Why does Polygonum multiflorum Thunb, a Chinese herbal medicine, still become a valuable medicinal material in Chinese medicine even though it is obviously toxic?

Polygonum multiflorum Thunb is a commonly used Chinese medicine, which is widely used in clinical treatment, prevention and health care. However, in recent years, it has been frequently reported that Polygonum multiflorum Thunb and some related preparations lead to liver injury, and some patients may have serious adverse outcomes, which has aroused widespread concern at home and abroad. In recent years, important progress has been made in the research on liver injury of Polygonum multiflorum Thunb.

First, the efficacy of Polygonum multiflorum Thunb

Raw Polygonum multiflorum Thunb has the effects of detoxifying, eliminating carbuncle, stopping malaria, moistening intestines and relaxing bowels; Can be used for treating sores, lymphoid tuberculosis, rubella pruritus, chronic malaria, intestinal dryness and constipation.

Radix Polygoni Multiflori Preparata has the effects of nourishing liver and kidney, nourishing essence and blood, blackening hair and beard, and strengthening bones and muscles. Can be used for treating blood deficiency and sallow, dizziness and tinnitus, premature graying of hair, soreness of waist and knees, numbness of limbs, metrorrhagia and leukorrhagia.

Caulis Polygoni Multiflori has the effects of nourishing heart, calming nerves, expelling wind and dredging collaterals; Used for insomnia, dreaminess, blood deficiency, body pain, skin numbness, rheumatism, rubella and itching.

Second, the chemical constituents and pharmacological effects of Polygonum multiflorum Thunb

The chemical constituents of Polygonum multiflorum Thunb mainly contain stilbenes, anthraquinones, flavonoids and phospholipids. The chemical constituents of Polygonum multiflorum Thunb are similar to those of Polygonum multiflorum Thunb, but the contents of stilbenes and anthraquinones are lower than those of Polygonum multiflorum Thunb.

Polygonum multiflorum Thunb. Has the activities of reducing blood fat, resisting atherosclerosis, resisting aging, enhancing immunity, regulating nerves, protecting liver, resisting inflammation and promoting hematopoietic cell production. Caulis Polygoni Multiflori has sedative, hypnotic, hypolipidemic and anti-atherosclerotic activities.

Three. Liver damage caused by Polygonum multiflorum Thunb.

(1) The adverse reactions of Polygonum multiflorum Thunb and its related preparations are mainly manifested in the hepatobiliary system and gastrointestinal system, with symptoms such as fatigue, nausea, vomiting, loss of appetite, liver discomfort, dry mouth, bitter taste, itchy skin, yellow urine, yellow eyes, yellow skin, abdominal pain, diarrhea, abdominal distension, and occasional rash, fever and eye pigmentation. Laboratory examination may lead to abnormal laboratory indexes such as transaminase and/or bilirubin increase.

(2) The dosage and incubation period of patients with liver injury caused by Polygonum multiflorum Thunb and related preparations are wide. Among them, the dosage is at least 1~3g/d and at most100g/d; The shortest incubation period is 1 ~ 3 days, the longest is more than half a year, and the median time is about 20 days. The dose and time of Polygonum multiflorum Thunb have no dependence on the occurrence of liver injury, suggesting that Polygonum multiflorum Thunb has a unique type of liver injury and there may be a susceptible population.

(3) The proportion of women is slightly higher than that of men, and the ratio of men to women is about 1: 1. 16. The onset age of liver injury caused by Polygonum multiflorum Thunb and its preparations is quite old, ranging from 8 to 87 years old. Men are mostly 20~49 years old, mostly for the treatment of diseases such as alopecia and eczema; Women are mostly 40 ~ 59 years old, mostly treating diseases such as white hair and palpitation.

(4) Liver injury cases caused by Polygonum multiflorum Thunb and its related preparations are common in seborrheic alopecia, gray hair, eczema, psoriasis, vitiligo, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus and other diseases, and most of them are accompanied by immune disorder or autoimmune diseases, suggesting that immune disorder may be one of the important risk factors for liver injury caused by Polygonum multiflorum Thunb and its related preparations. In addition, the liver injury caused by Polygonum multiflorum Thunb and related preparations has a worse prognosis in people with chronic liver disease (especially alcoholic liver disease), and it is easier to progress to chronic drug-induced liver disease and even death.

(5) Polygonum multiflorum Thunb. It is one of the varieties with the most reported cases of liver injury caused by single Chinese medicine. Most patients use it by themselves, mostly by dispersing, replacing tea, soaking in wine, cooking porridge and so on. Most Polygonum multiflorum Thunb. The product is unprocessed or the degree of processing is unknown. In the cases of liver injury caused by Polygonum multiflorum Thunb and its related preparations, about 20% people took more than the dose specified in the instructions or pharmacopoeia, suggesting that taking large doses may increase the risk of liver injury of Polygonum multiflorum Thunb.

Fourthly, the mechanism of liver injury caused by Polygonum multiflorum Thunb.

In modern toxicology research, no obvious hepatotoxic reaction has been found in the range of the maximum tolerated dose of experimental animals, whether it is raw Polygonum multiflorum Thunb, processed Polygonum multiflorum Thunb or its different extracted parts, suggesting that it is safe for human to use Polygonum multiflorum Thunb under normal conditions.

Combined with the toxicological study of the disease, it is found that Polygonum multiflorum Thunb can promote immune overactivation in the susceptible animal model mediated by immune stress, and can induce liver injury in the range equivalent to the commonly used clinical dose. Compatibility with traditional Chinese medicines such as Poria cocos and Glycyrrhiza uralensis can reduce the risk of liver injury.

Combined with pharmacogenomics research, it was confirmed that the liver injury of Polygonum multiflorum Thunb was related to the organism factors, especially the immune-related gene differences, and the susceptible gene HLA-B * 35: 0 1 was found, which indicated that Polygonum multiflorum Thunb had the risk of liver injury only for a few specific people, but it was safe for the vast majority of people.

Combined with knock-out and knock-in screening, it was found that the specific liver injury of Polygonum multiflorum Thunb was related to the structure and content of stilbenes and anthraquinone compounds contained in it. Cisstilbene glycoside and emodin -8-0-? -Glucoside can induce liver injury, and trans stilbene glycoside can synergistically enhance its liver injury. Processing can alleviate the liver injury of Polygonum multiflorum Thunb, suggesting that strengthening the quality and safety control of Polygonum multiflorum Thunb is helpful to reduce the risk of liver injury.

Based on various research results, some scholars suggest that immune stress is caused by Polygonum multiflorum Thunb. Three causes of poisoning? Mechanism hypothesis: when the immunity of the body is over-activated, the immune enhancer in Polygonum multiflorum Thunb can further promote the immune response of the body, enhance the sensitivity of the liver to the susceptible components of liver injury in Polygonum multiflorum Thunb, lead to the over-expression of immune inflammatory factors, and thus induce immune-specific liver injury.

Therefore, the hepatotoxicity of Polygonum multiflorum Thunb is only obvious to a small number of people, and it is related to susceptible genes, but it is undeniable that Polygonum multiflorum Thunb is a precious traditional Chinese medicine.