scholarly journals Anti-Melanogenesis Effects of Lotus Seedpod In Vitro and In Vivo

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3535
Author(s):  
Jen-Ying Hsu ◽  
Hui-Hsuan Lin ◽  
Ting-Shuan Li ◽  
Chaio-Yun Tseng ◽  
Yueching Wong ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Camp Response Element Binding ◽  
Anticancer Activities ◽  
Melanin Production ◽  
Melanocyte Stimulating Hormone ◽  
Element Binding Protein ◽  
Main Component ◽  
Lotus Seedpod

Melanogenesis has many important physiological functions. However, abnormal melanin production causes various pigmentation disorders. Melanin synthesis is stimulated by α-melanocyte stimulating hormone (α-MSH) and ultraviolet (UV) irradiation. Lotus seedpod extract (LSE) has been reported as possessing antioxidative, anti-aging, and anticancer activities. The present study examined the effect of LSE on melanogenesis and the involved signaling pathways in vitro and in vivo. Results showed that non-cytotoxic doses of LSE and its main component epigallocatechin (EGC) reduced both tyrosinase activity and melanin production in the α-MSH-induced melanoma cells. Western blotting data revealed that LSE and EGC inhibited expressions of tyrosinase and tyrosinase-related protein 1 (TRP-1). Phosphorylation of p38 and protein kinase A (PKA) stimulated by α-MSH was efficiently blocked by LSE treatment. Furthermore, LSE suppressed the nuclear level of cAMP-response element binding protein (CREB) and disturbed the activation of melanocyte inducing transcription factor (MITF) in the α-MSH-stimulated B16F0 cells. The in vivo study revealed that LSE inhibited melanin production in the ear skin of C57BL/6 mice after exposure to UVB. These findings suggested that the anti-melanogenesis of LSE involved both PKA and p38 signaling pathways. LSE is a potent novo natural depigmenting agent for cosmetics or pharmaceutical applications.

scholarly journals The chromatin-binding protein HMGN3 stimulates histone acetylation and transcription across the Glyt1 gene

2012 ◽  
Vol 442 (3) ◽  
pp. 495-505 ◽  
Author(s):  
Gráinne Barkess ◽  
Yuri Postnikov ◽  
Chrisanne D. Campos ◽  
Shivam Mishra ◽  
Gokula Mohan ◽  
...  
Keyword(s):  
Histone Modifications ◽  
Splice Variants ◽  
Binding Protein ◽  
Histone H3 ◽  
Camp Response Element Binding ◽  
Element Binding Protein ◽  
H3k14 Acetylation ◽  
H3 Acetylation

HMGNs are nucleosome-binding proteins that alter the pattern of histone modifications and modulate the binding of linker histones to chromatin. The HMGN3 family member exists as two splice forms, HMGN3a which is full-length and HMGN3b which lacks the C-terminal RD (regulatory domain). In the present study, we have used the Glyt1 (glycine transporter 1) gene as a model system to investigate where HMGN proteins are bound across the locus in vivo, and to study how the two HMGN3 splice variants affect histone modifications and gene expression. We demonstrate that HMGN1, HMGN2, HMGN3a and HMGN3b are bound across the Glyt1 gene locus and surrounding regions, and are not enriched more highly at the promoter or putative enhancer. We conclude that the peaks of H3K4me3 (trimethylated Lys4 of histone H3) and H3K9ac (acetylated Lys9 of histone H3) at the active Glyt1a promoter do not play a major role in recruiting HMGN proteins. HMGN3a/b binding leads to increased H3K14 (Lys14 of histone H3) acetylation and stimulates Glyt1a expression, but does not alter the levels of H3K4me3 or H3K9ac enrichment. Acetylation assays show that HMGN3a stimulates the ability of PCAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] to acetylate nucleosomal H3 in vitro, whereas HMGN3b does not. We propose a model where HMGN3a/b-stimulated H3K14 acetylation across the bodies of large genes such as Glyt1 can lead to more efficient transcription elongation and increased mRNA production.

scholarly journals Transcriptional Regulation of ZNF638 in Thermogenic Cells by the cAMP Response Element Binding Protein in Male Mice

2019 ◽  
Vol 3 (12) ◽  
pp. 2326-2340 ◽  
Author(s):  
Luce Perie ◽  
Narendra Verma ◽  
Lingyan Xu ◽  
Xinran Ma ◽  
Elisabetta Mueller
Keyword(s):  
Zinc Finger ◽  
Binding Protein ◽  
Regulatory Region ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein ◽  
Thermogenic Adipocytes

Abstract Zinc finger factors are implicated in a variety of cellular processes, including adipose tissue differentiation and thermogenesis. We have previously demonstrated that zinc finger protein 638 (ZNF638) is a transcriptional coactivator acting as an early regulator of adipogenesis in vitro. In this study, we show, to our knowledge for the first time, that, in vivo, ZNF638 abounds selectively in mature brown and subcutaneous fat tissues and in fully differentiated thermogenic adipocytes. Furthermore, gene expression studies revealed that ZNF638 is upregulated by cAMP modulators in vitro and by cold exposure and by pharmacological stimulation of β-adrenergic signaling in vivo. In silico analysis of the upstream regulatory region of the ZNF638 gene identified two putative cAMP response elements within 500 bp of the ZNF638 transcription start site. Detailed molecular analysis involving EMSA and chromatin immunoprecipitation assays demonstrated that cAMP response element binding protein (CREB) binds to these cAMP response element regions of the ZNF638 promoter, and functional studies revealed that CREB is necessary and sufficient to regulate the levels of ZNF638 transcripts. Taken together, these results demonstrate that ZNF638 is selectively expressed in mature thermogenic adipocytes and tissues and that its induction in response to classic stimuli that promote heat generation is mediated via CREB signaling, pointing to a possible novel role of ZNF638 in brown and beige fat tissues.

Interactions between CBP, NF-κB, and CREB in the lungs after hemorrhage and endotoxemia

2001 ◽  
Vol 281 (2) ◽  
pp. L418-L426 ◽  
Author(s):  
Robert Shenkar ◽  
Ho-Kee Yum ◽  
John Arcaroli ◽  
John Kupfner ◽  
Edward Abraham
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Xanthine Oxidase ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Proinflammatory Mediators ◽  
Element Binding Protein

The transcriptional regulatory factor nuclear factor (NF)-κB has a central role in modulating expression of proinflammatory mediators that are important in acute lung injury. In vitro studies have shown that competition between NF-κB and cAMP response element binding protein (CREB) for binding to the coactivator CREB-binding protein (CBP) is important in regulating transcriptional activity of these factors. In the present study, we examined in vivo interactions between CBP, CREB, and NF-κB in hemorrhage- or endotoxemia-induced acute lung injury. Association of CBP with CREB or the p65 subunit of NF-κB increased in the lungs after hemorrhage or endotoxemia. Inhibition of xanthine oxidase before hemorrhage, but not before endotoxemia, decreased p65-CBP interactions while increasing those between CREB and CBP. These alterations in CREB-CBP and p65-CBP interactions were functionally significant because xanthine oxidase inhibition before hemorrhage resulted in increased expression of the CREB-dependent gene c-Fos and decreased expression of macrophage inflammatory protein-2, a NF-κB-dependent gene. The present results show that the coactivator CBP has an important role in modulating transcription in vivo under clinically relevant pathophysiological conditions.

scholarly journals Preconditioning mice with activators of AMPK ameliorates ischemic acute kidney injury in vivo

2016 ◽  
Vol 311 (4) ◽  
pp. F731-F739 ◽  
Author(s):  
Wilfred Lieberthal ◽  
Meiyi Tang ◽  
Mark Lusco ◽  
Mersema Abate ◽  
Jerrold S. Levine
Keyword(s):  
Metabolic Stress ◽  
Kidney Injury ◽  
Camp Response Element Binding ◽  
Hexokinase Ii ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
Proximal Tubular ◽  
Amp Activated Protein Kinase

This study had two objectives: 1) to determine whether preconditioning cultured proximal tubular cells (PTCs) with pharmacological activators of AMP-activated protein kinase (AMPK) protects these cells from apoptosis induced by metabolic stress in vitro and 2) to assess the effects of preconditioning mice with these agents on the severity of ischemic acute renal kidney injury (AKI) in vivo. We demonstrate that preconditioning PTCs with 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) or A-769662 reduces apoptosis of PTCs induced by subsequent stress. We also show that the reduction in cell death during metabolic stress associated with pretreatment by AMPK activators is associated with an increase in the cytosolic level of ATP, which is mediated by an increase in the rate of glycolysis. In addition, we provide evidence that the effect of AMPK activators on glycolysis is mediated, at least in part, by an increased uptake of glucose, and by the induction of hexokinase II (HK II) expression. Our data also show that the increased in HK II expression associated with preconditioning with AMPK activators is mediated by the activation (phosphorylation) of the cAMP-response element binding protein (CREB). We also provide entirely novel evidence that that A-79662 is substantially more effective than AICAR in mediating these alterations in PTCs in vitro. Finally, we demonstrate that preconditioning mice with AICAR or A-769662 substantially reduces the severity of renal dysfunction and tubular injury in a model of ischemic AKI in vivo and that the efficacy of AICAR and A-768662 in ameliorating ischemic AKI in vivo is comparable.

scholarly journals Antimelanogenic activities of piperlongumine derived from Piper longum on murine B16F10 melanoma cells in vitro and zebrafish embryos in vivo: its molecular mode of depigmenting action

2019 ◽  
Vol 62 (1) ◽  
Author(s):  
Hwang-Ju Jeon ◽  
Kyeongnam Kim ◽  
Yong-Deuk Kim ◽  
Sung-Eun Lee
Keyword(s):  
Melanoma Cells ◽  
Positive Control ◽  
Zebrafish Embryos ◽  
B16f10 Melanoma ◽  
Melanin Production ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Melanoma Cells ◽  
Pharmaceutical Industries

Abstract In this study, the antimelanogenic activity of piperlongumine in murine B16F10 melanoma cells and zebrafish was investigated, and its mode of antimelanogenic action was elucidated using quantitative reverse transcription-polymerase chain reaction. A melanocyte-stimulating hormone (α-MSH, 200 nM) was used to induce melanin production in B16F10 melanoma cells, and kojic acid (200 μM) was used as a positive control. Piperlongumine had no inhibitory effects on cell growth at the treated concentrations (3 and 6 μM), and it significantly reduced total melanin production. Piperlongumine decreased the expression of Mitf, Tyr, Trp-1, and Trp-2 and tyrosinase activity was also dramatically reduced by the piper amide addition under α-MSH treatment. With these findings, zebrafish embryos were used to confirm antimelanogenic activity of piperlongumine, and it showed the potent antimelanogenic activity at the concentration of 1 μM. Altogether, piperlongumine has potent antimelanogenic activity, and these results support it as a candidate for natural depigmentation agent in a cosmetic and pharmaceutical industries.

scholarly journals Promising Anticancer Activities of Alismatis rhizome and Its Triterpenes via p38 and PI3K/Akt/mTOR Signaling Pathways

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2455
Author(s):  
Eungyeong Jang ◽  
Jang-Hoon Lee
Keyword(s):  
Cancer Cells ◽  
Signaling Pathways ◽  
Biological Activities ◽  
Experimental Models ◽  
Mtor Signaling ◽  
Flowering Plant ◽  
In Vivo Studies ◽  
Anticancer Activities

The flowering plant genus Alisma, which belongs to the family Alismataceae, comprises 11 species, including Alisma orientale, Alisma canaliculatum, and Alisma plantago-aquatica. Alismatis rhizome (Ze xie in Chinese, Takusha in Japanese, and Taeksa in Korean, AR), the tubers of medicinal plants from Alisma species, have long been used to treat inflammatory diseases, hyperlipidemia, diabetes, bacterial infection, edema, oliguria, diarrhea, and dizziness. Recent evidence has demonstrated that its extract showed pharmacological activities to effectively reverse cancer-related molecular targets. In particular, triterpenes naturally isolated from AR have been found to exhibit antitumor activity. This study aimed to describe the biological activities and plausible signaling cascades of AR and its main compounds in experimental models representing cancer-related physiology and pathology. Available in vitro and in vivo studies revealed that AR extract possesses anticancer activity against various cancer cells, and the efficacy might be attributed to the cytotoxic and antimetastatic effects of its alisol compounds, such as alisol A, alisol B, and alisol B 23-acetate. Several beneficial functions of triterpenoids found in AR might be due to p38 activation and inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways. Moreover, AR and its triterpenes inhibit the proliferation of cancer cells that are resistant to chemotherapy. Thus, AR and its triterpenes may play potential roles in tumor attack, as well as a therapeutic remedy alone and in combination with other chemotherapeutic drugs.

North American ginseng (Panax quinquefolius) suppresses β-adrenergic-dependent signalling, hypertrophy, and cardiac dysfunction

2016 ◽  
Vol 94 (12) ◽  
pp. 1325-1335 ◽  
Author(s):  
Xilan Tang ◽  
Xiaohong Tracey Gan ◽  
Venkatesh Rajapurohitam ◽  
Cathy Xiaoling Huang ◽  
Jenny Xue ◽  
...  
Keyword(s):  
Gene Expression ◽  
North American ◽  
American Ginseng ◽  
Camp Response Element Binding ◽  
Left Ventricular ◽  
Hypertrophic Response ◽  
Element Binding Protein ◽  
And Function

There is increasing evidence for a beneficial effect of ginseng on cardiac pathology. Here, we determined whether North American ginseng can modulate the deleterious effects of the β-adrenoceptor agonist isoproterenol on cardiac hypertrophy and function using in vitro and in vivo approaches. Isoproterenol was administered for 2 weeks at either 25 mg/kg per day or 50 mg/kg per day (ISO25 or ISO50) via a subcutaneously implanted osmotic mini-pump to either control rats or those receiving ginseng (0.9 g/L in the drinking water ad libitum). Isoproterenol produced time- and dose-dependent left ventricular dysfunction, although these effects were attenuated by ginseng. Improved cardiac functions were associated with reduced heart masses, as well as prevention in the upregulation of the hypertrophy-related fetal gene expression. Lung masses were similarly attenuated, suggesting reduced pulmonary congestion. In in vitro studies, ginseng (10 μg/mL) completely suppressed the hypertrophic response to 1 μmol/L isoproterenol in terms of myocyte surface area, as well as reduction in the upregulation of fetal gene expression. These effects were associated with attenuation in both protein kinase A and cAMP response element-binding protein phosphorylation. Ginseng attenuates adverse cardiac adrenergic responses and, therefore, may be an effective therapy to reduce hypertrophy and heart failure associated with excessive catecholamine production.

scholarly journals Hormonal Regulation of Autophagy in Thyroid PCCL3 Cells and the Thyroids of Male Mice

2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Tomomi Kurashige ◽  
Yasuyo Nakajima ◽  
Mika Shimamura ◽  
Masanobu Yamada ◽  
Yuji Nagayama
Keyword(s):  
Knockout Mice ◽  
Hormonal Regulation ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Pkc Signaling ◽  
Element Binding Protein ◽  
Autophagic Activity ◽  
Lc3 Puncta

Abstract Autophagy is an evolutionarily conserved catabolic process by which cells degrade intracellular proteins and organelles in the lysosomes and recycle their metabolites. We have recently demonstrated the crucial role for the basal level of autophagic activity in thyrocyte survival and homeostasis using the thyroid-specific autophagy knockout mice. Here, we first studied hormonal regulation of autophagy in thyrocytes in vitro using a rat thyroid cell line PCCl3 and in vivo with mice. In cultured PCCl3 cells, thyroxine decreased microtubule-associated protein 1 light chain 3 (LC3) puncta (a component of autophagosome) and increased p62 (an autophagy substrate) levels, showing thyroxine-suppression of autophagy. In contrast, TSH increased both LC3 puncta and p62 levels, but at the same time stabilized p62 protein by inhibiting p62 degradation, indicating TSH induction of autophagy. Our experiments with various inhibitors identified that both the cAMP-protein kinase (PK) A-cAMP response element binding protein/ERK and PKC signaling pathways regulates positively autophagic activity. The in vivo results obtained with wild-type mice treated with methimazole and perchlorate or thyroxine were consistent with in vitro results. Next, in thyroid-specific autophagy knockout mice treated with methimazole and perchlorate (that is, mice were placed under a stressed condition where enhanced autophagy was required) for 2 months, lower follicle sizes and lower thyroglobulin contents in thyrocytes were observed, suggesting impaired thyroglobulin production presumably from insufficient nutrient supply. We therefore conclude that TSH positively regulates autophagic activity through the cAMP-PKA-cAMP response element binding protein/ERK and PKC signaling pathways, whereas thyroid hormones inhibit its activity in thyrocytes. Metabolites produced by autophagy appear to be necessary for protein synthesis stimulated by TSH.

scholarly journals Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis via Repressing RANKL Signaling and Reactive Oxygen Species

2021 ◽  
Vol 12 ◽  
Author(s):  
Delong Chen ◽  
Qingqing Wang ◽  
Ying Li ◽  
Ping Sun ◽  
Vincent Kuek ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Wide Spectrum ◽  
Preclinical Model ◽  
Tartrate Resistant Acid Phosphatase ◽  
Ros Scavenging ◽  
Scavenging Enzymes ◽  
Main Component ◽  
Ros Scavenging Enzymes

Integrity of the skeleton is sustained through the balanced activities of osteoblasts and osteoclasts in bone remodeling unit. The balance can be disrupted by excessive osteoclasts activation commonly seen in osteoporosis. Notopterol (NOT) is a main component of Notopterygium incisum which exerts a wide spectrum effect on biomedical pharmacology. In our study, we found NOT serves as an inhibitor in regulating RANKL-activated osteoclasts formation and bone resorption function by calculating tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assays. Furthermore, RANKL-mediated signaling pathways including MAPK, NF-κB and calcium ossification were hampered, whereas ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathways were promoted by NOT. In addition, the activation of the essential transcription factor NFATc1 in RANKL-mediated osteoclastogenesis was almost totally suppressed by NOT. What is more, NOT diminished the loss of bone mass in preclinical model of OVX mice by blocking osteoclastogenesis determined by bone histomorphometry, TRAcP staining and H&E staining. Conclusively, our findings demonstrated that NOT could arrest osteoclastogenesis and bone resorptive activity by attenuating RANKL-mediated MAPK, NF-κB, calcium and NFATc1 signaling transduction pathways and enhancing ROS scavenging enzymes in Nrf2/Keap1/ARE pathways in vitro, and prohibit bone loss induced by OVX in vivo. Taken together, NOT may be identified to be a natural and novel treatment for osteolytic diseases.

scholarly journals Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Chunfang Liu ◽  
Yanfang Zheng ◽  
Wen Xu ◽  
Hui Wang ◽  
Na Lin
Keyword(s):  
Magnesium Sulphate ◽  
Camp Response Element Binding ◽  
Dependent Manner ◽  
Active Components ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
Dependent Protein ◽  
Ht 29

Tannins, a group of major active components of Chinese rhubarb and widely distributed in nature, have a significant antidiarrhoeal activity. Aquaporins (AQPs) 2 and 3 play important roles in regulating water transfer during diarrhoea. The present study aims to determine the effect of the total tannins extract of rhubarb on aquaporins (AQPs) 2 and 3 in diarrhoea mice and HT-29 cells both induced by magnesium sulphate (MgSO4). Our results showed that rhubarb tannins extract (RTE) significantly decreased the faecal water content in colon and evaluation index of defecation of diarrhoea mice. Interestingly, RTE could markedly reduce the mRNA and protein expression levels of AQPs 2 and 3 in apical and lateral mucosal epithelial cells in the colons of diarrhoea mice and HT-29 cells both induced by MgSO4in a dose-dependent manner. Furthermore, RTE suppressed the production of cyclic monophosphate- (cAMP-) dependent protein kinase A catalytic subunitsα(PKA C-α) and phosphorylated cAMP response element-binding protein (p-CREB, Ser133) in MgSO4-induced HT-29 cells. Our data showed for the first time that RTE inhibit AQPs 2 and 3 expressionin vivoandin vitrovia downregulating PKA/p-CREB signal pathway, which accounts for the antidiarrhoeal effect of RTE.

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