Yao-Haur Kuo

Anti-inflammatory Cembranoids from the Soft Corals Sinularia querciformis and Sinularia granosa

Four new cembranoids, querciformolides A-D (1-4), along with two known cembranoids, 7 and 8, have been isolated from the soft coral Sinularia querciformis. Furthermore, chemical investigation of Sinularia granosa has afforded three new cembranoids, querciformolide B (2) and granosolides A (5) and B (6). The structures of the new metabolites were elucidated on the basis of extensive spectroscopic methods, and that of 2 was further confirmed by X-ray diffraction analysis. The absolute configurations of 1 and 2 were determined by a modified Moshers method. Among these metabolites, 2-6 are rarely found cembranoids possessing a tetrahydrofuran moiety with a 4,7-ether linkage; in addition, 1 is the first epsilon-lactone cembrane found that possesses a tetrahydropyran moiety with a 4,8-ether linkage. None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. However, compounds 3, 7, and 8 significantly inhibited the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.

Five novel norcembranoids from Sinularia leptoclados and S. parva

Abstract Three new norcembrane-based diterpenoids, leptocladolides A ( 1 ), B ( 4 ) and C ( 5 ), along with five known metabolites 6 – 10 , have been isolated from the dichloromethane extract of a Taiwanese soft coral Sinularia leptoclados . Furthermore, a chemical investigation on the dichloromethane extract of S. parva has resulted in the isolation of two new related isomers, 1- epi -leptocladolide A ( 2 ) and 7 E -leptocladolide A ( 3 ), in addition to 1 and 7 . The structures of new metabolites 1 – 5 were elucidated on the basis of extensive spectroscopic analyses and their relative stereochemistries were determined by NOESY experiments. The new metabolites 1 and 3 have been shown to exhibit significant cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.

The hederagenin saponin SMG-1 is a natural FMLP receptor inhibitor that suppresses human neutrophil activation

The pericarp of Sapindus mukorossi Gaertn is traditionally used as an expectorant in Japan, China, and Taiwan. Activated neutrophils produce high concentrations of the superoxide anion (O(2)(-)) and elastase known to be involved in airway mucus hypersecretion. In the present study, the anti-inflammatory functions of hederagenin 3-O-(3,4-O-di-acetyl-alpha-L-arabinopyranoside)-(1-->3)-alpha-l-rhamnopyranosyl-(1-->2)-alpha-l-arabinopyranoside (SMG-1), a saponin isolated from S. mukorossi, and its underlying mechanisms were investigated in human neutrophils. SMG-1 potently and concentration-dependently inhibited O(2)(*-) generation and elastase release in N-Formyl-Met-Leu-Phe (FMLP)-activated human neutrophils. Furthermore, SMG-1 reduced membrane-associated p47(phox) expression in FMLP-induced intact neutrophils, but did not alter subcellular NADPH oxidase activity in reconstituted systems. SMG-1 attenuated FMLP-induced increase of cytosolic calcium concentration and phosphorylation of p38 MAPK, ERK, JNK, and AKT. However, SMG-1 displayed no effect on cellular cAMP levels and activity of adenylate cyclase and phosphodiesterase. Significantly, receptor-binding analysis showed that SMG-1 inhibited FMLP binding to its receptor in a concentration-dependent manner. In contrast, neither phorbol myristate acetate-induced O(2)(*-) generation and MAPKs activation nor thapsigargin-caused calcium mobilization was altered by SMG-1. Taken together, our results demonstrate that SMG-1 is a natural inhibitor of the FMLP receptor, which may have the potential to be developed into a useful new therapeutic agent for treating neutrophilic inflammatory diseases.

Monaphilones A−C, Three New Antiproliferative Azaphilone Derivatives from Monascus purpureus NTU 568

Monascus purpureus NTU 568 was a mutant strain from M. purpureus HM105. The methanol extract of red mold rice fermented by this strain exhibited four major yellow pigment signals on HPLC profile. By repeated chemical chromatography methods, three new azaphilone derivatives, namely, monaphilone A (1), B (2) and C (3), along with the known pigments ankaflavin (4) and monascin (5), were isolated and characterized. Based on spectroscopic analyses, mainly 1D and 2D NMR data, the structures of compounds 1-3 were completely elucidated; in addition, 1-3 were determined to be new azaphilone structures, due to the decrease of carbon monoxide for producing a gamma-lactone ring, compared with other azaphilone derivatives. Biological evaluations showed that monaphilone A (1) and B (2) exhibited an antiproliferative effect against HEp-2 (human laryngeal carcinoma cell line) and WiDr (human colon adenocarcinoma cell line), and none of the five compounds had toxicity to normal human lung cell lines (WI-38 and MRC-5) at 70 muM.

Simplexins A-I, eunicellin-based diterpenoids from the soft coral Klyxum simplex.

Nine new eunicellin-based diterpenoids, simplexins A-I (1-9), were isolated from a Dongsha Atoll soft coral, Klyxum simplex. The structures of these compounds were established by detailed spectroscopic analysis (IR, MS, 1D and 2D NMR) and by comparison with the physical and spectral data of related known compounds. The absolute configuration of 1 was determined by a modified Moshers method. Compounds 1, 4, and 5 were found to be cytotoxic toward a limited panel of cancer cell lines. Compound 5 was shown to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.

Astragalus membranaceus flavonoids (AMF) ameliorate chronic fatigue syndrome induced by food intake restriction plus forced swimming

AIM OF THE STUDY Alteration of immune function may be associated with chronic fatigue syndrome (CFS) and this study reveals the immunoregulatory effect of Astragalus membranaceus flavonoids (AMF). MATERIALS AND METHODS CF rats were induced by food intake restriction plus forced swimming for 6 weeks. RESULTS An atrophied spleen associated with a significantly decreased spleen/body weight ratio and a reduced spleen cells proliferation was found in CF rats when compared with home cage controls. AMF given orally at 20, 50 and 100 mg/kg body weight once a day consecutively for 6 weeks could recover the reduced cell proliferation. A switch to Th1-dominated immune regulation was observed in CF rats as the cultured splenocytes produced more interleukin-2 (IL-2) but less IL-4 when compared with controls. Supplementation with AMF could significantly counteract the aberrant cytokine production and rats received AMF exhibited higher endurance capacity to swim when compared with those without AMF administration. Checking the spectrum signals confirmed that the three major isoflavones contained in AMF were ononin, formononetin, and demethylhomopterocarpin. CONCLUSION Alterations of immune function may be associated with CFS and the tonic effects of AMF against CF may be attributable to balance the abnormal cytokine level by isoflavones.

Triterpenoid saponins from the fruits and galls of Sapindus mukorossi

Six saponins, sapinmusaponin K (1) [hederagenin-3-O-(3-O-acetyl-alpha-L-arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside], sapinmusaponin L (2) [hederagenin-3-O-(4-O-acetyl-alpha-L-arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabino-pyranoside], sapinmusaponin M (3) [hederagenin-3-O-(2,3-O-diacetyl-beta-D-xylopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside], sapinmusaponin N (4) [hederagenin-3-O-(2,4-O-diacetyl-beta-D-xylopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside], sapinmusaponin O (5) [3,7,20(S)-trihydroxydammar-24-ene-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside], and sapinmusaponin P (6) [3,7,20(R)-trihydroxydammar-24-ene-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-d-glucopyranoside], along with seven known saponins (7-13), were isolated from fruits and the galls of Sapindus mukorossi. Their structures were elucidated by 1D and 2D NMR spectroscopic techniques and acid hydrolysis. Biological evaluation indicated that saponins 1-4 and 7-13 showed moderate cytotoxicity against several human tumor cell lines.

Cytotoxic and anti-inflammatory cembranoids from the Dongsha Atoll soft coral Sarcophyton crassocaule.

Five new cembranoids, sarcocrassocolides A-E (1-5), along with three known cembranoids 6-8, have been isolated from a Formosan soft coral Sarcophyton crassocaule. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and the absolute configuration of 1 was determined by a modified Moshers method. Compounds 1-4 exhibited significantly cytotoxic activity against a limited panel of cancer cell lines. Compounds 1-4, 6 and 8 were shown to exert significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells. Compound 6 also significantly inhibited the accumulation of pro-inflammatory COX-2 protein.

Cytotoxic Hexacyclic Triterpene Acids from Euscaphis japonica.

Six hexacyclic triterpene acids (1-6), named euscaphic acids A-F, and eight known triterpene acid compounds (7-14) were isolated from an ethanolic extract of twigs of Euscaphis japonica. Compounds 8 and 10 were isolated for the first time from a natural source. Triterpenes 1-6 possess hexacyclic skeletons with a 13α,27-cyclopropane ring. Structural elucidation of compounds 1-6 was established by spectroscopic methods, especially 2D NMR techniques ((1)H-(1)H COSY, HMQC, HMBC, and NOESY). Compounds 3, 4, and 14 showed significant cytotoxicity against different cancer cell lines [IC50 = 2.54 (NCI-H460), 3.61 (MCF-7), and 3.27 μM (CEM) for 3, 4, and 14, respectively].

Cytotoxic Polyisoprenyl Benzophenonoids from Garcinia subelliptica

Six new polyisoprenyl benzophenonoids, (+/-)-garcinialiptone A (1, 2), garcinialiptone B (3), (-)-cycloxanthochymol (4), garcinialiptone C (5), and garcinialiptone D (6), along with three known compounds, xanthochymol (7), isoxanthochymol (8), and cycloxanthochymol (9), were isolated from the fruits of Garcinia subelliptica. The structures of 1-6 were elucidated by spectroscopic analysis. Biological evaluation showed that all compounds 1-9 exhibited cytotoxic activity against a small panel of human tumor cell lines (A549, DU145, KB, vincristine-resistant KB).