Dendrocandin U from Dendrobium officinale Kimura et Migo Inhibits M1 Polarization in Alveolar Macrophage by Suppressing NF-κB Signaling Pathway.

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-ß-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs.

Investigation of the effect for bisphenol A on oxidative stress in human hepatocytes and its interaction with catalase.

Bisphenol A (BPA) as a chemical raw material, is widely used in the manufacturing process of daily necessities. It was reported that BPA could induce oxidative stress, and catalase (CAT) can protect the body from oxidative stress. In this paper, the effect of BPA on CAT was carried out in vitro and in vivo. Firstly, we studied the effects of BPA on oxidative stress, cell viability and CAT activity in human hepatocytes, and the results of vitro experiments show that the survival rate of hepatocytes significant decreased along with the increase of BPA concentration. And when the BPA concentration was 100 µM, the hepatocyte survival decreased by 13.2%, ROS levels in the cells increased by 85%. However, the activity of intracellular CAT increased with the increasing concentration of BPA in 24 h. The results of vivo experiments showed that the activity of CAT in the high-dose group decreased by 29.1% compared with the control group. The long-term effects of BPA on rats reduced the CAT activity in liver, which reduced the resistance to oxidative stress. Meanwhile, the interaction mechanism between BPA and CAT at the molecule level was performed via multiple spectra methods and molecular docking, and the results illustrated that the structural change of CAT is mainly due to the strong combination of BPA with the residues of Trp185. In addition, the interaction mechanism between BPA and CAT were hydrophobic and electrostatic effect. This study provided experimental evidence for better understanding the toxicity of BPA.

Cucurbitacin B inhibits tumor angiogenesis by triggering the mitochondrial signaling pathway in endothelial cells.

Cucurbitacin B (CuB), the active component of a traditional Chinese herbal medicine, Pedicellus Melo, has been shown to exhibit antitumor and anti-inflammation effects, but its role in tumor angiogenesis, the key step involved in tumor growth and metastasis, and the involved molecular mechanism are unknown. Tumor angiogenesis is one of the hallmarks of the development in malignant neoplasias and metastasis. Effective targeting of tumor angiogenesis is a key area of interest for cancer therapy. Here, we demonstrated that CuB significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration, tubulogenesis in vitro, and blocked angiogenesis in chick embryo chorioallantoic membrane (CAM) assay in vivo. Furthermore, CuB induced HUVEC apoptosis and may induce apoptosis by triggering the mitochondrial apoptotic pathway. Finally, we found that CuB inhibiting angiogenesis was associated with inhibition of the activity of vascular endothelial growth factor receptor 2 (VEGFR2). Our investigations suggested that CuB was a potential drug candidate for angiogenesis related diseases.

Bioactivity-guided fractionation of the triglyceride-lowering component and in vivo and in vitro evaluation of hypolipidemic effects of Calyx seu Fructus Physalis.

BACKGROUND: In folklore, some people take the decoction of Calyx seu Fructus Physalis (CSFP) for lowering blood lipids. The present study is designed to evaluate the lipid-lowering activities of CSFP, and search for its pharmacodynamical material. METHODS: CSFP was extracted by water and 75% ethanol, respectively. The extracts of CSFP for reducing serum lipid levels were evaluated on mouse model of hyperlipidemia. The optimized extract was subjected to the bioactivity-guided fractionation in which the liquid-liquid extraction, collumn chromatography, the in vivo and in vitro models of hyperlipidemia were utilized. The structure of active component was determined by ¹³C-NMR and ¹H-NMR. RESULTS: The 75% ethanol extract of CSFP decreased the serum total cholesterol (TC) and triglyceride (TG) levels in mouse model of hyperlipidemia. Followed a separation process for the 75% ethanol extract of CSFP, the fraction B was proved to be an active fraction for lowering lipid in vivo and in vitro experiments, which could significantly decrease the serum TC and TG levels in mouse model of hyperlipidemia, and remarkably decrease the increase of TG in primary mouse hepatocytes induced by high glucose and the increase of TG in HepG2 cells induced by oleic acid. The fraction B2, isolated from B on bioactivity-guided fractionation, could significantly decrease TG level in HepG2 cells. One compound with the highest content in B2 was isolated and determined as luteolin-7-O-beta-D-glucopyranoside by NMR spectra. It could significantly reduce the TG level in HepG2 cells, and inhibited the accumulation of lipids by oil red O stain. CONCLUSION: Our results demonstrated that the 75% ethanol extract of CSFP could improve in vitro and in vivo lipid accumulation. Luteolin-7-O-beta-D-glucopyranoside might be a leading pharmacodynamical material of CSFP for lowering lipids.

Flavonoids from Chinese Viscum coloratum produce cytoprotective effects against ischemic myocardial injuries: inhibitory effect of flavonoids on PAF-induced Ca2+ overload.

Viscum coloratum has been used in the indigenous system of medicine for the treatment of various diseases such as myocardial ischemia and arrhythmia. Platelet-activating factor (PAF) is an important player in cardiovascular diseases. The aim of this study was to investigate the protective effects of Viscum coloratum flavonoids (VCF) against ischemic myocardial injuries in vivo and to further investigate its regulatory effect on PAF. Studies were performed in a rat model of myocardial infarction and in isolated myocytes. It was found that VCF relieved myocardial injuries during ischemia. PAF (10(-11) m) significantly increased the intracellular free Ca2+ concentration ([Ca2+]i) and VCF inhibited the changes induced by PAF in single cardiac myocytes. The results suggest that VCF can improve cardiac function and that VCF reduces ischemic myocardial injuries via blocking the signaling pathway of PAF. Therefore, PAF blockers may be candidate drugs for preventing cardiac injuries during ischemia/reperfusion, and subsequently improving cardiac function.