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Hypolipidemic action of curcumin, the active
principle of turmeric (Curcuma longa) in streptozotocin
induced diabetic rats
Babu PS; Srinivasan K
Department of Biochemistry and Nutrition, Central Food
Technological Research Institute, Mysore, India.
Molecular and Cellular Biochemistry (Netherlands), 1997,
166/1-2 (169-175)
Streptozotocin-induced diabetic rats were maintained on
0.5% curcumin containing diet for 8 weeks. Blood cholesterol
was lowered significantly by dietary curcumin in these
diabetic animals. Cholesterol decrease was exclusively from
LDL-VLDL fraction. Significant decrease in blood triglyceride
and phospholipids was also brought about by dietary curcumin
in diabetic rats. In a parallel study, wherein diabetic
animals were maintained on a high cholesterol diet, the
extents of hypercholesterolemia and phospholipidemia were
still higher compared to those maintained on control diet.
Curcumin exhibited lowering of cholesterol and phospholipid in
these animals also. Liver cholesterol, triglyceride and
phospholipid contents were emin showed a distinct tendency to
counter these changes in lipid fractions of liver. This effect
of curcumin was also seen in diabetic animals maintained on
high cholesterol diet. Dietary curcumin also showed
significant countering of renal cholesterol and triglycerides
elevated in diabetic rats. In order to understand the
mechanism of hypocholesterolemic action of dietary curcumin,
activities of hepatic cholesterol-7a-hydroxylase and HMG CoA
reductase were measured. Hepatic cholesterol-7a-hydroxylase
activity was markedly higher in curcumin fed diabetic animals
suggesting a higher rate of cholesterol catabolism.
Effects of S-allyl cysteine sulfoxide isolated from
Allium sativum Linn and gugulipid on some enzymes and fecal
excretions of bile acids and sterols in cholesterol fed
rats
Sheela C.G.; Augusti K.T.
Founder General Secretary, Kerala Academy of Sciences,
Medical College, Thiruvananthapuram 695 011 India
Indian Journal of Experimental Biology (India), 1995, 33/10
(749-751)
S-allyl cysteine sulfoxide, isolated from garlic, A.
sativum, is more or less as active as gugulipid in controlling
hypercholesterolemia, obesity and derangement of enzyme
activities in cholesterol diet fed rats. The beneficial
effects of the drugs are partly due to their inhibitory
effects on transaminases, alkaline phosphatase, lipogenic
enzymes and HMG CoA reductase and partly due to their
stimulatory effects on plasma lecithin-cholesterol acyl
transferase lipolytic enzymes and fecal excretion of sterols
and bile acids.
Antiperoxide effects of S-allyl cysteine sulphoxide
isolated from Allium sativum Linn and gugulipid in cholesterol
diet fed rats
Sheela C.G.; Augusti K.T.
Kerala Academy of Sciences, Jai Nagar, Thiruvananthapuram 695
011 India
Indian Journal of Experimental Biology (India), 1995, 33/5
(337-341)
Cholesterol containing diet significantly increased not
only the body weight, but also the weight of liver and adipose
tissue of rats. This is accompanied by a significant increase
in blood lipids, atherogenic index and lipid peroxidation and
a significant decrease in reduced glutathione level,
superoxide dismutase and catalase activities in tissues.
Treatment with S-allyl cysteine sulphoxide reverses the
deleterious effects of cholesterol diet significantly and
almost as effectively as gugulipid.
Recent trends in hyperlipoproteinemias and its
pharmacotherapy
Ghatak A.; Asthana O.P.
Division of Clinical, Experimental Medicine, Central Drug
Research Institute, P.O. Box No. 173, Lucknow - 226 001
India
Indian Journal of Pharmacology (India), 1995, 27/1
(14-29)
Hyperlipoproteinemias cause atherosclerosis which is a
major cause of death in the developed world and is also now
becoming a major cause of morbidity and mortality in India,
especially with changing lifestyles and increasing stress and
food habits shifting towards the 'fast food' era. If is
extremely important to understand the risk factors, the
criteria for starting treatment, the efficacy and safety
profile of drugs for hyperlipoproteinemia and the drugs which
are available for pharmacotherapy especially in the Indian
perspective. The significant contributions of Central Drug
Research Institute, Lucknow in developing potent lipid
lowering drugs like Gugulipid an already marketed product and
a new synthetic drug coded as compound 80/574 in the early
phase of clinical trials have been specially discussed in this
article. At present it is recommended that for mild to
moderate hyperlipoproteinemia Gugulipid would be an extremely
cost effective indigenous choice and with the further
development of the new CDRI compound 80/574 even moderate to
severe hyperlimia would be manageable. The other alternatives
like Gemfibrozil though highly effective for moderate to
severe hyperlipoproteinemia are extremely expensive and have
other side effects and only very few can afford to take it on
long term basis in India.
Cholesterol biosynthesis inhibitory component from
Zingiber officinale Roscoe
Tanabe M; Chen YD; Saito K; Kano Y
Nagakura Pharmaceutical Company Ltd., Osaka, Japan.
Chem Pharm Bull (Tokyo) (Japan) Apr 1993, 41 (4)
p710-3
We previously reported on the isolation and identification
of (E)-8 beta,17-epoxylabd-12-ene-15,16-dial (ZT) from ginger
(rhizome of Zingiber officinale Roscoe, Zingiberaceae). In
this paper, the pharmacological effects of ZT are reported.
The experimental mouse hypercholesterolemia induced by Triton
WR-1339 was treated after oral administration of ZT. In
homogenated rat liver with ZT, cholesterol biosynthesis was
decreased. In addition, the same activity was observed in the
homogenated rat liver which was resected after the oral
administration of ZT. According to the results of general
pharmacological screening, no remarkable activity of ZT was
observed except for an inhibitory effect on the cholesterol
biosynthesis.
Effect of psyllium in hypercholesterolemia at two
monounsaturated fatty acid intakes.
Jenkins DJ; Wolever TM; Vidgen E; Kendall CW; Ransom TP;
Mehling CC; Mueller S; Cunnane SC; O'Connell NC; Setchell KD;
Lau H; Teitel JM; Garvey MB; Fulgoni V 3rd; Connelly PW;
Patten R; Corey PN
Clinical Nutrition and Risk Factor Modification Center, J
Alick Little Core Lipid Laboratory, St Michael's Hospital,
Toronto, Ontario, Canada.
tina.perera@utoronto.ca
Am J Clin Nutr (United States) May 1997, 65 (5)
p1524-33
We performed two studies to determine whether the
lipid-lowering effect of viscous soluble fiber was modified by
monounsaturated fatty acid (MUFA). First, psyllium (1.4 g/MJ)
was compared with wheat bran (control) in 1-mo metabolic diets
by using a randomized crossover design (n = 32 hyperlipidemic
subjects). The background diet contained approximately 6% of
energy as MUFA (20% of total fat). The second study (n = 27
hyperlipidemic subjects) was similar to the first but the
background diet contained approximately 12% MUFA (29% of total
fat) because of the addition of canola oil. At both fat
intakes, psyllium resulted in significant reductions in total,
low-density-lipoprotein (LDL), and high-density-lipoprotein
(HDL) cholesterol compared with the wheat bran control. For
the psyllium diet at 6% compared with 12% MUFA, the decreases
in LDL cholesterol were 12.3 +/- 1.5% (P < 0.001) and 15.3
+/- 2.4% (P < 0.001), respectively. With the higher-MUFA
diet triacylglycerol fell significantly over the control phase
(16.6 +/- 5.5%, P = 0.006) and the ratio of LDL to HDL
cholesterol fell significantly over the psyllium phase (7.3
+/- 2.8%, P = 0.015). Psyllium and MUFA intakes were
negatively related to the percentage change in the ratio of
LDL to HDL cholesterol (r = -0.34, P = 0.019 and r = -0.44, P
= 0.002, respectively). Chenodeoxycholate synthesis rate
increased (30 +/- 13%, P = 0.038) with the psyllium diet in
the 12 subjects in whom this was assessed. We conclude that
psyllium lowered LDL- and HDL-cholesterol concentrations
similarly at both MUFA intakes. However, there may be some
advantage in combining soluble fiber and MUFA to reduce the
ratio of LDL to HDL cholesterol.
Wheat bread supplemented with depolymerized guar
gum reduces the plasma cholesterol concentration in
hypercholesterolemic human subjects.
Blake DE; Hamblett CJ; Frost PG; Judd PA; Ellis PR
Division of Life Sciences, King's College London, United
Kingdom.
Am J Clin Nutr (United States) Jan 1997, 65 (1)
p107-13
Recent human studies have shown that the physiologic
effects of guar gum are not diminished by partial
depolymerization of its galactomannan fraction. We evaluated
the effect of depolymerized guar galactomannan on fasting
plasma cholesterol and triacylglycerol concentrations in
healthy volunteers with moderately raised plasma cholesterol
concentrations (range: 5.2-8.0 mmol/L). This study was
designed as a randomized, double-blind crossover of two 3-wk
feeding periods separated by a 4-wk washout period. Control
and guar wheat breads were prepared by a commercial
bread-making process. Subjects (n = 11) were asked to replace
their normal bread with that provided, receiving control bread
for one 3-wk period and guar bread for the other period,
without altering their baseline diet. Subjects recorded their
intake of foods for 6 consecutive days on three occasions
during the study. Fasting venous blood samples (10 mL) were
taken from subjects on two consecutive mornings at the start
and end of each feeding period. No significant changes in body
weight or dietary intake were recorded in the control and guar
bread periods. There was a significant reduction (10%) in
total plasma cholesterol concentration after the guar
treatment (P < 0.001), mainly because of a reduction in the
low-density-lipoprotein-cholesterol fraction. No changes in
plasma high-density-lipoprotein-cholesterol or triacylglycerol
concentrations were seen. The cholesterol-lowering effect of
partially depolymerized guar gum appears to be of a magnitude
similar to that of high-molecular-weight guar gum used in
earlier studies.
Eicosapentaenoic acid, but not docosahexaenoic
acid, increases mitochondrial fatty acid oxidation and
upregulates 2,4-dienoyl-CoA reductase gene expression in
rats.
Willumsen N; Vaagenes H; Lie O; Rustan AC; Berge RK
University of Bergen, Department of Clinical Biology,
Haukeland Hospital, Norway.
Lipids (United States) Jun 1996, 31 (6) p579-92
The aim of the present study was to investigate whether
eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) was
responsible for the triglyceride-lowering effect of fish oil.
In rats fed a single dose of EPA as ethyl ester (EPA-EE), the
plasma concentration of triglycerides was decreased at 8 h
after acute administration. This was accompanied by an
increased hepatic fatty acid oxidation and mitochondrial
2,4-dienoyl-CoA reductase activity. The steady-state level of
2,4-dienoyl-CoA reductase mRNA increased in parallel with the
enzyme activity. An increased hepatic long-chain acyl-CoA
content, but a reduced amount of hepatic malonyl-CoA, was
obtained at 8 h after acute EPA-EE treatment. On EPA-EE
supplementation, both EPA (20:5n-3) and docosapentaenoic acid
(DPA, 22:5n-3) increased in the liver, whereas the hepatic DHA
(22:6n-3) concentration was unchanged. On DHA-EE
supplementation retroconversion to EPA occurred. No
statistically significant differences were found, however, for
mitochondrial enzyme activities, malonyl-CoA, long-chain
acyl-CoA, plasma lipid levels, and the amount of cellular
fatty acids between DHA-EE treated rats and their controls at
any time point studied. In cultured rat hepatocytes, the
oxidation of [1-14C]palmitic acid was reduced by DHA, whereas
it was stimulated by EPA. In the in vivo studies, the
activities of phosphatidate phosphohydrolase and acetyl-CoA
carboxylase were unaffected after acute EPA-EE and DHA-EE
administration, but the fatty acyl-CoA oxidase, the
rate-limiting enzyme in peroxisomal fatty acid oxidation, was
increased after feeding these n-3 fatty acids. The
hypocholesterolemic properties of EPA-EE may be due to
decreased 3-hydroxy-3-methylglutaryl-CoA reductase activity.
Furthermore, replacement of the ordinary fatty acids, i.e.,
the monoenes (16:1n-7, 18:1n-7, and 18:1n-9) with EPA and some
conversion to DPA concomitant with increased fatty acid
oxidation is probably the mechanism leading to changed fatty
acid composition. In contrast, DHA does not stimulate fatty
acid oxidation and, consequently, no such displacement
mechanism operates. In conclusion, we have obtained evidence
that EPA, and not DHA, is the fatty acid primarily responsible
for the triglyceride-lowering effect of fish oil in rats.
Dose-response characteristics of
cholesterol-lowering drug therapies: implications for
treatment.
Schectman G; Hiatt J
Division of General Internal Medicine, Medical College of
Wisconsin, Froedtert Lutheran Memorial Hospital, Milwaukee
53226, USA.
Ann Intern Med (United States) Dec 15 1996, 125 (12)
p990-1000
PURPOSE: To develop an optimal treatment strategy that
reduces low-density lipoprotein (LDL) cholesterol levels and
improves adherence to therapy by reviewing clinical trials
that define the dose-response characteristics for
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
(statins), bile acid sequestrants, and niacin.
DATA SOURCES: Data were obtained from a MEDLINE search of
the English-language literature published from 1975 through
November 1995 and from an extensive bibliography review.
STUDY SELECTION: Controlled, clinical trials were reviewed
if they evaluated 1) the effectiveness and toxicity of one LDL
cholesterol-lowering agent (statins, bile acid sequestrants,
or niacin, at two or more doses) or 2) monotherapy with two
LDL cholesterol-lowering agents at defined doses used alone
and in combination. Studies that had fewer than 10 patients in
a treatment group or that selected patients on the basis of
previous response to therapy were not included.
DATA EXTRACTION: Trials were reviewed for overall
methodology, inclusion and exclusion criteria, sources of
bias, and outcomes.
DATA SYNTHESIS: Dose-response relations for bile acid
sequestrants and statins are nonlinear, and most of their LDL
cholesterol-lowering effects can be obtained with lower doses.
The few dose-response studies of niacin that have been done
suggest that most of niacin's high-density lipoprotein
cholesterol-increasing effect can also be achieved with
relatively low doses, but higher doses are needed to
substantially reduce LDL cholesterol levels. If bile acid
sequestrants or niacin are added to statin therapy, the effect
of combined therapy on LDL cholesterol levels is additive.
CONCLUSION: The nonlinear dose-response relation of
statins, bile acid sequestrants, and niacin and their additive
LDL cholesterol-lowering effect when used together suggest a
strategy for treating hypercholesterolemia that may optimize
effectiveness while minimizing adverse effects and cost. (72
Refs.)
Soy protein concentrate and isolated soy protein
similarly lower blood serum cholesterol but differently affect
thyroid hormones in hamsters.
Potter SM; Pertile J; Berber-Jimenez MD
Department of Food Science and Human Nutrition, University of
Illinois at Urbana/Champaign, IL 61801, USA.
J Nutr (United States) Aug 1996, 126 (8)
p2007-11
There is a wide variation in the hypocholesterolemic
response to ingestion of soy protein in humans. One possible
explanation is that the different soy protein preparations
used contain different spectra of biologically active
components. This could affect a number of indices including
thyroid hormone status. An increased level of thyroxine has
been proposed as an underlying mechanism of the
hypocholesterolemic effect of soy protein. The objective of
this study was to determine if serum cholesterol and thyroid
hormone concentrations differed because of feeding soy protein
from different sources. Twenty-nine male weanling golden
Syrian hamsters were fed rations containing 25 g/100 g protein
from either isolated soy protein (ISP), soy protein
concentrate (SPC) or casein for 35 d. Serum total cholesterol
concentrations were lower in hamsters fed ISP and SPC compared
with those fed casein (P < 0.05). No differences in
cholesterol concentrations were observed in lipoprotein
fractions. Serum thyroxine and free thyroxine were greater
only in hamsters fed ISP than in those fed casein (P <
0.05), whereas triiodothyronine concentrations were higher in
casein-fed than in SPC-fed hamsters (P < 0.05). Results
indicate that protein from ISP and SPC are both effective in
lowering blood cholesterol concentrations, whereas only ISP
increases thyroxine concentrations. Therefore, it appears
unlikely that modulation of thyroid hormone status is
responsible for the cholesterol-lowering effect of soy
protein.
Ascorbate administration to normal and
cholesterol-fed rats inhibits in vitro TBARS formation in
serum and liver homogenates.
Santillo M; Mondola P; Milone A; Gioielli A; Bifulco M
Dipartimento di Neuroscienze e della Comunicazione
Interumana, Sezione Fisiologia, Universita di Napoli,
Italy.
Life Sci (England) 1996, 58 (14) p1101-8
We have recently shown that ascorbate has a
hypocholesterolemic and hypotriglyceridemic effect on rats fed
a diet enriched with 1.5% cholesterol and 25% hydrogenated
coconut oil (Nath diet). In this study we evaluated the effect
of intraperitoneal ascorbate administration on susceptibility
to lipoperoxidation either in rats fed standard or Nath diet.
In normal rats ascorbate treatment decreased (p<0.05) the
susceptibility to lipoperoxidation induced by incubation of
serum for 24 hours with 2.2 mM Cu++, without altering the
normal serum fatty acid profile. In rats fed Nath diet we
observed a reduced susceptibility of serum to CU++-induced
lipoperoxidation (36%), according with their low levels of
serum unsaturated fatty acids (40% less than rats fed standard
diet). In these animals ascorbate administration affects serum
fatty acid profile leading to a decrease of S/U ratio from 1.6
to 1.2 without significantly modifying the susceptibility of
serum to lipoperoxidation. Moreover, the production of
spontaneous lipid peroxides in liver homogenates, measured as
TBARS levels, was strongly inhibited by ascorbate (p<0.01)
in rats fed either standard or Nath diet. These data indicate
that ascorbate administration exerts an antioxidant effect and
that in hypercholesterolemic rats, in addition to a lipid
lowering effect, ascorbate exerts a protective role against
the peroxidative damage of lipids.
Cholesterol-lowering effect of soyabean lecithin in
normolipidaemic rats by stimulation of biliary lipid
secretion.
Polichetti E; Diaconescu N; De La Porte PL; Malli L; Portugal
H; Pauli AM ; Lafont H; Tuchweber B; Yousef I; Chanussot
F
INSERM U130 and Laboratoire Central, Hopital Sainte
Marguerite, Marseille, France.
Br J Nutr (England) Mar 1996, 75 (3) p471-8
The purpose of the present study was to assess the role of
the liver in the plasma-cholesterol-lowering effect of
soyabean lecithin. Normolipidaemic rats were fed on
lecithin-enriched or control diets with the same amount of
protein. The lecithin diets contained 200 g/kg high-fat
commercial semi-purified soyabean lecithin (230 g/kg total
lipids as soyabean phosphatidylcholine) or 200 g/kg high-fat
purified soyabean lecithin (930 g/kg total lipids as soyabean
phosphatidylcholine). The control diets were a lowfat diet (40
g fat/kg) and a high-fat triacylglycerol-rich diet (200 g
fat/kg). The high-fat diets were isoenergetic. The
cholesterol-lowering effect of the lecithin-enriched diets was
associated with significantly lower levels of plasma total-
and HDL-cholesterol and significantly higher levels of bile
phosphatidylcholine (PC), bile salts and cholesterol. These
findings suggest that the liver plays a major role in the
reduction of plasma cholesterol, the increased biliary lipid
being provided by both HDL and the hepatic microsomal pools of
PC and cholesterol.
Comparison of pravastatin with crystalline
nicotinic acid monotherapy in treatment of combined
hyperlipidemia.
Mostaza JM; Schulz I; Vega GL; Grundy SM
Veterans Affairs Medical Center, Department of Clinical
Nutrition, Center for Human Nutrition of the University of
Texas Southwestern Medical Center at Dallas, 75235-9052,
USA.
Am J Cardiol (United States) May 1 1997, 79 (9)
p1298-301
Pravastatin treatment of combined hyperlipidemia lowers
low-density lipoprotein effectively; nicotinic acid lowers
remnant cholesterol and raises high-density lipoprotein. A
combination of these 2 drugs may be indicated for optimal
treatment of lipoprotein abnormalities in combined
hyperlipidemia.
"Isolated" low high-density lipoprotein
cholesterol.
Wilt VM; Gums JG
Department of Pharmacy Practice, University of Florida,
Gainesville 32164, USA.
Ann Pharmacother (United States) Jan 1997, 31 (1)
p89-97
OBJECTIVE: To present information on the function,
structure, and importance of high-density lipoprotein
cholesterol (HDL-C) and to evaluate the current literature
regarding the controversy of managing patients with an
"isolated" low HDL-C concentration.
DATA SOURCE: A MEDLINE search was performed (1966-June
1996) to identify English-language clinical and review
articles pertaining to HDL-C. Some articles were identified
through the bibliography of selected articles.
STUDY SECTION: All articles were considered for possible
inclusion in the review. Pertinent information, as judged by
the authors, was selected for discussion.
DATA EXTRACTION: Important historical lipid studies, recent
review articles, and clinical trials involving therapy for
HDL-C were evaluated.
DATA SYNTHESIS: The structure, function, and measurement of
HDL-C and the state of an isolated low HDL-C are discussed for
background. Lifestyle modification measures to increase HDL-C,
medications to avoid, estrogen replacement, and lipid-altering
agents used to raise an isolated low HDL-C are presented.
CONCLUSIONS: An isolated low HDL-C concentration poses a
risk for coronary heart disease. The management of this state
is controversial. The first step in management is in agreement
with experts and includes lifestyle modification (e.g., weight
reduction, diet, smoking cessation, aerobic exercise).
Estrogen replacement therapy and discontinuance of drugs that
secondarily lower HDL-C are additional treatment options. The
use of lipid-altering agents has been used in some patients.
Nicotinic acid appears to be an effective agent for an
isolated low HDL-C. A large clinical trial evaluating the
effect of treating an isolated low HDL-C for primary and
secondary prevention of coronary events is needed. (65
Refs.)
Effect of a combination of gemfibrozil and niacin
on lipid levels.
Spencer GA; Wirebaugh S; Whitney EJ
Department of General Internal Medicine, Wilford Hall Medical
Center, Lackland AFB, Texas 78236-5300, USA.
J Clin Pharmacol (United States) Aug 1996, 36 (8)
p696-700
To determine the effect of the combination of niacin and
gemfibrozil on the lipid profile, a retrospective review was
conducted of 161 patients who were prescribed a combination of
gemfibrozil and niacin for 6 to 12 months at a community-based
lipid clinic. Low-density lipoprotein (LDL) and high-density
lipoprotein (HDL) cholesterol, total cholesterol,
triglycerides, ratio of total cholesterol to HDL, alanine
aminotransferase (ALT), and weight were measured at entry to
the clinic, 2 months after dietary instruction, during
single-agent therapy, and during combination therapy. Mean
doses of niacin and gemfibrozil were 1,229 mg/day and 1,200
mg/day, respectively. Patient weight decreased significantly
after dietary instruction and after institution of combination
therapy. There were no significant changes in ALT levels with
either single-agent therapy or with combination therapy. The
combination of niacin and gemfibrozil produced marked and
significant changes in lipid levels: total cholesterol and LDL
decreased by 14%, HDL increased by 24%, the ratio of total
cholesterol to HDL decreased by 30%, and triglycerides
decreased by 52%. The combination of niacin and gemfibrozil in
the setting of dietary instruction has a marked beneficial
effect on serum lipid levels, and was most effective in
patients with initial levels of HDL < 40 mg/dL,
triglycerides > 250 mg/dL, and LDL > 160 mg/dL. No
episodes of ALT elevation or symptomatic myositis were
seen.
New developments in the use of niacin for treatment
of hyperlipidemia: new considerations in the use of an old
drug.
Crouse JR 3rd
Bowman Gray School of Medicine, Winston Salem, North Carolina
27157, USA.
Coron Artery Dis (United States) Apr 1996, 7 (4)
p321-6
Niacin has been used for many years to treat
hyperlipidemia. It has been shown to reduce coronary death and
non-fatal myocardial infarction and, in a separate analysis of
long-term (15-year) follow-up, all cause mortality. It reduces
total cholesterol, low density lipoprotein cholesterol (LDL-C)
and triglycerides and increases high density lipoprotein
cholesterol (HDL-C). Sustained-release niacin may be
associated with more dramatic changes in LDL-C and
triglyceride, whereas the short acting preparation causes
greater increases in HDL-C. The increase of HDL-C occurs at a
lower dose (1500 mg/day) than the reduction of LDL-C (>
1500 mg/day). Niacin also favorably influences other lipid
parameters including lipoprotein(a) [Lp(a)], alimentary
lipemia, familial defective apolipoprotein B-100 and small
dense LDL. Combination of niacin with a bile acid sequestrant
or a reductase inhibitor represents a powerful lipid-altering
regimen. Whereas the reductase inhibitors and bile acid
binding resins primarily affect LDL-C, the combined therapy
has a synergistic effect to reduce LDL-C and, in addition, the
niacin reduces triglycerides and increases HDL-C. The major
drawback in the use of niacin is associated side effects
(flushing and palpitations) and toxicity (worsening of
diabetes control, exacerbation of peptic ulcer disease, gout,
hepatitis). Niacin has a long history of use as a lipid
lowering agent and has several attractive features.
Unfortunately, the side effect profile of this agent warrants
its use only in patients with marked dyslipidemia in whom side
effects and potential toxicity are closely monitored. (47
Refs.)
Effect of supplementary antioxidant vitamin intake
on carotid arterial wall intima-media thickness in a
controlled clinical trial of cholesterol lowering.
Azen SP; Qian D; Mack WJ; Sevanian A; Selzer RH; Liu CR; Liu
CH; Hodis HN
Statistical Consultation and Research Center, University of
Southern California, Los Angeles 90033, USA.
Circulation (United States) Nov 15 1996, 94 (10)
p2369-72
BACKGROUND: There is accumulating experimental,
epidemiological, and clinical evidence of an association
between anti-oxidant vitamin intake and reduced risk of
coronary heart disease. Using data from the Cholesterol
Lowering Atherosclerosis Study (CLAS), we explored the
association of self-selected supplementary antioxidant vitamin
intake on the rate of progression of early preintrusive
atherosclerosis.
METHODS AND RESULTS: CLAS was an arterial imaging trial in
which nonsmoking 40- to 59-year-old men with previous coronary
artery bypass graft surgery were randomized to
colestipol/niacin plus diet or placebo plus diet. The rate of
progression of early preintrusive atherosclerosis was
determined in 146 subjects using high-resolution B-mode
ultrasound quantification of the distal common carotid artery
far wall intima-media thickness (IMT). From the nutritional
supplement database, 22 subjects had an on-trial average
supplementary vitamin E intake of > or = 100 IU per day
(high users) and 29 subjects had an average on-trial
supplementary vitamin C intake of > or = 250 mg per day
(high users). Within the placebo group, less carotid IMT
progression was found for high supplementary vitamin E users
when compared with low vitamin E users (0.008 versus 0.023
mm/y, P = .03). No effect of vitamin E within the drug group
was found. No effect of vitamin C within the drug or placebo
group was found.
CONCLUSIONS: Supplementary vitamin E intake appears to be
effective in reducing the progression of atherosclerosis in
subjects not treated with lipid-lowering drugs while the
process is still confined to the arterial wall (early
preintrusive atherosclerosis).
Lipid management: current diet and drug treatment
options.
Stone NJ
Northwestern University Medical School and the Lipid Research
and Education Fund, Chicago, Illinois, USA.
Am J Med (United States) Oct 8 1996, 101 (4A) p4A40S-48S;
discussion 48S-49S
Diet and drug therapy are two of the principal approaches
to lipid management. The aim of both is to reduce
low-density-lipoprotein (LDL) cholesterol to goal levels
established by the National Cholesterol Education Program
Expert Panel in its second report, based on a patient's
short-term risk of a coronary event. In prescribing diet
therapy, it is important to determine patients' willingness to
initiate and adhere to dietary modifications, their skill at
reading nutritional labels, adapting recipes, and ordering
"heart-healthy" foods when eating out. Diet therapy should be
directed at modifying dietary factors known to adversely
influence blood cholesterol-saturated fats, cholesterol, and
obesity. Diet therapy (with exercise) is not always adequate.
High risk individuals with no overt coronary artery disease
but with >/=2 risk factors, as well as patients with
coronary artery disease, are potential candidates for drug
therapy, depending on their LDL cholesterol levels. The
"statins" are the drug of choice for patients with coronary
disease and elevated LDL cholesterol or familial
LDL-cholesterol abnormalities. These drugs increase
high-density-lipoprotein (HDL) cholesterol and reduce LDL
cholesterol, coronary artery disease, and total mortality.
Bile acid resins lower LDL cholesterol and are often used to
augment the effects of the statins and niacin. Niacin is
particularly useful in the management of patients with
combined hyperlipidemia and low HDL cholesterol levels.
Gemfibrozil is effective in familial dysbetalipoproteinemia
and is the drug of choice for patients with severely elevated
serum triglycerides. (74 Refs.)
Clinical trial of wax-matrix sustained-release
niacin in a Russian population with
hypercholesterolemia.
Aronov DM; Keenan JM; Akhmedzhanov NM; Perova NV; Oganov RY;
Kiseleva NY
National Research Centre for Preventive Medicine, Moscow,
Russia.
Arch Fam Med (United States) Nov-Dec 1996, 5 (10)
p567-75
OBJECTIVE: To assess the clinical effectiveness and
tolerability of wax-matrix, controlled-release nicotinic acid
(CNA) in persons with hypercholesterolemia.
DESIGN: Randomized, double-blind, placebo controlled,
crossover trial.
SETTING: Ambulatory clinic at an academic cardiology center
in Moscow, Russia.
PATIENTS: A volunteer sample of 135 men and women, aged 20
to 70 years, with hypercholesterolemia greater than 5.82
mmol/L (225 mg/dL) (70th-95th percentile for age and sex) who
otherwise met study inclusion and exclusion criteria, were
initially recruited into the study. Cholesterol levels were
reduced to less than 5.82 mmol/L (225 mg/dL) in 46 subjects
who participated in the initial diet intervention and were
excluded from the drug intervention. Eighty-nine subjects were
randomized into the clinical trial; 4 subjects (4.5%) dropped
out of the study because of intolerance of CNA.
INTERVENTION: Eight weeks of diet alone (American Heart
Association Step I Diet) was followed by randomization to 2
treatment groups (1500 mg/d CNA [ENDURACIN] or placebo) for 2
months followed by a crossover of treatments for 2 months,
followed by all subjects taking 2000 mg/d of CNA for 2
months.
MAIN OUTCOME MEASURES: Significant improvements in baseline
measures for total serum cholesterol (TC) and low-density
lipoprotein cholesterol (LDL-C) were observed after initial
diet (TC, 6%; LDL-C, 6%; P < .001, t test), after 1500 mg/d
CNA (TC, 14%; LDL-C, 18%; P < .001, t test), and after 2000
mg/d CNA (TC, 16%; LDL-C, 21%; P < .001, t test).
Triglyceride, high-density lipoprotein cholesterol, and
lipoprotein(a) levels also improved. No serious toxic
reactions were encountered, and 4 subjects withdrew from the
study because of intolerance of cutaneous and gastrointestinal
adverse effects.
CONCLUSION: Wax-matrix CNA is an effective and
well-tolerated pharmacological treatment for
hypercholesterolemia.
Combination therapy with low-dose lovastatin and
niacin is as effective as higher-dose lovastatin.
Gardner SF; Schneider EF; Granberry MC; Carter IR
Department of Pharmacy Practice, University of Arkansas for
Medical Sciences, Little Rock, USA.
Pharmacotherapy (United States) May-Jun 1996, 16 (3)
p419-23
STUDY OBJECTIVES. To determine if low-dose lovastatin in
combination with niacin causes a greater percentage reduction
in low-density lipoprotein (LDL) cholesterol than lovastatin
alone, and to determine if the combination increases the risk
of serious adverse effects. design. Prospective, randomized,
open-label, clinical trial. setting. Family medicine clinic of
a university-affiliated hospital. Patients. Patients with
fasting LDL cholesterol concentrations of at least 150 mg/dl
after 4 weeks of dietary stabilization and washout of any
cholesterol-lowering drugs.
INTERVENTIONS. Twenty-eight patients received lovastatin 20
mg/day for 4 weeks after dietary stabilization and washout. If
LDL cholesterol remained above 130 mg/dl (100 mg/dl in
patients with coronary artery disease), they were randomized
to receive either lovastatin 40 mg/day or a combination of
lovastatin 20 mg/day and niacin 500 mg 3 times/day.
MEASUREMENTS AND MAIN RESULTS. There was no difference in
actual or percentage reductions of LDL cholesterol, total
cholesterol, and triglycerides between the groups. A greater
increase in high-density lipoprotein (HDL) cholesterol
occurred with combination therapy (p = 0.024). There was no
difference in liver function tests, glucose, or uric acid
between the therapies. Based on drug-acquisition cost,
combination therapy is approximately 40% less expensive than
monotherapy.
CONCLUSION. Low-dose niacin plus low-dose lovastatin was as
effective as higher-dose lovastatin in lowering total
cholesterol, LDL cholesterol, and triglyceride levels. The
combination may offer benefit in raising HDL cholesterol
levels.
Fluvastatin in combination with other
lipid-lowering agents.
Jokubaitis LA
Cardiovascular Clinical Research, Sandoz Research Institute,
East Hanover, NJ 07936, USA.
Br J Clin Pract Symp Suppl (England) Jan 1996, 77A
p28-32
Fluvastatin, a new synthetic inhibitor of HMGCoA
(3-hydroxy-3-methylglutaryl coenzyme A) reductase, has been
studied in several models to examine its effects when used in
combination with other lipid-modifying agents such as
derivatives of fibric acid (bezafibrate), resins
(cholestyramine), and niacin. The combination of fluvastatin
with bezafibrate has been studied in a double-blind trial
involving patients with well-documented familial
hypercholesterolaemia. Fluvastatin 40 mg/day, combined with
either bezafibrate 400 mg/day or cholestyramine 8 g/day,
resulted in reductions in levels of low-density lipoprotein
cholesterol (LDL-C), these being indistinguishable between the
groups; however, significantly greater increases in levels of
high-density lipoprotein cholesterol (21.3%) and reductions in
levels of triglycerides (25.1%) were seen with the
fluvastatin-bezafibrate combination. No notable increases were
seen in levels of serum creatine kinase, aspartate
aminotransferase, or alanine aminotransferase, and no cases of
myopathy were observed. In a study model that examined
low-dose combinations of fluvastatin with cholestyramine,
reductions in levels of LDL-C of 15.8% and 19.3% were seen
with fluvastatin 10 mg and 20 mg, respectively. After an
8-week interval in which a daily dosage of cholestyramine 8 g
was added, from baseline, reductions of 26.3% in the 10 mg
fluvastatin-cholestyramine group and 31.2% in the 20 mg
fluvastatin-cholestyramine group were observed, whereas the
placebo-cholestyramine group displayed a reduction of 14.9%.
Doubling the resin dosage to 16 g/day for the final 8 weeks of
the study provided little additional benefit. Myotoxicity has
been observed when lovastatin is coadministered with niacin,
and so the combination of niacin with fluvastatin has also
been studied to examine the possibility of this effect
occurring. Patients were randomised to either fluvastatin 20
mg or placebo for 6 weeks, after which time open-label niacin
was administered to all patients and titrated to a final
dosage of 3 g/day. After 6 weeks, fluvastatin produced a 20.8%
reduction in LDL-C levels from baseline. When combined with
niacin, a 43.7% reduction was noted at the week 15 endpoint,
against the 26.5% reduction seen with niacin monotherapy. The
combination was well tolerated, with no reports of myopathy or
of significant elevations in creatine kinase or liver
transaminase levels. Combinations of fluvastatin with a
variety of other agents have been shown to have significant
effects on lipid profiles, with no evidence to date of
clinically remarkable safety findings. Thus, the use of
combination therapies may result in optimal management of
patients with moderately severe hypercholesterolaemia and
mixed dyslipidaemic profiles. (4 Refs.)
Clinical trials with gugulipid. A new
hypolipidaemic agent
Nityanand S; Srivastava JS; Asthana OP
J Assoc Physicians India (India) May 1989, 37 (5)
p323-8
Multicentric clinical trials of the efficacy of gugulipid
conducted at Bombay, Bangalore, Delhi, Jaipur, Lucknow, Nagpur
and Varanasi have been reported. Two hundred and five patients
completed 12 week open trial with gugulipid in a dose of 500
mg tds after 8 week diet and placebo therapy. One patient
showed gastrointestinal symptoms which did not necessitate
withdrawal of the drug. A significant lowering of serum
cholesterol (av. 23.6%) and serum triglycerides (av. 22.6%)
was observed in 70-80% patients Double-blind, crossover study
was completed in 125 patients with gugulipid therapy and in
108 patients with clofibrate therapy. Two patients had
flu-like syndrome with clofibrate and opted out from the
study. With gugulipid the average fall in serum cholesterol
and triglycerides was 11 and 16.8% respectively and with
clofibrate 10 and 21.6% respectively. The lipid lowering
effect of both drugs became evident 3-4 week after starting
the drug and had no relationship with age, sex, and
concomitant drug intake. Hypercholesterolaemic patients
responded better to gugulipid therapy than
hypertriglyceridaemic patients who responded better to
clofibrate therapy. In mixed hyperlipidaemic patients response
to both drugs was comparable. HDL-cholesterol was increased in
60% cases who responded to gugulipid therapy. Clofibrate had
no effect on HDL-cholesterol. A significant decrease in
LDL-cholesterol was observed in the responder group to both
drugs.
Hypolipidemic and antioxidant effects of Commiphora
mukul as an adjunct to dietary therapy in patients with
hypercholesterolemia
Singh RB; Niaz MA; Ghosh S
Heart Research Laboratory, Medical Hospital and Research
Centre, Moradabad, India.
Cardiovasc Drugs Ther (United States) Aug 1994, 8 (4)
p659-64
The effects of the administration of 50 mg of guggulipid or
placebo capsules twice daily for 24 weeks were compared as
adjuncts to a fruit- and vegetable-enriched prudent diet in
the management of 61 patients with hypercholesterolemia (31 in
the guggulipid group and 30 in the placebo group) in a
randomized, double-blind fashion. Guggulipid decreased the
total cholesterol level by 11.7%, the low density lipoprotein
cholesterol (LDL) by 12.5%, triglycerides by 12.0%, and the
total cholesterol/high density lipoprotein (HDL) cholesterol
ratio by 11.1% from the postdiet levels, whereas the levels
were unchanged in the placebo group. The HDL cholesterol level
showed no changes in the two groups. The lipid peroxides,
indicating oxidative stress, declined 33.3% in the guggulipid
group without any decrease in the placebo group. The
compliance of patients was greater than 96%. The combined
effect of diet and guggulipid at 36 weeks was as great as the
reported lipid-lowering effect of modern drugs. After a
washout period of another 12 weeks, changes in blood
lipoproteins were reversed in the guggulipid group without
such changes in the placebo group. Side effects of guggulipid
were headache, mild nausea, eructation, and hiccup in a few
patients.
Beneficial effects of Allium sativum (garlic),
Allium cepa and Commiphora mukul on experimental
hyperlipidemia and atherosclerosis--a comparative
evaluation.
Lata S; Saxena KK; Bhasin V; Saxena RS; Kumar A; Srivastava
VK
Department of Pharmacology, L. L. R. M. Medical College,
Meerut, Uttar Pradesh.
J Postgrad Med (India) Jul 1991, 37 (3) p132-5
Oral administration of petroleum ether extract of Allium
sativum, Allium cepa and ethylacetate extract of Commiphora
mukul in albino rats significantly prevented rise in serum
cholesterol and serum triglyceride level, caused by
atherogenic diet. All the three agents were also found to
confer significant protection against atherogenic diet induced
atherosclerosis.
Curcumin, a major component of food spice turmeric
(Curcuma longa) inhibits aggregation and alters eicosanoid
metabolism in human blood platelets
Srivastava K.C.; Bordia A.; Verma S.K.
Department of Medicine, R.N.T. Medical College, Udaipur
India
Prostaglandins Leukotrienes and Essential Fatty Acids (United
Kingdom), 1995, 52/4 (223-227)
In traditional medicine, Ayurveda, several spices and herbs
are held to possess medicinal properties. Earlier we have
reported that extracts from several spices, including
turmeric, inhibit platelet aggregation and modulate eicosanoid
biosynthesis. Due to their eicosanoid-modulating property, it
was suggested that the spices may serve to provide clues to
drugs directed to arachidonic acid (AA) pathway enzymes as
pharmacological targets. Curcumin, a major component of
turmeric, inhibited platelet aggregation induced by
arachidonate, adrenaline and collagen. This compound inhibited
thromboxane B2 (TXB2) production from exogenous (14C)
arachidonate in washed platelets with a concomitant increase
in the formation of 12-lipoxygenase products. Moreover,
curcumin inhibited the incorporation of (14C)AA into platelet
phospholipids and inhibited the deacylation of AA-labelled
phospholipids (liberation of free AA) on stimulation with
calcium ionophore A23187. Curcumin's anti-inflammatory
property may, in part, be explained by its effects on
eicosanoid biosynthesis.
Influence of capsaicin, eugenol, curcumin and
ferulic acid on sucrose-induced hypertriglyceridemia in
rats
Srinivasan M.R.; Satyanarayana M.N.
Biochemistry Section, Department of Food Chemistry, Central
Food Technological Research Institute, Mysore-570 013
India
Nutr. Rep. Int. (USA), 1988, 38/3 (571-581)
The spice active principles, capsaicin, eugenol curcumin
and 'ferulic acid' a common plant constituent were found to
counter many of the metabolic changes caused by a high sucrose
diet fed to rats. The compounds tested at high and low levels
were mostly found to lower or tend to lower liver weight,
liver triglycerides, free fatty acids, phospholipids, serum
total, VLDL+LDL and HDL triglycerides, VLDL+LDL cholesterol,
free fatty acids and also elevate serum total and HDL
cholesterol.
Inhibitory effect of curcumin, an anti-inflammatory
agent, on vascular smooth muscle cell proliferation
Huang H.-C.; Jan T.-R.; Yeh S.-F.
Department of Pharmacology, College of Medicine, National
Taiwan University, No. 1, Jen-Ai Road, Taipei Taiwan
Eur. J. Pharmacol. (Netherlands), 1992, 221/2-3
(381-384)
The effects of curcumin, an anti-inflammatory agent from
Curcuma longa, on the proliferation of blood mononuclear cells
and vascular smooth muscle cells were studied. Proliferative
responses were determined from the uptake of tritiated
thymidine. In human peripheral blood mononuclear cells,
curcumin dose dependently inhibited the responses to
phytohemagglutinin and mixed lymphocyte reaction at the dose
ranges of 10-6 to 3 x 10-5 and 3 x 10-6 to 3 x 10-5 M,
respectively. Curcumin (10-6 to 10-4 M) dose dependently
inhibited the proliferation of rabbit vascular smooth muscle
cells stimulated by fetal calf serum. Curcumin had a greater
inhibitory effect on platelet-derived growth factor-stimulated
proliferation than on serum-stimulated proliferation. Cinnamic
acid, coumaric acid and ferulic acid were much less effective
than curcumin as inhibitors of serum-induced smooth muscle
cell proliferation, suggesting that the cinnamic acid and
ferulic acid moieties alone are not sufficient for activity,
and that the characteristics of the diferuloylmethane molecule
itself are necessary for activity. Curcumin may be useful as a
new template for the development of better remedies for the
prevention of the pathological changes of atherosclerosis and
restenosis.
Polyphenols as cancer chemopreventive agents.
Stoner GD; Mukhtar H
Department of Preventive Medicine, Ohio State University,
Columbus OH 43210 USA.
J Cell Biochem Suppl (United States) 1995, 22
p169-80
This article summarizes available data on the
chemopreventive efficacies of tea polyphenols, curcumin and
ellagic acid in various model systems. Emphasis is placed upon
the anticarcinogenic activity of these polyphenols and their
proposed mechanism(s) of action. Tea is grown in about 30
countries and, next to water, is the most widely consumed
beverage in the world. Tea is manufactured as either green,
black, or oolong; black tea represents approximately 80% of
tea products. Epidemiological studies, though inconclusive,
suggest a protective effect of tea consumption on human
cancer. Experimental studies of the antimutagenic and
anticarcinogenic effects of tea have been conducted
principally with green tea polyphenols (GTPs). GTPs exhibit
antimutagenic activity in vitro, and they inhibit
carcinogen-induced skin, lung, forestomach, esophagus,
duodenum and colon tumors in rodents. In addition, GTPs
inhibit TPA-induced skin tumor promotion in mice. Although
several GTPs possess anticarcinogenic activity, the most
active is (-)-epigallocatechin-3-gallat e (EGCG), the major
constituent in the GTP fraction. Several mechanisms appear to
be responsible for the tumor-inhibitory properties of GTPs,
including enhancement of antioxidant (glutathione peroxidase,
catalase and quinone reductase) and phase II
(glutathione-S-transferase) enzyme activities; inhibition of
chemically induced lipid peroxidation; inhibition of
irradiation- and TPA-induced epidermal ornithine decarboxylase
(ODC) and cyclooxygenase activities; inhibition of protein
kinase C and cellular proliferation; antiinflammatory
activity; and enhancement of gap junction intercellular
communication. Curcumin is the yellow coloring agent in the
spice tumeric. It exhibits antimutagenic activity in the Ames
Salmonella test and has anticarcinogenic activity, inhibiting
chemically induced preneoplastic lesions in the breast and
colon and neoplastic lesions in the skin, forestomach,
duodenum and colon of rodents. In addition, curcumin inhibits
TPA-induced skin tumor promotion in mice. The mechanisms for
the anticarcinogenic effects of curcumin are similar to those
of the GTPs. Curcumin enhances glutathione content and
glutathione-S-transferase activity in liver; and it inhibits
lipid peroxidation and arachidonic acid metabolism in mouse
skin, protein kinase C activity in TPA-treated NIH 3T3 cells,
chemically induced ODC and tyrosine protein kinase activities
in rat colon, and 8-hydroxyguanosine formation in mouse
fibroblasts. Ellagic acid is a polyphenol found abundantly in
various fruits, nuts and vegetables. Ellagic acid is active in
antimutagenesis assays, and has been shown to inhibit
chemically induced cancer in the lung, liver, skin and
esophagus of rodents, and TPA-induced tumor promotion in mouse
skin.
Anti-tumour and antioxidant activity of natural
curcuminoids.
Ruby AJ; Kuttan G; Babu KD; Rajasekharan KN; Kuttan R
Amala Cancer Research Centre, Kerala, India.
Cancer Lett (Ireland) Jul 20 1995, 94 (1) p79-83
Matural curcuminoids, curcumin, I, II and III isolated from
turmeric (Curcuma longa) were compared for their cytotoxic,
tumour reducing and antioxidant activities. Curcumin III was
found to be more active than the other two as a cytotoxic
agent and in the inhibition of Ehrlich ascites tumour in mice
(ILS 74.1%). These compounds were also checked for their
antioxidant activity which possibly indicates their potential
use as anti-promoters. The amount of curcuminoids (I, II and
III) needed for 50% inhibition of lipid peroxidation was 20,
14 and 11 g/m. Concentrations needed for 50% inhibition of
superoxides were 6.25, 4.25 and 1.9 micrograms/ml and those
for hydroxyl radical were 2.3, 1.8 and 1.8 micrograms/ml,
respectively. The ability of these compounds to suppress the
superoxide production by macrophages activated with
phorbol-12-myristate-13-acetate (PMA) indicated that all the
three curcuminoids inhibited superoxide production and
curcumin III produced maximum effect. These results indicate
that curcumin III is the most active of the curcuminoids
present in turmeric. Synthetic curcumin I and III had similar
activity to natural curcumins.
Phospholipid epitopes for mouse antibodies against
bromelain-treated mouse erythrocytes.
Kawaguchi S
Department of Microbiology and Immunology, Shimane Medical
University, Izumo, Japan
Immunology (England) Sep 1987, 62 (1) p11-6
The reactivity of mouse antibodies against
bromelain-treated mouse erythrocytes (BrMRBC) with
phospholipid epitopes was assessed by ELISA, using four clones
of monoclonal anti-BrMRBC antibodies that had idiotypes
distinct from one another. The four antibodies could bind to
low-density lipoproteins (LDL) from human and chicken, but not
to LDL from mouse and rat. As to liposomes of natural
phospholipids, all the clones reacted with liposomes of
phosphatidylcholine, and some of them could react with
liposomes of sphingomyelin, phosphatidylglycerol,
phosphatidylic acid or cardiolipin. For liposomes of synthetic
phosphatidylcholine with different fatty acids, the length of
carbon chains and the number of unsaturated carbon chains of
the fatty acids markedly affected the binding of each
monoclonal antibody to the liposomes. The addition of dicetyl
phosphate or stearylamine to phosphatidylcholine liposomes
changed the reactivity of the liposomes. These results support
the view that mouse anti-BrMRBC antibodies can recognize
appropriately spaced phosphorylcholine residues on the surface
of phospholipid liposomes, LDL and cells. The four clones had
similar capacities for binding to LDL as well as to BrMRBC,
but they had obviously different capacities for binding to
phospholipid liposomes; the epitopes on phospholipid liposomes
used in the present study were not so perfect as to react well
with every anti-BrMRBC antibody.
The effect of spices on cholesterol 7
alpha-hydroxylase activity and on serum and hepatic
cholesterol levels in the rat.
Srinivasan K; Sambaiah K
Department of Food Chemistry, Central Food Technological
Research Institute, Mysore, India.
Int J Vitam Nutr Res (Switzerland) 1991, 61 (4)
p364-9
The effect of feeding curcumin, capsaicin, ginger, mustard,
black pepper and cumin on cholesterol and bile acid metabolism
was studied in rats. The activity of hepatic cholesterol-7
alpha-hydroxylase, the rate-limiting enzyme of bile acid
biosynthesis, was significantly elevated in curcumin
(turmeric), capsaicin (red pepper), ginger and mustard treated
animals. The enzyme activity was comparable to controls in
black pepper and cumin fed rats. Serum and liver microsomal
cholesterol contents were significantly higher in the curcumin
and capsaicin treated animals. Thus, this study has suggested
that the spices--turmeric, red pepper, ginger and mustard can
stimulate the conversion of cholesterol to bile acids, an
important pathway of elimination of cholesterol from the body.
However, simultaneous stimulation of cholesterol synthesis by
the spice principles--curcumin and capsaicin suggests that
there may not be any significant contribution of stimulation
of bile acid biosynthesis to the hypocholesterolemic action of
these spices, and the latter action may solely be due to
interference with exogenous cholesterol absorption.
Effect of gugulipid on bioavailability of diltiazem
and propranolol.
Dalvi SS; Nayak VK; Pohujani SM; Desai NK; Kshirsagar NA;
Gupta KC
Dept of Pharmacology, Seth GS Medical College, Parel,
Bombay.
J Assoc Physicians India (India) Jun 1994, 42 (6)
p454-5
The effect of single oral dose of 1 gm gugulipid was
studied on bioavailability of single oral dose of propranolol
(40 mg) and diltiazem (60 mg) in 10 and 7 normal healthy male
volunteers respectively. It was a randomised within group
crossover study. Blood samples were collected at hourly
intervals upto 8 hrs. Gugulipid significantly reduced (P <
.01) peak plasma concentration (Cmax) and area under curve
(AUC 0-8 hrs) of both the drugs in normal volunteers. Such
interaction in patients receiving propanolol or diltiazem with
gugulipid may lead to diminished efficacy or nonresponsiveness
due to significant reduction in bioavailability.
Biological effects of isoflavones in young women:
Importance of the chemical composition of soyabean
products
Cassidy A.; Bingham S.; Setchell K.
Dunn Clinical Nutrition Centre, Hills Road, Cambridge CB2 2DH
United Kingdom
British Journal of Nutrition (United Kingdom), 1995, 74/4
(587-601)
To examine the hormonal effects of isoflavones, of which
soyabean is a rich source, fifteen healthy non-vegetarian
premenopausal women were studied over 9 months. They lived in
a metabolic suite for between 4 and 6 months where their diet
and activity levels were kept constant and their hormonal
status was measured over two or three menstrual cycles. During
one (control) menstrual cycle a normal but constant diet
containing no soyabean products was fed. Then, over a second
complete cycle six subjects consumed a similar diet into which
60 g textured vegetable protein (TVP)/d, containing 45 mg
conjugated isoflavones, had been incorporated. Three
participants had 50 g miso (a fermented soyabean paste),
containing 25 mg unconjugated isoflavones, added daily to
their diet over a menstrual cycle, and six others consumed 28
g TVP/d, containing 23 mg conjugated isoflavones. Five
participants completed a third diet period where they were
randomly assigned to consume either the control diet over a
cycle, or a similar diet incorporating 60 g of a soyabean
product which had had the isoflavones chemically extracted
(Arcon F). Follicular phase length was significantly (P <
0.01) increased and peak progesterone concentrations were
delayed with 60 g TVP but no effects were observed with Arcon
F. The increase in menstrual cycle length did not reach
statistical significance in the three subjects who ate 50 g
miso/d, but peak progesterone levels were significantly (P
< 0.05) delayed. Mid-cycle peaks of luteinizing hormone
(LH) and follicle stimulating hormone CFSH) were suppressed
with 45 mg conjugated isoflavones as 60 g TVP (P < 0.05 and
P < 0.01 respectively). No other changes in sex-steroid
hormone levels were observed on any of the other diets. A
significant reduction in total cholesterol was found with 45
mg conjugated isoflavones (P < 0.05), but not with 23 mg
conjugated isoflavone-free Arcon F. There was no effect of
menstrual cycle phase on transit time.
Overview of proposed mechanisms for the
hypocholesterolemic effect of soy
Potter S.M.
Division of Foods/Nutrition, Division of Nutritional
Sciences, University of Illinois, Urbana, IL 61801 USA
Journal of Nutrition (USA), 1995, 125/3 Suppl.
(606S-611S)
A large body of literature indicates that protein from
soybeans reduces blood cholesterol concentrations in
experimental animals as well as in humans. The mechanism and
component of soy responsible has not been established fully.
Some suggest that when soy protein is fed, cholesterol
absorption and/or bile acid reabsorption is impaired. This is
observed in some animal species, such as rabbits and rats, but
not in humans nor when amino acids replace intact soy protein.
Others propose that changes in endocrine status, such as
alteration in insulin:glucagon ratio and thyroid hormone
concentrations, are responsible. The metabolic changes that
have been observed on soy protein feeding in a variety of
animal models, and in some cases humans, include increased
cholesterol synthesis, increased bile acid synthesis (or fecal
bile acid excretion), increased apolipoprotein B or E receptor
activity and decreased hepatic lipoprotein secretion and
cholesterol content, which are associated with an increased
clearance of cholesterol from the blood. One hypothesis
suggests amino acid composition or proportionality of soy
causes changes in cholesterol metabolism (possibly via the
endocrine system). Others have proposed that nonprotein
components (such as saponins, fiber, phytic acid, minerals and
the isoflavones) associated with soy protein affect
cholesterol metabolism either directly or indirectly.
Biological effects of a diet of soy protein rich in
isoflavones on the menstrual cycle of premenopausal
women
Cassidy A.; Bingham S.; Setchell K.D.R.
Div. of Clinical Mass Spectrometry, Department of Pediatrics,
Children's Hospital Medical Center, 3333 Burnet Avenue,
Cincinnati, OH 45229 USA
Am. J. Clin. Nutr. (USA), 1994, 60/3 (333-340)
The influence of a diet containing soy protein on the
hormonal status and regulation of the menstrual cycle was
examined in six premenopausal women with regular ovulatory
cycles. Soy protein (60 g containing 45 mg isoflavones) given
daily for 1 mo significantly (P < 0.01) increased
follicular phase length and/or delayed menstruation. Midcycle
surges of luteinizing hormone and follicle-stimulating hormone
were significantly suppressed during dietary intervention with
soy protein. Plasma estradiol concentrations increased in the
follicular phase and cholesterol concentrations decreased
9.6%. Similar responses occur with tamoxifen, an antiestrogen
undergoing clinical trial as a prophylactic agent in women at
high risk for breast cancer. These effects are presumed to be
due to nonsteroidal estrogens of the isoflavone class, which
behave as partial estrogen agonists/antagonists. The responses
to soy protein are potentially beneficial with respect to risk
factors for breast cancer and may in part explain the low
incidence of breast cancer and its correlation with a high soy
intake in Japanese and Chinese women.
A review of the clinical effects of
phytoestrogens
Knight D.C.; Eden J.A.
Frank Rundle House, Royal Hospital for Women, 188 Oxford
Street, Paddington, NSW 2021 Australia
Obstetrics and Gynecology (USA), 1996, 87/5 II Suppl.
(897-904)
Objective: To review the sources, metabolism, potencies,
and clinical effects of phytoestrogens on humans.
Data Sources: The MEDLINE data base for the years 1980-1995
and reference lists of published articles were searched for
relevant English-language articles concerning phytoestrogens,
soy products, and diets with high-phytoestrogen content.
Methods of Study Selection: We identified 861 articles as
being relevant. Human cell line studies, human epidemiologic
studies (case-control or cohort), randomized trials, and
review articles were included. Animal studies regarding
phytoestrogens were included when no human data were available
concerning an important clinical area.
Tabulation, Integration, and Results: Included were studies
containing information considered pertinent to clinical
practice in the areas of growth and development, menopause,
cancer, and cardiovascular disease. When findings varied,
those presented in this study reflect consensus. All studies
concurred that phytoestrogens are biologically active in
humans or animals. These compounds inhibit the growth of
different cancer cell lines in cell culture and animal models.
Human epidemiologic evidence supports the hypothesis that
phytoestrogens inhibit cancer formation and growth in humans.
Foods containing phytoestrogens reduce cholesterol levels in
humans, and cell line, animal, and human data show benefit in
treating osteoporosis.
Conclusion: This review suggests that phytoestrogens are
among the dietary factors affording protection against cancer
and heart disease in vegetarians. With this epidemiologic and
cell line evidence, intervention studies are now an
appropriate consideration to assess the clinical effects of
phytoestrogens because of the potentially important health
benefits associated with the consumption of foods containing
these compounds.
Nutritional interest of flavonoids
Remesy C.; Manach C.; Demigne C.; Texier O.; Regerat F.
Ctr. de Recherche/Nutrition Humaine, I.N.R.A., Unite des
Maladies Metaboliques, 63122 St-Genes-Champanelle France
Medecine et Nutrition (France), 1996, 32/1
(17-27)
Polyphenols represent a complex group of compounds
including several categories such as 4-oxo-flavonoids,
anthocyanins and tannins. Some of these molecules are present
in substantial amounts in various beverages and in plant foods
(fruits, vegetables...), and several investigations have
established that they were liable to cross the intestinal
barrier in mammals. Significant concentrations of flavonoid or
polyphenol metabolites are likely to circulate in blood plasma
in humans, and it appears thus important to assess their
potential biological effects. Some interesting properties have
already been reported, especially as to 4-oxo-flavonoids: they
have antioxidizing and metal-complexing properties, and they
are liable to modulate the activity of enzymes governing
important cell functions. By protecting L.D.L. from oxidative
alterations and by affecting platelet functions and plasma
cholesterol, flavonoids might play a protective role against
atherosclerosis. Some 4-oxo-flavonoids (quercetin,
genistein...) show antiproliferative properties in vitro and
inhibit the development of chimio-induced cancers in animal
models. Thus, together with other micronutriments, their
occurence in fruits and legumes could explain the preventive
effects towards cancer risk of plant foods. Isoflavones which
present a phytoestrogenic activity could be more specifically
involved in the prevention of breast cancer risk. Further
investigations are required to determine the actual
bioavailability of the different classes of flavonoids, and to
fully understand the underlying mechanisms of their biological
effects.
Inhibition of protein tyrosine kinase alters the
effect of serum basic protein I on triacylglycerols and
cholesterol differently in normal and hyperapoB
fibroblasts
Kwiterovich P.O. Jr.; Motevalli M.
Johns Hopkins Hospital, CMSC 604, 600 N Wolfe St, Baltimore,
MD 21287-3654 USA
Arteriosclerosis, Thrombosis, and Vascular Biology (USA),
1995, 15/8 (1195-1203)
We studied whether the stimulatory effect of human serum
basic protein I (BP I) on the formation of cell
triacylglycerols and cholesterol may be mediated through
protein tyrosine kinase in normal fibroblasts, and whether
there was a deficiency in such a process in cells from
subjects with hyperapobetalipoproteinemia hyperapoB).
Genistein, a highly specific inhibitor of tyrosine kinase
phosphorylation, was used as a probe. When BP I (428.0 nmol/L)
alone was added to F-12 medium without genistein, the mean
mass of cell triacylglycerols doubled in six normal cell lines
from healthy subjects, an effect that was decreased by 50% in
six cell lines from subjects with hyperapoB (P=.0007). The
addition of genistein with BP I to normal cells decreased the
stimulation of triacylglycerol formation by BP I by about 50%
(P=.008), whereas genistein had little effect in the BP
I-treated hyperapoB cells. The effect of genistein on the
stimulation of triglyceride and cholesterol production by BP I
was shown to be both time and concentration (92.5 nmol/mL
medium nadir) dependent. In normal fibroblasts, BP I
stimulated the rate of incorporation of both (14C)acetate
(P=.0001) and (3H)mevalonolactone (P=.002) into unesterified
cholesterol, an effect that was markedly deficient in the
hyperapoB cells (P=.0001 for (14C)acetate and P=.0002 for
(3H)mevalonolactone). In normal but not hyperapoB cells,
genistein inhibited the significant stimulation by BP I of the
rates of both (14C)acetate (P=.0001) and (3H)mevalonolactone
(P=.04) incorporation into unesterified cholesterol. There was
also a significantly greater stimulation by BP I of the rate
of (14C)acetate incorporation into cell esterified cholesterol
in normal cells than in hyperapoB cells (P=.003), an effect
that was inhibited by genistein in both normal (P=.0009) and
hyperapoB (P=.01) cells. BP I also stimulated to a greater
extent the mass of total cholesterol (P=.0009) and
unesterified cholesterol (P=.015), but to a lesser degree that
a esterified cholesterol (P=.44), in normal cells than in
hyperapoB cells. Herbimycin A and tyrphostin A47, two other
inhibition of protein tyrosine kinase, also significantly
inhibited the effects of BP I on triacylglycerol and
cholesterol mass in normal cells but not in hyperapoB cells.
The effect of BP I on triacylglycerols and cholesterol
formation in normal cells appeared to be mediated through a
tyrosine kinase-dependent process that was deficient in
hyperapoB cells.
Influence of dietary curcumin and cholesterol on
the progression of experimentally induced diabetes in albino
rat
Babu P.S.; Srinivasan K.
Department of Biochemistry/Nutrition, Food Technological Res.
Institute, Mysore 570013 India
Molecular and Cellular Biochemistry (USA), 1995, 152/1
(13-21)
Effect of feeding 0.5% curcumin diet or 1% cholesterol diet
was examined in albino rats rendered diabetic with
streptozotocin injection. Diabetic rats maintained on curcumin
diet for 8 weeks excreted Comparatively less amounts of
albumin, urea, creatinine and inorganic phosphorus. Urinary
excretion of the electrolytes sodium and potassium were also
significantly lowered under curcumin treatment. Dietary
curcumin also partially reversed the abnormities in plasma
albumin, urea, creatinine and inorganic phosphorus in diabetic
animals. On the other hand, glucose excretion or the fasting
sugar level was unaffected by dietary curcumin and so also the
body weights were not improved to any significant extent.
Diabetic rats fed curcumin diet had a lowered relative liver
weight at the end of the study compared to other diabetic rat
groups. Diabetic rats fed a curcumin diet also showed lowered
lipid peroxidation in plasma and urine when compared to other
diabetic groups. The extent of lipid peroxidation on the other
hand, was still higher in cholesterol fed diabetic groups
compared to diabetic rats fed with control diet. Thus, the
study reveals that curcumin feeding improves the metabolic
status in diabetic condition, despite no effect on
hyperglycemic status or the body weights. The mechanism by
which curcumin improves this situation is probably by virtue
of its hypocholesterolemic influence, antioxidant nature and
free radical scavenging property.
Effect of retinol deficiency and curcumin or
turmeric feeding on brain Na+-K+ adenosine triphosphatase
activity
Kaul S.; Krishnakanth T.P.
Department of Biochemistry/Nutrition, Central Food Technolog.
Res. Inst., Mysore - 570 013 India
Mol. Cell. Biochem. (USA), 1994, 137/2 (101-107)
The effect of retinol deficiency and curcumin and turmeric
feeding on brain microsomal Na+-K+ ATPase activity was
investigated. The brain Na+- K+ ATPase activity registered an
increase of 148.5% as compared to the control group. Upon
treating retinol deficient rats with curcumin or turmeric, the
abnormally elevated activity showed a decrease of 36.9 and
47.1%, respectively, when compared to the retinol deficient
group. An increase in V(max) by 67% and K(m) by 66% for ATP
was observed in the retinol deficient group. Curcumin or
turmeric fed retinol-deficient groups reduced the V(max) by 25
and 33%, while K(m) was reduced by 25 and 31%, respectively,
compared to the retinol deficient group. Arrhenius plot of
Na+-K+ ATPase showed a typical bi-phasic pattern in all the
groups. Cholesterol:Phospholipid ratio showed a decrease in
the retinol-deficient group by 67.8%, which showed a marked
increase in curcumin or turmeric treated groups. Detergents
could increase the Na+-K+ ATPase activity more in the control
group than in the retinol deficient groups. Curcumin or
turmeric improved the detergent action on the enzyme.
Subsequent freezing and thawing over a period of 30 min
decreased the enzyme activity by 22.8% in the retinol
deficient group compared to 15.9% decrease in the control
group. Curcumin or turmeric treated groups showed a decrease
in the enzyme activity by 22.0 and 19.2%, respectively, when
compared to the zero time in each group. In the presence of
concanavalin-A (Con-A) there was only 52.4% stimulation in the
enzyme activity in retinol deficient groups, compared to
108.0% in the control group. Curcumin or turmeric treated
retinol-deficient groups showed a stimulation in the presence
of con-A by 70 and 99.5%, respectively.
Bioactive substances in food: Identification and
potential uses
Kitts D.D.
Department of Food Science, University of British Columbia,
Vancouver, BC V6T 1Z4 Canada
Can. J. Physiol. Pharmacol. (Canada), 1994, 72/4
(423-434)
Bioactive substances in foods can represent
'extranutritional' constituents naturally present in small
quantities in the food matrix, produced upon either in vivo or
industrial enzymatic digestion, the latter being a result of
food-processing activities. Bioactive constituents of food
evoke physiological, behavioral, and immunological effects.
Evidence from both epidemiological and animal studies has
suggested chemopreventative roles for phytochemicals in
certain forms of cancers and in the control of hyperlipidemia.
Secondary products of plant metabolism can modulate xenobiotic
metabolizing and cholesterol synthetic enzymes. Unique
physicochemical properties of food-derived peptides with
characteristic amino acid composition and sequences have been
reported to influence intestinal transit, modify nutrient
absorption and excretion, and exhibit immunostimulating and
antihypertensive activity. Biologically active peptides
derived from casein, fish muscle, and plant protein
hydrolysates have been isolated, purified, and identified in
peptide sequence studies. Therapeutic proteins (e.g., specific
antibodies) derived from animal products such as milk may
offer the potential for developing specialized food products
with prophylactic as well as nutritive quality. This paper
discusses the physicochemical mechanism of action of specific
bioactive substances naturally present in or derived from
foods. The biotechnologies employed to develop these products
and the issues concerning acceptance by consumer and
regulatory bodies are also addressed.
Mechanism of antiinflammatory actions of curcumine
and boswellic acids
Ammon H.P.T.; Safayhi N.; Mack T.; Sabieraj J.
Department of Pharmacology, Institute of Pharmaceutical
Sciences, Eberhard-Karls University, D-W-7400 Tubingen
Germany
J. Ethnopharmacol. (Ireland), 1993, 38/2-3
(113-119)
Curcumine from Curcuma longa and the gum resin of Boswellia
serrata, which were demonstrated to act as antiinflammatories
in in vivo animal models, were studied in a set of in vitro
experiments in order to elucidate the mechanism of their
beneficial effects. Curcumine inhibited the 5-lipoxygenase
activity in rat peritoneal neutrophils as well as the
12-lipoxygenase and the cyclooxygenase activities in human
platelets. In a cell free peroxidation system curcumine
exerted strong antioxidative activity. Thus, its effects on
the dioxygenases are probably due to its reducing capacity.
Boswellic acids were isolated from the gum resin of Boswellia
serrata and identified as the active principles. Boswellic
acids inhibited the leukotriene synthesis via 5-lipoxygenase,
but did not affect the 12-lipoxygenase and the cyclooxygenase
activities. Additionally, boswellic acids did not impair the
peroxidation of arachidonic acid by iron and ascorbate. The
data suggest that boswellic acids are specific, non-redox
inhibitors of leukotriene synthesis either interacting
directly with 5-lipoxygenase or blocking its
translocation.
Influence of dietary spices on adrenal
steroidogenesis in rats
Babu P.S.; Srinivasan K.
Department of Food Chemistry, Central Food Technol. Research
Inst., Mysore- 570 013 India
Nutr. Res. (USA), 1993, 13/4 (435-444)
Experiments were carried on adult rats which were fed the
following diets for 2 months: Control, Curcumin (0.5%),
Capsaicin (15mg%), Ginger (50mg%), Black pepper (0.5%), Cumin
(1.25%), Mustard (250mg%), Fenugreek (2%) and Onion (3%).
Adrenal weights in the various experimental groups were
comparable to controls. Adrenal cholesterol was found to be
significantly lower in all the spice fed animals except
mustard suggesting a higher rate of cholesterol turnover to
corticosteroid hormones. Cholesterol depletion was accompanied
by reduced ascorbic acid content in the adrenals of curcumin,
capsaicin, fenugreek and onion fed rats. Urinary excretion of
17-oxo and 17- hydroxy steroids which are the metabolites of
corticosteroids was significantly higher in these spice fed
groups. These data are indicative of the stimulatory influence
of dietary spices on adrenal steroidogenesis.
Differential effects of dietary lipids and curcumin
on kidney microsomal fatty acids and Na+, K+ - ATPase activity
in rat
Joe B.; Prasad S.R.; Sambaiah K.; Krishnakanth T.P.; Lokesh
B.R.
Dept. of Food Chemistry, Central Food Technol. Research
Inst., Mysore - 570013 India
Nutr. Res. (USA), 1992, 12/7 (893-904)
The effect of dietary lipids and spice principle curcumin
on kidney microsomal lipids, Na+, K+ - ATPase activity and
serum lipid levels were studied. Rats were fed a diet
containing either coconut oil, safflower oil or menhaden oil
for 8 weeks. Safflower oil and menhaden oil feeding resulted
in the accumulation of n-6 polyunsaturated fatty acids (PUFA)
and n-3 PUFA respectively in the kidney microsomes. The
specific activity of Na+, K+ - ATPase was higher by 26% in
animals fed safflower oil when compared to animals fed coconut
oil or menhaden oil. Supplementation of curcumin in the diets
containing different lipids did not affect either the kidney
microsomal fatty acid profiles or Na+, K+ - ATPase activity.
However, dietary curcumin reduced the serum triglyceride level
by 44% in safflower oil fed animals and serum cholesterol
levels by 24% and 31% in animals fed safflower oil and
menhaden oil respectively. These studies indicated that
dietary lipids and curcumin differentially affect membrane
fatty acid composition, Na+, K+ - ATPase activity and serum
lipids.
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