Simultaneous Content Determination of 8 Components in Xuezhikang Capsules by HPLC-DAD / 中国药房

OBJECTIVE： To establish the method for simultaneous determination of 5 isoflavones （daidzin， genistin， daidzein， glycitein and genistein） and 3 statins （lovastatin hydroxy acid， mevastatin and lovastatin） in Xuezhikang capsules. METHODS： HPLC-DAD method was adopted. The determination was performed on Shimadzu Hypersil Gold C18 column with mobile phase consisted of 0.1％ formic acid water-acetonitrile using gradient elution. The flow rate was 1.0 mL/min， and the detection wavelengths were set at 256 nm （daidzin， genistin， daidzein， glycitein and genistein） and 237 nm （lovastatin hydroxy acid， mevastatin and lovastatin）. The column temperature was maintained at 30 ℃， and sample size was 10 μL. RESULTS： The linear range of daidzin， genistin， daidzein， glycitein， genistein， lovastatin hydroxy acid， mevastatin and lovastatin were 5.01-250.20， 3.02-150.91， 2.27-113.33， 3.01-150.58， 3.61-180.43， 4.03-201.19， 3.32-166.32， 5.02-250.82 μg/mL （r＝0.999 3-0.999 9）， respectively. The detection limits were 0.25， 0.13， 0.45， 0.12， 0.21， 0.24， 0.12 and 0.15 μg/mL； the quantitation limits were 0.84， 0.36， 1.29， 0.41， 0.65， 0.78， 0.33 and 0.50 μg/mL， respectively. RSDs of precision， stability （48 h） and reproducibility tests were all no more than 3.0％ （n＝6）. Average recoveries were 97.04％， 98.49％， 99.60％， 96.14％， 101.88％， 96.20％， 101.19％， 98.46％， and RSDs were 1.76-4.79％ （n＝6）. CONCLUSIONS： The established methods is simple， sensitive， accurate， and can be applied for simultaneous content determination of daidzin， genistin， daidzein， glycitein， genistein， lovastatin hydroxy acid， mevastatin and lovastatin in Xuezhikang capsules.

Isoflavones enhance pharmacokinetic exposure of active lovastatin acid via the upregulation of carboxylesterase in high-fat diet mice after oral administration of Xuezhikang capsules.

Xuezhikang capsule (XZK) is a traditional Chinese medicine that contains lovastatin (Lv) for hyperlipidemia treatment, although it has fewer side effects than Lv. However, the pharmacokinetic mechanisms contributing to its distinct efficacy and low side effects are unclear. Mice were fed a high-fat diet (HFD) for 6 weeks to induce hyperlipidemia. We first conducted the pharmacokinetic studies in HFD mice following oral administration of Lv (10 mg/kg, i.g.) and found that HFD remarkably decreased the active form of Lv (the lovastatin acid, LvA) exposure in the circulation system, especially in the targeting organ liver, with a declined conversion from Lv to LvA, whereas the Lv (responsible for myotoxicity) exposure in muscle markedly increased. Then we compared the pharmacokinetic profiles of Lv in HFD mice after the oral administration of XZK (1200 mg/kg, i.g.) or an equivalent dose of Lv (10 mg/kg, i.g.). A higher exposure of LvA and lower exposure of Lv were observed after XZK administration, suggesting a pharmacokinetic interaction of some ingredients in XZK. Further studies revealed that HFD promoted the inflammation and inhibited carboxylesterase (CES) activities in the intestine and the liver, thus contributing to the lower transformation of Lv into LvA. In contrast, XZK inhibited the inflammation and upregulated CES in the intestine and the liver. Finally, we evaluated the effects of monacolins and phytosterols, the fractional extracts of isoflavones, on inflammatory LS174T or HepG2 cells, which showed that isoflavones inhibited inflammation, upregulated CES, and markedly enhanced the conversion of Lv into LvA. For the first time, we provide evidence that isoflavones and Lv in XZK act in concert to enhance the efficacy and reduce the side effects of Lv.

[Chinese expert consensus on the use of Xuezhikang (2017 revised edition)].

Xuezhikang, a Chinese traditional medicine, contains natural statin and is effective on dyslipidemia by inhibiting cholesterol synthesis. Xuezhikang therapy for 8 weeks in patients with hyperlipidemia reduced total cholesterol (TC) by 23%, low density lipoprotein cholesterol (LDL-C) by 28.5% and triglyceride(TG) by 36.5%, and increased high density lipoprotein cholesterol (HDL-C) by 19.6%, respectively. Data from China Coronary Secondary Prevention Study (CCSPS) showed that treatment with Xuezhikang lowered the risks of major coronary events, death from coronary heart disease, and all cause death in patients with myocardial infarction, indicating that Xuezhikang can be used in the primary and secondary prevention of cardiovascular disease.

Clinical Contrasting Observation on Therapeutic Effect of Xuezhikang Capsules and Lovastatins / 国际中医中药杂志

Objective To evaluate the curative effect of Xuezhikang Capsules. Methods 92 cases of primary hyperlipidemia were randomly separated into experiment group and control group, Members in the experiment group were treated by Xuezhikang Capsules with 2 granules for one time and twice daily, lasting for 8 weeks. Members in the control group were treated by lovastatins after supper with 20mg for one time and once daily, lasting for 8 weeks, too. At the end of therapeutic courses, clinical efficacy of blood fat controlling was evaluated. Results There was no significant difference (P＞0.05 )between the two groups in terms of blood fat improvement and total effective rate. Conclusion Xuezhikang Capsules was effective in controlling hyperlipidemia.