Dianpeng Li

Exploring in vitro, in vivo metabolism of mogroside V and distribution of its metabolites in rats by HPLC-ESI-IT-TOF-MSn

Mogroside V, a cucurbitane-type saponin, is not only the major bioactive constituent of traditional Chinese medicine Siraitiae Fructus, but also a widely used sweetener. To clarify its biotransformation process and identify its effective forms in vivo, we studied its metabolism in a human intestinal bacteria incubation system, a rat hepatic 9000g supernatant (S9) incubation system, and rats. Meanwhile, the distribution of mogroside V and its metabolites was also reported firstly. Seventy-seven new metabolites, including 52 oxidation products formed by mono- to tetra- hydroxylation/dehydrogenation, were identified with the aid of HPLC in tandem with ESI ion trap (IT) TOF multistage mass spectrometry (HPLC-ESI-IT-TOF-MS(n)). Specifically, 14 metabolites were identified in human intestinal bacteria incubation system, 4 in hepatic S9 incubation system, 58 in faeces, 29 in urine, 14 in plasma, 34 in heart, 33 in liver, 39 in spleen, 39 in lungs, 42 in kidneys, 45 in stomach, and 51 in small intestine. The metabolic pathways of mogroside V were proposed and the identified metabolic reactions were deglycosylation, hydroxylation, dehydrogenation, isomerization, glucosylation, and methylation. Mogroside V and its metabolites were distributed unevenly in the organs of treated rats. Seven bioactive metabolites of mogroside V were identified, among which mogroside IIE was abundant in heart, liver, spleen and lung, suggesting that it may contribute to the bioactivities of mogroside V. Mogroside V was mainly excreted in urine, whereas its metabolites were mainly excreted in faeces. To our knowledge, this is the first report that a plant constituent can be biotransformed into more than 65 metabolites in vivo. These findings will improve understanding of the in vivo metabolism, distribution, and effective forms of mogroside V and congeneric molecules.

A cytotoxic cardenolide and a saponin from the rhizomes of Tupistra chinensis

A new cardenolide tupichinolide (1) and a new steroidal saponin tupichinin A (2), together with seven known compounds, were isolated from the rhizomes of Tupistra chinensis. Their structures were established using spectroscopic analysis and chemical methods. Compound 1 was the first cardenolide isolated from Tupistra chinensis and exhibited potent cytotoxicity against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480.

New clerodane diterpenoids from the twigs and leaves of Croton euryphyllus

Three new nor-clerodane diterpenoids, crotoeurins A-C (1-3), together with four known ones were isolated from the twigs and leaves of Croton euryphyllus. Among them, crotoeurin A (1) is a new nor-clerodane diterpenoid dimer with a unique cyclobutane ring via a [2+2] cycloaddition. Their structures were elucidated by spectroscopic analyses and the stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis. Compounds 1-3 exhibited neurite outgrowth-promoting activity on NGF-mediated PC12 cells at concentration of 10μM.

Studies on chemical fingerprints of Siraitia grosvenorii fruits (Luo Han Guo) by HPLC

A novel, efficient, and accurate fingerprinting method using high performance liquid chromatography–photodiode array detection has been developed and optimized for the investigation and demonstration of the variance in chemical properties among Siraitia grosvenorii fruits from different origins. The effects of growth stages, cultivated varieties, collection locations, and fruit portions of the herb on chromatographic fingerprints were examined. Eleven compounds were identified on chromatograms by comparing the retention time and UV spectrum of each peak separately with those of external references. The results revealed that chromatographic fingerprints, combining similarity or hierarchical clustering analysis along with reference compounds, could efficiently identify and distinguish S. grosvenorii fruits from different sources, which provided helpful clues for studying the plants’ secondary metabolites and benefitted quality control.

Triterpene hexahydroxydiphenoyl esters and a quinic acid purpurogallin carbonyl ester from the leaves of Castanopsis fissa.

Triterpene hexahydroxydiphenoyl (HHDP) esters have only been isolated from Castanopsis species, and the distribution of these esters in nature is of chemotaxonomical interest. In this study, the chemical constituents of the leaves of Castanopsis fissa were examined in detail to identify and isolate potential HHDP esters. Together with 53 known compounds, 3,4-di-O-galloyl-1-O-purpurogallin carbonyl quinic acid (1) and 3,24-(S)-HHDP-2α,3β,23,24-tetrahydroxytaraxastan-28,20β-olide (2) were isolated and their structures were elucidated by spectroscopic and chemical methods. The polyphenols of the leaves were mainly composed of galloyl quinic acids, triterpenes HHDP esters, ellagitannins and flavonol glycosides. In particular, the isolation yields of 1,3,4-trigalloyl quinic acid and compound 2 were 1.53% and 0.27%, respectively, from the fresh leaves. The presence of lipid soluble HHDP esters of oleanane-type triterpenes as one of the major metabolites is an important chemotaxonomical discovery. Lipase inhibition activities and ORAC values of the major constituents were compared. The triterpene HHDP ester showed moderate lipase inhibition activity and myricitrin gave the largest ORAC value.

Intermetallic compound identification and Kirkendall void formation in eutectic SnIn/Cu solder joint during solid-state aging

Microstructural investigations were performed on the interfacial reactions between eutectic SnIn solder and Cu substrate during reflowing at 433 K and solid-state aging at 373 K. Cu2(In,Sn) was identified as the only intermetallic compound (IMC) at the interface, which consists of two sublayers with different morphology, a fine-grained sublayer at the Cu side and a coarse-grained sublayer at the solder side. During solid-state aging, voids were found between these two Cu2(In,Sn) sublayers but not at the substrate interface, which is also attributed to the Kirkendall effect considering the different diffusion fluxes of Sn or In and Cu atoms in different sublayers.

A new triterpenoid saponin from the root of Croton lachnocarpus Benth.

A new triterpenoid saponin, 3-O-β-d-xylopyranosyl spathodic acid (1), was isolated from the EtOH extract of the root of Croton lachnocarpus Benth., together with four known compounds. These compounds were characterised on the basis of their spectral data and compatible with values in the literature. Compound 1 was the first triterpenoid glucoside isolated from the genus Croton. The known compound myriaboric acid (2) showed cytotoxic activity against human hepatocellular carcinoma SMMC-7721 cell line with an IC50 value of 42.2 μM.

New Pregnane Glycosides from Brucea javanica and Their Antifeedant Activity

Three new pregnane glycosides, 3‐O‐β‐D‐glucopyranosyl‐(1→2)‐α‐L‐arabinopyranosyl‐(20R)‐pregn‐5‐ene‐3β,20‐diol (1), 3‐O‐α‐L‐arabinopyranosyl‐(20R)‐pregn‐5‐ene‐3β,20‐diol‐20‐O‐β‐D‐glucopyranoside (2), 3‐O‐α‐L‐arabinopyranosyl‐(20R)‐pregn‐5‐ene‐3β,20‐diol‐20‐O‐β‐D‐glucopyranosyl‐(1→2)‐β‐D‐glucopyranoside (3) were isolated along with four known compounds, 4–7, from the leaves and stems of Brucea javanica. Their structures were determined by detailed analyses of 1D‐ and 2D‐NMR spectroscopic data. All of the compounds isolated from Brucea javanica were tested for the antifeedant activities against the larva of Pieris rapae. Compounds 1, 3, and 5 showed significant antifeedant activities after 72 h incubation.

Metabolites of Siamenoside I and Their Distributions in Rats

Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MSn) method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo.

A new daphnane diterpenoid from Excoecaria venenata with inhibitory effect on human leukaemia HL-60 cells

A new daphnane diterpenoid, venenatin (1), along with six known compounds, was isolated from the aerial parts of Excoecaria venenata. The structure of 1 was elucidated on the basis of extensive spectroscopic analysis. Compound 1 exhibited growth inhibitory effect on human leukaemia HL-60 cell line with IC50 value of 28.10 μM.