The combined use of acetazolamide and Rhodiola in the prevention and treatment of altitude sickness

Background: Altitude sickness (AS), which is caused by rapid exposure to low amounts of oxygen at high elevations, poses a great threat to humans working and traveling in these conditions. Acute mountain sickness includes high-altitude pulmonary edema and high-altitude cerebral edema. Acetazolamide (AZ) is often used to treat pulmonary edema caused by hypoxia. Additionally, the medicinal plant Rhodiola rosea L. (Rh) is often used to prevent AS in the Qinghai-Tibet plateau. However, the mechanisms of action of Rh and AZ in the treatment of AS remain unclear. To date, no research has been conducted to determine whether their combined use has better efficacy in the treatment and prevention of AS than their separate use. Methods: We used the method of network pharmacology to analyze the mechanisms of Rh and AZ in combination in the prevention and treatment of AS, and also verified our results. Results: The hypoxia-inducible factor (HIF)-1 signaling pathway, which is related to hypoxia, and other pathways related to pulmonary hypertension, became more enriched after the combined use of the 2 drugs. Additionally, Rh and AZ regulated most nodes in the AS network. Further, compared to their separate use, the combined use of Rh and AZ further downregulated the gene expression of HIF-1 alpha and improved hemodynamics in rats, and thus helped the body to reduce its sensitivity to hypoxic environments and pulmonary artery pressure. Conclusions: This study provides evidence supporting the combined use of AZ and Rh in the treatment of AS.