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| ABSTRACTS |
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| Year : 2014 | Volume
: 46
| Issue : 7 | Page : 3-6 |
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Gufic Prize
| Date of Web Publication | 26-Dec-2014 |
Correspondence Address:
 Source of Support: None, Conflict of Interest: None  | Check |
How to cite this article:
. Gufic Prize. Indian J Pharmacol 2014;46, Suppl S1:3-6 |
PZG-1
In vivo Metabolism and Pharmacokinetics of Picroside I and II from Kutkin in Rats using LC-ESI-MS Method
Dilawar Upadhyay 1 , Sheetal Anandjiwala 1 , Harish Padh 2 , Manish Nivsarkar 3
1 Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, c/o B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad - 380054, Gujarat, India, 2 Sardar Patel University, Vallabh Vidyanagar - 388120, Gujarat, India 3B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad - 380054, Gujarat, India
Objectives: Picroside I and II, iridoid glycosides, are the major active markers present in the roots and rhizomes of Picrorhiza kurroa Royle (family: Scrophulariaceae). Plant is reported to be effective in many ailments viz. liver disorders, cancer, asthma, inflammation etc. Various Ayurvedic and herbal drugs/formulations are used without any significant data regarding their pharmacokinetic/metabolic profile. P. kurroa is one of them, which is widely used in many Ayurvedic and herbal formulations like Arogyavardhani-Vati, Tikkadikwath etc. Previously, we reported that the bioavailabilty of picroside I and II is lower. While finding the reasons, previous reports suggest that most of the iridoid glycosides are primarily metabolized by Intestinal microbial flora. So, it was presumed that lower bioavailabilty could be due to metabolism of Picroside I and II. Therefore, this study was designed to check pharmacokinetic and metabolic profile of Picroside I and II. Materials and Methods: A sensitive and selective LC-ESI-MS method was developed for simultaneous determination of Picroside I and II in rat plasma. Chromatographic separations were performed on C 18 column. The mobile phase consisted of Acetonitrile: 10mM ammonium acetate buffer [90:10 v/v], pH adjusted to 3.5. A pharmacokinetic and metabolic profile of Picroside I and II from Kutkin (mixture of picroside I and II) was generated after oral administration to Sprague-Dawley rats. Results and Discussion: Various pharmacokinetic parameters viz. C max , T max , AUC (0-t) , K el , t 1/2 , V d were determined. In metabolic study, four metabolites for each Picroside I and Picroside II were identified from rat plasma.
PZG-2
Effect of Ethanolic Extract of Zingiber officinale on Cyclophosphamide Induced Genotoxicity in Male Albino Rats
Preetish Kumar Panigrahy, B.Rath, *S.Rath, Y.R Ramani, P.Das, J.P Behera, C.S Maharana
Department of pharmacology, MKCG Medical College, Berhampur *Department of Anatomy, MKCG Medical College, Berhampur
Objective : To investigate the effect of ethanolic extract of Zingiber officinaleon cyclophosphamide (CP) induced genotoxicity and oxidative stress in male wistar albino rats. Materials and Methods: Five Groups of 6-8 wks old male wistar albino rats treated with vehicle and test drug orally for 7 days as follows: Group-I (normal control) and Group-II (CP Control) were treated with vehicle only. Rats of Group-III and Group-IV were treated with ethanolic extract of Zingiber officinale100 mg/kg and 200 mg/kg wt. respectively. 24 hrs after the last test dose, rats of group I, II, and III were injected with cyclophosphamide (40 mg/kg i.p) Group-V rats were fed with of ethanolic extract of Zingiber officinale ( 200 mg/kg )only without CP injection. All the rats were sacrificed after 24 hrs of CP injection. 2mM Colchicine (0.5 ml/100gm b.w.) was injected to each rat before sacrificing. Bone-marrow was studied for frequency of micronuclei in polychromatic and normochromatic erythrocytes, P/N Ratio as well as different chromosomal aberrations. Oxidative stress markers (MDA, SOD, GSH) in liver of each rat were estimated. Result: Ethanolic extract of Zingiber officinaleat 100 mg/kg and 200 mg/kg inhibited CP induced increase in frequency of bone marrow micronuclei and various chromosomal abnormalities like chromosomal breaks, ring, deletion and other multiple aberrations. It also inhibited CP induced alterations in oxidative stress markers in-vivo. Conclusion: Zingiber officinaleInhibits CP induced genotoxicity and oxidative stress in-vivo. Therefore it appears to be a potential agent in protecting cancer chemo-therapy induced geno-toxicity.
PZG-3
Modulation of Transcriptional Regulator of Phase I Enzymes as a Potential Mechanism of Polymeric Black Tea Polyphenols for Anti-initiating Action
Khushboo Gandhi 1 , Tejal Gandhi 1 , Girish Maru 2
1 Anand Pharmacy college, Anand, 2 ACTREC, Tata memorial Centre, Kharghar, Navi Mumbai, India
Objective: Chemoprevention by dietary constituents has emerged as a novel approach to control cancer incidence. Polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, known to possess anti-initiating and anti- promoting activity in different animal models. But their anti-initiating properties are poorly elucidated. In present study, mechanism of PBPs-mediated anti-initiation was investigated in mouse skin employing Benzo(a)Pyrene (B(a)P) as a carcinogen. Materials and Methods: Swiss bare mice on dorsal skin were painted with Acetone (Vehicle) or 200μg of PBPs in acetone, 20 mins prior to application of acetone or 1mg B(a)P in acetone for three consecutive days. After 24 hour of last application animals were sacrificed, skin was removed and stored at -80°C. In epidermis of skin, enzyme activity, mRNA levels and expression of CYP1A1/1A2 were determined by spectroflourometry, RT-PCR and western blotting respectively. Subsequently expression of their transcriptional regulator, aryl hydrocarbon receptor (AhR) in different lysates, its Phosphorylation and subsequent binding to DNA was also studied by western blotting, immunoprecipiation and EMSA respectively. Finally DNA adduct formation was evaluated by immunohistochemistry. Results: Pretreatment with PBPs significantly decreased B(a)P-induced enzyme activity, mRNA levels and expression of CYP1A1/1A2. PBPs alone did not alter the basal levels of AhR, however they significantly diminishedB(a)P-induced AhR expression, its nuclear translocation, phosphorylation and subsequent DNA binding. Pre-treatment of PBPs also significantly inhibited B(a)P-induced DNA adduct formation. Conclusions: PBPs exhibit their anti-initiation activity via modulation of AhR and its downstream enzymes indicated by decreased DNA adducts.
PZG-4
Healing Effect of Sea buckthorn (Hippophaerhamnoides L.) Encapsulated PVA Cryogel Dressing for Burn Wounds
Asheesh Gupta 1* , Prasun K. Roy 2
1 Pharmacology Division, Defence Institute of Physiology and Allied Science (DIPAS), DRDO, Timarpur, Delhi-110054, India, 2 Environment Safety Division, Centre for Fire, Explosive and Environment Safety (CFEES), DRDO, Brig. S. K. Majumdar Marg, Delhi, India
Objective: Research on wound healing drugs from the natural sources and other effective and clinically relevant therapeutic interventions like active wound dressings are developing areas in modern biomedical sciences. In the present study, a poly (vinyl alcohol) (PVA) cryogel dressing encapsulated with Sea buckthorn (SBT) (Hippophaerhamnoides L.) extract was developed and its healing efficacy was evaluated on experimental burn wounds in rats. Materials and Methods: Aqueous lyophilized extract of SBT leaves was prepared and incorporated into a PVA cryogel construct prepared by freeze thaw method. The cryogel was physico-chemically characterized and its in-vivo healing efficacy evaluated on full-thickness burn wounds. Results: The introduction of SBT did not affect the mechanical properties of the PVA cryogel. The tensile strength and % elongation at break remained unaltered at 0.19 ± 0.01 kg/ cm 2 and 140 ± 4.08% respectively. The gel content of freeze thawed sample was 80-84%, which confirmed the stability of the hydrogels. The WVTRof 150 ± 8.8 and 19 ± 1.8 gm -2 day -1 at 0% and 32% relative humidity respectively advocate its potential as a wound healing material . Topical application of PVA cryogel loaded with SBT improved the healing rate in burn wounds as evidenced by enhanced hydroxyproline, hexosamine, total protein contents and wound contraction. Histopathological observations revealed significant healing by improvement in neo-vascularization, re-epithelialization, collagen deposition and less inflammatory responses in SBT encapsulated cryogel treated wounds compared to the cotton-gauze treated controls. Conclusion: The PVA cryogel encapsulated with SBT is a promising dressing for treatment of burn wounds.
PZG-5
Comparative Study of Antidiabetic and Antioxidant Activities of the Ethanolic Extracts of Leaves and Bark of Acacia farnesiana (L.)Willd. in Streptozocin Induced Type 1 Diabetic Experimental Animal Models
Dr. Mahanjit Konwar, Dr. Swarnamoni Das
Department of Pharmacology, Assam Medical College and Hospital, Dibrugarh, Assam
Objective: The present study was carried out to evaluate the antidiabetic and antioxidant effect of the ethanolic extract of the leaves and bark of Acacia farnesina (L.) Willd. in streptozotocin induced type1 diabetic animal model and also to explore the probable mechanism of their activities. Materials and Methods : A single intraperitoneal injection of streptozocin 150 mg/kg was injected in mice to induce diabetes. Mice with blood glucose level >200 mg was considered diabetic and taken in the experiment. Oral administration of the ethanolic extract of leaves (EELAF) and bark (EEBAF) of Acacia farnesiana were administered p.o for 14 days. Blood glucose was measured at repeated intervals and serum insulin, tissue glycogen and antioxidant parameters were evaluated at the 15 th day of experiment. The effect of the drugs on intestinal glucose absorption was evaluated on Wistar rats. Results : Streptozocin induced diabetic mice showed significant hyperglycaemia and loss of body weight with alteration of serum insulin, tissue glycogen and antioxidant levels. On treatment with EELAF, EEBAF and insulin there was significant fall in blood glucose level and increase in weight with normalization of the impaired glycogen and antioxidant variables. Both extracts also showed significant inhibitory activity on intestinal glucose absorption. Conclusion: In conclusion, our data suggests that both the plant extracts had potential anti-diabetic and antioxidant activitiy in STZ induce type 1 diabetic experimental model.
PZG-6
In-vitro and In-vivo analysis of Effect of Sodium Sulphated Polysaccharide extracted from Kappaphycus alvarazii in Ethylene Glycol induced Renal Stone in Wistar Albino Rats
Dr. Aiwale As, Dr. Shukla Ab, Dr. Mandavia D, Dr. Baxi S, Dr. Mody Hm, Dr. Mody Kh, Dr. Tripathi CB
Department of Pharmacology, Government Medical College, Bhavnagar, Gujarat, India
Objective: To observe antiurolithiatic effect of sulphated polysaccharide extracted from Kappaphycus alvarazii in ethylene glycol induced renal stone in wistar albino rats. Material and Methods: Sulphated polysaccharide extracted from Kappaphycus alvarezii by calcium hydroxide and sodium hydroxide methods. Extracted products i.e. sodium sulphated polysaccharide and calcium sulphated polysaccharide evaluated in-vitro analysis of anti-urolithiatic actions. It shows sodium sulphated polysachhride was found to be more effective. sodium sulphated polysaccharide was used for in-vivo analysis in wistar albino rats. Acute toxicity study was performed on mice. Doses were found to be 200 mg/kg and 400 mg/kg. wistar albino rats were divided into seven groups normal control, EG control, active control (Cystone 750 mg/kg P.O.), preventive group - low and high dose of sulphated polysaccharide and treatment group - low and high dose of sulphated polysaccharide. After 28 days, 24 hrs urine samples were collected for urine oxalate, urine phosphate and urine calcium measurments. Rats were anaesthetized, blood were collected from retro-orbital plexus for SGOT, SGPT, ALP, total bilirubin, serum creatinine and blood urea analysis. Kidneys were removed for measurement of kidney weight, histopathological study. Results: Urine oxalate in high and low doses and urine phosphate in preventive dose was found to effective. In serological parameters serum creatinine was found to be significant treatment group - high and low doses. Kidney weight significantly reduced in treatment - high dose group. Histopathological evaluation there were less damage to kidney structures compare to EG control group. Conclusion: Sodium sulphated polysaccharide was effective controlling urolithiatic action of ethylene glycol in rats.
PZG-7
Aqueous Extract of Ganoderma Lucidum Facilitates Tolerance in Rat Heart By Inducing Nuclear Factor (Erythroid-Derived 2)-Like 2 and Hypoxia Inducible Factor 1 Dependent Signaling
Rajkumar Tulsawani, Mrinalini, Manickam Manimaran
Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, India
Objective: To evaluate mechanism of action aqueous extract of Ganoderma lucidum in facilitating tolerance of rat heart against simulated hypobaric hypoxia. Materials and Methods: Rats were exposed to hypobaric hypoxia (25000 fts) for 7 days in the presence or absence of aqueous extract of Ganoderma lucidum. After exposure period, heart was homogenized in cell lysis buffer and tissue MDA, GSH, GPx and SOD levels and NFkB, TNFα, Nrf2, HO1, MT, HIF1α, pAKT and pERK expressions were measured. Results: Treatment of rats with standardized aqueous extract of Ganoderma lucidum significantly attenuated rise in MDA levels and changes in GSH, GPX and SOD levels observed following hypoxia exposure in comparison to heart tissue of untreated rats. Treatment of rat with the standardized extract improved expression of Nrf2, heme oxygenase 1 and metallothionein and showed stabilized levels of hypoxia inducible factor 1α. Further, extract treatment resulted in increased phosphorylation of AKT and ERK which are casually associated with nuclear factor (erythroid-derived 2)-like 2 and hypoxia inducible factor 1α signaling during hypoxia. In contrast, lower levels of nuclear factor kappa B and pro-inflammatory cytokine (tumor necrosis factor α) were observed in extract treated rat heart in comparison to the rats exposed to hypobaric hypoxia without extract. In conclusion, aqueous extract of Ganoderma lucidum reduced oxidative stress by maintaining higher HO1 and MT levels via Nrf2 and conferring tolerance to hypoxia by activating HIF1α dependent signalling. Conclusion: The findings from these studies suggest that aqueous extract of Ganoderma lucidum provide tolerance to rat heart by over-expressing nuclear factor (erythroid-derived 2)-like 2 and hypoxia inducible factor 1 dependent protein expressions.
PZG-8
Neuroprotective Potential of Geraniol in Murine Model of Parkinson's Disease: A Behavioral and Biochemical Evaluationstudy
Sachin K. Parmar*, MehulGohil, Samir Rabadiya, Rohit Bhatt, SaurabhThanki, MihirRaval, Vishavas L. Ranpariya, Navin R. Sheth
Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, Gujarat, India
Parkinson's disease (PD) is an age-related neurodegenerative disorder most prone to occur after middle age, in which the role of oxidative stress and reactive oxygen species (ROS) in the etiology and its progression is strongly implicated. The present study was undertaken to investigate the neuroprotective effects of geraniol (GOH) on 6-hydroxydopamine (6-OHDA)-induced PD in rats. GOH, an acyclic monoterpene alcoholic antioxidant, a common component of several essential oils, has been shown to have antioxidant and anti-inflammatory actions and therefore was tested for its beneficial effects using 6-OHDA induced PD rat model. 6-OHDAinjury produced marked elevationin lipid peroxidation (LPO) and nitric oxide (NO), whereas superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), Total thiols, glutathione reductase (GR) and glutathione peroxidase (GPx) levels were decreased in experimental animals. Furthermore, it also depleted the level of dopamine (DA) and its metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC) in rat striatum. Administration of GOH (50 and 100 mg/kg, p.o.) significantly heightened SOD, CAT, GSH, total thiols, GR and GPx activities, whereasreduced LPO and NO levels in the brain. The levels of dopamine and DOPAC were also restored near to normal in GOH-treated rats. Interestingly, histopathologystudy revealed a marked reversal of 6-OHDA provoked neuronal damage in the GOH treatmentgroups. Taken together, our study, for the first time, demonstrates neuroprotective potential of GOH against 6-OHDA induced neuronal injury in experimental rats. We propose that the neuroprotection offered by GOH could be attributed, at least in part, to its anti-oxidant property.
PZG-9
Standardized Fruit Extract of Momordica charantia L Protect Against vincristine induced neuropathic pain in rats by Modulating GABAergic action, antimitotoxic, NOS inhibition, anti-inflammatory and antioxidative activity
Vivek jain 1 , Ashutosh Pareek 1 , Yashumati Ratan 1 , Nirmal Singh 2 *
1 Department of Pharmacy, Banasthali University, Banasthali, Rajasthan-304022, India, 2 Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala-147002, Punjab, India
In present experimental work we investigate the protective potential of standardized Momordica charantia L fruit extract {Gallic acid 6 %; >8% bitters [momordicosides K ( 3%) and L (2%), and momordicines I (2%) and II (3%)]} (MC) comparable to its marker compound gallic acid (GA) in chemotoxic neuropathy induced by vincristine (75 μg/kg i.p. for 10 consecutive days) in rats. An array of behavioral examinations was carried out on day 1st, 12th and 21st, followed byvarious biochemical and histopathological studies the end. Vincristine induced significant cold and dynamic mechanical allodynia, mechanical and heat hyperalgesia; functional deficit in walking and rise in the levels of TNF-α, IL 6, mitochondrial complexes, MPO, TBARS, and Nitrite along with decrease in GSH. Administration of MC (400 and 800 mg/kg p.o.), GA (30 mg/kg p.o.) and gabapentin (100 mg/kg p.o.) attenuated vincristine induced behavioral and biochemical changes. MC demonstrated superior antinociceptive activity to GA. Histopathological evaluation also divulged defending effects of MC. Pretreatment of Saclofen (1 mg/kg, i.p.), picrotoxin (1 mg/kg, i.p.) upturned antinociceptive action of MC, but ingestion ofGABA (100 mg/kg i.p.) potentiated action of MC. Additionally, pretreatment of L-arginine (NO donor; 100 mg/kg i. p.) inverted the antinociceptive action of MC; Whereas, aminoguanidine (iNOS inhibitor) and 7-nitroindazole (nNOS inhibitor) potentiated it. Beside this a PPAR-α antagonist BADGE did not amend the effect of MC. Corroboratively, attenuating effect of MC invincristine induced neuropathy attributed to its modulating action on GABAergic system along with antimitotoxic, NOS inhibition, anti-inflammatory, and anti oxidative activities.
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