Therapeutic effect and molecular mechanism of Salvia Miltiorrhiza on rats with acute brain injury after carbon monoxide poisoning based on the strategy of internet pharmacology

Abstract

The pathogenesis of brain injury caused by carbon monoxide poisoning (COP) is very complex, and there is no exact and reliable treatment in clinic. In the present study, we screened the therapeutic target and related signal pathway of Salvia Miltiorrhiza for acute COP brain injury, and clarified the pharmacological mechanism of multicomponent, multitarget, and multisignal pathway in Salvia Miltiorrhiza by network pharmacology. To further verify the therapeutic effect of Salvia Miltiorrhiza on acute brain injury based on the results of network analysis, a total of 216 male healthy Sprague Dawley rats were collected in the present study and randomly assigned to a normal control group, a COP group and a Tanshinone IIA sulfonate treatment group (72 rats in each group). The rat model of acute severe COP was established by the secondary inhalation in a hyperbaric oxygen chamber. We found that Salvia Miltiorrhiza had multiple active components, and played a role in treating acute brain injury induced by COP through multiple targets and multiple pathways, among them, MAPK/ERK1/2 signaling pathway was one of the most important. COP can start apoptosis process, activate the MAPK/ERK1/2 signaling pathway, and promote the expression of VEGF‐A protein and the formation of brain edema. Tanshinone IIA can effectively inhibit apoptosis, up‐regulate the expressions of VEGF‐A, P‐MEK1/2 and P‐ERK1/2 proteins, thereby protect endothelial cells, promote angiogenesis and microcirculation, and finally alleviate brain edema.

Evidence of clinical efficacy and pharmacological mechanism of N-butylphthalide in the treatment of delayed encephalopathy after acute carbon monoxide poisoning

“…In the aftermath of a stroke, IL-17 is critical in boosting the inflammatory response and causing secondary brain damage ( 42 ). Studies have demonstrated that the MAPK/ERK signaling pathway could enhance microcirculation, encourage angiogenesis, prevent cell apoptosis, and shield the brain tissue from toxicity effect of carbon monoxide ( 43 ). The FoxO signaling pathway plays an important role in cell proliferation, apoptosis, differentiation, and resistance to oxidative stress.…”

Effect and molecular mechanism of Sulforaphane alleviates brain damage caused by acute carbon monoxide poisoning:Network pharmacology analysis, molecular docking, and experimental evidence

“…ACOP can make patients with systemic hypoxia, abnormal synthesis of adenosinetriphosphate (ATP), resulting in multiple organ function damage, 1,2 among which, the most direct and serious consequences are in the central nervous system and cardiovascular system. 3 At present, the pathogenesis of brain injury caused by ACOP is not clear, and there is no reliable detoxification therapy. Hyperbaric oxygen therapy is the main treatment strategy in clinical practice, however, it can cause many serious complications, especially in severe patients and experimental animal models, such as non-convulsive status epilepticus, pulmonary edema, cerebral edema, and cerebral hemorrhage.…”

“…Acute carbon monoxide poisoning (ACOP) is one of the important causes of poisoning death that endanger human life safety. ACOP can make patients with systemic hypoxia, abnormal synthesis of adenosine–triphosphate (ATP), resulting in multiple organ function damage, 1,2 among which, the most direct and serious consequences are in the central nervous system and cardiovascular system 3 . At present, the pathogenesis of brain injury caused by ACOP is not clear, and there is no reliable detoxification therapy.…”