DIA-based serum proteomics revealed the protective effect of modified siwu decoction against hypobaric hypoxia.

ETHNOPHARMACOLOGICAL RELEVANCE: Siwu decoction (SWD) is a common traditional formula for nourishing blood, and its derived formulas are also widely used in traditional Chinese medicine (TCM) clinic. However, the protective effects of SWD and its derived formulas on blood deficiency and blood stasis caused by rushing to the plateau are rarely reported, and the underlying mechanism has not been fully elucidated. AIM OF THE STUDY: This study explores the pharmacological effects and mechanisms of modified siwu decoction (MSWD) adding Persicae Semans (Prunus persica (L.) Batsch) and Carthami Flos (Carthamus tinctorius L.) against hypobaric hypoxia (HH). The acute toxicity of MSWD was also evaluated to further validate the potential of MSWD as a therapeutic candidate for HH. MATERIALS AND METHODS: Hypoxic models of C57BL/6 J and KM male mice were used to evaluate the pharmacological effect of MSWD. 2 µL serum sample of C57BL/6 J mice was digested into peptide mixtures and analyzed with DIA mode on an Orbitrap Fusion Lumos mass spectrometer after LC separation. The peptide and protein identifications were limited to a 1% FDR. Screening of differential expressed proteins, correlation analysis, hierarchical clustering analysis, principal components analysis and Mfuzz analysis were all performed by R packages. The protein-protein interaction network was analyzed using the STRING website and constructed with Cytoscape software. RESULTS: MSWD showed a protective effect against acute hypoxia exposure through increasing the number of red blood cells and improving hemodynamics indexes in mice. Meanwhile, the biochemical results showed that MSWD could reduce the inflammation and oxidative stress, reduce the content of organ injury biomarkers and significantly improve the high-intensity exercise ability of mice. Subsequently, serum DIA proteomic results revealed significant changes in proteomic characteristics after MSWD intervention. Specifically, proteins related to oxidative stress and ubiquitin-proteasome system, such as Sod1, Gstp1, Vcp and Usp14, were down-regulated after MSWD intervention, suggesting that the protective effect of MSWD involved the reduction of oxidative stress and energy expenditure. MSWD also intervened in energy metabolism and lipid metabolism processes by altering the expression levels of Eno1, Sphk1 and Apoa1 to ameliorate hypoxia-induced disorders. At the same time, MSWD acute toxicity test showed no obvious toxicity. CONCLUSIONS: MSWD has a good protective effect against HH by ameliorating hypoxia-induced disorders of energy and lipid metabolism, supporting MSWD as a safe drug candidate for the prevention and treatment of acute hypoxia fatigue.

[Application of quantitative proteomics in the study of acute mountain sickness].

Acute mountain sickness (AMS) is a clinical syndrome of multi-system physiological disorder after acute exposure to low pressure and low oxygen at high altitude. Quantitative proteomics can systematically quantify and describe protein composition and dynamic changes. In recent years, quantitative proteomics has been widely used in the prevention, diagnosis, treatment and pathogenesis of many diseases. This review summarizes the progress of quantitative proteomics techniques and its application in the prevention, diagnosis, treatment of AMS and mechanisms of rapidly acclimatizing to plateau, in order to provide a reference for the pathogenesis, early intervention, clinical treatment and proteomic research of AMS.

Dissection of scientific compatibility of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia from the perspective of toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar-Indigo naturalis formula (RIF), a first-line drug for the treatment of acute promyelocytic leukemia (APL),is also a TCM formula entirely designed based on TCM theories. There have been studies that explain the scientific connotation of the compatibility of RIF from the perspective of pharmacodynamics. However, as one of the arsenic-containing preparations, the safety of realgar is widely concerned, and there has not been systematic studies to explain the scientific connotation of RIF from the perspective of toxicology. AIM OF THIS STUDY: Dissection of scientific compatibility of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia from the perspective of toxicology. MATERIALS AND METHODS: We used normal mice and an APL model to explore (i) the effects of different components on intestinal permeability, (ii) the changes in intestinal flora, and (iii) toxic effects. At the same time, a bionic extraction method was used to study the effects of different components on the dissolution of soluble arsenic in realgar under the acidic environment in the stomach and the alkaline environment in the intestinal tract. RESULTS: Salvia miltiorrhiza Bunge can repair the intestinal mucosal barrier, maintain the homeostasis of intestinal flora, intervene in the dissolution process of realgar, reverse the increase in intestinal permeability and the disturbance of intestinal flora caused by realgar, and reduce toxicity. CONCLUSION: From the perspective of toxicology, we propose new insights into the definition of the roles of each component in the RIF formula, namely realgar is the monarch, Indigo naturalis is the minister, Salvia miltiorrhiza Bungeis the assistant.

From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors.

Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.