Salviplenoid A from Salvia plebeia attenuates acute lung inflammation via modulating NF-κB and Nrf2 signaling pathways.

Acute lung injury (ALI) involves series of inflammatory pathologies and cause high morbidity. Salviplenoid A (SA) was a new sesquiterpenoid from the traditional inflammatory herb Salvia plebeia. In our previous study, SA exhibited antiinflammatory activity in RAW264.7 cells. However, the extensive effects of SA in human cells and in vivo and the active mechanisms are unclear. Thus, in this study, we sought to access its effects in vitro and in vivo and to investigate its mechanisms. SA was proved to inhibit the induction of proinflammatory cytokines in human cell types, including pulmonary epithelial cells and endothetial cells. It also depressed monocyte adhesion. Moreover, SA potently attenuated the acute lung inflammation in the LPS-induced mouse model shown by down-regulation of proinflammatory mediators, inhibition of polymorphonuclear neutrophil infiltration, and alleviation of related symptoms like alveolar congestion and mucus secretion. Further evaluation confirmed that SA regulated NF-κB pathway by inhibiting the IκB-α phosphorylation. And it markedly mediated Nrf2/HO-1 pathway by activating the Nrf2/HO-1 expression and promoting Nrf2 nuclear translocation. Therefore, SA could attenuate acute lung inflammation via suppressing NF-κB and activating Nrf2, which provide a theoretical basis for the potential application of SA in clinic.

(+)-Isobicyclogermacrenal and spathulenol from Aristolochia yunnanensis alleviate cardiac fibrosis by inhibiting transforming growth factor ß/small mother against decapentaplegic signaling pathway.

Cardiac fibrosis contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. Antifibrotic therapies are likely to be a crucial strategy in curbing many fibrosis-related cardiac diseases. In our previous study, an ethyl acetate extract of a traditional Chinese medicine Aristolochia yunnanensis Franch. was found to have a therapeutic effect on myocardial fibrosis in vitro and in vivo. However, the exact chemicals and their mechanisms responsible for the activity of the crude extract have not been illustrated yet. In the current study, 10 sesquiterpenoids (1-10) were isolated from the active extract, and their antifibrotic effects were systematically evaluated in transforming growth factor ß 1 (TGFß1)-stimulated cardiac fibroblasts and NIH3T3 fibrosis models. (+)-Isobicyclogermacrenal (1) and spathulenol (2) were identified as the main active components, being more potent than the well-known natural antifibrotic agent oxymatrine. Compounds 1 and 2 could inhibit the TGFß1-induced cardiac fibroblasts proliferation and suppress the expression of the fibrosis biomarkers fibronectin and α-smooth muscle actin via down-regulation of their mRNA levels. The mechanism study revealed that 1 and 2 could inhibit the phosphorylation of TGFß type I receptor, leading to the decrease of the phosphorylation levels of downstream Smad2/3, then consequently blocking the nuclear translocation of Smad2/3 in the TGFß/Smad signaling pathway. These findings suggest that 1 and 2 may serve as promising natural leads for the development of anticardiac fibrosis drugs.

Anti-inflammatory sesquiterpenoids from the Traditional Chinese Medicine Salvia plebeia: Regulates pro-inflammatory mediators through inhibition of NF-κB and Erk1/2 signaling pathways in LPS-induced Raw264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia plebeia R. Brown, a traditional Chinese medicinal herb, has been used to treat inflammatory diseases such as cough, hepatitis, and diarrhea for a long history. AIM OF THE STUDY: The aim of the present study was to isolate and identify potential anti-inflammatory agents from the herb of S. plebeia, which may have contributed to its folk pharmacological use in the treatment of inflammatory diseases. MATERIAL AND METHODS: The aerial parts of S. plebeia were extracted with 95% ethanol and separated by silica gel, RP-C18, Sephadex LH-20, and HPLC. The structures of the isolated compounds were elucidated by extensive spectroscopic analysis (MS, NMR, and X-ray). Anti-inflammatory activities of all compounds were evaluated by the model of LPS-induced up-regulated of NO in Raw264.7 macrophages. The expression levels of cytokine (TNF-α) and proteins (iNOS and COX-2) were assessed by ELISA kit and Western blotting analysis, respectively. Furthermore, the influences of salviplenoid A (1) on NF-κB and MAPK signaling pathways were determined by Western blotting analysis and immunofluorescence assay. RESULTS: Six new (1-6, salviplenoids A-F) and ten known (7-16) sesquiterpenoids were isolated from the herb of S. plebeia. The absolute configurations of compounds 1, 2, and 7 were determined by X-ray diffraction. The new eudesmane-type sesquiterpenoid, salviplenoid A (1), significantly decreased the release of NO and TNF-α and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-κB dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of IκB and Erk1/2. CONCLUSIONS: Among all sesquiterpenoids isolated from S. plebeian, the new salviplenoid A (1) exhibited the most potent anti-inflammatory activity in LPS-induced Raw264.7 cells via inhibition of NF-κB and Erk1/2 signaling pathways.

A new bisabolane sesquiterpenoid and a new abietane diterpenoid from Cephalotaxus sinensis.

Phytochemical investigation of Cephalotaxus sinensis has led to the isolation of a new bisabolane sesquiterpenoid (1), a new abietane diterpenoid (2), and 13 known compounds (3-15). Their structures were elucidated by extensive spectroscopic analysis (MS, UV, IR, and NMR).

Bioactive diterpenoids from Croton laevigatus.

Eight previously undescribed diterpenoids, crolaevinoids A-H, including two halimanes, four clerodanes, and two laevinanes, along with six known analogues were isolated from the twigs of Croton laevigatus. The structures of the previously undescribed were elucidated by spectroscopic analysis, and their absolute configurations were determined by combination of a single crystal X-ray diffraction and CD analysis (exciton chirality and Rh2(OCOCF3)4-induced methods). Crolaevinoids A and B represent the first halimane diterpenoids with a unique lactone bridge between C-12 and C-17. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. Furocrotinsulolide A and 3,4,15,16-diepoxy-cleroda-13(16),14-diene-12,17-olide exhibited pronounced inhibition of NO production with IC50 values of 10.4 ± 0.8 and 6.0 ± 1.0 µM, respectively, being more potent than the positive control, quercetin (IC50 = 13.1 ± 1.9 µM).

Biscembranoids and Cembranoids from the Soft Coral Sarcophyton elegans.

Two novel biscembranoids, sarelengans A and B (1 and 2), five new cembranoids, sarelengans C-G (3-7), along with two known cembranoids (8 and 9) were isolated from the South China Sea soft coral Sarcophyton elegans. Their structures were determined by spectroscopic and chemical methods, and those of 1, 4, 5, and 6 were confirmed by single crystal X-ray diffraction. Compounds 1 and 2 represent the first example of biscembranoids featuring a trans-fused A/B-ring conjunction between the two cembranoid units. Their unique structures may shed light on an unusual biosynthetic pathway involving a cembranoid-∆8 rather than the normal cembranoid-∆¹ unit in the endo-Diels-Alder cycloaddition. Compounds 2 and 3 exhibited potential inhibitory effects on nitric oxide production in RAW 264.7 macrophages, with IC50 values being at 18.2 and 32.5 µM, respectively.

A Novel Heterodimer from Crotalaria ferruginea.

A new compound was isolated from the traditional Chinese folk herb Crotalaria ferruginea. The structure of the new compound was identified as (±)-crotaferruphenol (1) based on analyses of its spectroscopic data including NMR, MS, and specific rotation values. (±)-Crotaferruphenol was a novel heterodimer characteristic of a unique spiroketal moiety, which was produced by the condensation reaction of a chromanone and a 2-isopropenybenzofuran. (±)-Crotaferruphenol exhibited inhibitory activity (IC50 = 6.57 µM.) against phosphodiesterase-4 (PDE4), a drug target for the treatment of chronic obstructive pulmonary disease and asthma.

New Cembrane-Type Diterpenoids from the South China Sea Soft Coral Sarcophyton ehrenbergi.

Chemical investigation on the soft coral Sarcophyton ehrenbergi collected from the Xisha Islands of the South China Sea have led to the isolation of eight cembranoids including five new ones, sarcophytonoxides A-E (1-5). The structures of new cembranoids (1-5) were determined by spectroscopic analysis and comparison of the NMR data with those of related analogues. The cytotoxicities of compounds 1-8 against human ovarian cancer cell line A2780 were also evaluated.

Tunable bi-functional photonic device based on one-dimensional photonic crystal infiltrated with a bistable liquid-crystal layer.

We investigated the optical properties of a one-dimensional photonic crystal infiltrated with a bistable chiral tilted homeotropic nematic liquid crystal as the central defect layer. By modulating the nematic director orientation with applied voltage, the electrical tunability of the defect modes was observed in the transmission spectrum. The composite not only is a general tunable device but also involves the green concept in that it can operate in two stable states at 0 V. Under the parallel-polarizer scheme, the spectral characteristics suggest a potential application for this device as an energy-efficient multichannel optical switch.