Chemical proteomics unveils that seventy flavors pearl pill ameliorates ischemic stroke by regulating oxidative phosphorylation.

Ischemic stroke has high mortality and morbidity rates and is the second leading cause of death in the world, but there is no definitive medicine. Seventy Flavors Pearl Pill (SFPP) is a classic formula in Tibetan Medicine. Clinical practice has shown the attenuation effect of SFPP on blood pressure disorders, strokes and their sequelae and other neurological symptoms, but its mechanism remains to be elucidated. In this study, we established three animal models in vivo and three cell models to evaluate the anti-hypoxia, anti-ischemia, and reperfusion injury prevention effects of SFPP. Quantitative proteomics revealed that oxidative phosphorylation (OXPHOS) is essential for SFPP's efficacy. Then, cysteine-activity based protein profiling technology, which reflects redox stress at the proteome level, was employed to illustrate that SFPP brought functional differences of critical proteins in OXPHOS. In addition, quantitative metabolomics revealed that SFPP affects whole energy metabolism with OXPHOS as the core. Finally, we performed a compositional identification of SFPP to initially explore the components of potential interventions in OXPHOS. These results provide new perspectives and tools to explore the mechanism of herbal medicine. The study suggests that OXPHOS could be a potential target for further research and intervention of ischemic stroke treatment.

Azukisapogenol Triterpene Glycosides from Oxytropis chiliophylla Royle.

Eight azukisapogenol triterpene glycosides, including five new compounds, oxychiliotriterpenosides A⁻E (1⁻5), two new methyl glucuronide derivatives that proved to be artifacts, oxychiliotriterpenoside E-glucuronic acid methyl ester (6) and myrioside B-glucuronic acid methyl ester (7), and a known one, myrioside B (8), was isolated from the aerial part of Oxytropis chiliophylla Royle. Their structures were elucidated based on extensive spectroscopic analyses and chemical methods. Triterpene glycosides were first obtained from O. chiliophylla, and those containing a galactose unit (1, 2, 5 and 6) and diglucosidic or triglucosidic linkage at C-29 (1⁻4), were reported from Oxytropis species for the first time, which might be recognized as a chemotaxonomic feature of O. chiliophylla. All isolated compounds were evaluated for their anti-inflammatory activities against NO production using lipopolysaccharide (LPS)-induced RAW 264.7 cells, but no compounds showed potent inhibition on NO production.

Subacute toxicity and chemical analysis of Tibetan medicine Oxytropis falcata / 中国中药杂志

Four different extracts of Oxytropis falcata, including the aerial aqueous extract, and the underground aqueous extract, the aerial lipophilic extract, and the underground lipophilic extract were prepared and then administrated orally to mice at the maximum dose (50 g x kg(-1) x d(-1) calculated by raw material) for fifteen days respectively. Compared with the control group, which was administrated of 1.0% tween-80, the treatment groups did not show significant differences in appearance and behavior. However, the organcoefficient, blood biochemical indicator and pathological section results showed that the lipophilic extracts of the aerial and underground parts of O. flacata showed mild injury to the liver of mice, while the aerial and underground aqueous extracts and the underground lipophilic extract showed mild toxicity to the kidney of male mice. Chemical analysis showed that the lipophilic extracts of the aerial and underground parts, especially aerial lipophilic extract, consisted of large amount of flavonoid aglycones with little amount of polysaccharides and proteins, while the aqueous extracts contained much polysaccharides and proteins with almost no flavonoid aglycones detected.