Anti-inflammatory and anti-infectious effects of Evodia rutaecarpa (Wuzhuyu) and its major bioactive components

This article reviews the anti-inflammatory relative and anti-infectious effects of Evodia rutaecarpa and its major bioactive components and the involvement of the nitric oxide synthases, cyclooxygenase, NADPH oxidase, nuclear factor kappa B, hypoxia-inducible factor 1 alpha, reactive oxygen species, prostaglandins, tumor necrosis factor, LIGHT, amyloid protein and orexigenic neuropeptides. Their potential applications for the treatment of endotoxaemia, obesity, diabetes, Alzheimer's disease and their uses as cardiovascular and gastrointestinal protective agents, analgesics, anti-oxidant, anti-atherosclerosis agents, dermatological agents and anti-infectious agents are highlighted. Stimulation of calcitonin gene-related peptide release may partially explain the analgesic, cardiovascular and gastrointestinal protective, anti-obese activities of Evodia rutaecarpa and its major bioactive components

Protein kinase A-dependent Neuronal Nitric Oxide Synthase Activation Mediates the Enhancement of Baroreflex Response by Adrenomedullin in the Nucleus Tractus Solitarii of Rats

<p>Abstract</p> <p>Background</p> <p>Adrenomedullin (ADM) exerts its biological functions through the receptor-mediated enzymatic mechanisms that involve protein kinase A (PKA), or neuronal nitric oxide synthase (nNOS). We previously demonstrated that the receptor-mediated cAMP/PKA pathway involves in ADM-enhanced baroreceptor reflex (BRR) response. It remains unclear whether ADM may enhance BRR response via activation of nNOS-dependent mechanism in the nucleus tractus solitarii (NTS).</p> <p>Methods</p> <p>Intravenous injection of phenylephrine was administered to evoke the BRR before and at 10, 30, and 60 min after microinjection of the test agents into NTS of Sprague-Dawley rats. Western blotting analysis was used to measure the level and phosphorylation of proteins that involved in BRR-enhancing effects of ADM (0.2 pmol) in NTS. The colocalization of PKA and nNOS was examined by immunohistochemical staining and observed with a laser confocal microscope.</p> <p>Results</p> <p>We found that ADM-induced enhancement of BRR response was blunted by microinjection of NPLA or Rp-8-Br-cGMP, a selective inhibitor of nNOS or protein kinase G (PKG) respectively, into NTS. Western blot analysis further revealed that ADM induced an increase in the protein level of PKG-I which could be attenuated by co-microinjection with the ADM receptor antagonist ADM_22-52or NPLA. Moreover, we observed an increase in phosphorylation at Ser1416 of nNOS at 10, 30, and 60 min after intra-NTS administration of ADM. As such, nNOS/PKG signaling may also account for the enhancing effect of ADM on BRR response. Interestingly, biochemical evidence further showed that ADM-induced increase of nNOS phosphorylation was prevented by co-microinjection with Rp-8-Br-cAMP, a PKA inhibitor. The possibility of PKA-dependent nNOS activation was substantiated by immunohistochemical demonstration of co-localization of PKA and nNOS in putative NTS neurons.</p> <p>Conclusions</p> <p>The novel finding of this study is that the signal transduction cascade that underlies the enhancement of BRR response by ADM in NTS is composed sequentially of cAMP/PKA and nNOS/PKG pathways.</p

New bichalcone analogs as NF-κB inhibitors and as cytotoxic agents inducing Fas/CD95-dependent apoptosis

A series of novel bichalcone analogs were synthesized and evaluated in lipopolysaccharide (LPS)-activated microglial cells as inhibitors of nitric oxide (NO) and for in vitro anticancer activity using a limited panel of four human cancer cell lines. All analogs inhibited NO production. Compounds 4 and 11 exhibited optimal activity with IC50 values of 0.3 and 0.5 µM, respectively, and were at least 38-fold better than the positive control. A mechanism of action study showed that both compounds significantly blocked the nuclear translocation of NF-κB p65 and up-regulation of iNOS at 1.0 µM. Compound 4 and three other analogs (3, 20, and 23) exerted significant in vitro anticancer activity GI50 values ranging from 0.70~13.10 µM. A mode of action study using HT-29 colon cancer cells showed that 23 acts by inducing apoptosis signaling

NEUROPROTECTIVE EFFECT OF TERMINALIA CHEBULA EXTRACTS AND ELLAGIC ACID IN PC12 CELLS

Alzheimer’s disease (AD) is one of the most prevalent severe neurological disorders afflicting our aged population. The study was to determine neuroprotective effects of the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Ab25-35)-induced cell cytotoxicity in undifferentiated rat pheochromocytoma (PC12) cellular model. The methanolic and water extracts of T. chebula and ellagic acid exhibited the strongest neuroprotective activity against Ab25-35-induced undifferentiated PC12 cell deaths at 0.5–5.0 ug/ml. The ellagic acid also exhibited the partial neuroprotective activity against H2O2-induced undifferentiated PC12 cell deaths at 0.5–5.0 ug/ml. The methanolic and water extracts of T. chebula and ellagic acid protected undifferentiated PC12 cells from the damaging effects of Ab25-35 in several ways: (1) by securing cell viability; (2) by suppressing reactive oxygen species production; and (3) by eliminating calcium ion influx. The T. chebula extracts maybe represent a promising plant-source for medicine in the application of the treatment of AD. Further investigation of the ellagic acid is necessary to verify the neuroprotective efficacy and mechanisms in vivo

Camphoratins A−J, Potent Cytotoxic and Anti-inflammatory Triterpenoids from the Fruiting Body of Taiwanofungus camphoratus

Ten new triterpenoids, camphoratins A–J (1–10), along with 12 known compounds were isolated from the fruiting body of Taiwanofungus camphoratus. Their structures were established by spectroscopic analysis and chemical methods. Compound 10 is the first example of a naturally occurring ergosteroid with an unusual cis-C/D ring junction. Compounds 2–6 and 11 showed moderate to potent cytotoxicity with EC50 values ranging from 0.3 to 3 μM against KB and KB-VIN human cancer cell lines. Compounds 6, 10, 11, 14–16, 18, and 21 exhibited anti-inflammatory NO-production inhibition activity with IC50 values of less than 5 μM, which was more potent than the nonspecific NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME)

Anti-inflammatory effect of euphane- and tirucallane-type triterpenes isolated from the traditional herb Euphorbia neriifolia L

The Euphorbiaceae plant Euphorbia neriifolia L. is distributed widely in India, Thailand, Southeastern China, and Taiwan and used as a carminative and expectorant to treat several inflammation-related diseases, such as gonorrhoea, asthma, and cancer. In the course of our search for potential anti-inflammatory agents from the titled plant, 11 triterpenes from the stem of E. neriifolia were isolated and reported in our previous endeavor. Given its rich abundance in triterpenoids, the ethanolic extract in this follow-up exploration has led to the isolation of additional eight triterpenes, including six new euphanes—neritriterpenols H and J–N (1 and 3–7)—one new tirucallane, neritriterpenol I (2), and a known compound, 11-oxo-kansenonol (8). Their chemical structures were elucidated on the basis of spectroscopic data, including 1D- and 2D NMR, and HRESIMS spectra. The absolute stereochemistry of neritriterpenols was determined by single-crystal X-ray diffraction analysis, ICD spectra, and DP4+ NMR data calculations. Compounds 1–8 were also evaluated for their anti-inflammatory activity by using lipopolysaccharide (LPS)-stimulated IL-6 and TNF-α on RAW 264.7 macrophage cells. Intriguingly, the euphane-type triterpenes (1 and 3–8) showed an inhibitory effect on LPS-induced IL-6 but not on TNF-α, while tirucallane-type triterpene 2 showed strong inhibition on both IL-6 and TNF-α

Common and unique mechanisms of Chinese herbal remedies on ischemic stroke mice revealed by transcriptome analyses

Ethnopharmacological relevance: Four traditional Chinese herbal remedies (CHR) including Buyang Huanwu decoction (BHD), Xuefu Zhuyu decoction (XZD), Tianma Gouteng decoction (TGD) and Shengyu decoction (SYD) are popular used in treating brain-related dysfunction clinically with different syndrome/pattern based on traditional Chinese medicine (TCM) principles, yet their neuroprotective mechanisms are still unclear. Materials and methods: Mice were subjected to an acute ischemic stroke to examine the efficacy and molecular mechanisms of action underlying these CHR. Results: CHR treatment significantly enhanced the survival rate of stroke mice, with BHD being the most effective CHR. All CHR were superior to recombinant tissue-type plasminogen activator (rt-PA) treatment in successfully ameliorating brain function, infarction, and neurological deficits in stroke mice that also paralleled to improvements in blood-brain barrier damage, inflammation, apoptosis, and neurogenesis. Transcriptome analyses reveals that a total of 774 ischemia-induced probe sets were significantly modulated by four CHR, including 52 commonly upregulated genes and 54 commonly downregulated ones. Among them, activation of neurogenesis-associated signaling pathways and down-regulating inflammation and apoptosis pathways are key common mechanisms in ischemic stroke protection by all CHR. Besides, levels of plasma CX3CL1 and S100a9 in patients could be used as biomarkers for therapeutic evaluation before functional recovery could be observed. Conclusion: Our results suggest that using CHR, a combinatory cocktail therapy, is a better way than rt-PA for treating cerebral ischemic-associated diseases through modulating a common as well as a specific group of genes/pathways that may partially explain the syndrome differentiation and treatment principle in TCM. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Neuroprotective effect of Terminalia chebula extracts and ellagic acid in PC12 cells

Background: Alzheimer’s disease (AD) is one of the common neurodegenerative disorders among elderly. The purpose of this study was to determine the neuroprotective effect and mechanisms of action underlying the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Aβ25-35)-induced cell toxicity in an undifferentiated pheochromocytoma (PC12) cell line.Materials and Methods: The T. chebula extracts were prepared using the methanol, water, and 95% ethanol. Specifically, the ellagic acid was obtained in our laboratory. Assays including cell toxicity and changes in intracellular reactive oxygen species (ROS) and calcium level were evaluated to examine the neuroprotective effects and mechanisms of the T. chebula extracts and ellagic acid.Results: The methanolic and water extracts of T. chebula and ellagic acid exhibited the strongest neuroprotective activity against Aβ25-35-induced PC12 cell damages at 0.5–5.0 μg/ml. The ellagic acid also exhibited partial neuroprotective activity against H2O2-induced PC12 cell damages at 0.5–5.0 μg/ml. The methanolic and water extracts of T. chebula and ellagic acid protected PC12 cells from Aβ25-35-mediated cell damages and enhanced cell viability thorough two key mechanisms by: (1) inhibiting ROS production and (2) reducing calcium ion influx.Conclusion: The T. chebula represents a promising plant-source as medicine in the application for the treatment of AD. Further investigation focusing on the active component of T. chebula extracts e.g., ellagic acid is crucial to verify the neuroprotective efficacy and mechanisms in vivo.Keywords: Neuroprotective effect; Terminalia chebula; ellagic acid; beta-amyloi

Anti-inflammatory and Antiosteoporosis Flavonoids from the Rhizomes of <i>Helminthostachys zeylanica</i>

Chemical investigation of the rhizomes of <i>Helminthostachys zeylanica</i> led to the isolation of eight new flavonoids including six cyclized geranylflavonoids, ugonins V–X (<b>1</b>–<b>3</b>), (10<i>R</i>,11<i>S</i>)-ugonin N (<b>4</b>), (10<i>R</i>,11<i>S</i>)-ugonin S (<b>5</b>), and ugonin Y (<b>6</b>), as well as two quercetin glucosides, quercetin-4′-<i>O</i>-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (<b>7</b>) and quercetin-3-<i>O</i>-β-d-glucopyranosyl-4′-<i>O</i>-β-d-glucopyranosyl-(1→2)-β-d-glucopyranoside (<b>8</b>). The structures of these compounds were established by spectroscopic analyses and acid hydrolysis of the sugar moiety. Among the isolated compounds, <b>1</b>, <b>2</b>, <b>5</b>, <b>6</b>, ugonins J–S (<b>9</b>–<b>13</b>), ugonstilbene A (<b>14</b>), and ugonin L (<b>23</b>) were evaluated for their anti-inflammatory activity on lipopolysaccharide-induced nitric oxide (NO) production in microglial cells. Except for <b>1</b>, <b>5</b>, and <b>13</b>, all other compounds inhibited NO production with IC₅₀ values of 6.2–10.1 μM and were more potent than the positive control, pyrrolidine dithiocarbamate. Compounds <b>1</b>, <b>2</b>, <b>5</b>, <b>6</b>, and <b>10</b>–<b>13</b> were tested for antiosteoporotic activities, and ugonin K (<b>10</b>) exhibited the highest inhibitory activity against RANKL-induced osteoclast differentiation in RAW264.7 cells with an IC₅₀ value of 1.8 ± 0.2 μM