Anti-Psoriatic Effects of Antimony Compounds In Vitro

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes and a pro-inflammatory milieu in the skin. While patients with moderate to severe psoriasis are treated using targeted therapies (small molecules and monoclonal antibodies), patients suffering from milder forms are still in need of effective topical products without adverse effects. Antimony compounds (ACs) are regularly used as anti-inflammatory compounds in traditional and anthroposophic medicine and as antiprotozoan drugs. Here, we examined the effect of metallic antimony, natural antimony(III) sulfide and potassium antimonyl(III) tartrate in vitro on psoriasis-like keratinocytes and the human dendritic cell line THP-1 using qPCR, immunocytochemistry, ELISA and flow cytometry. In psoriatic keratinocytes, ACs inhibited the overexpression of the antimicrobial peptide β-defensin 2 and glucose transporter 1, as well as the hyperproliferation marker keratin 17. Furthermore, ACs mediated anti-inflammatory effects by reducing nuclear translocation of the p65 subunit of NF-κB and pSTAT3 and inhibited pro-inflammatory cytokine secretion by keratinocytes. In addition, ACs displayed anti-psoriatic effects by reducing the activation of IFN-α-treated THP-1 cells as well as the expression of the psoriasis-promoting master cytokine IL-23 by these cells. While all ACs showed anti-psoriatic effects, the most prominent results were seen with potassium antimonyl(III) tartrate. In summary, ACs display numerous anti-psoriatic effects in vitro at subtoxic concentrations. We conclude that ACs are interesting compounds for the topical treatment of psoriasis that warrant further investigation in clinical studies.

Download Full-text

The Effect of Herbal Medicinal Products on Psoriasis-Like Keratinocytes

Biomolecules ◽

10.3390/biom11030371 ◽

2021 ◽

Vol 11 (3) ◽

pp. 371

Author(s):

Fabian Gendrisch ◽

Birgit Haarhaus ◽

Nina Krieger ◽

Karl-Werner Quirin ◽

Christoph M. Schempp ◽

...

Keyword(s):

Plant Extracts ◽

Glucose Transporter ◽

Nuclear Translocation ◽

Ex Vivo ◽

Humulus Lupulus ◽

Biological Drugs ◽

Glucose Transporter 1 ◽

Tnf Α ◽

Interesting Candidate

Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes and expression of pro-inflammatory cytokines in the epidermis. New biological drugs were developed for the systemic treatment of moderate to severe psoriasis. However, products for the topical treatment of mild psoriasis are still required. Here, we examined the effect of natural compounds on psoriasis-like keratinocytes in vitro and ex vivo. Psoriasis-like keratinocytes were generated by treating human primary keratinocytes with the psoriasis-associated cytokines IL-17A, TNF-α and IL-22. Initially, 10 botanical extracts from Ayurvedic Medicine, Traditional Chinese Medicine, Northern American traditional medicine and Occidental Monastic Medicine were investigated using BrdU assays and IL-6 and IL-8 ELISAs. Curcuma amada, Humulus lupulus and Hypericum perforatum turned out to be the most effective plant extracts. In vitro, the plant extracts inhibited the expression of anti-microbial peptides (β-defensin 2), the hyperproliferation marker keratin 17, the glucose transporter 1 and downregulated the nuclear translocation of NF-κB and pSTAT3. In an ex vivo psoriasis model, Humulus lupulus displayed the most prominent anti-proliferative and anti-inflammatory effect. In conclusion, among the plant extracts investigated, Humulus lupulus showed the most promising anti-psoriatic effect. It is an interesting candidate for topical psoriasis treatment that should be further studied in clinical trials.

Download Full-text

Isoquinolinequinone Derivatives from a Marine Sponge (Haliclona sp.) Regulate Inflammation in In Vitro System of Intestine

Marine Drugs ◽

10.3390/md19020090 ◽

2021 ◽

Vol 19 (2) ◽

pp. 90

Author(s):

Yun Kim ◽

Yeong Ji ◽

Na-Hyun Kim ◽

Nguyen Van Tu ◽

Jung-Rae Rho ◽

...

Keyword(s):

Nitric Oxide ◽

Marine Sponge ◽

Nuclear Translocation ◽

Hydroxyl Group ◽

Subsequent Increase ◽

Inflammatory Bowel ◽

Anti Inflammatory ◽

Key Functional Groups ◽

Oxide Synthase

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1–8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.

Download Full-text

Influence of glucose transporter 1 activity inhibition on neuroblastoma in vitro

Gene ◽

10.1016/j.gene.2018.12.010 ◽

2019 ◽

Vol 689 ◽

pp. 11-17 ◽

Cited By ~ 3

Author(s):

Yan Peng ◽

Si-ning Xing ◽

Hu-ying Tang ◽

Chang-dong Wang ◽

Fa-ping Yi ◽

...

Keyword(s):

Glucose Transporter ◽

Glucose Transporter 1 ◽

Activity Inhibition

Download Full-text

Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in the microglia.

10.21203/rs.2.17969/v2 ◽

2020 ◽

Author(s):

Shao-Peng Lin ◽

Jue-Xian Wei ◽

Shan Ye ◽

Jiasong Hu ◽

Jingyi Bu ◽

...

Keyword(s):

Cognitive Impairment ◽

Inflammatory Cytokines ◽

Nuclear Translocation ◽

Neuronal Damage ◽

Protective Mechanism ◽

Protective Effects ◽

Neurocognitive Deficits ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Abstract Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in neurocognitive deficits associated with sepsis remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of artemisinin on cognitive impairment resulting from sepsis.Methods: Male C57BL/6 mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of sepsis. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical and ELISA analysis. Additionally, the protective mechanism of artemisinin was determined in vitro.Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. The in vitro experiment revealed that artemisinin could reduce the production of pro-inflammatory cytokines and suppress the microglial migration in the BV2 microglia cells. Meanwhile, western blot demonstrated that artemisinin suppressed nuclear translocation of nuclear factor kappa-B and the expression of pro-inflammatory cytokines (i.e. tumor necrosis factor alpha, interleukin-6) by activating adenosine monophosphate-activated protein kinaseα1 (AMPKα1) pathway. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin.Conclusion: Artemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect was probably mediated by the activation of AMPKα1 signalling pathway in microglia.

Download Full-text

Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NFκB Signaling Pathways in Primary Splenocytes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/3476212 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Hsin-Ling Yang ◽

Ting-Yu Yang ◽

Yugandhar Vudhya Gowrisankar ◽

Chun-Huei Liao ◽

Jiunn-Wang Liao ◽

...

Keyword(s):

Proinflammatory Cytokine ◽

Molecular Mechanisms ◽

Nuclear Translocation ◽

Ex Vivo ◽

Root Extract ◽

Piper Methysticum ◽

Serum Lipase ◽

Antioxidant Genes ◽

Anti Inflammatory

Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 μM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1β protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA’s potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF-α, IL-1β, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF-α/IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.

Download Full-text

Isoflurane protects against renal ischemia and reperfusion injury and modulates leukocyte infiltration in mice

AJP Renal Physiology ◽

10.1152/ajprenal.00161.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. F713-F722 ◽

Cited By ~ 70

Author(s):

H. Thomas Lee ◽

Mihwa Kim ◽

Minjae Kim ◽

NaLa Kim ◽

Frederic T. Billings ◽

...

Keyword(s):

Nuclear Translocation ◽

Ischemia Reperfusion ◽

Volatile Anesthetics ◽

Renal Ischemia ◽

Renal Protection ◽

Ischemia And Reperfusion Injury ◽

Pentobarbital Anesthesia ◽

Isoflurane Anesthesia ◽

Anti Inflammatory

Inflammation after renal ischemia-reperfusion (IR) injury is a major contributor to renal cell death. We previously demonstrated that several volatile anesthetics protect against renal IR injury and necrosis in rats in vivo. We subsequently showed that volatile anesthetics produced direct anti-inflammatory and anti-necrotic effects in cultured proximal tubule cells in vitro. In this study, we wanted to determine whether the volatile anesthetic isoflurane protects against renal IR injury by producing anti-inflammatory effects in mice. C57BL/6 mice subjected to renal IR under isoflurane anesthesia demonstrated improved renal function and reduced necrosis compared with mice subjected to renal IR under pentobarbital anesthesia. Mice subjected to renal IR under isoflurane anesthesia also showed a reduction in inflammation evidenced by a reduced renal influx of neutrophils and macrophages, reduced ICAM-1 expression, less upregulation of proinflammatory mRNAs (TNF-α, ICAM-1, KC, and IL-1β) as well as reduced nuclear translocation of NF-κB 24 h after renal IR injury. Analysis of specific lymphocyte subset trafficking to the kidney using flow cytometry demonstrated that isoflurane anesthesia reduced intrarenal influx of CD3+, CD4+, CD8+, and NK1.1+ lymphocytes at 3 h after renal ischemia compared with pentobarbital anesthesia. However, only the differential reduction of NK1.1+ lymphocytes persisted 24 h after renal ischemia. Therefore, we conclude that isoflurane anesthesia significantly attenuated renal IR injury in mice by reducing inflammation and modulating leukocyte influx. In particular, neutrophil, macrophage, and NK1.1+ lymphocyte cell modulation may play a significant role in renal protection by isoflurane anesthesia.

Download Full-text

Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽

10.3390/nu12072032 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2032

Author(s):

Vishnu Raj ◽

Balaji Venkataraman ◽

Saeeda Almarzooqi ◽

Sanjana Chandran ◽

Shreesh K. Ojha ◽

...

Keyword(s):

Nuclear Translocation ◽

In Vitro Models ◽

Mrna Levels ◽

Colonic Inflammation ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory ◽

Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

Download Full-text

Anti-Inflammatory and Antioxidant Effects of Anthocyanins of Trifolium pratense (Red Clover) in Lipopolysaccharide-Stimulated RAW-267.4 Macrophages

Nutrients ◽

10.3390/nu12041089 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1089 ◽

Cited By ~ 9

Author(s):

Sang Gil Lee ◽

Cindi R. Brownmiller ◽

Sun-Ok Lee ◽

Hye Won Kang

Keyword(s):

Trifolium Pratense ◽

Nuclear Translocation ◽

Red Clover ◽

Related Factor ◽

Nuclear Factor ◽

Expression Of Genes ◽

Nadph Oxidase 1 ◽

Anti Inflammatory ◽

Antioxidant Effects

Red clover (Trifolium pratense) possesses various dietary compounds that improve human health. However, the functions of anthocyanins in red clover remain unclear. Here we examined anti-inflammatory and antioxidant effects of red clover extract (RC) and red clover anthocyanins fraction (RCA) using lipopolysaccharide (LPS)-treated RAW 264.7 macrophages and identified dietary compounds. RC and RCA suppressed LPS-induced expression of genes such as tumor necrosis factor (TNF)α, interleukin (IL)1β, inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein (MCP)1, and cyclooxygenase (COX)2. LPS-stimulated intracellular reactive oxygen species (ROS) production also was prevented by both RC and RCA. NADPH oxidase 1 (NOX1) gene and phosphorylation of p47phox of NOX1 that were increased by LPS were inhibited in the cells treated with RCA. LPS-stimulated nuclear factor erythroid 2-related factor 2 (NRF2) gene expression and nuclear translocation of nuclear factor kappa B (NF-kB) subunit p65 were suppressed together with reduced iNOS and COX2 proteins by RCA. Additionally, 27 polyphenols and 7 anthocyanins from RC were identified and quantified. In conclusion, RC, especially RCA, exerted anti-inflammatory and anti-oxidative activities in vitro by regulating NF-κB and NRF2 signaling pathways, suggesting that anthocyanins in red clover are the potential candidates to reduce inflammation and oxidative stress.

Download Full-text

Transient Silencing of a Type IV P-Type ATPase,Atp10c, Results in Decreased Glucose Uptake in C2C12 Myotubes

Journal of Nutrition and Metabolism ◽

10.1155/2012/152902 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

S. E. Hurst ◽

S. C. Minkin ◽

J. Biggerstaff ◽

M. S. Dhar

Keyword(s):

Type 2 Diabetes ◽

Glucose Uptake ◽

Glucose Transporter ◽

Mapk Pathway ◽

Specific Inhibitor ◽

C2c12 Myotubes ◽

Glucose Transporter 1 ◽

Transfected Cells

Atp10cis a strong candidate gene for diet-induced obesity and type 2 diabetes. To identify molecular and cellular targets of ATP10C,Atp10cexpression was alteredin vitroin C2C12 skeletal muscle myotubes by transient transfection with anAtp10c-specific siRNA. Glucose uptake assays revealed that insulin stimulation caused a significant 2.54-fold decrease in 2-deoxyglucose uptake in transfected cells coupled with a significant upregulation of native mitogen-activated protein kinases (MAPKs), p38, and p44/42. Additionally, glucose transporter-1 (GLUT1) was significantly upregulated; no changes in glucose transporter-4 (GLUT4) expression were observed. The involvement of MAPKs was confirmed using the specific inhibitor SB203580, which downregulated the expression of native and phosphorylated MAPK proteins in transfected cells without any changes in insulin-stimulated glucose uptake. Results indicate thatAtp10cregulates glucose metabolism, at least in part via the MAPK pathway, and, thus, plays a significant role in the development of insulin resistance and type 2 diabetes.

Download Full-text