Ming-Kui Wang

Cytotoxic Phorbol Esters of Croton tiglium

Chemical investigation of the seeds of Croton tiglium afforded eight new phorbol diesters (three phorbol diesters, 1-3, and five 4-deoxy-4α-phorbol diesters, 4-8), together with 11 known phorbol diesters (nine phorbol diesters, 9-17, and two 4-deoxy-4α-phorbol diesters, 18 and 19). The structures of compounds 1-8 were determined by spectroscopic data information and chemical degradation experiments. The cytotoxic activities of the phorbol diesters were evaluated against the SNU387 hepatic tumor cell line, and compound 3 exhibited the most potent activity (IC50 1.2 μM).

Two new triterpenoid saponins from Gymnema sylvestre

Two new oleanane-type triterpenoid saponins, gymnemoside-W1 and W2, together with seven known compounds were isolated from the leaves of Gymnema sylvestre R. Br. By means of spectral and chemical analysis, the structures of the new compounds were elucidated as 16 beta-hydroxyl olean-12-en-3-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl]-28-O-beta-D-glucopyranoside(1) and 16 beta,21 beta,28-trihydroxyl-olean-12-ene-3-O-glucoronopyranoside (2). The EtOH/H(2)O extracts of this plant were shown to be able to inhibit glucose absorption in rats.

Curcusone D, a novel ubiquitin-proteasome pathway inhibitor via ROS-induced DUB inhibition, is synergistic with bortezomib against multiple myeloma cell growth.

BACKGROUND Ubiquitin-proteasome pathway (UPP) plays a very important role in the degradation of proteins. Finding novel UPP inhibitors is a promising strategy for treating multiple myeloma (MM). METHODS Ub-YFP reporter assays were used as cellular UPP models. MM cell growth, apoptosis and overall death were evaluated with the MTS assay, Annexin V/PI dual-staining flow cytometry, poly (ADP-ribose) polymerase (PARP) cleavage, and PI uptake, respectively. The mechanism of UPP inhibition was analyzed by western blotting for ubiquitin, in vitro and cellular proteasomal and deubiquitinases (DUBs) activity assays. Cellular reactive oxygen species (ROS) were measured with H2DCFDA. RESULTS Curcusone D, identified as a novel UPP inhibitor, causes cell growth inhibition and apoptosis in MM cells. Curcusone D induced the accumulation of poly-ubiquitin-conjugated proteins but could not inhibit proteasomal activity in vitro or in cells. Interestingly, the mono-ubiquitin level and the total cellular DUB activity were significantly downregulated following curcusone D treatment. Furthermore, curcusone D could induce ROS, which were closely correlated with DUB inhibition that could be nearly completely reversed by NAC. Finally, curcusone D and the proteasomal inhibitor bortezomib showed a strong synergistic effect against MM cells. CONCLUSIONS Curcusone D is novel UPP inhibitor that acts via the ROS-induced inhibition of DUBs to produce strong growth inhibition and apoptosis of MM cells and synergize with bortezomib. GENERAL SIGNIFICANCE The anti-MM molecular mechanism study of curcusone D will promote combination therapies with different UPP inhibitors against MM and further support the concept of oxidative stress regulating the activity of DUBs.

Cytotoxic Sesquiterpene Lactones from Aerial Parts of Xanthium sibiricum

Chemical investigation of the aerial parts of Xanthium sibiricum led to the isolation of four new xanthanolide-type sesquiterpene lactones, including two xanthanolide dimers, pungiolide D (1) and pungiolide E (2), and two xanthanolide monomers, 8-epi-xanthatin-1α,5α-epoxide (3) and 1β-hydroxyl-5α-chloro-8-epi-xanthatin (4), together with four known compounds, pungiolide A (5), 8-epi-xanthatin-1β,5β-epoxide (6), xanthatin (7), and 11α,13-dihydro-8-epi-xanthatin (8). The structures of these compounds were elucidated on the basis of spectroscopic data analysis. Pungiolide D (1) displayed an unusual structure featuring a 5/5/6-fused tricyclic system in the unit B. Compound 4 was shown to be a rare sesquiterpene lactone containing halogen, and its absolute configuration was determined by X-ray crystallographic analysis. The evaluation of the cytotoxic activities of the isolated new compounds against the SNU387 liver and A-549 lung human cancer cell lines showed that compound 4 possessed significant in vitro cytotoxicity with an IC50 value of 5.1 µM against SNU387 liver cells.

Phenolic antioxidants from Rosa soulieana flowers

Rosa soulieana has been widely used in traditional medicine to treat cardiovascular disorders. In this study, antioxidant activity-guided fractionation and purification of the methanol extract from the flowers of R. soulieana has led to the isolation of nine phenolic antioxidants, which were identified as catechin (1), tiliroside (2), astragalin (3), isoquercitrin (4), nicotiflorin (5), eugenol 4-O-β-d-(6′-O-galloyl) glucoside (6), michehedyosides D (7), citrusin C (8) and strictinin (9), respectively. Among them, compounds 5–9 were reported from the genus Rosa for the first time. All the compounds were also assayed by in vitro ABTS [2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt] radical cation scavenging activity. Among these bioactive isolates (1–9), compounds 1, 6, 7 and 9 exhibited strong scavenging activity in ABTS (SC50 = 10.17, 7.38, 8.60, 4.72 μmol/L, respectively) compared with the positive control l-ascorbic acid (SC50 = 15.97 μmol/L).

Neolignans, lignans and glycoside from the fruits of Melia toosendan

Four new neolignans, meliasendanins A-D (1-4), and a new glycoside, toosenoside A (5), together with ten known ones (6-15), were isolated from a n-BuOH partition of the fruits of Melia toosendan. Their structures were elucidated by analyses of extensive spectroscopic data and comparison of the NMR data with those reported previously. Meliasendanin A (1) was a rare neolignan containing isochroman moiety, and its absolute configuration was determined using a CD spectrum. Toosenoside A (5) was an unusual glycoside with a rare naturally occurring aglycone and its structure was confirmed by X-ray single crystal diffraction analysis. The antioxidant activity of the isolated neolignans and lignans was evaluated by ABTS radical-scavenging assay. Compounds 1 and 13 exhibited strong antioxidant activity, with IC₅₀ values of 62.8 and 45.1 μM, respectively.

Triterpenoid saponins from Berneuxia thebetica

Four triterpenoid saponins were isolated from Berneuxia thibetica. On the basis of chemical and spectroscopic evidence, three new saponins, berneuxia saponins A, B and C, were elucidated as 21-tigloylbarringtogenol C-3 beta-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->3)[bet a- D-glucopyranosyl(1-->2)-beta-D-glucuronopyranoside], 28-tigloylbarringtogenol C-3 beta-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->3)[bet a- D-glucopyranosyl(1-->2)-beta-D-glucuronopyranoside] and 16 alpha-28-dihydroxyolean-12-en-21-one-3-O-alpha-L-rhamnopyranosyl(1 -->2) -beta-D-galactopyranosyl(1-->3)[beta-D-glucopyranosyl(1-->2)-beta-D- glucuronopyranoside]. The known saponin was desacyl jegosaponin.

Isolation and Characterization of New Phenolic Compounds with Estrogen Biosynthesis-Inhibiting and Antioxidation Activities from Broussonetia papyrifera Leaves

Broussonetia papyrifera leaves (BPL) as a traditional Chinese medicine are also used in livestock feed for stimulating reproduction, adipose tissue and muscle development; however, the mechanism of their action is still unknown. Through estrogen biosynthesis-guided fractionation in human ovarian granulosa-like KGN cells, five new phenolic glycosides, broussoside A–E(1–5), along with fifteen known dietary phenolic compounds, were isolated from the n-butanol extract of BPL, and their structures were elucidated on the basis of NMR spectra analysis and chemical evidence. New compounds 3, 4, 5 and the known compounds 9 and 10 were found to potently inhibit estrogen biosynthesis in KGN cells. In addition, compounds 9, 17, 18, and 20 showed strong antioxidant activity against ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) and DPPH (1, 1′-diphenyl -2-picryl-hydrazyl radical) assays. These findings suggest that BPL may improve meat quality through the regulation of estrogen biosynthesis. Furthermore, they may be useful for the discovery of potential aromatase modulators from natural products. Finally, they could be considered as a new source for natural antioxidants.

Discrimination of the seeds of Notopterygium incisum and Notopterygium franchetii by validated HPLC-DAD–ESI-MS method and principal component analysis

A validated HPLC-DAD-ESI-MS method has been developed to simultaneously quantify 12 bioactive compounds in the seeds of Notopterygium incisum Ting ex H.T. Chang and Notopterygium franchetii H. de Boiss whose rhizomes and roots are widely used as traditional Chinese medicine. This method was validated to be sensitive, precise and accurate and was applied to evaluate the difference in the chemical profiles and contents of these analytes in 37 batches of N. incisum and 31 batches of N. franchetii samples collected from different locations. Principal component analysis showed that the two species were separated into two groups obviously. This study established a validated method for identification of the authenticity of the seeds of N. incisum and N. franchetii and supplied effective guidance for artificial cultivation.

Two new triterpene saponins from the aerial parts of Paraquilegia microphylla.

Two new triterpene saponins, paraquinosides A (1) and B (2) were isolated from the aerial parts of Paraquilegia microphylla (Royle) Dromm. et Hutch, a Tibetan ethnic medicine distributed in the Qinghai-Tibet Plateau. On the basis of 1D and 2D NMR evidence, their structure was elucidated as 3-O-alpha-L-rhamnopyranosyl (1-->2)-beta-D-glucopyranosyl-15-dehydroxyl-16-O-methyl-24, 25-deoxy-26-hydroxylshengmanol-26-O-beta-D-glucopyranoside (1) and 3-O-alpha-L-Rhamnopyranosyl (1-->2)-[beta-D-glucopyranosyl(1-->3)]-beta-D-glucopyranosyl-15-dehydroxyl-16-O-methyl-24, 25-deoxy-26-hydroxylshengmanol-26-O-beta-D- glucopyranoside (2), respectively.