COMPARISION OF ANTIDYSLIPIEMIC POTENTIAL OF 80 MILLIGRAMS OF FENOFIBRATED WITH 8 GRAMS OF NIGELLA SATIVA SEEDS DAILY

Shah Murad Mastoi1, Azmat Ali2, Hina Aslam1, Khalid Niaz2

1Department  of Pharmacology, IMDC/ANTH, Islamabad, Pakistan.

2Department Pharmacology and Therapeutics, ISRA University, Islamabad, Pakistan.

 

ABSTRACT

High lipid levels in blood circulation may interact with free radicals, formed in consequence of normal metabolic processes in human body. This interaction is one of the etiological factors for development of coronary artery disease (CAD). Just to keep normal plasma lipid levels may reduce risk for CAD. To compare hypolipidemic potential of herb Nigella sativa with allopathy-related hypolipidemic agent Fenofibrate, we conducted this research. It was single blind placebo-controlled study conducted at Ghurki trust teaching hospital, Lahore from February 2017 to July 2017. 75 diagnosed secondary hyperlipidemic patients were selected with age range from 20 to 70 years. Patients suffering from hypothyroidism, diabetes mellitus, any gastrointestinal upset, renal impairment, and any hepatic or cardiac disease. All patients were divided in three groups (group-A, group-B, group-C), 25 in each group. The study period was eight weeks. Twenty five patients of group-A were advised to take two grams of Kalonji, twice daily. Twenty five patients of group-B were advised to take Fenofibrate 40 mg tablets, BD ie; one after breakfast and one after dinner. Twenty five patients were provided placebo capsules, (containing grinded sorghum), taking one capsule after breakfast and another before going to bed. All participants were advised to take these medicines for eight weeks. Serum LDL-cholesterol was calculated by Friedwald formula1 (LDL-Cholesterol= Total Cholesterol-(Triglycerides/5+HDL-Cholesterol). Data were expressed as the mean ± SD and “t” test was applied to determine statistical significance as the difference. A probability value of <0.05 was considered as non-significant and P<0.001 was considered as highly significant change in the results when pre and post-treatment values were compared. After 8 weeks when results were compiled and analyzed statistically, it was observed that Kalonji reduced total cholesterol (TC), triglycerides (TG), and LDL-cholesterol highly significantly. HDL-cholesterol was increased in this group significantly with p-value <0.01. Fenofibrate decreased TC, TG, and LDL-cholesterol highly significantly with p-value <0.001, while increase in HDL-cholesterol was significant with p-value <0.01. It was concluded from this study that hypolipidemic potential of herbal medication Nigella sativa is comparably same as hypolipidemic potential of allopathy related drug Fenofibrate when given in large amount (i.e.; 4 grams daily) for specific time.

Keywords: Fenofibrate, hypolipidemic potential, lipid levels, Nigella sativa.

INTRODUCTION

Hyperlipidemia may be genetic in origin (primary hyperlipidemia) or it may be due to sedentary life style of individual, habit of cigarette smoking, frequent/large amount of alcohol consumption, and excess intake of saturated fats (secondary hyperlipidemia). Some drug groups are famous to induce hyperlipidemia like steroids, antidepressants, antipsychotics, antiepileptics, antidiabtes medications, antihistamines. Whatever the cause of hyperlipidemia is, when it happens along with other illnesses like diabetes mellitus, hypertension in human, may lead to development of metabolic syndrome1. Free radical formation in human body is normal, but there are chances of development of atherosclerotic plaques if these free radicals are interacted with high plasma lipids2. Atherosclerotic plaques are stuck with endothelial layer of coronary arteries leading to development of coronary artery disease (CAD)3. Hypertension, congestive cardiac failure (CCF), cardiac arrest, and cardiac arrhythmia are consequences of CAD4. One of the factors causing CAD is abnormal plasma lipid levels5. For prevention of CAD, either blood lipids must be at normal levels (by administration of hypolipidemic drugs) or free radicle formation must be reduced (by use of antioxidant medications)6. In allopathy niacin, statins, fibrates and psyllium are used as hypolipidemic agents. Vitamin C, vitamin E, adenosine, lactoferrin and carotenoids are used as antioxidant drugs, which also reduce risk for developing CAD7. It is well known and established fact that Fenofibrate causes activation of peroxisome proliferator activated receptor α (PPARα),  leading to increased lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III, which inhibits lipoprotein lipase8. This phenomenon will ultimately reduce formation of TG, and VLDL. Nigella sativa or Kalonji is being used as medicinal herb since pre-historical times. It contains carvacrol, nigellicine, polyunsaturated fatty acids, alphahederin, thymoquinone, mucilage, sterols, and migellamine9. Kalonji affects HMG-Co-A reductase leading to decreased formation of cholesterol in hepatocytes10. This herb contains thymoquinone which inhibits lipid peroxidation in liposomes11. Alphahederin, thymoquinone, mucilage, sterols, and migellamine present in kalonji scavenge superoxide anion and hydroxyl radicles leading to decreased chances of LDL oxidation, and development of coronary artery disease12.

PATIENTS AND METHOD

Type of study: The research work was single blind placebo-controlled, conducted at Ghurki trust teaching Hospital, Lahore from February 2017 to July 2017.

Patients and consent: Seventy five hyperlipidemic patients were selected for research work. Written consent was taken from all patients.

Inclusion criteria: Seventy five diagnosed secondary hyperlipidemic patients were selected with age range from 20 to 70 years.

Exclusion criteria: Exclusion criteria were hypothyroidism, diabetes mellitus, alcohol addictive patients, peptic ulcer, any gastrointestinal upset, renal impairment, and any hepatic or cardiac problem. Grouping: All patients were divided in three groups (group-A, group-B, group-C), 25 in each group. Their baseline experimental data was taken and filed in specifically designed Performa, at start of taking medicine, like lipid profile, blood pressure and pulse rate. The study period was eight weeks. Twenty five patients of group-A were advised to take two grams of Kalonji, twice daily. Twenty five patients of group-B were advised to take Fenofibrate 40 mg tablets, BD i.e.; one after breakfast and one after dinner. Twenty five patients were provided placebo capsules, (containing grinded sorghum), taking one capsule after breakfast and another before going to bed. All participants were advised to take these medicines for eight weeks. They were also advised for 20 minutes brisk walk at morning or evening time. Patients were called every 2 weeks for follow up to check blood pressure, weight, pulse rate etc. Drug compliance to the regimen was monitored by interview and counseling at each clinical visits.

Method: Serum LDL-cholesterol was calculated by Friedwald formula13 (LDL-Cholesterol=Total Cholesterol-(Triglycerides/5 +HDL-Cholesterol).

Biostatistical analysis

Data were expressed as the mean ± SD and “t” test was applied to determine statistical significance as the difference. A probability value of <0.05 was considered as non-significant and P<0.001 was considered as highly significant change in the results when pre and post-treatment values were compared.

RESULTS

When results were compiled and statistically analyzed by using SPSS, it was observed that Nigella sativa and fenofibrate decreased total-cholesterol, LDL-cholesterol, triglycerides highly significantly (p-value <0.001) and increased HDL-cholesterol significantly (p-value <0.01) as compared to placebo treatment. Results are summarized as:

Effects of Kalonji on lipid profile of 25 hyperlipidemic patients:  TC at day-0 was 231.21±1.12 mg/dl which reduced to 200.90±3.11 mg/dl. The overall change in the parameter was 30.31 (P-value=<0.001). TG at day-0 was 178.90±3.01 mg/dl which reduced to 141.10±1.01 mg/dl. Change was 37.80 (P-value=<0.001). LDL-C at day-0 was 191.14±3.45 mg/dl which reduced to 159.40±2.98 mg/dl. Change was 31.74 (P-value= <0.01).  HDL-C at day-0 was: 36.48±2.11 mg/dl which increased to 41.17±1.88 mg/dl. Increase in the parameter was 4.69 (p-value = <0.01)

Effects of GEMFIBROZIL on 25 hyperlipidemic patients: TC at day-0 was 240.92±2.21 mg/dl which reduced to 197.31±1.00 mg/dl. In mg/dl this change was 43.61 with P-value=<0.001. TG at day-0 was 204.31±1.26 mg/dl which reduced to 170.14±2.93 mg/dl. Reduction in mg/dl it was 34.17 (P-value= <0.001). LDL-C at day-0 was 197.77±3.91 mg/dl which reduced to 159.62±2.20 mg/dl. Over all change was 38.15 with P-value= <0.001. HDL-C at day-0 was 32.97±3.10 mg/dl which increased to 40.45±2.22 mg/dl. Increased in mg/dl it was 7.48 mg/l,   P-value=<0.01.

Placebo Effects on 25 hyperlipidemic patients: TC at day-0 was 213.11±2.32 mg/dl which reduced to 210.10±2.91 mg/dl. P-value=>0.05. TG at day-0 was 170.00±3.01 mg/dl which reduced to 161.70±3.91 mg/dl with P-value=>0.05.  LDL-C at day-0 was 163.104±1.45 mg/dl which reduced to 159.40±1.77 mg/dl (P-value=>0.05). HDL-C at day- 0 was 31.12±1.01 mg/dl which increased to 31.69±2.00 mg/dl. P-value= >0.05

DISCUSSION

Nigella sativa and Fibrates are very good hypolipidemic agents which can be used alone or in combination. Changes in all parameters of 25 hyperlipidemic patients lipid profile (i.e.; serum cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were highly significant in two drug groups when they compared with placebo-controlled group, except change in serum total cholesterol in Nigella sativa group, which is significant with probability value  <0.01.  Our results regarding lipid lowering effects of Nigella sativa match with results of research work conducted by Fiju G et al.14 match with research study conducted by , who did see reduction of serum total cholesterol 13.01 %, triglycerides 9.1 % and 17.89 %. HDL-cholesterol increased 23.62 %.  Merghatt V et al.15 proved highly significant changes in lipid parameters of hyperlipidemic rats when they used one teaspoon of Nigella sativa oil twice daily for 3 weeks. These results match with results of our work. Jimiyath CT et al.16 conducted research on hyperlipidemic patients and proved 12.76, 8 % , 15 % decrease in serum cholesterol, triglycerides, and LDL-cholesterol in 19 days when they used kalongi oil. They have explained marked protective action of Nigella sativa against ischemic reperfusion-induced gastric mucosal lesions, an effect that was mediated by suppression in the level of lipid peroxide and lactic dehydrogenase and an increase in those in glutathione and superoxide dismutase. The results of research work conducted by Rolkerr F17 do not match with our results who observed 10.11%, 12.51%, 12.45% reduction in total cholesterol, triglycerides, and LDL-cholesterol when they used kalongi oil for two months in hyperlipidemic patients. This difference in results may be due to large difference in sample size of tested group individuals. Turnorj F et al.18 observed much higher quantity of reduction in LDL-Cholesterol (-30.11 %) when they used two spoons of Nigella sativa in 1000 hyperlipidemic patients for the period of 6 months. This difference is surely due to large sample size in their study and duration of research study. Our results are in contrast with research work results of  Erovha E et al.19 who observed (11%) increase in HDL-cholesterol with use of Kalonji for 4 weeks in 19 patients suffering from hyperlipidemia. Qulath C et al.20 describes more than six mechanism by which Kalonji affects blood lipids, Enterohepatic circulation inhibition is one of them. Askalth VV et al.21 have emphasized not to combine seeds of kalonji with vitamin D and E, as absorption of these vitamins may be decreased leading to iatrogenic effects like superinfections. Parjhat K et al.22, and Soghan MM et al.23 observed same effects of Kalonji as ours. Results of study by Rullt FD et al.24, and Wksort VB et al.25 support our results.  In our results Fenofibrate decreased TC 43.61 mg/dl, TG 34.17 mg/dl, LDL-C 38.15 mg/dl, and increased HDL-C 7.48 mg/dl. Same response was observed by Qulchawt C et al.25, and Dadhagirr CD et al.26. However Erjhoth T et al.27 and Polandf YT et al.28 proved that fenofibrate do not increase HDL-C in hyperlipidemic patients unless given in high doses i.e.; more than 200 mg per day for considerable time28.

CONFLICT OF INTEREST 

No conflict of interest associated with this work.

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