Both enzymatic and non-enzymatic reactions in the body may produce free radicals, which are closely related to aging. The production and elimination of free radicals in normal body are in dynamic balance. Once this balance is broken, free radicals will damage biological macromolecules such as lipids, protein and nucleic acids, leading to the destruction of cell structure and the aging of the body. Melatonin can protect cell structure, prevent DNA damage and reduce the content of peroxide in the body by scavenging free radicals, resisting oxidation and inhibiting lipid peroxidation. Russel et al. found that melatonin can protect DNA damage caused by safrole (a carcinogen that destroys DNA by releasing free radicals) up to 99%, and it has a dose-response relationship. Melatonin has obvious antagonistic effect on peroxidation caused by exogenous poisons (such as paraquat) and tissue damage caused by generated free radicals. Melatonin can also reduce the content of LPO in the brain, and its effects in different areas of the brain, such as cerebral cortex, cerebellum, hippocampus, hypothalamus and striatum, are basically the same, and all of them are dose-dependent. But different strains of rats, such as Sprague-Dawlay and Wistar rats, have different sensitivities to melatonin.
Fight tumor
Vijayalaxmi et al. (1995) found that melatonin has obvious protective effect on chromosome damage of human peripheral blood lymphocytes caused by 137Cs γ rays (150cGy) in a dose-dependent manner. It has antagonistic effect on the physical and chemical mutagenicity and carcinogenicity of free radicals. In vitro experiments show that melatonin can also protect the mutagenicity caused by zilmycin C. Melatonin can reduce the formation of DNA adducts induced by chemical carcinogen (safrole) and prevent DNA damage. Yan Jianjun and others studied the anti-tumor effect of melatonin on H22 liver cancer mice, and found that melatonin can inhibit the tumor growth of tumor-bearing mice and prolong their survival time, which has obvious synergistic effect with IL-2. Danforth et al. measured the 24-hour plasma melatonin levels of normal women, breast cancer patients and breast cancer patients respectively. The results show that normal women have circadian rhythm. The circadian rhythm of breast cancer patients is obviously related to the amount of steroid receptors in primary tumors. The mean value of plasma melatonin in patients with estrogen (er) or progesterone (PR) receptor positive day and night is significantly lower than that in patients with ER or PR negative tumor, and it is negatively correlated with the amount of ER or PR receptor in primary tumor, indicating that melatonin is related to hormone-dependent human breast cancer. Melatonin can promote endogenous granulocytes/macrophages to produce accumulation factors through bone marrow T cells, which can be used for adjuvant treatment of tumors.
Improve sleep
It can shorten the time of waking up and falling asleep before going to bed, improve the quality of sleep, obviously reduce the number of waking up during sleep, shorten the shallow sleep stage, prolong the deep sleep stage and lower the threshold of waking up the next morning. It has powerful time difference adjustment function. [1] Mainly used for whitening and moisturizing cosmetics, and also commonly used for hair growth products. The biological function of melatonin, especially as a dietary supplement, has been widely studied at home and abroad, which shows that melatonin has many physiological functions, such as promoting sleep, regulating jet lag, anti-aging, regulating immunity and anti-tumor. The health care function of melatonin at home and abroad involves regulating endocrine (inhibiting ovulation), protecting encephalitis virus infection, reducing post-infection mortality, treating AIDS and protecting cardiovascular system.
Holmes studied the hypnotic effect of melatonin and its influence on neurochemistry. After melatonin 10 mg/kg BW was given to rats, the time of falling asleep was reduced by half, the time of awakening was also shortened obviously, the slow wave sleep and heterogeneous sleep were obviously prolonged, and it was easy to wake up. When the dosage was 2.5 mg/kg body weight, a slightly lower hypnotic effect was obtained. Any dose of melatonin will not change the standard EEC model, nor will it interfere with the normal sleep mode. The hypnotic effect of intraperitoneal injection of melatonin (25mg/kg body weight) in mice is similar to that of cyclohexene barbital (hypnotic) (100 mg/kg body weight).
Dollins et al. (1994) studied the hypnotic effect of low dose melatonin on 20 young healthy volunteers. After volunteers took 0. 1 ~ 10 mg melatonin orally in the morning 165438, the serum concentration at night reached the average level of normal people. 0. 1, 0.3, 1.0 and 10.0, etc. The oral temperature, sleep time, sleep duration, energy, fatigue, mood and the correct response rate to Wilkinson's auditory arousal test decreased in all dose groups.
Waldhauser et al. (1990) also studied the hypnotic effect of oral melatonin 80 mg on 20 young healthy volunteers. It was observed that after taking 1 h, the plasma concentration reached the peak (average 25 8 17 pg/mL), which was significantly higher than that of normal people. The waking time and sleeping time before going to bed are shortened, the quality of sleep is improved, and the number of waking times during sleep is obviously reduced. Moreover, the sleep structure was adjusted, and the shallow sleep stage was shortened, the deep sleep stage was prolonged, and the threshold of waking up the next morning was lowered. Irina et al. (1995) gave volunteers 0.3 mg and 1.0 mg melatonin orally at 18, 20 and 2 1 respectively, which could shorten the time of falling asleep and entering the second stage of sleep, but did not affect the REM (rapid eye movement) period, indicating that melatonin was helpful to improve.
The US FDA (US Food and Drug Administration) believes that melatonin can be used as a common dietary supplement. Up to now, China's Ministry of Health has successively approved 20 kinds of products containing melatonin (including 8 kinds made in China and 2 kinds imported 12) as "sleep-improving" health food. Supplementing melatonin in vitro can keep the melatonin level in the body young, adjust and restore the circadian rhythm, not only deepen sleep and improve the quality of sleep, but also improve the functional state of the whole body, improve the quality of life, delay the aging process and reduce glucocorticoid.
Therefore, melatonin, as a new hypnotic drug, has the following unique advantages:
(1) Low dose (1 ~ 3 mg) has ideal hypnotic effect;
(2) It is an endogenous substance and plays a regulatory role in the endocrine system. It is not a foreign body to the body, has its own metabolic pathway in the body, and will not cause the accumulation of drugs and their metabolites in the body;
(3) The biological half-life is short, and it will drop to the physiological level of normal people after a few hours of oral administration;
(4) little toxicity.
Regulating immunity
Maestron found that functional or drug inhibition of melatonin biosynthesis can lead to inhibition of humoral and cellular immune effects in mice. Melatonin can antagonize the stress immunosuppression induced by mental factors (acute anxiety) in mice and prevent paralysis and death caused by acute stress induced by infectious factors (sublethal dose of brain myocardial virus). Yan Jianjun and others studied the immunomodulatory effect of melatonin on H22 liver cancer mice, and found that melatonin can increase the CD4+CD8+ value of tumor-bearing mice, increase the number of peripheral blood lymphocytes and eosinophils in cooperation with IL-2, enhance the NK and LAK activities of spleen cells, and promote the induction of IL-2. The regulatory effect of melatonin on macrophage function in mice with H22 liver cancer was also studied. It was found that the killing activity of macrophages and the induced level of IL- 1 increased significantly after injection, indicating that melatonin has a selective regulatory effect on macrophage function. Kethleen et al. (1994) found that melatonin can activate human monocytes, induce their cytotoxicity and secrete IL- 1.