scholarly journals Silymarin: Friend or Foe of UV Exposed Keratinocytes?

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1652 ◽  
Author(s):  
Fidrus ◽  
Ujhelyi ◽  
Fehér ◽  
Hegedűs ◽  
Janka ◽  
...  
Keyword(s):  
Pyrimidine Dimer ◽  
Ros Generation ◽  
Keratinocyte Cell ◽  
Pre Treatment ◽  
Different Origins ◽  
Apoptotic Effects ◽  
Dose Dependent ◽  
Higher Doses

The application of natural plant extracts in UV-protection is popular and intensively studied. Silymarin (from Silibum marianum), a naturally occurring polyphenol, has recently received attention due to its antioxidant, anti-inflammatory and anti-apoptotic effects. However, its role in the UV-mediated keratinocyte cell response is still controversial. In this study, we investigated the effects of Silibum marianum extracts with different origins and formulations on UVA-exposed HaCaT keratinocytes in vitro. Our results show, that silymarin treatment caused an inverse dose-dependent photosensitivity relationship (at higher doses, a decrease in cell viability and ROS production) after UVA exposure. The attenuation of the UVA-induced ROS generation after silymarin treatment was also observed. Moreover, silymarin pre-treatment increased the cyclobutane pyrimidine dimer photolesions in keratinocytes after UVA exposure. These results indicated the dual role of silymarin in UVA-exposed keratinocytes. It scavenges ROS but still induces phototoxicity. Based on our results dermatological applications of silymarin and related compounds should be considered very carefully.

scholarly journals Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes

2021 ◽  
Vol 22 (5) ◽  
pp. 2347
Author(s):  
Manu N. Capoor ◽  
Anna Konieczna ◽  
Andrew McDowell ◽  
Filip Ruzicka ◽  
Martin Smrcka ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Acne Vulgaris ◽  
Opportunistic Pathogen ◽  
Intervertebral Discs ◽  
Disc Disease ◽  
Gene Target ◽  
Cutibacterium Acnes ◽  
Pre Treatment

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1β and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

scholarly journals Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

2021 ◽  
Vol 22 (9) ◽  
pp. 4717
Author(s):  
Jin-Young Lee ◽  
Da-Ae Kim ◽  
Eun-Young Kim ◽  
Eun-Ju Chang ◽  
So-Jeong Park ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Map Kinases ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Dual Action ◽  
Dose Dependent ◽  
Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

scholarly journals A Novel Tetrapeptide Derivative Exhibits In Vitro Inhibition of Neutrophil-Derived Reactive Oxygen Species and Lysosomal Enzymes Release

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sumitra Miriyala ◽  
Manikandan Panchatcharam ◽  
Meera Ramanujam ◽  
Rengarajulu Puvanakrishnan
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Anion ◽  
Lysosomal Enzymes ◽  
Reactive Oxygen ◽  
Peptide Sequence ◽  
Ros Generation ◽  
Oxygen Species ◽  
Complement Factors

Neutrophil infiltration plays a major role in the pathogenesis of myocardial injury. Oxidative injury is suggested to be a central mechanism of the cellular damage after acute myocardial infarction. This study is pertained to the prognostic role of a tetrapeptide derivative PEP1261 (BOC-Lys(BOC)-Arg-Asp-Ser(tBu)-OtBU), a peptide sequence (39–42) of lactoferrin, studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation, lysosomal enzymes release, and enhanced expression of C proteins. The groundwork experimentation was concerned with the isolation of neutrophils from the normal and acute myocardial infarct rats to find out the efficacy of PEP1261 in the presence of a powerful neutrophil stimulant, phorbol 12-myristate 13 acetate (PMA). Stimulation of neutrophils with PMA resulted in an oxidative burst of superoxide anion and enhanced release of lysosomal enzymes and expression of complement proteins. The present study further demonstrated that the free radicals increase the complement factors in the neutrophils confirming the role of ROS. PEP1261 treatment significantly reduced the levels of superoxide anion and inhibited the release of lysosomal enzymes in the stimulated control and infarct rat neutrophils. This study demonstrated that PEP1261 significantly inhibited the effect on the ROS generation as well as the mRNA synthesis and expression of the complement factors in neutrophils isolated from infarct heart.

Inhibitory Effects of Purple Sweet Potato Leaf Extract on the Proliferation and Lipogenesis of the 3T3-L1 Preadipocytes

2015 ◽  
Vol 43 (05) ◽  
pp. 915-925 ◽  
Author(s):  
Shou-Lun Lee ◽  
Hsien-Kuang Lee ◽  
Ting-Yu Chin ◽  
Ssu-Chieh Tu ◽  
Ming-Hsun Kuo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sweet Potato ◽  
Early Stage ◽  
Water Extract ◽  
Potato Leaf ◽  
Purple Sweet Potato ◽  
Pre Treatment ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Purple sweet potato leaves (PSPLs) are healthy vegetable that is rich in anti-oxidants. A solution of boiling water extract of PSPL (PSPLE) is believed to be able to prevent obesity and metabolic syndrome in the countryside of Taiwan, but its efficacy has not yet been verified. The purpose of this study was to investigate the possible anti-adipogenesis effect of PSPLE in vitro. PSPLE was used to treat the 3T3-L1 cells, and the effects on cell proliferation and adipogenesis were investigated. The results showed that PSPLE caused a dose-dependent decrease in the cell proliferation of 3T3-L1 preadipocytes, but did not alter the cell viability. In addition, PSPLE induced ERK inactivation in the 3T3-L1 preadipocytes. Furthermore, pre-treatment of confluent 3T3-L1 cells with PSPLE led to reduced lipid accumulation in differentiated 3T3-L1 cells. The inhibition of lipogenesis could result from the PSPLE-induced down-regulation of the expression of the C/EBPα and SREBP-1 transcription factors during 3T3-L1 adipocyte differentiation. These results suggest that PSPLE not only inhibits cell proliferation at an early stage but also inhibits adipogenesis at a later stage of the differentiation program.

Human vascular smooth muscle responses mediated by α2 mechanisms in vivo and in vitro

1985 ◽  
Vol 68 (s10) ◽  
pp. 147s-150s ◽  
Author(s):  
S. Thom ◽  
J. Calvete ◽  
R. Hayes ◽  
G. Martin ◽  
P. Sever
Keyword(s):  
Smooth Muscle ◽  
Physiological Role ◽  
Smooth Muscle Contraction ◽  
Α1 Receptors ◽  
Dose Dependent ◽  
Higher Doses ◽  
Α2 Receptors ◽  
Autoregulatory Mechanism

1. The effects of compounds with α2-agonist and α2-antagonist properties on human forearm blood flow and on isolated human arterial segments have been studied. 2. The findings from these studies in vivo and in vitro did not provide evidence in support of the hypothesis that postsynaptic α2-receptors mediate smooth muscle contraction in the tissues under investigation. 3. The constriction of the forearm vascular bed in response to low intra-arterial doses of idazoxan (RX 781094), an α2-antagonist, provides evidence for a physiological role for a presynaptic α2 autoregulatory mechanism. 4. The variability of the forearm vascular responses to higher doses of idazoxan highlights the pitfalls that may have misled previous authors in their interpretation of the results of similar studies. A U-shaped dose-response curve to compounds with mixed α2-and α1-antagonist properties may be constructed, which emphasizes the importance of the dose-dependent selectivity of these antagonists at α2- and α1-receptors. 5. The effect of idazoxan on the responses of arterial segments in vitro to exogenous catecholamines was dependent on the integrity of the endothelium, and provides evidence that α2-receptors may mediate release of the endothelium-derived relaxing factor.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

scholarly journals A75 ROLE OF LRRK2 IN INFLAMMATORY BOWEL DISEASE

2018 ◽  
Vol 1 (suppl_2) ◽  
pp. 118-118
Author(s):  
J Rocha ◽  
C Sun ◽  
M Glogauer ◽  
D Philpott
Keyword(s):  
Listeria Monocytogenes ◽  
Myeloid Cell ◽  
Mucosal Barrier ◽  
Ros Generation ◽  
Transwell Assay ◽  
Bacteria Growth ◽  
Tlr4 Ligand

Abstract Background Variants of the leucine-rich repeat kinase 2 (LRRK2) are associated with an increased susceptibility to Parkinson disease but also Crohn’s disease (CD). Aims The present research is designed to develop a comprehensive understanding of the role of LRRK2 in immune system modulation, and how dysfunction of this pathway may lead to the development of CD. Methods WT and LRRK2-deficient neutrophil were infected with Gram-positive Bacteria (Listeria monocytogenes-LM) in a gentamicin protection assays and colony-forming unit assessment will determine the competence of LRRK2 deficient cells for bacterial phagocytosis as well as killing capacity). To examine how LRRK2 is involved in the generation of ROS during the respiratory burst, we will first examine if neutrophil from LRRK2-KO mice have altered ROS generation upon infection with LM and addition of PMA. We evaluate in vitro the ability of neutrophils from LRRK2-KO versus WT mice to transmigrate in vitro in a transwell assay using fMLP as a chemattractant. Also, we investigate the peritoneal cells (by FACS analysis) after injection of different microbial stimuli including FK105 (NOD1 ligand), MDP (NOD2 ligand) and LPS (TLR4 ligand) and anti-cd3 model of ielitis. Results We found that LRRK2 KO mice have a defect in migration of neutrophils to the peritoneal cavity after injection of different microbial stimuli including FK10565 (NOD1 ligand), MDP (NOD2 ligand) and LPS (TLR4 ligand). Neutrophils from LRRK2 mice were compromised in their ability to transmigrate in vitro in a transwell assay using fMLP as a chemoattractant. Chemotaxis was also compromised. In parallel, we designed experiments to examine reactive oxygen species (ROS) produced in response to infection of myeloid cells with bacteria. Neutrophils from LRRK2 KO mice infected with Listeria monocytogenes were less able to restrict bacteria growth compared to WT cells. Consistent with these findings, cells from LRRK2 KO mice produced lower levels of ROS following bacterial infection. In order to determine whether myeloid cell migration is compromised in vivo during inflammation, we performed experiments in WT and KO mice looking at different models of ileitis/colitis. Conclusions With this work we will further characterize the role of LRRK2 in intestinal homeostasis and mucosal barrier maintenance, including how its deficiency may predispose an individual to developing CD. Funding Agencies CAG, CIHR

scholarly journals Antioxidant Therapy in Graves’ Orbitopathy

2020 ◽  
Vol 11 ◽  
Author(s):  
Giulia Lanzolla ◽  
Claudio Marcocci ◽  
Michele Marinò
Keyword(s):  
Ros Generation ◽  
Related Condition ◽  
Orbital Radiotherapy ◽  
Antioxidant Agents ◽  
Graves Orbitopathy ◽  
High Doses

The balance of the cell redox state is a key point for the maintenance of cellular homeostasis. Increased reactive oxygen species (ROS) generation leads to oxidative damage of tissues, which is involved in the development of several diseases, including autoimmune diseases. Graves’ Orbitopathy (GO) is a disfiguring autoimmune-related condition associated with Graves’ Disease (GD). Patients with active, moderate-to-severe GO, are generally treated with high doses intravenous glucocorticoids (ivGCs) and/or orbital radiotherapy. On the contrary, up to recently, local ointments were the treatment most frequently offered to patients with mild GO, because the risks related to ivGCs does not justify the relatively poor benefits expected in mild GO. However, a medical treatment for these patients is heavily wanted, considering that GO can progress into more severe forms and also patients with mild GO complain with an impairment in their quality of life. Thus, based on the role of oxidative stress in the pathogenesis of GO, a therapy with antioxidant agents has been proposed and a number of studies have been performed, both in vitro and in vivo, which is reviewed here.

scholarly journals Ethnopharmacological basis for antispasmodic, antidiarrheal and antiemetic activities of Ceratonia siliqua pods

2017 ◽  
Vol 12 (4) ◽  
pp. 384
Author(s):  
Irfan Hamid ◽  
Khalid Hussain Janbaz
Keyword(s):  
Crude Extract ◽  
Video Clip ◽  
Dependent Manner ◽  
Ceratonia Siliqua ◽  
Spasmolytic Activity ◽  
Rabbit Jejunum ◽  
Pre Treatment ◽  
Dose Dependent

<p class="Abstract">The study was conducted to provide the ethnopharmacological bases of the crude extract of seed pods of <em>Ceratonia siliqua</em> in the gastrointestinal spasm, diarrhea and emesis. In segregated rabbit jejunum, it showed dose-dependent (0.01-10 mg/mL) relaxation of spontaneous as well as carbachol (1 µM)-induced contraction. Pre-treatment of segregated rat ileum with <em>C. siliqua</em>, significantly (p&lt;0.0001) suppressed the carbachol (1 µM)-induced contraction similar to atropine (1 µM). These results indicated that <em>C. siliqua</em> possesses spasmolytic activity through possible blockage of muscarinic receptor in jejunum preparations. Furthermore, the crude extract inhibited the castor oil-induced diarrhea, charcoal meal propulsion in mice and copper sulfate-induced retches in chicks in a dose-dependent manner (100, 200, 300 mg/kg). These in vitro and in vivo results indicate that <em>C. siliqua</em> possesses the spasmolytic and antidiarrheal activities mediated possibly through blockage of muscarinic receptors. Thus, this study provides a rationale for its folkloric use.</p><p><strong>Video Clip of Methodology</strong>:</p><p>12 min 42 sec   <a href="https://www.youtube.com/v/BQGWdIZqpsY">Full Screen</a>   <a href="https://www.youtube.com/watch?v=BQGWdIZqpsY">Alternate</a></p>

cAMP-stimulated rise of [Ca2+]i in rabbit connecting tubules: role of peritubular Ca

1990 ◽  
Vol 258 (3) ◽  
pp. F751-F755 ◽  
Author(s):  
J. E. Bourdeau ◽  
B. K. Eby
Keyword(s):  
Parathyroid Hormone ◽  
Ethylene Glycol ◽  
Cell Activation ◽  
Proximal Tubules ◽  
Tetraacetic Acid ◽  
Luminal Membrane ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Parathyroid hormone (PTH) increases cytosolic free Ca concentration ([ Ca2+]i) by mechanisms that depend on extracellular Ca in both cultured renal proximal tubules and isolated rabbit connecting tubules (CNTs). In CNTs 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) mimics this action, implicating cAMP as a second messenger, and part of the rise, due to increased luminal membrane Ca entry, is likely related to Ca absorption. In cultured proximal tubules the rise in [Ca2+]i, presumably mediated by increased Ca entry across the basolateral plasmalemma, activates gluconeogenesis and shortens microvilli. In the present study we examined cAMP-mediated Ca entry across the basolateral membranes of CNT cells, an effect potentially related to cell activation. Single CNTs were dissected from rabbit kidneys and loaded with fura-2. [Ca2+]i was measured by dual-wavelength excitation during perfusion of isolated segments in vitro. With 1.8 or 2.0 mM Ca in the lumen and the bath, suffusate 8-BrcAMP increased [Ca2+]i within minutes in a dose-dependent fashion. The increase persisted as long as 8-BrcAMP was present and reversed on its withdrawal. With 0.1 microM Ca in the lumen and the bath, 8-BrcAMP, but not ionomycin, failed to increase [Ca2+]i, implying that extracellular Ca is the major source. In tubules perfused with 2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to eliminate luminal Ca, but suffused with 1.8 or 2.0 mM Ca, 8-BrcAMP increased [Ca2+]i (though less so than with Ca in the lumen), implying Ca entry across basolateral cell membranes. This rise in [Ca2+]i was attenuated markedly by the presence of 50 microM LaCl3 in the bath.(ABSTRACT TRUNCATED AT 250 WORDS)

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