Effect of Musa sapientum Stem Extract on Animal Models of Depression.

BACKGROUND: Musa sapientum, the banana plant, has shown to possess antioxidant activity in previous studies. Oxidative stress has been linked to the pathogenesis of major depressive disorder (MDD) with evidence of increased serum levels of oxidative stress biomarkers in MDD patients. OBJECTIVE: The present study aimed to evaluate the antidepressant activity of M. sapientum stem extract (MSSE) in experimental models in mice. MATERIALS AND METHODS: Forced swim test (FST) and tail suspension test (TST) were carried out in five different groups (n = 6/group) of mice. The vehicle, standard drug, and the three test groups were orally administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and incremental doses of 25, 50, and 100 mg of MSSE, respectively, 45 min prior to the experiment. RESULTS: On FST, the duration of immobility in control group, which was 161.5 ± 6.78 (in seconds, mean ± standard error of mean [SEM]), decreased to 149.33 ± 2.70 (25 mg/kg MSSE), 120.17 ± 8.35 (50 mg/kg MSSE), and 45.17 ± 4.11 (100 mg/kg MSSE) in the treated groups. On TST, the duration of immobility in control group, which was 173.83 ± 12.65 (mean ± SEM), decreased to 163.17 ± 6.91 (25 mg/kg MSSE), 139.0 ± 5.9 (50 mg/kg MSSE), and 124.0 ± 4.42 (100 mg/kg MSSE) in the treated groups. The difference in the duration of immobility was statistically significant at middle and higher doses, i.e. 50 and 100 mg/kg MSSE (P < 0.05) respectively, when compared with the control group in both the tests. CONCLUSION: A significant antidepressant-like activity was found in MSSE, which could be a potential natural compound for use in depression. SUMMARY: The five groups - vehicle, standard drug, and the three test groups were administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and incremental doses of 25, 50, and 100 mg of Musa sapientum stem extract (MSSE), respectivelyThe duration of immobility decreased in the treated groups as compared to the control group on both, forced swim and tail suspension, testsThe difference in the duration of immobility was statistically significant at middle and higher doses, i.e., 50 and 100 mg/kg MSSE (P < 0.05), when compared with the control group in both the tests. Abbreviations Used: MDD: Major depressive disorder; MSSE: Musa sapientum stem extract; FST: Forced swim test; TST: Tail suspension test; GSH: Glutathione, MDA: Malondialdehyde; SOD: Superoxide dismutase.

Antihypercholesterolemic and antioxidant effect of sterol rich methanol extract of stem of Musa sapientum (banana) in cholesterol fed wistar rats.

Musa sapientum Linn. (English 'Banana' family Musaceae), is a plant with nutritive, as well as medicinal value. Antihypercholesterolemic and antioxidant effect of methanolic extract of stem of this plant was investigated in hypercholesterolemic rats. Rats were made hypercholesterolemic by feeding cholesterol (100 mg/kg/day) suspended in soya oil. Treatment groups received extract at a dose of 10, 20 and 40 mg/kg/day in addition to cholesterol orally once daily. Fasting blood samples were collected before and after 6 weeks treatment. Animals were sacrificed and liver stored at -80 °C. Total cholesterol, HDL-cholesterol and triacylglycerol were estimated in blood. Malondialdehyde, reduced glutathione, superoxide dismutase and catalase were measured in blood and liver. Total lipids, HMG CoA redutase and lipoprotein lipase were investigated in liver. Most effective dose was found to be 20 mg/kg/day. Rise in total cholesterol, LDL + VLDL-cholesterol and triacylglycerol in animals receiving only cholesterol was 179 %, 417 % and 74 % respectively, while in animals receiving 20 mg/kg dose rise in these parameters was restricted to 40 %, 106 % and 24 %. HDL-cholesterol decreased by 12 % in extract treated group, while it decreased to 36 % in untreated hypercholesterolemic rats. Malonaldialdehyde, marker of lipid peroxidation decreased while reduced glutathione and enzymes superoxide dismutase and catalase increased significantly in blood and liver (p < 0.01). Total lipids in liver decreased and enzymes of lipid metabolism viz. HMG CoA redutase and lipoprotein lipase were restored to near normal. Gas chromatography mass spectroscopy indicated high content of sterols in extract. Study demonstrated that methanol extract of stem of Musa sapientum has significant antihypercholesterolemic and antioxidant effects.

Association of glutathione-S-transferase with patients of type 2 diabetes mellitus with and without nephropathy.

STATEMENTS OF THE PROBLEM: Hyperglycemia induced oxidative stress is implicated as a contributor to the onset and progression of type 2 diabetes mellitus (T2DM) and its complications like diabetic nephropathy (DN). Glutathione-S-transferase (GST) is primarily involved in the neutralization of reactive oxygen species (ROS) by enzymatic conjugation with the scavenger peptide glutathione (GSH). Therefore, present study was aimed to evaluate the role of GST along with oxidative stress markers and their correlation in patients with Type 2 diabetes mellitus with and without nephropathy. METHODS: This study comprised of 300 participants divided into three groups of 100 each: healthy controls (HC), T2DM without complications and DN. Plasma GST, malondialdehyde (MDA), reduced GSH levels and ferric reducing ability of plasma (FRAP) were estimated spectrophotometrically. RESULTS: Highest GST levels was observed in T2DM which was significantly higher (p<0.05) as compared to DN and HC. However, GSH and FRAP levels were found to be significantly lowest whereas MDA levels were significantly highest in DN as compared to T2DM and HC. GST showed a significant negative correlation with GSH, FRAP and positive correlation with MDA in both patients groups. CONCLUSIONS: Highest activity of GST in T2DM might be as a compensatory mechanism in response to oxidative stress. GST is found to have significant negative association with decreased GSH. Altered redox milieu in DN collectively conspire to increase the risk of renal damage in T2DM.

Genetic association of NAD(P)H quinone oxidoreductase (NQO1*2) polymorphism with NQO1 levels and risk of diabetic nephropathy.

NAD(P)H quinone oxidoreductase 1 (NQO1) catalyzes reactions having a cyto-protective effect against redox cycling and oxidative stress. A single base polymorphism (C/T) at nucleotide 609 of the NQO1 gene impairs the stability and function of its protein. Its role in the development of diabetic nephropathy (DN) has not been deciphered. Therefore, this study aimed to evaluate the association of NQO1*2 (rs1800566) polymorphism with plasma NQO1 levels and DN. This study screened 600 participants including healthy controls (HC), type 2 diabetes mellitus without complications (T2DM) and diabetic nephropathy (DN): 200 each for studying NQO1*2 gene polymorphism using the PCR-RFLP. Plasma NQO1 levels were measured by ELISA. Analysis of variance and logistic regression were used to evaluate the association of NQO1 polymorphism with plasma NQO1 levels and DN. The allelic frequencies of NQO1*1/NQO1*2 were 0.88/0.12 in HC, 0.765/0.235 in T2DM and 0.65/0.35 in DN. Carriers of the NQO1*2 allele had significantly lower plasma NQO1 levels (p<0.05) and revealed higher risk towards the development of DN (OR=1.717, p=0.010). NQO1*2 SNP is a functional polymorphism having a significant effect on NQO1 levels. Our results indicate that NQO1*2 genotype may increase susceptibility to DN in north Indian subjects with T2DM.

Association of tumor necrosis factor (TNF) promoter polymorphisms with plasma TNF-α levels and susceptibility to diabetic nephropathy in North Indian population.

AIM: The concept of diabetic nephropathy (DN) as a metabolic disease is now being replaced by chronic low-grade inflammatory disease. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine which plays an important role in the pathogenesis and clinical outcome of DN. Therefore, this work was planned to evaluate the association of -863C/A (rs1800630) and -1031T/C (rs1799964) polymorphisms in TNF gene with plasma TNF-α levels and DN among subjects with type 2 diabetes (T2DM) in a population from North India. METHODS: Age and sex matched 100 healthy controls (HC), 100 T2DM subjects without nephropathy (DM) and 100 subjects with DN were screened for above polymorphisms using the PCR-RFLP methods. Plasma TNF-α levels were measured by ELISA. Analysis of variance and logistic regression were used to associate individual polymorphisms with plasma TNF-α levels and DN. RESULTS: The allelic frequencies of -863C/A were 0.86/0.14 in HC, 0.72/0.23 in DM and 0.84/0.16 in DN, and that of -1031T/C were 0.89/0.11 in HC, 0.95/0.05 in DM and 0.80/0.20 in DN. The carriers of -863A allele had significantly lower plasma TNF-α levels (p<0.05). The -863C/A (OR=0.439, 95% CI=0.244-0.789, p=0.006) and -1031T/C (OR=3.0, 95% CI=1.355-6.642, p=0.007) were strongly associated with risk of development of DN. CONCLUSIONS: -863C/A was associated with low whereas -1031T/C with high TNF-α levels. The, results suggest that -863C/A polymorphism might be protective whereas -1031T/C may be associated with increased risk for DN in subjects with T2DM from North India.

Hypolipidemic and antioxidant activity of aqueous extract of fruit of Withania coagulans (Stocks) Dunal in cholesterol-fed hyperlipidemic rabbit model.

Withania coagulans (family: Solanaceae, English: Indian Cheese Maker, Hindi: Doda Paneer) fruit is known for its ethanopharmacological significance in health care system of India. Diet rich in high-fat is an important risk factor for diabetes, atherosclerosis and macro and microvascular complications. Treatment with aqueous extract of fruit of W. coagulans (aqWC; 250 mg/kg body weight) in cholesterol-fed animals resulted in significant decrease in the levels of total cholesterol, triacylglycerol, low density lipoprotein, tissue lipid content and acetyl CoA carboxylase activity whereas, the level of high density lipoprotein and activity of HMGCoA reductase also recovered partially. Treatment with aqWC also significantly decreased plasma lipid peroxide levels and increased reduced glutathione and superoxide dismutase activities. These results suggest that the aqueous extract of W. coagulans has potent lipid lowering and antioxidant activities.

Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population.

Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide. It results from diverse etiologies, diabetes being a frontrunner amongst them. Type 2 diabetes mellitus (DM) is being increasingly recognized as a proinflammatory state with increased oxidative stress which enormously increases the risk of micro and macro vascular diseases. This study was planned to explore the possible association between tumor necrosis factor-alpha (TNF-α), urinary monocyte chemoattractant protein-1 (uMCP-1), high-sensitivity C-reactive protein (hsCRP) and parameters of oxidative stress in patients with Type 2 diabetes mellitus (DM) and diabetic chronic kidney disease (DM-CKD). Fifty patients each were recruited in DM, DM-CKD and healthy control groups. Plasma TNF-α, hsCRP and uMCP-1 levels as inflammatory mediators were measured by ELISA, reduced glutathione (GSH), ferric reducing ability of plasma (FRAP) as parameters of antioxidant activity and malondialdehyde (MDA) as marker of oxidative stress, were measured spectrophotometrically. Plasma TNF-α, hsCRP and uMCP-1 were significantly higher in DM-CKD compared to DM and healthy controls. Lipid peroxidation, measured as MDA was significantly higher in patients with DM-CKD as compared to patients with DM and healthy controls. Further, antioxidant capacity of blood measured as FRAP and GSH was found to be significantly lower in patients with DM and DM-CKD as compared to healthy controls (p<0.001). Plasma TNF-α and uMCP-1 showed a significant positive correlation with HbA1c (r=0.441, 0.643), hsCRP (r=0.400, 0.584) and MDA (r=0.423, 0.759) and significant negative correlation with GSH (R=-0.370, -0.800) and FRAP (r=-0.344, -0.684) Increased inflammatory markers viz. TNF-α, hsCRP and uMCP-1 and markers of oxidative stress i.e. increased MDA and decreased GSH and FRAP in DM-CKD suggest an important role of inflammation and oxidative stress in the pathogenesis of renal damage in diabetic patients.

The aqueous extract of Withania coagulans fruit partially reverses nicotinamide/streptozotocin-induced diabetes mellitus in rats.

Withania coagulans fruit has been shown to possess antihyperglycemic properties and is used in the traditional Indian system of medicine. However, there has no systematic study of its mechanism of action. In a rat model diabetes mellitus (DM) was induced by intraperitoneal injection of nicotinamide (230 mg/kg of body weight) followed by streptozotocin at 55 mg/kg of body weight. After 96 h, mildly diabetic (MD) (fasting plasma glucose [FPG]=7-11.1 mmol/L) and severely diabetic (SD) (FPG>11.1 mmol/L) rats were treated with aqueous extract of W. coagulans fruit at doses of 125, 250, and 500 mg/kg of body weight/day orally. FPG, postprandial plasma glucose (PPPG), glycosylated hemoglobin (HbA(1c)), plasma insulin, tissue glycogen, and glucose-metabolizing enzymes were assayed at Day 30. Treatment of diabetic animals (MD and SD) with different doses of aqueous W. coagulans resulted in significantly decreased FPG, PPPG, and HbA(1c) (P<.01), whereas serum insulin increased significantly compared with that in diabetic-untreated rats (P<.01). MD and SD animals treated with aqueous W. coagulans also showed significant increases in liver and muscle glycogen compared with diabetic-untreated animals (P<.01). Moreover, activities of glucokinase and phosphofructokinase were also significantly increased (P<.01), whereas glucose-6-phosphatase activity was significantly decreased (P<.01) in MD and SD groups treated with aqueous W. coagulans compared with diabetic-untreated groups. The most effective dose of aqueous W. coagulans was 250 mg/kg of body weight. These results show that the aqueous extract of W. coagulans fruit has significant antihyperglycemic effects, which may be through the modulation of insulin levels and related enzyme activities.

Ameliorative effect of Withania coagulans on dyslipidemia and oxidative stress in nicotinamide-streptozotocin induced diabetes mellitus.

Present study aims to evaluate the effect of Withania coagulans fruit (aqWC) on diabetic-dyslipidemia and antioxidant/oxidant status in DM. Diabetic animals were treated with aqWC at a dose of 250 mg/kg bw for 30 days. Lipid profile, MDA, GSH, SOD, FRAP, HMG CoA reductase and acetyl CoA carboxylase activities were estimated in blood and tissues. Total cholesterol, TAG and LDL were significantly elevated whereas HDL was decreased in diabetic animals (p<0.05), simultaneously the lipid content and HMG CoA reductase activities were also increased, whereas acetyl CoA carboxylase activity decreased significantly in tissues of diabetic animals. MDA was increased and antioxidants such as SOD, GSH and FRAP decreased significantly in DM (p<0.05). Oral administration of aqWC to diabetic animals produced significant improvement in serum lipid profile and tissue lipid content. Activity of HMG CoA reductase decreased, whereas acetyl CoA carboxylase activity increased significantly in tissues after aqWC treatment. Administration of aqWC to diabetic animals also showed significant increase in antioxidant levels i.e., GSH, SOD, FRAP and reduced level of MDA in blood and tissue homogenates as compared to diabetic controls (p<0.05). These results suggest that aqWC treatment improved lipid profile and decreased oxidative stress in diabetes mellitus.

Antidiabetic and antihyperlipidemic effects of the stem of Musa sapientum Linn. in streptozotocin-induced diabetic rats.

BACKGROUND: Musa sapientum Linn. is a herbaceous plant of the Musaceae family. It has been used in India for the treatment of gastric ulcer, hypertension, diarrhea, dysentery, and diabetes. The antidiabetic effect of the fruit, root, and flower has been demonstrated. The aim of the present study was to assess the antidiabetic and antihyperlipidemic effects of the stem of M. sapientum Linn. METHODS: Diabetes was induced in rats by streptozotocin injection (45 mg/kg, i.p.). Diabetic rats were treated for 2 weeks with different doses of lyophilized stem juice of M. sapientum Linn. (25, 50, and 100 mg/kg) to select the most effective dose. The effects of 4 weeks treatment with this dose (50 mg/kg) on fasting and postprandial plasma glucose (FPG, PPG) levels, body weight, lipid profile, HbA1c, insulin, liver enzymes (i.e. glucokinase, glucose-6-phosphatase and 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase) and muscle and liver glycogen were evaluated. RESULTS: The most effective dose of lyophilized stem juice of M. sapientum Linn. was 50 mg/kg. Four weeks treatment with this dose resulted in significant decreases in FPG and PPG (P < 0.05). Serum insulin increased (P < 0.05) whereas HbA1c decreased (P < 0.05). Diabetes-induced changes to the lipid profile, muscle and liver glycogen, and enzyme activity (i.e. glucokinase, glucose-6-phosphatase, and HMG-CoA reductase) were restored near to normal levels (P < 0.05). CONCLUSION: Diabetic rats responded favorably to treatment with lyophilized stem juice of M. sapientum Linn., which exhibits antidiabetic and antihyperlipidemic effects.

Hepatoprotective effect of stem of Musa sapientum Linn in rats intoxicated with carbon tetrachloride.

METHODS: The study was designed to evaluate the hepatoprotective activity of aqueous extract of central stem of Musa sapientum (AqMS) against carbon tetrachloride induced hepatotoxicity in rats. Animals were divided into six groups. Group I served as normal control. Group II, III, IV, V & VI were administered CCl(4) mixed with olive oil 1:1 (1.5 mL/kg) I.P., twice a week for 5 weeks. Group II was maintained as CCl(4) intoxicated control. Group III, IV and V received AqMS at a dose of 25, 50 and 100 mg/kg. Group VI received silymarin 100 mg/kg for 5 weeks orally once daily. Marker enzymes of hepatic functions estimated in serum were AST, ALT and ALP. Antioxidant parameters estimated were MDA and GSH in blood and liver and SOD in blood, after fifth week, animals were sacrificed, livers dissected out and evaluated for histomorphological changes. RESULTS: There was significant rise in AST, ALT and ALP in CCl(4) intoxicated control group II. Treatment with AqMS prevented rise in levels of these enzymes. There was significant rise in MDA and fall in GSH in blood and liver in group II, indicating increased lipid peroxidation and oxidative stress upon CCl(4) administration. Treatment with AqMS prevented rise in MDA & increased GSH in treated group. SOD levels were decreased in group II while groups treated with AqMS showed significant rise (p < 0.05). Maximum hepatoprotective effect was observed with 50 mg/kg dose. Hepatoprotective effect observed with this dose was comparable to standard hepatoprotective drug silymarin. The results of pathological study also support the results of biochemical findings. CONCLUSION: the results of the present study indicate that stem of Musa sapientum possess hepatoprotective effect and probably it is due to it's antioxidant property.

Antidiabetic, antihypercholesterolaemic and antioxidant effect of Ocimum sanctum (Linn) seed oil.

Antihyperlipidaemic and antioxidant effect of Ocimum sanctum Linn. seed oil (OSSO) was investigated in rabbits. Administration of OSSO (0.8 g/kg body weight/day) for four weeks, in cholesterol (100 mg/kg body weight/day) fed rabbits significantly decreased serum cholesterol, triacylglycerol and LDL-+VLDL-cholesterol as compared to untreated cholesterol fed group. There was significant fall in atherogenic index in OSSO treated group. In addition, treatment with OSSO decreased lipid peroxidation and increased reduced glutathione content in blood. Antidiabetic effect of O. sanctum seed oil was evaluated in alloxan diabetic rabbits. Two weeks treatment of diabetic rabbits with OSSO (0.8 gm/kg/day) showed no significant hypoglycaemic effect. Results of the present study show that OSSO has hypocholesterolaemic and antioxidant effects but it does not have antidiabetic effect.

Postprandial hypertriglyceridemia and oxidative stress in patients of type 2 diabetes mellitus with macrovascular complications.

BACKGROUND: Oxidative stress has been implicated in vascular complications of diabetes mellitus (DM). This study aims to evaluate the relationship between postprandial hypertriglyceridemia (PP-HTG) and oxidative stress in Indian patients of type 2 DM with macrovascular complications. METHODS: Plasma triglycerides (TG), thiobarbituric acid reactive substances (TBARS), erythrocyte reduced glutathione (GSH) and superoxide dismutase (SOD) were measured in fasting and postprandial (PP) state at 2, 4, 6 and 8 h after a high fat meal challenge in controls (Group I) and patients of type 2 DM without (Group II) and with macrovascular complications (Group III). RESULTS: Postprandial TGs increased significantly in patients with type 2 DM, which showed an exaggerated response to high fat meal challenge in Group III as compared to Group II. Highest PP-TBARS were also observed in Group III which correlated positively with TG. However, GSH and SOD were lower in both groups of diabetics as compared to controls. CONCLUSIONS: The magnitude of PP-HTG appears to be the major determinant of oxidative stress in type 2 DM, which along with a compromised antioxidant status may lead to endothelial dysfunction and macrovascular complications.

Antioxidant effect of aqueous extract of the bark of Ficus bengalensis in hypercholesterolaemic rabbits.

The antioxidant effect of aqueous extract of the bark of Ficus bengalensis has been evaluated in hypercholesterolaemic rabbits. Rabbits were divided into three groups, Group I served as healthy control; groups II and III were made hypercholesterolaemic by feeding cholesterol suspended in groundnut oil (100 mg/kg body weight per day) for 6 weeks. Rabbits of Group III received water extract of the bark of Ficus bengalensis at a dose of 50 mg/kg body weight per day in addition to cholesterol suspended in oil. Feeding cholesterol increased serum cholesterol, triacylglycerol and LDL + VLDL-cholesterol significantly in Group II as compared to Group I (P = 0.001). Treatment with water extract decreased the serum cholesterol level by 59%, triacylglycerol by 54% and LDL + VLDL-cholesterol by 60% in Group III as compared to Group II. In addition, treatment with this extract led to a decrease in lipid peroxidation as evidenced by fall in thiobarbituric acid reactive substances with a corresponding increase in blood glutathione content (P = 0.001). Further, there was significant increase in the activities of antioxidant enzymes; superoxide dismutase (P < 0.001), catalase (P < 0.03), glutathione peroxidase (P = 0.03) and glutathione reductase (P < 0.01); which were depressed in Group II rabbits after cholesterol feeding. Thus, our results show that the water extract of the bark of Ficus bengalensis has significant antioxidant effect, in addition to hypolipidaemic effect.

Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy.

OBJECTIVES: Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications including nephropathy. The aim of the present study was to evaluate oxidative stress status in Asian Indian patients of type 2 DM with nephropathy. DESIGN AND METHODS: Serum levels of malondialdehyde (MDA) and nitric oxide end products (nitrite and nitrate), activities of erythrocyte superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) content were estimated in controls, patients of type 2 DM without nephropathy (group 1) and with nephropathy (group 2). RESULTS: Serum MDA concentration was significantly high in both the groups of diabetic patients as compared to controls, (p < 0.05), with group 2 having a significantly higher value than group 1 (p < 0.05). Significantly elevated serum nitrite levels were found in diabetic patients as compared to controls (p < 0.001), however, no significant difference was found between group 1 and group 2. Moreover, serum nitrate as well as nitrite + nitrate levels were significantly higher in group 2 as compared to controls (p < 0.05). Activity of erythrocyte SOD and CAT was significantly reduced in both groups as compared to controls (p < 0.001) with catalase activity in group 2 being significantly lower than group 1 (p < 0.05). Erythrocyte GSH content was significantly lower in group 2 as compared to controls (p < 0.05) and group 1 (p < 0.05). CONCLUSIONS: Results of the present study indicate that oxidative stress is increased and antioxidant defenses are compromised in type 2 DM. These derangements are of a higher magnitude in patients of type 2 DM with nephropathy.

Effect of partial ileal bypass on the lipid profile in the hyperlipedemic rabbits.

The hypocholesterolemic effect of partial ideal bypass was studied in two groups of healthy albino rabbits. Both groups of rabbits were made hypercholesterolemic by feeding them cholesterol suspended in groundnut oil (1 ml/kg bw) at a dose of 100 ml/kg bw/day for one week. Group I rabbits were subjected to partial ileal bypass and group II rabbits were sham operated. Weekly estimation of serum lipid profiles were done for four more weeks while continuing cholesterol feed. After end of 5th week, it was found that partial ileal bypass not only prevented but also brought down its level from 132.8 mg% to 44.8 + 2.24 mg%, as compared to sham operates group where cholesterol level was 279 + 5.84 mg%. There was improvement in other parameters of lipid profiles namely HDL-C & LDL-C + VLDL-C and TAG.