Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.

Post-infarction ventricular septal rupture complicated with cardiogenic shock and multiple organ hemorrhage: An autopsy case report.

Ventricular septal rupture (VSR) is a catastrophic mechanical complication of acute myocardial infarction (AMI) that can result in acute heart failure. Delaying operative intervention frequently leads to cardiogenic shock and multi-organ failure. Here we report a case of massive anterior MI complicated with VSR that was discovered through cardiac Doppler ultrasound and suspected multiple organ hemorrhage. The patient showed signs of rapid cardiogenic shock and eventually died. The morphological changes of VSR and MI were identified during necropsy, and microscopic examinations of the heart, brain, and kidney revealed multiple organ hemorrhage. This autopsy case suggested that the complication of VSR caused by AMI results in a reduction of oxygen and nutrient content of the circulating blood throughout the body and, eventually, functional failure of multiple organs. We provide clinical and pathological evidence elucidating changes in multiple organs under the severe condition of post-infarction VSR and demonstrate the consequences of a lack of immediate surgery and sufficient medical intervention for a patient suffering from AMI with VSR.

[Yiqi Tongluo Particles improve Qi-deficiency and blood stasis in multiple cerebral infarction rats by promoting angiogenesis].

This research was aimed to evaluate the protective effect and potential mechanism of Yiqi Tongluo Particles(YQTLs).Firstly,an animal model of multiple cerebral infarction(MCI) with Qi deficiency and blood stasis was established.Rats were randomly divided into six groups:SHAM group,Vehicle group,Buyang Huanwu decoction original group(BYHWO),EGb761 group,high and low dose of YQTLs group.Rats underwent sleep deprivation after one week of MCI and the tongues and pulses of rats after six weeks of sleep deprivation were detected,followed by collecting blood to analysis the blood coagulation.Differential expression of angiogenesis associated proteins was examined using proteomic research and verified by immunohistochemical.RESULTS: showed that neurological function score was obviously declined,G and B value of tongue surface was increased significantly and the pulse distension,the activated partial thromboplatin time(APTT) as well as prothrombin time(PT) were recovered following YQTLs 7.56 g·kg-1 treatment.Furthermore,G value of tongue surface,APTT and PT were also improved by YQTLs 3.78 g·kg-1.The results of proteomic technology showed that proteins associated with angiogenesis were reversed compared with Vehicle group.Moreover,the expression of VEGFR2 from immunohistochemical was promoted after YQTLs treatment.The MCI with Qi deficiency and blood stasis was alleviated obviously following YQTLs treatment and the possible mechanism was that YQTLs may enhance angiogenesis during cerebral ischemia.

[Quantitative proteomic research of biological basis of Buyang Huanwu decoction therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome].

Chinese medicine Buyang Huanwu decoction (BYHW) is widely used in treating cerebral infarction combined with Qi-deficiency and blood-stasis syndrome, but the pharmacological basis is still not clear. This study aims to uncover the biological basis of BYHW therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome using label-free proteomic technology. Using Qi deficiency and blood stasis rat cerebral infarction model as the research object, the protein expression of rat brain tissue was compared among the sham operation group, the model group and the drug group. Quantitative analysis of the 3 groups of tissue samples detected 3 959, 3 996 and 4 055 proteins in the sham operation group, the model group and the drug group, respectively. Take model group as the control group, 391 proteins were identified to be upregulated or downregulated for more than 2 folds. Biological analysis and functional enrichment of the differentially expressed proteins revealed that BYHW may treat cerebral infarction combined with Qi-deficiency and blood-stasis syndrome through energy metabolism, nervous system and several signal pathways. This study preliminarily revealed the pharmacological mechanism of BYHW at the protein level, and provided a molecular basis for clinical treatment and traditional Chinese medicine research on cerebral infarction combined with Qi-deficiency and blood-stasis syndrome.