Porcine epidemic diarrhea virus (PEDV) infections have resulted in a severe economic loss in the swine industry in many countries due to no effective treatment approach. Fifteen oleanane triterpenes (1-15), including nine new ones (1-4 and 10-14), were isolated from the flowers of Camellia japonica, and their molecular structures were determined by extensive spectroscopic methods. These compounds were evaluated for their antiviral activity against PEDV replication, and the structure-activity relationships (SARs) were discussed. Compounds 6, 9, 11, and 13 showed most potent inhibitory effects on PEDV replication. They were found to inhibit PEDV genes encoding GP6 nucleocapsid, GP2 spike, and GP5 membrane protein synthesis based on RT-PCR data. Western blot analysis also demonstrated their inhibitory effects on PEDV GP6 nucleocapsid and GP2 spike protein synthesis during viral replication. The present study suggested the potential of compounds 6, 9, 11, and 13 as promising scaffolds for treating PEDV infection via inhibiting viral replication.

a b s t r a c tSwine based agro-industries throughout the world are in big threat of new PEDV infection due to lack of efficient prophylactic defenses as well as dependable curing agents. Bioactivity-guided fractionation of a methanol soluble extract from radix of Saposhnikovia divaricata led to the isolation of three new (1e3) together with 10 known coumarins (4e13). The structures of new isolates (1e3) were established by extensive spectroscopic analysis and their absolute configurations were assigned based on ECD spectra calculation and analysis. Among all isolates, compound 5 revealed strongest inhibitory effect on PEDV replication. Quantitative real-time PCR data showed inhibitory effect of 5 on genes responsible for synthesis of PEDV vital structural proteins (GP6 nucleocapsid, GP2 spike, and GP5 membrane) in a dosedependent manner. Also, compound 5 demonstrated the inhibitory effect on PEDV GP6 nucleocapsid and GP2 spike protein synthesis as analyzed by western blotting. This study represents a new class of chemical entities for developing anti-PEDV agents.

During a search for SIRT1 activators originating in nature, three new dammarane triterpenes, 6α,20(S)-dihydroxydammar-3,12-dione-24-ene (1), 6α,20(S),24(S)-trihydroxydammar-3,12-dione-25-ene (2), and 6α,20(S),25-trihydroxydammar-3,12-dione-23-ene (3), as well as two known triterpenes, dammar-20(22),24-diene-3β,6α,12β-triol (4) and 20(S)-ginsenoside Rg3 (5), were isolated from Panax ginseng leaves. Compounds 1 and 3-5 showed potential as SIRT1 activators, as analyzed by in vitro enzyme-based SIRT1-NAD/NADH and SIRT1-p53 luciferase cell-based assays. They were also found to increase the level of NAD(+)/NADH ratio in HEK293 cells. This study presents a new class of chemical entities that may be able to be developed as SIRT1 activators for antiaging and treatment of age-associated diseases.

Cystic fibrosis (CF) is a life-threatening, inherited, multi-organ disease that renders patients susceptible throughout their lives to chronic and ultimately deteriorating protracted pulmonary infections. Those infections are dominated in adulthood by the opportunistic pathogen, Pseudomonas aeruginosa (Pa). As with other advancing respiratory illnesses, people with CF (pwCF) also frequently suffer from gastroesophageal reflux disease (GERD), including bile aspiration into the lung. GERD is a major co-morbidity factor in people with pwCF, with a reported prevalence of 35–81% in affected individuals. Bile is associated with the early acquisition of Pa in CF patients and in vitro studies show that it causes Pa to adopt a chronic lifestyle. We hypothesized that Pa is chemoattracted to bile in the lung environment. To evaluate, we developed a novel chemotaxis experimental system mimicking the lung environment using CF-derived bronchial epithelial (CFBE) cells which allowed for the evaluation of Pa (strain PAO1) chemotaxis in a physiological scenario superior to the standard in vitro systems. We performed qualitative and quantitative chemotaxis tests using this new experimental system, and microcapillary assays to demonstrate that bovine bile is a chemoattractant for Pa and is positively correlated with bile concentration. These results further buttress the hypothesis that bile likely contributes to the colonization and pathogenesis of Pa in the lung, particularly in pwCF.

Humulus japonicus is an annual plant belonging to the Cannabacea family, and it has been traditionally used to treat pulmonary tuberculosis, dysentery, chronic colitis, and hypertension. We investigated the active components against Parkinson’s disease from H. japonicus fraction (HJF) using high performance liquid chromatography (HPLC) coupled with quadruple-time-of-flight mass spectroscopy (qTOF-MS) and NMR. Fourteen compounds were isolated from HJF, including one new compound, using HPLC-qTOF-MS and NMR. The major compounds of HJF were luteolin-7-O-glucoside and apigenin-7-O-glucoside, and there was approximately 12.57- and 9.68-folds increase in the contents of these flavonoids compared to those of the 70% EtOH extract. Apigenin and luteolin exhibited the strongest inhibitory effects on monoamine oxidase (MAO) B enzyme activity. In animal studies, limb-use behavior was significantly reduced by unilateral 6-OHDA lesion and ipsilateral rotations. These results indicated that oral administration of 300 mg/kg HJF resulted in the improvement of motor asymmetry and motor impairment in unilateral 6-OHDA-lesioned mice. HJF, including active components leads to an improvement of motor behavior in a Parkinson’s disease mouse model.