Anti-tumor and anti-inflammatory properties of ankaflavin and monaphilone A from monascus purpureus NTU 568

An azaphilonidal derivative monaphilone A (MA) was recently isolated from the fermented products of Monascus purpureus NTU 568 by our laboratory. We report here the exploration of apoptosis-related and anti-inflammatory properties of MA and ankaflavin (AK) by some experiments about inducing death of human laryngeal carcinoma cell line HEp-2 and reducing inflammatory responses on murine macrophage RAW 264.7 cells. We employed a ssDNA enzyme-linked immunosorbent assay (ELISA) kit to investigate the nuclear changes of early apoptosis induced by AK and MA on HEp-2 cells and used a western blot and an enzyme activity assay to demonstrate the activation of caspase-3, caspase-8, and caspase-9 by MA and AK. Our studies revealed that AK and MA may decrease lipopolysaccharide (LPS)-induced inflammatory responses, including nitrite productions and expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in RAW 264.7 cells. All evidence support that azaphilonidal derivatives from M. purpureus NTU 568, such as AK and MA, are suitable for the development of chemotherapy or chemopreventive agents.     

Ginger suppresses phthalate ester-induced airway remodeling

This study has two novel findings: it is not only the first to demonstrate inflammatory cytokines, which are produced by the bronchial epithelium after exposure to phthalate esters and contribute to airway remodeling by increasing human bronchial smooth muscle cells (BSMC) migration and proliferation, but it is also the first to reveal that ginger reverses phthalate ester-mediated airway remodeling. Human bronchial epithelial cell lines BEAS-2B and HBE135-E6E7 (HBE) were treated with butylbenzyl phthalate (BBP), bis(2-ethylhexyl) phthalate (BEHP), dibutyl phthalate (DBP), and diethyl phthalate (DEP), and the conditioned medium (CM) was harvested and then added to BSMC. Cultures of BSMC with BBP-, BEHP-, DBP-, and DEP-BEAS-2B-CM and DEP-HBE-CM increased BSMC proliferation and migration, which are major features in asthma remodeling. Exposure of BEAS-2B and HBE to DBP caused epithelial cells to produce inflammatory cytokines IL-8 and RANTES, which subsequently induced BSMC proliferation and migration. Depleting both IL-8 and RANTES completely reversed the effect of DBP-BEAS-2B-CM and DBP-HBE-CM-mediated BSMC proliferation and migration, suggesting this effect is a synergistic influence of IL-8 and RANTES. Moreover, [6]-shogaol, [6]-gingerol, [8]-gingerol, and [10]-gingerol, which are major bioactive compounds present in Zingiber officinale , suppress phthalate ester-mediated airway remodeling. This study suggests that ginger is capable of preventing phthalate ester-associated asthma.     

Phytoestrogenic compounds in alfalfa sprout (Medicago sativa) beyond coumestrol

Coumestrol has long been known as the phytoestrogenic compound in alfalfa. However, it has been demonstrated that the ethyl acetate extract of alfalfa sprout (AEA) attenuated the disease severity and increased survival and life span of autoimmune-prone MRL-lpr/lpr mice. Coumestrol, on the contrary, decreased the survival. This study thus aimed to isolate and identify phytoestrogenic compounds other than coumestrol in AEA. AEA was fractionated and separated by successive silica gel chromatography and preparative HPLC. The activity of collected fractions was tracked by a transactivation assay for ERα and ERβ, respectively. In addition to coumestrol, liquiritigenin, isoliquiritigenin, loliolide, and (4S,6S)- and (4R,6S)-4-hydroxy-6-pentadecyltetrahydropyr-2-one were isolated and chemically identified. Except for loliolide, these compounds showed higher transactivation via ERβ than via ERα. The maximal activation via ERα of coumestrol reached 80% that of 1 nM 17β-estradiol (E(2)), whereas the activations of the remaining five compounds as well as AEA ranged from 8 to 49%. In addition, isoliquiritigenin, loliolide, and (4S,6S)- and (4R,6S)-4-hydroxy-6-pentadecyltetrahydropyr-2-one, but not coumestrol, preferentially inhibited 1 nM E(2) induced ERα activation, compared to that ERβ activation. The selectivity of these phytoestrogens might account for the difference between the effects of AEA and coumestrol in autoimmune-prone MRL-lpr/lpr mice observed previously.     

Dermatophytic pseudomycetomas in four cats

The aim of this retrospective study was to describe the clinical characteristics and treatment of four cats with dermatophytic pseudomycetoma. Four Persian cats, one female and three males, with age ranging from 1.4 to 5 years, were diagnosed with dermatophytic pseudomycetoma by histological examination and fungal culture. Wood's lamp examination revealed positive fluorescence of hairs in all four cats. Characteristic skin lesions consisted of multifocal, raised, firm and nodular to dome-shaped lesions varying in size from 1 to 8 cm in diameter, with ulcers or fistulas in some of the lesions. One cat was treated and cured with 3 months of oral itraconazole; lesions completely regressed, and at the time of writing there has been no recurrence. One cat was treated with surgical excision alone, and recurrence of lesions occurred after a disease-free interval of 15 months. Two cats were treated with surgical excision and systemic itraconazole therapy. Itraconazole therapy was started 1-2 months before surgery and continued for 3 months after surgery. Surgical margins were wide in both cats, and underlying adipose tissue and/or deeper fascia was removed. One cat relapsed, but had a disease-free interval of 18 months. The other cat has been disease free for 32 months. This case series suggests that aggressive, wide surgical excision and concurrent oral itraconazole are highly beneficial in treating dermatophytic pseudomycetoma in cats.     

Coexposure of dioxin-like polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins and dibenzofurans in free-range hens and implications derived from congener profile analysis

The consumption of free-range eggs is becoming more popular worldwide. We analyzed the levels of 12 dioxin-like polychlorinated biphenyls (dl-PCBs) and their congener profiles from 6 free-range and 12 caged egg samples. The mean levels of dl-PCBs in the free-range samples were 5.4 times higher than those in caged eggs. All egg samples exhibited at least two characteristic dl-PCB congener patterns, which reflected distinctive contamination sources. Additionally, for the first time, we demonstrated that the dl-PCB levels in the free-range eggs were highly correlated with elevated levels of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) (r = 0.986; p < 0.001), indicating a coexposure scenario in free-range hens. Cluster analysis of congener patterns implied that this coexposure scenario could be attributed to distinct dl-PCB and PCDD/F sources. This congener profile information provides insights from a different perspective for further identifying potential dl-PCB and PCDD/F sources in the polluted free-range eggs.     

Ankaflavin and monascin regulate endothelial adhesion molecules and endothelial NO synthase (eNOS) expression induced by tumor necrosis factor-α (TNF-α) in human umbilical vein endothelial cells (HUVECs)

Previous studies have established that red mold rice can regulate blood pressure in spontaneously hypertensive rats (SHR) and that Monascus -fermented products, including monacolin K, ankaflavin (AF), and monascin (MS), can inhibit expression of adhesion factors such as E-selectin and endothelin-1 to prevent human acute monocytic leukemia cell line THP-1 monocytes from adhering to human aortic endothelial cells. However, it remains unknown whether AF and MS act directly on human umbilical endothelial cells (HUVECs) to enhance nitric oxide (NO) synthesis through the stimulation of endothelial NO synthase (eNOS) expression. To address this knowledge gap, this study investigated whether AF and MS directly regulate NO synthesis and attenuate adhesion factor expression induced by treatment with tumor necrosis factor-α (TNF-α) in HUVECs. The results revealed that both AF and MS (20 μM) treatments promoted increases in eNOS expression and decreases in vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and endothelin-1 mRNA and protein expression resulting from 12 h of TNF-α treatment. These effects are attributed to the ability of AF and MS to inhibit extracellular signal-regulated protein kinase (ERK) phosphorylation and nuclear factor κB (NF-κB) translocation from the cytoplasm into the nucleus, thereby exerting antihypertensive activity.     

In vivo antioxidant activities of essential oils and their constituents from leaves of the Taiwanese Cinnamomum osmophloeum

Cinnamomum osmophloeum Kaneh is an indigenous tree species in Taiwan. In this study, phytochemical characteristics and antioxidant activities of the essential oils and key constituents from the leaves of two C. osmophloeum clones were investigated. The two trees possess two chemotypes, which were classified as the cinnamaldehyde type and camphor type. We demonstrated that the essential oils from C. osmophloeum leaves exerted in vivo antioxidant activities in Caenorhabditis elegans. In addition, trans-cinnamaldehyde and D-(+)-camphor, which respectively represent the major compounds in the cinnamaldehyde-type and camphor-type trees, exerted significant in vivo antioxidant activities against juglone-induced oxidative stress in C. elegans. Moreover, expressions of antioxidative-related genes, including superoxide dismutase (SOD) and glutathione S-transferase (GST), were significantly induced by trans-cinnamaldehyde and D-(+)-camphor from C. osmophloeum leaves. Our results showed that the essential oils from C. osmophloeum leaves and their major compounds might have good potential for further development as nutraceuticals or antioxidant remedies.     

Cytotoxic and Anti-Inflammatory Metabolites from the Soft Coral Scleronephthya gracillimum

Five new pregnane-type steroids, sclerosteroids J–N (1–5), and a diterpenoid with a new chemotype 3-methyl-5-(10′-acetoxy-2′,6′,10′-trimethylundecyl)-2-penten-5-olide (6), have been isolated from a soft coral Scleronephthya gracillimum. The structures of the metabolites were determined by extensive spectroscopic analysis. Compound 4 exhibited cytotoxicity against HepG2, A549, and MDA-MB-231 cancer cell lines. Furthermore, steroids 2 and 4 were found to significantly inhibit the accumulation of the pro-inflammatory iNOS protein, and 1, 2, 4 and 5 could effectively reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.