Limonene on Regulating Metabolism-related Fatty Liver Disease (MAFLD) and Analysis of TCM Constitution — DL-MAFLD-TCM  

Fatty Liver Clinical Trial

Official title: Clinical Trial of Limonene on Regulating Metabolism-related Fatty Liver Disease (MAFLD) and Analysis of TCM Constitution

Status Completed

Clinical Trial Summary

The prevention and treatment of metabolic-related fatty liver disease (MAFLD) involves many fields in preventive medicine and clinical medicine. So far, western medicine has not yet completed the elucidation of the mechanism of this type of disease, and there is a lack of effective therapeutic drugs.The purpose of this study was to evaluate the effectiveness and safety of limonene capsules (marketed product in China) in the treatment of metabolic-related fatty liver disease and related lipid-lowering mechanisms.

Clinical Trial Description

In April 2020, in the famous journal "Journal of Hepatology" in the field of liver disease, an internationally renowned liver disease expert group jointly proposed to replace non-alcoholic fatty liver disease (NAFLD) with metabolic associated fatty liver disease (MAFLD) . The concept of non-alcoholic fatty liver disease (NAFLD) was first proposed by Ludwig in 1980. It specifically refers to the excessive deposition of liver fat without excessive drinking. It is a type of liver that is closely related to insulin resistance and genetic susceptibility. Non-alcoholic fatty liver disease (NAFLD) is China country's largest chronic liver disease and the primary cause of abnormal liver enzymes in health examinations. It can lead to liver disability and death. It is also closely related to a variety of metabolic diseases and the high incidence of colorectal tumors. Western medicine has not yet fully elucidated its mechanism, and no drugs have been officially approved for the clinical treatment of NAFLD. The new MAFLD nomenclature highlights the central role of metabolic factors in causing liver fat deposition in this type of liver disease. Traditional Chinese medicine believes that the abnormal accumulation of fat in the liver of such fatty liver patients is a pathological product of the microscopic loss of water and valley essence. It belongs to phlegm stasis, which blocks the liver collaterals. It coincides with the core of the metabolic etiology of recent liver disease experts. Limonene is widely found in the essential oils of traditional Chinese medicine tangerine peel, green peel and other plants. Its taste is sour, sweet and pungent.It is returned to the liver and gallbladder meridian. It has an aromatic odor effect. A large number of animal and cell experiments in the early stage have shown that limonene can inhibit the differentiation of adipocytes (pre-adipocytes) and promote the apoptosis of mature adipocytes, which is related to the inhibition of fatty acid synthesis. Toxicity load experiments show that limonene has very low toxicity. The accumulation of lipids in the liver of mice has a regulatory effect with significantly reducing the content of liver cholesterol and triglycerides, and also has a certain effect on lipid metabolism disorders, hyperglycemia and other metabolic syndromes. It can alleviate the effects of high-fat diet and N- Efficacy of nitro-L-arginine methyl ester-induced resistance to non-alcoholic fatty liver in rats. The main indication of limonene capsules (marketed product in China) is liver and gallbladder diseases. Traditional Chinese medicine believes that liver and gallbladder are related to each other. This comprehensively shows that limonene capsules are promising to be developed as a pure Chinese medicine product for the safe and effective treatment of MAFLD. However, there has been no clinical evaluation of the clinical efficacy of limonene in the treatment of metabolic-related fatty liver disease. As a typical aromatic Chinese medicine, the mechanism of limonene in the treatment of fatty liver urgently needs to be revealed by modern medicine and molecular biology techniques. This study intends to use a randomized, double-blind, placebo-controlled method to evaluate the effect of limonene on improving the degree of fat infiltration in patients with metabolic-related fatty liver disease (MAFLD), and to evaluate its body mass index BMI, waist circumference, waist-to-hip ratio, subcutaneous fat thickness, fat percentage, changes in metabolic components, safety,etc. The study also intends to use metabonomics, genomics, and molecular biology techniques to study the clinical relationship between metabolites and physiological and pathological changes in patients with liver fat infiltration, and to detect changes in key proteins and lipid components after drug intervention, which is to reveal mechanism on treatment of metabolic-related fatty liver disease by limonene. It is aimed to study the difference in the efficacy of limonene for people with different constitutions of traditional Chinese medicine (TCM) combined with the analysis of the constitution of TCM, and to clarify the modern scientific attributes of TCM therapy. Finally the study will develop a safe and efficient drug treatment technology to control liver fat infiltration , and to promote the development of clinical disciplines in the treatment of metabolic-related fatty liver disease. ;

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases

• NCT number: NCT04853082
• Study type: Interventional
• Source: Shanghai Jiao Tong University School of Medicine
• Status: Completed
• Phase: Early Phase 1
• Start date: February 22, 2021
• Completion date: October 25, 2021