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Jie Mao, Hongbao Yang, Tingting Cui, Pan Pan, Nadia Kabir, Duo Chen, Jinyan Ma, Xingyi Chen, Yijun Chen, Yong Yang
Silibinin, a nontoxic bioactive component in milk thistle, is used as a liver-protective drug in the clinic mainly because of its antioxidant and anti-inflammation activities. In this study, we studied the cytotoxic effects of silibinin combined with sorafenib on hepatocellular carcinoma (HCC). The results indicated that silibinin combined with sorafenib potently inhibited the proliferation of various HCC cells and induced significant apoptosis. In an HCC subcutaneous transplantation tumor model, the combination of silibinin and sorafenib significantly suppressed tumor growth compared with monotherapy...
May 18, 2018: European Journal of Pharmacology
Zhuan-Li Bai, Vincent Tay, Shu-Zhong Guo, Juan Ren, Mao-Guo Shu
Silibinin, also known as silybin, is the major flavonolignan isolated from Silybum marianum . Although previous reports demonstrated that silibinin exhibits significant tumor suppressor activities in various cancers by promoting cell apoptosis, it was also shown to trigger autophagy to counteract apoptosis induced by exogenous stresses in several types of cells. However, there is no report to address the role of silibinin induced autophagy in human A172 and SR glioblastoma cells. Our study showed that silibinin treatment not only inhibited the metabolic activities of glioblastoma cells but also promoted their apoptosis through the regulation of caspase 3 and PARP-1 in concentration- and time-dependent manners...
2018: BioMed Research International
Nagaraju Chinthakunta, Srinivasulu Cheemanapalli, Surekha Chinthakunta, C M Anuradha, Suresh Kumar Chitta
G-protein coupled receptor (GPR120) is an omega-3 fatty acid receptor that inhibits macrophage-induced tissue inflammation. Recent studies revealed GPR120 promotes colorectal carcinoma through modulation of VEGF, IL-8, PGE2, and NF-kB expression. However, three-dimensional structure of GPR120 is not yet available in Protein Data Bank (PDB). In the present study, we focused on a 3-D structural model of GPR120 has been constructed using homology modeling techniques. The structural quality of the predicted GPR120 model was verified using Procheck, Whatif, ProSA, and Verify 3D...
2018: Network Modeling and Analysis in Health Informatics and Bioinformatics
Subramaniyam Rajalakshmi, Selvaraj Vimalraj, Sekaran Saravanan, Desingh Raj Preeth, Manickaraj Shairam, Dhanasekaran Anuradha
In the recent decades, flavonoid metal complexes have been widely investigated for their multifaceted role in enabling osteoblast differentiation and bone formation. Silibinin complexed with copper(II) ion has been synthesized along with two mixed ligand complexes, namely copper(II) silibinin-phenanthroline and neocuproine as co-ligands, and their positive role in promoting neovacularization and osteoblast differentiation was investigated. Silibinin mono complex [Cu(sil)(H2 O)2 ] and [Cu(sil)(phen)] showed similar UV-visible absorption in the region of 315 and 222 nm, whereas Cu(silibinin)(neocuproine) [Cu(sil)(neo)] showed a blueshift in the 320 nm transition...
May 19, 2018: Journal of Biological Inorganic Chemistry: JBIC
Fabienne Langlois, Jennifer Chu, Maria Fleseriu
Cushing's disease (CD) is caused by a pituitary corticotroph neuroendocrine tumor inducing uncontrolled hypercortisolism. Transsphenoidal surgery is the first-line treatment in most cases. Nonetheless, some patients will not achieve cure even in expert hands, others may not be surgical candidates and a significant percentage will experience recurrence. Many patients will thus require medical therapy to achieve disease control. Pharmacologic options to treat CD have increased in recent years, with an explosion in knowledge related to pathophysiology at the molecular level...
2018: Frontiers in Endocrinology
Niki Vakili Zahir, Maryam Nakhjavani, Parastoo Hajian, Farshad H Shirazi, Hamidreza Mirzaei
Human hepatocellular carcinoma is one of the most common recurrent malignancies since there is no effective therapy for it. Silibinin, a widely used drug and supplement for various liver disorders, demonstrated anti-cancer effects on human hepatocellular carcinoma, human prostate adenocarcinoma cells, human breast carcinoma cells, human ectocervical carcinoma cells, and human colon cancer cells. Considering the anti-hepatotoxic activity of silibinin and its strong preventive and anti-cancer efficacy against various epithelial cancers, we investigated the efficacy of silibinin against human HCC and HUVEC cell lines...
2018: Iranian Journal of Pharmaceutical Research: IJPR
Roghiyeh Faridnia, Hamed Kalani, Mahdi Fakhar, Javad Akhtari
Cutaneous leishmaniosis is an important zoonotic disease caused by various Leishmania species. The aim of this study was to investigate the effects of silibinin and silymarin on the in vitro growth and proliferation of promastigotes and amastigotes of Leishmania major compared to glucantime-treated parasites. The promastigotes and amastigotes of this parasite were treated with the two drugs, silibinin and silymarin, in several concentrations (25–100 μM). The highest effect on promastigotes was for silymarin in concentration of 100 μM with 90% and 91% death rate at hours 48 and 72, respectively...
2018: Annals of Parasitology
Zi-Wei Zhao, Jen-Chih Chang, Li-Wei Lin, Fan-Hsuan Tsai, Hung-Chi Chang, Chi-Rei Wu
Species of Cirsium (Asteraceae family) have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species—including the aerial part of Cirsium arisanense (CAH), the aerial part of Cirsium kawakamii (CKH), the flower part of Cirsium japonicum DC. var. australe (CJF), and Cirsii Herba (CH)—and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography⁻photodiode array detector (HPLC-DAD)...
April 30, 2018: International Journal of Molecular Sciences
Miklós Poór, Gabriella Boda, Violetta Mohos, Mónika Kuzma, Mónika Bálint, Csaba Hetényi, Tímea Bencsik
Diosmin and silibinin (SIL) are polyphenolic compounds which are the active components of several drugs and dietary supplements. After the oral administration of diosmin (flavonoid glycoside), only its aglycone diosmetin (DIO) reaches the systemic circulation. Both DIO and SIL form complexes with serum albumin and are able to inhibit several cytochrome P450 enzymes. Therefore, it is reasonable to hypothesize that these polyphenols may displace some drugs from serum albumin and inhibit their biotransformation, potentially leading to the disruption of drug therapy...
March 31, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yan-Jiao Li, Yu-Jiao Li, Liu-Di Yang, Kun Zhang, Kai-Yin Zheng, Xin-Miao Wei, Qi Yang, Wen-Min Niu, Ming-Gao Zhao, Yu-Mei Wu
Classic antidepressants benefit depression patients partially by improving neurogenesis and/or brain-derived neurotrophic factor (BDNF)/TrkB pathway which were impaired in depression. In this study, we demonstrated that Silibinin (SLB), a polyphenolic flavanoid from Silybum marianum, ameliorated reserpinized mouse depressant-like behaviors. The antidepressants of SLB administration was associated with increased neural stem cells (NSCs) proliferation and further confirmed in BDNF/TrkB signaling transduction...
April 20, 2018: Behavioural Brain Research
Sara Verdura, Elisabet Cuyàs, Laura Llorach-Parés, Almudena Pérez-Sánchez, Vicente Micol, Alfons Nonell-Canals, Jorge Joven, Manuel Valiente, Melchor Sánchez-Martínez, Joaquim Bosch-Barrera, Javier A Menendez
We herein combined experimental and computational efforts to delineate the mechanism of action through which the flavonolignan silibinin targets STAT3. Silibinin reduced IL-6 inducible, constitutive, and acquired feedback activation of STAT3 at tyrosine 705 (Y705). Silibinin attenuated the inducible phospho-activation of Y705 in GFP-STAT3 genetic fusions without drastically altering the kinase activity of the STAT3 upstream kinases JAK1 and JAK2. A comparative computational study based on docking and molecular dynamics simulation over 14 different STAT3 inhibitors (STAT3i) predicted that silibinin could directly bind with high affinity to both the Src homology-2 (SH2) domain and the DNA-binding domain (DBD) of STAT3...
April 14, 2018: Food and Chemical Toxicology
Da-You Ma, Li-Chao Zhang, Kun-Jian Peng, Jiang Zeng, Li-Jun Liu, Zhi-Yong Luo, Su-You Liu
A series of 7-O-aminoalkyl-2,3-dehydrosilibinin derivatives were synthesized and evaluated for their antiproliferative activities against several cancer cell lines. A number of them exhibited greatly enhanced potency with 50% growth inhibition at low micromolar concentrations. Structure activity study indicated that the distance between N and 7-O on the side chain has a limited influence on the antiproliferative activity, while the presence of a morpholino group decreases the antiproliferative activities dramatically...
April 2, 2018: Anti-cancer Agents in Medicinal Chemistry
Yu Chen, Peng Ye, Chongwu Ren, Pengfei Ren, Zheng Ma, Lin Zhang, Wenliang Zhou, Changjie Jiang
To evaluate the pharmacoeconomics of three therapeutic schemes in treating anti-tuberluosis therapy -induced liver injury (anti-TB DILI). Methods: In the construction of a decision tree model, the efficacy and safety parameters came from the results of the randomized, controlled trial conducted here, the effect parameters were derived from expert advice, and the cost parameters, such as usage specification, number, and unit price, came from literature, expert advice, and so on. Results: The cost-effectiveness analysis (CEA) based on the effect degrees showed that bicyclol had the best effect (4...
2018: Open Medicine (Warsaw, Poland)
Jia-Yi Cai, Jian Li, Yong-Na Hou, Kai Ma, Guo-Dong Yao, Wei-Wei Liu, Toshihiko Hayashi, Kikuji Itoh, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima
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. S. aureus treated with low concentration of silibinin (L, 6.2 μM) showed enhanced resistance to kanamycin through increased level of hydrogen peroxide (H2 O2 ). However, S. aureus treated with medium concentration of silibinin (M, 50 μM) showed increased susceptibility to kanamycin through reduced level of H2 O2 ...
March 28, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jing Yang, Yue Sun, Fanxing Xu, Weiwei Liu, Toshihiko Hayashi, Satoshi Onodera, Shin-Ichi Tashiro, Takashi Ikejima
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). This study reports the effect of silibinin on the rat pancreatic β-cell line, INS-1, damaged with pro-inflammatory cytokine, TNFα or IL-1β...
March 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Saba Ershadi, Ali Shayanfar
The limit of detection (LOD) and the limit of quantification (LOQ) are common parameters to assess the sensitivity of analytical methods. In this study, the LOD and LOQ of previously reported terbium sensitized analysis methods were calculated by different methods, and the results were compared with sensitivity parameters [lower limit of quantification (LLOQ)] of U.S. Food and Drug Administration guidelines. The details of the calibration curve and standard deviation of blank samples of three different terbium-sensitized luminescence methods for the quantification of mycophenolic acid, enrofloxacin, and silibinin were used for the calculation of LOD and LOQ...
March 22, 2018: Journal of AOAC International
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
AIM OF THE STUDY: 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. The present study was designed with an aim to investigate the neuroprotective effects of Silibinin against LPS induced oxido-inflammatory cascade and astrocyte activation...
March 15, 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
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