Docosahexaenoic acid-enriched phospholipids and eicosapentaenoic acid-enriched phospholipids inhibit tumor necrosis factor-alpha-induced lipolysis in 3T3-L1 adipocytes via activating sirtuin 1 pathways

Some chronic diseases such as cancer-associated cachexia (CAC) and obesity are associated with overproduction of tumor necrosis factor-alpha (TNF-α), which stimulates excess lipolysis in adipocytes. Our previous studies manifested that...

Qualitative and quantitative determination of ligustilide as bioactive marker in apiaceous botanicals

Variety of bioactivities has been associated with ligustilide present in root of Angelica sinensis, and predominantly used for the treatment of irregular menstrual cycles and premenstrual syndrome. Recent pharmacological studies showed that medicinal plants containing ligustilide, have anti-inflammatory effects and contribute to the improvement of cognitive functions, alleviate brain damage, inhibit tumor necrosis factor of some cell lines, and have nephron-protective effects and neuroprotective activity. In this work, quantification of ligustilide using quantitative 1H NMR (qHNMR) in sealed tubes was performed. Four plant species were investigated: A. sinensis, Ligusticum porteri, Ligusticum striatum, andLigusticum sinense. Modified supercritical CO2 extraction of essential oil from root of four investigated species, was performed. qHNMR spectroscopy showed following percentage of ligustilide: L. porteri essential oil 3.74 (%); L. sinense essential oil 1.16 (%); L. striatum essential oil 6.61 (%) and A. sinensis essential oil 14.56 (%). The highest percentage of oil was obtained from the root of L. porteri but the highest percentage of ligustilide was obtained from A. sinensis essential oil.

Resolution of post-adalimumab vitiligo with secukinumab in a patient with psoriasis vulgaris

Plaque psoriasis is a chronic debilitating condition, and biologic agents that inhibit tumor necrosis factor-α (TNF-α) are widely employed in management of the condition. Notwithstanding, several paradoxical adverse reactions have been reported with TNF-α inhibitors, including vasculitis, vitiligo, alopecia areata, sarcoidosis and other granulomatous diseases. Herein, we report the case of a 63-year-old man who developed vitiligo while on therapy with adalimumab following failure of conventional agents for plaque psoriasis. After discontinuation of adalimumab and initiation of secukinumab, vitiligo and other psoriatic symptoms gradually resolved. After 1 year of treatment, only small plaque areas were present in the flexor site with complete remission in the extensor area along with near complete resolution of depigmented areas. In this case of possible adalimumab-induced vitiligo in a patient with plaque psoriasis, secukinumab resolved both the symptoms of psoriasis and the likely adalimumab-related vitiligo.

Progestins Inhibit Tumor Necrosis Factor α–Induced Matrix Metalloproteinase 9 Activity via the Glucocorticoid Receptor in Primary Amnion Epithelial Cells

Progestins have been recommended for preterm birth prevention in high-risk women; however, their mechanism of action still remains an area of debate. Medroxyprogesterone acetate (MPA) has previously been shown to significantly inhibit tumor necrosis factor α (TNFα)-induced matrix metalloproteinase 9 (MMP9) messenger RNA (mRNA) expression and activity in primary amnion epithelial cells, a process that may lead to preterm premature rupture of membranes. A mechanism that explains MPA’s inhibition of TNFα-induced MMP9 mRNA expression and activity in primary amnion epithelial cells is unclear since these cells lack the classic nuclear progesterone receptor but express a membrane-associated progesterone receptor—progesterone receptor membrane component 1 (PGRMC1) along with the glucocorticoid receptor (GR). Primary amnion epithelial cells harvested from healthy term pregnant women at cesarean section were treated with PGRMC1 (to knockdown PGRMC1 expression), GR (to knockdown GR expression), or control small interfering RNA (siRNA; 10 nm) for 72 hours, pretreated with ethanol or MPA (10−6 M) for 6 hours, and then stimulated with or without TNFα 10 ng/mL for 24 hours. Real-time quantitative polymerase chain reaction and gelatin zymography were used to quantify MMP9 mRNA expression and activity, respectively. Experimental groups were compared using 1-way analysis of variance. Both TNFα-induced MMP9 mRNA expression and activity were significantly inhibited by pretreatment with MPA; however, only the inhibition of TNFα-induced MMP9 activity was partially reversed with PGRMC1 siRNA. However, GR siRNA reversed both the inhibition of TNFα-induced MMP9 mRNA expression and activity by MPA. This study demonstrates that MPA mediates its anti-inflammatory effects primarily through GR and partially through PGRMC1 in primary amnion epithelial cells.

Open-Ring Butenolides from a Marine-Derived Anti-Neuroinflammatory Fungus Aspergillus terreus Y10

To investigate structurally novel and anti-neuroinflammatory natural compounds from marine-derived microorganisms, the secondary metabolites of Aspergillus terreus Y10, a fungus separated from the sediment of the coast in the South China Sea, were studied. Three new compounds (2–4), with novel open-ring butenolide skeletons, were isolated from the ethyl acetate extract of the culture medium. In addition, a typical new butenolide, asperteretal F (1), was found to dose-dependently inhibit tumor necrosis factor (TNF-α) generation with an IC50 of 7.6 μg/mL. The present study shows the existence of open-ring butenolides, and suggests that butenolides such as asperteretal F (1) are a promising new anti-neuroinflammatroy candidate for neurodegenerative diseases.

De novo design of helical peptides to inhibit tumor necrosis factor-α by disrupting its trimer formation

Helical peptide TNFα inhibitors were designed by targeting their dimer structure.

Synthesis of 8-alkoxy-1,3-dimethyl-2, 6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides as analgesic and anti-inflammatory agents

A series of new 8-alkoxy-1,3-dimethyl-2,6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides 6–12 was synthesized and evaluated for the analgesic activity in two in vivo models: the writhing syndrome and the hot-plate tests. Among the investigated derivatives, compounds with N′-arylidenehydrazide moiety 9–12 show analgesic activity significantly higher than that of acetylsalicylic acid, which may indicate the importance of this structural element for analgesic properties. The lack of the activity in the hot-plate test may suggest that the analgesic activity of the newly synthesized compounds is mediated by a peripheral mechanism. The selected compounds 7 and 12 inhibit tumor necrosis factor α production in a rat model of lipopolysaccharide-induced endotoxemia, similarly to theophylline, which may confirm their anti-inflammatory properties.