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

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 allopathyrelated 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/5HDL-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.


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 syndrome 1 . 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 lipids 2 . 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 CAD 4 . One of the factors causing CAD is abnormal plasma lipid levels 5 . 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 CAD 7 . 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 lipase 8 . 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 migellamine 9 . Kalonji affects HMG-Co-A reductase leading to decreased formation of cholesterol in hepatocytes 10 . This herb contains thymoquinone which inhibits lipid peroxidation in liposomes 11 . 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 disease 12 .

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.

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, LDLcholesterol, 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 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 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 time 28 .