Phytoformulation with hydroxycitric acid and capsaicin protects against high-fat-diet-induced obesity cardiomyopathy by reducing cardiac lipid deposition and ameliorating inflammation and apoptosis in the heart.

Background and aim: Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. Experimental procedure: Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16. Results and conclusion: We found that HFD supplementation resulted in significant hyperglycemia and caused an increase in cardiac lipid deposition, inflammation and apoptosis in the heart. Phytoformulation therapy not only significantly decreased blood levels of glucose, cholesterol, triglycerides, free fatty acids, and inflammatory cytokines in obese rats, but also protected cardiac tissue, as shown by histological analysis. Conversely, phytoformulation therapy decreased mRNA levels for sterol regulatory element-binding factor 1, fatty acid synthase, acetyl-CoA carboxylase, and fatty acid binding protein 1 genes involved in fatty acid synthesis and absorption in obese rats. It increased the levels of lysosomal acid lipase, hormone-sensitive lipase, and lipoprotein lipase genes involved in fatty acid degradation in the heart. In addition, the phytoformulation improved cardiac inflammation and apoptosis by downregulating the genes nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumour necrosis factor α, interleukin-6, toll-like receptor-4 (TLR-4), BCL2-associated X and caspase-3. In conclusion, our results show that the phytoformulation improved insulin sensitivity and attenuated myocardial lipid accumulation, inflammation, and apoptosis in the heart of HFD-induced obese rats by regulating fatty acid metabolism genes and downregulating NF-kB/TLR-4/caspase-3.

Pathophysiology of obesity-related infertility and its prevention and treatment by potential phytotherapeutics.

BACKGROUND: Obesity is a complex multifactorial disease in which the accumulation of excess body fat has adverse health effects, as it can increase the risk of several problems, including infertility, in both men and women. Obesity and infertility have risen together in recent years. Against this background, the present review aims to highlight the impact of obesity on infertility and the underlying pathophysiology of obesity-related infertility (ORI) in men and women, and to provide readers with knowledge of current trends in the effective development of phytotherapeutics for its treatment. METHODS: We thoroughly searched in PubMed, MEDLINE, Scopus, EMBASE, and Google Scholar to find all relevant papers on ORI and the therapeutic effects of phytotherapeutics on ORI in men and women. RESULTS: The extensive search of the available literature revealed that obesity affects reproductive function through several complex mechanisms such as hyperlipidaemia, hyperinsulinaemia, hyperandrogenism, increased body mass index, disruption of the hormonal milieu, systemic inflammation, oxidative stress, alterations in epigenetics and dysbiosis. On the other hand, several studies reported that phytotherapeutics has a broad therapeutic spectrum of action by improving sex hormone homeostasis, ovarian dysfunction, menstrual cycle and inhibiting ovarian hyperplasia, as well as down-regulating ovarian apoptosis, inflammation and oxidative stress, and controlling metabolic dysfunction in obese women. Male infertility is also addressed by phytotherapeutics by suppressing lipogenesis, increasing testosterone, 3ß-HSD and 17ß-HSD levels, improving sperm parameters and attenuating testicular dyslipidaemia, oxidative stress, inflammation and germ cell apoptosis. CONCLUSIONS: In the present review, we discussed the effects of obesity on reproductive dysfunction in men and women and the underlying pathophysiology of ORI. In addition, the therapeutic effect of phytotherapeutics against ORI was highlighted.

Linalool attenuates lipid accumulation and oxidative stress in metabolic dysfunction-associated steatotic liver disease via Sirt1/Akt/PPRA-α/AMPK and Nrf-2/HO-1 signaling pathways.

INTRODUCTION: Linalool is a monoterpene that occurs naturally in various aromatic plants and is identified in our previous study as a potential candidate for protection against high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD). However, little is known about its direct effects on hepatic lipid metabolism and oxidative stress. Therefore, this study aims to investigate the therapeutic effect of linalool against MASLD and the underlying mechanism. METHODS: To establish a rat model of MASLD, male Wistar rats were fed HFD for 16 weeks and orally administered linalool (100 mg/kg body weight) for 45 days starting from week 14. RESULTS: Linalool significantly reduced HFD-induced liver lipid accumulation and restored altered adipokine levels. Mechanistically, linalool downregulated the mRNA expression of sterol regulatory element binding protein 1 and its lipogenesis target genes fatty acid synthase and acetyl-CoA carboxylase, and upregulated the mRNA expression of genes involved in fatty acid oxidation (peroxisome proliferator-activated receptor (PPAR)-alpha [PPAR-α], lipoprotein lipase and protein kinase B [Akt]) as well as the upstream mediators sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) in the liver of MASLD rats. In addition, linalool also curbed oxidative stress by increasing antioxidant enzymes and activating nuclear erythroid-2-related factor 2 (Nrf-2) and its downstream target genes involved in antioxidant properties. CONCLUSION: Therefore, this study concludes that linalool attenuates lipid accumulation in the liver by inhibiting de novo lipogenesis, promoting fatty acid oxidation, and attenuating oxidative stress by regulating Sirt1/Akt/PPRA-α/AMPK and Nrf-2/ HO-1 signaling pathways.

Phenolic fraction extracted from Kedrostis foetidissima leaves ameliorated isoproterenol-induced cardiotoxicity in rats through restoration of cardiac antioxidant status.

In this study, the cardioprotective effects of partially purified phenolic fraction of Kedrostis foetidissima leaves (PFK) were evaluated in isoproterenol (ISO)-induced myocardial infarction rat model. ISO induction to experimental rats for two consecutive days significantly increased the levels of triglycerides, cholesterol, phospholipids, free fatty acids, low-density lipoproteins, and cardiac biomarker enzymes, and decreased the levels of high-density lipoproteins and antioxidant enzyme activity. Pretreatment of experimental rats with PFK for 45 days led to a significant elevation in antioxidant enzyme activity. PFK-pretreated rats exhibited significantly reduced levels of circulating lipids and cardiac-specific biomarker enzymes compared to ISO-treated rats. Thus, the present study demonstrated that PFK ameliorated ISO-induced cardiotoxicity through the augmentation of the endogenous cardiac antioxidant system, thereby modulating the lipid peroxidation caused by ISO-induced free radicals, and prevented the myocardial damage, which was confirmed through histopathological analysis. PRACTICAL APPLICATIONS: Kedrostis foetidissima is edible medicinal plant and phenolic fraction extracted from the leaves of this plant may help the common man in the protection of heart. The phenolic fraction shows significant antioxidant activity, so this might be referred to as dietary supplement and also helps to develop new pharmaceutical formulations.

Excitation-induced tunable luminescence of luminomagnetic Dy and Ce co-doped ZnO nanoparticles.

Here, 1 mol% Dy,Ce co-doped ZnO nanoparticles were synthesized via a simple, cost-effective combustion method which could produce large-scale products. The structure and phase purity of synthesized nanoparticles were shown by X-ray diffraction, selected-area-electron-diffraction patterns and Raman spectroscopy to be a hexagonal wurtzite structure with no secondary peaks. Spherical morphology was shown by field emission scanning electron microscopy and high-resolution transmission electron microscopy. The presence of dopants with elemental composition was authenticated by energy dispersive spectroscopy and elemental mapping. Enhanced reflectance in the visible region for Ce-doped ZnO samples was noted by diffuse reflectance spectroscopy. An increase in the bandgap for doped samples was indicated by the Kubelka-Munk function. Significant visible luminescence was observed, which varied with different excitations. The room-temperature weak ferromagnetic behaviour of 2 mol% Ce-doped ZnO and distinct paramagnetic behaviour of 1 mol% Dy,Ce co-doped ZnO was detected using vibrating sample magnetometry.

Effect of Morphology of Platinum Nanoparticles on Benzene Oxidation Activity.

The effect of morphology of Platinum (Pt) nanoparticles supported on alumina (γ-Al2O3) for complete catalytic oxidation of volatile organic compounds (VOCs) was investigated. Pt nanoparticles were synthesized through a simple method comprising of reduction followed by calcination of metal precursor coated chitosan templates using three different reducing agents: sodium borohydride (NaBH4), hydrazine (N2H4) and hydrogen (H2). The morphology and facet orientation of Pt nanoparticles were influenced by the reducing agents. The catalytic oxidation performance studies of these Pt nanoparticles loaded on γ-Al2O3 for VOCs showed strong dependence of their activities on their morphologies. High indexed facet (220) Pt nanosheets synthesized through NaBH4 reduction showed superior catalytic oxidation activity compared to the catalysts prepared using other reducing agents. Cyclic performance studies on these catalysts showed stable benzene oxidation performance implying their thermal stability. The absence of any shape directing agents in the synthesis of Pt nanoparticles with homogeneous morphologies and preferential orientation is an aspect that can be extended to other catalytic applications.

An overview of quinazolines: Pharmacological significance and recent developments.

Most of the drugs and pharmacologically relevant molecules possess heterocyclic ring structures and presence of hetero atoms or groupings divulges privileged specificities in their pharmacological targets. Especially the heterocyclic systems, quinazoline is a biologically imperative scaffold known to be linked with several pharmacological activities. Some of the protuberant pharmacological responses attributed to this system are analgesic, anti-inflammatory, anti-convulsant, sedative-hypnotic, anti-histaminic, anti-hypertensive, anti-cancer, anti-microbial, anti-tubercular and anti-viral activities. This multiplicity in the pharmacological response contours of quinazoline has attracted the consideration of medicinal chemists to explore this system to its multiple potential against numerous activities. Several of these synthetic and pharmacological investigations have been successively studied for structure-activity relationship (SAR) to correlate the particular structural features for their pharmacological target. The emerging understanding of quinazoline derivatives on their pharmacological target offer opportunities for novel therapeutics. This review principally emphases on the medicinal chemistry aspects including drug design, structure-activity relationships (SARs), and mechanism of actions of quinazoline derivatives. This review gives detailed attention on in vitro and in vivo pharmacological activities of quinazoline and its analogs in the perspective of drug discovery and its development.

Phosphatidylglycerol is implicated in divisome formation and metabolic processes of cyanobacteria.

Phosphatidylglycerol is an essential phospholipid for photosynthesis and other cellular processes. We investigated the role of phosphatidylglycerol in cell division and metabolism in a phophatidylglycerol-auxotrophic strain of Synechococcus PCC7942. Here we show that phosphatidylglycerol is essential for the photosynthetic electron transfer and for the oligomerisation of the photosynthetic complexes, notably, we revealed that this lipid is important for non-linear electron transport. Furthermore, we demonstrate that phosphatidylglycerol starvation elevated the expressions of proteins of nitrogen and carbon metabolism. Moreover, we show that phosphatidylglycerol-deficient cells changed the morphology, became elongated, the FtsZ ring did not assemble correctly, and subsequently the division was hindered. However, supplementation with phosphatidylglycerol restored the ring-like structure at the mid-cell region and the normal cell size, demonstrating the phosphatidylglycerol is needed for normal septum formation. Taken together, central roles of phosphatidylglycerol were revealed; it is implicated in the photosynthetic activity, the metabolism and the fission of bacteria.

Therapeutical Perspectives of S-Allylcysteine: Effect on diabetes and other disorders in Animal Models.

Plants derived constituents with impending therapeutic values have been used long time to cure various diseases and disorders including Diabetes mellitus (DM). Many of the medicinal plants and herbs are also part of our diet as spices, vegetables and fruits. In recent years, there is growing evidence that plant-foods molecules, due to their biological properties, may be unique nutraceuticals and supplementary treatments for various aspects of Diabetes mellitus. In this review, we addressed the potential efficacies of S-Allylcysteine (SAC), a sulfur containing amino acid, derived from garlic, on Diabetes mellitus and other disorders. Substantiate with several in vitro, animal models and some human studies, SAC revise carbohydrate and lipid metabolism, alter hyperglycemia, hyperlipidemia and insulin resistance, recuperate adipose tissue metabolism, and improve oxidative stress and stress-sensitive signaling pathways and inflammatory processes. In Conclusion, S-Allycysteine showed several beneficial effects on various disorders and there is no scientific evidence against S-Allycysteine adverse effects, and proved that consumption of S-Allylcysteine has numerous pharmacological benefits.

Cardioprotective activity of Amaranthus viridis Linn: effect on serum marker enzymes, cardiac troponin and antioxidant system in experimental myocardial infarcted rats.

BACKGROUND: Cardiovascular diseases (CVDs) have a high prevalence in developing and developed countries and myocardial infarction accounts for majority of deaths and disabilities. The current study dealt with the protective role of Amaranthus viridis Linn on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. METHODS: Subcutaneous injection of ISO (20 mg/kg body weight in 1 ml saline) to rats for two consecutive days offered significant alteration in cardiac marker enzymes (AST, ALT, LDH and CPK), cardiac troponin, lipid peroxidation products (TBARS and hydroperoxide) and antioxidant system (CAT, SOD, GPx, GST, GSH and GSSG). ISO-induced myocardial damage was indicated by increased activities of marker enzymes in serum and the levels of cardiac troponin in the serum. In addition to these diagnostic markers, the levels of lipid peroxidation products in the heart were significantly (p<0.05) increased and the activities of enzymic antioxidants and non-enzymic antioxidant such as glutathione in the heart was significantly (p<0.05) decreased and GSSG in the heart was increased in ISO-induced rats. RESULTS: Effect of Amaranthus viridis oral treatment (100, 200 and 300 mg/kg body weight) for 45 days elicited a significant cardio protective activity by lowering the levels of serum marker enzymes, cardiac troponin, GSSG and lipid peroxidation and elevated the levels of antioxidant enzymes and GSH. The effect at a dose of 300 mg/kg of A. viridis was more pronounced than that of the dose 100 mg/kg and 200mg/kg and brought back all the parameters to near normal. The effect produced by A. viridis was compared with α-tocopherol. CONCLUSIONS: The present findings have demonstrated that the cardioprotective effects of A. viridis in ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation of membrane.

Synthesis, analgesic, anti-inflammatory and ulcerogenic properties of some novel N'-((1-(substituted amino)methyl)-2-oxoindolin-3-ylidene)-4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl)benzohydrazide derivatives.

A new series of N'-((1-(substituted amino)methyl)-2-oxoindolin-3-ylidene)-4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4H)-yl)benzohydrazide derivatives 4a-4l were designed and synthesized from anthranilic acid. All the synthesized compounds were characterized by spectroscopic means and elemental analyses. The tail-flick technique and the carrageenan-induced foot paw edema test were performed for screening analgesic and anti-inflammatory activity, respectively. All of the compounds were also examined for their ulcerogenicity. Some of the compounds showed significant activity. Among the test compounds, 4b exhibited 53% and 69% analgesic activity at a dose of 10 and 20 mg/kg, respectively. It also displayed 47% (10 mg/kg) and 65% (20 mg/kg) anti-inflammatory activity with one-fourth of ulcer index of the reference drugs diclofenac and aspirin.

Antidiabetic effect of S-allylcysteine: Effect on plasma and tissue glycoproteins in experimental diabetes.

The present study was conducted to investigate the effect of S-allylcysteine (SAC) on dearrangement in glycoprotein levels in the streptozotocin induced diabetic model. SAC (150 mg/kg b.w./day) was administered orally for 45 days to normal and diabetic rats. STZ-induced diabetic rats showed significant increase in blood glucose and glycoprotein components such as hexose, hexosamine, fucose and sialic acid in plasma, liver and kidneys of diabetic rats. Oral administration of SAC to diabetic rats for a period of 45 days normalized all the above-mentioned biochemical parameters. The antihyperglycemic effect of SAC was compared with glyclazide, a well-known antihyperglycemic drug. The present study indicates that SAC possesses a significantly beneficial effect on the glycoprotein moiety in addition to its antidiabetic effect.

Synthesis and pharmacological evaluation of schiff bases of 4-(2-aminophenyl)-morpholines.

In the present study, a novel series of 4-(2-aminophenyl)morpholines were synthesized and characterized by IR, (1)H-NMR, (13)C NMR and mass spectral analysis. The synthesized compounds were screened for analgesic (100 and 200 mg/kg), antiinflammatory (200 and 400 mg/kg), antibacterial (Bacillus subtilis, Bacillus cereus, Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli) and antifungal (Candida albicans and Aspergillus niger) activities. The minimum inhibitory concentrations of the compounds were also ascertained by agar streak dilution method. N-benzylidine-2-morpholoino benzenamine (1) and N-(3-nitro benzylidine)-2-morpholino benzenamine (3) exhibited significant analgesic, antiinflammatory and antimicrobial activities.

Synthesis, in vitro antibacterial and antifungal evaluations of 2-amino-4-(1-naphthyl)-6-arylpyrimidines.

A series of 2-amino-4-(1-naphthyl)-6-arylpyrimidines have been synthesized and characterized by IR, NMR, MS, elemental analyses and evaluated for in vitro antibacterial and antifungal activities. Some of the compounds were found to be active against a limited panel of bacteria and fungi. In particular, compounds 4b and 4e were found to be the most effective analogs against the tested bacterial and fungal strains.

Effect of garlic (Allium sativum) on lipid peroxidation in experimental myocardial infarction in rats.

The present study was conducted to elucidate the antioxidant role of garlic oil in isoproterenol (IPL)-induced myocardial infarction in rats. In myocardial necrosis induced by isoproterenol, a significant increase in serum iron content with a significant decrease in plasma iron binding capacity, ceruloplasmin activity and glutathione (GSH) level were observed. There was also a significant increase in lipid peroxides levels on isoproterenol administration. Activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GRD) were decreased significantly in heart with isoproterenol-induced myocardial necrosis. Garlic oil produced a marked reversal of these metabolic changes related to myocardial infarction induced by isoproterenol. In conclusion, garlic oil exerts its effects by modulating lipid peroxidation and enhancing antioxidant and detoxifying enzyme systems.

Effect of Cogent db, a herbal drug, on serum and tissue lipid metabolism in experimental hyperglycaemic rats.

AIMS: We have previously reported the antidiabetic effect of Cogent db. The present study with alloxan-induced hyperglycaemic rats is focused on the mechanism of action, specifically on the activity of hepatic lipogenic enzymes, serum and tissue lipids. METHODS: Male Wistar rats body weight of 180-200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes: normal rats; diabetic control; diabetic rats given Cogent db (0.45 g/kg body weight); diabetic rats given glibenclamide (600 micro g/kg body weight). After 40 days treatment, fasting blood glucose, plasma insulin, activities of hepatic lipogenic enzymes, serum and tissue lipids were determined in normal and experimental animals. RESULTS: Oral administration of Cogent db for 40 days resulted in significant reduction in blood glucose, serum and tissue (liver and kidney) lipids, whereas the level of plasma insulin and the activity of hepatic lipogenic enzymes were significantly increased in alloxan diabetic rats. Similar studies using glibenclamide have been conducted to compare the mode of action of these two drugs. CONCLUSIONS: Thus our study shows that Cogent db exhibits a strong antihyperlipidaemic effect, which could exert a beneficial action against macrovascular complications (cardiovascular disease) associated with diabetes mellitus.

Familial clustering of diabetic retinopathy in South Indian Type 2 diabetic patients.

AIM: The aim of the study was to determine whether there is familial clustering of diabetic retinopathy among South Indian Type 2 diabetic subjects. METHODS: During the period September 1991 to September 1997, 322 families with at least two diabetic siblings who were registered at our centre and had undergone a retinal examination were selected for the study. The sibling with the longest duration of diabetes was defined as the proband. The prevalence of retinopathy was compared between the siblings of probands with and without retinopathy. RESULTS: Diabetic retinopathy was diagnosed in 11.2% of the siblings of the probands without diabetic retinopathy and in 35.3% of the siblings of the probands with diabetic retinopathy (P < 0.0001). The increased prevalence of retinopathy among siblings of probands with retinopathy represented all grades of retinopathy, namely non-proliferative diabetic retinopathy with and without maculopathy and proliferative diabetic retinopathy, although the latter did not reach statistical significance due to the small numbers. Hypertension, metabolic control and the duration of diabetes among the probands did not affect the clustering of retinopathy. The odds ratio for retinopathy in the siblings of probands with retinopathy after adjusting for age, glycosylated haemoglobin, duration of diabetes, proteinuria and other confounding variables was 3.37(95% confidence interval 1.56-7.29, P = 0.002). CONCLUSIONS: Familial clustering of diabetic retinopathy was three times higher in siblings of Type 2 diabetic subjects with diabetic retinopathy.

Effect of cogent db, a herbal drug, on plasma insulin and hepatic enzymes of glucose metabolism in experimental diabetes.

AIMS: The present study was designed to investigate the effect of cogent db, a polyherbal drug on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats. METHODS: Male Wistar rats body weight of 180-200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group: Group 1, normal rats given 2 ml of saline; Group 2, diabetic control rats given 2 ml of saline; Group 3, diabetic rats given aqueous solution of cogent db (0.45 g/body kg weight); and Group 4, diabetic rats given aqueous solution of glibenclamide (600 micro g/kg body weight). The treatment was given for 40 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals. RESULTS: Treatment with cogent db resulted in a significant reduction in blood glucose and the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity were significantly increased in alloxan-diabetic rats. CONCLUSIONS: The present investigation suggests that cogent db controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible because it regulates the activities of hepatic glucose metabolic enzymes.

Lipoprotein(a) in South Indian type 2 diabetic subjects in relation to diabetic vascular complications.

OBJECTIVES: Lipoprotein(a) [LP(a)] has been reported to be an independent risk factor for coronary artery disease (CAD). However, its relationship with other vascular complications is not clear. The aim of the study was to determine the relation of lipoprotein(a) with micro- and macrovascular complications seen in type 2 diabetic patients. METHODS: We studied 725 type 2 diabetic patients with and without diabetic complications at the MV Diabetes Specialities Centre, Chennai. The mean age of the study group was 54 +/- 10 years and 70% were males. Diabetic complications viz retinopathy, proteinuria, peripheral vascular disease and coronary artery disease were diagnosed using standardized definitions. Lipoprotein(a) levels were measured using enzyme linked immunosorbant assay (ELISA). Since the frequency distribution of Lp(a) was skewed Lp(a) values were log transformed and geometric mean was used for statistical analysis. RESULTS: The mean Lp(a) level of patients with any vascular complication was significantly higher compared to the subjects without any complications. Multiple logistic regression analysis revealed that lipoprotein(a) had as independent association with CAD (Odds Ratio -1.16, p=0.04) and proteinuria (Odds Ratio -1.69, p < 0.001). The association of Lp(a) with retinopathy and PVD turned out to be non-significant when CAD and proteinuria was introduced as cofactors in the regression model. CONCLUSION: Lp(a) concentrations are found to be higher in those with CAD and proteinuria. There appears to be no association between Lp(a) and retinopathy or PVD in South Indian type 2 diabetic patients.

Relationship of tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen with coronary artery disease in South Indian male subjects.

AIM: Prevalence rates of coronary artery disease (CAD) are reported to be very high in Asian Indians. Conventional risk factors do not explain the high rates of CAD among Indians. Recently, several newer risk factors have been reported to be associated with CAD. We measured tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen levels in South Indian diabetic and non-diabetic subjects with and without CAD. METHODS: Four groups of subjects were studied (all males); Group 1 comprised of non-diabetic subjects without CAD (n=50). Non-diabetic subjects with CAD formed group 2 (n=50); group 3 comprised of type 2 diabetic patients without CAD (n=50) and group 4 consisted of type 2 diabetic patients with CAD (n=50). CAD was diagnosed based on coronary angiographic evidence of severe double or triple vessel disease. RESULTS: Both diabetic and non-diabetic patients with CAD had significantly higher levels of tPA, PAI-1 and fibrinogen compared to non-diabetic without CAD (p < 0.05). Patients with CAD were distributed more in the upper tertiles of these risk factors compared to those without CAD. A strong association between tPA and PAI-1 was noted in the Pearson's correlation analysis (p < 0.001). Univariate regression analysis showed tPA (Odds ratio--1.12, p = 0.03), PAI-1 (Odds ratio--1.03, p = 0.008), fibrinogen (Odds ratio--1.01, p < 0.0001), serum cholesterol (Odds ratio--1.008, p = 0.04) and hypertension (Odds ratio--3.7, p = 0.0001) to be associated with CAD. Multiple logistic regression analysis revealed hypertension (Odds ratio--4.6, 95% confidence interval--2.113-9.950, p = 0.0001) and fibrinogen (Odds ratio--1.012, 95% confidence interval--1.007-1.018, p = 0.0001) as risk factors for CAD. CONCLUSION: Our study suggests that prothrombogenic risk factors particularly fibrinogen may be associated with CAD in South Indians.