New Research on Berberine! Boosts Succinate Production—This Herbal Medicine Also Fights Gout!

New Research on Berberine! Boosts Succinate Production—This Herbal Medicine Also Fights Gout!

Hyperuricemia is a pathological condition characterized by elevated uric acid levels in the blood, resulting from excessive production and insufficient excretion of uric acid in the body. It is a metabolic disorder caused by purine metabolism dysfunction, also known as gout. 

According to data from the <Lancet Rheumatology>, in 2020, the global prevalence of gout was 55.8 million (95% uncertainty interval: 44.4 million to 69.8 million), with an age-standardized prevalence rate of 659.3 per 100,000 (525.4 to 822.3). By 2050, the number of gout cases is projected to reach 95.8 million (81.1 million to 116 million), representing an increase of over 70% compared to 2020, primarily driven by population growth and aging. The age-standardized prevalence rate is expected to be 667 per 100,000 (531 to 830) by 2050.

On August 19, 2025, a team led by Wang Yan and Jiang Jiandong from the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, published an article titled "Bacteroides fragilis-derived succinic acid promotes uric acid degradation by inhibiting hepatic AMPD2: insights into how plant-based berberine ameliorates hyperuricemia" in the Journal of the American Chemical Society. The study revealed that berberine (BBR) is a promising natural drug for treating hyperuricemia, with its mechanism potentially involving the regulation of gut microbiota and its metabolite succinic acid.

Source: sciencedirect

1. How does berberine improve hyperuricemia?

Uric acid is mainly synthesized in the liver and is the end product of nucleoside metabolism in food. It is also a precursor to nucleotide synthesis and endogenous purine metabolism. In recent years, studies have shown that gut microbiota plays an important role in hyperuricemia and gout. 

In animal experiments, researchers established chronic/acute hyperuricemia ICR mouse models, intervened with BBR, and collected blood samples to measure plasma uric acid levels at the end of the experiment. The results showed that in the chronic/acute hyperuricemia mouse model, berberine reduced blood uric acid levels in a time - and dose-dependent manner (the high-dose group reduced uric acid levels by 54% within 2 weeks).

Plasma uric acid levels in mice with chronic hyperuricemia after 1 week (left) and 2 weeks (right) of treatment

Due to the difficulty in absorption after oral administration of BBR, it inevitably interacts with intestinal bacteria upon entering the intestine. Therefore, researchers studied the regulatory effect of berberine on the composition of intestinal microbiota in a mouse model of chronic hyperuricemia. The results showed that berberine significantly altered the gut microbiota structure under hyperuricemia conditions. BBR reduced Chao1 and Shannon indices, leading to a shift in the microbiota towards a more orderly and healthy state. In addition, BBR administration significantly increased the abundance of Verrucomicrobia and decreased the proportion of Actinobacteria, increased the production of succinic acid by Anaerotruncus (a bacterial genus in the family Ruminococcus), and significantly increased the abundance of Bacteroides (268% higher than the model group), restoring the composition and function of the gut microbiota.

BBR alters gut microbiota composition in animal models of chronic hyperuricemia

In this study, researchers discovered a unique mechanism by which BBR reduces uric acid levels through the gut liver axis: BBR can regulate gut microbiota, increase the abundance of succinic acid producing bacteria such as Bacteroidetes, thereby increasing succinic acid production and reducing uric acid production in the liver. In addition, BBR can also inhibit the activity and expression of AMPD2 protein through its metabolite succinic acid, thereby reducing uric acid levels.

2. What is berberine?

Berberine is the main active ingredient of traditional Chinese medicine Huanglian, also known as berberine. It was first discovered by Buchner and Herberger in 1830. This is a benzyltetraisoquinoline alkaloid, whose chemical structure belongs to quaternary ammonium salts, with the chemical formula C20H18NO4+. 

Berberine is yellow in color, has a bitter taste, and is widely present in various plants. In addition to the Berberidaceae family (Berberidaceae), berberine is also found in plants of the Ranunculaceae family (Coptis chinensis), Rutaceae family (Berberidaceae), Annonaceae family, Papaveraceae family, and Menispermaceae family. It mainly exists in the roots, stems, or bark of these plants.

Berberine is used as a traditional folk medicine in countries such as China and India, and plants containing berberine have a long history of use in Ayurveda and traditional Chinese medicine. Traditionally, doctors and herbalists use berberine rich herbs to improve inflammation, gastrointestinal diseases, and diabetes. In the early 1960s, Indian researchers demonstrated the efficacy of berberine in improving cholera, severe diarrhea, and amoebiasis. As a natural medicine with a long history of use, its safety and effectiveness have been proven through years of use.

In the United States, berberine can be legally sold as a dietary supplement ingredient, but it cannot be labeled for therapeutic purposes; 

In Europe, most member states can sell it as a food supplement, but it must comply with EFSA dosage and safety guidelines (adult ≤ 500 mg/day); 

3. Other benefits of berberine

Modern research has found that berberine has various pharmacological effects such as antibacterial, anti-inflammatory, and hypoglycemic effects, and is widely used in clinical and healthcare fields.

1) Improve gut microbiota

Due to absorption difficulties, berberine will remain in the intestine and inevitably interact with intestinal bacteria. Studies have shown that berberine can combat gout by regulating gut microbiota, and there are also studies suggesting that berberine can enhance insulin resistance by regulating gut microbiota. These studies on berberine provide favorable evidence for its regulation of gut microbiota. A study by Zhang et al. showed that berberine can regulate the production of short chain fatty acids, thereby enriching bacterial diversity and benefiting their hosts, confirming that berberine can promote changes in gut microbiota structure.

2) Anti diabetes

The main cause of diabetes and its complications is the low or missing function of pancreatic islets, including insulin resistance. Berberine shows good potential in the treatment of diabetes. Research has found that it can have a positive impact on blood sugar, insulin and triglycerides. In addition, it has been found to enhance the body's sensitivity to insulin, which means it can help cells in the body better respond to insulin. By improving insulin sensitivity, berberine can help control blood glucose levels and reduce the risk of weight gain associated with insulin resistance and type 2 diabetes.

3) Improving polycystic ovary syndrome 

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of childbearing age, characterized by a multifactorial unhealthy condition associated with hormonal imbalances, metabolic abnormalities, and inflammation. Women with polycystic ovary syndrome (PCOS) often experience insulin resistance, and worsening insulin resistance can lead to a vicious cycle of PCOS hormone levels. Berberine may help alleviate insulin resistance in these situations. 

A study investigated women with polycystic ovary syndrome who were of normal weight and overweight. Participants took 550 milligrams of berberine twice a day for 60 days. At the end of the study, participants showed a decrease in C-reactive protein, triglycerides, testosterone, body mass index, and visceral fat. Their levels of sex hormone binding globulin (SHBG) also increased. This study suggests that berberine may have a positive effect in reducing insulin resistance, androgens and inflammation, as well as regulating lipid metabolism, making it a novel clinical complementary strategy for polycystic ovary syndrome (PCOS).