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27
UDC 616.153.455-008.61
NEW SLANT ON HYPOLIPIDEMIC CHARACTERISTICS OF VITAMIN-E
AND RED DATE
ASHRAF MEMON, SHAHINA HAKRO, KHALID NIAZ, ABDUL QUDOOS, ABDUL QUDOOS, SHAH MURAD
Islamabad Medical and dental college, Islamabad-Pakistan
Ashraf Memon - Professor of Pharmacology Shahina Hakro - AP Biochemistry Khalid Niaz - AP Pharmacology Abdul Qudoos - AP Pharmacology Abdul Qudoos - AP Pharmacology Shah Murad - Professor and HOD of Pharmacology/Therapeutics,
tel.: +923142243415, e-mail: [email protected].
Abstract.
Background: High plasma lipids can cause complications leading to development of metabolic syndrome, including hypercholesterolemia, hypertension and hyperglycemia. To treat syndrome by allopathic regimn of allopathic drugs is difficult to treat. Herbal medicine are replacing drug treatment of hyperglycemia, hypertension and hyperlipidemia especially by antioxidant effects of their active ingredients. We have compared antioxident characteristics of vitamin-E and red Dates.
Type/place/duration of Study: It was placebo-controlled conducted study conducted at general hospital Lahore Pakistan from January 2014 to march 2014.
Inclusion and exclusion criteria: 120 male hyperlipidemic patients were included with age range from 18 to 70 years. We excluded patients already suffering from renal, hepatic, pulmonary, or thyroid diseases. We also excluded patients already on cardio and hepato-protective drugs.
Sample size and division of patients: 120 hyperlipidemic patients were divided in three equal number of patients, 40 patients in each group. Group-I (n=40) was on placebo. They were provided capsules which were filled with grounded brown rice taking 8 hourly daily for one month. Group-II (n=40) was on capsules of vitamin E 400 mg taking eight hourly daily for one month. Group-II (n=40) was advised to take red dates 20 grams thrice daily for the period of one month.
Method of lipid profile determination: LDL-cholesterol was calculated as total cholesterol- HDL-cholesterol-VLDL-cholesterol;VLDL-cholesterol was measured directly after ultracentrifugation.
Observations and Results: After one month therapy their post treatment lipid profile was determined and analyzed statistically by using SPSS version 2.2.01 2013. Paired 't' test was applied for mean values with SD of the parameters before and after treatment. Results showed highly significant change in LDL-cholesterol of group-II patients but HDL-cholesterol was increased 6.6 mg/dl, still it was significant change with p-value of <0.01. In group-III LDL-cholesterol was decreased 10.9 mg/dl which is significant change with p-value <0.01. HDL-cholesterol in this group was increased 4.2 mg/dl which is non significant with p-value of >0.05. Conclusion: We concluded from the study that Z. Jujube has antioxidant potential by lowering LDL-cholesterol in human plasma. But This effect is not comparable with hypolipidemic effects of Vitamin E as it also increases good cholesterol i.e. HDL-cholesterol.
Keywords: LDL-cholesterol, HDL-cholesterol-VLDL-cholesterol, herbal medicine, drug treatment, hypertension, hyperlipidemia.
INTRODUCTION
Simple consumption of high saturated common foods can cause hyperlipidemia1. High lipids levels in plasma can be cause of coronary artery disease predetermining to morbidity or mortality due to myocardial infarction2-8. Superoxide radical and hydroxyl radical may contribute
to the oxidation of LDL. Thus, a strategy directed at the use of antioxidants such as vitamin E has been advocated to decrease the susceptibility of LDL to oxidation by interrupting free radical peroxidative chain reactions and to increase the resistance to atherosclerosis by protecting against endothelial dysfunction in hypocholesterolemic
patients910. Vitamin-E performs its functions as antioxidant in the glutathione peroxidase pathway and it protects cell membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. This removes the free radical intermediates and prevents the oxidation reaction from continuing. The oxidized a-tocopheroxyl radicals produced in this process may be recycled back to the active reduced form through reduction by other antioxidants, such as a scorbate, retinol or ubiquinol11,12. Chylomicrons carry vitamin-E from the enterocyte to the liver, where they are incorporated into parenchymal cells as chylomicron remnants13. The catabolism of chylomicrons takes place in the systemic circulation through the action of cellular lipoprotein lipase. During this process vitamin-E can be transferred to high-density lipoproteins. This vitamin-E in high density lipoproteins can transfer to other circulating lipoproteins, such as low density lipoproteins and very low-density lipoproteins, causing less oxidative process to occur14,15. A full range of plant derived nutritional supplements, phytochemicals, and pro-vitamins which help in sustaining good health and fighting diseases is now being described as functional foods, nutriceuticals, and nutraceuticals16"20. Red date is one of them. The hepato-cardio-protective effect is attributed to red date's antioxidant mechanisms and inhibition of oxidative degradation of lipids. Jujube contain higher phenol levels, exhibiting diphenylpicrylhydrazyl antioxidant activity, ferric ion reducing antioxidant power and protective effects against DNA damage21. Treatment with red dates significantly inhibits serum lipoprotein oxidation, reduce the impact of free redicals on aspartate aminotransferase and alanine aminotransferase. It also inhibits the generation of 8-hydroxy-2-deoxyguanosine, lowers the levels of malondialdehyd and increases the activity of hepatic glutathione peroxidase22,23.
PATIENTS AND METHOD
It was placebo-controlled research conducted at general hospital Lahore Pakistan from January 2014 to march 2014. 120 male hyperlipidemic patients were included with age range from 18 to 70 years. We excluded patients already suffering from renal, hepatic, pulmonary, or thyroid diseases. Patients already taking medicines for any cardiac problem were also excluded. Written and already explained consent was taken from all participants. Patients were divided in three equal numbers, ie; 40 patients in each group. Group-I (n=40) was on placebo. They were provided capsules which were filled with grounded brown rice taking 8 hourly daily for one month. Group-II (n=40) was on capsules of vitamin E 400 mg taking eight hourly daily for one month. Group-II (n=40) was advised to take red dates 20 grams thrice daily for the period of one month. Their separate folder was made to keep their medical record regarding their progress to
drug treatment, follow-up and drug compliance. They were advised to visit clinic (research centre) fortnightly for checkup and follow-up or any other miscellaneous advice/query. Their lipid profile was determined in biochemistry laboratory of the hospital. LDL-cholesterol was calculated as total cholesterol - HDL-cholesterol -VLDL-cholesterol; VLDL-cholesterol was measured directly after ultracentrifugation. Biostatistical analysis was determined by applying paired 't' test using SPSS version 2.2.01 2013. P-value >0.05 was considered as non-significant change, p-value <0.01 was significant change in the parameters and p-value <0.001 was considered as highly significant change in the parameter. We emphasized on changes in LDL-cholesterol and HDL-cholesterol because these two parameters are core factors for development of atherosclerosis leading to development of coronary artery disease which is again core cause of hypertension or even metabolic syndrome.
OBSERVATIONS AND RESULTS
After one month therapy by vitamin-E and red dates when pre and post-treatment results were compared, it was observed that Vitamin E reduced TC 19.3, TG 14.2, LDL-c 20.2 mg/dl. HDL increased in this group 6.6 mg/dl. Red dates decreased TC 8.2, TG 4.0, LDL-c 10.9 mg/dl. HDL-c in this group increased non-significantly ie; only 4.2 mg/dl. Changes in mean values with SD and statistical significance is shown in following table.
TABLE showing before and after treatment values, changes and biostatistical significance in lipid profile of placebo group and two tested groups of hyperlipidemic patients
Parameter/ Group BT AT Change p-value
PG_(n=40)
TC 270.11±1.98 265.11±2.00 5.0 >0.05
TG 210.33±2.10 200.98±1.54 9.4 <0.01
LDL-c 180.54±2.19 178.29±1.63 2.3 >0.05
HDL-c 34.76±2.65 35.11±1.56 0.4 >0.05
TG-I (n=38)
TC 289.14±1.93 269.88±1.94 19.3 <0.001
TG 270.27±2.11 256.12±2.66 14.2 <0.001
LDL-c 241.61±1.46 221.38±2.22 20.2 <0.001
HDL-c 33.51±1.19 40.15±1.90 6.6 <0.01
TG-II (n=35)
TC 243.61±1.88 235.44±3.11 8.2 >0.05
TG 231.86±2.16 227.91±2.11 4.0 >0.05
LDL-c 203.28±3.11 192.39±2.97 10.9 <0.01
HDL-c 37.83±2.04 41.99±1.96 4.2 >0.05
KEY: 'n' in Parameter/Group column = sample size, BT=before treatment, AT=after treatment, PG in
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parameter /Group=placebo group, TG-I in parameter/ Group=tested group-I (vitamin-E), TG-II in parameter/ group=tested group-II (red dates), TC=total-cholesterol, TG=triglycerides, LDL-c=low density lipoprotein cholesterol, HDL-c=high density lipoprotein cholesterol. All parametesrs are measured in mg/dl. P-value >0.05 was considered as non-significant change, p-value <0.01 was considered as significant and p-value <0.001 was considered as highly significant change in the parameter.
DISCUSSION
Oxidation and free radical damage have long been believed to be a risk factor of many chronic diseases that accompany aging, including heart disease, eye degeneration, memory loss, damage from UV light and cancer. Fortunately, there is one thing that can offset oxidation caused by free radical damage: antioxidants. Various studies have proved that vitamin E significantly lowers C-reactive protein, and also reduces urinary F2-isoprostanes ie; a measure of oxidative stress24. Remarkable number of research works had have mentioned about reduced release by monocytes of superoxide and tumor necrosis factor ie; inflammatory cytokine. In our research study 1200 mg per day consumption of vitamin E for one month reduced LDL-cholesterol 20.2 mg/dl in 38 hyperlipidemic patients. Our results match with results of Meydani SN et al25, magliano D et al26 who proved same highly significant results from small sample size to meta analysis that high doses of vitamin E can lower LDL-cholesterol and enhance plasma HDL-cholesterol even used for short period of time in moderately to severe hyperlipidemic patients. In our results HDL-cholesterol increased only 6.6 mg/dl when vitamin E was used in 35 hyperlipidemic patients. But it is biostatistically significant change in the parameter. Same results were proved in study conducted by Lonn E et al27 when they used 1200 mg vitamin E in fifty six hyperlipidemic patients for three months. Our results are in contrast with results achieved by Salonen RM et al28 who proved lesser amount of reduction in LDL-cholesterol and less increase in HDL-cholesterol in 10 hyperlipidemic patients. Even they used 1500 mg vitamin E for the period of three months. This contrast in two studies is self explanatory ie; due to lesser sample size in the study work. Red dates in our results reduced LDL-cholesterol of 35 hyperlipidemic patients 10.9 mg/dl which is significant change in the parameter causing atherosclerosis, and increased HDL-cholesterol 4.2 mg/dl which is non-significant change in this parameter. These results match with study of Ghedira K et al29 who proved almost same changes in LDL and HDL-cholesterol. Abddel-zaher A et al30 have mentioned that mucous secretion and content of red dates may inhibit enterohepatic circulation of bile acids leading to induction of hepatocytes to synthesize bile acids instead of cholesterol. Same mechanism of action of red dates
is mentioned by Abdul Rahim Al-J et al31. Hala M et al32 proved very high level of reduction in 40 hyperlipidemic patients ie; 31 mg/dl reduction in LDL-cholesterol when they used half kilograms of red dates in eighty one hyperlipidemic patients for the period of two months. This difference in two study results are guessed to be due to some environmental factors and large sample size in their research work. Abdell LL et al33 observed high increase in HDL-cholesterol in twenty three hyperlipidemic patients ie; 13.28 mg/dl when they used 250 grams of red dates for the period of only three weeks. Again this contrast or difference in two studies results are due to environmental factors. In both studies they put their enrolled patients in close environment advised with strict aerobic exercise one hour daily for whole period of their research work. CONCLUSION
We concluded from this study that when used in high doses of vitamin E, it surely reduces LDL-cholesterol but increase in HDL-cholesterol moderately. When regular aerobic exercise is added with this vitamin its response may be doubled especially in enhancement of HDL-cholesterol. Red Dates decreases LDL-cholesterol in amount half than vitamin E. For increase in HDL-cholesterol, Red Dates are not sufficient when used vaguely or without exercise and strict limitations for taking fatty diets. References:
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21. Foroughinia F, Eshraghi A, Asgari S, Movahedian A, Naderi GA, Badiee A. Antioxidant effects of water and ethanolic extract of Ziziphus vulgaris, Berberis integerima, Portulaca oleracea, and Gundelia tournefortti on cell membrane of hepatocytes and red blood cell hemolysis. J Med Plants 2011;10(40):80-88.
22. Glombitza K, Mahran G, Mirhom Y, Michel K, Motawi T. Hypoglycemic and antihyperglycemic effects of Zizyphus spinachristi in rats. Planta Med. 2012;60:244.
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29. Ghedira, K., R. Chemli, B. Richard, J. Nuzillard, M. Zeches and L. Le. Two cyclopeptide alkaloids from Zizyphus lotus. J. Phytochem. 2010;32:1591-94.
30. Abdel-Zaher, A., S. Salim, M. Assaf and R. Abdel-Hady. Antihyperlipidemic activity and toxicity of red dates. J. Ethnopharmacol 2012;131:129-38.
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32. Hala, M., M. Eman and A. Aataa, Sofia S, larapika K. Antihyperglycemic, Antihyperlipidemic and Antioxidant Effects of Zizyphus species. Int. J. Pharmacol 2011;2:563-70.
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EaTbic ^a3a^CTaH Meg^HHa ^ypH&nbi 3 (55) 2017
ТУИ1Н
Е ВИТАМИН1 МЕН ЗИЗИФУСТЬЩ ГИПОЛИПИДЕМИЯЛЬЩ СИПАТТАМАЛАРЫНА ЖАЦАША КОЗЦАРАС
АШРАФ МЕМОН, ШАХИНА ХАКРО, ХАЛИД НИАЗ, АБДУЛ КУДОУС, АБДУЛ КУДОУС,
ШАХ МУРАД
Исламабад медицинальщ стоматологиялык колледжi, Исламабад, Пакистан
Ашраф Мемон - фармакология кафедрасыньщ профессоры;
Шахина Хакро - биохимия кафедрасыньщ кауымдастырылган профессоры;
Халид Ниаз - фармакология кафедрасыныц кауымдастырылган профессоры;
Абдул Кудоус - фармакология кафедрасыныц кауымдастырылган профессоры;
Абдул Кудоус - фармакология кафедрасыныц кауымдастырылган профессоры;
Шах Мурад - фармакология-терапия кафедрасыныц жетекшга, профессор, тел.: +923142243415, e-mail: [email protected].
Шркпе. Плазманыц жогары липидтер1 гиперхолестеринемия, гипертония жэне гипергликемиямен коса, метаболикалык синдромныц дамуына экелетш аскынуларды тудыруы мумшн. Синдромды дэршк шептермен емдеу киындыктар тудырады. Гипергликемия, гипертония жэне гиперлипидемия кезшде дэршк шептерден жасалган препараттарды тагайындау дэстурл1 дэршк емд1 алмастыра алады.
Зерттеу материалдары мен эдктерь Б1з Е витамиш мен зизифустыц антиоксидантты сипаттамасын салыстырдык. 2014 жылдыц кацтар-наурыз айларында Лахор каласыныц (Пэк1стан) когамдык ауруханасында плацебо-бакылау зерттеу1 жург1з1лд1. Зерттеуге 18-ден 70 жаска дешнп аралыктагы гиперлипидемиямен ауыратын 120 пациент (ер адам) катысты. Зерттеуге буйрек, бауыр, екпе жэне калканша без1 аурулары бар пацменттер, сонымен катар, кардио жэне гепатопротекторлы перпараттар кабылдайтын пациенттер катыстырылмады.
Гиперлипидемиясы бар 120 пациент эркайсысыныц курамы 40 пациенттен туратын 3 б1рдей топка бетнда. I топ (n = 40) б1р ай бойына кун1ге эр 8 сагат сайын кун1ге плацебо кабылдады, капсулалар тазартылмаган суры куршпен толтырылды. II топ (n = 40) б1р ай бойына тэулжпк мелшер1 400 мг 8 сагат сайын кушге капсуладагы Е витаминш кабылдады. III тобына (n = 40) 1 ай бойына кунше 3 реттен 20 г зизифус тагайындалды.
LDL-холестериндi жалпы HDL-VLDL-холестерин репнде есептед^ VLDL-холестериндi ультрацентрифугалаудан кейiн пкелей елшедi. Липидтi кескiндi емдеуден бiр бурын жэне бiр ай кешн аныктады. Керсеткiштер SPSS 2.2.01 2013. нускасы колданыла отырып, статистикалык тургыда енделдi. Т тестi емдеуге дешн жэне кейiн SD параметрлерiмен орта белгшер Yшiн колданылды.
Нэтижелерь Нэтижелерi II топтыц пациенттерiнде LDL-холестеринiнiц едэуiр езгергендiгiн, бiрак HDL-холестерин 6,6 мг/дл-ге (р <0,01) ескендiгiн керсетп. III топта LDL-холестерин децгейi 10,9 мг/дл-ге (p<0,01) азайды. Бул топтыц HDL-холестериш 4,2 мг/дл-ге (p> 0,05) есп.
Т^жырым. Зизифус адам плазмасында LDL-холестериннiц децгейiн темендете отырып, антиоксидантты потенциалга ие болады. Е витаминш колданганнан кейiн HDL-холестерин децгейi кетершгенджтен, оны тагайындау гиполипидемиялык эсер бердг
Heeisei свздер: гипергликемия, метаболикалыц синдром, гипертония, Е витамин!, HDL-холестерин, LDL-холестерин, зизифус.
РЕЗЮМЕ
НОВЫЙ ПОДХОД К ГИПОЛИПИДЕМИЧЕСКИМ ХАРАКТЕРИСТИКАМ
ВИТАМИНА-E И ЗИЗИФУСА
АШРАФ МЕМОН, ШАХИНА ХАКРО, ХАЛИД НИАЗ, АБДУЛ КУДОУС, АБДУЛ КУДОУС,
ШАХ МУРАД
Исламабадский медицинский стоматологический колледж, Исламабад, Пакистан
Ашраф Мемон - Профессор кафедры фармакологии;
Шахина Хакро - Ассоциированный профессор кафедры биохимии;
Халид Ниаз - Ассоциированный Профессор кафедры фармакологии;
Абдул Кудоус - Ассоциированный Профессор кафедры фармакологии;
Абдул Кудоус - Ассоциированный Профессор кафедры фармакологии;
Шах Мурад - Профессор, руководитель кафедры фармакологии / терапии моб. тел.: +923142243415, e-mail: [email protected].
Введение. Высокие липиды плазмы могут вызывать осложнения, приводящие к развитию метаболического синдрома, включая гиперхолестеринемию, гипертонию и гипергликемию. Лечение синдрома лекарственными препаратами вызывает трудности. Назначение препаратов из лекарственных растений может заменить традиционную лекарственную терапию гипергликемии, гипертонии и гиперлипидемии.
Материалы и методы исследования. Мы сравнили антиоксидантные характеристики витамина Е и зизи-фуса. Было проведено плацебо-контролируемое исследование в общей больнице г. Лахор (Пакистан) с января 2014 года по март 2014 года. В исследовании участвовали 120 пациентов (мужчины), страдающие гиперлипи-демией, в возрасте от 18 до 70 лет. Из исследования были исключены пациенты с заболеваниями почек, печени, легких и щитовидной железы, а также пациенты, принимающие кардио- и гепатопротекторные препараты.
120 пациентов с гиперлипидемией были разделены на три группы по 40 пациентов в каждой. Группа I (n = 40) принимала плацебо через каждые 8 часов ежедневно в течение одного месяца, капсулы заполнялись неочищенным коричневым рисом. Группа II (n = 40) принимала витамин Е в капсулах через каждые 8 часов ежедневно в суточной дозе 400 мг в течение одного месяца. Группе III (n = 40) был прописан зизифус по 20 г три раза в день в течение одного месяца. LDL-холестерин рассчитывали как общий холестерин-HDL-VLDL, VLDL-холестерин измеряли непосредственно после ультрацентрифугирования. Липидный профиль определяли до и после одного месяца лечения.Показатели обрабатывались статистически, используя версию SPSS 2.2.01 2013. Тест T применялся для средних значений SD параметров до и после лечения.
Результаты: Результаты показали очень значимое изменение LDL- холестерина у пациентов II группы, но HDL-холестерин был увеличен на 6,6 мг/дл. (р <0,01). В группе III уровень LDL-холестерина уменьшался на 10,9 мг/дл.(р<0,01). HDL-холестерин в этой группе был увеличен на 4,2 мг/дл (p> 0,05).
Вывод. Зизифус обладает антиоксидантным потенциалом, понижая уровень LDL-холестерина в плазме человека. Назначение витамина Е также оказывало гиполипидемический эффект, так как после его применения повышался уровень HDL-холестерина.
Ключевые слова: гипергликемия, метаболический синдром, гипертония, витамин Е, HDL-холестерин, LDL-холестерин, зизифус.
