Secondary metabolites of the endophytic fungus Aspergillus sp.Dq-25 from barnacle / 中国药科大学学报

@#The chemical constituents of solid rice culture of the endophytic fungus Aspergillus sp.Dq-25 from barnacle were isolated and purified by silica gel, Sephadex LH-20, C18 reversed silica gel column chromatography and recrystallization.Their structures were identified by the physical and chemical properties, and by various spectroscopic methods.Six compounds were isolated and identified as: demethyldihydropenicillic acid (1), dihydropenicillic acid (2), penicillic acid (3), fortisterol (4), 22E, 24R-3P, 5a-dihydroxyerogosta-7, 22-diene-6-one (5), and (22E, 24R)-ergosterol-7, 22-diene-3β, 5α, 9α-triol-6-one (6).Compound 1 was a new butyrolactone.MTT method was used to analyze cytotoxicity, and the result showed that compound 3 exhibited inhibitory activity on five cell lines, including K562, HeLa, SGC-7901, A542 and BEL-7402, with IC50 values of 38.0 ~ 105.0 μmol/L.

Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.

Detection of Exogenous γ-Hydroxybutyric Acid in Rat Blood Exosomes / 法医学杂志

OBJECTIVES@#To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood.@*METHODS@#Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected.@*RESULTS@#The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively.@*CONCLUSIONS@#GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.

A new γ-alkylated-γ-butyrolactone from the roots of Solanum melongena / 中国天然药物

A new γ-alkylated-γ-butyrolactone, named melongenolide A (1), along with nine known compounds were obtained from the roots of Solanum melongena, and their structures were identified as melongenolide A (1), (+)-syringaresinol (2), (+)-lyoniresinol (3), 5,5'-dimethoxy lariciresinol (4), (+)-(7R,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7, 9-diol-7'-aldehyde (5), kaempferol-3-O-(2″,6″-di-O-p-trans-coumaroyl)-β-glucoside (6), arjunolic acid (7), vanillic acid (8), scoparone (9), and β-sitosterol (10). Compounds 2, 6, and 7 showed potent inhibitory effects on nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophages, with IC50 values being 5.62 ± 0.86, 11.47 ± 0.98, and 27.75 ± 1.26 μmol·L(-1), respectively.

Quantification of α-methylene-λ-butyrolactone extracted from different parts ofAlstroemeria wilhelmina and evaluation of it's antigenicity using the guinea-pig maximization test

To detect the type of contact dermatitis caused due to the handling ofAlstroemeria wilhelmina, 1% α-methylene-λ-butyrolactone (α-MBL) dissolved in physiological alien and a five-fold diluted saline solution of original extracts of flowers, leaves and stems of the flower were applied to guinea-pigs for extracts were applied to the animals as the challenge treatment in compliance with the guinea-pig maximization test (GMT). As a consequence, not only primary irritant dermatitis was observed, but also delayed type allergic contact dermatitis due toAlstroemeria wilhelmina was observed. α-MBL determined in the extracts using high-performance liquid chromatography (HPLC) was found to be the biochemical material cause of the contact dermatitis. the flower region contained α-MBL in the highest concentrations compared with those of the leaves and stems. Therefore, the quantification of α-MBL in the extracts was concluded as being a useful evaluating method for contact dermatitis due to the handling ofAlstroemeria.

Quantification of $\alpha$-Methylene-$\gamma$-butyrolactone Extracted from Different Parts of \it{Alstroemeria wilhelmina} and Evaluation of it's Antigenicity Using the Guinea-Pig Maximization Test

To detect the type of contact dermatitis caused due to the handling of Alstroemeria wilhelmina, 1% α-methylene-γ-butyrolactone (α-MBL) dissolved in physiological saline and a five-fold diluted saline solution of original extracts of flowers, leaves and stems of the flower were applied to guinea-pigs for induction treatment, and 0.1% α-MBL physiological saline and a ten-fold diluted solution of the original extracts were applied to the animals as the challenge treatment in compliance with the guinea-pig maximization test (GMT). As a consequence, not only primary irritant dermatitis was observed, but also delayed type allergic contact dermatitis due to Alstroemeria wilhelmina was observed. α-MBL determined in the extracts using high-performance liquid chromatography (HPLC) was found to be the biochemical material cause of the contact dermatitis. The flower region contained α-MBL in the highest concentrations compared with those of the leaves and stems. Therefore, the quantification of α-MBL in the extracts was concluded as being a useful evaluating method for contact dermatitis due to the handling of Alstroemeria.