Yue-Hu Pei

Trichodermatides A−D, Novel Polyketides from the Marine-Derived Fungus Trichoderma reesei

Four new polyketide derivatives, Trichodermatides A-D (1-4) were isolated from the marine-derived fungus Trichoderma reesei. Trichodermatide A (1) is an unprecedented example of a polyketide with a ketal-containing pentacyclic skeleton. The chemical structures and absolute configurations of compounds 1-4 were elucidated by extensive spectroscopic methods, especially 2D NMR and CD spectral analysis, and supported by their proposed biosynthesis pathway. The cytotoxicity of 1-4 was evaluated against A375-S2 human melanoma cell line.

Peganumine A, a β-Carboline Dimer with a New Octacyclic Scaffold from Peganum harmala

Peganumine A (1), a new dimeric β-carboline alkaloid characterized by a unique 3,9-diazatetracyclo[6.5.2.0(1,9).0(3,8)]pentadec-2-one scaffold, was isolated from the seeds of Peganum harmala. The structure including the absolute configuration was determined by spectroscopic data, X-ray crystallography, ECD calculation, and CD exciton chirality approaches. Compound 1 showed moderate cytotoxic activity against MCF-7, PC-3, and HepG2 cells and selective effects on HL-60 cells with an IC50 value of 5.8 μM.

Anti-inflammatory Diterpenoids from the Roots of Euphorbia ebracteolata

Thirteen diterpenoids (1-13), including two new norditerpene lactones (1-2) and eight new rosane diterpenoids (3-10), were isolated from the roots of Euphorbia ebracteolata. The structures were determined by 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD). The ECD-based empirical rule for α,β-unsaturated-γ-lactones was applied to determine the absolute configurations of 1 and 2. Compounds 7, 10, and 13 exhibited significant inhibition of nitric oxide production in RAW 264.7 lipopolysaccharide-induced macrophages, with IC50 values of 2.44, 2.76, and 1.02 μM, respectively.

Steroidal saponins from Tribulus terrestris.

Five new steroidal saponins were isolated from the fruits of Tribulus terrestris. Their structures were fully established by spectroscopic and chemical analysis as (23S,25S)-5alpha-spirostane-24-one-3beta,23-diol-3-O-{alpha-l-rhamnopyranosyl-(1-->2)-O-[beta-d-glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (1), (24S,25S)-5alpha-spirostane-3beta,24-diol-3-O-{alpha-l-rhamnopyranosyl-(1-->2)-O-[beta-d-glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (2), 26-O-beta-d-glucopyranosyl-(25R)-5alpha-furostan-2alpha,3beta,22alpha,26-tetraol-3-O-{beta-d-glucopyranosyl-(1-->2)-O-beta-d-glucopyranosyl-(1-->4)-beta-d-galactopyranoside} (3), 26-O-beta-d-glucopyranosyl-(25R)-5alpha-furostan-20(22)-en-2alpha,3beta,26-triol-3-O-{beta-d-glucopyranosyl-(1-->2)-O-beta-d-glucopyranosyl-(1-->4)-beta-d-galactopyranoside} (4), and 26-O-beta-d-glucopyranosyl-(25S)-5alpha-furostan-12-one-22-methoxy-3beta,26-diol-3-O-{alpha-l-rhamnopyranosyl-(1-->2)-O-[beta-d-glucopyranosyl-(1-->4)]-beta-d-galactopyranoside} (5). The isolated compounds were evaluated for cytostatic activity against HL-60 cells.

Sg17-1-4, a Novel Isocoumarin from a Marine Fungus Alternaria tenuis Sg17-1

One novel isocoumarin, named Sg17-1-4, along with two known isocoumarins AI-77-B and AI-77-F were obtained from a marine fungus Alternaria tenuis Sg17-1. Their structures were elucidated based on detailed NMR analysis. The cytotoxicities of these compounds were evaluated in vitro.

Steroidal glycosides from the roots of Cynanchum amplexicaule Sieb. et Zucc.

Seven new steroidal glycosides (amplexicosides A (4), B (7), C (8), D (9), E (10), F (11), and G (12)), along with six known compounds (cynatratoside A (1), tylophoside A (2), cynatratoside B (3), glaucogenin A (5), glaucoside A (6), and hancoside A (13)) were isolated from the 95% ethanol extract of the roots of Cynanchum amplexicaule (Sieb. et Zucc.). Their structures were determined based on spectral and chemical evidence. Compound 12 has a 14, 15-secopregnane-type skeleton aglycone, which has not been reported in literature.

Lanostane-Type Triterpenoids from the Roots of Kadsura coccinea

Seven new lanostane-type triterpenoids, seco-coccinic acids A-F (1- 6) and coccinilactone A (7), were isolated from the roots of Kadsura coccinea. Their structures were established on the basis of spectroscopic data analysis. The absolute configuration at C-24 of compound 5 was confirmed by the modified Moshers method. The cell growth inhibitory effects of these compounds were determined in human leukemia HL-60 cells, and it was found that compounds 1, 2, 3, and 5 exhibited antiproliferative effects with GI 50 values ranging from 6.8 to 42.1 microM.

A metabolic profiling analysis of the acute hepatotoxicity and nephrotoxicity of Zhusha Anshen Wan compared with cinnabar in rats using ^1H NMR spectroscopy

ETHNOPHARMACOLOGICAL RELEVANCE Zhusha Anshen Wan (ZSASW), a traditional Chinese medicine (TCM) prescription, composed of cinnabar (cinnabaris), Coptidis Rhizoma (Coptis chinensis French.), Angelicae Sinensis Radix (Angelica sinensis (oliv.) Diels), uncooked Rehmanniae Radix (Rehmannia glutinosa Libosch.), honey fried Glycyrrhizae Radix Et Rhizoma (Glycyrrhiza uralensis Fisch.), has been widely used for sedative therapy. Cinnabar, the chief component of ZSASW, has been proved to possess the toxicities. AIM OF THE STUDY In this study, a metabonomics approach based on high-resolution (1)H nuclear magnetic resonance spectroscopy was applied to investigate the protective effects of ZSASW on the toxic effects induced by cinnabar alone. MATERIALS AND METHODS Male Wistar rats were divided into three groups: control group, ZSASW group and cinnabar group. Partial least squares-discriminant analysis (PLS-DA) was performed to identify different metabolic profiles of urine and serum from rats. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. RESULTS The significant difference in metabolic profiling of urine and serum of the rats was observed between cinnabar treated group, control group, and the changes of endogenous metabolites related to the toxicities were identified. The results were also certified by the liver and kidney histopathology examinations and biochemical analysis of blood. CONCLUSION Our results suggested that the four combined herbal medicines of ZSASW had the effects of protecting from the toxicity induced by cinnabar alone. This work showed that the NMR-based metabonomics approach might be a promising approach to study detoxification of Chinese medicines and reasonable combination of TCM prescriptions.

1H NMR-based metabonomics study on the toxicity alleviation effect of other traditional Chinese medicines in Niuhuang Jiedu tablet to realgar (As2S2)

ETHNOPHARMACOLOGICAL RELEVANCE Niuhuang Jiedu Tablet (NJT) is an effective prescription of traditional Chinese medicine (TCM) used in treating acute tonsillitis, pharyngitis, periodontitis and mouth ulcer. NJT is prepared from Xionghuang (Realgar, As2S2), Rengong Niuhuang (Bovis Calculus Artificialis), Bingpian (Borneolum Synthcticum), Shigao (Gypsum Fibrosum), Dahuang (Rhei Radix et Rhizoma), Huangqin (Scutellariae Radix), Jiegeng (Platycodonis Radix) and Gancao (Glycyrrhizae Radix et Rhizoma). In the prescription, significant level of realgar (As2S2) as a potentially toxic element is contained. AIM OF THE STUDY In this study, (1)H NMR-based metabonomics approach has been used to investigate the toxicity of realgar (As2S2) after being counterbalanced by other TCMs in NJT. MATERIALS AND METHODS Male Wistar rats were divided into five groups: control, group I (treated with Realgar), group II (treated with Realgar, Bovis Calculus Artificialis, Borneolum Synthcticum, Gypsum Fibrosum, Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix and Glycyrrhizae Radix et Rhizoma), group III (treated with Realgar, Bovis Calculus Artificialis, Borneolum Synthcticum and Gypsum Fibrosum) and group IV (treated with Realgar, Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix and Glycyrrhizae Radix et Rhizoma). Based on (1)H-NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. RESULTS PLS-DA scores plots demonstrated that the cluster of group I was separated from that of control rats, while group II was located close to control rats, indicating that metabolic profiles of group II were restored toward those of control rats. The metabolic profiles of group III were similar to those of group I, while the metabolic profiles of group II were almost in line with those of group II. Statistics results were confirmed by the histopathological examination and biochemical assay. CONCLUSION Our results indicated that it was more secure and much less toxic for counterbalanced realgar (As2S2) in NJT. The effective material bases of toxicity alleviation to realgar (As2S2) were Dahuang (Rhei Radix et Rhizoma), Huangqin (Scutellariae Radix), Jiegeng (Platycodonis Radix) and Gancao (Glycyrrhizae Radix et Rhizoma), which regulated energy metabolism, choline metabolism, amino acid metabolism and gut flora disorder affected by realgar (As2S2) exposure.

2,5-diketopiperazines from the marine-derived fungus Aspergillus fumigatus YK-7.

Five new diketopiperazines, prenylcyclotryprostatin B (1), 20‐hydroxycyclotryprostatin B (2), 9‐hydroxyfumitremorgin C (3), 6‐hydroxytryprostatin B (4), and spirogliotoxin (5), were isolated from the marine‐derived fungus Aspergillus fumigatus YK‐7, along with nine known compounds, 6–14. Their structures were elucidated by spectroscopic methods, and their antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC‐3 cell lines were assessed in vitro. Compounds 10, 12, and 13 exhibited significant cell growth‐inhibitory activities against U937 cell line, with the IC50 values of 1.8, 0.2, and 0.5 μM, respectively.