Deng Ruitang
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Cardiovasc Drug Rev. 2007 Winter;25(4):375-90. doi: 10.1111/j.1527-3466.2007.00023.x.
Oleogum resin (known as guggul) from the guggul tree, Commiphora mukul, found in India, Bangladesh, and Pakistan, has been used to treat various diseases including hyper-cholesterolemia, atherosclerosis, rheumatism, and obesity over several thousands of years. Guggulsterone isolated from guggul has been identified as the bioactive constituent responsible for guggul's therapeutic effects. Since the first study demonstrating the therapeutic effects of guggul in an animal model in 1966, numerous preclinical and clinical trails have been carried out. Although differences in study design, methodological quality, statistical analysis, sample size, and subject population result in certain inconsistencies in the response to therapy, the cumulative data from in vitro, preclinical, and clinical studies largely support the therapeutic claims for guggul described in the ancient Ayurvedic text. However, future clinical studies with much larger size and longer term are required to confirm these claims. The cardiovascular benefits of the therapy are derived from the multiple pharmacological activities associated with guggul or guggulsterone, notably its hypolipidemic, antioxidant, and antiinflammatory activities. It has been established that guggulsterone is an antagonist at farnesoid x receptor (FXR), a key transcriptional regulator for the maintenance of cholesterol and bile acid homeostasis. The FXR antagonism by guggulsterone has been proposed as a mechanism for its hypolipidemic effect. A recent study demonstrates that guggulsterone upregulates the bile salt export pump (BSEP), an efflux transporter responsible for removal of cholesterol metabolites, bile acids from the liver. Such upregulation of BSEP expression by guggulsterone favors cholesterol metabolism into bile acids, and thus represents another possible mechanism for its hypolipidemic activity. Guggulsterone has been found to potently inhibit the activation of nuclear factor-kappaB (NF-kappaB), a critical regulator of inflammatory responses. Such repression of NF-kappaB activation by guggulsterone has been proposed as a mechanism of the antiinflammatory effect of guggulsterone.
源自印度、孟加拉国和巴基斯坦的没药树（Commiphora mukul）的油树脂（称为古古勒），数千年来一直被用于治疗各种疾病，包括高胆固醇血症、动脉粥样硬化、风湿病和肥胖症。从古古勒中分离出的古古勒甾酮已被确定为具有古古勒治疗作用的生物活性成分。自1966年首次在动物模型中证明古古勒的治疗作用以来，已经进行了大量的临床前和临床试验。尽管研究设计、方法质量、统计分析、样本量和受试者群体的差异导致治疗反应存在一定的不一致性，但来自体外、临床前和临床研究的累积数据在很大程度上支持了古代阿育吠陀文献中描述的古古勒的治疗效果。然而，需要未来更大规模和更长期的临床研究来证实这些说法。该疗法的心血管益处源自与古古勒或古古勒甾酮相关的多种药理活性，特别是其降血脂、抗氧化和抗炎活性。已经确定古古勒甾酮是法尼醇X受体（FXR）的拮抗剂，FXR是维持胆固醇和胆汁酸稳态的关键转录调节因子。古古勒甾酮对FXR的拮抗作用被认为是其降血脂作用的一种机制。最近的一项研究表明，古古勒甾酮上调胆汁盐输出泵（BSEP），BSEP是一种负责从肝脏清除胆固醇代谢物、胆汁酸的外流转运蛋白。古古勒甾酮对BSEP表达的这种上调有利于胆固醇代谢为胆汁酸，因此代表了其降血脂活性的另一种可能机制。已发现古古勒甾酮能有效抑制核因子-κB（NF-κB）的激活，NF-κB是炎症反应的关键调节因子。古古勒甾酮对NF-κB激活的这种抑制作用被认为是古古勒甾酮抗炎作用的一种机制。
