Protective Effects of Yinchenhao Decoction on Cholesterol Gallstone in Mice Fed a Lithogenic Diet by Regulating LXR, CYP7A1, CYP7B1, and HMGCR Pathways.

Yong Meng,Donghua Li,Xin Zhao,Qiaoying Gao,Yunfeng Cui,Ke Meng,Shangwei Wu

doi:10.1155/2018/8134918

Abstract

The study attempted to elucidate whether lipid genes are closely associated with lipid metabolic abnormalities during the lithogenic time and how Yinchenhao Decoction (YCHD) works on the transcriptions of lipid genes against cholesterol gallstone model. C57BL/6J mice fed on lithogenic diet (LD) were used for model establishment and randomized into 5 groups. All groups received LD for different weeks with isometrically intragastric administration of YCHD or NS. Biochemical tests were measured and liver tissues were harvested for histological and genetic detection. It was found that all groups with increasing LD showed a following tendency of gallstone incidence, bile cholesterol, phospholipids, total bile acid, and cholesterol saturation index (CSI). Conversely, YCHD could significantly normalize the levels of gallstone incidence, bile lipids, and CSI (CSI<1). As lithogenic time progressed, ABCG5, ABCG8, PPAR-α, and ABCB4 were upregulated, and SREBP2, CYP7A1, and CYP7B1 were downregulated, while CYP7A1, CYP7B1, LXR, and HMGCR mRNA were increased 3-fold under the administration of YCHD. It was concluded that abnormal expressions of the mentioned genes may eventually progress to cholesterol gallstone. CYP7A1, CYP7B1, LXR, and HMGCR mRNA may be efficient targets of YCHD, which may be a preventive drug to reverse liver injury, normalize bile lipids, facilitate gallstone dissolution, and attenuate gallstone formation.

Highlights

Gallstone disease is one of the most common gastrointestinal disorders encountered in clinical practice [1]
With prolonged lithogenic diet (LD) feeding, a series of abnormal symptoms like hypokinesia, inactivated state, weight loss, slow growth, and even jaundice on legs began to appear gradually, which were similar to the reported results
We found that liver X receptor (LXR), hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), CYP7A1, and CYP7B1 mRNA in Yinchenhao Decoction (YCHD) group possessed approximately 3-fold increasing levels in contrast to NS group

Summary

Introduction

Gallstone disease is one of the most common gastrointestinal disorders encountered in clinical practice [1]. The incidence of gallstone disease is racially diverse. From the perspective of pathogenesis, the stones are primarily ascribed to excessive cholesterol accumulation in bile, gallbladder hypomotility, and gastrointestinal dysfunction [6, 7]. Most patients with cholecystolithiasis have no obvious clinical symptoms. 40% of patients have clinical symptoms and severe complications after 40 years of age and need to be operated on [8]. The incidence of biliary injury during LC is 0.39%, which can be long lasting morbidity and fatal to the patients. They may increase the cost involved in treatment and result in medical litigation.

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Discussion

Conclusion