Author:
Kong Xiu mei,Song Dan,Li Jie,Jiang Yi,Zhang Xiao ying,Wu Xiao Jun,Ge Ming juan,Xu Jiao jiao,Gao Xiao min,Zhao Qin
Abstract
Abstract
Background
Anoxia is characterized by changes in the morphology, metabolism, and function of tissues and organs due to insufficient oxygen supply or oxygen dysfunction. Gentiana straminea Maxim (G.s Maxim) is a traditional Tibetan medicine. Our previous work found that G.s Maxim mediates resistance to hypoxia, and we found that the ethyl acetate extract had the best effect. Nevertheless, the primary anti-hypoxia components and mechanisms of action remain unclear.
Methods
Compounds from the ethyl acetate extraction of G.s Maxim were identified using UPLC-Triple TOF MS/MS. Then Traditional Chinese Medicine Systematic Pharmacology Database was used to filtrate them. Network pharmacology was used to forecast the mechanisms of these compounds. Male specific pathogen-free Sprague Dawley rats were randomly divided into six groups: (1) Control; (2) Model; (3) 228 mg/kg body weight Rhodiola capsules; (4) 6.66 g/kg body weight the G.s Maxim’s ethyl acetate extraction; (5) 3.33 g/kg body weight the G.s Maxim’s ethyl acetate extraction; (6) 1.67 g/kg body weight the G.s Maxim’s ethyl acetate extraction. After administering intragastric ally for 15 consecutive days, an anoxia model was established using a hypobaric oxygen chamber (7000 m, 24 h). Then Histology, enzyme-linked immunosorbent assays, and western blots were performed to determine these compounds’ anti-hypoxic effects and mechanisms. Finally, we performed a molecular docking test to test these compounds using Auto Dock.
Results
Eight drug-like compounds in G.s Maxim were confirmed using UPLC-Triple TOF MS/MS and Lipinski’s rule. The tumor necrosis factor (TNF) signaling pathway, the hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the nuclear factor kappa-B (NF-κB) signaling pathway was signaling pathways that G.s Maxim mediated anti-anoxia effects. The critical targets were TNF, Jun proto-oncogene (JUN), tumor protein p53 (TP53), and threonine kinase 1 (AKT1). Animal experiments showed that the ethyl acetate extraction of G.s Maxim ameliorated the hypoxia-induced damage of hippocampal nerve cells in the CA1 region and reversed elevated serum expression of TNF-α, IL-6, and NF-κ B in hypoxic rats. The compound also reduced the expression of HIF-1α and p65 and increased the Bcl-2/Bax ratio in brain tissue. These findings suggest that G.s Maxim significantly protects against brain tissue damage in hypoxic rats by suppressing hypoxia-induced apoptosis and inflammation. Ccorosolic acid, oleanolic acid, and ursolic acid had a strong affinity with core targets.
Conclusions
The ethyl acetate extraction of G.s Maxim mediates anti-hypoxic effects, possibly related to inhibiting apoptosis and inflammatory responses through the HIF-1/NF-κB pathway. The primary active components might be corosolic, oleanolic, and ursolic acids.
Publisher
Springer Science and Business Media LLC
Subject
Complementary and alternative medicine
Reference59 articles.
1. Phillips L, et al. Findings of cognitive impairment at high altitude: relationships to acetazolamide use and Acute Mountain sickness. High Alt Med Biol. 2017;18(2):121–7.
2. Gudbjartsson T, et al. High altitude illness and related diseases - a review. Laeknabladid. 2019;105(11):499–507.
3. Urushida Y, et al. Improved neuroimaging findings and cognitive function in a case of high-altitude cerebral edema. Intern Med. 2021;60(8):1299–302.
4. Bao T, et al. Study on anti-inflammatory effects of effects of ethanol extract form different parts of Tibetan medicine Gentiana straminea. China Pharm. 2018;29(22):3114–8.
5. Jia N, Cui J, Wen A. Effects of ethanol extract of Tibetan medicine Gentiana stramine on the expression of NF-κB p65 in synovial tissue of collagen-induced arthritis model mice. China Pharm. 2018;29(15):2082–5.