ligustilide and falcarindiol

Recently, the resources of medicinal plants have been exhausting. The root of Angelica acutiloba is one of the most important ingredients in Japanese Kampo medicine for the treatment of gynecological diseases. In our search for alternative medicinal plant resources of the root of A. acutiloba, we found that its aerial part has the anti-inflammatory potency as well as the root. Phytochemical investigation of the aerial part resulted in the isolation of four compounds including a new dimeric phthalide, namely tokiaerialide (2), along with Z-ligustilide (1), falcarindiol (3), and bergaptol (4). Next, we investigated the in vitro anti-inflammatory activity of 1-4 in lipopolysaccharide-stimulated RAW264 macrophages. Among the isolated compounds, 1 exhibited the most potent inhibition against lipopolysaccharide-induced production of prostaglandin E2 , nitric oxide, and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Compounds 3 and 4 also inhibited all inflammatory mediators, but their inhibitory abilities were weaker than those of 1. Furthermore, 1, 3, and 4 strongly also induced heme oxygenase-1. These results suggest that 1, 3, and 4 potentially exert anti-inflammatory activity, and the aerial part of A. acutiloba may be considered to be a useful medicinal resource for inflammatory diseases.

Topics: 4-Butyrolactone; Angelica; Animals; Anti-Inflammatory Agents; Benzofurans; Dinoprostone; Diynes; Fatty Alcohols; Furocoumarins; Heme Oxygenase-1; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; Molecular Structure; Nitric Oxide; Phytochemicals; Plant Components, Aerial; Plant Extracts; Plant Roots; Plants, Medicinal; RAW 264.7 Cells; Tumor Necrosis Factor-alpha

The n-hexane extract of Lovage root was found to significantly inhibit the growth of both Mycobacterium smegmatis mc²155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, α-prethapsenol, falcarindiol, levistolide A, psoralen and bergapten were isolated by chromatographic techniques, characterized by NMR spectroscopy and MS, and evaluated for their growth inhibition activity against Mycobacterium tuberculosis H₃₇Rv using the whole-cell phenotypic spot culture growth inhibition assay (SPOTi). Cytotoxicity against RAW 264.7 murine macrophage cells was employed for assessing their degree of selectivity. Falcarindiol was the most potent compound with a minimum inhibitory concentration (MIC) value of 20 mg/L against the virulent H₃₇Rv strain; however, it was found to be cytotoxic with a half-growth inhibitory concentration (GIC₅₀) in the same order of magnitude (SI < 1). Interestingly the sesquiterpene alcohol α-prethapsenol was found to inhibit the growth of the pathogenic mycobacteria with an MIC value of 60 mg/L, being more specific towards mycobacteria than mammalian cells (SI ~ 2). Colony forming unit analysis at different concentrations of this phytochemical showed mycobacteriostatic mode of action.

Topics: 4-Butyrolactone; Animals; Antibiotics, Antitubercular; Cytotoxins; Diynes; Fatty Alcohols; Furocoumarins; Ligusticum; Macrophages; Mice; Mycobacterium bovis; Mycobacterium smegmatis; Mycobacterium tuberculosis; Phytotherapy; Plant Extracts; Plant Roots; Sesquiterpenes

A valid chromatographic fingerprint method using liquid chromatography-diode array detection-atmospheric pressure chemical ionization mass spectrometry in negative mode (LC-DAD-APCI-MS) is proposed for studying the absorption and metabolites of a traditional Chinese medicine (TCM) Angelica sinensis (danggui) in rabbit plasma, after the rabbit is administered with danggui oral solution (DOS). More than thirty-two common components were detected in both DOS and rabbit plasma, which shows that the components in the DOS were absorbed into the body of the rabbit. Of these, senkyunolide I, senkyunolide H, Z-6,7-epoxyligustilide, 3-butylidene-7-hydroxyphthalide, Z-ligustilide, Z-butylidenephthalide, Diels-Alder dimers of ligustilide, linolenic acid, linoleic acid and falcarindiol were tentatively identified from their MS, UV spectra and retention behavior by comparing the results with the published literature. At least ten components were found in rabbit plasma but not in DOS, indicating that these components must be metabolites of some of the components in the original extract. The results prove that the proposed method can be used to rapidly analyze multiple constituents in TCMs, and to screen for bioactive compounds by comparing and contrasting the chromatographic fingerprints of DOS and plasma samples.

Topics: 4-Butyrolactone; Absorption; Administration, Oral; Aldehydes; alpha-Linolenic Acid; Angelica sinensis; Animals; Benzofurans; Diynes; Drugs, Chinese Herbal; Fatty Alcohols; Linoleic Acid; Mass Spectrometry; Phthalic Anhydrides; Plant Extracts; Rabbits