INTRODUCTION

Xuezhikang is a new Chinese Traditional Medicine for lipid regulation.[1,2] Meanwhile, Mevalotin is a new HMG-CoA reductase inhibitor [3] with the performance of decreasing serum total cholesterol. Different from Mevalotin, Xuezhikang possesses not only rich of HMG-CoA reductase inhibitor Lovastatin, but also various unsaturated fatty acids and essental amino-acids. As a result, the two medicines have different mechanism on lipid regulation. In this study, we compared the effects of Xuezhikang with that of Mevalotin.

PATIENTS AND METHODS

Patients
Hyperlipoidemia patients either outpatient or inpatient who had not taken any lipid-lowering agent at present, after 2-week diet education and adjustment, were tested with plasma lipid level. Those with serum TC ³ 5.96 mmol/L (230mg/dl) and/or TG ³ 2.25 ~ 4.52 mmol/L (³ 200mg/dl ~ £ 400mg/dl) were chosen totalling 44 cases. In addition, medical history was inquired and physical examination or other tests were conducted to exclude the following cases from the patients: i.e. patients with distinct diseases of liver, kidney and internal secretion system; or hyperlipoidemia caused by medicine; pregnant and lactation women; or myocardinal infarction, cerebral stroke, or moderate to serious injury or major operations on brain within 6 months).

Methods
Randomized, single-blind comparison method was employed in the study.

Group Division and Medicine Administration
ll 44 patients were randomly divided into two groups: Xuezhikang group and Mevalotin group with 22 cases in each group. Four capsules of Xuezhikang (developed by WBL Peking University Biotech Co. Ltd.) were administrated twice a day with two in the morning and two in the evening by patients in Xuezhikang group. Whereas 10 mg Mevalotin was taken draught in every evening. The treatment lasted for 12 weeks and every patient finished the overall treatment.

Testing Methods
During the treatment, patients kept their diet but be prohibited from alcohol and high cholesterol food the dinner before blood sampling. Blood samples were taken from 12-h fasting patients the next morning. The concentrations of serum TC, TG and HDL-C were identified by automatic series analyzer with enzyme reagent method and LDL-C level calculated by the formula:
LDL-C = TC - HDL-C - 0.2´TG
Meanwhile, Atherogenic Index (AI) by the following formula:
AI = (TC - HDL-C)/HDL-C

The determination of plasma lipid was carried out in accordance with unified quality control system and QC of plasma lipid testing of this hospital met the standards of USA Disease Control Center. Immunochemical method was adopted to identify the level of ApoB-I and APOB (the cartridge is manufactured by RANDOX Company of Britain). Every test was conducted by a designated person.

Observational Indexes
Serum TC, TG, HDL-C, ApoA-I and APOB were tested twice (with 2 ~ 4 weeks interval) before the treatment. After the treatment, the above indexes were tested once at the end of 4 weeks and 12 weeks separately. Meanwhile, the assay of liver and renal function, fasting blood-glucose, conventional blood and urine analysis were carried out before, 4 weeks after and 12 weeks after the treatment. And consequent side-effects were inquired and recorded.

Criteria for Effects
The determination of effects referred to Guiding Principles on Clinical Study for Cardiovascular Medicine stipulated by the Ministry of Public Health in 1988.

• Highly effective
  TC reduction ³ 20% or TG reduction ³ 40%, or HDL-C elevation ³ 0.26 mmol/L (10 mg/dl), or Atherogenic Index reduction ³ 20% ;
• Effective
  TC decrease 10% ~ < 20% or TG reduction by 20% ~ < 40%, or HDL-C elevation by 0.1 ~ 0.26 mmol/L (4 ~ 10mg/dl), or Atherogenic Index reduction 10% ~ < 20%;
• Ineffective
  Laboratory test indexes could not reach any one of the above standards.
  
  

RESULTS

Basic Clinical Characteristics
Xuezhikang group had basic clinical characteristics similar to that of Mevalotin group before the treatment. The male to female ratio was 12/10 in Xuezhikang group and 13/9 in Mevalotin group. Whereas the age reached 52 ± 14 years old in Xuezhikang group and 55 ± 15 in Mevalotin group. Before the treatment, no statistic difference existed between the concentrations of serum TC, TG, HDL-C, APOA-I and APOB of the two groups.

Change of Plasma Lipid Level
Before the treatment, serum TC, LDL-C and Atherogenic Index were 6.81 ± 0.54, 4.38 ± 0.58, 4.86 ± 1.28 respectively in Xuezhikang group. The above levels decreased by 22.02%, 26.59% and 28.29% respectively at the end of 4-week treatment and 33.32%, 33.39% and 33.68% respectively at the end of 12-week's treatment, all had significantly different from that of before the treatment (P < 0.01). Compared with 4-week's treatment, the 12-week's reduction of TC and LDL-C seemed more distinct (P < 0.05). Whereas in Mevalotin group, the reduction of serum TC, LDL-C and TG reached by 20.98%, 18.92% and 28.12% at the end of 4-week's treatment 24.24%, 26.18% and 20.55% respectively at the end of 12 weeks treatment. However, no statistic difference existed between the above indexes of 4-week treatment and that of 12-week treatment (P > 0.05).

It was worth noting that, Xuezhikang group, TG dropped 31.89% at the end of 4 weeks treatment and 32.81% at the end of 12 weeks treatment while serum HDL-C elevated 13.90% at the end of 12 weeks treatment.

In addition, APOB level of Xuezhikang group decrease by 10.82% at the end of 4-week treatment and 18.42% 12-week later (P < 0.01). APOA-I level raised by 20.83% and 32.09% respectively (P < 0.01). The reduction of APOB of 12-week Xuezhikang treatment was more significant than that of 4-week treatment (P < 0.01). In Mevalotin group, however, APOB reduction and the rise of APOA-I/APOB ratio were lower than that of Xuezhikang group.

Individual Effects
There were significant difference in total efficacy of TC and Atherogenic Index between Xuezhikang group and Mevalotin group 4-week and 12-week later. The efficiency of serum TG reduction and HDL-C elevation by Xuezhikang was higher than by Mevalotin, but without any statistic difference. The two treatment groups possessed quite similar effects.

Side-effects
At the end of 4-week or 12-week treatment, no clear side-effects appeared in terms of routine blood and urine tests, liver and renal functions and general electrocardiogram examination.

DISCUSSION

Mevalotin is a new special inhibitor for speed control enzyme - HMG-CoA reductase among cholesterol synthesis enzyme series. It is reported that [4,5] Mevalotin could suppress the synthesis of TC in liver cells, decline TC level in cells, decrease serum TC, stimulate and accelerate LDL-C receptor synthesis through feedback regulation, increase the number of LDL-C receptor expression on cell surface, enhance LDL metabolism and reduce LDL-C level in blood, thus having the function of anti-atherosclerosis.

Xuezhikang is manufactured and refined from Hongqu (red yeast rice or Monascus purpureus). And the pharmacodynamics on lipid and lipoprotein regulation is still not completely clear. It was found in the study that 4-week Xuezhikang treatment produced effects similar to 4-week Mevalotin treatment in terms of the reduction of serum TC, LDL-C and Ar. However, Xuezhikang obtained better results on the decrease of TC, LDL-C and Atherogenic Index levels after 12 weeks administration compared with 4-week treatment. Meanwhile, it performed more effectively than Mevalotin to reduce serum TC, LDL-C and TG.

Moreover, Xuezhikang could elevate HDL-C level and significantly decrease TG level. It was assumed that the functional mechanism may have something to do with rich composition of HMG-CoA reductase inhibitor and various kinds of unsaturated fatty acids and essential amino-acids in Xuezhikang. The latter components, apart from facilitating cholesterol excretion and enhancing the reduction of serum TC and LDL-C, could promote TG decomposition and HDL-C production. Therefore, it acted more effective than Mevalotin to regulate plasma lipid metabolism disorder. As a result, Xuezhikang can be regarded as one of the ideal lipid-regulating medicines to prevent and control atherosclerosis in clinical hyperlipoidemia treatment.

REFERENCES