions exhibited atropine-sensitive gut stimulant effects except Pet.EH.

Conclusion: The crude extract of E. hirta possesses antidiarrheal effect possibly mediated through Ca antagonist like gut inhibitory constituents, while its laxative effect was mediated primarily through muscarinic receptor agonist like gut stimulant constituents. Thus, these findings provide an evidence to the folkloric use of E. hirta in diarrhea and constipation.
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http://dx.doi.org/10.1186/s12906-019-2793-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076812PMC
January 2020

Pharmacological basis for the medicinal use of Alcea rosea in airways disorders and chemical characterization of its fixed oils through GC-MS.

Pak J Pharm Sci 2019 Sep;32(5(Supplementary)):2347-2355

Natural Product Research Division, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, Sindh, Pakistan.

Alcea rosea L. also known as Althea rosea belongs to the Malvaceae family. This medicinal herb, traditionally used to treat several conditions including airway disorders like asthma and chronic bronchitis. This study evaluated the bronchodilatory effects and possible mechanism of A. rosea on guinea-pig tracheal tissues. Moreover lipophilic profiling of A. rosea has been carried out by using Gas-Chromatography-Mass-Spectrometry. A total of 19 compounds have been identified from the plant, n-hexane fraction. These compounds have been further confirmed from their Van den Dool and Kratz (I) Indices. Major class of metabolite identified from the plant includes fatty acid, saturated and unsaturated fatty acid esters. Hydrocarbons have also been detected from the n-hexane fraction. These fatty acid esters have not been reported previously by GC-MS and were identified first time from the flowers of Alcea rosea. In-vitro experiments were performed on guinea-pig tracheal tissues, mounted in Kreb's solution at 37°C and bubbled with carbogen. In isolated guinea-pig trachea, A. rosea inhibited carbamylcholine and K+ (80 mM)-induced contractions, potentiated isoprenaline concentration-response curves (CRCs) and suppressed Ca CRCs. These results suggest that A. rosea cause bronchodilation through dual inhibition of phosphodiesterase enzyme and Ca influx, which substantiate its potential in airways disorders.
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September 2019

Evaluation of prokinetic and laxative effects of Hippophae rhamnoides in rodents.

Pak J Pharm Sci 2019 Sep;32(5(Special)):2527-2533

Natural Product Research Division, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, Sindh, Pakistan.

Hippophae rhamnoides (Family; Elaeagnaceae) fruit extract was investigated for prokinetic and gut excitatory effects to rationalize its therapeutic utility in gastrointestinal complaints like delayed gastric emptying and constipation. The fruit extract of Hippophae rhamnoides (Hr.Cr) prepared in hydro-methanol (30:70) was verified for flavonoids, tannins, coumarins and terpenes as plant constituents. In mice, Hr.Cr administration caused an increased in faecal production and charcoal meal transport (50-300mg/kg, per-oral.), similar to activity pattern of carbamylcholine (1 mg/kg). Laxative and prokinetic effects of Hr.Cr were found partially atropine-sensitive. On challenge with isolated intestinal tissues, Hr.Cr charged a dose-dependent spasmogenic effect on jejunum (0.01-1mg/mL) preparations of rabbit and in ileal tissues (guinea-pig) at the dose range of 0.03 to 3mg/mL, following predominant relaxing impact at increased concentrations. Unlike carbamylcholine, stimulant effect of Hr.Cr was partly antagonized in atropine incubated tissues. These data attest the laxative, prokinetic and gut excitatory activities of Hippophae rhamnoides probably mediated through partial activation of muscarinic receptors. Further in agreement of the current findings with earlier reports on gastric emptying effects of Hippophae rhamnoides seed oil, this is the first study of its kind providing insight into mechanism to the laxative potential of Hippophae rhamnoides fruit, thus rationalizing its medicinal use in constipation.
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September 2019

Role of cadmium and arsenic as endocrine disruptors in the metabolism of carbohydrates: Inserting the association into perspectives.

Biomed Pharmacother 2019 Jun 25;114:108802. Epub 2019 Mar 25.

Institute of Pharmacy, Physiology and Pharmacy, University of Agriculture, Faisalabad, Pakistan. Electronic address:

Endocrine disrupting chemicals (EDCs) have widespread environmental distribution originated from both natural and anthropogenic sources. From the last few decades, their contamination has been raised dramatically owing to continuous discharge in sewage and untreated industrial effluents. They have rapidly gained a considerable attention due to their critical role in the development of multiple endocrine-related disorders notably diabetes mellitus (DM). Cadmium and arsenic, among the most hazardous EDCs, are not only widely spread in our environment, but they are also found to be associated with wide range of health hazards. After entering into the human body, they are preferably accumulated in the liver, kidney and pancreas where they exhibit deleterious effects on carbohydrate metabolism pathways notably glycolysis, glucogenesis and gluconeogenesis through the modification and impairment of relevant key enzymes activity. Impairment of hepatic glucose homeostasis plays a crucial role in the pathogenesis of DM. Along with compromised function of pancreas and muscles, diminished liver and kidney functions also contribute considerably to increase the blood glucose level. These metals have potential to bring conformational changes in these enzymes and make them inactive. Additionally, these metals also disturb the hormonal balance, such as insulin, glucocorticoids and catecholamines; by damaging pancreas and adrenal gland, respectively. Moreover, these metals also enhance the production of reactive oxygen species and depress the anti-oxidative defense mechanism with subsequent disruption of multiple organs. In this article, we have briefly highlighted the impact of arsenic and cadmium on the metabolism of carbohydrates and the enzymes that are involved in carbohydrate metabolism and glucose homeostasis.
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http://dx.doi.org/10.1016/j.biopha.2019.108802DOI Listing
June 2019

Medical simulator, an innovative tool for experiential learning, application and reflection of knowledge.

J Pak Med Assoc 2018 Jul;68(7):1142

Department of Biological & Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

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July 2018

Faculty Development Initiatives: A prerequisite for capacity building and enhanced productivity in a medical institution.

J Pak Med Assoc 2018 Jun;68(6):848-851

Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, Pakistan.

Objective: To determine the contribution of teaching, learning and assessment forum's initiatives on professional development of faculty and staff.

Methods: This retrospective study was conducted at the Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, from July to December 2016, and comprised teaching, learning and assessment activities carried out from 2012 to 2015. The responses acquired from feedback evaluation were recorded at the end of activity on a Likert-type scale ranging from 1-5. Positive responses were presented for each variable with respective activity type across the study years. The association of the effectiveness of teaching, learning and assessment between type of event and yearly outcome was also assessed.

Results: A total of 66activities were held during the study period. Of them, 49(74.24%) were workshops/human resource trainings, 5(7.57%) were courses and 12(18.18%) were seminars. Together, they involved over 500 participants. Objectives, disclosure statement, contents, level of interaction, acquired knowledge, time management, queries responded, organisational activity, course material and overall assessment showed consistent positive response across the years, but the acquisition of new knowledge differed significantly (p<0.05) through the study years.

Conclusions: Teaching, learning and assessment initiatives, play a positive role in professional development of faculty and staff.
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June 2018

Helicobacter pylori outer membrane protein Q genotypes and their susceptibility to anti-adhesive phytotherapeutic agents.

J Integr Med 2017 09;15(5):398-406

Department of Medicine, Aga Khan University, Karachi 74800, Pakistan.

Objective: Helicobacter pylori is a Gram-negative organism. Its outer membrane protein Q (HopQ) mediates host-pathogen interactions; HopQ genotypes 1 and 2 are found associating with gastroduodenal pathologies. The authors measured the anti-adhesion effects of the extracts of Abelmoschus esculentus, Zingiber officinale, Trachyspermum ammi, Glycyrrhiza glabra, Curcuma longa and Capsicum annum against HopQ genotypes and H. pylori cytotoxin-associated gene A (CagA).

Methods: DNA was extracted by polymerase chain reaction of the HopQ genotypes (i.e., type 1, type 2 and CagA) from 115 H. pylori strains. The effect of the extracts from selected dietary ingredients was determined using a gastric adenocarcinoma cell line and a quantitative DNA fragmentation assay. The anti-adhesive effect of these extracts on H. pylori was tested using an anti-adhesion analysis.

Results: C. annum, C. longa and A. esculentus showed prominent anti-adhesion effects with resultant values of 17.3% ± 2.9%, 14.6% ± 3.7%, 13.8% ± 3.6%, respectively, against HopQ type 1 and 13.1% ± 1.7%, 12.1% ± 2%, 11.1% ± 1.6%, respectively, against HopQ type 2. C. longa (93%), C. annum (89%) and A. esculentus (75%) had better anti-adhesive activity against H. pylori with HopQ type 1 compared to HopQ type 2 with respective values of 70%, 64% and 51%. Extracts of C. annum (14.7% ± 4.1%), A. esculentus (12.3% ± 4.1%) and Z. officinale (8.4% ± 2.8%) had an anti-adhesion effect against CagA-positive H. pylori strains compared to CagA-negative strains.

Conclusion: The anti-adhesion properties of the tested phytotherapeutic dietary ingredients were varied with HopQ genotypes. HopQ type 1 was found to be more sensitive to extracts of C. annum, C. longa and A. esculentus compared to the HopQ type 2 genotype.
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http://dx.doi.org/10.1016/S2095-4964(17)60359-5DOI Listing
September 2017

Studies on antihyperlipidemic and endothelium modulatory activities of polyherbal formulation (POL4) and its ingredients in high fat diet-fed rats.

Pak J Pharm Sci 2017 Jan;30(1 Suppl):295-301

Natural Product Research Division, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, Pakistan / Pakistan Council for Science and Technology, G-5/2, Islamabad, Pakistan.

A compound herbal formulation (POL) is used traditionally in interior parts (Distt. Badin) of Sindh, Pakistan, for the treatment of metabolic disorders like diabetes and hyperlipidemia. This study is aimed to determine the effectiveness of POL and its ingredients in hyperlipidemia and associated endothelial dysfunction and hypertension. POL is composed of equal proportion of Nigella sativa, Cichorium intybus, Trigonella foenum graecum and Gymnema sylvestre mixed in powdered form. Chronic (6 to 7 weeks) administration of POL and its ingredients mixed in diet caused a notable attenuation in total cholesterol, low density lipoprotein cholesterol, triglycerides, atherogenic index, C-reactive protein and glucose, while it has increased high density lipoprotein levels. POL4 intervention markedly (p<0.01) reduced systolic blood pressure in rats to 127±1.92 vs. 145.4±1.07 mm of Hg using tail-cuff method and significantly (p<0.05) improved endothelium-dependent relaxation (75±2.88 vs. 82.75±1.22%) to acetylcholine in isolated aortae of rats in treatment groups using force transducer and PowerLab system. Similar activities were assessed on the part of ingredients of POL. These findings indicate that POL4 and its ingredients possess antihyperlipidemic, endothelium-dependent modulatory and antihypertensive activities, thus providing an evidence to the vernacular use of POL in hyperlipidemia and hypertension.
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January 2017

Cytokine changes in gastric and colonic epithelial cell in response to Planta ovata extract.

J Complement Integr Med 2017 Mar;14(2)

Background Psyllium (Planta ovata, Ispaghul) seed and husk are used for treatment of altered bowel habit, i. e. constipation and diarrhea. We studied the effect of Ispaghul extract on secretion of interleukin-1 beta (IL-1β) by AGS (ATCC CRL 1739) and SW480 (ATCC CCL-227) epithelial cell lines and determined whether Ispaghul extract has an effect on IL-1β secretion by Helicobacter pylori (H. pylori)-stimulated AGS cell and Escherichia coli K-12 (E. coli K-12)-stimulated SW480 cells in vitro. Methods The AGS cells and SW480 cells were pretreated with Ispaghul extract in concentrations, i. e. 3.5 and 7 μg/mL prior to infection with H. pylori and E. coli K-12. Results DNA fragmentation in AGS and SW480 cells treated with Ispaghul extract was not significant (2.3±0.8 %) compared with untreated cells (2.2±0.6 %). Ispaghul extract decreased the H. pylori-stimulated secretion of IL-1β by AGS cell (p<0.0001). This effect did not increase as the concentration of extract was increased. Ispaghul extract also decreased E. coli K-12-stimulated IL-1β secretion by SW480 cell (p<0.0001). This effect increased as the concentration of extracts was increased. Conclusions Ispaghul extract had an effect on stimulated secretion of IL-1β by the AGS and SW480 cell. It decreased pro-inflammatory reaction from both cell lines stimulated by bacteria.
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http://dx.doi.org/10.1515/jcim-2015-0075DOI Listing
March 2017

Pharmacological basis for the medicinal use of polyherbal formulation and its ingredients in cardiovascular disorders using rodents.

BMC Complement Altern Med 2017 Mar 7;17(1):142. Epub 2017 Mar 7.

Natural Product Research Division, Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.

Background: A compound herbal formulation (POL) has been used in the indigenous system of medicine to treat cardiometabolic disorders like diabetes and associated hypertension. POL and most of its constituents have not been studied widely for its therapeutic use in hypertension. This study is aimed to determine the efficacy and possible insight into mechanism(s) for the medicinal use of POL and its ingredients in hypertension.

Methods: The aqueous methanolic extracts of POL (POL.Cr) and its components [Cichorium intybus (Ci.Cr), Gymnema sylvestre (Gs.Cr), Nigella sativa (Ns.Cr) and Trigonella foenum graecum (Tfg.Cr)] were tested for blood pressure lowering activity in anaesthetized Sprague-Dawley rats. To assess the vasomodulatory effect, isolated tissue experiments were performed on rat aortic strips using isometric force transducer coupled with PowerLab data acquisition system.

Results: Administration of POL to rats caused a dose-dependent (1-100 mg/kg) fall in mean arterial pressure (MAP) with maximum effect of 85.33 ± 1.76% at 100 mg/kg, similar to the effect of verapamil. All ingredients of POL also decreased blood pressure with varying efficacy in following order Ns.Cr ≅ Ci.Cr > Tfg.Cr > Gs.Cr. In rat aortic preparations, POL and its ingredients inhibited K (80 mM)-induced contractions, Ci.Cr was the most potent followed by Ns.Cr > Tfg.Cr > Gs.Cr ≅ POL. Against phenylephrine (P.E) contractions, Ci.Cr and Tfg.Cr exhibited complete relaxation, while POL.Cr, Gs.Cr and Ns.Cr showed vasomodulatory effect. The Ca antagonist activity was confirmed when POL and its ingredients shifted Ca concentrations-response curves to the right in a manner similar to that of verapamil. On baseline of rat aorta, the parent formulation and its ingredients (except Tfg.Cr) exhibited partially phentolamine (1 μM)-sensitive vasoconstriction.

Conclusion: These data show that POL and its constituents possess blood pressure lowering activity mediated through inhibition of Ca influx via membranous Ca channels and receptor (α-adrenergic) operated pathways. Thus, this study provides a rationale to the medicinal use of POL and its constituents in hypertension.
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http://dx.doi.org/10.1186/s12906-017-1644-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341478PMC
March 2017

The Prokinetic, Laxative, and Antidiarrheal Effects of Morus nigra: Possible Muscarinic, Ca(2+) Channel Blocking, and Antimuscarinic Mechanisms.

Phytother Res 2016 Aug 27;30(8):1362-76. Epub 2016 May 27.

H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi, Karachi, Sindh, 75270, Pakistan.

Morus nigra Linn. (black mulberry) is used in gastrointestinal ailments. This study demonstrates gut modulatory properties of M. nigra. The prokinetic, laxative, and antidiarrheal activities of M. nigra were assessed in mice, while isolated rabbit jejunum and guinea-pig ileum were used to explore insight into mechanism(s). At 30 and 70 mg/kg, the crude extract of M. nigra (Mn.Cr) exhibited atropine-sensitive prokinetic and laxative effects, similar to carbachol (CCh). While at higher doses (100, 300, and 500 mg/kg), Mn.Cr offered protection against castor oil-induced diarrhea. In rabbit jejunum, Mn.Cr and its chloroform fraction inhibited CCh-induced contractions more potently compared with high K(+) (80 mm). Conversely, petroleum fraction was more potent against high-K(+) -induced contractions. At 0.01 mg/mL, Mn.Cr caused a parallel shift in acetylcholine concentration-response curves (CRCs) followed by a non-parallel shift at 0.03 mg/mL, similar to dicyclomine. At further tested concentrations, Mn.Cr (0.1 and 0.3 mg/mL) and petroleum fraction suppressed Ca(2+) CRCs, similar to verapamil. In guinea-pig ileum, Mn.Cr, its aqueous and ethyl acetate fractions exhibited atropine-sensitive gut stimulant activity along with additional uncharacterized excitatory response in the aqueous fraction only. These results suggest that black mulberry possesses prokinetic, laxative, and antidiarrheal effects, putatively mediated through cholinomimetic, antimuscarinic, and Ca(2+) antagonist mechanisms, respectively. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/ptr.5641DOI Listing
August 2016

Immunomodulatory Effects of Psyllium Extract on Helicobacter pylori Interaction With Gastric Epithelial Cells.

J Evid Based Complementary Altern Med 2016 Oct 16;21(4):NP18-24. Epub 2015 Oct 16.

Aga Khan University, Karachi, Pakistan.

Natural plant product Psyllium has anti-inflammatory activity that can modulate the function of cytokines. We determined the effect of Psyllium husk extract on interleukin (IL)-8 and NF-κB secretion by gastric epithelial cells in response to Helicobacter pylori Human gastric adenocarcinoma cell line (AGS) cells were pretreated with Psyllium extract in different concentrations before H pylori infection. Cell culture supernatant was analyzed for IL-8 and NF-κB by ELISA. RNA from cells was used for real-time polymerase chain reaction for messenger RNA expression of IL-8. Psyllium extract 5 and 10 μg/mL markedly (P < .001) lowered basal IL-8 by 64.71% and 74.51%, respectively, and H pylori-stimulated IL-8 was also (P < .001) lowered by 41.67% and 66.67%, respectively. Psyllium 5 and 10 μg/mL also reduced (P < .0001) cagA-positive H pylori-induced IL-8 mRNA expression by 42.3% and 67.6%, respectively. Psyllium also reduced (P = .0001) NF-κB in response to H pylori strains confirming its role as an anti-inflammatory agent.
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http://dx.doi.org/10.1177/2156587215611517DOI Listing
October 2016

Antidiarrhoeal, antisecretory and antispasmodic activities of Matricaria chamomilla are mediated predominantly through K(+)-channels activation.

BMC Complement Altern Med 2015 Mar 24;15:75. Epub 2015 Mar 24.

Natural Product Research Division, Department of Biological and Biomedical Sciences, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, 74800, Pakistan.

Background: Matricaria chamomilla commonly known as "Chamomile" (Asteraceae) is a popular medicinal herb widely used in indigenous system of medicine for a variety of ailments. However, there is no detailed study available showing its effectiveness in hyperactive gut disorders like, abdominal colic and diarrhoea. This study was designed to determine the pharmacological basis for the folkloric use of Matricaria chamomilla in diarrhoea.

Methods: The crude aqueous-methanolic extract of Matricaria chamomilla (Mc.Cr) was studied for its protective effect in mice against castor oil-induced diarrhoea and intestinal fluid accumulation. The isolated rabbit jejunum was selected for the in-vitro experiments using tissue bath assembly coupled with PowerLab data acquisition system.

Results: Oral administration of Mc.Cr to mice at 150 and 300 mg/kg showed marked antidiarrhoeal and antisecretory effects against castor oil-induced diarrhoea and intestinal fluid accumulation, simultaneously, similar to the effects of cromakalim and loperamide. These effects of plant extract were attenuated in animals pretreated with K(+) channel antagonist, glibenclamide (GB) or 4-aminopyridine (4-AP). When tested in isolated rabbit jejunum, Mc.Cr caused a dose-dependent (0.3-3 mg/ml) relaxation of spontaneous and low K(+) (25 mM)-induced contractions, while it exhibited weak inhibitory effect on high K(+) (80 mM). The inhibitory effect of Mc.Cr on low K(+)-induced contractions was partially inhibited in the presence of GB, while completely blocked by 4-AP. Cromakalim, an ATP-sensitive K(+) channel opener, caused complete relaxation of low K(+)-induced contractions with little effect on high K(+). Pretreatment of tissues with GB blocked the inhibitory effects of cromakalim on low K(+), while the presence of 4-AP did not alter the original effect. Verapamil, a Ca(++) channel antagonist, caused complete relaxation of both low and high K(+)-induced contractions with similar potency. The inhibitory effect of verapamil was insensitive to GB or 4-AP. When assessed for Ca(++) antagonist like activity, Mc.Cr at high concentrations caused rightward shift in the Ca(++) concentration-response curves with suppression of the maximum response, similar to the effect of verapamil, while cromakalim did not show similar effect.

Conclusions: This study indicates that Matricaria chamomilla possesses antidiarrhoeal, antisecretory and antispasmodic activities mediated predominantly through K(+)-channels activation along with weak Ca(++) antagonist effect.
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http://dx.doi.org/10.1186/s12906-015-0595-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410481PMC
March 2015

Coadministration of black seeds and turmeric shows enhanced efficacy in preventing metabolic syndrome in fructose-fed rats.

J Cardiovasc Pharmacol 2015 Feb;65(2):176-83

*Natural Product Research Unit, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, Pakistan; †H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan; and ‡College of Health Sciences, Mekelle University, Mekelle, Ethiopia.

Among noncommunicable diseases, metabolic syndrome (MS), a cluster of metabolic disorders including obesity, hyperglycemia, hyperlipidemia and hypertension, is highly prevalent in modern society. Its management requires lifestyle modifications and/or the life-long use of multiple medications, hence demanding development of safe alternative remedies. This study was aimed to establish the efficacy of combined use of black seeds and turmeric using fructose-fed rat model of MS. The high-performance liquid chromatographic fingerprints of turmeric and black seeds showed the presence of curcumin and thymoquinone, respectively, as their major constitutes. Different doses of black seeds and turmeric, individually and in combination, were administered to fructose-fed rats for up to 6 weeks representing characteristic features of MS. At 3 weeks of the treatment, black seeds and turmeric lowered (P < 0.01) high blood pressure and low-density lipoprotein cholesterol, respectively, whereas their coadministration reduced (P < 0.01) both high blood pressure and hypertriglyceridemia. At 6 weeks, the coadministration of both herbs, at half the doses of individual herbs, was the most effective (P < 0.001) in preventing hypertension, hyperglycemia, dyslipidemia, hyperinsulinemia, and endothelial dysfunction than the individual herbs. This study demonstrates the therapeutic superiority of the combination of black seeds and turmeric at low doses over individually tested herbs, in improving features of MS.
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http://dx.doi.org/10.1097/FJC.0000000000000179DOI Listing
February 2015

Pharmacological basis for the medicinal use of Carissa carandas in constipation and diarrhea.

J Ethnopharmacol 2014 Apr 25;153(2):359-67. Epub 2014 Feb 25.

Natural Product Research Division, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan; Department of Pharmacy, College of Health Sciences, Mekelle University, P.O. Box 1871, Mekelle, Ethiopia. Electronic address:

Ethnopharmacological Relevance: Carissa carandas Linn. commonly known as "Karaunda" (Apocynaceae) is a popular medicinal herb widely distributed in different parts of Pakistan. In addition to other medicinal uses, Carissa carandas is popular in indigenous system of medicine for its medicinal use in gut motility disorders like, constipation and diarrhea.

Objective: This study was planned to provide pharmacological basis to the medicinal use of Carissa carandas in constipation and diarrhea.

Materials And Methods: The crude extract of the leaves of Carissa carandas (Cc.Cr) was prepared in methanol and its fractionation was carried out with ethylacetate, petroleum ether and n-butanol. In-vivo studies were conducted on mice, while isolated rabbit jejunum and guinea-pig ileum preparations were used for the in-vitro experiments. The spasmogenic and spasmolytic responses of gut tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system.

Results: The HPLC fingerprints of Cc.Cr, its petroleum (Cc.Pef), ethylacetate (Cc.Eaf) and n-butanol (Cc.Baf) fractions showed the presence of oleanolic acid, ursolic acid, stigmasterol and β-sitosterol. Oral administration of Cc.Cr to mice increased fecal output at lower doses (30 and 50 mg/kg), while it showed protection against castor oil-induced diarrhea at higher doses (300 and 600 mg/kg). In isolated guinea-pig ileum and rabbit jejunum, Cc.Cr and Cc.Baf exhibited stimulatory effect at 0.003-3 mg/ml, which was partially sensitive to atropine or pyrillamine or partially/fully sensitive to atropine+pyrillamine, followed by relaxation at higher tested concentrations, being more potent in rabbit tissues. The ethylacetate fraction (0.1-5 mg/ml) exhibited fully atropine-sensitive contractions in both guinea-pig and rabbit tissues, being more potent in guinea-pig while more efficacious in rabbit tissues. However, the petroleum fraction (0.003-1.0 mg/ml) showed only spasmolytic activity in spontaneously contracting rabbit tissues, similar to nifedipine. In guinea-tissue, Cc.Pef did not cause any stimulant effect. When studied against high K(+) (80 mM)-induced contraction, the crude extract and its fractions caused a dose-dependent inhibition, with the following order of potency: Cc.Pef>Cc.Eaf>Cc.Cr≥Cc.Baf, similar to nifedipine indicating Ca(++) channel antagonist like activity, which was further confirmed when the plant extract displaced Ca(++) curves to the right with suppression of maximum effect similar to that of nifedipine.

Conclusion: This study demonstrates that the crude extract of Carissa carandas possesses a gut-stimulatory effect mediated primarily through the activation of muscarinic and histaminergic receptors while its spasmolytic effect was mediated possibly through Ca(++) antagonist pathway. Thus, this study provides a clear evidence for the dual effectiveness of Carissa carandas in constipation and diarrhea, thus validating its medicinal use.
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http://dx.doi.org/10.1016/j.jep.2014.02.024DOI Listing
April 2014

Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities.

BMC Complement Altern Med 2013 Dec 26;13:371. Epub 2013 Dec 26.

Natural Product Research Division, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan.

Background: Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs.

Methods: To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay.

Results: Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO.

Conclusion: The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO.
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http://dx.doi.org/10.1186/1472-6882-13-371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029524PMC
December 2013

Antispasmodic and antidiarrheal activities of rhizomes of Polygonatum verticillatum maneuvered predominately through activation of K⁺ channels: Components identification through TLC.

Toxicol Ind Health 2016 Apr 8;32(4):677-85. Epub 2013 Nov 8.

International Centre for Chemical Sciences, HEJ Research Institute of Chemistry, University of Karachi, Karachi, Pakistan.

Polygonatum verticillatum has traditionally been used for various purposes. The present study was aimed to validate the antispasmodic and antidiarrheal properties of crude methanolic extract of rhizomes of P. verticillatum (PR). Isolated rabbit jejunum preparations were suspended in tissue baths to measure the isotonic responses using Power Lab data acquisition system for the antispasmodic activity of PR, while the antidiarrheal activity was conducted in vivo in mice. PR caused complete relaxation of the spontaneous contractions of isolated rabbit jejunum preparations in a dose-dependent mode. A complete inhibition was observed against low potassium (K(+); 25 mM)-induced contractions, while the plant extract partially inhibited the high K(+)(80 mM)-induced contractions. From a mechanistic point of view, the spasmolytic effect of PR against low K(+)was antagonized by glibenclamide similar to the effect of cromakalim, thus showing the presence of constituents in PR mediating spasmolytic activity predominantly through the activation of adenosine triphosphate-sensitive K(+)channels. When tested against castor oil-induced diarrhea in mice, oral administration of the plant extract manifested marked antidiarrheal activity at the doses of 500 and 1000 mg/kg similar to loperamide. This study provided a pharmacological basis for the medicinal use of PR in abdominal colic and diarrhea.
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http://dx.doi.org/10.1177/0748233713506956DOI Listing
April 2016

Studies on tracheorelaxant and anti-inflammatory activities of rhizomes of Polygonatum verticillatum.

BMC Complement Altern Med 2013 Jul 29;13:197. Epub 2013 Jul 29.

Background: The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders.

Methods: The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode's solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the lipoxygenase inhibitory activity was performed in the in-vitro assay. Various chromatographic and spectroscopic techniques were used for the isolation and characterization of pure molecules.

Results: In isolated guinea-pig tracheal preparations, PR caused complete inhibition of the high K+ (80 mM) and carbachol-induced contractions however, it was more potent against K+ than CCh, similar to verapamil. Pretreatment of the tissue with PR, displaced the Ca2+ concentration-response curves to the right, similar to that induced by verapamil, indicating the presence of Ca2+ channel blocking like activity. When tested on carrageenan-induced rat paw edema, PR demonstrated a marked reduction in edema with 65.22% protection at 200 mg/kg, similar to aspirin. In the in-vitro assay, PR showed lipoxygenase inhibitory activity (IC50: 102 ± 0.19 μg/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and β-sitosterol.

Conclusions: These results indicate that the plant possesses tracheorelaxant, mediated possibly through a Ca2+ channel blockade mechanism, and anti-inflammatory activities, which may explain the medicinal use of this plant in airway disorders and inflammation.
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http://dx.doi.org/10.1186/1472-6882-13-197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772698PMC
July 2013

Bronchodilator activity of aerial parts of Polygonatum verticillatum augmented by anti-inflammatory activity: attenuation of Ca²⁺ channels and lipoxygenase.

Phytother Res 2013 Sep 29;27(9):1288-92. Epub 2012 Oct 29.

Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan.

Polygonatum verticillatum is commonly used for the treatment of asthma and inflammation. The current study was aimed to scrutinize the pharmacological profile of methanolic extract of the aerial parts (PA). Isolated tracheal preparations were used for the evaluation of bronchodilatory activity, whilst the in vivo carrageenan-induced paw oedema test and an in vitro lipoxygenase (LOX) inhibitory assay were used for the assessment of the anti-inflammatory profile of PA. When tested against carbachol and K⁺ (80 mM)-induced contractions, PA caused complete inhibition of isolated rabbit tracheal preparations in a dose-dependent mode, similar to verapamil. While elucidating possible mechanism, PA shifted the Ca²⁺ concentration-response curves to the right, analogous to that produced by verapamil, confirming a Ca²⁺ channel blocker-like activity. PA provoked profound reduction in paw oedema with a maximum protection of 60.87% at 200 mg/kg i.p. in a dose-dependent manner which was augmented by its prominent LOX inhibitory activity (IC₅₀ : 125 µg/mL). These findings authenticated its therapeutic potential in the treatment of asthmatic and inflammatory conditions.
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http://dx.doi.org/10.1002/ptr.4860DOI Listing
September 2013

Evaluation of gut modulatory and bronchodilator activities of Amaranthus spinosus Linn.

BMC Complement Altern Med 2012 Oct 1;12:166. Epub 2012 Oct 1.

Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.

Background: The aqueous-methanolic extract of Amaranthus spinosus (A. spinosus Linn.,) whole plant, was studied for its laxative, spasmolytic and bronchodilator activities to validate some of its medicinal uses.

Methods: The crude extract of A. spinosus was studied in-vivo for bronchodilator and laxative activities and in-vitro using isolated tissue preparations which were mounted in tissue baths assembly containing physiological salt solutions, maintained at 37°C and aerated with carbogen, to assess the spasmolytic effect and to find out the possible underlying mechanisms.

Results: In the in-vivo experiments in mice, the administration of A. spinosus increased fecal output at doses of 100 and 300 mg/kg showing laxative activity. It also inhibited carbachol-induced bronchospasm in anesthetized rats at 1, 3, 10 and 30 mg/kg indicative of bronchodilator activity. When tested on isolated gut preparations, the plant extract showed a concentration-dependent (0.01-10.0 mg/ml) spasmogenic effect in spontaneously contracting rabbit jejunum and guinea-pig ileum. The spasmogenic effect was partially blocked in tissues pretreated with atropine (0.1 μM). When tested on K+ (80 mM)-induced sustained contractions in isolated rabbit jejunum, the plant extract caused complete relaxation and also produced a shift in the Ca++ concentration-response curves (CRCs) towards right, similar to diltiazem. In rabbit trachea, the plant extract completely inhibited K+ (80 mM) and carbachol (CCh, 1 μM)-induced contractions at 1 mg/ml but pretreatment of tissue with propranolol (1 μM), caused around 10 fold shift in the inhibitory CRCs of the plant extract constructed against CCh-induced contraction. The plant extract (up to 0.3 mg/ml) also increased both force and rate of spontaneous contractions of isolated guinea-pig atria, followed by relaxation at higher concentration (1.0-5.0 mg/ml). The cardio-stimulant effect was abolished in the presence of propranolol, similar to that of isoprenaline. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the organic fraction, whereas the spasmogenic component was concentrated in the aqueous fraction.

Conclusion: These results indicate that A. spinosus possesses laxative activity partially mediated through cholinergic action. The spasmolytic effect was mediated through calcium channel blocking (CCB), while bronchodilator activity through a combination of β-adrenergic and CCB pathways, which may explain the traditional uses of A. spinosus in gut and airways disorders.
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http://dx.doi.org/10.1186/1472-6882-12-166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545920PMC
October 2012

Species differences in the antidiarrheal and antispasmodic activities of Lepidium sativum and insight into underlying mechanisms.

Phytother Res 2013 Jul 25;27(7):1086-94. Epub 2012 Sep 25.

Natural Product Research Unit, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan.

The aim of this study was to see if the crude extract of Lepidium sativum (Ls.Cr) exhibits species specificity in its antidiarrheal and antispasmodic activities along with insight into the underlying mechanisms using the in-vivo and in-vitro experiments. Ls.Cr inhibited castor oil-induced diarrhea in mice at doses (300 and 1000 mg/kg) three times higher dose than for rats. In isolated rat ileum and jejunum, Ls.Cr completely inhibited carbachol (CCh), low K⁺ (25 mM) and high K⁺ (80 mM)-induced contractions, while in guinea-pig tissues, Ls.Cr caused complete inhibition of only CCh-induced contraction. In rabbit tissues, Ls.Cr completely inhibited CCh and low K⁺-induced contractions sensitive to K⁺ channel antagonists. Pretreatment of guinea-pig and rat tissues with Ls.Cr caused a rightward shift in CCh-induced contractions in a pattern similar to dicyclomine, while in rabbit and rat tissues, Ls.Cr shifted isoprenaline curves to the left similar to papaverine. These data indicate that the antidiarrheal and antispasmodic activities of L. sativum are species dependent, mediating its antispasmodic effect through combinations of multiple pathways including activation of K⁺ channels, and inhibition of muscarinic receptors, Ca⁺⁺ channels and PDE enzyme. Rat tissues showed the highest potency. Based on the results, we recommend using multiple species to know the real pharmacological profile of medicinal products.
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http://dx.doi.org/10.1002/ptr.4819DOI Listing
July 2013

Studies on prokinetic, laxative and spasmodic activities of Phyllanthus emblica in experimental animals.

Phytother Res 2013 Jul 12;27(7):1054-60. Epub 2012 Sep 12.

Natural Product Research Division, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi 74800, Pakistan.

This study was aimed to provide pharmacological basis for the medicinal use of Phyllanthus emblica fruit in indigestion and constipation using the in-vivo and in-vitro assays. The crude extract of the dried fruits of Phyllanthus emblica (Pe.Cr) and its fractions were tested positive for alkaloids, saponins, tannins, terpenes, flavonoids, sterols and coumarins. Pe.Cr at the doses of 100 and 300 mg/kg exhibited the prokinetic and laxative activities in mice, which were found partially sensitive to atropine. In isolated guinea-pig ileum and rabbit jejunum, the crude extract and its aqueous fraction (Pe.Aq) caused concentration-dependent and partially atropine-sensitive stimulatory effects followed by relaxation at higher tested concentrations, being more efficacious in guinea pig, while more potent in rabbit tissues. The petroleum fraction (0.003-0.1 mg/mL) exhibited fully atropine-sensitive contractions in both guinea-pig and rabbit tissues. However, the ethyl acetate and chloroform fractions (0.003-1.0 mg/mL) showed only spasmolytic activity when studied in spontaneously contracting rabbit jejunum. This study showed that the Phyllanthus emblica possesses prokinetic and laxative activities in mice along with spasmodic effect in the isolated tissues of guinea pig and rabbit, mediated partially through activation of muscarinic receptors; thus, this study provides a rationale for the medicinal use of Phyllanthus emblica fruits in indigestion and constipation.
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http://dx.doi.org/10.1002/ptr.4821DOI Listing
July 2013
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