Department of Internal Medicine, University of Genoa, Viale Benedetto XV n. 6, 16132, Genoa, Italy.
Lipids Health Dis. 2012 Sep 22;11:123. doi: 10.1186/1476-511X-11-123.
Although statins (STs) are drugs of first choice in hypercholesterolemic patients, especially in those at high cardiovascular risk, some of them are intolerant to STs or refuse treatment with these drugs. In view of this, we have evaluated the lipid-lowering effect of a nutraceutical pill containing berberine (BBR) and of ezetimibe, as alternative treatments, in monotherapy or in combination, in 228 subjects with primary hypercholesterolemia (HCH), with history of STs intolerance or refusing STs treatment. In addition, since PCSK9 was found up-regulated by STs dampening their effect through an LDL receptors (LDLRs) degradation, and BBR suppressed PCSK9 expression in cellular studies, we supplemented the stable lipid-lowering therapy of 30 genotype-confirmed Familial Hypercholesterolemia heterozygotes (HeFH) with BBR, searching for a further plasma cholesterol reduction. Plasma lipid pattern was evaluated at baseline and during treatments.
In HCH subjects the nutraceutical pill resulted more effective than EZE in lowering LDL cholesterol (-31.7% vs -25.4%, P < 0.001) and better tolerated. On treatment, LDL-C level below 3.36 mmol/L (≤130 mg/dl) was observed in 28.9% of subjects treated with the nutraceutical pill and 11.8% of those treated with EZE (P <0.007). In the group treated with EZE the subjects carrying the G allele of the g.1679 C > G silent polymorphism of NPC1L1 gene showed a higher response to EZE than homozygous for the common allele (GG + CG: LDL-C -29.4±5.0%, CC -23.6±6.5%, P <0.001). Combined treatment with these drugs was as effective as STs in moderate doses (LDL cholesterol -37%, triglycerides -23%). In HeFH patients the addition of BBR resulted in LDL cholesterol reductions inversely related to those induced by the stable therapy (r = -0.617, P <0.0001), with mean 10.5% further decrease.
The alternative treatments tested in our HCH subjects were rather effective and safe. The findings in HeFH patients suggest that BBR might act in vivo increasing expression and stability of LDLRs and/or suppressing PCSK9 expression.
尽管他汀类药物（STs）是高胆固醇血症患者的首选药物，尤其是心血管风险高的患者，但其中一些患者不能耐受 STs 或拒绝使用这些药物。鉴于此，我们评估了含有黄连素（BBR）和依折麦布的营养丸作为替代治疗的降脂效果，无论是单独使用还是联合使用，在 228 例原发性高胆固醇血症（HCH）患者中，这些患者有 STs 不耐受或拒绝 STs 治疗的病史。此外，由于 PCSK9 被发现通过 LDL 受体（LDLRs）降解被 STs 上调，并且 BBR 在细胞研究中抑制 PCSK9 的表达，我们在 30 名经基因确认的家族性高胆固醇血症杂合子（HeFH）患者中补充 BBR 进行稳定的降脂治疗，以寻找进一步降低血浆胆固醇。在基线和治疗期间评估了血浆脂质模式。
在 HCH 患者中，营养丸比依折麦布更有效地降低 LDL 胆固醇（-31.7%比-25.4%，P<0.001），且耐受性更好。在治疗中，用营养丸治疗的患者中有 28.9%，用依折麦布治疗的患者中有 11.8%（P<0.007）的 LDL-C 水平低于 3.36mmol/L（≤130mg/dl）。在依折麦布治疗组中，携带 NPC1L1 基因 g.1679C>G 沉默多态性的 G 等位基因的患者比纯合常见等位基因（GG+CG：LDL-C-29.4±5.0%，CC-23.6±6.5%，P<0.001）对依折麦布的反应更高。这些药物的联合治疗与中等剂量的 STs 一样有效（LDL 胆固醇-37%，甘油三酯-23%）。在 HeFH 患者中，BBR 的加入导致 LDL 胆固醇降低，与稳定治疗诱导的降低呈负相关（r=-0.617，P<0.0001），平均进一步降低 10.5%。
在我们的 HCH 患者中测试的替代治疗方法相当有效且安全。HeFH 患者的发现表明，BBR 可能在体内通过增加 LDLRs 的表达和稳定性以及/或抑制 PCSK9 的表达来发挥作用。
