Sulawesi propolis induces higher apoptotic activity and lower inflammatory activity in a rat endometriosis model
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ABSTRACT:
SUBMITTER: Situmorang H
PROVIDER: S-EPMC10518513 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
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Project description:Successful lung transplantation has been limited by the high incidence of acute graft rejection. There is mounting evidence that the stress response gene heme oxygenase-1 (HO-1) and/or its catalytic by-product carbon monoxide (CO) confers cytoprotection against tissue and cellular injury. This led us to hypothesize that CO may protect against lung transplant rejection via its anti-inflammatory and antiapoptotic effects. Orthotopic left lung transplantation was performed in Lewis rat recipients from Brown-Norway rat donors. HO-1 mRNA and protein expression were markedly induced in transplanted rat lungs compared to sham-operated control lungs. Transplanted lungs developed severe intraalveolar hemorrhage, marked infiltration of inflammatory cells, and intravascular coagulation. However, in the presence of CO exposure (500 ppm), the gross anatomy and histology of transplanted lungs showed marked preservation. Furthermore, transplanted lungs displayed increased apoptotic cell death compared with the transplanted lungs of CO-exposed recipients, as assessed by TUNEL and caspase-3 immunostaining. CO exposure inhibited the induction of IL-6 mRNA and protein expression in lung and serum, respectively. Gene array analysis revealed that CO also down-regulated other proinflammatory genes, including MIP-1alpha and MIF, and growth factors such as platelet-derived growth factor, which were up-regulated by transplantation. These data suggest that the anti-inflammatory and antiapoptotic properties of CO confer potent cytoprotection in a rat model of lung transplantation.
| S-EPMC1868152 | biostudies-literature
Project description:IntroductionEndometriosis is a disease that impacts around 10% of all women in reproductive age, with pelvic pain and infertility as its main clinical features. Current medical treatment targeting lowering estrogen activity has not shown sufficient result due its side effects and reproductive function suppression. Propolis has been widely studied, showing anti inflammation and pro-apoptosis property, that could potentially be used in the treatment of endometriosis. This study investigates the interaction between Sulawesi Propolis' active components and receptors and protein related to endometriosis pathogenesis.MethodsActive components of Sulawesi Propolis were initially identified with their targeted protein receptors. Lipinski rules were used to screen potential components. The ligands and proteins were tested using Autodock program to predict the most active compound and possible binding sites between propolis and some target proteins associated with inflammatory and apoptotic activity in endometriosis models. Receptor modelling is then performed using Swiss-Model.ResultsThese active components of Sulawesi Propolis showed a strong binding potential towards TNF- α, NF-kb, Estrogen-α, Estrogen-β, progesterone B, PGE2 EP2 and EP3 subtype respectively: Sanggenon C, Sanggenon H, Epicryptoacetalide, Chrysin-7-O-β-D-glucopyranodside, Irilone, Polydatin and Epicryptoacetalide. Compared to its negative ligand, Sulawesi Propolis displayed a stronger binding capacity to TNF-α, Estrogen-α, and Progesterone B receptors.ConclusionSulawesi Propolis has the ability to interact with receptors related to reproductive function, apoptotic reactions and inflammatory processes, a significant factor associated with the pathogenesis of endometriosis.
| S-EPMC8237281 | biostudies-literature
Project description:Innate immunity is the body's first line of defense against disease, and regulated cell death is a central component of this response that balances pathogen clearance and inflammation. Cell death pathways are generally categorized as non-lytic and lytic. While non-lytic apoptosis has been extensively studied in health and disease, lytic cell death pathways are also increasingly implicated in infectious and inflammatory diseases and cancers. Staurosporine (STS) is a well-known inducer of non-lytic apoptosis. However, in this study, we observed that STS also induces lytic cell death at later timepoints. Using biochemical assessments with genetic knockouts, pharmacological inhibitors, and gene silencing, we identified that STS triggered PANoptosis via the caspase-8/RIPK3 axis, which was mediated by RIPK1. PANoptosis is a lytic, innate immune cell death pathway initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes. Deletion of caspase-8 and RIPK3, core components of the PANoptosome complex, protected against STS-induced lytic cell death. Overall, our study identifies STS as a time-dependent inducer of lytic cell death, PANoptosis. These findings emphasize the importance of understanding trigger- and time-specific activation of distinct cell death pathways to advance our understanding of the molecular mechanisms of innate immunity and cell death for clinical translation.
| S-EPMC11418131 | biostudies-literature
Project description:Methamphetamine (METH) use disorder (MUD) is often accompanied by psychotic symptoms, cognitive deficits, and pathological changes in the brains of users. Animals that experimenters injected with drugs also show neurodegenerative changes in their brains. Recently, we have been investigating METH-induced molecular and biochemical consequences in animals that had infused themselves with METH using the drug self-administration (SA) paradigm. In that model, footshocks administered contingently help to separate rats that had already escalated their METH intake into resilient-to-drug (shock-sensitive, SS) or compulsive (shock-resistant, SR) METH takers. Herein, we used that model to test the idea that compulsive METH takers might show evidence of drug-induced autophagic changes in their brains. There were significant increases in mRNA levels of autophagy-related genes including Atg2a, Atg5, Atg14, and Atg16L1 in the rat dorsal striatum. Levels of two autophagy biomarkers, autophagy activating kinase (ULK1) and phospho-Beclin1, were also increased. In addition, we found increased p53 but decreased Bcl-2 protein levels. Moreover, the expression of cleaved initiator caspase-9 and effector caspase-6 was higher in compulsive METH takers in comparison to shock-sensitive rats. When taken together, these results suggest that the striata of rats that had escalated and continue to take METH compulsively the presence of adverse consequences exhibit some pathological changes similar to those reported in post-mortem human striatal tissues. These results provide supporting evidence that compulsive METH taking is neurotoxic. Our observations also support the notion of developing neuro-regenerative agents to add to the therapeutic armamentarium against METH addiction.
| S-EPMC7502530 | biostudies-literature
Project description:Leptin, a hormone that is predominantly produced by adipose tissue, is closely associated with various liver diseases. However, there is a lack of understanding as to whether leptin directly induces cytotoxic effects in hepatocytes as well as the mechanisms that are involved. Inflammasomes, which are critical components in the innate immune system, have been recently shown to modulate cell death. In this study, we examined the effect of leptin on the viability of rat hepatocytes and the underlying mechanisms, with a particular focus on the role of inflammasomes activation. Leptin treatment induced cytotoxicity in rat hepatocytes, as determined by decreased cell viability, increased caspase-3 activity, and the enhanced release of lactate dehydrogenase. NLRP3 inflammasomes were activated by leptin both in vitro and in vivo, as determined by the maturation of interleukin-1β and caspase-1, and the increased expression of inflammasome components, including NLRP3 and ASC. Mechanistically, leptin-induced inflammasome activation is mediated via the axis of ROS production, ER stress, and autophagy. Notably, the inhibition of inflammasomes by treatment with the NLRP3 inhibitor or the IL-1 receptor antagonist protected the hepatocytes from leptin-induced cell death. Together, these results indicate that leptin exerts cytotoxic effects in hepatocytes, at least in part, via the activation of NLRP3 inflammasomes.
| S-EPMC8622994 | biostudies-literature
Project description:BackgroundPropolis (bee glue) is a resinous honeybee product having a long history of application in many countries as a traditional remedy for treating wounds, burns, soar throat, stomach disorders, etc. It has been proved to possess beneficial biological effects, including antimicrobial, antioxidant, anti-inflammatory, cytotoxic, antiulcer, and many others. Bees gather propolis from diverse resinous plant parts and in different phytogeographic regions its chemical composition might vary significantly. In this article we report the results of the first study on the chemical profiles of propolis from Oman, its plant origin and antibacterial activity.ResultsThe chemical profiles of Omani propolis extracts were obtained by GC-MS analysis after silylation. Over 50 individual compounds were identified in the samples, belonging to different compound types: sugars, polyols, hydroxy acids, fatty acids, cardanols and cardols, anacardic acids, flavan derivatives, triterpenes, prenylated flavanones and chalcones. The profiles were dissimilar from other known propolis types. They demonstrate that although Oman is not a large country, the plant sources of propolis vary significantly, even in the same apiary and the same season. Based on chemical profiles, and isolation and identification of major marker compounds (new propolis constituents), new plant sources of propolis were found: Azadiracta indica (neem tree) and Acacia spp. (most probably A. nilotica). The ethanol extracts of the studied propolis samples demonstrated activity against S. aureus (MIC < 100 μg. mL-1) and E. coli (MIC < 380 μg. mL-1).ConclusionOmani propolis is different form the known propolis types and demonstrates significant chemical diversity. Its most important plant source is the resin of Azadirachta indica, and as a result its typical components are С5-prenyl flavanones. Other plant sources have been identified, too, playing some role in resin collection by bees in Oman: Acacia spp. (most probably A. nilotica) and Mangifera indica. The results demonstrate also the potential of Omani propolis as antimicrobial.
| S-EPMC3851436 | biostudies-literature
Project description:PurposeGlutamate receptor activation-induced excitotoxicity has been hypothesized to cause retinal ganglion cell (RGC) death in glaucoma and to link mitochondrial dysfunction in both acute and chronic neurodegenerative disorders. However, the relationships among elevated intraocular pressure (IOP), glutamate receptor-mediated excitotoxicity, and mitochondrial dysfunction in glaucoma remains unknown. The goal of this study was to determine whether the N- methyl D-aspartate (NMDA) glutamate receptor antagonist MK801 can block optic atrophy 1 (OPA1) release and subsequent apoptotic cell death, as well as whether acute IOP elevation triggers OPA1 release and alters OPA1 gene and protein expression in the rat retina after ischemia.MethodsSprague Dawley rats received injections of MK801 (10 mg/kg) or vehicle and then transient retinal ischemia was induced by acute IOP elevation. Following subcellular fractionation, changes in cytoplasmic and mitochondrial OPA1 were assessed by western blot analysis. Also, the expression of OPA1 mRNA was measured by Taqman qPCR, the distribution of OPA1 protein was assessed by immunohistochemistry, and apoptotic cell death was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.ResultsThe ~65 and 90 kDa isoforms of OPA1 were increased in the cytosol in the rat retina at 6 h and at 12 h, but only the 90 kDa isoform of OPA1 was decreased at 12 h after ischemia induced by acute IOP elevation. This suggests that ischemic insult induced OPA1 release from the mitochondria in retinas. Pretreatment with MK801 blocked this effect and significantly increased OPA1 immunoreactivity in the inner retinal layers, as well as OPA1 gene expression and total protein expression in retinas at 12 h after ischemia. Further, pretreatment with MK801 prevented apoptotic cell death in retinas at 12 h after ischemia. Following acute IOP elevation, Bcl-2 mRNA expression in retinas was decreased at 3 h and 6 h but increased at 12 h and 24 h. In contrast, Bax mRNA expression in these retinas was increased in the first 12 h and then plateaued. Moreover, pretreatment with MK801 increased Bcl-2 mRNA expression, but did not alter the course of Bax mRNA expression.ConclusionsThese results indicate that OPA1 release from mitochondria triggered by acute IOP elevation is inhibited by blockade of glutamate receptor activation. Because this effect was accompanied by increases of Bcl-2 expression, no changes of Bax expression, and blockade of apoptosis, these findings indicate that glutamate receptor activation following acute IOP elevation may lead to a distinct mitochondria-mediated cell death pathway in ischemic retina. These results support further studies to determine whether ischemia-induced OPA1 release may be an important component of the biochemical cascade leading to pressure-related ischemic damage in glaucomatous retina.
| S-EPMC2613079 | biostudies-literature
Project description:The presence of albuminuria is strongly associated with progression of chronic kidney disease. While albuminuria has been shown to injure renal proximal tubular cells, the effects of albumin on podocytes have been less well studied. We have addressed the hypothesis that exposure of podocytes to albumin initiates an injury response. We studied transformed human-urine derived podocytes-like epithelial cells (HUPECS, or podocytes). Upon differentiation, these cells retain certain characteristics of differentiated podocytes, including expression of synaptopodin, CD2AP, and nestin. We exposed podocytes to recombinant human albumin, which lacks lipids and proteins that bind serum albumin; this reagent allowed a direct examination of the effects of albumin. Podocytes endocytosed fluoresceinated albumin and this process was inhibited at 4°C, suggesting an energy-dependent process. Exposure to albumin at concentrations of 5 and 10 mg/ml was associated with increased cell death in a dose-dependent manner. The mechanism of cell death may involve apoptosis, as caspase 3/7 were activated and the pan-caspase inhibitor z-VAD reduced cell death. Albumin exposure also increased nuclear factor (NF)-κB activation and increased transcription and release of interleukin (IL-) 1β, tumor necrosis factor (TNF), and IL-6. We extended these findings to an in vivo model. Glomeruli isolated from mice with nephrotic syndrome also had increased expression of IL-1β and TNF RNA. These data suggest that while podocyte injury begets albuminuria, albumin in the glomerular ultrafiltrate may also beget podocyte injury. Thus, an additional mechanism by which anti-proteinuric therapies are beneficial in the treatment of glomerular diseases may be a reduction in injury to the podocyte by albumin.
| S-EPMC3557279 | biostudies-literature
Project description:Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Honey, propolis, and royal jelly were evaluated for their ability to protect against nephrotoxicity caused by DOX. Forty-two adult albino rats were divided into control groups. The DOX group was injected i.p. with a weekly dose of 3 mg/kg of DOX for six weeks. The DOX plus honey treated group was injected with DOX and on the next day, received 500 mg/kg/day of honey orally for 21 days. The DOX plus royal jelly treated group was injected with DOX and on the following day, received 100 mg/kg/day of royal jelly orally for 21 days. The DOX plus propolis treated group received DOX and on the following day, was treated orally with 50 mg/kg/day of propolis for 21 days. The DOX plus combined treatment group received DOX and on the following day, was treated with a mix of honey, royal jelly, and propolis orally for 21 days. Results confirmed that DOX raised creatinine, urea, MDA, and TNF-α while decreasing GPX and SOD. Damages and elevated caspase-3 expression were discovered during renal tissue's histopathological and immunohistochemical studies. Combined treatment with honey, royal jelly, and propolis improved biochemical, histological, and immunohistochemical studies in the renal tissue. qRT-PCR revealed increased expression of poly (ADP-Ribose) polymerase-1 (PARP-1) and a decline of Bcl-2 in the DOX group. However, combined treatment induced a significant decrease in the PARP-1 gene and increased Bcl-2 expression levels. In addition, the combined treatment led to significant improvement in the expression of both PARP-1 and Bcl-2 genes. In conclusion, the combined treatment effectively inhibited nephrotoxicity induced by DOX.
| S-EPMC9137495 | biostudies-literature
Project description:The pathogenesis of plantar fasciitis is unclear, which hampers the development of an effective treatment. The altered fate of plantar fascia stem/progenitor cells (PFSCs) under overuse-induced inflammation might contribute to the pathogenesis. This study aimed to isolate rat PFSCs and compared their stem cell-related properties with bone marrow stromal cells (BMSCs). The effects of inflammation and intensive mechanical loading on PFSCs' functions were also examined. We showed that plantar fascia-derived cells (PFCs) expressed common MSC surface markers and embryonic stemness markers. They expressed lower Nanog but higher Oct4 and Sox2, proliferated faster and formed more colonies compared to BMSCs. Although PFCs showed higher chondrogenic differentiation potential, they showed low osteogenic and adipogenic differentiation potential upon induction compared to BMSCs. The expression of ligament markers was higher in PFCs than in BMSCs. The isolated PFCs were hence PFSCs. Both IL-1β and intensive mechanical loading suppressed the mRNA expression of ligament markers but increased the expression of inflammatory cytokines and matrix-degrading enzymes in PFSCs. In summary, rat PFSCs were successfully isolated. They had poor multi-lineage differentiation potential compared to BMSCs. Inflammation after overuse altered the fate and inflammatory status of PFSCs, which might lead to poor ligament differentiation of PFSCs and extracellular matrix degeneration. Rat PFSCs can be used as an in vitro model for studying the effects of intensive mechanical loading-induced inflammation on matrix degeneration and erroneous stem/progenitor cell differentiation in plantar fasciitis.
| S-EPMC10526819 | biostudies-literature