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One new bisabolane-type sesquiterpenoid, together with four known bisabolane-type sesquiterpenoid derivatives and seven phenolics, was isolated from the rhizomes of Curcuma longa. Their structures were elucidated by extensive spectroscopic (IR, HR-ESI-MS, and NMR) data analysis. The possible anti-Alzheimer's disease (AD) activities of the isolated compounds were also evaluated using Caenorhabditis elegans AD pathological model, and 1β-hydroxybisabola-2,10-dien-4-one had the highest possible anti-AD activity.

Two new pregnane glycosides, 2α, 3β-dihydroxy-5α-pregn-16-en-20-one-3-O-{α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-galactopyranoside} (1) and 2α, 3β-dihydroxy-5α-pregn-16-en-20-one-3-O-{β-D-glucopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside}(2), have been isolated along with two known spirostanol saponins from the underground parts of Hosta ventricosa. Their structures were elucidated on the basis of chemical and spectral evidence. The anti-inflammatory activities of these steroidal glycosides were evaluated using a xylene-induced ear edema model. Our results indicated that the compounds exhibited promising anti-inflammatory activities.

This study reports the discovery of a novel sulfonated oxysterol found at high levels in the mitochondria and nuclei of primary rat hepatocytes after overexpression of the gene encoding steroidogenic acute regulatory protein (StarD1). Forty-eight hours after infection of primary rat hepatocytes with recombinant adenovirus encoding StarD1, rates of bile acid synthesis increased by 4-fold. Concurrently, [(14)C]cholesterol metabolites (oxysterols) were increased dramatically in both the mitochondria and nuclei of StarD1-overexpressing cells, but not in culture medium. A water-soluble [(14)C]oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Enzymatic digestion, HPLC, and tandem mass spectrometry analysis identified the water-soluble oxysterol as 5-cholesten-3beta,25-diol 3-sulfonate. Further experiments detected this cholesterol metabolite in the nuclei of normal human liver tissues. Based upon these observations, we hypothesized a new pathway by which cholesterol is metabolized in the mitochondrion.

High performance liquid chromatography with atmospheric pressure ionization (API) mass spectrometry has been essential to a large number of quantitative analytical applications for a variety of compounds. Poor detection sensitivity however is a problem observed for a number of analytes because detection sensitivity can be affected by many factors. The two most critical factors are the chemical and physical properties of the analyte and the composition of the mobile phase. In order to address these critical factors which may lead to poor sensitivity, either the structure of the analyte must be modified or the mobile phase composition optimized. The introduction of permanently charged moieties or readily ionized species may dramatically improve the ionization efficiency for electrospray ionization (ESI), and thus the sensitivity of detection. Detection sensitivity may also be enhanced via introduction of moieties with high proton affinity or electron affinity. Mobile phase component modification is an alternative way to enhance sensitivity by changing the form of the analytes in solution thereby improving ionization efficiency. pH adjustment and adduct formation have been commonly used to optimize detection conditions. The sensitivity of detection for analytes in bio-matrices could also be enhanced by decreasing ion-suppression from the matrix through derivatization or mobile phase addition. In this review, we will discuss detection-oriented derivatization as well as the application of mobile phase additives to enhance the sensitivity of detection in liquid chromatograph/atmospheric ionization/mass spectrometry (LC/API/MS), focusing in particular on the applications involving small molecules in bio-matrices.

Jasmonic acid (JA) is strongly implicated in the long-distance signal transduction cascade increasing nicotine synthesis in the roots of plants after leaf wounding. In order to explore the structural requirements of the inducing signal, we examined jasmonates, mimics, and a biosynthetic precursor for nicotine-inducing activity (NIA). We examine the importance of the keto group on the five-membered ring and the double bond in then-pentenyl chain by comparing the NIA of methyl jasmonate (MJ) with that of cucurbic acid, 1,3-dithiolane-MJ, 1,3-dioxolane-MJ, methyl dihydrojasmonate (DHMJ), 1,3-dioxolane-DHMJ, 1-oxo-indan-4-carboxylic acid ILE-methyl ester, and 1-hydroxyl-indan-4-carboxylic acid ILE-methyl ester. We found that: 1,3-dioxolane MJ, cucurbic acid, and 1,3-dioxolane DHMJ were less active than MJ and that the isoleucine (ILE) conjugates of 1-oxo- and l-hydroxyindanon-4-carboxylic acid had the same NIA as MJ. The activities of these indanon amino acid conjugates may be due to the structural similarity of their keto or hydroxyl groups on the five-membered ring to MJ or to the keto-enolized MJ. These results support the hypothesis that the enolization of the keto group during or prior to its interaction with the putative JA receptor is required for activity. We explore the importance of the esterification of the carboxyl functional group by comparing the NIAs of cucurbic acid and cucurbic acid methyl ester, l-oxo-indan-4-carboxylic acid, 1-oxo-indan-4-carboxylic acid methyl ester, and l-oxo-indan-4-carboxylic acid ILE-methyl ester. In all cases, the esters were more active than the free acids. We compared the NIA of MJ of different epimeric composition (8% and 20% 3R,7S-MJ); 12-oxophytodienoic acid (12-oxo-PDA) methyl ester, an important precursor of JA; and coronatine (a well-known phytotoxin and putative structural mimic of 12-oxo-PDA).We found that: (1) the epimeric composition of MJ did not affect its NIA; (2) 12-oxo-PDA methyl ester had lower NIA than MJ; and (3) coronatine significantly inhibited plant growth but did not increase nicotine biosynthesis. In summary, JA, rather than its biosynthetic precursor, 12-oxo-PDA, is likely the endogenous signal inNicotiana sylvestris, and the keto functional group on the five-membered ring and the double bond in then-pentenyl side chain are crucial components of JA for NIA.

Five new taxane diterpenes were isolated from the leaves and stems of Texus chinensis . Their structures were established as 2-deacetyl-5-decinnamatetaxagifine, taxagifine III, 4-deacetyltaxagifine III, 2α,13α-dihydroxy-9α,10β-diacetoxy-5α-cinnamatetaxa-4(20),11-diene and 10β-hydroxy-2α,9α,13α-triacetoxy-5α-cinnamatetaxa-4(20),11-diene.

The formation of multiple molecular ions, especially due to sodium adduct ion formation, is commonly observed in electrospray mass spectrometry and may make reproducible and sensitive quantitation difficult. The objective of this work was to investigate the underlying mechanism involved in the suppression of multiple molecular ion formation and to improve the sensitivity of detection for the two anti-neoplastic agents paclitaxel and docetaxel. The results showed that alkylamine additives could significantly improve the detection of paclitaxel and docetaxel by suppression of multiple molecular ions through preferential formation of a predominant alkylamine adduct ion. Possible binding sites, binding interactions and binding competition were investigated for the sodium adduct and alkylamine adduct ions using various experimental techniques. The formation of a predominant amine adduct ion may be due to increased surface activity in the droplet. The optimal alkylamine for both analytes was octylamine, which increased peak heights of paclitaxel and docetaxel 4.8 and 3.7-fold (n = 3), respectively. The precision of the signals for the analytes was also improved 5.7-fold. A quantitative assay in plasma for paclitaxel was partially validated for the calibration range 1.0-1000 ng/mL (r = 0.9977) when using 0.05% octylamine as a reconstitution solution additive. The limit of detection (LOD) and limit of quantitation (LOQ) were 0.5 and 0.9 ng/mL, respectively. Acceptable precision, accuracy, specificity and sample stability were demonstrated for this assay. This approach may prove useful for other analytes with similar binding sites.

We examined the effects of inhibitors of the octadecanoid pathway (n-propyl gallate, acetosalicylic acid, salicylhydroxamic acid, methyl salicylate, and antipyrine) on wound- and jasmonate-induced nicotine accumulation and compared the nicotine-inducing ability of exogeneous additions of linolenic acid (18:3) and its methyl ester, linoleic acid (18:2), abscisic acid, traumatic acid, and methyl dihydrojasmonate to the nicotine-inducing ability of exogenous additions of methyl jasmonate (MJ). The first four of these inhibitors significantly reduced wound-induced nicotine accumulation when applied in a lanolin paste to wounded tissues immediately after wounding at concentrations of 89-90µg/plant. When methyl salicylate and propyl gallate were mixed individually with MJ, neither inhibited MJ-induced nicotine synthesis, which suggests that the inhibitors block jasmonate synthesis or release from stored pools and not its effects. Linolenic acid or its methyl ester applied to undamaged plants or damaged plants (to either damaged or undamaged leaves) or to the roots of hydroponically growing plants did not induce nicotine accumulation or increase nicotine accumulation above levels found in damaged plants. Similarly, traumatic acid, linoleic acid, and abscisic acid did not induce nicotine accumulations. Methyl dihydrojasmonate, which is biosynthetically derived from linoleic acid, had 12-56% of the nicotine-inducing acitivity of MJ when added to the roots of hydroponically grown plants. The signal transduction pathway mediating wound-induced nicotine production therefore shares many features of the pathway eliciting wound-induced proteinase inhibitor production but differs in not being regulated at the lipase step in jasmonic acid production and not being responsive to abscisic acid.