Iron Tree Fruit: A Traditional Chinese Medicine with Diverse Medicinal Properties

April 2, 2024

Iron tree fruit, a traditional Chinese medicine. It is the seed of the plant Cycas siamensis Miq. in the Cycadaceae family. Yunnan Cycas is distributed in southwestern Yunnan Province, including Simao, Jinghong, Lancang, and Luxi, as well as in Guangxi and Guangdong where it is cultivated. It can also be found in Myanmar, Thailand, and Vietnam. It has the effects of clearing dampness and reversing qi, strengthening the spleen and stomach, and relieving phlegm and cough. It is mainly used to treat enteritis, dysentery, dyspepsia, belching, bronchitis, and bronchial asthma.

The source is the seed of the Cycadaceae plant Cycas siamensis. The plant has a "phoenix tail banana leaf" appearance.

The chemical composition of the fruit (including the seed) includes cycasin (0.086%, with a seed content of about 0.2-0.3%), new cycasin A, B, C, D, E, F, G, a large amount of free palmitic acid (6.95% in the outer seed coat), a large amount of starch, as well as beta-carotene, lutein, and zeaxanthin pigments.

Pharmacological effects:

① Carcinogenic effect: Since the discovery in 1962 that feeding rats with cycasin mixed in food can cause tumors in the liver and kidneys, cycasin has been synthesized as a carcinogenic agent. It is generally believed that it is similar to dimethylnitrosamine and can be metabolized into heavy diazomethane in the body, exerting carcinogenic effects on various cells. Cycasin must be broken down into cycasin A in the intestine by enzymes or bacteria in order to be effective. It can only cause cancer when taken orally, not by injection (although newborn rats have enzymes in their subcutaneous tissue, causing cancer by subcutaneous injection, this enzyme disappears after 3-4 weeks after birth). Cycasin A is effective when taken orally or by injection, and a single dose is sufficient to cause tumors in most rats. Rats fed for a shorter period of time are more likely to develop kidney tumors, while those fed for a longer period of time are more likely to develop liver tumors. There are fewer tumors in the large intestine, and the occurrence of tumors is unrelated to the feeding time. Immature young rats are more likely to develop true renal tumors, renal sarcomas, and renal interstitial tumors, while renal adenomas are unrelated to maturity. Tumors always occur after 6 months of cycasin administration (even if there is fetal exposure, tumors will only appear after 6 months). The carcinogenic rate of cycasin A in rats is 100%, while that of cycasin is 85%, which is not related to the rat species. In addition to rats, it can also cause cancer in mice, guinea pigs, and hamsters. Cycasin A can produce various tumors caused by cycasin, such as duodenal tumors when injected into the abdominal cavity. The induced tumors can be transplanted. The morphology of rat renal adenomas is similar to that of humans or other animals, and it is caused by direct action on renal tubular epithelial cells.

② Neurotoxicity: Feeding cows with iron tree fruit seeds can cause paralysis and often leads to muscular atrophy and anterior horn sclerosis. There is demyelination in the lateral spinothalamic tract and posterior spinocerebellar tract, and there is deposition of osmium-loving substances. However, no abnormal lesions have been found in the central nervous system of rats. If the fetus of rats or hamsters is exposed to cycasin A in the mother's body, it can cause obvious deformities in the central nervous system after birth, preventing normal development (mainly in the cerebral hemispheres) and forming "microcephaly". The bony cranial vault becomes narrow, but the survival time is still relatively long. Some rats develop glioma after 13-15 months.

The mechanism of the toxic effect is not yet fully understood. The most significant lesions in rats occur in the liver, which appears early. The degree of lesions is related to the dosage. Mild cases result in loss of alkaline and glycogen in the cytoplasm of cells, and a decrease in glucose-6-phosphatase. Severe cases show widespread central lobule hemorrhage and necrosis, decreased liver ribonucleic acid and total phospholipids, and decreased liver protein synthesis. In mouse liver, the incorporation of H3-thymidine nucleoside into RNA and C14-thymine nucleoside into DNA is inhibited. Protein synthesis in the kidney, spleen, and small intestine is not affected. Cycasin and its aglycone have "alkylation" activity in vivo and in vitro. In experiments with fruit flies and Salmonella typhi, cycasin A has been found to be a powerful mutagen. When injected subcutaneously into mice with ascitic carcinoma, it has a similar anti-tumor effect to mitomycin C and nitrogen mustard. Cycasin has very little toxicity to cold-blooded animals. When fed to mice, there is no immediate poisoning phenomenon. Respiratory difficulties appear after 12-18 hours, and paralysis ultimately leads to death. The median lethal dose when orally administered to mice is 1.67 mg/kg, and the lethal dose when ingested by rats is 1.0 g/kg. After autopsy of the animals, congestion and hemorrhage are the main pathological findings. Cycasin has minor effects on respiration, blood pressure, heart, blood vessels, intestines, or uterus.

It has a bitter and astringent taste, and is neutral. It is toxic.

① "Modern Practical Chinese Medicine": "Bitter, neutral, sour and astringent, non-toxic."

② "Lu Chuan Materia Medica": "Light taste, cold in nature."

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