A biological clock, also known as a circadian rhythm, is a biological process that regulates bodily function. Our sleep cycle, temperature fluctuations, when we eat more easily to gain weight, the efficacy of medication, etc. , are closely related to the body’s biological clock. Recent restrictions on international travel may have prevented many people from acute biological clock disorders, but long-term biological clock disorders are plaguing more and more modern people. Long-term biological clock disorders are harmful to health and can cause obesity, cardiovascular disease, mental disorders and even cancer. Unfortunately, despite all the efforts, scientists still know little about the biological mechanisms of circadian rhythms, and there are few approved drugs to help regulate the biological clock.
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Recently, a team of researchers led by Dr. Zhang Andijun of the Beijing Institute of Life Sciences (NIBS) and Dr. Qi Xiangbing led a new study that sifted through a compound from nearly 10,000 experimental drugs that regulate the biological clock. In the mouse experiment, the number of days required to reverse the time difference in the animals was reduced by half. The research paper is published in Science Translational Medicine, a sub-journal of clinical transformation research.
In this study, scientists screened tens of thousands of molecules, including clinical and preclinical experimental drugs, purified natural products, and synthetic compounds, based on cell experiments. After some effort, they found that cordycepin may regulate the biological clock gene.
Insect herb, or 3′-deoxy adenosine, is a nucleoside derivative first obtained from a fungus called Cordyce militarpsis and is a natural bioactive substance. The team found that pyrogens had a very strong and stable effect on some biological clock genes, causing a 12-hour violent “displacement” of expression patterns that completely reversed their circadian rhythms.
It was originally a natural compound extracted from the fungus aphid (photo: http://commons.wikimedia.org/wiki/file:2008-12-14_Cordyceps_militaris_3107128906.jpg)
Natural herbicides extracted directly from aphids are very expensive. Fortunately, chemists have a way of synthesizing insects and herbs. The team used synthetic insectherin to conduct further tests on animals.
By artificially altering the time of light and darkness, the researchers asked mice living in the lab to simulate the problem of jet lag encountered during international travel. In one case, the time of the mouse was moved forward for 8 hours, and in the other case, it was moved back by 8 hours. At the same time, they injected some mice with synthetic herbicides to see how long it would take them to adjust their sleep cycles to adapt to the new environment.
Normally, the mice in the control group took 8 days, and after injecting the pyrobutt, the mice needed only an average of 4 days to reverse the time difference, twice as fast as the biological clock needed to dial fast or slow.
In both cases where the biological clock needs to be dialed forward or backward, the insect herb makes the process faster (Photo: Resources 1)
Further analysis of the reasons for the effects of the pyrobotin, the researchers found that it binds to an enzyme called RUVBL2. The protein is abundant in the brains of mice, especially in the heart of the visual cross- – the brain region that regulates circadian rhythm-related behavior, and it affects the transcription of certain biological clock genes. In other words, pyretin may be ruVBL2 to turn on or off the expression of the biological clock gene.
“The insecticidal can penetrate the blood-brain barrier, quickly act, and reverse the circadian rhythm phenotype for 12 hours, making it potentially a potential candidate for the treatment of jet lag,” the study authors concluded in their paper. In addition to acute circadian disorders, it is also expected to be used to treat a wide range of chronic rhythmic disorders associated with the biological clock. “
The circadian expression pattern of the bioclocking gene is regulated by RUVBL2 (Photo: Resources, Credit: Zhancong Xu)
Is that if taking insectherin can help us adjust the biological clock? The researchers also pointed lying carefully about several limitations of the work, such as mice used in animal experiments, which are known to be active at night and have circadian rhythms that are the opposite of what we are, so whether the results can be repeated in humans is a question to be answered. In addition, the intake of insects in the experiment requires a high dose (15 mg per kilogram of body weight) and, if used in clinical settings in the future, further development of similars will be required to produce better efficacy.