The most bioactive fraction of stir-fried Radix Paeoniae Alba regulating IL-6/STAT3 signaling pathway in allergic asthma mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Paeoniae Alba (RPA), a traditional Chinese medicine, has been used frequently in the treatment of asthma. Previous studies demonstrated the dichloromethane fraction of Stir-Frying RPA (FDCM) enhanced the effect of anti-allergic asthma compared with the dichloromethane fraction of RPA (DCM). AIM OF THE STUDY: The significant increasing of Paeoniflorin (PF), ethyl gallate (EG), 1,2,3,4,6-pentagalloylglucose (PGG) had been observed in FDCM. This study aimed to investigate the effects and mechanisms of these compounds from FDCM in ovalbumin (OVA)-induced allergic asthma mouse model. MATERIALS AND METHODS: The significant difference contents compounds fraction (FB-40) and other fractions in FDCM were enriched by Medium Pressure Liquid Chromatography (MPLC). The pharmacodynamics was verified among all fractions in OVA-induced allergic asthma mice. Moreover, the drug dose dependence of FB-40 (0.42 mg/kg, 0.21 mg/kg, and 0.07 mg/kg), which were the most active fraction from FDCM for anti-allergic asthma, was explored. The expression of IL-6, p-STAT3, and STAT3 was analyzed by Western blot analysis. In addition, the main components of FB-40 were identified by UPLC with standards. Finally, the anti-inflammatory effects of the main components from FB-40 were detected by LPS-stimulated BEAS-2B cells using an Elisa assay. RESULTS: The results showed that FB-40 was the most active fraction from FDCM, which could significantly improve the lung tissue pathological condition, and decrease the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). It had greater pharmacological activity than its main component PF. FB-40 also showed dose dependence and regulated the IL-6/STAT3 signaling pathway in allergic asthma mice. Besides, PF, Albiflorin (AF), PGG, EG, and 1,2,3,6-Tetra-O-galloyl-ß-D-glucose (TGG) from FB-40 were identified by UPLC with the standard. At last, in the LPS-induced BEAS-2B cell experiments, EG, PGG, 1,2,3,6-Tetra-O-galloyl-ß-D-glucose (TGG) showed stronger inhibiting activities of cytokine than the monoterpenoid glycosides (PF and AF). CONCLUSION: The research proved that FB-40 was an active fraction in FDCM, which regulates IL-6/STAT3 Signaling Pathway to ameliorate allergic asthma. Gallic acids including TGG and PGG, and EG also play a role in the treatment of allergic asthma in FB-40.

Screening of Bioactive Fraction of Radix Paeoniae Alba and Enhancing Anti-Allergic Asthma by Stir-Frying Through Regulating PI3K/AKT Signaling Pathway.

Allergic asthma is a common respiratory inflammation disease. The crude Radix Paeoniae Alba (RPA) and its processed products have been used frequently as antipyretic and anti-inflammatory agents in traditional medicine. To evaluate the effect of honey and bran processing, different fractions of RPA were used for treating anti-allergic asthma in the ovalbumin (OVA)-induced mice model, and then, the most effective fraction of RPA and stir-frying Radix Paeoniae Alba with honey and bran (FRPA) for treating anti-allergic asthma were compared mutually for pharmacological effects. The results showed that the treatment of the dichloromethane fraction of RPA significantly improved the pathological condition of lung tissues, decreased the number of eosinophils and other cells in bronchoalveolar lavage fluid (BALF), and the increased the expression of various inflammatory factors. Furthermore, the study discovered that the lung pathological conditions, compared with the high dose of dichloromethane RPA fraction, could be ameliorated by high dose of dichloromethane FRPA fraction treatment. Moreover, the expression of inflammatory factors and the phosphorylation of the PI3K/AKT signaling pathway could be diminished by FRPA. Finally, the contents of compounds with a significant difference in the FRPA dichloromethane fraction were paeoniflorin, ethyl gallate, pentagalloylglucose, galloylpaeoniflorin, and others by UPLC/Q-TOF-MS analysis. These findings suggest that the dichloromethane fraction of FRPA has an enhancement effect on anti-allergic asthma and provide the experimental basis for exploring the processed mechanism of RPA.

Processing and Polyherbal Formulation of Tetradium ruticarpum (A. Juss.) Hartley: Phytochemistry, Pharmacokinetics, and Toxicity.

Herbal medicine is a major part of traditional Chinese medicine (TCM), which is evolved as a system of medical practice from ancient China. The use of herbal medicine is mainly based on practice and theories and concepts rooted in ancient philosophy. In the era of evidence-based medicine, it is essential to accurately evaluate herbal remedy with standard/modern medical practice approaches. Tetradium ruticarpum (A. Juss.) Hartley (TR), a medicinal plant with diversify bioactive components, has been broadly used to treat pain and gastrointestinal disorders in TCM. However, TR has also been reported to have potential toxicity by long-term use or excessive doses, though the associated compounds are yet to be identified. TR is usually processed, and/or combined with other herbs in TCM formulas in order to achieve a synergistic effect or reduce its toxicity. Since processing or polyherbal formulation of TR may lead to changes in its chemical composition and contents, quality, efficacy and toxicity, comparison of TR samples before and after processing, as well as its combination with other medicines, would provide useful knowledge of bioactive compounds, efficacy and toxicity of this valuable medicinal plant. Here we reviewed the recent studies about the phytochemistry, pharmacokinetic behaviors and toxicity of TR under various processing or polyherbal formulation conditions, which would expand our understanding of mechanisms of TR's efficacy and toxicity and be valuable for quality control in industrial manufacturing, future medicinal research, and safety and rational use of TR in TCM.

Three new tetralol analogs from soil-derived fungus Myrothecium verrucaria with anti-inflammatory activity.

Three new tetralol analogs, myrochromanols A-C (1-3), together with 11 known trichothecenes (4-14), were isolated from a soil fungus Myrothecium verrucaria HL-P-1. The structures of the three new compounds were elucidated by extensive spectroscopic analysis including HRESIMS, NMR, and ECD calculation. All of the new compounds were tested for their anti-inflammatory activity and cytotoxicity. Compounds 1 and 3 inhibited lipopolysaccharide (LPS)-induced NO production in BV2 cells with IC50 values of 26.04 and 25.80 µM, respectively.

C21 steroidal glycosides from Cynanchum taihangense.

Two new C21 steroidal glycosides, cynataihosides E (1) and F (2), together with a known one, sublanceoside H2 (3), were isolated from Cynanchum taihangense. The aglycone of cynataihoside F (2) was also a new compound. Their structures were elucidated on the basis of NMR spectroscopic data, HR-ESI-MS analysis, and chemical evidence. Their cytotoxic activities against three human tumor cell lines (HL-60, THP1, and Caco2) were reported.

α-Pyrone derivatives with cytotoxic activities, from the endophytic fungus Phoma sp. YN02-P-3.

Four new α-pyrone derivatives phomones C-F (1-4) together with four known compounds (5-8) were isolated from the endophytic fungus Phoma sp. YN02-P-3. Compound 1 is the first example of 6-α,ß-unsaturated ester-2-pyrone dimers via intermolecular symmetrical [2+2] cycloaddition. The chemical structures of these compounds were determined from spectroscopic data (1D/2D NMR, MS and IR). The acetylated product (9) of 1 along with compounds 1-8 were then tested for their cytotoxicity against HL-60, PC-3 and HCT-116 cell lines. Compounds 2, 3, 5 and 9 with acetyl groups showed significant inhibitory activities against the three cell lines with IC50 values in the range 0.52-9.85µM. while compounds 1, 4 and 6-8 that possess no acetyl group showed no inhibitory activity (IC50>50µM), indicating that the acetyl group at 10- or 12- are essential for their cytotoxic activities. The structure-activity relationships of these phomones were also reported.

A novel 3,4-dihydronaphthalen-1(2H)-one with spiro-butyrolactone and a new isocoumarin isolated from the endophytic fungus Phoma sp. YN02-P-3.

A novel 3,4-dihydronaphthalen-1(2H)-one with spiro-butyrolactone phomol (1) and a new isocoumarin phomasatin (2), together with two known compounds (3-4) were isolated from the solid culture of the endophytic fungus Phoma sp. YN02-P-3. Their structures including the absolute configurations were characterized on the basis of extensive 1D, 2D NMR (HSQC, HMBC, NOESY), MS, and CD spectral data. Compound 1 showed selective cytotoxic activity against HL-60 cell line with the IC50 value of 29.05 µM.