Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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On Aug 2018




Dr. Mamta Gupta,
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Aug 2018




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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
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Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Experimental Research
Year : 2009 | Month : April | Volume : 3 | Issue : 2 | Page : 1460 - 1465

NIDDM Antidiabetic Activity Of Saponins Of Momordica Cymbalaria In Streptozotocin-Nicotinamide NIDDM Mice

FIRDOUS M**, KONERI R*, SARVARAIDU C H*, HARISH M*, SHUBHAPRIYA KH*

**RR College of Pharmacy, *Visveswarupa Institute of Pharmaceutical Science, Bangalore.

Correspondence Address :
S. M. Firdous Mumtaz, Dept. of Pharmacology,
R R College of Pharmacy, Bangalore: 560090,
Karnataka, India. Phone 09886501454
E mail: firdous_cology@rediffmail.com

Abstract

Objective: To evaluate the Type 2 anti-diabetic activity of saponins obtained from Momordica Cymbalaria in Streptozotocin–Nicotinamide Induced Type 2 diabetic mice.
Materials and Method: Type 2 diabetes in BALB/c mice was induced by a single intra-peritoneal injection of Streptozotocin (100 mg/ kg, i.p), 15 min after the intra-peritoneal administration of Nicotinamide (240 mg/ kg, i.p). Hyperglycaemia was confirmed by elevated blood glucose levels determined on day 7 after the injection. The saponin mixture was obtained from the ethanolic extract of Momordica Cymbalaria. Saponins of MC (SMC) 175mg/kg,p.o/30 days and Metformin350mg/kg,p.o/30 days were administered to the Type 2 diabetic mice. At the end of the treatment, their serum was analyzed for glucose, cholesterol, triglycerides and insulin; The pancreas of each mouse was studied to check whether there were any histological changes.
Result: Treatment of Type 2 diabetic mice with SMC (175mg/kg, p.o/30 days) and Metformin (350mg/kg,p.o/30 days) produced a significant fall in blood glucose (p<0.001), cholesterol (p<0.001), triglycerides (p<0.001) and an increase in the serum insulin level (p<0.001). Pancreatic islets and beta cells showed an increase in numbers.
Conclusion: Saponins of MC have significant Type 2 anti-diabetic activity and the activity may be due to increasing insulin secretion, probably by the regeneration of pancreatic beta cells.

Introduction
Diabetes mellitus (DM) is a chronic disease caused by inherited and/ or acquired deficiency in the production of insulin by the pancreas, or by the ineffectiveness of the insulin produced (1) . Reports from the World Health Organization (WHO) indicate that diabetes mellitus is one of the major killers of our time, with people in Southeast Asia and the Western Pacific being most at risk (2).

Plants have always been an exemplary source of drugs and many of the currently available drugs have been derived directly or indirectly from them. The ethno-botanical information reports about 800 plants that may possess anti-diabetic activity when being assessed using the presently available experimental techniques (3).

Momordica cymbalaria Fenzl (MC) (Cucurbitaceae) is a species found in the states of Karnataka and Andhra Pradesh, India. Its tuber is traditionally used as an abortifacient (4) and it is also used locally for the treatment of diabetes mellitus. We have reported its anti-ovulatory, abortifacient, anti-implantation and cardio-protective activities (5),(6),(7). Fruits of MC are also reported to have antimicrobial activity (8).The fruit powder and extracts of MC were previously reported to have Type 1 anti-diabetic activity in experimental diabetic models (9),(10),(11) .Researchers have reported that SMC have anti-diabetic activity and the anti-diabetic activity may be due to reversing of the atrophy of the pancreatic islets of β-cells, as a result of which there may be increased insulin secretion and increase in the hepatic glycogen level and these may attenuate Hyperinsulinaemia. The alpha-adrenergic blocking effect might contribute to their insulin secretion and sensitizing effects (12).

Type 2 diabetes is more prevalent than Type 1 but interestingly, the effect of Momordica Cymbalaria on Type 2 diabetes is not being reported. Hence, in the present study, an attempt has been made to elucidate the effect of Momordica Cymbalaria on Type 2 diabetes.

Material and Methods

Drugs and chemicals
The fresh roots of Momordica Cymbalaria, Fenzl, were collected from Gadag district of Karnataka and were identified and authenticated by Dr.Sreenath, Department of Botany, Bangalore University, Bangalore. The roots of Momordica Cymbalaria were isolated, chopped into small pieces, dried under shade at room temperature for seven days and were powdered. The powder was extracted with ethyl alcohol to get a yield of 14.1 % w/w. The ethanolic extract of Momordica Cymbalaria was dissolved in hot distilled water and was partitioned between water saturated n-butanol and a water layer. The organic layer (n-butanolic layer) was separated and evaporated to get a residue. This n-butanolic residue was dissolved in methanol and was poured in diethyl ether (Et2O) to obtain a flocculent precipitate. This precipitate was separated by using a filter paper and was washed with excess of Et2O and dried to yield a crude fraction of saponins –(13).The saponin mixture was dissolved in distilled water (SMC) and was used for the study. All other chemicals and reagents used, were of analytical grade

Animals
Male BALB/c mice weighing 20-25 g, of either sex and male Swiss albino mice weighing 20 ± 5 g, were procured from NIMHANS (National Institute of Mental Health and Neuro Science), Bangalore, at least 2 weeks prior to the study. The animals were maintained under controlled standard animal house conditions with ad libitum access to food and water. They were fed with standard mice feed (Amrut rat and mice feed, Pranav agro industries Ltd. Sangli, India). The Institutional Animal Ethics Committee’s permission was obtained before starting the experiments on the animals. The oral acute toxicity study was performed using the up and down procedure (OPPTS guidelines).

Induction of Experimental Diabetes
Streptozotocin (STZ) was dissolved in cold 50mM-citric acid buffer and Nicotinamide was dissolved in normal saline at the time of use. Type 2 diabetes mellitus was induced (14) in overnight-fasted BALB/c mice by a single intra-peritoneal injection of 100 mg/ kg of Streptozotocin, 15 min after the intra-peritoneal administration of 240 mg/ kg of Nicotinamide. Hyperglycaemia was confirmed by elevated blood glucose levels determined on day 7 after the injection. Only mice which were confirmed to have permanent Type 2 diabetes were used for the anti-diabetic study (23).

Experimental Design
A total of 24 mice (18 diabetic surviving mice, 6 control mice) were divided into four groups of six mice each.

Group 1 - Control mice,
Group 2 - Diabetic mice – Administered intra-peritoneal with Streptozotocin (100mg/kg i.p.) and Nicotinamide (240mg/kg i.p)
Group 3 - Diabetic mice administered orally with SMC 175 mg/kg, p.o/30days,
Group 4 - Diabetic mice administered orally with Metformin (350mg/kg, p.o/30days).

At the end of the experimental period on the 31st day, the mice were deprived of food overnight and blood was collected in a tube containing potassium oxalate and sodium fluoride for the estimation of plasma glucose, cholesterol, triglycerides, HDL and insulin by puncturing the retro orbital. The animals were sacrificed immediately. The pancreas of each was isolated, they were fixed in 10% formalin buffer for 24 h, dehydrated in alcohol and were then embedded in paraffin. The paraffin blocks were sectioned at 5 mm intervals and were stained with haematoxylin-eosin for histological examinations (22).

Biochemical Procedures
Serum glucose, triglycerides, cholesterol and HDL-cholesterol were analyzed by using an Auto span diagnostic kit. Serum insulin was measured using The ADVIA Centaur analyzer (RIA) (Bayer diagnostics.)

HPTLC Fingerprinting

The HPTLC fingerprinting of SMC was performed. Silica gel 60F254 (Merck) was used as a stationary phase. Chloroform: Glacial acetic acid (9.5:0.5) was used as a mobile phase. The dried plate was scanned to visualize the migrated components under UV radiation at 254 nm, 336 and 540 ηm using Reprostar 3 with a digital camera (CAMAG).

Statistical Analysis
All the data were analyzed using One-Way ANOVA, followed by Tukey’s multiple comparison tests. All values were reported as mean +/- SEM.




Results

Acute Toxicity Test
Mortality in the acute toxicity test of SMC was seen in the limit test at the dose of 5000 mg/kg. Mortality was not seen in the main test up to a dose of 1750 mg/kg and hence, 1/10th of 1750mg/kg (175 mg/kg) was selected for the study.

Effect On Type 2 Diabetes
Type 2 diabetic rats treated with SMC (175mg/kg, p.o/day/30days) showed a significant (p<0.001) decrease in serum glucose, cholesterol and triglyceride levels, whereas there was a significant (p<0.001) increase in the serum insulin level. Type 2 diabetic rats treated with Metformin (350mg/kg, p.o/day/30days) also showed a significant decrease in serum glucose, cholesterol and triglyceride levels and a significant increase in serum insulin levels (Table/Fig 1).

Histopathology
Histopathology studies in the NIDDM control group showed reduction in the number of pancreatic islets as well as in the number of beta cells. The islets were irregularly shaped, relatively small and atrophic. Most of the beta cells were destroyed and even if present, they were destroyed partially (Table/Fig 2). Most cells of the islets were small and degranulated, with scanty cytoplasm. Insulin producing beta cells were drastically decreased, whereas glucagon producing alpha cells were predominantly present. Severe vacuolation and degranulation were present in the beta cells of a maximum number of islets. The treatment group (SMC) showed an increase in the number of pancreatic islets and in the number of beta cells in the pancreas. Beta cells were seen in clusters.


Discussion

Streptozotocin (STZ) is a widely used chemical inducer for Type 1 diabetes (15). STZ has been shown to produce free radicals in the body, which specifically cut DNA chains in the pancreatic beta cells, resulting in disorder of the function of the pancreatic beta cells and at a later phase, destruction of the beta cells by necrosis (16). Nicotinamide dinucleotide(NA) (17) causes activation of the poly ADP ribose synthase to repair the damaged DNA (18) and STZ/NA. The Type 2 diabetic model possesses characteristics quite similar to the Type 2 non-obese diabetes, which constitutes a majority of East Asian diabetic cases (Table/Fig 3).

Fruits of MC and its extracts have been shown to have Type 1 anti-diabetic activity(9),(10),(11). The present study showed that the anti-diabetic activity of SMC may be due to reversing of the atrophy of the pancreatic islets of the beta-cells, as a result of which there may be increase in insulin secretion, increase in the hepatic glycogen level and attenuation of Hyperinsulinemia. The alpha-adrenergic blocking effect might contribute to insulin secretion and sensitizing properties (12) .


Hypoglycaemic phytochemicals in Momordica Charantia include a mixture of steroidal saponins known as charantins which are insulin-like peptides (19). The anti-diabetic activity in the present study is also attributed to Saponins. SMC significantly lowered the serum glucose levels and increased serum insulin levels in Type 2 diabetic mice. Histopathology of the pancreas was done to study the effect of SMC on beta cells. The SMC treated group showed an increase in the number of pancreatic islets and beta cells in the pancreas. This indicated that SMC was regenerating beta cells. The regeneration of the beta cells of the STZ-destructed islets is probably due to the fact that the pancreas contains stable (Quiescent) cells which have the capacity of regeneration. Therefore, the surviving cells can proliferate to replace the lost cells. Gynmnema Sylvestre also increases insulin secretion, probably by the regeneration of pancreatic beta cells (20). Many other plants are being reported to regenerate atrophied pancreatic islets, restore the secretion of insulin, and thus correct hyperglycaemia.

Diabetes is associated with hypercholesterolaemia and hypertriglyceridaemia. STZ-diabetes showed increased plasma levels of cholesterol, triglycerides, free fatty acids and phospholipids (21). Insulin deficiency may be responsible for dyslipidaemia. Insulin has an inhibitory action on HMG-COA reductase, a key rate-limiting enzyme responsible for the metabolism of cholesterol rich LDL particles. The mechanisms responsible for the development of hypertriglyceridaemia in uncontrolled diabetes in humans are due to a number of metabolic abnormalities that occur sequentially. SMC significantly lowered serum cholesterol and triglyceride levels. As reported earlier (12), this effect may be due to increased insulin secretion and the inhibition of the HMG CoA enzyme.

Hence, Saponins of MC in the present study have shown significant Type 2 anti-diabetic activity and the activity may be due to increased insulin secretion, probably by the regeneration of the pancreatic beta cells.

References

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. Pulok K, Kuntal M, PeterJ, Mukherji KA. Review on Leads from Indian medicinal plants with hypoglycemic potentials.2006; 106(1):1-28.
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. Koneri R, Balaraman R, Saraswati CD . Antiovulatory and abortifacient potential of the ethanolic extract of roots of Momordica cymbalaria Fenzl in rats. Indian J Pharmacol. 2006; 38:111-14
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. Koneri R, C.D Saraswati., R. Balaraman, E.A Ajeesha.. Antiimplantation activity of the ethanolic root extract of Momordica cymbalaria Fenzl in rats. Indian J Pharmacol. 2007; 9:90-6
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. Koneri R, Balaraman R, Hariprasad, Vinoth Kumar M, Ali A. Cardioprotective effect of Momordica Cymbalaria fenzl in rats with Isoproterenol-induced Myocardial injury. Journal of Clinical and Diagnostic Research. 2008; 2:699-705
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. Swamy VBM, Jayaveera KN. Antimicrobial properties of Momordica cymbalaria hook. F.Pharmacologyonline.2007;3:505-10
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. Kameswararao B, Kesavulu MM, Apparao C. Evaluation of antidiabetic effect of Momordica cymbalaria fruit in alloxan-diabetic rats. Fitoterpia. 2003; 74:7-13.
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. Kameswararao B., Kesavulu MM, Ch Apparao. Antihyperglycemic activity of Momordica Cymbalaria in alloxan diabetic rats.J. Ethnopharmacol. 2001;78: 67-71
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. Kameswararao B, Kesavulu MM, Giri R, Apparao C. Antidiabetic and hypolipidemic effect of Momordica Cymbalaria Hook. fruit powder in alloxan-diabetic rats J. Ethnopharmacol. 1999;67:103-9
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. Raju K, Balaraman R. Antidiabetic Mechanisms of Saponins of Momordica Cymbalaria. Phcog Mag. 2008; 4(14): 160
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