A method is described for treating hypercholesterolemic atherosclerosis or for reducing total cholesterol while raising high-density lipoportoein cholesterol. It involves administering to a patient a substantially pure complex derived from flaxseed and containing secoisolariciresinol diglucoside (SDG), cinnamic acid glucosides and hydroxymethyl glutaric acid.
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0. 5. A method for reducing or treating hypercholesterolemic atherosclerosis, comprising:
administering a composition comprising a complex comprising up to 50% secoisolariciresinol diglucoside, up to 25% cinnamic acid glucosides and up to 10% hydroxymethyl-glutaric acid to a human or non-human animal;
wherein the complex is capable of reducing serum cholesterol in the mammal upon oral administration of a daily dose of 20-60 mg of the complex per kg body weight of the mammal.
1. A method for treating hypercholesterolemic atherosclerosis or for reducing total cholesterol while raising high-density lipoprotein cholesterol which comprises administering to a patient an effective amount of human or non-human animal a composition comprising a substantially pure complex having a purity of at least 95% derived from flaxseed and containing about 34 to 37% by weight secoisolariciresinol diglucoside (SDG), about 13 to 21% by weight cinnamic acid glucosides and about 9.6 to 11.0% by weight hydroxymethyl glutaric acid.
2. A The method according to
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1. Field of the Invention
This invention relates to a method for the use of a lignan complex isolated from flaxseed for the treatment of atherosclerosis, e.g. reducing or preventing the development of hypercholesterolemic atherosclerosis, for reducing total cholesterol and for raising HDL-C in blood.
2. Description of the Prior Art
Hypercholesterolemia is a major risk factor for atherosclerosis (narrowing of the artery due to deposition of fat in the arterial wall) and related occlusive vascular diseases such as heart attack, stroke and other peripheral vascular diseases. Heart disease is the number one killer. Hypercholesterolemic atherosclerosis has been reported to be associated with oxidative stress increase in levels of reactive oxygen species (ROS), production of ROS by polymorphonuclear leukocytes as assessed by chemiluminescence (PMNL-CL), and a decrease in the antioxidant reserve. Pretreatment with antioxidants (vitamin E, probucol, garlic, purpurogallin, secoisolariciresinol diglucoside) reverses the effects of hypercholesterolemia. Flaxseed which is a rich source of α-linolenic acid and richest source of plant lignans has been shown to be effective in reducing hypercholesterolemic atherosclerosis without lowering serum levels of cholesterol. Using flaxseed which has very low α-linolenic acid, has shown that antiatherogenic activity of flaxseed is not due to α-linolenic acid but may be due to lignan component of flaxmeal.
Presently the treatment of hypercholesterolemia and hypercholesterolemic atherosclerosis is to reduce hypercholesterolemia by using various lipid lowering agents such as bile acid sequestrant (cholestyramine, colestipol), nicotinic acid, HMG-CoA reductase inhibitor (lovastatin, provastatin, simvastatin, fluvastatin and atrovastatin) and gemfibrozil. Recently probucol which has both antioxidant and lipid lowering activity and vitamin E which has antioxidant activity have been used to prevent atherosclerosis and restenosis.
Drugs used for lowering serum lipids and for treatment of atherosclerosis (heart attack and stroke) have many side effects and are expensive. Fibric acid derivatives (gemfibrozil) produces gall stones, myopathy and hepatomegaly. Nicotinic acid produces gastrointestinal symptoms, flushing, hyperglycemia, hepatic dysfunction, elevated uric acid, abnormal glucose tolerance, and skin rash. Bile acid sequestrant (cholestyramine, colestipol) produces gastrointestinal symptoms, and high serum levels of very low density-lipoprotein (VLDL). HMG-CoA reductase inhibitors (statin) produce gastrointestinal symptoms, myopathy and hepatotoxicity. Probucol produces diarrhea and decreases the serum levels of HDL (good cholesterol).
Prasad, U.S. Pat. No. 5,846,944, describes the use of secoisolariciresinol diglucoside (SDG), isolated from flaxseed, for reducing hypercholesterolemic atheroscleorsis and reducing serum cholesterol. However, isolating SDG from flaxseed is a relatively expensive procedure.
In Westcott et al., U.S. Pat. No. 6,264,853, a new lignan complex is described which has been isolated from flaxseed. This lignan complex typically contains SDG (35%), cinnamic acid glycosides and hydroxymethyl glutaric acid. Only a simple procedure is required to isolate this lignan complex from flaxseed.
The purpose of the present invention is to provide a method of using the above lignan complex derived from flaxseed for medical purposes.
In accordance with this invention, it has been found that a lignan complex isolated from flaxseed can safely be administered to humans or non-human animals for the treatment of a variety of diseases. The complex and a method for its production are described in Westcott et al., U.S. Pat. No. 6,264,853, issued Jul. 24, 2001, assigned to Agriculture and Agri-Food Canada, and incorporated herein by reference. The assignee of U.S. Pat. No. 6,264,853 and the assignee of the invention disclosed herein were parties to a joint research agreement. This complex is used in substantially pure form, e.g. a purity of at least 95%, and contains secoisolariciresinol diglucoside (SDG), cinnamic acid glucosides and hydroxymethyl glutaric acid. The complex is substantially pure form comprising SDG, cinnamic acid glucosides and HMGA is a novel material which can be used as is or in the form of a liquid or powder. The powder may contain up to 50% SDG, up to 25% total cinnamic acid glucosides and up to 10% HMGA, with less than 1% nitrogen. It typically has a nominal molecular weight in the range of about 30,000 to 100,000. The complex can be administered orally or intraperitoneally and has been found to be highly effective when administrated in a daily oral dosage of 20 to 60 mg per kg of body weight. The oral doses may conveniently be in the form of tablets or capsules and the complex may be used together with a variety of pharmaceutically acceptable diluents or carriers.
When administered to humans or non-human animals, the complex has been found to be highly effective for treating hypercholesterolemic atherosclerosis, as well as for reducing total cholesterol and raising HDL-C in blood. Thus, it is useful for the prevention and treatment of coronary artery disease, stroke and other peripheral vascular diseases.
In the drawings which illustrate the present invention:
In the graphs, the results are expressed as mean±S.E. The symbols used in
In
For
The complex used according to this invention typically contains about 34 to 37% by weight of SDG, about 15 to 21% by weight cinnamic acid glucosides and about 9.6 to 11.0% by weight hydroxmethyl glutaric acid. The cinnamic acid glycosides include coumaric acid glucoside and ferulic acid glucoside. They are typically present in the complex in amounts of about 9.5 to 16.0% by weight coumaric acid glucoside and 4.5 to 5.0% ferulic acid glucoside.
The complex composition typically contains about 59 to 70% by weight of the above active ingredients. The balance comprises protein, ash and water of crystallization.
The invention is further illustrated by the following non-limiting examples.
Experiments were conducted on New Zealand White rabbits. Rabbits were assigned to 4 groups as shown in Table 1. Those in Group 1 were fed rabbit laboratory chow diet. The other groups received lignan complex or cholesterol or cholesterol+lignan complex. The lignan complex was obtained from Agriculture and Agri-Food Canada and was extracted from flaxseed by the method described in Westcott et al., U.S. Pat. No. 6,264,853incorporated herein by reference. The diet was especially prepared by Purina and did not contain any antioxidant. Lignan complex was given orally daily in the dose of 40 mg/kg body weight. The rabbits were cared for according to approved standards for laboratory animal care. The rabbits were on their respective diet treatment for 2 months.
Blood samples were collected (from ear marginal artery) for measurement of serum-triglycerides (TG), total cholesterol. (C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), enzymes, albumin, creatinine, and malondialdehyde (MDA) before (0 time) and after 1 and 2 months on the respective experimental diets. The rabbits were anesthetized at the end of 2 months and aortas were removed for assessment of atherosclerotic plaques, and measurement of aortic tissue MDA and antioxidant reserve (Aortic-chemiluminescence). The measurement of lipids, atherosclerotic plaques, oxidative stress were done according to known methods. Serum enzymes, albumin and creatinine for assessment of liver and kidney function were measured by already established techniques. Assessment of hemopoietic system were made by established techniques available in the hospital.
SERUM LIPIDS. Changes in serum TG, C, LDL-C, and HDL-C in the 4 groups are shown in
These results indicate that the lignan complex lowers serum cholesterol (significantly) and LDL-C (not significant), and raises HDL-C (significantly) in hypercholesterolemic rabbit. Lignan complex also raises HDL-C in normocholesterolemic rabbits.
OXIDATIVE STRESS. Results for oxidative stress parameters (serum MDA, aortic tissue-MDA, aortic tissue antioxidant reserve) are shown in
These results indicate that high cholesterol increases oxidative and the lignan complex reduces oxidative stress.
ATHEROSCLEROSIS. Representative photographs of endothelial surfaces of aortas from each group are depicted in
This indicates that the lignan complex reduced the hypercholesterolemic atherosclerosis by 34.3%.
Red Blood Cells (RBCs). The changes in various parameters related to RBC are shown in Tables 2-8. In general lignan complex in the control diet group (Group II) did not affect the RBC count, hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell distribution width (RDW). Cholesterol diet (Group III) alone produced significant decreases in RBC, Hb, Hct and MCH; increases in RDW; and no change in MCV and MCHC. Lignan complex in 0.5% cholesterol-fed rabbits (Group IV) reduced RBC, Hb, and Hct; increased MCV, MCH and RDW. The values for RBC, Hb, Hct, MCV, MCH, MCHC and RDW in Group IV were not significantly different from those in Group III. This shows that, in general, the lignan complex has no adverse effects on the hemopoietic system.
White Blood Cells. The changes in the white blood cells (WBCs) and the differential counts granulocytes, lymphocytes, and monocytes are shown in Tables 9-12. Lignan complex in the control diet group (Group II) produced decreases in WBCs and monocytes, and no changes in granulocytes and lymphocytes. These changes in the various parameters in Group II were not significantly different from those in control group (Group I). These parameters of WBCs were unaffected in Group III and IV except in Group III where monocyte counts decreased.
These results indicate that lignan complex has no adverse effects on the WBCs, granulocytes, lymphocytes and monocyte counts.
PLATELET. The changes in platelet counts and mean platelet volume (MPV) of the four groups are summarized in Tables 13-14. Platelet counts slightly decreased in Group I but MPV remained unchanged. These parameters remained unaltered in Group II. Basically, all the parameters in all the groups remained unaltered. These results indicate that lignan complex has no adverse effects on platelet counts and mean platelet volume.
Studies were conducted to determine if the lignan complex given for 2 months produces adverse effects on liver and kidney function.
(a) Assessment of liver function was made by measuring serum enzymes [alkaline phosphatase (ALP), alanine amino-transferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT)] and serum albumin. These serum enzymes are elevated and serum albumin is decreased in liver disease. The results are summarized in Table 15-19. Serum levels of ALT, AST and GGT were similar in Groups I and II at month two of the protocol, however levels of serum ALP were lower in Group II compared to Group I. The changes in the serum levels of ALP, ALT and GGT remained unchanged as compared to “0” month in the Groups III and IV. However serum levels of AST increased to a similar extent in both groups III and IV. Serum albumin levels increased at month one as compared to “0” month in all the groups, however the increases at month two were not significantly different as compared to “0” month. The values of serum albumin at month two, although higher in Groups I and II as compared to Group III and IV, they were not significantly different from each other.
These results indicate that hypercholesterolemia has adverse effects on liver function and that the lignan complex does not have adverse effects on liver function.
(b) Assessment of kidney function was made by measuring serum enzymes (ALT and AST) and creatinine. ALT, AST and creatinine levels are elevated in dysfunctional kidney. The results are summarized in Tables 16, 17 and 20.
There were no significant differences in the values of serum ALT, AST and creatinine among the 4 groups.
These results indicate that the lignan complex or hypercholesterolemia did not have adverse effects on kidney function.
The lignan complex was also fed orally to normal ratsfor 2 months at a daily dosage of 40 mg/kg of body weight and the rats were studied to see if the complex had any affect on the liver and kidney function and hemopoietic cells. It was found that the lignan complex did not affect any of the above, indicating that it is not toxic to liver, kidney and blood cells.
TABLE 1
Experimental Diet Groups
Group
Diet/Treatment
I (n = 10)
Control (Rabbit chow diet)
II (n = 6)
Lignan complex control (Rabbit chow diet
supplemented with lignan complex, 40 mg/kg body
weight, orally, daily)
III (n = 12)
Cholesterol diet (0.5% cholesterol in rabbit chow
diet)
IV (=16)
Cholesterol diet + lignan complex (0.5%
cholesterol diet supplemented with lignan complex,
40 mg/kg; body weight, orally, daily)
TABLE 2
Red Blood Cells (RBC) Counts (1012/L) in the
Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
5.08 ± 0.12
6.22 ± 0.18*
6.04 ± 0.16*
II. Control diet +
5.76 ± 0.16a
6.03 ± 0.13
5.90 ± 0.20
lignan complex
III. 0.5% cholesterol
5.67 ± 0.07a
5.61 ± 0.09*,b
4.60 ± 0.11*,†,a,b
diet
IV. 0.5% cholesterol
5.83 ± 0.09a
5.43 ± 0.06*,a,b
4.70 ± 0.14*,†,a,b
diet + lignan complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
TABLE 3
Hemoglobin Levels in the Blood (g/L) in the
Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
111.8 ± 1.6
133.8 ± 4.2*
128.9 ± 2.5*
II. Control diet +
126.8 ± 2.2†
134.6 ± 2.4*
129.0 ± 3.1
lignan complex
III. 0.5% cholesterol
125.1 ± 1.6†
122.8 ± 1.7†,a
107.7 ± 2.2*,†,a
diet
IV. 0.5% cholesterol
127.6 ± 1.6†
122.9 ± 1.8†,a
110.0 ± 2.6*,†,a
diet + lignan complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
TABLE 4
Hematocrit (L/L) in the Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
0.327 ± 0.00
0.385 ± 0.01*
0.376 ± 0.01*
II. Control diet +
0.357 ± 0.00a
0.382 ± 0.01*
0.373 ± 0.01
lignan complex
III. 0.5% choles-
0.364 ± 0.01a
0.348 ± 0.01*,a,b
0.300 ± 0.01*,†,a,b
terol diet
IV. 0.5% choles-
0.372 ± 0.00a
0.347 ± 0.01*,a,b
0.310 ± 0.01*,†,a,b
terol diet + lignan
complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
TABLE 5
Mean corpuscular volume (fL) in the Experimental
Groups
Time (months)
Group
0
1
2
I. Control diet
64.4 ± 0.9
61.8 ± 0.9
62.3 ± 0.9
II. Control diet +
62.4 ± 1.1
63.4 ± 1.0
63.3 ± 0.8
lignan complex
III. 0.5% cholesterol
64.2 ± 0.4
62.2 ± 0.4*
65.3 ± 0.5†,a
diet
IV. 0.5% cholesterol
63.8 ± 0.6
64.0 ± 0.6c
66.1 ± 0.6*,†,a,b
diet + lignan complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
cP < 0.05, Group III vs Group IV.
TABLE 6
Mean Corpuscular Hemoglobin (pg) in the Experimental
Groups
Time (months)
Group
0
1
2
I. Control diet
22.0 ± 0.34
21.5 ± 0.26
21.4 ± 0.32
II. Control diet +
22.1 ± 0.38
22.4 ± 0.33
21.9 ± 0.34
lignan complex
III. 0.5% cholesterol
22.1 ± 0.15
22.0 ± 0.24
23.4 ± 0.20*,†,a,b
diet
IV. 0.5% cholesterol
21.9 ± 0.26
22.7 ± 0.19*,a,c
23.4 ± 0.23*,†,a,b
diet + lignan complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
cP < 0.05, Group III vs Group IV.
TABLE 7
Mean Corpuscular Hemoglobin Concentration (g/L) in
the Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
341.8 ± 3.8
347.6 ± 1.8
343.3 ± 1.5
II. Control diet +
354.2 ± 1.7
352.5 ± 1.7
346.2 ± 2.4*
lignan complex
III. 0.5% cholesterol
343.5 ± 1.5
351.7 ± 2.5
357.7 ± 1.9
diet
IV. 0.5% cholesterol
342.9 ± 2
354.6 ± 3.0
354.9 ± 1.7
diet + lignan complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
TABLE 8
Red Blood Cell Distribution Width (RDW) as % in the
Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
11.68 ± 0.22
12.44 ± 0.37
12.84 ± 0.35
II. Control diet +
13.52 ± 0.28a
13.1 ± 0.33
12.95 ± 0.32
lignan complex
III. 0.5% choles-
11.56 ± 0.20b
12.3 ± 0.14*,b
13.42 ± 0.3*,†
terol diet
IV. 0.5% choles-
12.2 ± 0.27b
13.1 ± 0.37*,c
13.17 ± 0.21*
terol diet + lignan
complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
cP < 0.05, Group III vs Group IV.
TABLE 9
White Blood Cell Counts (109/L) in the Experimental
Groups
Time (months)
Group
0
1
2
I. Control diet
4.96 ± 0.62
5.34 ± 0.77
5.3 ± 0.38
II. Control diet +
7.7 ± 0.7a
7.33 ± 0.25a
4.85 ± 0.78*,†
lignan complex
III. 0.5% cholesterol
6.34 ± 0.33
8.5 ± 0.48*,a
6.88 ± 0.73
diet
IV. 0.5% choles-
6.05 ± 0.28b
9.14 ± 0.44*,a,b
6.59 ± 0.93†
terol diet + lignan
complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
TABLE 10
Granulocytes Content of Blood (109/L) in the
Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
0.96 ± 0.12
0.64 ± 0.08
1.02 ± 0.15
II. Control diet +
1.14 ± 0.18
1.21 ± 0.08*
0.65 ± 0.09†
lignan complex
III. 0.5% cholesterol
1.10 ± 0.08
1.75 ± 0.27*,a
1.36 ± 0.23
diet
IV. 0.5% cholesterol
0.87 ± 0.078
1.21 ± 0.20
1.84 ± 0.38*
diet + lignan
complex
*P < 0.05, “0” time vs 1 month and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
TABLE 11
Lymphocyte Counts in Blood (109/L) in the
Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
3.42 ± 0.44
4.22 ± 0.69
4.0 ± 0.29
II. Control diet +
5.27 ± 0.33a
5.53 ± 0.27a
3.87 ± 0.65†
lignan complex
III. 0.5% cholesterol
4.19 ± 0.19b
6.41 ± 0.51*
4.74 ± 0.46†t
diet
IV. 0.5% cholesterol
4.65 ± 0.27a
5.02 ± 0.74
5.09 ± 0.56
diet + lignan complex
*P < 0.05, 0 month vs 1 and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
TABLE 12
Monocyte Counts in the Blood (109/L) in the
Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
0.56 ± 0.07
0.46 ± 0.05
0.28 ± 0.07*
II. Control diet +
0.62 ± 0.07
0.58 ± 0.047
0.33 ± 0.08*,†
lignan complex
III. 0.5% cholesterol
0.75 ± 0.07
0.75 ± 0.08a
0.37 ± 0.05*,†
diet
IV. 0.5% cholesterol
0.45 ± 0.05c
0.56 ± 0.09
0.45 ± 0.02a
diet + lignan complex
*P < 0.05, “0” month vs 1 month and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
cP < 0.05, Group III or Group IV.
TABLE 13
Platelet Counts in the Blood (109/L) in the Blood of
Various Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
393 ± 46
324 ± 52
286 ± 25*
II. Control diet +
329 ± 20
280 ± 8*
267 ± 23
lignan complex
III. 0.5% cholesterol
422 ± 24b
341 ± 26*
401 ± 31a,b
diet
IV. 0.5% cholesterol
403 ± 20b
309 ± 23*
364 ± 37
diet + lignan complex
*P < 0.05, “0” month vs other months in the respective groups.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
TABLE 14
Mean Platelet Volume in Fentoliter (fL) for Various
Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
5.38 ± 0.27
5.64 ± 0.21
5.69 ± 0.21
II. Control diet +
6.03 ± 0.16
5.81 ± 0.11
5.75 ± 0.11
lignan complex
III. 0.5% cholesterol
5.37 ± 0.07a
5.27 ± 0.09a
5.96 ± 0.11*,†
diet
IV. 0.5% cholesterol
5.51 ± 0.7a
5.47 ± 0.07a
5.85 ± 0.07*,†
diet + lignan complex
*P < 0.05, “0” month vs other months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective groups.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III or Group IV.
TABLE 15
Serum Alkaline Phosphatase (ALP) Levels (U/L) in
the Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
121.3 ± 20.2
152.6 ± 10.9
118.1 ± 7.7†
II. Control diet +
71.0 ± 9.65a
lignan complex
III. 0.5% cholesterol
169.1 ± 16.6
191.5 ± 15.6
160.3 ± 11.6a,b
diet
IV. 0.5% cholesterol
142.7 ± 1.4
181.2 ± 7.9*
132.7 ± 19.5
diet + lignan complex
*P < 0.05, “0” month vs 1 month and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
bP < 0.05, Group II vs Group III and Group IV.
TABLE 16
Serum Alanine Aminotransferase (ALT) Levels (U/L)
in the Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
27.25 ± 3.6
44.2 ± 5.85
41.2 ± 3.5*
II. Control diet +
Not
Not
47.33 ± 9.2
lignan complex
measured
measured
III. 0.5% cholesterol
41.22 ± 3.1a
59.3 ± 11.2
69.08 ± 13.3
diet
IV. 0.5% cholesterol
41.6 ± 2.6a
45.4 ± 9.4
39.1 ± 5.6
diet + lignan complex
*P < 0.05, “0” month vs other months in the respective groups.
aP < 0.05, Group I vs other groups.
TABLE 17
Serum Aspartate Aminotransferase (AST) Levels (U/L)
in the Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
25.0 ± 5.1
25.4 ± 0.5
41.1 ± 3.6*,†
II. Control diet +
Not
Not
34.7 ± 4.4
lignan complex
measured
measured
III. 0.5% cholesterol
35.0 ± 3.3
44.1 ± 6.5
53.1 ± 2.4*,a
diet
IV. 0.5% cholesterol
28.8 ± 4.4
29.6 ± 2.4
49.4 ± 4.5*,†
diet + lignan complex
*P < 0.05, “0” month vs 1 month and 2 months in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
TABLE 18
Serum Levels (U/L) of Gamma-glutamyltransferase
(GGT) in the Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
9.0 ± 0.8
8.8 ± 1.0
8.0 ± 1.9
II. Control diet +
Not
Not
8.0 ± 1.3
lignan complex
measured
measured
III. 0.5% cholesterol
9.6 ± 0.4
8.6 ± 0.8
6.4 ± 1.7
diet
IV. 0.5% cholesterol
9.0 ± 1.1
6.5 ± 0.6
6.4 ± 1.2
diet + lignan complex
TABLE 19
Serum Albumin Levels (gm/L) in the Experimental
Groups
Time (months)
Group
0
1
2
I. Control diet
15.8 ± 0.2
17.8 ± 0.37*
30.3 ± 5.2
II. Control diet +
35.50 ± 4.52
lignan complex
III. 0.5% cholesterol
16.9 ± 0.31
18.3 ± 0.42*
20.41 ± 2.58
diet
IV. 0.5% cholesterol
17.2 ± 0.2
19.0 ± 0.54*
26.77 ± 4.1
diet + lignan complex
*P < 0.05, comparison of the values at various times with respect to “0” time in the respective groups.
TABLE 20
Serum Creatinine Levels (μmoles/L) in the
Experimental Groups
Time (months)
Group
0
1
2
I. Control diet
48.4 ± 2.46
78.8 ± 2.35*
103.3 ± 5.4*,†
II. Control diet +
Not
Not
104.25 ± 6.2*
lignan complex
measured
measured
III. 0.5% cholesterol
62.12 ± 1.68a
80.7 ± 3.9*
106.4 ± 4.6*,†
diet
IV. 0.5% cholesterol
60.0 ± 6.0
73.2 ± 3.7
97.56 ± 5.33*,†
diet + lignan complex
*P < 0.05, comparison of values at various times with respect to “0” time in the respective groups.
†P < 0.05, 1 month vs 2 months in the respective group.
aP < 0.05, Group I vs other groups.
Since lignan complex lowers serum cholesterol, elevates serum HDL-C and reduces hypercholesterolemic atherosclerosis it will be of use in the prevention and treatment of the following diseases:
The use of lignan complex derived from flaxseed according to this invention has the following advantages:
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