Silibinin's regulation of proliferation and collagen gene expressions of rat pancreatic β-cells cultured on types I and V collagen involves β-catenin nuclear translocation.

Extracellular matrix (ECM) molecules have multiple functions; prevention of cytotoxicity, provision of mechanical support, cell adhesive substrates and structural integrity in addition to mediation of cellular signaling. In this study, we report that the proliferation of INS-1 cells cultured on collagen I-coated dishes is enhanced, but it is inhibited on collagen V-coated dishes. Inhibitory proliferation on collagen V-coated is not due to apoptosis induction.

Silibinin protects rat pancreatic β-cell through up-regulation of estrogen receptors' signaling against amylin- or Aβ -induced reactive oxygen species/reactive nitrogen species generation.

Amylin and amyloid-β (Aβ) were found to induce reactive oxygen species (ROS) and reactive nitrogen species (RNS) in rat pancreatic β-cell line, INS-1 cells, leading to cell death. In this study, we report on reciprocal relationship between the expression of estrogen receptors (ERs) α and β (ERα and ERβ) and generation of ROS/RNS in amylin/Aβ -treated INS-1 cells. That is, pharmacological activation of ERs in INS-1 cells significantly decreases ROS/RNS generation, but blockage of ERs increases ROS/RNS generation.

Activated toll-like receptor 4 is involved in oridonin-induced phagocytosis via promotion of migration and autophagy-lysosome pathway in RAW264.7 macrophages.

In our previous study, we demonstrated that oridonin enhances phagocytosis of apoptotic bodies by macrophage-like cells by inducing autophagy. However, the direct sensor of autophagy and the key event controlling phagocytosis remains unknown. Herein, we showed that Toll-like receptor 4 (TLR4), known to mediate immune responses, was activated by oridonin.

Persistent IKKα phosphorylation induced apoptosis in UVB and Poly I:C co-treated HaCaT cells plausibly through pro-apoptotic p73 and abrogation of IκBα.

Toll-like receptor 3 (TLR3), a member of pattern recognition receptors, is reported to initiate skin inflammation by recognizing double-strand RNA (dsRNA) released from UVB-irradiated cells. Recently, we have discovered the NF-κB pathway activated by TLR3 is involved in apoptosis of UVB-Poly I:C-treated HaCaT cells. The real culprit for apoptosis has not been precisely identified since the system of NF-κB pathway is complex.

Reactive oxygen species are responsible for the cell aggregation and production of pro-inflammatory mediators in phorbol ester (PMA)-treated U937 cells on gelatin-coated dishes through upregulation of autophagy.

: Our previous studies indicate that phorbol 12-myristate 13-acetate (PMA)-treated U937 cells cultured on collagen I-coated dishes express lowered production of pro-inflammatory mediators in parallel through reduced reactive oxygen species (ROS) levels. By contrast, PMA-treated U937 cells on gelatin, the denatured collagen, show enhanced production of pro-inflammatory mediators, mediated by up-regulating autophagy levels. The present study is aimed to investigate the effect of ROS levels in PMA-treated U937 cells cultured on gelatin-coated surface.

Silibinin ameliorates amylin-induced pancreatic β-cell apoptosis partly via upregulation of GLP-1R/PKA pathway.

The objective was to investigate the mechanism of the protective effect of silibinin on amylin/Aβ-induced INS-1 cell apoptosis, with special reference to the roles of glucagon-like peptide-1 receptor (GLP-1R) and protein kinase A (PKA). The effects of silibinin on apoptosis, insulin secretion, GLP-1R, and PKA expression in the INS-1 cells treated with amylin/Aβ were examined. INS-1 cells exposed to amylin showed increased TUNEL-positive ratio, reduced expression of GLP-1R and PKA.

Silibinin-induced autophagy mediated by PPARα-sirt1-AMPK pathway participated in the regulation of type I collagen-enhanced migration in murine 3T3-L1 preadipocytes.

Preadipocyte migration is a fundamental and important process for the development of tissue organization, especially in the development of primitive adipose tissue and adipocyte tissue wound healing. However, excessive migration may result in abnormal development and fibrosis-related diseases such as hypertrophic scar. We previously reported that type I collagen (collagen I) enhanced migration of 3T3-L1 preadipocytes via phosphorylation and/or acetylation of NF-κB p65, and the enhanced cell migration is repressed by silibinin treatment through sirt1.

L-A03, a dihydroartemisinin derivative, promotes apoptotic cell death of human breast cancer MCF-7 cells by targeting c-Jun N-terminal kinase.

L-A03 is a dihydroartemisinin derivative and exerts distinct anti-tumor activity in vitro. Previous studies showed that induction of autophagy and deficiency in nitric oxide (NO) generation contributed to apoptotic cell death in L-A03-treated MCF-7 cells. However, the detailed mechanism is still unclear.

Type I collagen-induced YAP nuclear expression promotes primary cilia growth and contributes to cell migration in confluent mouse embryo fibroblast 3T3-L1 cells.

The extracellular matrix (ECM) is a major biomechanical environment for all cells in vivo, and tightly controls wound healing and cancer progression. Type I collagen (Col I) is the most abundant component in ECM and plays an essential role for cell motility control and migration beyond structural support. Our previous results showed that Col I increased the length of primary cilia and the expression of primary cilia-associated proteins in 3T3-L1 cells.

Prostaglandin E2 attenuates synergistic bactericidal effects between COX inhibitors and antibiotics on Staphylococcus aureus.

PGE2 is found to attenuate the bactericidal effects of kanamycin or ampicillin in Staphylococcus aureus, as well as the methicillin-resistant S. aureus (MRSA). Co-treatment with cyclooxygenase (COX) inhibitors (celecoxib, aspirin or naproxen) synergistically enhances kanamycin or ampicillin-induced cell death of S.

Type I collagen induces mesenchymal cell differentiation into myofibroblasts through YAP-induced TGF-β1 activation.

In organ fibrosis, mechanical stress and transforming growth factor beta-1 (TGF-β1) promote differentiation into myofibroblast from mesenchymal cells, leading to extracellular matrix (ECM) remodeling or active synthesis, deposition or degradation of ECM components. A major component of ECM, type I collagen (col I) triple helical molecules assemble into fibrils or are denatured to gelatin without triple-helicity in remodeling. However, whether changes of ECM components in remodeling have influence on mesenchymal cell differentiation remains elusive.

Differential levels of reactive oxygen species in murine preadipocyte 3T3-L1 cells cultured on type I collagen molecule-coated and gel-covered dishes exert opposite effects on NF-κB-mediated proliferation and migration.

Reactive oxygen species (ROS) participate in various cell responses in association with cell proliferation, migration, differentiation, and death. Extracellular matrix (ECM) serves as cellular microenvironments for many kinds of cells, affecting cell activities. However, whether or not ECM influences cellular ROS levels has not been well studied.

Sub-lethal ultraviolet B irradiation and Poly I:C treatment synergistically induced apoptosis of HaCaT cells through NF-κB pathway.

Ultraviolet B (UVB) irradiation exerts multiple effects on skin cells, inducing apoptosis, senescence and carcinogenesis. Toll-like receptor 3, a member of pattern recognition receptors, is reported to initiate inflammation by recognizing double-strand RNA (dsRNA) released from UVB-irradiated cells. It has not been studied, however, whether apoptosis induction in UVB irradiation is attributed to TLR3 activation.

Concentration-dependent dual effects of silibinin on kanamycin-induced cells death in Staphylococcus aureus.

Silibinin has dual effects on bacteria, depending on the concentrations or living contexts. The mechanism of either action has not yet been elucidated. Present study suggests that silibinin has yinyang impacts on the growth of Staphylococcus aureus depending on doses.

Involvement of estrogen receptors in silibinin protection of pancreatic β-cells from TNFα- or IL-1β-induced cytotoxicity.

Silibinin is a polyphenolic flavonoid that exhibits anticarcinogenic, anti-inflammatory and cytoprotective effects. The effect of silibinin on pancreatic islet β-cell is yet largely unknown in spite of well documented-hepatoprotective effects. Protecting the functional insulin-producing β-cells in the pancreas is a major therapeutic challenge in the patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM).

Salicylate induces reactive oxygen species and reduces ultraviolet C susceptibility in Staphylococcus aureus.

This study demonstrates that growth of Staphylococcus aureus in the presence of salicylate reduces ultraviolet C (UVC)-induced cell death and increases the generation of reactive oxygen species (ROS). In addition, compounds that scavenge ROS (N-acetylcysteine, glutathione, catalase and superoxide dismutase) reverse the increased UVC survival induced by growth in the presence of salicylate, while ROS donors (tert-butylhydroperoxide, H2O2 and NaClO) enhance survival of salicylate challenged cultures. Collectively, these findings suggest that ROS production induced by growth in the presence of salicylate protects S.

Estrogen Receptors Are Involved in the Neuroprotective Effect of Silibinin in Aβ-Treated Rats.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by a cascade of pathologic changes. A widely discussed theory indicates that amyloid β (Aβ) peptides are the causative agents of AD. Silibinin, a flavonoid derived from milk thistle, is well known for its hepato-protective activities and we have reported the neuroprotective effects of silibinin.

Gelatin promotes cell aggregation and pro-inflammatory cytokine production in PMA-stimulated U937 cells by augmenting endocytosis-autophagy pathway.

Gelatin, denatured collagen, temporarily exists in tissues and may well be pathophysiologically involved in tissue remodeling, inflammation or tissue damage. The present study is aimed to investigate possible biological roles of gelatin by examining its effects on monocyte-like histiocytic lymphoma cell line U937. Once stimulated by phorbol 12-myristate 13-acetate (PMA), U937 cells differentiate into macrophage-like cells, changing from non-adherent to adherent cells with extended pseudopodia.

Phorbol ester (PMA)-treated U937 cells cultured on type I collagen-coated dish express a lower production of pro-inflammatory cytokines through lowered ROS levels in parallel with cell aggregate formation.

The present study is aimed to investigate the effect of collagen I on U937 cells, human monocyte-like histiocytic lymphoma cell line. Differentiation of U937 cells was induced by phorbol ester (PMA) treatment. The cells were cultured on the collagen I-coated plate.

Enhanced migration of murine fibroblast-like 3T3-L1Â preadipocytes on type I collagen-coated dish is reversed by silibinin treatment.

Migration of fibroblast-like preadipocytes is important for the development of adipose tissue, whereas excessive migration is often responsible for impaired adipose tissue related with obesity and fibrotic diseases. Type I collagen (collagen I) is the most abundant component of extracellular matrix and has been shown to regulate fibroblast migration in vitro, but its role in adipose tissue is not known. Silibinin is a bioactive natural flavonoid with antioxidant and antimetastasis activities.

Type I collagen promotes primary cilia growth through down-regulating HDAC6-mediated autophagy in confluent mouse embryo fibroblast 3T3-L1 cells.

Primary cilia are microtubule-based organelles that extend from nearly all vertebrate cells. Abnormal ciliogenesis and cilia length are suggested to be associated with hypertension and obesity as well as diseases such as Meckel-Gruber syndrome. Extracellular matrix (ECM), comprising cellular microenvironment, influences cell shape and proliferation.

Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus.

Depression is one of the most frequent psychiatric disorders of Alzheimer's disease (AD). Depression and anxiety are associated with increased risk of developing AD. Silibinin, a flavonoid derived from milk thistle (Silybum marianum), has been used as a hepato-protectant in the clinical treatment of liver diseases.

Blocking the utilization of glucose induces the switch from senescence to apoptosis in pseudolaric acid B-treated human lung cancer cells in vitro.

Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi Gordon, exerts anti-tumor effects in several cancer cell lines. Our previous study showed that PAB mainly induced senescence via p53-p21 activation rather than apoptosis in suppression of the growth of human lung cancer A549 cells (p53 wild-type). In p53-null human lung cancer H1299 cells, however, PAB caused apoptosis without senescence.

Silibinin ameliorates Aβ-induced memory deficits in rats by modulating autophagy and attenuating neuroinflammation as well as oxidative stress.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid β (Aβ)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities.

Crosstalk of ROS/RNS and autophagy in silibinin-induced apoptosis of MCF-7 human breast cancer cells in vitro.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in regulating cell survival and death. Silibinin is a natural polyphenolic flavonoid isolated from milk thistle with anti-tumor activities, but it was found to induce cytoprotective ROS/RNS in human breast cancer MCF-7 cells. Furthermore, treatment with silibinin down-regulates ERα expression in MCF-7 cells, and inducing both autophagy and apoptosis.