Lupeol reduces triglyceride and cholesterol synthesis in human hepatoma cells

Lupeol suppressed triglyceride and cholesterol secretion from HepG2-Lipo human hepatoma cells in a dose-dependent manner. Quantitative real-time RT-PCR analysis demonstrated that lupeol inhibited the expressions of sterol regulatory element-binding protein-1c and -2, fatty acid synthase, 3-hydroxy-3-methylglutaryl-Coenzyme A synthetase-1, and farnesyl-diphosphate farnesyl transferase-1, which are required for lipid synthesis in HepG2-Lipo cells. Furthermore, lupeol markedly inhibited apolipoproteinB-100 and microsomal triglyceride transfer protein in cells at the mRNA level. These results suggest that lupeol lowers lipid secretion from HepG2-Lipo cells by attenuating synthesis within the cells.     

Comparison of tetrahydrofuran,fetal calf serum,and Tween 40 for the delivery of astaxanthin and canthaxanthin to HepG2 cells

The present investigation aimed to compare fetal calf serum (FCS) and Tween 40 with the commonly employed tetrahydrofuran (THF) with respect to cytotoxicity, stability of the solubilized carotenoids, and uptake and accumulation of the xanthophylls astaxanthin (AX) and canthaxanthin (CX) in cultured human liver cells (HepG2). Incubation of HepG2 cells for 24 h with THF (≥1.25%) or FCS (≥11.25%) with or without AX (≥25 μmol/L) or CX (≥25 μmol/L) did not affect cell viability. Tween 40 (0.25–1.25% in medium) reduced cell viability by 75–99%. The stabilities of AX and CX in cell-free RPMI 1640 medium for ≤24 h were higher when delivered with THF instead of FCS. The dose- and time-dependent accumulations of AX and CX (1–10 μmol/L) in HepG2 cells were higher when carotenoids were delivered with FCS compared to THF. In conclusion, FCS and THF, but not Tween 40, were suitable solvent systems for the delivery of AX and CX to HepG2 cells. In our experiments FCS was superior with regard to the uptake and accumulation of both carotenoids.     

Effect of Acetylcholine Precursors on Proliferation and Differentiation of Astroglial Cells in Primary Cultures

Effects of acetylcholine and of the cholinergic precursors choline, cytidine 5′-diphosphocholine (CDP-choline) and α-glyceril-phosphorylcholine (α-GPC) on transglutaminase (TG) and cyclin D1 expression were studied in primary astrocyte cultures by confocal laser microscopy (CLSM) with monodansyl-cadaverine uptake as a marker of enzyme activity and by immunochemistry (Western blotting). CLSM analysis showed an increased cytofluorescence in 0.1 μM choline-treated astrocytes. Treatment with CDP-choline dose-dependently increased TG. A total of 1 μM CDP-choline exposure in 14 days in vitro (DIV) astrocyte cultures increased cytofluorescence. A total of 1 μM α-GPC 24 h-treated cultures revealed increased cytofluorescence both in cytosol and nuclei. Western blot analysis showed an increased TG expression in cultures exposed for 24 h to 1 μM choline or α-GPC, whereas in 24 h 1 μM CDP-choline and acetylcholine-treated astrocytes TG expression was unaffected. Treatment with 1 μM acetylcholine reduced TG expression at 21 DIV. In cultures at 14 and 35 DIV cholinergic precursor treatment for 24 h induced a marked down-regulation of cyclin D1 expression, with reduced cyclin D1 expression in 1 μM α-GPC treated astrocytes. Our data suggest a role of cholinergic precursors investigated independent from acetylcholine on maturation and differentiation of astroglial cells in vitro, rather than on their growth, proliferation and development in culture. Special issue article in honor of Dr. Anna Maria Giuffrida-Stella.     

Effect of cell cholesterol content on apolipoprotein B secretion and LDL receptor activity in the human hepatoma cell line, HepG2

Human hepatoma HepG2 cells were used to study the effects of cholesterol loading and depletion on apolipoprotein B (apoB) secretion and low-density lipoprotein (LDL) receptor activity. Exposure of HepG2 cells to cholesterol and oleic acid, which elevated intracellular cholesterol levels, stimulated apoB secretion and reduced receptor-mediated uptake of LDL, whereas recombinant complexes of apolipoprotein A-I with dimyristoylphosphatidylcholine, which depleted the cellular cholesterol pool, inhibited apoB secretion and up-regulated LDL receptors. Significant negative correlation (r = -0.92, P less than 0.001) between the levels of apoB secretion and LDL uptake was found. These data suggest that the cholesterol content of the cells may induce concomitant changes in apoB secretion and LDL receptor activity.     

Effects of Chromium(III) Picolinate on Cortisol and DHEAs Secretion in H295R Human Adrenocortical Cells

Dietary chromium(III) picolinate (CrPic) effects on circulating steroid hormones have been reported in various experimental animals. However, direct effects of CrPic on adrenocortical steroidogenesis are uncertain. Therefore, the objective was to determine the effects of CrPic on cortisol and dehydroepiandrosterone sulfate (DHEAs) secretion from H295R cells. In experiment 1, a 24-h exposure to CrPic (0 to 200 μM) had both linear (p < 0.001) and quadratic (p < 0.001) effects on cortisol secretion from forskolin-stimulated cells with the highest cortisol secretion at 0.1 μM of CrPic and the lowest at 200 μM of CrPic. In experiment 2, a 48-h exposure to CrPic (200 μM) decreased cortisol (p < 0.07) release from forskolin-stimulated cells during a 24-h collection period. In experiment 3, a 48-h exposure to CrPic (100 μM) decreased cortisol (p < 0.05) and DHEAs (p < 0.01) from forskolin-stimulated cells during a 24-h sampling period. In experiment 4, a 24-h exposure to forskolin followed by a 24-h exposure to both forskolin and CrPic (100 and 200 μM) decreased both cortisol and DHEAs secretion (p < 0.01). This study suggests that at high concentrations, CrPic inhibits aspects of steroidogenesis in agonist-stimulated adrenocortical cells.     

Effects of 15-deoxy-∆<Superscript>12,14</Superscript>-prostaglandin J<Subscript>2</Subscript> on the production of IL-8 and the expression of Toll-like receptor 2 in human primary keratinocytes stimulated with lipopolysaccharide

15-deoxy-∆^12,14-prostaglandin J₂ (15d-PGJ₂) is an anti-inflammatory prostaglandin that plays a role in promoting the resolution of inflammation. We investigated the effects of 15d-PGJ₂ on the production of IL-8 and on the expression of Toll-like receptors (TLRs) 2 in human primary keratinocytes stimulated with lipopolysaccharide (LPS). Cell proliferation was analyzed using the MTT assay, TLR2 and -4 mRNA expression was detected by RT–PCR, and IL-8 production and NF-κB p65 activities were determined by ELISA. LPS and 15d-PGJ₂ did not influence the proliferation rate at low concentrations (0.5 and 2.0 μM) in keratinocytes, and showed toxicity at high concentrations (5.0 μM). LPS, compared with control, induced the expression of TLR2 mRNA, increased IL-8 production, and enhanced NF-κB activity. 15d-PGJ₂ decreased TLR2 mRNA, increased IL-8 production, and suppressed NF-κB activity. Costimulation with LPS and 15d-PGJ₂, compared with LPS stimulation alone, decreased TLR2 mRNA (1.8-fold), increased IL-8 production (1.8-fold at 0.5 μM and 3.7-fold at 2.0 μM), and inhibited NF-κB activity (3.3-fold at 0.5 μM and 5.1-fold at 2.0 μM). TLR4 mRNA was not expressed in primary keratinocytes. These results suggest that 15d-PGJ₂ suppresses TLR2 expression and that it up-regulates the production of IL-8 by inhibiting the NF-κB signaling pathway in primary keratinocytes. Thus, 15d-PGJ₂ can have both anti- and pro-inflammatory effects, and 15d-PGJ₂-mediated IL-8 up-regulation is related to the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways.     

Lipoprotein-associated phospholipase A2 decreases oxidized lipoprotein cellular association by human macrophages and hepatocytes

We investigated whether the presence of endogenous or exogenous lipoprotein-associated phospholipase A2 (Lp-PLA2) can modify the cellular association of oxidized low density lipoprotein (oxLDL) and oxidized lipoprotein(a) (oxLp(a)) by human monocyte-derived macrophages (MDM) and hepatocytes (HepG2). Purified recombinant Lp-PLA2 was used as a source of exogenous enzyme whereas Pefabloc (serine esterase inhibitor) was used to inhibit the endogenous Lp-PLA2 activity associated with isolated lipoproteins. Cellular association studies were performed with DiI-labeled oxLDL or oxLp(a) and human monocyte-derived macrophages and HepG2 cells. Active Lp-PLA2 decreased the cellular association of oxLDL and oxLp(a) in macrophages and HepG2 cells by approximately 30–40%, whereas the inactive enzyme did not significantly change oxidized lipoprotein cellular association by either cell type. OxLDL pretreated by Pefabloc increased oxLDL cellular association by MDM and HepG2 cells compared to untreated oxLDL. Therefore, unlike some lipases, Lp-PLA2 did not appear to have any catalytic independent function in oxLDL cellular association. To assess whether the reduced cellular association mediated by Lp-PLA2 was due to the hydrolysis of oxidized phosphatidylcholine (oxPC), we measured the concentration of lysophosphatidylcholine (lysoPC) in lipoprotein fractions after Lp-PLA2 treatment. LysoPC was increased by 20% (0.4 μM) and 87% (0.7 μM) by active Lp-PLA2 compared to inactive Lp-PLA2 for oxLDL and Lp(a), respectively. LysoPC at higher concentration dose-dependently increased the cellular association of oxLDL and oxLp(a) in MDM and HepG2 cells. We conclude that Lp-PLA2 mediates a decrease in oxidized lipoprotein cellular association in human macrophages and HepG2 cells by reducing the concentration of oxPC within these lipoproteins.     

ABA enhances plant regeneration of somatic embryos derived from cell suspension cultures of plantain cv. Spambia (<Emphasis Type="Italic">Musa</Emphasis> sp.)

Creamy friable calli were induced from meristems (scalps) of proliferating shoots of plantain (Musa sp.) cv. Spambia (genome AAB) incubated on a semi-solid modified Murashige and Skoog (MS) medium supplemented with 4.5 μM 2,4-dichlorophenoxyacetic acid (2,4-D) and 1.0 μM zeatin. About 25% of shoot-tip explants formed scalps, and about 98% of scalps developed embryogenic calli. Small dense aggregates of cells, were obtained when these calli were transferred to liquid MS medium supplemented with 4.5 μM 2,4-D and 1.0 μM zeatin. Upon transfer to semi-solid MS medium of the same composition as described above, aggregates of cells formed somatic embryos. In the presence of 2.5 μM abscisic acid (ABA), maturation of somatic embryos was 2.6-fold higher than that of control (lacking ABA), and regardless of the type of cytokinin used in the medium. Upon transfer to MS medium supplemented with 1.25 μM 6-benzyladenine (BA), 80% of germinated embryos developed into plantlets.     

Relationships between the expression of hepatocyte nuclear factors and factors essential for lipoprotein production in a human mesenchymal stem cell line,UE7T-13

To clarify the mechanisms regulating lipoprotein production by hepatocyte nuclear factors (HNFs), we generated four kinds of transfectants in human bone marrow mesenchymal stem cells: UE7T-13, stably expressing FOXA2 (also known as HNF3β), HNF4α, HNF1α or co-expressing HNF4α, and HNF1α (HNF4α/HNF1α). In HNF4α/HNF1α transfectants, cellular contents of triglycerides (TG) and cholesterol were markedly higher than in UE7T-13 cells and comparable to those in human hepatoma HepG2 cells. However, TG and cholesterol, which are secreted from cells as components of lipoproteins, were hardly detected in the medium for any of the transfectants. ApoB100 and MTP, which are essential for the formation and secretion of lipoproteins, were undetectable and detected at low levels, respectively, in HNF4α/HNF1α transfectants. We suggest that enforced co-expression of HNF4α and HNF1α is effective for cellular lipid accumulation, while additional factors are probably required for lipoprotein formation and secretion.     

Effect of salicylic acid and methyl jasmonate on antioxidant systems of <Emphasis Type="Italic">Haematococcus pluvialis</Emphasis>

The influence of phytohormones, salicylic acid (SA) and methyl jasmonate (MJ) on the antioxidant systems in Haematococcus pluvialis was investigated. Both SA and MJ at 500 μM concentration reduced the growth of alga with salicylic acid, having more pronounced effect. Carotenoid and chlorophyll contents were decreased by SA and increased by MJ. Salicylic acid (100 μM) increased astaxanthin content to 6.8-fold under low light (30 μmol m⁻² s⁻¹), while MJ (10 μM) showed marginal increase in astaxanthin. Salicylic acid (500 μM) increased superoxide dismutase activity to 4.5- and 3.3-fold and ascorbate peroxidase (APX) activity to 15.5- and 7.1-fold under low and high light, respectively. Methyl jasmonate increased catalase activity (1.4-fold) under high light and APX activity (5.4-fold) under low light. Different mechanism of oxidative stress induced antioxidant production may be the plausible reason for this varied response for salicylic acid and methyl jasmonate. Higher concentrations of SA and MJ inhibited astaxanthin accumulation by different mechanisms either by scavenging the free radicals or by increasing primary carotenoids production. At lower concentrations, these phytohormones could be used for elicitation of secondary carotenoid production.     

Effect of Cu2+, Mn2+ and aromatic compounds on the production of laccase isoforms by Coprinus comatus

Six different extracellular laccase isoforms were identified in submerged cultures of the commercially important edible mushroom, Coprinus comatus. Although laccase activity (~55 IU/L) was readily detectable in unsupplemented control cultures containing 1.6 μM Cu²⁺ after 22-day incubation, mean enzyme levels (~150–185 IU/L) were 2.7–3.4-fold higher in cultures supplemented with 0.5–3.0 mM Cu²⁺. Laccase production was also stimulated by Mn supplementation over the range 0.05–0.8 mM Mn²⁺, and the peak value of ~225 IU/L recorded after 22 days in cultures containing 0.8 mM added Mn²⁺ was 4.5-fold higher compared with unsupplemented controls. Of 12 aromatic compounds tested for their effect on laccase isozyme production by C. comatus, highest laccase levels (~188 IU/L), equivalent to a 4.4-fold increase compared with unsupplemented controls (~43 IU/L), were recorded after 22 days in cultures supplemented with 3.0 mM caffeic acid. Other aromatic compounds tested all stimulated laccase production, with peak enzyme levels 1.3–3.3-fold higher compared with unsupplemented controls. Extracellular laccase levels in cultures supplemented with optimal concentrations of Mn²⁺ and caffeic acid together were 38% and 15% lower, respectively, compared with cultures containing the separate supplements. Lac1 was the most abundant laccase isoform produced under all the conditions tested, but marked differences were observed in the production patterns of Lac2–Lac6.     

Dexamethasone protects cultured rat hepatocytes against cadmium toxicity: involvement of cellular thiols

In the present study, the effects of dexamethasone on cadmium-induced toxicity were evaluated in isolated rat hepatocytes. Hepatocytes were cultured for 24 h in William’s E medium containing fetal calf serum (10%), insulin (0.1 IU/ml), and glucagon (0.01 μM) in the absence or presence of 0.1 μM dexamethasone. Cadmium chloride, 5 or 10 μM, was added to the medium and the toxicity was evaluated for up to 48 h after treatment. Lactate dehydrogenase (LDH) release, the reduced and oxidized glutathione ratio (GSH/GSSG), protein-SH groups, and lipid peroxidation levels were evaluated. Cadmium induced a dose- and time-dependent LDH release in control hepatocytes at 24 h (Cd 10 μM 42%) while hepatocytes pretreated with dexamethasone showed lower necrosis (Cd 10 μM 12% at 24 h). GSH/GSSH ratio and protein-SH groups were higher while lipid peroxidation was lower in dexamethasone-treated hepatocytes as compared with untreated cells. In conclusion, cadmium toxicity was associated with an increase in intracellular oxidative stress responsible for accelerated cell death. The use of dexamethasone prevented cadmium damage, suggesting that the cytoprotective action of this hormone is related to its effect in preventing changes in thiols such as glutathione and protein-SH groups.     

LDL and HDL enriched in triglyceride promote abnormal cholesterol transport

Hypertriglyceridemia induces multiple changes in lipoprotein composition. Here we investigate how one of these modifications, triglyceride (TG) enrichment, affects HDL and LDL function when this alteration occurs under conditions in which more polar components can naturally re-equilibrate. TG-enriched lipoproteins were produced by co-incubating VLDL, LDL, and HDL with cholesteryl ester (CE) transfer protein. The resulting 2.5-fold increase in TG/CE ratio did not measurably alter the apoprotein composition of LDL or HDL, or modify LDL size. HDL mean diameter increased slightly from 9.1 to 9.4 nm. Modified LDL was internalized by fibroblasts normally, but its protein was degraded much less efficiently. This likely reflects an aberrant apolipoprotein B (apoB) conformation, as suggested by its resistance to V8 protease digestion and altered LDL electrophoretic mobility. TG-enriched LDL ineffectively down-regulated cholesterol biosynthesis compared with control LDL at the same protein concentration, but was equivalent in sterol regulation when compared on a cholesterol basis. TG-enriched HDL promoted greater net cholesterol efflux from cholesterol-loaded J774 cells. However, cholesterol associated with TG-enriched HDL was inefficiently esterified by lecithin:cholesterol acyltransferase, and TG-enriched HDLs were poor donors of CE to HepG2 hepatocytes by selective uptake. We conclude that TG-enrichment, in the absence of other significant alterations in lipoprotein composition, is sufficient to alter both cholesterol delivery and removal mechanisms. Some of these abnormalities may contribute to increased coronary disease in hypertriglyceridemia.     

Regulation of Root Growth in Lactuca sativa L. Seedlings by the Ent-Kaurane Diterpenoid Epinodosin

Epinodosin, an ent-kaurane diterpenoid isolated from Isodon japonica var. galaucocalyx, had a biphasic, dose-dependent effect on root growth and a strong inhibitory effect on root hair development in Lactuca sativa L. seedlings. Lower levels of epinodosin (25–100 μM) significantly promoted root growth, but higher concentrations (150–200 μM), by contrast, had inhibitory effects. In addition, all of the tested concentrations (20–80 μM) inhibited root hair development of lettuce seedlings in a dose-dependent manner. Further investigations on the underlying mechanism revealed that the promotion effect of epinodosin (25–100 μM) resulted from increasing the cell length in the mature region and enhancing the mitotic activity of meristematic cells in lettuce seedling root tips. On the other hand, epinodosin at higher concentrations inhibited root growth by strongly affecting both the cell length in the mature region and the division of meristematic cells. Comet assay analysis demonstrated that the decrease of mitotic activity of root meristematic cells was due to DNA damage induced by higher levels of epinodosin.     

Modification of chromium (VI) phytotoxicity by exogenous gibberellic acid application in <Emphasis Type="Italic">Pisum sativum</Emphasis> (L.) seedlings

Effects of exogenous gibberellic acid (GA; 10 and 100 μM) application on growth, protein and nitrogen contents, ammonium (NH₄ ⁺) content, enzymes of nitrogen assimilation and antioxidant system in pea seedlings were investigated under chromium (VI) phytotoxicity (Cr VI; 50, 100 and 250 μM). Exposure of pea seedlings to Cr and 100 μM GA resulted in decreased seed germination, fresh and dry weight and length of root and shoot, and protein and nitrogen contents compared to control. Compared to control, Cr and 100 μM GA led to the significant alteration in nitrogen assimilation in pea. These treatments decreased root and shoot nitrate reductase (NR), glutamine synthetase (GS) and glutamine 2-oxoglutarate aminotransferase (GOGAT) activities (except 50 μM Cr alone for GOGAT) while glutamate dehydrogenase (GDH) activity and NH₄ ⁺ content increased. Compared to control, the root and shoot activities of superoxide dismutase (SOD) and ascorbate peroxidase (APX) increased (except APX activity at 250 μM Cr + 100 μM GA) while catalase (CAT), glutathione reductase (GR) and dehydroascorbate reductase (DHAR) activities were decreased (except GR at 100 μM GA alone) following exposure of Cr and 100 μM GA. Total ascorbate and total glutathione in root and shoot decreased by the treatments of Cr and 100 μM GA while their levels were increased by the application of 10 μM GA compared to Cr treatments alone. It has been reported that application of 10 μM GA together with Cr alleviated inhibited levels of growth, nitrogen assimilation and antioxidant system compared to Cr treatments alone. This study showed that application of 10 μM GA counteracts some of the adverse effects of Cr phytotoxicity with the increased levels of antioxidants and sustained activities of enzymes of nitrogen assimilation; however, 100 μM GA showed apparently reverse effect under Cr phytotoxicity.     

Induction of metal binding compounds and antioxidative defence in callus cultures of two black poplar (<Emphasis Type="Italic">P. nigra</Emphasis>) clones with different tolerance to cadmium

Callus cultures of two parental clones of Populus nigra L., Poli and 58-861, originating from contrasting environments, were exposed to different cadmium concentrations (0, 150 and 250 μM CdSO₄). Clones showed different growth responses to cadmium, evaluated by the tolerance index (Ti), with Poli being more tolerant to the metal at both concentrations. The cadmium concentration at the end of the treatment was very similar between clones at 150 μM CdSO₄, while a higher value in 58-861 compared to Poli was detected at 250 μM CdSO₄. The bioconcentration factor evidenced the lowest value in Poli at 250 μM CdSO₄. Unlike 58-861, cadmium provoked a strong induction of thiols and phytochelatins in clone Poli. In both clones, organic acid concentration differed notably in untreated calli and cadmium treatment induced a general lowering of these compounds. A notably higher antioxidant enzyme activity (ascorbate peroxidase, APX; catalase, CAT; guaiacol peroxidase, GPX) was measured in control calli of clone Poli compared to 58-861. Cadmium induced a remarkable enhancement of APX and CAT, but not GPX, activity at 150 μM CdSO₄ in Poli. Conversely, in 58-861 at 150 μM CdSO₄, and in both clones at 250 μM CdSO₄, a decrease in the antioxidant activity occurred. This investigation provided evidence that these two contrasting genotypes of P. nigra are characterised by a different response to cadmium in callus cultures. In particular, in Poli, the higher tolerance to cadmium is associated with a higher activity of antioxidative enzymes and the ability to strongly increase thiol and PC concentration in response to metal exposure.     

Adaptation to short-term extreme fat consumption alters intestinal lipid handling in male and female mice

The small intestine is a highly adaptable organ serving as both a barrier to the external environment and a conduit for nutrient absorption. Enterocytes package dietary triglycerides (TG) into chylomicrons for transport into circulation; the remaining TGs are stored in cytosolic lipid droplets (CLDs). The current study aimed to characterize the impact of diet composition on intestinal lipid handling in male and female wild-type mice. Mice were continued on their grain-based diet (GBD) and switched to either a high-fat, high cholesterol Western-style diet (WD) or a ketogenic diet (KD) for 3 or 5 weeks. KD-fed mice displayed significantly higher plasma TG levels in response to an olive oil gavage than WD- and GBD-fed mice; TG levels were ~2-fold higher in male KD-fed mice than female KD-fed mice. Poloxamer-407 experiments revealed enhanced intestinal-TG secretion rates in male mice fed a KD upon olive oil gavage, whereas secretion rates were unchanged in female mice. Surprisingly, jejunal CLD size and TG mass after oil gavage were similar among the groups. At fasting, TG mass was significantly higher in the jejunum of male KD-fed mice and the duodenum of female KD-fed mice, providing increased substrate for chylomicron formation. In addition to greater fasting intestinal TG stores, KD-fed male mice displayed longer small intestinal lengths, while female mice displayed markedly longer jejunal villi lengths. After 5 weeks of diet, 12 h fasting-2 h refeeding experiments revealed jejunal TG levels were similar between diet groups in male mice; however, in female mice, jejunal TG mass was significantly higher in KD-fed mice compared to GBD- and WD-fed mice. These experiments reveal that KD feeding promotes distinct morphological and functional changes to the murine small intestine compared to the WD diet. Moreover, changes to intestinal lipid handling in response to carbohydrate and protein restriction manifest differently in male and female mice.     

The Effects of Rosuvastatin on the Serum Cortisol,Serum Lipid,and Serum Mevalonic Acid Levels in the Healthy Indian Male Population

In this open-label, balanced, randomized, placebo-controlled, parallel study, healthy male volunteers were randomly divided into two groups. Each group received either a single oral dose of rosuvastatin 20 mg or placebo. Estimations were done at predose on day 1 of dosing (baseline) and 24 h postdose after days 7 and 14. Serum cortisol and serum lipid levels were estimated using enzyme-linked immunosorbent assay kits and serum mevalonic acid (MVA) levels were measured using validated liquid chromatography–tandem mass spectrometry method. Rosuvastatin produced a statistically significant (P < 0.05) decrease in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides. However, the increase in high-density lipoprotein cholesterol and decrease in cortisol and MVA were not statistically significant when compared to the placebo-treated group. The study showed that rosuvastatin at a dose of 20 mg/day for a period of 14 days was very potent as cholesterol-lowering agent, without any significant change in serum cortisol level in the healthy Indian male population.