|Year : 2014 | Volume
| Issue : 3 | Page : 167-179
Evaluation of a classical unani pharmacopeial formulation safoof-e-muhazzil in hyperlipidemia: A randomized, standard controlled clinical study
Umar Jahangir1, Asim Ali Khan1, Prem Kapoor2, Farhan Jalees3, Shaista Urooj4
1 Department of Moalejat (Medicine), Faculty of Medicine (U), Jamia Hamdard, New Delhi, India
2 Department of Medicine, Hamdard Institute of Medical Sciences and Research, New Delhi, India
3 Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
4 Department of AYUSH, LRIUM, CCRUM, Hamdard Nagar, New Delhi, India
|Date of Submission||06-Sep-2013|
|Date of Decision||29-Sep-2013|
|Date of Acceptance||22-Jan-2014|
|Date of Web Publication||24-Jun-2014|
Department of Moalejat (Medicine), Faculty of Medicine (U), Jamia Hamdard, New Delhi
Source of Support: None, Conflict of Interest: None
Clinical trial registration NCT01332747
| Abstract|| |
Aim of the Study: The aim of the following study is to evaluate the efficacy and tolerability of a compound Unani formulation in hyperlipidemia on clinical and biochemical parameters. Materials and Methods: A total of 90 patients with total cholesterol level of 220 mg/dl and above were included. In Group 'A' thirty patients with total cholesterol 243.5 ± 5.294 mg/dl received Unani formulation safoof-e-muhazzil (SM) in its classical powder form 5 g twice daily orally, in Group 'B' thirty patients with total cholesterol 234 ± 3.822 mg/dl received the SM but in compressed tablet form in the same dosage and in Group 'C' 30 patients with total cholesterol 242.7 ± 5.563 mg/dl received atorvastatin 10 mg as a standard control. Follow-up was carried out on second, fourth and 6th week and patients were evaluated on clinical as well as biochemical parameters. Results: Group A before treatment had mean total cholesterol of 243.5 ± 5.294 mg/dl which decreased significantly after treatment to 225.6 ± 5.953 mg/dl (P < 0.001) with a percentage change of 7.35%. Group B had mean total cholesterol of 234 ± 3.822 mg/dl which was significantly reduced to 212.67 ± 3.94 mg/dl (P < 0.001) post-treatment with a percentage change of 9.11%. Control Group C having mean total cholesterol of 242.7 ± 5.563 mg/dl before treatment was significantly decreased to 178.73 ± 4.669 mg/dl (P < 0.001) post-treatment with a percentage change of 26.3%. Group A had significant relief 20.72% (P < 0.001) in fatigue, 16.09% (P > 0.5) relief in palpitation and 26.17% (P < 0.001) relief in dyspnea post-treatment. Group B fatigue decreased significantly by 18.14% (P < 0.01), palpitation by 22.91% (P < 0.01) and dyspnea by 20.46% (P < 0.01). In Group C a non-significant increase of 2.2% was observed in fatigue post-treatment, palpitation decreased by 10.22% non-significantly and dyspnea decreased significantly by 17.64% (P < 0.001). Results indicate that the test drug safely and effectively ameliorates the clinical condition of patients with hyperlipidemia while decreasing cholesterol level as well.
Keywords: Hyperlipidemia, safoof-e-muhazzil, unani formulation
|How to cite this article:|
Jahangir U, Khan AA, Kapoor P, Jalees F, Urooj S. Evaluation of a classical unani pharmacopeial formulation safoof-e-muhazzil in hyperlipidemia: A randomized, standard controlled clinical study. J Pharm Bioall Sci 2014;6:167-79
|How to cite this URL:|
Jahangir U, Khan AA, Kapoor P, Jalees F, Urooj S. Evaluation of a classical unani pharmacopeial formulation safoof-e-muhazzil in hyperlipidemia: A randomized, standard controlled clinical study. J Pharm Bioall Sci [serial online] 2014 [cited 2020 May 31];6:167-79. Available from: http://www.jpbsonline.org/text.asp?2014/6/3/167/130975
Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis-associated conditions, such as coronary heart disease (CHD), ischemic cerebrovascular disease and peripheral vascular disease. 
Lipoproteins are complexes of lipids and proteins that are essential for the transport of cholesterol, triglycerides (TGs) and fat-soluble vitamins. Previously, lipoprotein disorders were the purview of specialized lipidologists, but the demonstration that lipid-lowering therapy significantly reduces the clinical complications of atherosclerotic cardiovascular disease (CVD) has brought the diagnosis and treatment of these disorders into the domain of the internist. The number of individuals who are candidates for lipid-lowering therapy has continued to increase. 
It has long been known that lipid abnormalities are major risk factors for premature coronary artery disease (CAD). , Nearly 85% of the global mortality and disease burden from CVD is borne by low and middle-income countries.  South Asians around the globe have the highest rates of CAD.  In India, approximately 53% of CVD deaths are in people younger than 70 years of age; in China, the corresponding figure is 35%.  About 29.8 million people were estimated to have CHD in India in 2003; 14.1 million in urban areas and 15.7 million in rural areas.  According to National Commission on Macroeconomics and Health, a Government of India undertaking, there would be around 62 million patients with CAD by 2015 in India and of these, 23 million would be patients younger than 40 years of age. 
Many herbs and other drugs mentioned in Unani pharmacopeia and their formulations have been found to correct endothelial dysfunction, dyslipidemia, dysglycemia, coagulation abnormalities and have immunomodulating properties. As it is known that oxidation of low-density lipoprotein cholesterol leads to atherosclerosis  and the antioxidant properties of plant phenolics cause its inhibition.  It has also been suggested that in addition to reducing serum lipid level, drugs with anti-oxidation action will be beneficial to prevent atherosclerosis. In the light of above it would only be appropriate to explore the utility of those reputed pharmacopeial drug or a formulation their off for such activities.
The study test drug Safoof-e-Muhazzil (SM) is a classical Unani pharmacopeial formulation indicated for obesity.  In each 5 g it contains five herbal ingredients Tukhme badyan (Foeniculum vulgare) - 1 g, Nankhwa (Trachyspermum ammi) - 1 g, Zeera Siyah (Carum carvi) - 1 g, Sudab (Ruta graveolens) - 1 g, Marzanjosh (Origanum vulgare) - 0.25 g, one animal origin drug Luc Magsool (purified stick lac) - 0.5 g and a mineral origin drug Bura Armani (Borax) - 0.25 g. These constituents of SM have been attributed by Unani physicians to have deobstruent, dessicant and mulatif-e-urooq (vessel relaxant) properties and many of them have been proven to be antihyperlipidemic as well. The study hypothesis was "hyperlipidemia falls under the category of sue-e-mizaj-barid (deranged temperament toward cold/saman-e-mufrit); so on the basis of its treatment as mentioned in Unani classical literature, SM will prove effective in lowering hyperlipidemia and also due to its hot and dry temperament on the principal of Ilaj Bil Zid (treatment with drugs of opposing temperament). On the basis of above current study was designed to elucidate the effect of SM; primarily a classical Unani anti-obesity drug on hyperlipidemia in human subjects in its classical powder form in comparison to its compressed tablets in equivalent dose in a randomized, open label, standard controlled clinical trial.
| Materials and Methods|| |
The study was conducted at a Hospital in New Delhi after obtaining written informed consent from patients and approval from the Institutional Ethics Committee prior to enrollment for the study. During the trial Helsinki declaration, GCP and ICMR guidelines were strictly adhered to. Out of total screened patients, 128 were enrolled in the study fulfilling the inclusion criteria and having total cholesterol 220 mg/dl and above. Randomization was carried out on the basis of pre-assigned case numbers as per computer generated chart.
The study test drug SM of a single batch (N-274) manufactured by a GMP compliant leading Unani pharmaceutical company was procured from the market to prevent any batch to batch variation. The test drug SM is pale brown colored powder, aromatic and mildly bitter. Loss of weight on drying at 105°C was 3.8%. On analysis SM had total ash 9.4-9.6%, water soluble ash 6.8%, sulfated 11.8% and acid insoluble ash 12.2%. On chemical analysis successive extractives were petroleum ether 16%, chloroform 3.6%, methanol 8.72% and water 16.44% respectively.
The patients were randomized into test Groups A, test Group B and a control Group C. 90 patients completed the trial with 30 in each group. The test Group A was given SM in its conventional powdered form 5 g twice a day orally with water. The test Group B was put on compressed tablets of SM 5 tablets orally twice daily with water. The control group was prescribed atorvastatin 10 mg orally once daily. All the subjects were advised to adhere to the prescribed diet of 1600 calories and prescribed exercise which was defined as half an hour brisk walk daily. Duration of protocol therapy was 6 weeks with follow-up on second, fourth and 6 th week.
Patients aged 20-70 years with hyperlipidemia (total cholesterol above 220 mg/dl and other elevated lipoprotein fractions) were enrolled in the study and randomized in different groups. Patients with pregnancy, thyroid disease and diabetes mellitus type I, acquired immunodeficiency syndrome, liver and renal diseases and intake of certain drugs were excluded from the trial. Out of total patients, 5.55% belonged to age group 20-29 years, 23.33% belonged to 30-39 years, 30% belonged to age group 40-49 years, 24.44% belonged to age group 50-59 years and 16.66% belonged to 60-70 years age group. The average age Group A was 45.2 ± 1.91, Group B 45.86 ± 2.01 and Group C 46.63 ± 2.27. Out of total study subjects 17 (18.88) patients were vegetarian while as 73 (81.11) were non-vegetarian.
Assessment of efficacy and tolerability was carried out on clinical as well as biochemical parameters before, at each follow-up and after the completion of therapy as per the approved protocol.
For clinical parameters grading was carried out based on New York Heart Association scale which was modified for cardiac as well as non-cardiac patients as under:
- Grade I: Ordinary physical activities do not cause undue fatigue, palpitation, dyspnea or anginal pain
- Grade II: Ordinary physical activities results in fatigue, palpitation, dyspnea or anginal pain
- Grade III: Less than ordinary physical activities cause fatigue, palpitation, dyspnea or anginal pain. They are comfortable at rest
- Grade IV: Inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activities are undertaken, discomfort is increased.
Hemogram, liver function test (LFT) and kidney function test (KFT) were carried out before and after the study to record the safety and tolerability of the drug.
Adverse effects if any either reported or observed by the patient were recorded in clinical research file at each follow-up with information about severity, date of onset, duration and action taken regarding the study.
Assessment of results was carried out as per the protocol using Graphpad Instat 3.10 32 for Windows[Graphpad softwares Inc., San Diego, California, USA] created July 10, 2009 by using paired t-test, repeated measures ANOVA and Tukey-Kramer Multiple Comparisons Test. Test results were ranked as:
ns - non significant, *P < 0.05 significant, **P < 0.01 very significant, ***P < 0.001 extremely significant.
Percentage change was calculated by: (y2 − y1)/y1 × 100 formula.
| Results|| |
Group A consisted of 18 men and 12 women with an average age 45.2 ± 1.91, Group B also had men and women in the same ratio with an average age 45.86 ± 2.01 and Group C consisted of 12 men and 18 women with an average age of 46.63 ± 2.27 [Table 1.1] and [Graph 1.1]. [Additional file 1] Only 12.22% of total patients had significant/relevant past history such as hypertension, ischemic heart disease while as 87.77% did not have any significant history [Table 1.2] and [Graph 1.2]. [Additional file 2]
|Table 1.2: Distribution of patients according to significant personal history|
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Family history such as stroke, myocardial infarction, HT was significant in 17.77% patients while as it was non-significant for remaining 82.22% patients [Table 1.3] and [Graph 1.3] [Additional file 3].
|Table 1.3: Distribution of patients according to significant family history|
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In the study Group A out of 30 patients before treatment 12 had Grade I, 13 Grade II and 5 Grade III fatigue. At first follow-up 13, 13 and 4 Grade I, II and III respectively. At second follow-up 15, 13 and 2 as Grade I, II and III respectively. And after treatment at 6 weeks 19 patients were having Grade I, 10 patients II and 1 Grade III [Table 2.1] and [Graph 2.1] [Additional file 4].
|Table 2.1: Assessment of efficacy, clinical parameters: Effect on fatigue|
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There is a non-significant decrease by 3.62% and 11.2% at the first and second follow-up respectively when compared with before treatment. However, there is a significant relief 20.72% (P < 0.001) in fatigue among patients after 6 weeks of treatment.
In the study Group B out of 30 patients before treatment 17, 12 and 1 had Grade I, II and III fatigue respectively. After 2 weeks, i.e., at first follow-up 19 and 11 had Grade I and II fatigue respectively. At second follow-up after 4 weeks 22 had Grade I and 8 had Grade II. After treatment 24 Grade I and 6 had Grade II.
There is a non-significant decrease at first follow-up by 6.82%. At second follow-up a significant decrease of 13.64% (P < 0.05) and after treatment it decreased significantly at 18.14% (P < 0.01).
In the control Group C out of 30 patients 16 as Grade I, 13 as Grade II and 1 were graded as Grade III before treatment. At first follow 17, 12 and 1were Grade I, II and III respectively. At second follow-up 18 had Grade as I, 11 as II and 1 as III. After treatment 15 as Grade I, 14 as Grade II and 1 was graded as Grade III.
At first follow-up there was a non-significant decrease of 2.26%; and at second follow-up to 4.46%. But after the treatment, it non-significantly increased to 2.2%. Perhaps it was due to the reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin. 
In Group A out of 30 patients 14, 16 and 0 had Grade I, II and III palpitation respectively. There was no change at first follow-up. At second follow-up 21, 9 and 0 patients had Grade I, II and III. After treatment 24, 5 and 1 had Grade I, II and III palpitation respectively. This indicates that one of the patients developed Grade III palpitation at the end of the protocol therapy. But it seems unrelated to the drug as other than this particular patient no one else in both study groups had any such complaint [Table 2.2] and [Graph 2.2] [Additional file 5].
Statistically, there was 11.32% and 16.09% (P > 0.5) relief in palpitation among patients at second follow-up and after treatment respectively.
Group B had 17, 12 and 1 patient with Grade I, II and III palpitation respectively before the treatment. At first follow-up 19, 10 and 1 patient had Grade I, II and III palpitation. At second follow-up 24 and 6 patients were having Grade I and II palpitation respectively and no one complained of Grade III palpitation. After treatment 26 and 4 were graded as I and II respectively.
In this group, a non-significant change of 4.5% at first follow-up was observed. At second follow-up patients had 18.14% (P < 0.05) relief in palpitation. After treatment patients were significantly relieved of palpitation by a decrease of 22.91% (P < 0.01).
In the control Group C 13, 15 and 2 patients were having Grade I, II and III palpitation at the beginning of the treatment. At first follow-up 14, 15 and 1 had Grade I, II and III respectively. At second follow-up 16, 13 and 1 had Grade I, II and III respectively. After treatment 16 and 14 patients had Grade I and Grade II palpitation respectively.
No significant changes were observed at first (4.10%) and second follow-up (8.14%) and after treatment (10.22%).
Although minimal and non-significant statistically but this change seems due to the increased endurance due to prescribed exercise.
In Group A 16, 8 and 6 patients had Grade I, II and III dyspnea respectively before treatment. At first follow-up 17, 11 and 2 had I, II and Grade III respectively. 22, 7 and 1 had Grade I, II and III respectively at second follow-up. After treatment 23 and 7 patients had Grade I and II respectively [Table 2.3] and [Graph 2.3] [Additional file 6].
Statistically a non-significant change at first follow-up was 9.96%. At second follow-up dyspnea significantly was decreased by 21.96% (P < 0.01) and after treatment it significantly was reduced by 26.17% (P < 0.001).
Group B patients had 17, 12 and 1 with I, II and Grade III dyspnea respectively before treatment. 18, 10 and 2 with Grade I, II and III respectively at first follow-up. At second follow-up 22 and 8 patients respectively had Grade I and II dyspnea. After treatment 25 and 5 had Grade I and II dyspnea respectively.
Statistically at first follow-up there was no change. At second follow-up a non-significant decrease of 13.64% was registered. And after treatment dyspnea decreased significantly by 20.46% (P < 0.01).
In Group C 14, 11 and 5 patients had Grade I, II and III dyspnea before treatment. At first follow-up 14, 14 and 2 patients had I, II and Grade III dyspnea respectively. 17, 12 and 1 were having Grade I, II and III at second follow-up. After treatment 18 and 12 patients had Grade I and II dyspnea respectively.
Statistically, there was a non-significant decrease in dyspnea of 5.88% at first follow-up. At second follow-up and after treatment dyspnea significantly relieved by 14.11% (P < 0.01) and 17.64% (P < 0.001) respectively.
Although atorvastatin is said to cause dyspnea itself but that is on long term use of the drug. The change we see here although significant could be due to the fact that patients adhered to prescribed exercise during the course of study. Controlled studies have shown that exertional dyspnea decreases and exercise tolerance, improves in response to exercise training, even in patients with advanced disease.  However, at the same time difference in percentage change between the test Groups A, B and control Group C clearly depicts the benefit of test drugs in dyspnea.
Group A before treatment had mean total cholesterol of 243.5 ± 5.294 mg/dl which significantly was reduced to 225.6 ± 5.953 mg/dl (P < 0.001) with a percentage change of 7.35% [Table 3.1] and [Graph 3.1] [Additional file 7].
|Table 3.1: Assessment of efficacy, biochemical parameters: Effect on total cholesterol|
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Group B had mean total cholesterol of 234 ± 3.822 mg/dl which was significantly reduced to 212.67 ± 3.94 mg/dl (P < 0.001) post treatment with a percentage change of 9.11%.
Group C with 242.7 ± 5.563 mg/dl mean total cholesterol before treatment was significantly reduced to 178.73 ± 4.669 mg/dl (P < 0.001) post-treatment with a percentage change of 26.3%.
Group A before treatment had a mean TG level of 147.73 ± 7.674 mg/dl which was significantly reduced to 130.9 ± 7.128 mg/dl (P < 0.05) with the percentage change of 11.39% within 6 weeks [Table 3.2] and [Graph 3.2] [Additional file 8].
Group B had 153.366 ± 7.708 mg/dl mean TG level before treatment which was significantly reduced to 131.033 ± 7.104 mg/dl (P < 0.01) at the percentage change of 14.56% within a period 6 weeks.
In Group C TG level before treatment was 195.633 ± 11.948 mg/dl which was significantly reduced to 138.533 ± 9.763 mg/dl (P < 0.001) at a percentage change of 29.18%.
High density lipoprotein
In Group A mean HDL before treatment was 42.133 ± 0.3917 mg/dl which non-significantly was 42.4 ± 0.4196 mg/dl (P > 0.05) with a percentage change of 0.63% post-treatment [Table 3.3] and [Graph 3.3] [Additional file 9].
Group B had mean HDL 41.533 ± 0.3674 mg/dl before treatment which significantly increased to 42.6 ± 0.4085 mg/dl (P < 0.05) post-treatment with a percentage change of 2.56%.
Group C had mean HDL of 41.366 ± 0.5017 mg/dl before treatment which significantly increased to 43.833 ± 0.4291 mg/dl (P < 0.001) post-treatment with a percentage change of 5.96%.
Low density lipoprotein
Group A had mean LDL 172.9 ± 5.625 mg/dl before treatment which was significantly reduced post-treatment to 157.166 ± 5.4393 mg/dl (P < 0.01) with the percentage change of 9.1% [Table 3.4] and [Graph 3.4] [Additional file 10].
Group B pre-treatment had 163.96 ± 3.824 mg/dl mean LDL level which got significantly reduced to 144.56 ± 4.195 mg/dl (P < 0.001) with the percentage change of 11.83%.
Group C with 164.2 ± 6.823 mg/dl mean LDL pre-treatment was significantly reduced to 106.83 ± 4.822 mg/dl (P < 0.001) with 34.93% percentage change post-treatment.
Very low density lipoprotein
Group A with 28.8 ± 1.449 mg/dl mean VLDL level pre-treatment was significantly reduced to 25.86 ± 1.437 mg/dl (P < 0.05) with the percentage change of 10.2% [Table 3.5] and [Graph 3.5] [Additional file 11].
Group B pre-treatment had a mean VLDL level of 30 ± 1.520 mg/dl which was decreased significantly to 25.76 ± 1.430 mg/dl (P < 0.01) post treatment with the percentage change of 14.13%.
Group C with the pre-treatment mean of VLDL at 38.76 ± 2.400 mg/dl was significantly reduced to 27.66 ± 1.953 mg/dl (P < 0.001) post-treatment with the percentage change of 28.63%.
None of the parameters exhibited any adverse change due to the test drug during protocol therapy [Table 4.1], [Table 4.2], [Table 4.3], [Table 4.4] and [Graph 4.1(i)-4.4] [Additional file 12][Additional file 13] [Additional file 14] [Additional file 15].
| Discussion|| |
On evaluation of patients enrolled for the study on clinical, hematological and biochemical parameters, it was observed that the test drug in both forms (powder and compressed tablets) was very effective in significantly ameliorating the clinical parameters/symptoms such as fatigue, palpitation and dyspnea in comparison to control drug. Perhaps these effects could be attributed to the constituents of the test drug as many of them are known to possess tonic, stimulant, bronchodilator, relaxant and other related effects. ,,
On biochemical parameters the results in all three groups are indicative of statistically significant decrease in total cholesterol, TGs, LDL and VLDL. The hypolipidemic effect of the test drug is perhaps attributable to the synergistic effect of constituents of the test drug as they are known to possess such properties singularly as well. ,,,,,,
The above results are suggestive of better antihyperlipidemic activity of control drug in comparison to test the drug. Group B was slightly more effective than Group A amongst both the study groups perhaps due to better palatability. However, test drug had a better effect in emulating the associated clinical symptoms in comparison to control drug as the test drug also has proven antihypertensive as well as antiobesity properties. 
The test drug did not raise any safety issue. All hematological variants did not exhibit any unwarranted change and remained within normal range after treatment as well [Table 4.1], Graph 4.1(i) and (ii)]. LFT also remained within normal range [Table 4.2], Graph 4.2(i) and (ii)]. KFT also despite some significant variation remained within normal range in all the three groups [Table 4.3] and [Graph 4.3]. Among serum electrolytes serum potassium exhibited a minimal increase in both the study groups but within the normal range [Table 4.4] and [Graph 4.4].
| Conclusion|| |
Overall the results in all three groups are indicative of a significant decrease in total cholesterol, TGs, LDL and VLDL. The test drug also increased HDL. Test drug was better than control in relieving the associated clinical symptoms hence enhancing the quality of life. Another advantage of the test drug was its safety and tolerability. The study results are still limited and need further study on a larger sample size and a longer study period.
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[Table 1.1], [Table 1.2], [Table 1.3], [Table 2.1], [Table 2.2], [Table 2.3], [Table 3.1], [Table 3.2], [Table 3.3], [Table 3.4], [Table 3.5], [Table 4.1], [Table 4.2], [Table 4.3], [Table 4.4]