Study on coumarins and alkaloids from stems of Clausena lenis / 中草药

Objective: To study the coumarins and alkaloids from the stems of Clausena lenis. Methods: The chemical constituents from the stems of C. lenis were separated and purified by silica gel, ODS, Sephadex LH-20 gel column chromatographies and preparative HPLC. Their structures were identified by physicochemical properties, spectroscopic analysis, as well as the comparisons with the data reported in literatures. Results: A total of 18 compounds were isolated from the 90% ethanol extract of the stems of C. lenis, which were identified as 6,8-diprenylumbelliferone (1), byakangelicin (2), tert-O-methylheraclenol (3), pabularinone (4), isogosferol (5), heraclenol (6), imperatorin (7), decursinol (8), xanthyletin (9), marmesin (10), skimmianine (11), kokusaginine (12), N-metilatanina (13), clausine Z (14), murrayanine (15), 2-methoxy-1-(3-methyl-buten-1-yl)-9H-carbazole-3-carbaldehyde (16), claulansine I (17) and clausehainanine A (18). Among them, compounds 1-10 were coumarins and 11-18 were alkaloids. Conclusion: All compounds are isolated from C. lenis for the first time, compounds 2, 3 and 8 are separated from the genus Clausena for the first time.

Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

Potentiation of decursinol angelate on pentobarbital-induced sleeping behaviors via the activation of GABA(A)-ergic systems in rodents

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of GABA(A)-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and 0.1 µg/ml) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase (GAD(65/67)) and GABA(A) receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of GABA(A)-ergic systems, and can be useful in the treatment of insomnia.

Chemical constituents from roots of Ficus auriculata / 中草药

Objective: To study the chemical constituents from the roots of Ficus auriculata. Methods: The chemical constituents were isolated and purified by various chromatographic methods, including silica gel, ODS, Sephadex LH-20 columns, and recrystallization. Structures of the isolated compounds were elucidated based on NMR and ESI-MS data, as well as physicochemical properties. Results: Thirteen compounds were obtained in the EtOAc fraction of ethanol extract from the roots of F. auriculata and identified as β-sitosterol (1), α-amyrin (2), 6β-hydroxystigmast-4-en-3one (3), stigmasta-3, 6-dione (4), (22E, 24S)-24-methyl-5α- choleata-7, 22-diene-3β, 5, 6β-triol (5), 3-(1-hydroxyethyl)-7-hydroxy-1-isobenzofuranone (6), (R)-(+)-de-O-methyllasiodiplodin (7), decursinol (8), (-)-3, 5-dimethyl-8-methoxy-3, 4-dihydroisocoumarin (9), (R)-(-)-mellein methyl ether (10), 5-formyl-8-hydroxy-3, 4-dihydroisocoumarin (11), (R)-(-)-5-methoxycarbonyl mellein (12), and β-daucosterol (13). Conclusion: All the compounds except compound 1 are firstly isolated from F. auriculata, and compounds 4-12 are found in the plants of Ficus Linn. for the first time.

Protective Effect of Decursinol on Mouse Models of Sepsis: Enhancement of Interleukin-10

The effects of decursinol on various models of sepsis were investigated. Intra-peritoneal pretreatment of mice with various doses of decursinol (1~100 mg/kg) effectively suppressed lethality induced in three mouse models of experimental sepsis, i.e., lipopolysaccharide (LPS)/D-galactosamine (GalN), high-dose LPS (20 mg/kg), and cecal ligation and puncture (CLP). Intra-peritoneal pretreatment of mice with decursinol (50 mg/kg) markedly enhanced the LPS/GalN-induced increase of plasma interleukin-10 (IL-10) levels, without affecting plasma TNF-alpha, IL-6 and IL-12 levels. These results suggest that decursinol could be effective for prevention or treatment of sepsis.