healthmedicinet

Crataegus oxyacantha extract

Patients were given the Crataegus oxyacantha extract in Cratagol tablets form. Cratagol
was produced at Goldaru pharmaceutical company (Isfahan, Iran) as a Coated tablets
in packs of 30 tablets containing 240 mg of dried extract of Crataegus (Hawthorn)
leaves and flowers that had been standardized as 4–6 mg Vitexin-2- ramnozide per each
tablet. Crataegus oxyacantha extract in Cratagol tablets was produced at EPO Istituto
Farmochimico Fltoterapico S.r.l. company (20141 Milano, Italy) (Additional file 1: Appendix A. Supplementary Information). Also Cratagol tablets containing adjuvants
Avicel, corn starch, talc, magnesium stearate and Arvzyl. In addition, the researchers
had no organizational or financial dependence to the company manufacturing crataegus
extract.

Placebo tablets

Placebo tablets were prepared from Goldaru pharmaceutical company (Isfahan, Iran).
The placebo was prepared from granulated of inert powder of lactose and the core of
pressed tablets was coated similar to that of Cratagol and the produced tablets were
entirely similar to the original product in terms of color, size and appearance. The
tablets were encoded and they were used in clinical studies through the Double Blind
Method. Original and placebo tablets were previously coded and after the required
experiments the type of drugs based on their codes in studied subjects were determined,
then statistical analysis were performed.

Expriments

Subjects were included patients with stable angina who were under treatment at the
Imam Ali cardioligy sub-specialty polyclinic of Shahrekord, Iran. The diagnosis of
stable angina pectoris in the patients was performed by Professor of Cardiology with
coronary angiography test. Patients whose angiography test history was carried out
between 1 and 12 months ago and there were no new symptoms of pain or discomfort during
this period and also their coronary atherosclerosis was less than 50 %, with clear
treatment history within past 3 months, aged between 45 and 65 years were selected
for this study. 1500 potential cases of stable angina patients who were under treatment
at the Imam Ali cardioligy sub-specialty polyclinic of Shahrekord, Iran were investigated.
Most of these patients were out of our entrance requirements, also unwillingness to
participate the study, severe heart failure, lack of accessibility, pharmacological
interventions and death were of the criteria for which the participants were eliminated
and also patients with severe heart failure and/or treated with digoxin, cisapride,
anticoagulant, anti-arrhythmic drugs were excluded. Finally, 80 patients (44 male
and 36 female) suffering from ischemic heart disease of stable angina were recruited
and randomly assigned into four groups (20 patients (11 male and 9 female)): three
experimental groups including aerobic exercise and placebo (E), Crataegus oxyacantha
extract (S), aerobic exercise and Crataegus oxyacantha extract (S?+?E) and one control
group (C) and were followed for 12 weeks. Patients in each group were homogenate with
regards to age, sex, weight, and Body Mass Index (BMI). Because of the relationship
between individual characteristics such as sex, age, BMI, and weight and inflammatory
markers measured in this study, we attract the reviewer’s attention to the fact that
the researchers tried to reduce bias in the results by choosing four homogenated groups.
In particular, in order to excluding the effect of sex on the results, the number
of males and females were equal in both groups, however, the distribution of men and
women based on their number was accidental. Random number tables were used where each
value was randomly selected with an equal chance of choosing any integer among 1–44
(men) and 45–80 (women) by QuickCalcs online calculator (http://www.graphpad.com/quickcalcs/randomn2.cfm) (Additional file 2: Table S1 and S2), which allocated the numbers randomly to control and experimental
groups. Also, the amount of physical activity, nutrition, diet, smoking, alcohol,
symptoms and duration of angina were accurately determined through medical record
questionnaires and reports contained in patient records. As well as, we had no crossover
or contamination between groups and the current study was carried out as multiple
parallel groups until the end of experiments. The patients in all 4 groups were administered
with Methoral (50 mg/day), Aspirin (80 mg/day), and sublingual Nitroglycerin in case
of discomfort. Crataegus oxyacantha extract were additionally taken by patients in
the experimental groups (S) and (S+E), twice a day, and each time one tablet along
with chemical medication with a little water before meals. The control group (C) did
not take any Crataegus oxyacantha extract. The control group in this study was not
influenced by any intervention and also did not receive the placebo tablets, but during
the experimental period, the weekly report of their nutritional status and physical
activity were recorded and were under control. This project was approved by the ethics
committee of the Medical University of Shahrekord, Iran and was recorded in the clinical
trial center with registration number IRCT201303098435N1. The participants had sufficient
information and awareness to participate in the study and the process by which they
filled out the consent form was controlled and documented (Fig. 1).

Fig. 1. Flow diagram of the trial

Exercise program

Aerobic exercise program was performed on a treadmill (after one week pre-adaptation)
with an intensity of 40–60 % of heart rate reserve (HRR) and a rating of perceived
exertion (RPE) of 11–13 (on 6–20 Borg scale), twice a week, each time 20–30 min, for
3 month (12 week) 21]. Meanwhile, The patient’s conditions and emotions, intensity and duration of exercise,
blood pressure, resting and exercise heart rate were controlled at the beginning,
during, and after exercise by digital stethoscope (Geratherm Medical AG, German) and
recorded. The exercise was stopped in case of discomfort in the chest, asthma, dizziness,
fatigue and loss of systolic blood pressure more than 10 mm Hg and the exercises were
continued, modified or interrupted under the opinion of psychiatrists. The data obtained
from exercise and blood tests were collectively recorded in separate sheets for final
analysis. Training exercise was carried out by specialized expert, under the direction
of Professor of Cardiology in the Imam Ali sub-specialty polyclinic of Shahrekord,
Iran.

Blood tests

Fasting blood test was performed 24 h before study and also after 12 weeks. Blood
tests were performed in specialized laboratories from 5 ml blood sample of arm vein
of each patient. After 5 min of coagulation time, the samples were centrifuged at
3000 rpm for 10 min. Immediately blood tests were performed to determine the levels
of ICAM-1 and E-Selectin in serum using a detection kit in specialized laboratories.

Measurements

Serum concentrations of ICAM-1, and E-selectin were carried out using standard ELISA
Kit (Boster, USA), with a sensitivity of 10 pg/ml and 4 pg/ml respectively. An ELISA
reader (Ststfax 2100, USA) was also used.

Statistical analysis

Data were analyzed using SPSS 17 and the results presented as mean?±?standard deviation.
Comparisons between groups were made using the Kolmogorov-Smirnov test as well as
ANOVA followed by Least significant difference (LSD) test. A two-sided P-value of 0.05 was considered as statistically significant.