Researchers from South Ural State University (SUSU), together with Indian colleagues, for the first time studied the molecular mechanisms of action of berberine, a natural alkaloid found in barberry. They compared the proteins with which the compound can interact and the genes associated with depression. The results may be useful for pharmacologists and neurobiologists in creating new antidepressants.
During laboratory studies, scientists identified four key targets of berberine. The first is the AKT1 protein, responsible for the survival and plasticity of nerve cells. The second is STAT3, which regulates inflammatory processes in the brain. The third is HSP90AA1, a chaperone protein that affects the stability of many molecular systems. The fourth is SRC, which is involved in signal transduction and amplification of inflammation.
As noted at SUSU, berberine showed high affinity for the AKT1 protein, and even surpassed it in binding strength. Scientists found that the natural compound binds to the same sites of proteins as synthetic drug blockers, which makes it a potential competitor to existing antidepressants.
In another stage, researchers modeled the movement of molecules for 10 nanoseconds. The "berberine-protein" complexes were stable and maintained strong hydrogen and hydrophobic bonds – the molecule was held in the active sites without structural destruction. This confirms the promise of berberine for further preclinical trials.
The university emphasized that the work is particularly relevant due to the limitations of existing drugs, which do not help all patients and only take effect after weeks. Berberine, as a natural compound, can become the basis for more accessible and safer remedies. After preclinical trials, it is considered as a potential basis for future medicines or auxiliary dietary supplements against depression.