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(A,B) Fetal membranes and (C,D) myometrium were incubated 24 h in the absence or presence of 10 μg/ml LPS with or without 200 μM silibinin (n = 6 patients). (E,F) Human amnion cells and (G,H) myometrial cells were incubated 24 h in the absence or presence of IL-1β with or without silibinin (n = 6 patients). (A,C,E,G) Gene expression for COX-2 was analysed by qRT-PCR. COX-2 mRNA expression was normalized to GAPDH mRNA expression and the fold change was calculated relative to LPS or IL-1β-stimulated expression. Data is displayed as mean ± SEM (one-way ANOVA). *P<0.05 vs. LPS or IL-1β-stimulated expression. (B,D,F,H) The incubation medium was assayed for concentration of PGE2 and PGF2α release by ELISA. Each bar represents mean concentration ± SEM (one-way ANOVA). *P<0.05 vs. LPS or IL-1β-stimulated release.
Source publication
Infection-induced preterm birth is the largest cause of infant death and of neurological disabilities in survivors. Silibinin, from milk thistle, exerts potent anti-inflammatory activities in non-gestational tissues. The aims of this study were to determine the effect of silibinin on pro-inflammatory mediators in (i) human fetal membranes and myome...
Citations
... The use of natural drugs has a long history and can be suggested as a candidate for cancer therapy (12,13) . Silibinin is a polyphonic flavonoid with a wide range of properties (14,15), such as hepatoprotective activity, antioxidant (5), immunomodulatory, antiviral properties, and anticancer (14,15). Due to low solubility in water, silibinin has a deficiency in absorption into the cell. ...
... The use of natural drugs has a long history and can be suggested as a candidate for cancer therapy (12,13) . Silibinin is a polyphonic flavonoid with a wide range of properties (14,15), such as hepatoprotective activity, antioxidant (5), immunomodulatory, antiviral properties, and anticancer (14,15). Due to low solubility in water, silibinin has a deficiency in absorption into the cell. ...
Background: Colorectal Cancer (CRC) is the most common malignant gastrointestinal cancer. Cancer stem cells (CSCs) are the major cause of cancer recurrence and cancer drug resistance. Silibinin, as an herbal compound, has anticancer properties. Objectives: The present study aimed to evaluate the antiproliferative effects of silibinin on HT29 stem-like cells (spheroids). Methods: In this study, antiproliferative and apoptotic properties of Silibinin encapsulated in Polymersome Nanoparticles (SPNs) were evaluated by MTT assay, propidium iodide (PI) /AnnexinV assay, cell cycle analysis, and DAPI (4',6-diamidino-2-phenylindole) staining. The expression of some miRNAs and their potential targets was evaluated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). Results: IC50 of SPNs was determined at 28.13±0.78µg/ml after 24 h. SPNs (28µg/ml) induced apoptosis by 32.36% in HT29 cells after 24 h. DAPI staining indicated a decrease in stained nuclei after SPNs induction. SPNs treatment increased the expression of miR-34a, as well as P53, BAX, CASP9, CASP3, and CASP8. The downregulation of miR-221 and miR-222 was observed in SPNs treated cells. Moreover, SPNs decrease the expression level of CD markers in HT29 spheroids (cancer stem cells) compared to untreated spheroids. Spheroids were completely destroyed after 72 h treatment with SPNs (28µg/ml). Conclusion: As evidenced by the obtained results, SPNs can be used as an effective anticancer agent in multi-layer (cancer stem cells) and mono-layer cancerous cells with the upregulation of tumor suppressive miRs and genes, as well as downregulation of oncomiRs and oncogenes.
... When evaluated in the gestational context, treatment of fetal membranes and myometrium (both tissue explants and primary cells) with silibinin proved to be beneficial, by reducing LPS-stimulated expression of IL-6, IL-8, COX-2, PGE 2 and PGF 2α in human fetal membranes, reducing MMP-9 expression induced by IL-1β in primary amnion and myometrial cells, as well as decreasing IL-6, IL-8, and matrix metalloproteinase-9 (MMP-9) expression in preterm fetal membranes. Regarding offspring fetal brains from pregnant C57BL/6 mice injected with silibinin or/and LPS on E16, silibilin was able to reduce IL-8 and brain injury induced by LPS (R. Lim et al. 2014). ...
During pregnancy, the body undergoes a great amount of changes in order to support a healthy developing fetus. In this context, maternal dietary supplementation is widely encouraged to provide adequate nutrition for the newborn. In the past few years, studies have emerged highlighting the benefits of polyphenols intake during pregnancy. Indeed, despite differences among reports, such as experimental model, polyphenol employed, dosage and regimen of administration, there is no doubt that the ingestion of these molecules has a protective effect in relation to three pregnancy-associated diseases or conditions: preeclampsia, gestational diabetes and fetal growth restriction. In this review, we describe the effects of different polyphenols and polyphenol-rich extracts or juices on the main outcomes of these common pregnancy-associated complications, obtained in human, animal and in vitro studies. Therefore, this work provides a critical analysis of the literature, and a summary of evidences, from which future research using polyphenols can be designed and evaluated.
... Silibinin is a flavonoid isolated from the Silybum marianum species [23]. Recently, the research has explored the influence of silibinin on oxidative stress [178,179]. An investigation on the impact of silibinin therapy on locomotor activity and learning took place. ...
Background
Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various pieces of evidences assembled during preceding years reveal the pertinent role of ionizing radiation-induced oxidative stress in the progression of neurodegenerative insults such as Parkinson’s disease, which have been contributing to increased proliferation and generation of reactive oxygen species.
Objective
This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson’s disease and proposes novel therapeutic interventions of flavonoid family offering effective management and slowing down the progression of Parkinson’s disease. Method: Published papers were searched via MEDLINE, PubMed, etc. published to date for in-depth database collection.
Results
The potential of oxidative damage may harm the non-targeted cells. It can also modulate the functions of central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerates the progression of Parkinson’s disease at the molecular, cellular, or tissue levels. In Parkinson’s disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms.
Conclusion
Rising interest has extensively engrossed on the clinical trial designs based on the plant derived family of antioxidants. They are known to exert multifarious impact either way in neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.
... It is the main component of silymarin, welldocumented as a hepatoprotective natural compound. Silibinin exhibits a wide spectrum of pharmacological activity in vitro, in vivo, and in clinical trials, mainly anti-oxidant and anti-inflammatory [75,76], anti-cancer and chemopreventive properties [77]. Recently, it was shown that silibinin can reduce systolic pressure, downregulating the expression of C-X-C chemokine receptor type 4 (CXCR4) in pulmonary arteries [78], upregulating the expression of CXCR4 in bone marrow [79], and inhibiting the production of cytokines (NF-κB, TNF-α, IL-1β) [80]. ...
... Recently, it was shown that silibinin can reduce systolic pressure, downregulating the expression of C-X-C chemokine receptor type 4 (CXCR4) in pulmonary arteries [78], upregulating the expression of CXCR4 in bone marrow [79], and inhibiting the production of cytokines (NF-κB, TNF-α, IL-1β) [80]. Lim et al. [76] observed that this flavonolignan can reduce the response of inflammatory pathways during infection-induced preterm birth. The activity of silibinin in experimental preeclampsia was studied by Souza et al. [81]. ...
... Another study showed that silibinin (70 mg/kg by injection) can reduce inflammation in human fetal membranes and myometrium by decreasing the expression of IL-6, IL-8, COX-2, and PGE 2 and PGF 2α . [76]. Moreover, silibinin showed hepatoprotective effects in different periods of pregnancy through improving the hepatic cellular architecture and the muscular wall if hepatic arteries are impaired by L-NAME [81]. ...
The current health requirements set the direction in pharmacological research, especially as regards diseases that require improvement of existing therapeutic regimens. Such diseases include preeclampsia, which is a hypertensive disorder of pregnancy during which there occurs progressive increasing activation of the immune system through elevation of pro-inflammatory cytokines and antiangiogenic factors, which is dangerous for the mother and fetus. A promising field of research for new drugs to treat this disease is the study of natural phenolic compounds of plant origin and herbal extracts, which are complex matrices of chemical compounds with broad biological activities. Many plant substances with anti‑inflammatory and anti‑hypertensive properties are known, but studies in animal models of preeclampsia and clinical trials concerning this disease constitute a new and developing research trend of significant medical importance. The aim of our research review was to identify and analyze the results of already available studies on baicalin, curcumin, epigallocatechin gallate, punicalagin, quercetin, resveratrol, salvianolic acid A (danshensu), silibinin, and vitexin, as well as plant extracts from Brassica oleracea L., Euterpe oleracea Mart., Moringa oleifera Lam., Punica granatum L., Silybum marianum (L.) Gaertner, Thymus schimperi Ronniger, Uncaria rhynchophylla (Miq.) Miq. ex Havil., and Vitis vinifera L., which are potential and promising candidates for further research and for potential new therapies.
... Silibinin is a polyphonic avonoid which has widely properties such as hepatoprotective activity, antioxidant, immunomodulatory, antiviral properties and anticancer. [18] [19]. In addition, over the last decades, it has been demonstrated that Silibinin has capability to arrest the cell cycle, inhibit the DNA synthesis and cell division, activate the caspase cascade and apoptotic cell death, consequently. ...
Colorectal Cancer (CRC) has the most common malignant gastrointestinal cancer which representing about13% of all malignant tumor. CRC Cancer Stem Cell is the major reasons for recurrence of disease cause of solid tumor metastasis, relapse of cancer after treatment and drug resistance. Silibinin, an herbal extract from milk thistle plant, has been identified as a potential cancer medicine that can target the signaling pathway of CSCs and change their abilities. In our study, the results of CSC confirmation test such as specific surface CD markers and ability to form colonospheres was indicated the HT-29 cells as CSC-CRC. To increase the effectiveness of Silibinin, and also, to evaluate therapeutic intentions on HT-29 cancer stem-like cells, we encapsulated Silibinin in polymersome nanoparticle and validated the anti-proliferative and apoptotic activities of this new patent by MTT assay, AnnexinV/PI method, cell cycle analysis and DAPI staining. Furthermore, the efficacy of drug on Multicellular Tumor Spheroid (MCTS) and single cell suspension was showed that SPN had succeed to decrees the expression level of CSC CD markers compared with control group. Follow by using miRNAs as a novel and minus invasive expertise for prognostic, RT-qPCR confirmed that SPNs can repress oncogenic miRNAs such as miR-221 and miR-222. Silibinin encapsulated in Polymersome Nanoparticles (SPNs) can also enhance the expression of tumor suppressor miR-34a and some of its proapoptotic target genes such as P53, BAX, CASP9, CASP3, and CASP8. Our results suggested that SPNs can be recognized as a new stimulant factor to direct the HT-29 cancer cells toward apoptosis pathways thorough modify expression of some miRNAs and their apoptotic target genes directly and/or indirectly.
... In the last decades, silymarin has received much attention in virtue of its antiinflammatory and antioxidant activity in liver disorders [76]. In particular, it has been demonstrated that silymarin participates in the regulation of the antioxidant system by modulating several transcription factors including Nrf2 and NF-kB [77] and modulates inflammatory processes by reducing the expression of inflammatory molecules such as COX-2, IL-6, IL-1b, and also in gestational tissues [78]. According to European Pharmacopoeia, milk thistle dry extract contains 30%e65% silymarin [79]; however, even if consumed in high doses (>1500 mg/day) that have been shown to be safe in humans, silymarin components have a poor bioavailability and absorption, are rapidly metabolized by phase I and phase II enzymes in the liver, and are excreted in bile and urine [80]. ...
... Silibinin (200 mM) also reduces inflammation induced by LPS and IL-1b in human gestational tissues. An in vivo study shows that silibinin downregulates IL-8 mRNA expression in fetal brain and does not modify inflammatory parameters, such as IL-6, IL-8, IL-1b, COX-2, and MMP-9, in the placenta and myometrium isolated from mice injected with LPS [78]. Of note, silibinin (50 mM) reverts the high spontaneous levels of O 2 , H 2 O 2 , and TNF-a and the lower levels of IL-10 and TGF-b observed in monocytes [123] and counteracts the increases in the endogenous activation of NF-kB and IL-1b release in peripheral blood mononuclear cells [124] obtained from preeclamptic women compared with normotensive pregnant. ...
Maternal nutrition deeply influences fetal growth and development with long-lasting effects. Increasing evidence indicates that a healthy diet rich in fruit and vegetables reduces the risk of maternal and fetal complications. Phenolic compounds contained in plant-derived food possess potential benefits to human health because of their capability to interact and modulate several cellular signaling pathways and molecules. This chapter provides an overview, based on the latest literature data, of the effects of dietary polyphenols on molecular mechanisms governing the various stages of pregnancy. Particular attention will be given to the influence of polyphenols on inflammatory and oxidative processes, as well as on vascular, endocrine, and neuronal factors. The potential harmful effects of specific polyphenols will be also discussed.
... Mice were fed on high-fat -diet for 8 weeks until becoming obese, followed by injection with silibinin intraperitoneally with a dose of 50 mg/kg. Silibinin dose was selected based on previous studies demonstrating sufficient dose ranges to induce beneficial biological effects [13][14][15][16][17]. Mice in control group were injected with vehicle injection. ...
Background:
Obesity is a multifactorial chronic disease that comprises several pathological events, such as adipose hypertrophy, fatty liver and insulin resistance. Inflammation is a key contributer to development of these events, and therefore, targeting inflammation is increasingly considered for management of obesity and its complications. The aim of the current study was to investigate therapeutic outcomes of anti-inflammatory activities of the natural compound Silibinin in reversing obesity and its complication in mice.
Methods:
C57BL/6 male mice were fed high-fat diet for 8 weeks until development of obesity, and then injected with 50 mg/kg silibinin intraperitoneally twice per week, or vehicle for 8 weeks. Throughout the experiment, mice were continuously checked for body weight and food intake, and glucose tolerance test was performed toward the end of the experiment. Animals were sacrificed and serum and tissues were collected for biochemical, histological, and gene expression analysis to assess silibinin effects on adipose inflammation, fat accumulation, liver adipogenesis and glucose homeostasis.
Results:
Silibinin treatment reversed adipose tissue inflammation and adipocyte hypertrophy, and blocked progression in weight gain and obesity development with no significant effects on rates of food intake. Silibinin also reversed fatty liver disease and restored glucose homeostasis in treated animals, and reversed hyperglycemia, hyperinsulinemia and hypertriglyceridemia.
Conclusion:
In this study, we demonstrated that silibinin as an anti-inflammatory therapy is a potential alternative to manage obesity, as well as its related complications. Moreover, silibinin-based therapies could further evolve as a novel treatment to manage various inflammation-driven disorders.
... ); Protection against cardiovascular disease(Perez-Vizcaino et al. 2006); Infection(Lee et al. 2015); Anticancer(Gibellini et al. 2011); Radioprotection(Benkovic et al. 2008); Radiosensitization(Lin et al. 2012) Genistein 5,7-Dihydroxy-3-(4-hydroxyphenyl)chromen-4-one Therapeutic role in menopause(Arena et al. 2002); Inhibition of bone loss(Legette et al. 2011); Anti-cancer(Li Y et al. 2006); Radioprotection(Landauer et al. 2003;Davis et al. 2008); Radiosensitization(Yashar et al. Haddad et al. 2011); Antiinflammatory(Lim et al. 2014); Anti-cancer(Tiwari et al. 2011; Mishra 2015, 2017) Radioprotection(Tiwari et al. 2010); Radiosensitization(Nambiar et al. Zhou et al. 2016); Anti-inflammatory(Ye et al. 2014); Antiviral(Kwon et al. 2016); Anti-cancer(Li HN et al. 2009); Radiosensitization (Tan et al. ...
Purpose: Radiobiological research continues to focus on finding newer strategies for enhanced killing of tumor cells by ionizing radiation. In recent years, chemotherapeutic drugs have been found to possess the capabilities to sensitize tumor cells without affecting the normal cells. There have been increasing research efforts to identify novel and non-toxic compounds which cause minimal or no harm to normal cells but maximize tumor toxicity response to radiation exposure. Extensive researches on flavonoids that are compounds derived from plants have shown that these have promising abilities as radioprotectors and radiosensitizers.
Conclusions: In this review, we examine the role of flavonoids as potential radiosensitizers, review the underlying molecular mechanisms and discuss their potential usefulness in improving cancer radiotherapy. It is emphasized that obtaining a deeper insight into the molecular mechanisms underlying the combined action of flavonoids and ionizing radiation may provide new directions for radiobiological research applicable to the much needed enhanced selective tumor cytotoxicity to treatment agents.
... Resveratrol, a stilbene, found largely in the skins of red grapes, decreases LPS-induced pro-inflammatory cytokines and prostaglandin secretion in human fetal membranes [44]. Various flavonoids have also been shown to reduce LPS-and/or IL-1β-induced IL-6 and IL-8 mRNA expression and secretion, COX-2 mRNA expression, prostaglandins PGE 2 and PGF 2α secretion, and MMP-9 expression and activity in fetal membranes or primary amnion cells [45][46][47][48][49]. These polyphenols include, naringenin (flavanone from grapefruit), apigenin (flavone from parsley and chamomile), luteolin (flavone found in high amounts in parsley, thyme, peppermint, basil, herb, celery, and artichoke), kaempferol (flavonol found in apples, grapes, broccoli, cabbage, kale, beans, tomatoes and strawberries), nobiletin (flavone that abundantly exist in the bitter, white pith beneath peels of citrus genus and in smaller amounts in the juices of these fruits), silibinin (flavonolignan derived from milk thistle the main component of milk thistle) and honokiol (a lignan, derived from the bark, leaves and seed cones of the Magnolia officcinalis tree). ...
... These polyphenols include, naringenin (flavanone from grapefruit), apigenin (flavone from parsley and chamomile), luteolin (flavone found in high amounts in parsley, thyme, peppermint, basil, herb, celery, and artichoke), kaempferol (flavonol found in apples, grapes, broccoli, cabbage, kale, beans, tomatoes and strawberries), nobiletin (flavone that abundantly exist in the bitter, white pith beneath peels of citrus genus and in smaller amounts in the juices of these fruits), silibinin (flavonolignan derived from milk thistle the main component of milk thistle) and honokiol (a lignan, derived from the bark, leaves and seed cones of the Magnolia officcinalis tree). Notably, nobiletin [47] and silibinin [48] were also able to reduce the expression and production of proinflammatory cytokines and MMP-9 in fetal membranes taken from women after spontaneous preterm birth. ...
Preterm birth is the single major cause of infant mortality. Short and long term outcomes for infants are often worse in cases of preterm premature rupture of the fetal membranes (pPROM). Thus, increased knowledge of the structure characteristics of fetal membranes as well as the mechanisms of membrane rupture are essential if we are to develop effective treatment strategies to prevent pPROM. In this review, we focus on the role of inflammation and senescence in fetal membrane biology.
... Furthermore, when silibinin is coadministered with the conventional chemotherapeutic drug paclitaxel to ovarian cancer cells, it produces a synergistic effect by increasing drug sensitivity of drug-resistant cancer cells, thereby indicating its potential as an anticancer supplement agent (Zhou et al., 2008). Moreover, in complications of pregnancy, including preeclampsia and inflammation-induced preterm birth, silibinin modulates the levels of proinflammatory cytokines, such as nuclear factor kappa B, interleukin 10 (IL-10), and tumor necrosis factor alpha (TNF-α) to suppress inflammation (Giorgi, Bannwart-Castro, Peracoli, & Peracoli, 2012;Lim, Morwood, Barker, & Lappas, 2014). However, silibinin has not been used as a therapeutic agent for endometriosis thus far. ...
... Similarly, our results showed that silibinin possesses anti-inflammatory properties and suppresses the growth of endometriotic lesions by downregulating the expression of proinflammatory cytokines in the mouse model of endometriosis. In agreement with our results, silibinin was shown to suppress lipopolysaccharide (LPS)-induced IL-1β, IL8, and COX2 production in the human fetal membrane, myometrial cells, and in a preterm birth mouse model (Lim et al., 2014). In addition, silibinin protects against allergic airway inflammation in mice by inactivating TNF-α, IL-1β, IL-4, IL-5, and IL-13, highlighting its potential as a drug for treatment of asthma (Choi et al., 2012). ...
Silibinin is a flavonolignan extracted from milk thistle, which has been used for treating liver disorders, various cancers, and gynecological diseases. However, attempts for treating endometriosis with silibinin are lacking. In this study, we observed that silibinin exerts antiproliferative and apoptotic effects on human endometriotic cell lines VK2/E6E7 and End1/E6E7. We also identified that silibinin‐induced oxidative stress and lipid peroxidation in human endometriotic cells. Moreover, we observed upregulation of calcium concentration in the cytosol and mitochondrial matrix, which resulted in mitochondrial dysfunction. Furthermore, induction of endoplasmic reticulum stress signals with rapid mitogen‐activated protein kinase (MAPK) pathway signaling resulted in apoptosis of both cells. Using an animal model mimicking the retrograde menstruation hypothesis, we verified the effects of silibinin on reducing endometriotic lesions by inhibiting the expression of inflammatory cytokines in mice. Silibinin might be used as a novel therapeutic agent or supplement for inhibiting progression of endometriosis in vitro and in vivo. In this study, we demonstrated the effects of silibinin on progression of endometriosis in in vitro and in vivo models. Therefore, silibinin might be used as a novel therapeutic agent for prevention and treatment of endometriosis.
