Study on the therapeutic effect of Yunnan distracted wood extract on mouse hyperuricemia model
Hyperuricemia (HUA) is a metabolic disorder caused by an increase in uric acid (UA) synthesis and/or a decrease in uric acid excretion. Hyperuricemia is a risk factor for diseases such as gouty arthritis and gouty nephropathy. In recent years, the global incidence rate of gout continues to rise. At present, the western medicines used to treat HUA include allopurinol, benzbromarone, and febuxostat. Although the efficacy is still acceptable, they are all accompanied by side effects such as hepatotoxicity, drug rash, and drug resistance. Therefore, exploring effective drugs with minimal toxic side effects is of great significance.
Juglans regia L., also known as walnut, is a plant belonging to the Juglandaceae family and the Juglans L. genus. Diaphragma Juglandis Fructus (DJF), also known as Xeloseptum Juglandis in Latin, is a woody septum in the fruit compartment of walnuts. It is neutral, non-toxic, and has the effect of strengthening the spleen and kidneys. Yunnan is the birthplace of walnuts in China, with the unique Yangbi Bubble Walnut (Juglans sigillata Dode). As a result, Yangbi Yi Autonomous County is also known as the “Hometown of Chinese Walnuts”, with a production of 57000 tons in 2020 and a comprehensive output value of over 1 billion yuan, becoming a pillar industry of the local economy. As one of the earliest research teams in China engaged in related studies, our research group conducted preliminary research on Yunnan Yangbi walnut distraction wood from 2009 to 2012, and isolated and identified nearly 20 components including gallic acid, emodin, dihydroquercetin, etc., which provided us with a preliminary understanding of the chemical components contained in walnut distraction wood for the first time. Modern pharmacological research has shown that walnut distraction wood has the effects of tonifying the kidney, antioxidation, antibacterial, anti-inflammatory, regulating immunity, and inhibiting xanthine oxidase (XOD). However, the effect of walnut distraction wood on hyperuricemia has not been reported so far. This article explores the therapeutic effect of distracted wood extract on HUA in a mouse model by intervening with walnut distracted wood produced in Yunnan.

Uric acid (UA) is the end product of purine compound metabolism, and xanthine oxidase is a key enzyme in its metabolic process. Therefore, its activity can be used as a key indicator to evaluate the body’s ability to produce uric acid. The kidney is the main organ for human metabolism of uric acid (UA). UA is prone to form uric acid crystals and deposit in the kidney, which can cause uric acid nephropathy (UAN). It can also stimulate strong inflammatory reactions, leading to abnormal kidney structure and function.
During the continuous evolution of humans, mutations in the uricase gene lead to the inactivation of uricase, making uric acid the final product of purine metabolism. Unlike humans, rodents can further break down uric acid through uricase, making it easier to excrete from the body. This study administered potassium oxonate and adenine to Kunming mice, and intervened in blood uric acid levels by increasing the source and inhibiting the pathway. The blood collection time after administering the inducer was strictly controlled, and an animal model with significantly elevated blood uric acid levels and kidney damage was replicated, approaching the state of human hyperuricemia.
According to traditional ethnic and folk medicine records, distracted wood has the effects of astringency and astringency, as well as strengthening the spleen and kidneys. In recent years, the use of distraction wood has become increasingly widespread and research has been increasing. Jing Yuanchao and others investigated the in vitro inhibition of XOD activity by components in distracted wood, and the results showed that some of its components had good inhibitory activity. The combination of inhibiting XOD activity and inflammatory response is an effective target for treating HUA induced kidney injury, as well as the pharmacological records and modern research of distraction wood. Our research group investigated the therapeutic effect of distraction wood on hyperuricemia mice. The results showed that compared with the model group, the activity level of XOD in the liver of mice in the 2g/kg distracted wood alcohol extract group was significantly downregulated; The UA content in the serum also significantly decreased. XOD is a key rate controlling enzyme for the generation of UA, which directly determines the amount of UA produced. This indicates that the alcohol extract of Yunnan distracted wood can reduce blood UA levels by inhibiting the activity of XOD. The crystallization and free state of uric acid can synergistically affect the expression of inflammatory factors, directly affecting the production of pro-inflammatory cytokines such as interleukin-1 β (IL-1 β) and tumor necrosis factor alpha (TNF – α). Excessive production of IL-1 β can induce glomerulosclerosis and proliferation of mesangial cells, and a large amount of TNF – α can also exacerbate the inflammatory response. The levels of inflammatory factors TNF – α, IL-1 β, and serum Cr and BUN in the kidney tissue of mice in the Yunnan distracted wood alcohol extract group were significantly lower than those in the model group, indicating that distracted wood alcohol extract has the effect of clearing inflammatory factors and is superior to allopurinol. It can also downregulate the indirect indicators of renal function, Cr and BUN, and improve renal function.
Trace elements have a wide range of physiological and biochemical functions and are the basis for normal bodily activities. For example, zinc is an essential nutrient and reducing agent for the body, and can also play important roles in the reproductive and urinary systems. The preliminary research results of the research group show that Yunnan distraction wood contains Cu In order to verify the effect of trace elements such as Zn, Fe, Mn, Mg in Yunnan distraction wood on the treatment of HUA, this study compared the pharmacological effects of the water extract of distraction wood after removing inorganic elements with the water extract. The results showed that the removal effect of zinc element in the deionized extract DJF-S1 treated with strong acid cation exchange resin (FPC14Na) was significantly higher than that in the deionized extract DJF-S2 treated with strong acid styrene cation exchange resin (732 type). At the same dose, the therapeutic effect of DJF-S1 sample on HUA mice was weaker than that of DJF-S2 sample, and the therapeutic effect of both deionized samples on HUA mice was weaker than that of DJF-W sample, indicating that the zinc element rich in distraction wood It may be an important component in the treatment of hyperuricemia, and this study provides direction for further research on the mechanism of trace elements acting on hyperuricemia.
In summary, the ethanol extract of distracted wood has the effects of improving kidney function, inhibiting XOD activity, and anti-inflammatory effects, which can to some extent reduce uric acid levels in hyperuricemia mice. At present, Western medicine has certain advantages in treating HUA, but its adverse reactions cannot be ignored. Plant medicine has obvious advantages in high safety and multi-target synergistic therapy. The research results of this article provide important clues for subsequent mechanism research, clarify research directions, and provide a basis for finding efficient and low toxicity active ingredients in the later stage. At the same time, it also provides new ideas for the development and utilization of distracted wood.