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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.

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 β 1 (TGFβ1)-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 TGFβ1-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 TGFβ 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 TGFβ/Smad signaling pathway. These findings suggest that 1 and 2 may serve as promising natural leads for the development of anticardiac fibrosis drugs.

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.

Norhypersampsone A ( 1 ), a novel degraded polycyclic polyprenylated acylphloroglucinol (PPAP) derivative, 3-(2-hydroxy-7-methyl-3-methyleneoct-6-enyl)-5-isoprenyl-2,4,6-trihydroxybenzophenone ( 2 ), a new polyprenylated benzophenone derivative, and nine known compounds ( 3 – 11 ) were isolated from Hypericum sampsonii . Their structures were elucidated by comprehensive spectroscopic techniques. Compound 1 represents a novel cyclohexenone monocyclic-PPAP formed by losing the fragment of C-2–C-4 and the side chains at C-3 and C-5 in the phloroglucinol ring. The results of the inhibitory effects of compounds 1 – 11 on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages showed that compounds 1 , 6 – 8 , and 10 exhibited weak activities with IC 50 values in the range of 20.3–37.1 μM.

One new halimane diterpenoid, marrubasch C (1), two new labdane diterpenoids, marrubaschs D and E (2 and 3), and three known labdane diterpenoids, marrubasch F (4), marrubiin (5), and marrubenol (6), were isolated from the ethanol extract of Marrubium aschersonii Magnus (Lamiaceae). Structures of these compounds were elucidated on the basis of spectroscopic analysis. The inhibitory effects of compounds 1–6 on nitric oxide (NO) production in RAW 264.7 macrophage cells activated by lipopolysaccharide (LPS) were investigated and all the compounds showed weak activity.

Chemical investigation of the aerial parts of Hypericum sampsonii led to the isolation of seven new polycyclic polyprenylated acylphloroglucinols, hypersampsonones A–G (1–7), together with 23 known analogs (8–30). Their structures including the absolute configurations were elucidated by combined spectroscopic analysis, quantum chemical ECD calculations, and chemical methods. Compound 1 represents an unprecedented cyclocitral monoterpene-coupled bicyclo[3.3.1]nonane skeleton, while 2 features an unusual hexahydrofuro[2,3-b]furan-diepoxy ring system fused in a tricyclo[4.3.1.15,7]undecane skeleton. All the compounds were screened by using tritium-labeled adenosine 3′,5′-cyclic monophosphate ([3H]-cAMP) as substrate for their inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 1, 18–19, 21, and 25–30 exhibited inhibition with IC50 values less than 10 μM, in which compound 19 represented the most active compound (IC50 = 0.64 μM), being comparable to the positive control, rolipram (IC50 = 0.62 μM).

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).

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.