Oral Drug With Hyodeoxycholic Acid That Helps Treat Diabetes and Fatty Liver Is Expected to Be Developed Within 5 Years: HKBU Research

Non-alcoholic fatty liver disease (NAFLD) is one of the urban syndromes. About 28 to 30 percent of adults in Hong Kong suffer from this disease, and the proportion is continuously on the rise. Some patients will even develop non-alcoholic steatohepatitis, which can lead to cirrhosis and liver failure in severe cases, and there are still no drugs to treat it. Hong Kong Baptist University’s (HKBU) latest research has found that a bile acid component, “hyodeoxycholic acid” (HDCA), produced in the human intestine, can reduce fat accumulation and inflammation in the liver and has great therapeutic potential.NAFLD is one of the major causes of chronic liver disease and is characterized by the accumulation of excessive fat in liver cells and is not caused by alcohol consumption. A 2022 meta-analysis estimated that NAFLD affects 32 percent of adults. Some patients can develop non-alcoholic steatohepatitis, which is characterized by inflammation of the liver, or may progress to cirrhosis and liver failure. There are currently no approved drugs on the market for the treatment of non-alcoholic steatohepatitis.Since NAFLD is often accompanied by other metabolic diseases, including type 2 diabetes, the team set out to study whether HDCA can help regulate fatty liver. After analyzing samples from a cohort of 178 patients with NAFLD and 73 healthy individuals, the team found that the HDCA level in the patients’ samples accounted for only 0.5 percent of the overall bile acid, a level significantly lower than the 2 percent in the healthy individuals, indicating a negative correlation between NAFLD and HDCA level. Through mouse model experiments, the team also found that HDCA can significantly improve symptoms of NAFLD in mice, as well as risk factors such as type 2 diabetes and insulin resistance. The research results have been published in the renowned scientific journal “Cell Metabolism.”Professor Jia Wei, Acting Dean and Chair Professor in Chinese Medicine and Systems Biology of the School of Chinese Medicine at HKBU, said that the Compendium of Materia Medica mentions that pig gallbladder can “quench thirst” (that means it treats type 2 diabetes). Studies have shown that the more bile acid, the lower the blood sugar and insulin levels, the better it is for the treatment of diabetes. Mr. Jia explained that HDCA reduces liver lipid accumulation through two pathways. First, it inhibits intestinal FXR receptors, activates the production of hepatic bile acid replacement synthase, and accelerates cholesterol metabolism. He described HDCA as having advantages as a drug because of its hypolipidemic, hypoglycemic, and anti-inflammatory properties, as well as its low toxicity. The team also found that HDCA can improve the structure of intestinal flora and produce a large amount of Parabacteroides distasonis, allowing it to produce the metabolite γ-linolenic acid to stimulate liver PPARα, increase liver bile acid replacement synthase, and promote liver cholesterol and metabolism of triglycerides.Mr. Jia mentioned that the team has conducted clinical trials at the First Affiliated Hospital of Xi’an Jiaotong University and plans to conduct similar trials at the Sixth People’s Hospital of Shanghai Jiaotong University to evaluate the safety and efficacy of HDCA drugs. He predicts that it will take at least five years for HDCA drugs to be launched on the market. At that time, it is expected to be launched in the form of pills or capsules, and patients will need to take it orally for three to six months. However, the drug should not be overly costly because HDCA can be extracted from pig gallbladder in massive quantities and is also not difficult to synthesize.Related Stories

Oral Drug With Hyodeoxycholic Acid That Helps Treat Diabetes and Fatty Liver Is Expected to Be Developed Within 5 Years: HKBU Research

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Non-alcoholic fatty liver disease (NAFLD) is one of the urban syndromes. About 28 to 30 percent of adults in Hong Kong suffer from this disease, and the proportion is continuously on the rise. Some patients will even develop non-alcoholic steatohepatitis, which can lead to cirrhosis and liver failure in severe cases, and there are still no drugs to treat it. Hong Kong Baptist University’s (HKBU) latest research has found that a bile acid component, “hyodeoxycholic acid” (HDCA), produced in the human intestine, can reduce fat accumulation and inflammation in the liver and has great therapeutic potential.

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NAFLD is one of the major causes of chronic liver disease and is characterized by the accumulation of excessive fat in liver cells and is not caused by alcohol consumption. A 2022 meta-analysis estimated that NAFLD affects 32 percent of adults. Some patients can develop non-alcoholic steatohepatitis, which is characterized by inflammation of the liver, or may progress to cirrhosis and liver failure. There are currently no approved drugs on the market for the treatment of non-alcoholic steatohepatitis.

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Since NAFLD is often accompanied by other metabolic diseases, including type 2 diabetes, the team set out to study whether HDCA can help regulate fatty liver. After analyzing samples from a cohort of 178 patients with NAFLD and 73 healthy individuals, the team found that the HDCA level in the patients’ samples accounted for only 0.5 percent of the overall bile acid, a level significantly lower than the 2 percent in the healthy individuals, indicating a negative correlation between NAFLD and HDCA level. Through mouse model experiments, the team also found that HDCA can significantly improve symptoms of NAFLD in mice, as well as risk factors such as type 2 diabetes and insulin resistance. The research results have been published in the renowned scientific journal “Cell Metabolism.”

.

Professor Jia Wei, Acting Dean and Chair Professor in Chinese Medicine and Systems Biology of the School of Chinese Medicine at HKBU, said that the Compendium of Materia Medica mentions that pig gallbladder can “quench thirst” (that means it treats type 2 diabetes). Studies have shown that the more bile acid, the lower the blood sugar and insulin levels, the better it is for the treatment of diabetes. Mr. Jia explained that HDCA reduces liver lipid accumulation through two pathways. First, it inhibits intestinal FXR receptors, activates the production of hepatic bile acid replacement synthase, and accelerates cholesterol metabolism. He described HDCA as having advantages as a drug because of its hypolipidemic, hypoglycemic, and anti-inflammatory properties, as well as its low toxicity. 

.

The team also found that HDCA can improve the structure of intestinal flora and produce a large amount of Parabacteroides distasonis, allowing it to produce the metabolite γ-linolenic acid to stimulate liver PPARα, increase liver bile acid replacement synthase, and promote liver cholesterol and metabolism of triglycerides.

.

Mr. Jia mentioned that the team has conducted clinical trials at the First Affiliated Hospital of Xi’an Jiaotong University and plans to conduct similar trials at the Sixth People’s Hospital of Shanghai Jiaotong University to evaluate the safety and efficacy of HDCA drugs. He predicts that it will take at least five years for HDCA drugs to be launched on the market. At that time, it is expected to be launched in the form of pills or capsules, and patients will need to take it orally for three to six months. However, the drug should not be overly costly because HDCA can be extracted from pig gallbladder in massive quantities and is also not difficult to synthesize.

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