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Matharage Gayani Dilshara, Rajapaksha Gedara Prasad Tharanga Jayasooriya, Ilandarage Menu Neelaka Molagoda, Jin-Woo Jeong, Seungheon Lee, Sang Rul Park, Gi-Young Kim, Yung Hyun Choi
In this study, we addressed how silibinin enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in various cancer cells. Combined treatment with silibinin and TRAIL (silibinin/TRAIL) induced apoptosis accompanied by the activation of caspase-3, caspase-8, caspase-9, and Bax, and cytosolic accumulation of cytochrome c. Anti-apoptotic proteins such as Bcl-2, IAP-1, and IAP-2 were inhibited as well. Silibinin also triggered TRAIL-induced apoptosis in A549 cells through upregulation of death receptor 5 (DR5)...
February 13, 2018: Oncotarget
Xiaoying Hou, Hongzhi Du, Xingping Quan, Lei Shi, Qianqian Zhang, Yao Wu, Yang Liu, Jing Xiao, Yong Li, Ligong Lu, Xun Ai, Meixiao Zhan, Shengtao Yuan, Li Sun
Tumor metastasis is the most lethal and debilitating process that threatens cancer patients. Among the regulators involved in tumor metastasis, lysyl oxidase (LOX) is an important contributor for tumor invasion, migration and the formation of the pre-metastatic niche. Although the relationship between LOX and poor prognosis of lung patients has been preliminary reported, the mechanism remains poorly understood. Here, we found that LOX overexpression is closely related to the survival of lung adenocarcinoma patients but not squamous cell carcinoma patients...
2018: Frontiers in Pharmacology
Valencia Fernandes, Dilip Sharma, Kiran Kalia, Vinod Tiwari
Astrogliosis is a key contributor for many neurological disorders involving apoptosis, neuroinflammation and subsequent neuronal death. Silibinin, a polyphenol isolated from milk thistle (Silybum marianum), has been shown to suppress the astrocyte activation in various neurodegenerative disorders and also exhibit a neuroprotective role in neuroinflammation-driven oxidative damage. In the present study, we found that treatment with silibinin significantly attenuates LPS- oxidative-nitrosative stress in C6 astrocytoma cells...
February 21, 2018: International Journal of Neuroscience
W W Tong, C Zhang, T Hong, D H Liu, C Wang, J Li, X K He, W D Xu
Silibinin, a natural polyphenolic flavonoid, possesses anti-oxidant, anti-inflammation and anti-cancer properties. The present study was designed to investigate the effects of silibinin on rheumatoid arthritis (RA) pathogenesis-related cells and collagen-induced arthritis (CIA) and further explore the potential underlying mechanisms. Our results showed that silibinin suppressed cell viability and increased the percentage of apoptotic RA-fibroblast-like synoviocytes (FLS). Furthermore, the production of inflammatory cytokines in RA-FLS and a CIA rat model was effectively inhibited by silibinin...
February 19, 2018: Scientific Reports
Hayder Gaeed Oufi
The use of herbal drugs for disease treatment has increased worldwide. Flavonolignan silibinin, the major biologically active component of milk thistle (Silybum marianum), has various biological effects. This study is designed to evaluate the cytogenetic effects of flavonolignan silibinin in mouse bone marrow cells alone and in combination with methotrexate. In this study, the cytogenetic effects of flavonolignan silibinin were observed in mouse bone marrow cells after five days of treatment with a single intraperitoneal (IP) dose of either 50, 100 or 150 mg/kg body weight of silibinin hemisuccinate (SHS), alone or in combination with a single dose of 20 mg/kg methotrexate (MTX)...
February 10, 2018: European Journal of Pharmacology
Lu Han, Kai Guo, Fen Gu, Yun-Fei Zhang, Ke Li, Xi-Xi Mu, Hai-Jing Liu, Xiao-Dong Zhou, Wen Luo
In the present study, the effects of silibinin-loaded thermosensitive liposome-microbubble complex (STLMC) on rabbit liver VX2 tumors in sub-hyperthermia fields were investigated using two-dimensional ultrasonography (2D US), contrast-enhanced US (CEUS), hematoxylin and eosin (H&E) staining, immunohistochemistry and ultrastructure observation. 50 rabbits with VX2 liver tumors were divided into five groups: Sub-hyperthermia microwave ablation group (SHM), STLMC injection group (STLMC), SHM ablation plus STLMC injection group (SHM + STLMC), microbubble injection group and blank control group without any treatment...
February 2018: Experimental and Therapeutic Medicine
Valeria Romanucci, Chapla Agarwal, Rajesh Agarwal, Christophe Pannecouque, Mauro Iuliano, Gaetano De Tommaso, Tonino Caruso, Giovanni Di Fabio, Armando Zarrelli
New silibinin phosphodiester glyco-conjugates were synthesized by efficient phosphoramidite chemistry and were fully characterized by 2D-NMR. A wide-ranging study focused on the determination of their pKa and E° values as well as on their radical scavenging activities by different assays (DPPH, ABTS+ and HRSA) was conducted. The new glyco-conjugates are more water-soluble than silibinin, and their radical scavenging activities are higher than those of silibinin. The conjugation therefore improves both the water solubilities and antioxidant activities of the flavonolignan moieties...
January 31, 2018: Bioorganic Chemistry
Simon Schramm, Guozheng Huang, Sandra Gunesch, Florian Lang, Judit Roa, Petra Högger, Raimon Sabaté, Pamela Maher, Michael Decker
A series of neuroprotective hybrid compounds was synthesized by conjugation of the flavonolignan silibinin with natural phenolic acids, such as ferulic, cinnamic and syringic acid. Selective 7-O-esterfication without protection groups was achieved by applying the respective acyl chlorides. Sixteen compounds were obtained and SARs were established by evaluating antioxidative properties in the physicochemical FRAP assay, as well as in a cell-based neuroprotection assay using murine hippocampal HT-22 cells. Despite weak activities in the FRAP assay, esters of the α,β-unsaturated acids showed pronounced overadditive effects at low concentrations greatly exceeding the effects of equimolar mixtures of silibinin and the respective acids in the neuroprotection assay...
January 12, 2018: European Journal of Medicinal Chemistry
E Kieslichova, S Frankova, M Protus, D Merta, E Uchytilova, J Fronek, J Sperl
INTRODUCTION: Amanita phalloides poisoning is a potentially fatal cause of acute liver failure. The aim of this study was to analyze the impact of initial patients' characteristics and different treatment modalities on the outcome of patients with liver failure caused by Amanita poisoning. MATERIAL AND METHODS: We retrospectively evaluated 23 patients admitted to our center between July 2007 and August 2016. RESULTS: Mean time interval between Amanita phalloides ingestion and the onset of gastrointestinal symptoms was 12...
January 2018: Transplantation Proceedings
Xiaoyu Song, Bo Liu, Lingyu Cui, Biao Zhou, Lu Liu, Weiwei Liu, Guodong Yao, Mingyu Xia, Toshihiko Hayashi, Shunji Hattori, Yuko Ushiki-Kaku, Shin-Ichi Tashiro, Takashi Ikejima
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. In this study, we investigated the role of estrogen receptors (ERs) in silibinin's neuroprotective effect on Aβ1-42-injected rats...
February 3, 2018: Neurochemical Research
Aysa Rezabakhsh, Farzaneh Fathi, Hesam Bagheri Saghaei, Hassan Malekinejad, Azadeh Montaseri, Reza Rahbarghazi, Alireza Garjani
Silibin, a flavonoid from the seeds of Silybum marianum (L.) Gaertn. (Asteraceae) has been reported to produce curative properties in diabetes. Autophagy is generated by a vast array of insults for removal of damaged proteins and organelles from the cell. Inadequate autophagy promotes endothelial cells dysfunction and delays in diabetic ulcers recovery. We hypothesized that silibinin could protect endothelial cells against high glucose-induced damage by engaging autophagic responses. HUVECs viability was evaluated by MTT assay...
February 1, 2018: Journal of Cellular Biochemistry
Yumei Li, Chunmei Zhang, Danfeng Cai, Congde Chen, Dongmei Mu
Rhabdoid tumors, which tend to occur prior to the age of 2 years, are one of the most aggressive malignancies and have a poor prognosis due to the frequency of metastasis. Silibinin, a natural extract, has been approved as a potential tumor suppressor in various studies, however, whether or not it also exerts its antitumor capacity in rhabdoid tumors, particularly with regards to tumor migration and invasion, is unclear. The rhabdoid tumor G401 cell line was used in the present in vitro study. An MTT assay was used to assess the cytotoxicity of silibinin on G401 cells, cell migration was studied using a wound healing assay and a Transwell migration assay, and cell invasion was determined using a Transwell invasion assay...
December 2017: Oncology Letters
Shuming Lu, Zhuqing Zhang, Meiru Chen, Chunyan Li, Lina Liu, Yan Li
The objective of the present study was to observe the effects of silibinin and the p38 mitogen-activated protein kinase (MAPK) signaling pathway inhibitor SB203580 on the migration and invasion capabilities of SGC7901 cells, and to explore the underlying associated mechanisms. Scratch, Transwell and Matrigel invasion assays were performed to study the effects of silibinin on cell migration and invasion. Western blot analysis was used to determine the expression levels of p38MAPK, phosphorylated (p-)p38MAPK, matrix metalloproteinase (MMP)-2 and MMP-9...
December 2017: Oncology Letters
Enas Hussein Ali, Fatemeh Sharifpanah, Maria Wartenberg, Heinrich Sauer
Silibinin, the bioactive compound of milk thistle (Silybum marianum), exerts tissue protective and regenerative effects that may include stem cell differentiation toward vascular cells. The purpose of the present study was to investigate whether silibinin stimulates blood vessel formation from mouse embryonic stem (ES) cells and to unravel the underlying signaling cascade. Vascular branching points were assessed by confocal laser scanning microscopy and computer-assisted image analysis of CD31-positive cell structures...
January 12, 2018: Planta Medica
Aynur Sahin, Mualla Aylin Arici, Yeliz Yilmaz, Sule Kalkan, Nergiz Durmus, Bekir Ugur Ergur, Ilkay Yakut Aksu, Neşe Atabey, Yesim Tuncok
Amanita phalloides species mushrooms containing alpha-amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models...
December 29, 2017: Basic & Clinical Pharmacology & Toxicology
Magdalena Szaryńska, Agata Olejniczak, Jarosław Kobiela, Piotr Spychalski, Zbigniew Kmieć
Colorectal cancer (CRC) is the third most frequent malignancy and represents the fourth most common cause of cancer-associated mortalities in the world. Despite many advances in the treatment of CRC, the 5-year survival rate of patients with CRC remains unsatisfactory due to tumor recurrence and metastases. Recently, cancer stem cells (CSCs), have been suggested to be responsible for the initiation and relapse of the disease, and have been identified in CRC. Due to their basic biological features, which include self-renewal and pluripotency, CSCs may be novel therapeutic targets for CRC and other cancer types...
December 2017: Oncology Letters
Wenhao Zheng, Zhenhua Feng, Yiting Lou, Chunhui Chen, Chuanxu Zhang, Zhenyu Tao, Hang Li, Liang Cheng, Xiaozhou Ying
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. Silibinin, a polyphenolic flavonoid derived from fruits and seeds of Silybum marianum, has been reported to possess various potent beneficial biological effects, such as antioxidant, anti-cancer, hepatoprotective and anti-inflammatory activities. However, the anti-inflammatory effects of silibinin on OA have not been reported. This study aimed to assess the effects of silibinin on OA both in vitro and in vivo...
November 21, 2017: Oncotarget
Mitsuho Imai-Sumida, Takeshi Chiyomaru, Shahana Majid, Sharanjot Saini, Hannah Nip, Rajvir Dahiya, Yuichiro Tanaka, Soichiro Yamamura
Silibinin is the major active constituent of silymarin, an extract of milk thistle seeds. Silibinin has been shown to have significant anti-cancer effects in a variety of malignancies. However, the molecular mechanisms of silibinin action in bladder cancer have not been studied extensively. In the present study, we found that silibinin (10 μM) significantly suppressed proliferation, migration, invasion and induced apoptosis of T24 and UM-UC-3 human bladder cancer cells. Silibinin down-regulated the actin cytoskeleton and phosphatidylinositide 3-kinase (PI3K)/Akt signaling pathways in these cancer cell lines...
November 3, 2017: Oncotarget
Jasmine M Manouchehri, Michael Kalafatis
BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is the most fatal form of breast cancer due to the shortcomings of therapies. However, recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is a promising anticancer therapeutic that possesses the capability to promote the induction of apoptosis in cancer cells, but some TNBCs are resistant to rhTRAIL's pro-apoptotic effects. Therefore, a combinatorial treatment approach with silibinin and rhTRAIL was considered in order to sensitize rhTRAIL-resistant TNBCs...
December 2017: Anticancer Research
Hai Zou, Xing-Xing Zhu, Guo-Bing Zhang, Yuan Ma, Yi Wu, Dong-Sheng Huang
Introduction: Silibinin (silybin), a non-toxic natural polyphenolic flavonoid, is the principal and the most biologically active component of silymarin. It is efficient in the treatment of acute and chronic liver disorders caused by toxins, drug, alcohol, hepatitis, and gall bladder disorders. Further, in our previous studies, we explored the anti-cancer efficacy in common cancers, such as lung, prostatic, colon, breast, bladder, as well as, hepatocellular carcinoma. Interestingly, silibinin is still not solely limited to the treatment of these diseases...
October 24, 2017: Oncotarget
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