Anti-inflammatory secondary metabolites from the stems of Millettia dielsiana Harms ex Diels.

A phytochemical investigation for the constituents of the stems of Millettia dielsiana Harms ex Diels resulted in the isolation of a new isoflavone glycoside, mildiside A (1), and 14 known compounds (2-15). Their chemical structures were determined using a combination of IR, NMR, MS, and optical rotation analysis, as well as comparison with the literature data. The ethanolic (EtOH) extract and several isolated compounds exert the inflammatory effect of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells.

Impressic acid from Acanthopanax koreanum, possesses matrix metalloproteinase-13 down-regulating capacity and protects cartilage destruction.

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax koreanum (Araliaceae) has been used in traditional medicine for enhancing vitality, rheumatism, and bone-related pains. But its activity on cartilage protection has not been known yet. AIM OF THE STUDY: Matrix metalloproteinase (MMP)-13 has an important role in degrading cartilage materials under pathologic conditions such as arthritis. The present study was designed to find the inhibitory activity of impressic acid on MMP-13 expression and cartilage protective action. MATERIALS AND METHODS: 70% ethanol extract of Acanthopanax koreanum leaves and impressic acid, a major constituent isolated from the same plant materials, were examined on MMP-13 down-regulating capacity in IL-1ß-treated human chondrocyte cell line (SW1353) and rabbit cartilage explants. RESULTS: In IL-1ß-treated SW1353 cells, impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 0.5-10µM. Impressic acid was found to be able to inhibit MMP-13 expression by blocking the phosphorylation of signal transducer and activator of transcription-1/-2 (STAT-1/-2) and activation of c-Jun and c-Fos among the cellular signaling pathways involved. Further, impressic acid was found to inhibit the expression of MMP-13 mRNA (47.7% inhibition at 10µM), glycosaminoglycan release (42.2% reduction at 10µM) and proteoglycan loss in IL-1-treated rabbit cartilage explants culture. In addition, a total of 21 lupane-type triterpenoids structurally-related to impressic acid were isolated from the same plant materials and their suppressive activities against MMP-13 expression were also examined. Among these derivatives, compounds 2, 3, 16, and 18 clearly down-regulated MMP-13 expression. However, impressic acid was more potent than these derivatives in down-regulating MMP-13 expression. CONCLUSIONS: Impressic acid, its related triterpenoids, and A. koreanum extract have potential as therapeutic agents to prevent cartilage degradation by inhibiting matrix protein degradation.

Identification of six new lupane-type triterpenoids from Acanthopanax koreanum leaves and their tyrosinase inhibitory activities.

Chemical investigation of Acanthopanax koreanum leaves resulted in the isolation of 13 compounds (1-13), including six new (20,29)-dehydrolupane-type triterpenoids: 3α,11α,30-trihydroxylup-20(29)-en-23,28-dioic acid (1), 3α,11α,30-trihydroxylup-20(29)-en-28-oic acid (2), 3α,11α,30-trihydroxylup-23-al-20(29)-en-28-oic acid (3), 3α, 11α-dihydroxy-20-oxo-30-norlupane-23,28-dioic acid (5), (20S)-3α-hydroxy-30 oxolupane-23,28-dioic acid (8), (20S)-3ß,7ß,29-trihydroxy-lupane-23-al-28-oic acid (10), and one novel compound isolated for the first time, named 3α,20α,29-trihydroxylupane-23,28-dioic acid (9), together with six known compounds (4, 6, 7, and 11-13). Chemical structures of the isolated compounds were evaluated by analyzing and comparing spectroscopic data with those reported in the literature. These compounds were also evaluated for their tyrosinase inhibitory effects. Among them, compounds 3, 7, 9, and 12 showed significant inhibitory effects, with inhibitory concentrations of 50% (IC50) values ranging from 8.61 to 63.5 µM.

Two new naphthalene glucosides and other bioactive compounds from the carnivorous plant Nepenthes mirabilis.

Two new naphthalene diglucosides named nepenthosides A (1) and B (2), together with eleven known compounds (3-13), were isolated from the carnivorous plant Nepenthes mirabilis. The structures of these compounds were elucidated based on extensive spectroscopic analysis, including 1D- and 2D-NMR, and MS. The antioxidant activities of compounds 1-13 were evaluated in terms of their peroxyl radical-scavenging (trolox equivalent, TE) and reducing capacities. All isolates showed peroxyl radical-scavenging and reducing activities at concentrations of 1.0 and 10.0 µM. Anti-osteoporotic activities were investigated using murine osteoclastic RAW 264.7 cells. Compounds 1-7 and 9-12 significantly suppressed tartrate-resistant acid phosphatase activity down to 91.13 ± 1.18 to 42.39 ± 1.11%, relative to the control (100%) in nuclear factor-κB ligand (RANκL)-induced osteoclastic RAW 264.7 macrophage cells.

Chemical constituents from Kandelia candel with their inhibitory effects on pro-inflammatory cytokines production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs).

Chemical investigation of Kandelia candel resulted in the isolation of 19 compounds (1-19), including one new sesquiterpene glycoside, kandelside (1), three megastigman glycoside compounds (7-9), 16 known phenolic compounds (2-6 and 10-19). Structures of the isolated compounds were elucidated based on spectral data comparison with reported values. Isolated compounds were also evaluated for their inhibitory effects on the production of pro-inflammatory cytokines interleukin (IL)-12 p40, IL-6, and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among these compounds, compound 9 exhibited strong inhibitory activity against IL-6 production (IC50=0.07 ± 0.05 µM) and moderate inhibitory activity against TNF-α production (IC50=49.86 ± 1.02 µM), but exhibited no activity on IL-12 p40 production. Compounds 5 and 6 significantly inhibited IL-12 p40, IL-6, and TNF-α production with IC50 values of 11.68 ± 0.38, 44.52 ± 1.08, and 28.73 ± 0.96 µM, respectively.

Two novel iridoids from Morinda longifolia.

Six secondary metabolites, including two novel iridoids, longifolides A (1) and B (2), were isolated by various chromatographic methods from a methanol extract of branches and leaves of Morinda longifolia Craib. The structures of the compounds were determined on the basis of NMR spectroscopic (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, NOESY) and FTICR-MS data, as well as by comparison of them with literature values.