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   2007| July-August  | Volume 39 | Issue 4  
 
 
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REVIEW ARTICLE
Silymarin: A review of pharmacological aspects and bioavailability enhancement approaches
Nitin Dixit, Sanjula Baboota, Kanchan Kohli, S Ahmad, Javed Ali
July-August 2007, 39(4):172-179
DOI:10.4103/0253-7613.36534  
Silymarin, a flavonolignan from the seeds of 'milk thistle' (Silybum marianum), has been widely used from ancient times because of its excellent hepatoprotective action. It is a mixture of mainly three flavonolignans, viz, silybin, silidianin, and silychristine, with silybin being the most active. Silymarin has been used medicinally to treat liver disorders, including acute and chronic viral hepatitis, toxin/drug-induced hepatitis, and cirrhosis and alcoholic liver diseases. It has also been reported to be effective in certain cancers. Its mechanism of action includes inhibition of hepatotoxin binding to receptor sites on the hepatocyte membrane; reduction of glutathione oxidation to enhance its level in the liver and intestine; antioxidant activity; and stimulation of ribosomal RNA polymerase and subsequent protein synthesis, leading to enhanced hepatocyte regeneration. It is orally absorbed but has very poor bioavailability due to its poor water solubility. This review focuses on the various pharmacological activities of silymarin including the clinical trials. For the first time, the review also looks at the formulation work that has been done to enhance its solubility, so as to increase its bioavailability and thus, its hepatoprotective action.
  48 67,822 3,177
RESEARCH PAPERS
Protective effect of Kalanchoe pinnata pers. (Crassulaceae) on gentamicin-induced nephrotoxicity in rats
Gaurav Vijay Harlalka, Chandragauda Raosaheb Patil, Mahesh Ramu Patil
July-August 2007, 39(4):201-205
DOI:10.4103/0253-7613.36540  
Objective : The present study was undertaken to evaluate the aqueous extract of K. pinnata for its protective effects on gentamicin-induced nephrotoxicity in rats. Materials and Methods : Nephrotoxicity was induced in Wistar rats by intraperitoneal administration of gentamicin 100 mg/kg/day for eight days. Effect of concurrent administration of K. pinnata leaf extract at a dose of 125 mg/kg/day given by intraperitoneal route was determined using serum and urinary creatinine and blood urea nitrogen as indicators of kidney damage. The study groups contained six rats in each group. As nephrotoxicity of gentamicin is known to involve induction of oxidative stress, in vitro antioxidant activity and free radical-scavenging activity of this extract were evaluated. Result : It was observed that the aqueous extract of K. pinnata leaves significantly protects rat kidneys from gentamicin-induced histopathological changes. Gentamicin-induced glomerular congestion, peritubular and blood vessel congestion, epithelial desquamation, accumulation of inflammatory cells and necrosis of the kidney cells were found to be reduced in the group receiving the leaf extract of K. pinnata along with gentamicin. This extract also normalized the gentamicin-induced increases in urine and plasma creatinine, blood urea and blood urea nitrogen levels. In vitro studies revealed that the K. pinnata leaf extract possesses significant antioxidant as well as oxidative radical scavenging activities. Conclusion : It is proposed that the nephroprotective effect of the aqueous extract of K. pinnata leaves in gentamicin-induced nephrotoxicity may involve its antioxidant and oxidative radical scavenging activities.
  32 13,966 1,026
Efficacy study of the bioactive fraction (F-3) of Acorus calamus in hyperlipidemia
T D'Souza, SA Mengi, S Hassarajani, S Chattopadhayay
July-August 2007, 39(4):196-200
DOI:10.4103/0253-7613.36539  
Objective : To investigate the effect of the bioactive F-3 fraction from the rhizomes of Acorus calamus in experimentally induced hyperlipidemic rats. Materials and Methods : Doses of 10, 20 and 40 mg/kg of the bioactive fraction were evaluated for its effect on the lipid profile and fibrinogen levels in diet-induced hyperlipidemia. Additionally, apoprotein A1 and apoprotein B levels were estimated using immunoturbidimetric assays. Furthermore, the bioactive F-3 fraction was investigated for its mechanism of action by estimating HMG-CoA reductase activity and fecal cholesterol levels. Besides evaluating the free radical-scavenging activity using the Diphenyl picryl hydrazyl (DPPH) method, the high performance thin layer chromatography (HPTLC) fingerprint of the bioactive fraction was also developed. Results : At doses of 20 and 40 mg/kg, the bioactive fraction significantly (P < 0.05) decreased the total cholesterol (TC) and low-density lipoprotein (LDL) levels. The bioactive F-3 fraction also attenuated the raised plasma fibrinogen levels. Fecal cholesterol excretion was significantly (P < 0.05) enhanced by the F-3 fraction while 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) activity was depressed. Furthermore, the F-3 fraction also possessed an appreciable free radical scavenging activity. Conclusion : The results of the present study revealed that the bioactive F-3 fraction demonstrated its cholesterol-reducing effect by increasing fecal cholesterol excretion and decreasing cholesterol biosynthesis in the liver. Additionally, the effects on fibrinogen levels and free radicals indicate that the bioactive F-3 fraction could have a potentially beneficial effect in atherosclerosis associated with hyperlipidemia.
  19 5,267 522
Immunosuppressive effect of medicinal plants of Kolli hills on mitogen-stimulated proliferation of the human peripheral blood mononuclear cells in vitro
S Arokiyaraj, K Perinbam, P Agastian, K Balaraju
July-August 2007, 39(4):180-183
DOI:10.4103/0253-7613.36535  
Four medicinal plant species were collected from the Kolli hills of Tamil Nadu and were screened for their immunosuppressive effect. The plants were shade dried and extracted with methanol. The crude methanol extracts were tested for inhibition of lymphocyte proliferation via lymphocyte proliferation assay by 3thymidine uptake. The test plants were Justicia gendarussa, Plumbago indica, Aloe vera, and Aegle marmelos. Among the plants tested J. gendarussa (100 g/ml) showed the highest lymphocyte inhibition (84%). Sequential extraction of J. gendarussa in various solvents (n-hexane, benzene, ethyl acetate, chloroform, acetone, ethanol, and water) confirmed that all of the above extracts at 50 g/ml, aqueous extract inhibited lymphocyte proliferation. Further, 17 high performance liquid chromatography fractions were collected for the aqueous extract and fraction no. 15 showed maximum inhibition of lymphocyte proliferation. The present study indicates that these extracts should be investigated further for the possible presence of immunosuppressive components.
  14 9,827 649
RESEARCH LETTERS
Counterfeit and substandard quality of drugs: The need for an effective and stringent regulatory control in India and other developing countries
Azhar Yaqoob Khan, Naushad M. Khan Ghilzai
July-August 2007, 39(4):206-207
DOI:10.4103/0253-7613.36541  
  12 9,129 426
RESEARCH PAPERS
Antitumor activity of biflavonoids from Ouratea and Luxemburgia on human cancer cell lines
Juliana Feijo de Souza Daniel, Cassia Cristina Fernandes Alves, Ivana Grivicich, Adriana Brondani da Rocha, Mario Geraldo de Carvalho
July-August 2007, 39(4):184-186
DOI:10.4103/0253-7613.36536  
The biflavones 7,7"-dimethyllanaraflavone (1), agathisflavone (2), and 7"-methylagathisflavone (3) isolated from the leaves of Ouratea hexasperma and luxenchalcone (4) isolated from the leaves and branches of Luxemburgia octandra, as well as a mixture of 7,7"-dimethyllanaraflavone and 7"-methylagathisflavone, were assayed against HT-29 colon adenocarcinoma, NCl-H460 non-small cell lung carcinoma, MCF-7 breast cancer cell, OVCAR-3 ovarian adenocarcinoma cells, and RXF-393 renal cell carcinoma. The results show significant activities, particularly for 7,7"-dimethyllanaraflavone (IC 50 0.77 0.08, 2.42 0.22, and 2.59 0.32 mg/ml for NCl-H460, MCF-7, and OVCAR-3, respectively), and for 7"-methylagathisflavone (IC 50 values of 4 mg/ml). Luxenchalcone revealed significant cytotoxicity on the five cell lines tested.
  12 5,432 643
RESEARCH LETTERS
Cardiovascular effects of cetyl trimethyl ammonium bromide-protected gold nanoparticles
Kishori Apte, Shantesh Hede
July-August 2007, 39(4):210-213
DOI:10.4103/0253-7613.36543  
  6 4,076 298
EDITORIAL
Postgraduate education in medical pharmacology
RK Dikshit
July-August 2007, 39(4):171-171
DOI:10.4103/0253-7613.36533  
  5 4,381 665
LETTER TO EDITOR
Paroxetine-induced hyponatremia
Ranjib Ghosh, Prasenjit Deka
July-August 2007, 39(4):214-215
DOI:10.4103/0253-7613.36544  
  4 4,287 202
RESEARCH PAPERS
Pharmacokinetics of rectal compared to intramuscular paracetamol in children undergoing minor surgery
Renuka Kulkarni, Nandini Dave, Ashish Bartakke, Abhijeet Nair, PP Kadam, UM Thatte, SN Oak
July-August 2007, 39(4):187-191
DOI:10.4103/0253-7613.36537  
Objectives : Although paracetamol is a widely accepted and safe analgesic, guidelines regarding its definite analgesic dose are lacking. This study was, therefore, undertaken to compare the pharmacokinetics of paracetamol when administered by two routes, viz, intramuscular and rectal, in children undergoing minor surgery. Design : Randomized, controlled, assessor-blind, comparative clinical trial. Materials and Methods: Following Institutional Ethics Committee approval and valid consent, children undergoing minor surgery were randomized to receive paracetamol either intramuscularly or rectally. Blood samples were collected at fixed intervals for estimation of drug levels. Results : Fifty children (43 boys, 7 girls; ages 3 to 12 years; weight 10 to 40 kg) were enrolled in the study. 26 patients were randomized to receive paracetamol intramuscularly (mean dose 14.8 0.9 mg/kg) and 24 to receive the paracetamol as a rectal suppository (mean dose 29.5 1.4 mg/kg). Complete pharmacokinetic analysis was possible in only 29 patients, as the blood samples of the others were either not received or were inadequate for analysis. The mean maximum plasma concentration (C max ) with rectal paracetamol (n = 13) was 6.04 2.21 mg/ml with a T max of 2.5 0.89 h, while with intramuscular paracetamol (n = 16), the C max was 10.34 7.09 mg/ml and the T max 1.47 0.64 h. The area under the concentration-time curve (AUC 0-12 ) was 42.26 22.29 g.h/ml and 43.60 26.45 g.hr/ml for rectal and intramuscular paracetamol, respectively. Patients in the intramuscular group needed rescue medication earlier as compared to those in the rectal group (P < 0.05). Conclusion : Although the drug levels achieved with rectal paracetamol were less than that achieved with intramuscular administration, it was higher than the lower limit for analgesic effect (3-5 g/ml). Patients who received paracetamol intramuscularly needed rescue medication earlier compared to those receiving paracetamol rectally, indicating a more prolonged duration of action with rectally administered paracetamol. Hence, rectal paracetamol can be used as a safe, effective, and more acceptable analgesic alternative in children.
  2 12,968 519
RESEARCH LETTERS
In vitro cytotoxic properties of O-methylsolanocapsine isolated from Solanum pseudocapsicum leaves
Santoshkumar H Dongre, Shrishailappa Badami, Godavarthi Ashok, S Ravi, Rudresh Kottani
July-August 2007, 39(4):208-209
DOI:10.4103/0253-7613.36542  
  1 4,046 369
RESEARCH PAPERS
Hematological and nonhematological toxicities of imatinib mesylate in patients with chronic myeloid leukemia and gastrointestinal stromal tumor
Mohammad Usman, Naveen Naz Syed, Ghulam Nabi Kakepoto, Salman Naseem Adil, Mohammad Khurshid
July-August 2007, 39(4):192-195
DOI:10.4103/0253-7613.36538  
Objectives : To determine the hematological and nonhematological toxicities of imatinib mesylate in patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST) and to review the literature to compile a list of the etiologic agents responsible for these events. Materials and Methods : This was a prospective study conducted from May 2001 to February, 2007. Two hundred and thirty-two patients with CML and GIST treated with imatinib mesylate at the Aga Khan University Hospital were included in the study. Side effects were graded according to the common toxicity criteria of the National Cancer Institute version 3.0. Results : Ninety-seven patients experienced various side effects which, in decreasing order of frequency, were: generalized hypopigmentation, periorbital edema, nausea, and weight gain. Hematological toxicities included mainly grade I/II anemia and thrombocytopenia. Grade III/ IV hematological adverse events were rare in our group. The frequency of all events is equally distributed in all phases of CML and GIST. The side effects rarely lead to permanent discontinuation of therapy. Conclusion : Imatinib mesylate is a well-tolerated drug with some adverse events that are only rarely a permanent barrier to therapy.
  1 7,780 259
BOOK REVIEW
Fundamentals of experimental pharmacology
MN Ghosh
July-August 2007, 39(4):216-216
  - 24,664 1,682
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