Abstract
Eight new cafestol-type diterpenoids, tricalysins A-H (1-8), along with five known analogues (9-13), were isolated from the twigs of Tricalysia fruticosa. The structures of 1-8 were elucidated by the application of spectroscopic methods. Inhibitory effects of the isolates on nitric oxide (NO) production in lipopolysaccaride-activated RAW 264.7 macrophages were evaluated, and compound 8 exhibited the most potent bioactivity, with an IC50 value of 6.6 ± 0.4 μM. It was shown further that compound 8 inhibits inflammatory responses via suppression of the expression of iNOS and reduction of the production of the pro-inflammatory cytokines IL-6 and TNF-α, resulting from activation of nuclear factor-kappaB (NF-κB) and phosphorylation of MAPKs (ERK, JNK, and p38).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / isolation & purification*
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Anti-Inflammatory Agents / pharmacology*
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Cytokines / metabolism
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Diterpenes / chemistry
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Diterpenes / isolation & purification*
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Diterpenes / pharmacology*
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Drugs, Chinese Herbal / chemistry
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Drugs, Chinese Herbal / isolation & purification*
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Drugs, Chinese Herbal / pharmacology*
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Interleukin-6 / metabolism
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects
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Molecular Structure
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NF-kappa B / antagonists & inhibitors
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type II / antagonists & inhibitors
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Phosphorylation / drug effects
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Plant Stems / chemistry
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Rubiaceae / chemistry*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents
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Cytokines
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Diterpenes
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Drugs, Chinese Herbal
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Interleukin-6
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Lipopolysaccharides
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NF-kappa B
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Tumor Necrosis Factor-alpha
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tricalysin H
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Nitric Oxide
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cafestol
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NOS2 protein, human
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Nitric Oxide Synthase Type II