Myrtucommulone from Myrtus communis exhibits potent anti-inflammatory effectiveness in vivo.
ABSTRACT Myrtucommulone (MC), a nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis), has been reported to suppress the biosynthesis of eicosanoids by inhibition of 5-lipoxygenase and cyclooxygenase-1 in vitro and to inhibit the release of elastase and the formation of reactive oxygen species in activated polymorphonuclear leukocytes. Here, in view of the ability of MC to suppress typical proinflammatory cellular responses in vitro, we have investigated the effects of MC in in vivo models of inflammation. MC was administered to mice intraperitoneally, and paw edema and pleurisy were induced by the subplantar and intrapleural injection of carrageenan, respectively. MC (0.5, 1.5, and 4.5 mg/kg i.p.) reduced the development of mouse carrageenan-induced paw edema in a dose-dependent manner. Moreover, MC (4.5 mg/kg i.p. 30 min before and after carrageenan) exerted anti-inflammatory effects in the pleurisy model. In particular, 4 h after carrageenan injection in the pleurisy model, MC reduced: 1) the exudate volume and leukocyte numbers; 2) lung injury (histological analysis) and neutrophil infiltration (myeloperoxidase activity); 3) the lung intercellular adhesion molecule-1 and P-selectin immunohistochemical localization; 4) the cytokine levels (tumor necrosis factor-alpha and interleukin-1beta) in the pleural exudate and their immunohistochemical localization in the lung; 5) the leukotriene B(4), but not prostaglandin E(2), levels in the pleural exudates; and 6) lung peroxidation (thiobarbituric acid-reactant substance) and nitrotyrosine and poly (ADP-ribose) immunostaining. In conclusion, our results demonstrate that MC exerts potent anti-inflammatory effects in vivo and offer a novel therapeutic approach for the management of acute inflammation.
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ABSTRACT: Hypericum perforatum (St. John's wort) is an herb widely used as supplement for mild to moderate depression. Our prior studies established synergistic anti-inflammatory activity associated with 4 bioactive compounds in a fraction of a H. perforatum ethanol extract. Whether these 4 compounds also contributed to the ethanol extract activity was addressed in the research reported here. Despite the popularity of H. perforatum, other Hypericum species with different phytochemical profiles could have their anti-inflammatory potentials attributed to these or other compounds. In the current study, ethanol extracts of different Hypericum species were compared for their inhibitory effect on LPS-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 mouse macrophages. Among these extracts, those made from H. perforatum and H. gentianoides demonstrated stronger overall efficacy. LC-MS analysis established the 4 compounds were present in the H. perforatum extract and pseudohypericin in all active fractions. The 4 compounds accounted for a significant part of the extract's inhibitory activity on PGE2, NO, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW 264.7 as well as peritoneal macrophages. Pseudohypericin was the most important contributor of the anti-inflammatory potential among the 4 compounds. The lipophilic fractions of H. gentianoides extract, which did not contain the previously identified active constituents, decreased PGE2 and NO potently. These fractions were rich in acylphloroglucinols, including uliginosin A that accounted for a proportion of the anti-inflammatory activity observed with the active fractions. Overall, the current study established that a different group of major anti-inflammatory constituents were present in H. gentianoides, while showing that the previously identified 4 compound combination was important for H. perforatum's anti-inflammatory potential.Phytochemistry 08/2011; 72(16):2015-23. · 3.05 Impact Factor
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ABSTRACT: Recently, studies have been reported on the optimal immunohistochemical markers for subclassification of non-small cell lung carcinoma (NSCLC). The main pitfall in subclassification of NSCLC is small specimen with poorly differentiated area. In this study, we added newly proposed markers (e.g., napsin A, SOX2) to conventional markers (p63, TTF-1, CK5/6, and CK7) and evaluated optimal combination for subtyping of NSCLC, primarily focusing on the poorly differentiated area. Eighty two resected NSCLCs with poorly differentiated areas were classified based on histologic findings. After histologic review, only poorly differentiated areas were selected and tissue microarrays were constructed to simulate small biopsy conditions. A total of 36 adenocarcinomas (ADCs), 38 squamous cell carcinomas (SQCCs), and 8 large cell carcinomas were included. All specimens were stained with TTF-1, napsin A, CK7, p63, CK5/6, and SOX2. With respect to ADC, TTF-1 was positive in 19 of 36 cases (53%) and napsin A was in 25 of 36 (69%). Both markers were specific for ADC (100% and 98%, respectively). With TTF-1 and napsin A in combination, sensitivity increased to 75%. CK7 was sensitive (92%) but not specific marker (76%) for ADC. With respect to SQCC, p63 was positive in 35 of 38 cases (92%) and CK5/6 was in 23 (61%). Both markers were specific for SQCC (both 93%). With p63 and CK5/6 in combination, sensitivity increased slightly to 95%, but specificity was lower at 91%. SOX2 was specific (100%) but not sensitive marker (53%) for SQCC. Combinations did not substantially increase the diagnostic performance. A simple panel of napsin A, TTF-1, and p63 can be sufficient to reliably subclassify poorly differentiated areas of NSCLC.Lung cancer (Amsterdam, Netherlands) 10/2011; 76(1):51-5. · 3.14 Impact Factor
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ABSTRACT: Based on its capacity to inhibit in vitro HIV-1 replication in T cells and the release of pro-inflammatory cytokines in monocytes, the prenylated heterodimeric phloroglucinyl α-pyrone arzanol was identified as the major anti-inflammatory and anti-viral constituent from Helichrysum italicum. We have now investigated the activity of arzanol on the biosynthesis of pro-inflammatory eicosanoids, evaluating its anti-inflammatory efficacy in vitro and in vivo. Arzanol inhibited 5-lipoxygenase (EC 188.8.131.52) activity and related leukotriene formation in neutrophils, as well as the activity of cyclooxygenase (COX)-1 (EC 184.108.40.206) and the formation of COX-2-derived prostaglandin (PG)E(2)in vitro (IC(50)=2.3-9μM). Detailed studies revealed that arzanol primarily inhibits microsomal PGE(2) synthase (mPGES)-1 (EC 220.127.116.11, IC(50)=0.4μM) rather than COX-2. In fact, arzanol could block COX-2/mPGES-1-mediated PGE(2) biosynthesis in lipopolysaccharide-stimulated human monocytes and human whole blood, but not the concomitant COX-2-derived biosynthesis of thromboxane B(2) or of 6-keto PGF(1α), and the expression of COX-2 or mPGES-1 protein was not affected. Arzanol potently suppressed the inflammatory response of the carrageenan-induced pleurisy in rats (3.6mg/kg, i.p.), with significantly reduced levels of PGE(2) in the pleural exudates. Taken together, our data show that arzanol potently inhibits the biosynthesis of pro-inflammatory lipid mediators like PGE(2)in vitro and in vivo, providing a mechanistic rationale for the anti-inflammatory activity of H. italicum, and a rationale for further pre-clinical evaluation of this novel anti-inflammatory lead.Biochemical pharmacology 10/2010; 81(2):259-68. · 4.25 Impact Factor