Jing-Mei Bao

Selaginpulvilins A-D, new phosphodiesterase-4 inhibitors with an unprecedented skeleton from Selaginella pulvinata.

Selaginpulvilins A-D (1-4), four new phenols with an unprecedented 9,9-diphenyl-1-(phenylethynyl)-9H-fluorene skeleton, together with four known selaginellins (5-8) were isolated from Selaginella pulvinata. Their structures were elucidated by spectroscopic analysis and chemical correlation. The structure of 1 was confirmed by single-crystal X-ray diffraction. Compounds 1-8 exhibited remarkable inhibitory activities (IC50 values in the range of 0.11-5.13 μM) against phosphodiesterase-4 (PDE4), a drug target for the treatment of asthma and chronic obstructive pulmonary disease.

Natural thioredoxin reductase inhibitors from Jatropha integerrima

Nine new diterpenoids, jatrointelones A–I (1–9), including seven lathyranes (1–7) and two jatropholanes (8 and 9), along with 12 known analogues (10–21) were isolated from the trunks of Jatropha integerrima. The structures were elucidated by spectroscopic analysis, and the absolute configurations of 1–7 were determined by combination of single crystal X-ray diffraction, CD analysis (exciton chirality and Rh2(OCOCF3)4-induced methods), and chemical correlations. All of the isolates were screened for inhibitory activity against thioredoxin reductase (TrxR), which is a potential target for cancer chemotherapy with redox balance and antioxidant functions. Compounds 1, 3, 6, 7, and 15–21 exhibited stronger activity than the positive control, curcumin (IC50 = 25.0 μM), in which 17 and 19 represented the most active compounds with IC50 values of 9.4 and 6.8 μM, respectively. The active diterpenoids represent the rare examples of non-aromatic TrxR inhibitors from nature, and a preliminary structure–activity relationship is also proposed.

Natural nitric oxide (NO) inhibitors from Aristolochia mollissima

Six new sesquiterpenoids, aristomollins A–F (1–6), and 24 known analogues (7–30) were isolated from the leaves and stems of Aristolochia mollissima. Their structures were elucidated by spectroscopic analysis, and the absolute configurations of compounds 2–5 were determined by the chemical correlations and quantum chemical ECD calculations. Compound 1 represented an unprecedented 5,6-seco-4,5-cyclohumulane skeleton. All the compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 microglial cells, and compounds 4, 9, 28, and 30 exhibited pronounced inhibition of NO production with IC50 values in the range of 5.7–9.9 μM, being more active than the positive control, quercetin (IC50 = 15.7 μM).

Jatrocurcadiones A and B: two novel diterpenoids with an unusual 10,11-seco-premyrsinane skeleton from Jatropha curcas

Two novel diterpenoids, jatrocurcadiones A (1) and B (2), possessing an unusual 10,11-seco-premyrsinane skeleton were isolated from the twigs of Jatropha curcas. Their structures were determined by combined spectroscopic and chemical methods, and the absolute configurations were elucidated by quantum chemical calculations and Rh2(OCOCF3)4-induced CD analysis. Jatrocurcadione A exhibited more potent inhibitory activity (IC50 = 10.0 μM) than the positive control (curcumin, IC50 = 25.0 μM) against thioredoxin reductase (TrxR), a potential target for cancer chemotherapy with redox balance and antioxidant functions.

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.

New lanostane-type triterpenoids from the fruiting body of Ganoderma hainanense

Five new lanostane-type triterpenoids, ganoderenses A-E (1-5), two new lanostane nor-triterpenoids, ganoderenses F and G (6 and 7), along with 13 known analogues (8-20) were isolated from the fruiting body of Ganoderma hainanense. Their structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds 1 and 13 were confirmed by single crystal X-ray diffraction. All compounds were evaluated for inhibitory activity against thioredoxin reductase (TrxR), a potential target for cancer chemotherapy with redox balance and antioxidant functions, but were inactive.

Aristoyunnolin H attenuates extracellular matrix secretion in cardiac fibroblasts by inhibiting calcium influx

Aristoyunnolin H is a novel aristophyllene sesquiterpenoid isolated from the traditional Chinese medicine Aristolochia yunnanensis Franch. The present research was designed to explore the anti-fibrotic effects of aristoyunnolin H in adult rat cardiac fibroblasts (CFs) stimulated with angiotensin II (Ang II). Western blot analysis data showed that aristoyunnolin H reduced the upregulation of fibronectin (FN), connective tissue growth factor and collagen I(Col I) production induced by Ang II in CFs. By studying the dynamic intracellular changes of Ca2+, we further found that while aristoyunnolin H relieved the calcium influx, it has no effect on intracellular calcium store release. Meanwhile, aristoyunnolin H also inhibited the Ang II-stimulated phosphorylation of Ca2+/calmodulin-dependent protein kinase II. In conclusion, aristoyunnolin H may attenuate extracellular matrix secretion in vitro by inhibiting Ang II-induced calcium signaling.