Schisandrae Fructus ethanol extract ameliorates inflammatory responses and articular cartilage damage in monosodium iodoacetate-induced osteoarthritis in rats

Schisandrae Fructus, the fruit of Schisandra chinensis (Turcz.) Baill., is widely used in traditional medicine for the treatment of a number of chronic diseases. Although, Schisandrae Fructus was recently reported to attenuate the interleukin (IL)-1β-induced inflammatory response in chondrocytes in vitro, its protective and therapeutic potential against osteoarthritis (OA) in an animal model remains unclear. Therefore, we investigated the effects of the ethanol extract of Schisandrae Fructus (SF) on inflammatory responses and cartilage degradation in a monosodium iodoacetate (MIA)-induced OA rat model. Our results demonstrated that administration with SF had a tendency to attenuate MIA-induced damage of articular cartilage as determined by a histological grade of OA. SF significantly suppressed the production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in MIA-induced OA rats. SF also effectively inhibited expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, thereby inhibiting the release of NO and prostaglandin E2. In addition, the elevated levels of matrix metalloproteinases-13 and two biomarkers for diagnosis and progression of OA, such as cartilage oligomeric matrix protein and C-telopeptide of type II collagen, were markedly ameliorated by SF administration. These findings indicate that SF could be a potential candidate for the treatment of OA

Schisandrae Fructus ethanol extract ameliorates inflammatory responses and articular cartilage damage in monosodium iodoacetate-induced osteoarthritis in rats

Schisandrae Fructus, the fruit of Schisandra chinensis (Turcz.) Baill., is widely used in traditional medicine for the treatment of a number of chronic diseases. Although, Schisandrae Fructus was recently reported to attenuate the interleukin (IL)-1β-induced inflammatory response in chondrocytes in vitro, its protective and therapeutic potential against osteoarthritis (OA) in an animal model remains unclear. Therefore, we investigated the effects of the ethanol extract of Schisandrae Fructus (SF) on inflammatory responses and cartilage degradation in a monosodium iodoacetate (MIA)-induced OA rat model. Our results demonstrated that administration with SF had a tendency to attenuate MIA-induced damage of articular cartilage as determined by a histological grade of OA. SF significantly suppressed the production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in MIA-induced OA rats. SF also effectively inhibited expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, thereby inhibiting the release of NO and prostaglandin E2. In addition, the elevated levels of matrix metalloproteinases-13 and two biomarkers for diagnosis and progression of OA, such as cartilage oligomeric matrix protein and C-telopeptide of type II collagen, were markedly ameliorated by SF administration. These findings indicate that SF could be a potential candidate for the treatment of OA

ANTIPROLIFERATION EFFECTS OF SELECTED TANZANIA PLANTS

Background: Plants still remain a prime source of drugs for the treatment of cancer and can provide leads for the development of novel anticancer agents. Our screening of indigenous medicinal plants from Tanzania has led to the identification of the number of anticancer activity. Material and methods: The current study investigates the cytotoxic activity of methanol extracts of one hundred and thirty seven Tanzania plants used locally for the traditional medicine herb using the MTS assay on the HepG2 cell lines. Result 16% of the tested plant extracts showed moderate to strong inhibitory activity with IC50 values ranging from 17.1 ± 1.1 μg/ml to 79.2 ± 0.7 μg/ml ; meanwhile, ten extracts (7.3%) could demonstrate cytotoxic activity with IC50 values less than 27.6 ± 2.0 μg/ml; twelve extracts (8.8%) could demonstrate cytotoxic activity with IC50 values ranging from 30.4 ± 1.6 μg/ml to 79.2 ± 0.7μg/ml. Conclusion : Especially, a methanol extract from the bark extract of Erythrophleum zimmermannii (Fabaceae) was found to be the most cytotoxicity against HepG2 cell lines (IC50 = 17.1 ± 1.1 μg/ml)

Platelet-activating Factor–mediated NF-κB Dependency of a Late Anaphylactic Reaction

Anaphylaxis is a life-threatening systemic allergic reaction with the potential for a recurrent or biphasic pattern. Despite an incidence of biphasic reaction between 5 and 20%, the molecular mechanism for the reaction is unknown. Using a murine model of penicillin V–induced systemic anaphylaxis, we show an autoregulatory cascade of biphasic anaphylactic reactions. Induction of anaphylaxis caused a rapid increase in circulating platelet-activating factor (PAF) levels. In turn, the elevated PAF contributes to the early phase of anaphylaxis as well as the subsequent activation of the nuclear factor (NF)-κB, a crucial transcription factor regulating the expression of many proinflammatory cytokines and immunoregulatory molecules. The induction of NF-κB activity is accompanied by TNF-α production, which, in turn, promotes late phase PAF synthesis. This secondary wave of PAF production leads eventually to the late phase of anaphylactic reactions. Mast cells do not appear to be required for development of the late phase anaphylaxis. Together, this work reveals the first mechanistic basis for biphasic anaphylactic reactions and provides possible therapeutic strategies for human anaphylaxis

IN VITRO ANTI-INFLAMMATORY ACTIVITY OF THE COMPONENTS OF AMOMUM TSAO-KO IN MURINE MACROPHAGE RAW 264.7 CELLS

Background: Plants still remain the prime source of drugs for the treatment of inflammation and can provide leads for the development of novel anti-inflammatory agents. Material and methods: An in vitro bioassay guide revealed that the 80% ethanol (EtOH) extract of the whole plant, Amomum tsao-ko (Zingiberaceae), displayed anti-inflammatory activity after assessing its effects on murine macrophage RAW 264.7 cells. Result: Phytochemical study of the 80% EtOH extract of Amomum tsao-ko led to the isolation of eight compounds: 4-hydroxy-3-methoxy-benzoic acid (1), meso-hannokinol (2), (+)-hannokinol (3), coumaric acid (4), 4-hydroxy-benzoic acid (5), (+)-epicatechin (6), (-)-catechin (7), and myrciaphenone A (8). The results indicated that two of the isolated components, (+)-epicatechin (6) and (-)-catechin (7), inhibited the production of nitric oxide (NO) significantly in lipopolysaccharide treated RAW 264.7 cells. Conclusion: LPS-induced interleukin tumor necrosis factor-alpha (TNF-), IL-1β and IL-10 production was also decreased in a dose-dependent manner. In addition, western blot analysis revealed that (+)-epicatechin (6) and (-)-catechin (7) reduced the expression of inducible nitric oxide synthase and inhibited nuclear localization of nuclear factor kappa-B (NF-κB)

PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloid β

PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-β-(Aβ-) induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS-) stimulated murine BV2 microglia. Intracerebroventricular injection of Aβ25-35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day) in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aβ expression and activation of microglia and astrocytes in the Aβ25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aβ-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD

The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation

P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Methods Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. Results The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. Conclusion P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement