Triterpenoid and Coumarin Isolated from Astilbe grandis with Anti-Inflammatory Effects through Inhibiting the NF-κB Pathway in LPS-Induced RAW264.7 Cells.

The roots of Astilbe grandis, known as "Ma sang gou bang", are used as a Miao traditional medicine with anti-inflammatory and analgesic properties. However, the active components and mechanism of action of this plant remain mostly uncharacterized. The aim of this study was to identify its active components and verify their pharmacological activity. The extract of A. grandis root was separated using various chromatographic methods. As a result, we obtained one novel triterpenoid, named astigranlactone (1), which has an unusual lactone moiety formed between C-7 and C-27. Additionally, a known coumarin compound, 11-O-galloyl bergenin (2) was isolated from this plant. The structures of these two compounds were elucidated by extensive NMR experiments in conjunction with HR-ESI-MS data. To the best of our knowledge, both compounds were isolated from this species for the first time. Moreover, we tested the anti-inflammation effect of the two compounds by establishing a cellular inflammation model induced by LPS in RAW264.7 cells. The effect of different concentrations of these compounds on the activity of RAW264.7 cells was assessed using a CCK8 assay. The levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in the supernatant of each group were evaluated using the Griess method and an enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time PCR (qRT-RCR) were used to measure the levels of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) gene expression. Our findings revealed that these two compounds inhibited the high levels of NO, TNF-α, IL-6, IL-1ß, COX-2, and iNOS (induced by LPS). Mechanistic studies demonstrated that these two compounds reduced the activation of the nuclear transcription factor-B (NF-κB) signaling pathway by inhibiting the phosphorylation of p65. Therefore, our study indicates that compounds 1 and 2 can exert a definite anti-inflammatory effect by inhibiting the NF-κB signaling pathway.

Rubesanolides F and G: Two Novel Lactone-Type Norditerpenoids from Isodon rubescens.

A phytochemical investigation of the leaves of the medicinal plant Isodon rubescens led to the isolation of the two new degraded abietane lactone diterpenoids rubesanolides F (1) and G (2). Their structures were elucidated based on the analyses of the HRESIMS and 1D/2D NMR spectral data, and their absolute configurations were determined by ECD spectrum calculations and X-ray single crystal diffraction methods. Compounds 1 and 2, with a unique γ-lactone subgroup between C-8 and C-20, were found to form a carbonyl carbon at C-13 by removal of the isopropyl group in an abietane diterpene skeleton. Rubesanolide G (2) is a rare case of abietane that possesses a cis-fused configuration between rings B and C. The two isolates were evaluated for their biological activities against two cancer cell lines (A549 and HL60), three fungal strains (Candida alba, Aspergillus niger and Rhizopus nigricans) and three bacterial strains (Escherichia coli, Staphylococcus aureus and Bacillus subtilis).

Two cytotoxic 6,7-seco-spiro-lacton-ent-kauranoids from Isodon rubescens.

The present study was performed to investigate the chemical components of the branches and leaves of Isodon rubescens. Two 6,7-seco-spiro-lacton-ent-kauranoids were obtained. Based on the extensive spectroscopic analyses, their structures were elucidated as 6-epi-11-O-acetylangustifolin (1) and 11-O-acetylangustifolin (2), respectively. The structure of 2 was further comfirmed by X-ray crystallography analysis. MTT method was employed to evaluate their cytotoxity against human lung cancer cell lines A549 and leukemia cell lines K562.

Abietane diterpenoids from Isodon amethystoides and their biological activities.

Seven undescribed abietane diterpenoids [abietamethinols A-G (1-7)] were isolated from the twigs and leaves of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic methods including 2D NMR, and they were further confirmed by X-ray crystallographic data. Lophanic acid was considered as the precursor of 1-7 in the biosynthesis pathway hypothesis. These compounds were evaluated for their cytotoxic, anti-bacterial and anti-AIV (avian influenza virus) activities. Compound 5 showed 42.9% inhibitory activity against the cancer cell line SMMC-7721 at the concentration of 40 µM, 3 and 4 could inhibit the bacterial growth of Streptococcus sobrinus by 55.3% and 63.2% at the concentrations of 148.6 and 141.9 µM, respectively, and 4 was demonstrated with antiviral activity against AIV with the inhibitory effect of 68.4% at 25 µM.

Bioactive icetexane and abietane diterpenes from Isodon phyllopodus.

A new icetexane diterpenoid, 11, 12, 20α-trihydroxyl-7ß-methoxyicetexa-8, 11, 13-triene-19, 10-lactone [Phyllane A (1)], and a new abietane diterpenoid, 7ß, 20-epoxy-3ß, 17-acetoxy-abieta-8, 11, 13-teriene-11, 12-diol [phyllane B (2)], along with two known compounds (3 and 4) were isolated from the methanol (MeOH) extract of twigs and leaves of the folk medicinal Isodon phyllopodus. Their structures were determined by spectroscopic analyses including 2 D NMR spectral data, and further confirmed by X-ray single crystal diffraction. Moreover, the compounds were evaluated for their cytotoxicity and anti-HIV activities, and phyllane A showed anti-HIV activity with an IC50 value of 15.7 µM, but phyllane B was found to be cytotoxic to the A549 host cells with a CC50 value of 108.5 µM.

Isolation, evaluation of bioactivity and structure determination of amethinol A, a prototypic amethane diterpene from Isodon amethystoides bearing a six/five/seven-membered carbon-ring system.

We report the isolation of a novel diterpene, designated as `amethane', from Isodon amethystoides (Lamiaceae). The diterpene [amethinol A; systematic name: (4aR,4bR,7R,10aS)-4b,7-dihydroxy-7-isopropyl-1,1-dimethyl-9-oxododecahydrobenzo[a]azulene-4a(2H)-carboxylic acid], possesses a unique skeleton containing a six/five/seven-membered tricyclic system. Intermolecular O-H...O close contacts were found to the carboxyl, carbonyl and hydroxy groups, connecting molecules into a two-dimensional structure. A possible biosynthetic pathway has been proposed. In addition, the compound was evaluated for its biological activities against different disease targets, and was found to significantly attenuate RORγt-dependent autoimmune responses.