Pathogenesis And Research Progress Of Traditional Chinese Medicine in Treating Hyperuricemia And Related Diseases
Jan 17, 2025
Abstract:
Hyperuricemia is a common metabolic disease with a wide range of causative factors. It is closely related to the occurrence of a series of diseases, including cardiovascular disease, gout, renal system diseases, and non-alcoholic fatty liver disease. The treatment of hyperuricemia in traditional Chinese medicine (TCM) is based on the etiology and mechanism of the disease. According to the theoretical basis of Chinese medicine, hyperuricemia is considered to be a symptom of deficiency, primarily caused by deficiencies in the spleen and kidney.
The treatment of hyperuricemia with Chinese medicine focuses on the disease's etiology and mechanism. Clinical treatment is based on the identification of symptoms to alleviate the patient's symptoms and reduce organ damage, reflecting the advantages of TCM treatment. This article reviews the research progress on the pathogenesis and treatment of hyperuricemia and related diseases.
Keywords:
Hyperuricemia
Cardiovascular Diseases
Renal System Diseases
Metabolic Syndrome
Etiology
Chinese Medicine Treatment
Uric acid (UA) is the end product of purine metabolism in the body. It is closely related to the liver and kidneys. Most of it is metabolized by the liver, stored in the body's uric acid pool, and then excreted. Renal excretion accounts for 70%, and the remaining 30% is excreted through the intestines. Purines come from food intake and the decomposition of purine nucleotides in the body. In the human body, purine intake and purine metabolism maintain a dynamic equilibrium relationship to ensure the normal functioning of the body. However, excessive dietary purine intake or reduced purine metabolism in the body can lead to hyperuricemia (HUA) [1]. The "Guidelines for the Diagnosis and Treatment of Hyperuricemia and Gout in China" indicate that in daily eating habits, if the fasting UA level in the blood is >420μmol/L on two different days, HUA can be diagnosed [2-3].
With the development of social economy and the improvement of quality of life, the abnormal purine metabolism caused by diet has increased the uric acid content in the blood, the prevalence of HUA has continued to rise, and the age of patients has tended to be younger. HUA patients often have no obvious symptoms in the early stage and are not easy to detect. HUA is often a cause of kidney-related diseases, metabolic diseases, and cardiovascular diseases. Therefore, early detection, early diagnosis, and early intervention are the key to treatment. Early treatment can not only improve the patient's prognosis, but also reduce the occurrence of corresponding diseases [4].
Cistanche For Kidney Diseases And High Uric acid
1 Pathogenesis of HUA
1.1 Modern medical mechanism of HUA
Uric acid is produced by xanthine oxidase in the liver acting on purine compounds in the body[5]. These purine compounds include endogenous synthesis and dietary purine compounds. Endogenous synthesis refers to the synthesis of the human body itself, while dietary purine compounds are also called exogenous, which are ingested from daily diet. Uric acid is divided into endogenous uric acid and exogenous uric acid. The ratio of endogenous uric acid to exogenous uric acid in the total uric acid in the body is about 8:2. Therefore, long-term intake of a high-purine diet will increase the risk of hyperuricemia[6]. The main cause of hyperuricemia is increased uric acid in the body or decreased uric acid excretion. Uric acid oxidase exists in the human body and can quickly reduce blood uric acid levels. When the human body produces too much uric acid, the uric acid oxidase gene expression is silenced, and the inactivated uric acid oxidase cannot be activated normally to reduce uric acid levels.
Gene silencing is due to mutations in the promoter region of this gene and the subsequent protein coding sequence. Uric acid levels cannot be reduced, thus causing hyperuricemia[7]. The occurrence of HUA will cause urate crystals to deposit in relevant parts of the body, and in severe cases, will form tophi, leading to the occurrence of gout [8]. Hyperuricemia is also one of the high-risk factors for coronary heart disease, which will lead to an increase in the incidence and mortality of coronary heart disease. Hyperuricemia is also a predisposing factor for atrial fibrillation, hypertension, non-alcoholic fatty liver disease and other diseases, increasing the risk of disease.
1.2 TCM Mechanism of HUA
Hyperuricemia (HUA) is recorded in many ancient books, but there is no clear name, and it is often called "lijie", "bi syndrome", "gout", etc. The Suwen Bi Lun states: "When the three Qis of wind, cold and dampness come together, they combine to form Bi. If the wind prevails, it is called wandering Bi; if the cold prevails, it is called painful Bi; if the dampness prevails, it is called fixed Bi." "If it does not combine with wind, cold and dampness, it will not form Bi." [9] The Jin Kui Yao Lue states: "In a healthy patient, the pulse is small and astringent, the breath is short, and there is spontaneous sweating. There is pain in the joints and the patient cannot bend or stretch. This is all caused by drinking alcohol and sweating in the face of wind." [10] Zhu Danxi's Ge Zhi Yu Lun states: "Gout is generally caused by the blood boiling due to heat, followed by wading through water or standing in wet places… The coldness attacks the hot blood, causing the sweat to stagnate, resulting in pain. The pain is worse at night, and it is caused by the Yang." Ancient books state that the cause of this disease is mostly due to long-term consumption of greasy food, accumulation of dampness and heat in the body, long-term stagnation of dampness and toxins, combined with external pathogens and blocked meridians. In summary, hyperuricemia is often caused by factors such as congenital deficiency, internal dampness and heat, phlegm stagnation, blood stasis, and meridian obstruction [11].
2 Cardiovascular disease
2.1 Modern medical research
SHEHABA et al. [12] studied the relationship between serum uric acid levels and cardiovascular problems and found that the risk of cardiovascular diseases in American adolescent females aged 12 to 18 years old may increase with the increase of serum uric acid levels. Increased uric acid levels can cause cardiovascular diseases including coronary atherosclerosis, congestive heart failure, hypertension and atrial fibrillation [13-14]. Both experimental and clinical studies have shown that increased serum uric acid levels can lead to the occurrence of cardiovascular diseases, produce oxidative stress, promote inflammation, reduce the availability of nitric oxide and endothelial dysfunction, constrict blood vessels and proliferate vascular smooth muscle cells, insulin resistance and metabolic imbalance [15].
In developed countries, arteriosclerotic cardiovascular disease (ASCVD) is a relatively common disease [12]. In recent years, a large number of studies have shown that hyperuricemia can cause coronary heart disease, among which coronary artery sclerosis is related to oxidative stress that causes cell dysfunction. In the process of uric acid production, xanthine oxidase participates in the production of reactive oxygen species (ROS) that significantly enhance vascular oxidative stress. This process may be involved in the formation of atherosclerosis and the inhibition of endothelial function [16].
YAMAMOTOY et al. [17] studied whether hyperuricemia can cause hypertension and showed that hyperuricemia is a risk factor for hypertension. HUA causes endothelial dysfunction, inhibits the synthesis and release of nitric oxide, reduces the level of nitric oxide, causes vasoconstriction and increased blood pressure, and causes hypertension. In addition, it activates the renin-angiotensin system, generates angiotensin, further constricts blood vessels, and induces vascular smooth muscle proliferation, leading to hypertension. Hypertension can cause vascular stenosis, lesions, and decreased blood volume, causing ischemia and hypoxia in the body, leading to increased lactate dehydrogenase, thereby increasing uric acid absorption and decreasing excretion, leading to HUA [18]. HUA is an independent risk factor for atrial fibrillation. In the study by LIS et al. [19], it was found that HUA can cause atrial fibrillation. The continuous increase in serum uric acid levels may lead to the occurrence of atrial fibrillation. The relationship between the two is that for every 10mmol/L increase in SUA, the risk of atrial fibrillation increases by 1.3 times. High expression of HUA is an important cause of atrial fibrillation, which can cause the atrium to not contract normally, thus causing atrial fibrillation to transition from paroxysmal to persistent, and ultimately lead to thrombosis [20].
2.2 Treatment with Traditional Chinese Medicine
Traditional Chinese medicine generally believes that Qi is the leader of blood and Qi drives blood circulation. If the Qi is deficient, it cannot drive blood circulation. Blood circulation is slow and blood stasis forms where it stops. Qi deficiency and weakness will cause blood stasis if it cannot drive blood circulation. Qi deficiency and blood stasis coexist, and Qi deficiency and blood stasis are the causes of cardiovascular diseases[21]. "Medical Error Correction: On Convulsions Are Not Wind" states: "When the Qi is deficient, it cannot reach the blood vessels. When the blood vessels are without Qi, they will stop and cause blood stasis." Chest pain and heart blockage are caused by deficiency of the root and excess of the symptoms. The root deficiency refers to deficiency of Qi in the heart, deficiency of Yang Qi, and deficiency of Yin and blood. The excess of the symptoms is cold stagnation leading to blood stasis, Qi stagnation, phlegm stasis, and turbidity[22]. For blocked meridians and Qi deficiency and blood stasis, Buyang Huanwu Decoction can be used with modifications. The treatment of this disease is mainly to replenish Qi and Qi, and the key is to assist in promoting blood circulation[23]. In addition, Compound Danshen Drop Pills, Qishen Yiqi Drop Pills, and Shexiang Baoxin Pills are commonly used for treatment.
According to traditional Chinese medicine, HUA and hypertension have the same etiology and pathogenesis, and they can be treated the same way. Liver and kidney deficiency, liver yang hyperactivity, spleen deficiency and qi weakness, blood stasis and phlegm obstruction, or even yin and yang deficiency are all caused by factors such as improper diet, emotional disorders, congenital deficiency, or old age, long-term illness and overwork. Due to deficiency or excess, phlegm and stasis obstruction causes the blood supply function of important organs in the body to be disordered, and it is necessary to increase blood pressure to compensate for the insufficient blood perfusion, thus suffering from hypertension[24]. According to the etiology and pathogenesis, the symptoms and root causes can be treated by tonifying the kidney and replenishing qi, promoting blood circulation and removing blood stasis. Huashi Jiangzhu Decoction is often used to promote serum uric acid excretion and reduce serum uric acid levels, and it also has a hypotensive effect. According to the analysis of the rules of traditional Chinese medicine, heat-clearing and dampness-removing drugs, qi-tonifying drugs, blood-activating and stasis-removing drugs, and wind-removing and analgesic drugs are the first choice. Commonly used medicinal materials include Smilax glabra, Radix Dioscoreae, Atractylodes macrocephala, Plantago seed, and Rhizoma Alismatis[25]. The Compendium of Materia Medica states: "Smilax glabra can strengthen the spleen and stomach and remove rheumatism. When the spleen and stomach are healthy, the body's defense system will be in good condition. When rheumatism is removed, the tendons and bones will be healthy." Smilax glabra has the functions of clearing away heat and detoxifying, unblocking joints, promoting uric acid excretion, and lowering blood pressure [26]. Radix Dioscoreae has a bitter taste and is neutral in nature. It belongs to the kidney and stomach meridians. It has the functions of removing dampness and numbness, removing wind and removing turbidity. It can promote uric acid excretion, reduce kidney damage, and lower blood pressure. Plantago seed can promote diuresis and eliminate dampness, clear heat and resolve phlegm. It can promote uric acid excretion by reducing uric acid synthesis, lower uric acid levels, and lower blood pressure by inhibiting angiotensin-converting enzyme.
2.3 Gout
2.3.1 Modern medical research
Gout is a disease caused by excessive deposition of uric acid. It is an inflammatory reaction induced by the deposition of monosodium urate (MSU) crystals. Gout patients will show symptoms of hyperuricemia within a certain period of time. Hyperuricemia is a high-risk factor for gout attacks. Hyperuricemia and gout are the same disease but different states. About 90% of gout patients are caused by uric acid excretion disorders, and about 36% of HUA will further develop into gout [27]. During the hyperuricemia period, urate in the human body is in a saturated state for a long time, resulting in the continuous aggravation of inflammatory reactions and oxidative stress. A large amount of urate is deposited in the internal organs and joints, resulting in joint pain and swelling, causing gout. As the blood uric acid level in the body continues to rise, the pain and swelling symptoms caused by inflammation and oxidative stress continue to intensify, and the probability of gout also continues to increase [28-29].
2.3.2 Treatment with Traditional Chinese Medicine
TCM diagnosis of gout is divided into acute and chronic stages. The acute stage is mostly heat arthralgia, including rheumatic heat arthralgia and damp-heat arthralgia. Traditional Chinese medicines that dispel wind and dredge collaterals, clear heat and remove dampness are often used. In the chronic stage, uric acid levels vary. Different drugs are used according to uric acid levels to control uric acid and enhance excretion. At the same time, they are also used to resolve phlegm and remove turbidity, and remove blood stasis and dredge collaterals. Qiu Xiaolian et al. [30] statistically analyzed gout symptoms and divided gout into six syndromes: damp-heat accumulation syndrome, damp-heat stasis syndrome, liver-kidney yin deficiency syndrome, rheumatic heat arthralgia syndrome, cold-damp arthralgia syndrome, and phlegm and turbidity stagnation syndrome.
Corresponding diagnosis and treatment methods are used for different syndromes. Gout patients with damp-heat accumulation syndrome have internal dampness and heat due to eating too much fatty and greasy food. In addition, external turbidity invades the body, resulting in internal dampness and turbidity. They are often treated with heat-clearing, dampness-promoting and turbidity-removing methods [31]. Li Shugang et al. [32-33] found that the Qingre Lishi Decoction is effective in treating patients with acute gouty arthritis (damp-heat stasis syndrome), and the medication is safe and reliable. At the same time, Gu Huimin et al. [34] used Canshi Decoction with modifications to treat damp-heat stagnation type gout with significant results. This prescription has a synergistic effect with colchicine.
The blood circulation and blood stasis removal method is used to treat blood stasis type gout, and Danxi Gout Recipe and Blood Circulation Pain Relief Paste are often used. Wang Xiaoyue et al. found that the combination of the two prescriptions can significantly improve blood stasis and heat stagnation type gout, achieving the effects of blood circulation, blood stasis, detoxification and dispersing stagnation [35]. In addition, Ermiao Powder and Shentong Zhuyu Decoction also have the effects of blood circulation, arthralgia removal, wind and pain relief for blood stasis type gout.
Phlegm-blocking gout mainly uses the method of resolving phlegm and lowering turbidity. Compound prescriptions such as Wuling Powder, Shenling Baizhu Powder, Jinkui Shenqi Pills, Qufeng Huoluo Xiezhu Decoction, Yiyiren Decoction, and self-made Fengfeng Recipe are often used to resolve phlegm and lower turbidity to treat phlegm-blocking gout. Among them, Xiang Xuyang et al. [36] found that Qufeng Huoluo Xiezhu Decoction can effectively reduce the patient's blood uric acid level in the treatment of phlegm-blocking gout. Li Taicheng [37] believes that Wuling Powder can relieve pain, improve uric acid and erythrocyte sedimentation rate levels, and is effective in treating patients with phlegm-blocking gouty arthritis.
The liver-kidney yin deficiency type gout is treated by the method of tonifying the liver and kidney. Cen Jie et al. [38] treated gout by tonifying the liver and kidney. The compound prescriptions include Sanwu Duhuo Jisheng Decoction and Guishao Dihuang Decoction. Both of them have the effects of nourishing the liver and kidney, dispelling wind and relieving pain, and unblocking the meridians. Among them, Guishao Dihuang Decoction can reduce uric acid levels and inhibit inflammatory reactions. It has a significant effect in treating this type of gout.
Gout is often treated with Chinese medicines that dispel wind and dampness, clear heat and dredge the meridians, including honeysuckle, trillium, plantain, white peony, radix dactylospermi, qinpi, chuanxiong, polygonum cuspidatum, and kudzu root. Trillium has the effects of clearing heat and detoxifying, removing blood stasis and relieving pain, and reducing swelling. Trillium and chuanxiong clear heat and dampness, and unblock joints. Polygonum cuspidatum has the effects of dispersing blood stasis and relieving pain. It also has the effects of anti-inflammatory and analgesic, lowering uric acid levels, protecting renal tubular epithelial cells and reducing cell damage [39]. Studies have shown that white peony root may relieve inflammation by reducing serum inflammatory factors, including IL-6 and IL-1β[40].
