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Year : 2015  |  Volume : 47  |  Issue : 7  |  Page : 4-7

Gufic Prize

Date of Web Publication11-Dec-2015

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How to cite this article:
. Gufic Prize. Indian J Pharmacol 2015;47, Suppl S1:4-7

How to cite this URL:
. Gufic Prize. Indian J Pharmacol [serial online] 2015 [cited 2023 Jun 10];47, Suppl S1:4-7. Available from: https://www.ijp-online.com/text.asp?2015/47/7/4/171562


Effectiveness of Malabaricone-A in Multidrug Resistant Cancer Cell Lines

Nafisha Yasmin 1 , Alak Manna 1 , Sritama De Sarkar 1 , Ajay K Bauri 2 , Subrata Chattopadhyay 2 , Mitali Chatterjee 1

1 Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India, 2 Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai, Maharashtra, India

Objectives: A major impediment in treatment for cancers is resistance to chemotherapy which has been attributed to over expression of efflux pumps. The cytotoxicity of malabaricones has been demonstrated in leukemic cell lines, but its effectiveness in drug resistant cell lines has not been evaluated. This study aimed to evaluate the cytotoxicity of malabaricones in human hematopoietic cancer cell lines having a high level of multidrug resistance as evident by enhanced activity of P-glycoprotein. Materials and Methods: Cell lines (leukemias and multiple myelomas) were indirectly evaluated for their multidrug resistance status by examining the expression of P-glycoprotein (P-gp) by Flow cytometry using calcein-AM and verapamil. Cell viability of malabaricone-A was assessed by the tetrazolium 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium (MTS-PMS) assay. Results: The fluorescence of calcein was significantly decreased in three cell lines LP-1, RPMI-8226 and CEM ADR 5000, and its reversal with verapamil confirmed their increased presence of P-glycoprotein. The mean IC 50 of MAL-A in these three MDR + cell lines ranged from 5.40 ± 1.41 to 12.33 ± 0.78 μg/ml and was comparable with the MDR - cell lines whose IC 50 ranged from 9.72 ± 1.08 to 19.26 ± 0.75 μg/ml in leukemic cell lines and 9.65 ± 0.39 to 18.05 ± 0.17 μg/ml in multiple myeloma cell lines. Conclusion: The cytotoxicity of MAL-A in cell lines having high P-gp activity was comparable with cell lines having low P-gp activity, making it worthy of future pharmacological consideration.


Antifibrotic Effect of Nox-II Inhibitor Apocynin in Rat Model of Bile Duct Ligation-induced Liver Fibrosis

Rudra Vyas S, Madhuri Panchakshari K, Kirti Patel V, Rathod SP

Department of Pharmacy, MS University, Vadodara, Gujarat, India

Objectives: Excessive extracellular matrix deposition based on complex interactions between matrix-producing hepatic stellate cells, liver regeneration is the key mechanism of liver fibrosis. Complete biliary obstruction causes cholestatic injury to the liver, including hepatocellular necrosis and apoptosis, bile duct epithelial cell proliferation, stellate cell activation, and, finally liver fibrosis. NOX-II is an enzyme from NADPH oxidase family which triggers the generation of oxidative stress in liver leading to fibrotic condition. So NOX-II inhibition would be the novel approach to treat liver fibrosis. To evaluate effect of apocynin a NOX-II inhibitor (120 mg/kg, 240 mg/kg; p.o; 3 weeks) in BDL induced liver fibrosis. Materials and Methods: Male Sprague-Dawley rats (300-400 g; 6-8 weeks) were randomly allocated in 7 groups (normal control, model control, sham operated, STD, vehicle control, Apo-1 and Apo-2 groups). All groups (n = 6) except normal control were operated for BDL. Results: The BDL group showed abnormal liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], total bilirubin content), increased TGF-β1, hydroxyproline content, liver weight, spleen weight and decrease in plasma retinol content. Apocynin treatment prevented BDL-induced changes. Biochemical analysis of redox status including thiobarbituric acid reactive substances, reduced glutathione conforming BDL-induced oxidative stress were alleviated by apocynin. It abrogated BDL-induced Histopathology changes like portal inflammation, cellular necrosis, collagen deposition, portal fibrous expansion, reticulin fibre collapse (H & E, Masson trichome and Reticulin staining), suggesting the protection against BDL-induced pathogenesis of liver fibrosis. The results were comparable with the silymarin used as standard in the study. Conclusion: Apocynin ameliorated BDL induced liver fibrosis in rat.


A Herbomineral Formulation Accentuates Fracture Healing in Femoral Dexter Osteotomized Rats

Mukesh Nandave 1 , Anup Ramdhave 1 , Milind Patil 2 , Khemraj Mourya 2

SPP School of Pharmacy and Technology Management, SVKM's NMIMS, Vile Parle (W), Mumbai, Maharashtra, India, 2 Charak Pharma Pvt. Ltd., Mumbai, Maharashtra India

Objectives: The present study was designed to investigate the possible fracture healing activity of a herbomineral formulation comprising Cissus quadrangularis, Terminalia arjuna, Carthamus tinctorius, Withania somnifera, Commiphora mukul, Laccifera lacca and Zinc oxide (Yashad Bhasma). Materials and Methods: Plant components of formulation were standardized with respect to their principle components including ketosterone, withanaloid, tannins, using HPTLC. Thirty six male SD rats were randomly divided into six groups (n = 6) as follows: sham, disease control, standard (150 mg/kg CaCO 3 ) treatment, herbomineral formulation (HMF-100, 130, and 150 mg/kg) treatment. Two weeks after femoral dexter osteotomy procedure in all animals except sham, they received corresponding treatment for 4 weeks. Pre- and post-treatment X-ray was done in all groups. At the end of study, plasma alkaline phosphatase (ALP), malondialdehyde (MDA) and superoxide dismutase (SOD) were estimated and bone histology was also done. Results: Herbomineral formulation significantly attenuated ALP level at all three doses and this effect was comparable to standard drug (p < 0.001). The MDA level was also found to be reduced significantly (p < 0.001) by all three doses. The reduction in MDA level was also significant (p < 0.01) in rats treated with standard, when compared with disease control animals. The SOD level was found to be significantly (p < 0.001) accentuated by HMF-100, 130, and 150 mg/kg. Benefits of HMF on biochemical parameters translated into histoarchitectural healing as evidenced by X-ray and histology data where 150 mg/kg dose showed maximal fracture healing activity. Conclusion: Study results demonstrated dose dependent fracture healing activity of HMF at 130 and 150 mg/kg, better than CaCO 3 , which may be attributed to its pleiotropic effect including bone calcification, formation, healing, anti-inflammatory, antioxidant, and attenuation of lipid peroxidation.


Secoisolariciresinol Diglucoside Lignan Concentrate of L. usitatissimum Exhibits Chemoprotective Role in Skin Cancer Through Inhibition of CDK4 and Upregulation of P53

Patel BM, Yash Patel S

Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India

Objectives: Cyclin dependent kinases (CDKs) are novel target for skin cancer. Secoisolariciresinoldiglucoside (SDG) and lignans are reported to exert anti-cancer effect on colon cancer. However, reports of SDG lignan concentrate (SLC) of L. usitatissimum on skin cancer are not available. To study the effect of SLC of L. usitatissimum on skin cancer and determine mechanism of action. Materials and Methods: Cell viability studies were done using A-375 cell line. Skin cancer was induced by dimethyl benz (a) anthracene and croton oil in female balb/c mice. 5% SLC was administered from 7 th to 16 th week after which we evaluated serum and tissue parameters. Results: The IC 50 value of SLC was found to be 93.7 μg/ml on A-375 cell line. Skin cancer control animals exhibited increased tumor volume and burden and increase in non-specific serum and tissue markers. Treatment with SLC decreased tumor volume and burden, and serum and tissue markers. Histopathological studies also depicted protection with SLC treatment. Docking studies revealed that SDG exhibits good binding score with CDK4. Skin cancer control mice showed significantly increased CDK4 mRNA and decreased p53 mRNA levels which were prevented by SLC treatment. Conclusion: SLC exhibited chemopreventive effect in skin cancer depicted by reduction in serum biomarker, oxidative stress, collagen levels, tumor volume, tumor burden and histopathological studies. These effects are mediated through the inhibition of CDK4 and upregulation of p53.


Evaluation of Momordica dioica Seed Extract for Alpha Amylase Inhibitory Activity and Antioxidant Potential in Rat Model

Sailaja Rao P 1 , Krishna Mohan G 2 , Prathima Srinivas 3

1 Department of Pharmacology, Sri Venkateswara College of Pharmacy and Research Centre, Madhapur, Hyderabad, Telangana, India, 2 Centre for Pharmaceutical Sciences, JNTUH, Hyderabad, Telangana, India, 3 Sri Venkateswara College of Pharmacy and Research Centre, Madhapur, Hyderabad, Telangana, India

Objectives: To study the effect of ethylacetate extract of Momordica dioica seeds by in vitro alpha amylase assay and in vivo anti-oxidant potential in streptozotocin-induced diabetic rats. Materials and Methods: Type II diabetes was induced in albino Wistar rats by a single intraperitoneal injection of streptozotocin (STZ) at the dose of 60 mg/kg body weight. In vitro α-amylase activity was performed by using dinitrosalicylic acid solution in ethylacetate extract of M. dioica. Experiment for in vivo antioxidant effect was carried out after a continuous treatment with ethylacetate extract for 15 days at the dose of 100 and 200 mg/kg body weight. Serum glucose levels were estimated by GOD-POD method on the 11 th day of treatment. Results: The ethylacetate extract of Momordica dioica seeds at the dose of 200 mg/kg body weight showed significant reduction in serum glucose levels at 2 hrs, 4 hrs, 6 hrs and 8 hrs respectively in STZ-induced diabetic rats (p < 0.0001). In in vitro α-amylase assay, there was a significant inhibition with IC 50 of 58 ± 0.091 μg/ml in comparable to the standard acarbose. Treatment for a period of 15 days showed significant elevation of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), but malondialdehyde (MDA) levels were significantly reduced in STZ-challenged diabetic rats (p < 0.0001). Conclusion: Our results revealed that the ethylacetate extract of Momordica dioica seeds possessed potent α-amylase, anti-diabetic and antioxidant activities.


Aqueous Leaf Extract of Aegle marmelos Favorably Resets Insulin Signaling Pathway (Pi3k/Mtor) Skewed by Fructose in Insulin Resistance Hepatic Cells

Aggarwal H, Sehgal R, Tiwari M, Mathur R

Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India

Objectives: Insulin resistance (IR) is a multifactorial disorder with only symptomatic treatment available till date. The plant Aegle marmelos (Rutaceae) is traditionally used due to its anti-diabetic properties. The present study investigated its role and mechanism in prevention of IR (a precursor of type 2 diabetes and metabolic syndrome). To investigate the effect and mechanism of action of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of IR induced by fructose and hyperinsulinemic state, vis-à-vis, carbohydrate metabolizing enzymes, secondary messengers of insulin signaling and hypoxic and inflammatory mediators. Materials and Methods: A combination of insulin and fructose was used to induce IR in HepG2 cells. Comparison was made between normal control, insulin resistant and AM treated insulin resistant cells along with rutin, metformin and pioglitazone treated insulin resistant cells by accessing the following biomarkers of IR: hexokinase, phosphofructokinase, aldehyde dehydrogenase, PI3K, STAT-3, mTOR, HIF-1α, VEGF and TNF-α. Results: Fructose and hyperinsulinemia raised the levels of hepatic biomarkers of IR in HepG2 cells significantly (p < 0.05), which were favorably re-set by AM. For the first time, potential and mechanism of AM in the management of IR arising from fructose is reported in in-vitro. Conclusion: These results confirm that Aegle marmelos can prevent IR in hepatocytes. The identified changes in hepatic biomarkers of insulin resistance indicate the potential mechanism of AM action reflecting cumulative effect of the multiple bioactive compounds present in AM.


Effect of Nutmeg (Myristica fragrans Houtt.) in Helicobacter pylori and Alcohol-induced Gastric Ulcer in Wistar Albino Rats

Jadeja DK, Vachhani AV, Tripathi SK, Baxi S, Mukhopadhyay A, Tripathi CB

Department of Pharmacology, Government Medical College, Bhavnagar, Gujarat, Inida

Objectives: Evaluation of anti-inflammatory and antiulcer effect of Myristica fragrans Houtt. in Helicobacter pylori and alcohol-induced gastric ulcer in Wistar albino rats. Materials and Methods: Wistar albino rats of either sex randomly divided into eight subgroups: Group 1: received H. pylori only. Group 2 and 3, received H. pylori plus low dose and high dose of M. fragrans respectively. Group 4: received H. pylori plus omeprazole. Group 5: received normal saline only. Group 6: received ethanol only. Group 7 and 8, received ethanol plus low and high dose of M. fragrans respectively. Retro-orbital blood was collected and biochemical and haematological parameters were measured. After that rats were sacrificed and stomachs were removed, for biomarkers of oxidative stress and for histopathology. Results: (1) Levels of biomarkers of oxidative stress like catalase was increased and of MDA was decreased significantly. (2) M. fragrans significantly increases the level of red blood cells, white blood cells and haemoglobin. (3) In gross examination no visible ulcer in M. fragrans groups compared to alcohol control group. Conclusion: In conclusion, we have found that aqueous extract of M. fragrans Houtt. has an antiulcerogenic effect against H. pylori and ethanol-induced gastric ulcer in Wistar albino rats, this action was might be due to its antimicrobial as well as anti-inflammatory activity.


Evaluation of Anticoagulant Effect of Sulphated Polysaccharide from Codium dwarkense Bψrgesen in Hypercoagulable State in Wistar Albino Rats

Golakiya HN 1 , Hirapara HN 1 , Naik V 1 , Mody KH 2 , Goswami A 3 , Tripathi CB 1

1 Department of Pharmacology, Government Medical College, Bhavnagar, Gujarat, India, 2 Central Salt and Marine Research Institute, Bhavnagar, Gujarat, India, 3 Department of Pathology, Government Medical College, Bhavnagar, Gujarat, India

Objectives: To evaluate the anticoagulant effect of sulphated polysaccharide from Codium dwarkense Borgesen in kappa carrageenan induced hypercoagulable state in Wistar albino rats. Materials and Methods: 48 Wistar albino rats of either sex were randomly divided into 6 groups - disease control, active control, treatment low & high dose and preventive low & high dose. Kappa carrageenan (3 mg/kg) single dose intravenously was given in rat tail vein at pre-decided time to produce hypercoagulable state. Baseline, 24, 48 and 72 hours duration blood samples was collected for PT, INR, aPTT, platelet count and fibrinogen level, FDP and D-Dimer measurement. At the end of experiment, animals were sacrificed for histopathological analysis of lung, liver and mesentery. Results: In present study, SPS significantly restored altered coagulation parameters (PT, INR, aPTT, Platelet count and fibrinogen level) without affecting fibrinolytic parameters (FDP and D-Dimer). Administration of SPS both as a treatment and preventive therapy reduced the number of microthrombi along with less histopathological damage in lung, liver and mesentery. Heparin served as active control and its administration significantly prolonged aPTT and restored PT. Conclusion: In present study, SPS extracted from Codium dwarkense Bψrgesen showed an anticoagulant activity in hypercoagulable state produced in Wistar albino rats.


Evaluation of the Effect of Indian Medicinal Plants on Fertility and Maintenance of Pregnancy in Fertile Rats

Vaidya PH, Radhakrishnan M, Kamat SK, Gajbhiye SV, Jalgaonkar SV

Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Mumbai, Maharashtra, India

Objectives: Durva (Cynodon dactylon) and Shatavari (Asparagus racemosus) are Indian medicinal plants described in Ayurveda as procreative, fertility promoters and sustainers of pregnancy. In this study, their effect on ovulation in immature female Wistar rats and on implantation and pregnancy outcome in adult female Wistar rats was evaluated. Materials and Methods: The female rats (n = 120) were divided into five groups of 8 rats each, for each of the three phases as follows: control, low dose C. dactylon 123.75 mg/kg/day, high dose C. dactylon 247.5 mg/kg/day, low dose A. racemosus 225 mg/kg/day and high dose A. racemosus 450 mg/kg/day for each of the three phases. In phase 1, number of oocytes were counted after inducing ovulation in immature rats primed with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). In phase 2, effect on implantation was evaluated in adult pregnant rats at day 10 of pregnancy by assessing uterine and ovarian weight, number of implantation sites, number of Corpora lutea, implantation index and pre-implantation loss. In phase 3, the effect on pregnancy outcome was assessed by counting the number of viable and dead litters, weight of the litters, duration of gestation and the reproductive indices. Results: Low dose C. dactylon increased the number of ovulated oocytes in immature rats (p < 0.05). Number of implantation sites and the implantation index was also significantly higher with low dose of C. dactylon and A. racemosus. Pre-implantation loss in all treatment groups decreased significantly. Rats in the low dose C. dactylon and A. racemosus groups delivered more number of viable litters with improved reproductive indices (p < 0.05). Conclusion: C. dactylon possesses potential fertility enhancing effect by induction of ovulation and facilitation of implantation whereas A. racemosus enhances fertility by assisting implantation.


Efficacy and Safety of Aqueous Extract and Guduchi Satwa (Starch) of Tinospora cordifolia in Patients with Rheumatoid Arthritis

Shah PA, Shah GB

Department of Pharmacology, KB Institute of Pharmaceutical Education and Research, Gandhinagar, Gujarat, India

Objectives: To evaluate anti-rheumatoid activity of aqueous extract (TCE) and guduchi satwa i. e., starch (GS) of Tinospora cordifolia in patients with moderate rheumatoid arthritis (RA). Materials and Methods: This was randomized, open label, parallel group and comparative clinical study in patients with moderate RA activity as per American College of Rheumatology criteria (ACR). Total 60 patients (age between 18 and 65) with Disease Activity Score i.e., DAS28(4)ESR or DAS28(4)CRP score (≥3.2 but <5.1) were randomized to 3 groups each containing 20. TCE and GS were administered as add on therapy to MTX. Patients in Group I received MTX (10 mg/week, p.o., once a week). Patients in group II and III received TCE (500 mg, p.o., oid) and GS (500 mg, p.o., bid) respectively for 16 weeks in addition to MTX. Number of ACR responders (ACR20), ESR, CRP, RF, DAS28(4)ESR score and DAS28(4)CRP score were measured. Patient reported outcomes (PROs) such as pain VAS, duration of morning stiffness, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) score and SF-36 (36-item Short Form Health Survey) were assessed. Results: GS improved ESR. Both TCE and GS significantly improved RF, DAS scores, VAS, duration of morning stiffness, SDAI, CDAI and SF-36 score. ACR responders were higher in TCE and GS groups. Improvement was higher in GS group as compared to TCE. Conclusion: GS treatment was found better than TCE.


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