Cough variant asthma (CVA) is one of the primary causes of chronic cough. And we found that Fritillariae thunbergii Bulbus (FTB) exhibited promising antitussive and expectorant functions. Thus, we explore the role and mechanism of FTB on CVA based on metabolomics. CVA mice models were established using ovalbumin and treated with different concentrations of FTB (1–4 g/kg). Then cough numbers, airway resistance, inflammatory factor levels, inflammatory cell numbers, EOS contents, and lung histopathology were determined. Furthermore, TLR4-MyD88-NF-κB pathway-related protein expressions were evaluated. Besides, UPLC-MS/MS analysis was applied to detect serum differential metabolites of CVA mice with FTB treatment. We found that FTB showed obvious effects on CVA mice by reducing cough number and airway resistance, alleviating inflammation response in serum and BALF, and improving lung pathological damage. Furthermore, FTB decreased TLR4-MyD88-NF-κB pathway-associated protein expressions in the lung tissue of CVA mice. The results of metabolomics found that FTB recovered the levels of nucleosides, analogues, organic acids and derivatives as well as organoheterocyclic compounds in CVA mice serum, the modulation may relate to metabolic pathways, purine metabolism and regulation of lipolysis in adipocytes. FTB suppressed inflammation in CVA via inhibiting TLR4-MyD88-NF-κB signaling pathway and serum metabolic levels, indicating that FTB might act as a novel drug for treating CVA.

Ischemia/reperfusion (I/R) is a primary cause of morbidity and mortality in acute myocardial infarction (AMI). L-Borneol 7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside (LBAG), extracted from the Radix Ophiopogonis, is the main bioactive component that may be exerting cardiovascular protection in AMI. The purpose was to examine the effects of LBAG on myocardial I/R injury (MIRI) in rats and H9c2 cells treated with hypoxia/reoxygenation (H/R). MIRI was induced through the combination of ischemia with reperfusion for 30 min and 24 h, respectively. LBAG was administered 7 days before vascular ligation. Myocardial function was detected by an electrocardiograph, histological, TTC, and TUNEL staining analyses. The influences of LBAG on the content concentration of cardiac enzymes in the serum were measured by ELISA. Moreover, H9c2 cells were exposed to LBAG or combined with AKT inhibitor (perifosine) and then exposed to H/R for simulating the cardiac injury process. Afterward, cell viability, LDH, CD-KM release, apoptosis, and autophagy were evaluated by CCK-8 and ELISA assays, flow cytometry, TUNEL, and immunofluorescence staining, respectively. Additionally, the proteins of apoptosis, autophagy, and PI3K/mTOR pathway were determined by western blotting. In I/R rats, LBAG pretreatment significantly ameliorated cardiac function, as illustrated by reducing the infarct size, myocardial autophagy, and apoptosis levels. In H/R-induced H9c2 cells, LBAG pretreatment significantly decreased cell apoptosis, LC3 II/I, and Beclin 1 levels, elevated the Bcl-2 levels, attenuated LDH, and CD-KM production. Moreover, LBAG pretreatment markedly increased the PI3K/mTOR pathway activation, and the protective influences of LBAG were partly abolished with the AKT inhibitor perifosine treatment. These findings demonstrated the protective functions of LBAG on I/R by regulating apoptosis and autophagy in vitro and in vivo by activating the PI3K/mTOR pathway.

Ophiopogon japonicas has a protective effect on myocardial ischemia/reperfusion injury-related diseases. Using network pharmacology and molecular docking approaches, we aimed to investigate the potential role of OJPs in myocardial damage. Also, the effects of OJPs and verapamil on cardiac function, cardiac marker enzymes, oxidative stress, inflammation, histopathological changes, apoptosis, TLR4/Myd88/NF-κB, PI3K/AKT/mTOR, as well Nrf2/HO-1 pathways were determined by echocardiography, hematoxylin-eosin and staining, Enzyme-Linked Immunosorbnent Assay, TdT-mediated dUTP nick end labeling, IHC and Western blot assays in MI/RI rats, respectively. A total of 28 absorbable compounds of OJPs and 65 OJPs-MI/RI-related targets were screened. Regulation of inflammatory response and apoptotic signaling pathway might contribute to OJPs against MI/RI. Besides, molecular docking presented that there are 6 core targets including AKT1, IL6, TNF, VEGFA, EGFR, and Caspase 3 with a certain binding affinity on the absorbable components of OJPs. The in vivo experiments illustrated that OJPs ameliorated cardiac function, oxidative stress, inflammation, and histopathological injury in I/R rats. Moreover, OJPs also could repress levels of apoptosis and TLR4/Myd88/NF-κB-related targets, as well as activate PI3K/AKT/mTOR and Nrf2/HO-1 pathways. Collectively, our findings suggest OJPs could attenuate MI/RI by weakening the TLR4/Myd88/NF-κB signaling, as well as activating PI3K/AKT/mTOR and Nrf2/HO-1 pathways.