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https://www.readbyqxmd.com/read/29902661/a-feasibility-study-of-the-toxic-responses-of-human-induced-pluripotent-stem-cell-derived-hepatocytes-to-phytochemicals
#1
Tomáš Smutný, Riina Harjumäki, Liisa Kanninen, Marjo Yliperttula, Petr Pávek, Yan-Ru Lou
Herbal medicines have been increasingly used in the last three decades. Despite their popularity, safety issues with herbal products need to be addressed. We performed a feasibility study of the toxic responses of human induced pluripotent stem cell-derived hepatocytes (iHep cells) to phytochemicals in comparison with hepatoblasoma-derived HepG2 cells and long-term human hepatocytes (LTHHs). The iHep cells expressed typical hepatocyte markers cytochrome P450 3A4 (CYP3A4), hepatocyte nuclear factor 4α, and albumin despite the expression of immature markers α-fetoprotein and cytokeratin 19...
June 11, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29864943/biochemical-and-computational-evaluation-of-triptolide-induced-cytotoxicity-against-nsclc
#2
Aida M Hamdi, Zhen-Zhou Jiang, Mounia Guerram, Bashir A Yousef, Hozeifa M Hassan, Jia-Wei Ling, Lu-Yong Zhang
Triptolide is the major bioactive component isolated from the Chinese Medicinal plant Tripterygium wilfordii. Despite the growing interest and the plethora of reports discussing the pharmacological activity of this diterpenoid, no clear consensus regarding its cellular targets and full mechanism of action has been reached. In the present work, a combined in vitro and in silico approach was used to evaluate the biological activity of Triptolide on Non-small cell lung cancer (NSCLC). In vitro, Triptolide treatment induced apoptosis in NSCLC cell lines and down-regulated the phosphorylation of AKT, mTOR, and p70S6K...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29807227/broad-targeting-of-triptolide-to-resistance-and-sensitization-for-cancer-therapy
#3
REVIEW
Zhen-Yan Hou, Xiao-Pei Tong, Yong-Bo Peng, Bi-Kui Zhang, Miao Yan
Cancer cell resistance to current anticancer therapeutics as well as the side effects are still obstacles to successful cancer therapy. Hence, the development of novel anticancer agents or therapeutics is of vital significance, and especially rational adjuvant therapies containing low-cost natural products with multiple targets have attracted great interests. Triptolide, the main biocomponent of Tripterygium wilfordii Hook F, is restricted in clinical applications mainly due to its severe systemic toxicities, although it has shown strong antitumor activities in preclinical studies...
May 25, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29799631/metabolic-alterations-in-triptolide-induced-acute-hepatotoxicity
#4
Jie Zhao, Cen Xie, Xiyan Mu, Kristopher W Krausz, Daxesh P Patel, Xiaowei Shi, Xiaoxia Gao, Qiao Wang, Frank J Gonzalez
Triptolide, a major active constitute of Tripterygium wilfordii Hook. F, is prescribed for the treatment of autoimmune diseases in China. One of its most severe adverse effects observed in the clinical use is hepatotoxicity, but the mechanism is still unknown. Therefore, the present study applied an LC/MS-based metabolomic analysis to characterize the metabolomic changed in serum and liver induced by triptolide in mice. Mice were administered triptolide by gavage to establish the acute liver injury model, and serum biochemical and liver histological analysis were applied to assess the degree of toxicity...
May 25, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29791258/licorice-root-extract-and-magnesium-isoglycyrrhizinate-protect-against-triptolide-induced-hepatotoxicity-via-up-regulation-of-the-nrf2-pathway
#5
Qin-You Tan, Qian Hu, Sheng-Nan Zhu, Lu-Lu Jia, Juan Xiao, Hua-Zhen Su, Shao-Yuan Huang, Jing Zhang, Junfei Jin
Triptolide, the predominant biologically active component of the Chinese herb Tripterygium wilfordii Hook f., possesses numerous pharmacological activities, including anti-inflammatory, anti-fertility, anti-neoplastic, and immunosuppressive effects. However, toxicity and severe adverse effects, particularly hepatotoxicity, limit the clinical application of triptolide. Licorice root extract contains various bioactive compounds and is potent hepatoprotective. Magnesium isoglycyrrhizinate, a magnesium salt of the 18α-glycyrrhizic acid stereoisomer of glycyrrhizic acid, is used clinically in China to treat chronic viral hepatitis and acute drug-induced liver injury...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29723566/triptolide-induced-mitochondrial-damage-dysregulates-fatty-acid-metabolism-in-mouse-sertoli-cells
#6
Yisen Cheng, Gaojian Chen, Li Wang, Jiamin Kong, Ji Pan, Yue Xi, Feihai Shen, Zhiying Huang
Triptolide is a major active ingredient of tripterygium glycosides, used for the therapy of immune and inflammatory diseases. However, its clinical applications are limited by severe male fertility toxicity associated with decreased sperm count, mobility and testicular injures. In this study, we determined that triptoide-induced mitochondrial dysfunction triggered reduction of lactate and dysregulation of fatty acid metabolism in mouse Sertoli cells. First, triptolide induced mitochondrial damage through the suppressing of proliferator-activated receptor coactivator-1 alpha (PGC-1α) activity and protein...
April 30, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29713369/extrahepatic-cytochrome-p450s-play-an-insignificant-role-in-triptolide-induced-toxicity
#7
Yuan Wei, Dujun Wang, Meng Chen, Zhen Ouyang, Shuo Wang, Jun Gu
Background: Triptolide, an active ingredient of Chinese medicine plant Tripterygium wilfordii Hook.f., has been shown to exert anti-tumor, immunosuppressive, anti-inflammatory, and anti-fertility pharmacological effects. However, triptolide also causes severe side effects, which are manifested as toxicities in multiple organs. The aim of this study was to analyze the role of extrahepatic cytochrome P450 enzymes in triptolide-induced toxicity. Methods: Xh-CL mouse model with normal liver, but low extrahepatic P450 expression levels was used in this study...
2018: Chinese Medicine
https://www.readbyqxmd.com/read/29693706/effects-of-triptolide-on-the-expression-of-mhc-ii-in-microglia-in-kainic-acid%C3%A2-induced-epilepsy
#8
Zheng Sun, Meng Du, Yao Lu, Chang-Qian Zeng
The purpose of the present study was to determine whether triptolide (T10) had any effect on major histocompatibility complex class II (MHC II) expression in kainic acid (KA)‑activated microglia, and to investigate the underlying molecular mechanism. BV‑2 microglia were pretreated with T10 prior to activation with KA. The expression level of MHC II and class II transactivator (CIITA) mRNA was determined via reverse transcription‑polymerase chain reaction. The expression of MHC II, CIITA and the phosphorylation level of c‑Jun and proto‑oncogene c‑Fos (c‑Fos) was determined by western blotting...
April 18, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29676120/-preparation-and-transdermal-permeation-of-triptolide-and-ferulic-acid-ethosomes-gel-in-vitro
#9
Ling Tao, Liang-Fei He, Yong-Mei Guan, Li-Hua Chen, Wei-Feng Zhu, Chen Jin, Lu Wu
The aim of this study was to prepare triptolide and ferulic acid ethosomes gel, investigate its transdermal permeation, and compare the results with ordinary gel and cream. Improved Franz diffusion cell method was used in the transdermal delivery experiment with rat abdominal skin as in vitro model. The receptor fluid at different time points was collected; ferulic acid concentration was determined by high performance liquid chromatography (HPLC) and triptolide concentration was determined by liquid chromatography-electrospray ionization mass spectrometry (LC-MS/MS)...
March 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29670349/fabrication-of-a-triptolide-loaded-and-poly-%C3%AE-glutamic-acid-based-amphiphilic-nanoparticle-for-the-treatment-of-rheumatoid-arthritis
#10
Li Zhang, Junli Chang, Yongjian Zhao, Hao Xu, Tengteng Wang, Qiang Li, Lianping Xing, Jing Huang, Yongjun Wang, Qianqian Liang
Triptolide (TP) exhibits immunosuppressive, cartilage-protective and anti-inflammatory effects in rheumatoid arthritis. However, the toxicity of TP limits its widespread use. To decrease the toxic effects, we developed a novel nano-drug carrier system containing TP using poly-γ-glutamic acid-grafted di-tert-butyl L-aspartate hydrochloride (PAT). PAT had an average diameter of 79±18 nm, a narrow polydispersity index (0.18), a strong zeta potential (-32 mV) and a high drug encapsulation efficiency (EE1 =48...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29665897/-effects-of-triptolide-combined-with-homoharringtonine-on-proliferation-and-apoptosis-of-kg-1%C3%AE-cells
#11
Xin Li, Jia-Yan Liu, Xiao-Hong Yuan, Zhen-Xing Lin, Yong Wu
OBJECTIVE: To investigate the effect and possible mechanism of low concentration of triptolide (TPL) combined with homoharringtonine (HHT) on the proliferation and apoptosis of KG-1α cells. METHODS: CCK-8 method was used to detect the antiproliferating effects of different concentrations of TPL and HHT single-use and combined use on KG-1α cells, and the combined index (CI) was calculated. The colony formation ability was also determined by methylcellulose colony formation assay, cell surface molecules, apoptosis rate and cell cycle changes were detected by flow cytometry...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29649522/triptolide-up-regulates-metabotropic-glutamate-receptor-5-to-inhibit-microglia-activation-in-the-lipopolysaccharide-induced-model-of-parkinson-s-disease
#12
Yi-Ying Huang, Qian Zhang, Jian-Nan Zhang, Ya-Nan Zhang, Li Gu, Hui-Min Yang, Ning Xia, Xiao-Min Wang, Hong Zhang
Metabotropic glutamate receptor (mGlu)5 regulates microglia activation, which contributes to inflammation. However, the role of mGlu5 in neuroinflammation associated with Parkinson's disease (PD) remains unclear. Triptolide (T10) exerts potent immunosuppressive and anti-inflammatory effects and protects neurons by inhibiting microglia activation. In this study, we investigated the role of mGlu5 in the anti-inflammatory effect of T10 in a lipopolysaccharide (LPS)-induced PD model. In cultured BV2 cells and primary microglia, blocking mGlu5 activity or knocking down its expression abolished T10-inhibited release of proinflammatory cytokines induced by LPS...
April 9, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29618945/inducers-of-senescence-toxic-compounds-and-senolytics-the-multiple-faces-of-nrf2-activating-phytochemicals-in-cancer-adjuvant-therapy
#13
REVIEW
Marco Malavolta, Massimo Bracci, Lory Santarelli, Md Abu Sayeed, Elisa Pierpaoli, Robertina Giacconi, Laura Costarelli, Francesco Piacenza, Andrea Basso, Maurizio Cardelli, Mauro Provinciali
The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29615906/mechanisms-of-triptolide-induced-hepatotoxicity-and-protective-effect-of-combined-use-of-isoliquiritigenin-possible-roles-of-nrf2-and-hepatic-transporters
#14
Zhenyan Hou, Lei Chen, Pingfei Fang, Hualin Cai, Huaibo Tang, Yongbo Peng, Yang Deng, Lingjuan Cao, Huande Li, Bikui Zhang, Miao Yan
Triptolide (TP), the main bioactive component of Tripterygium wilfordii Hook F, can cause severe hepatotoxicity. Isoliquiritigenin (ISL) has been reported to be able to protect against TP-induced liver injury, but the mechanisms are not fully elucidated. This study aims to explore the role of nuclear transcription factor E2-related factor 2 (Nrf2) and hepatic transporters in TP-induced hepatotoxicity and the reversal protective effect of ISL. TP treatment caused both cytotoxicity in L02 hepatocytes and acute liver injury in mice...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29606369/various-signaling-pathways-in-multiple-myeloma-cells-and-effects-of-treatment-on-these-pathways
#15
REVIEW
Ali Dehghanifard, Saeid Kaviani, Saeid Abroun, Mahshad Mehdizadeh, Sajedeh Saiedi, Amirhosein Maali, Sasan Ghaffari, Mehdi Azad
Multiple myeloma (MM) results from malignancy in plasma cells and occurs at ages > 50 years. MM is the second most common hematologic malignancy after non-Hodgkin lymphoma, which constitutes 1% of all malignancies. Despite the great advances in the discovery of useful drugs for this disease such as dexamethasone and bortezomib, it is still an incurable malignancy owing to the development of drug resistance. The tumor cells develop resistance to apoptosis, resulting in greater cell survival, and, ultimately, develop drug resistance by changing the various signaling pathways involved in cell proliferation, survival, differentiation, and apoptosis...
May 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29576708/further-study-of-influence-of-panax-notoginseng-on-intestinal-absorption-characteristics-of-triptolide-and-tripterine-in-rats-with-tripterygium-wilfordii
#16
Yiqun Li, Benyong Zhang, Mengzhu Liu, Xinlong Zhang, Donglei Shi, Liwei Guo, Jinao Duan, Xueping Zhou, Huaxu Zhu, Qichun Zhang
Background: Tripterygium wilfordii (TW) is widely employed to treat rheumatoid arthritis and autoimmune disorders clinically, which, however, accompany with disturbing hepatotoxicity and nephrotoxicity. The previous research showed that Panax notoginseng (PN) compatibly and significantly reduces the TW-induced hepatotoxicity. Objective: To explore the underlying mechanism, the present study was designed to reveal the influence of PN on the intestinal absorption process of TW-derived active components in rat...
January 2018: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29552824/-low-dose-of-triptolide-ameliorates-podocyte-epithelial-mesenchymal-transition-induced-by-high-dose-of-d-glucose-via-inhibiting-wnt3%C3%AE-%C3%AE-catenin-signaling-pathway-activation
#17
Ge Shi, Wei Wu, Yi-Gang Wan, He Wei-Ming Hex, Yue Tu, Wen-Bei Han, Bu-Hui Liu, Ying-Lu Liu, Zi-Yue Wan
To explore the effects and molecular mechanisms of triptolide(TP)on improving podocyte epithelial-mesenchymal transition(EMT)induced by high dose of D-glucose(HG), the immortalized podocytes of mice in vitro were divided into the normal group(N), the high dose of D-glucose group(HG), the low dose of TP group(L-TP), the high dose of TP group(H-TP)and the mannitol group(MNT), and treated by the different measures respectively. More specifically, the podocytes in each group were separately treated by D-glucose(DG, 5 mmol·L⁻¹)or HG(25 mmol·L⁻¹)or HG(25 mmol·L⁻¹)+ TP(3 μg·L⁻¹)or HG(25 mmol·L⁻¹)+ TP(10 μg·L⁻¹)or DG(5 mmol·L⁻¹)+ MNT(24...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29545863/triptolide-induces-autophagy-and-apoptosis-through-erk-activation-in-human-breast-cancer-mcf-7-cells
#18
Huan Gao, Yue Zhang, Lei Dong, Xiao-Yu Qu, Li-Na Tao, Yue-Ming Zhang, Jing-Hui Zhai, Yan-Qing Song
To investigate the effects of triptolide (TPI) on proliferation, autophagy and death in human breast cancer MCF-7 cells, and to elucidate the associated molecular mechanisms, intracellular alterations were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The results of the MTT assay revealed that TPI significantly reduced the MCF-7 cell survival rate when the concentration was >10 nmol/l. TPI activated a caspase cascade reaction by regulating Bcl-2-associated X protein (Bax), caspase-3 and B-cell lymphoma 2 expression, and promoted programmed cell death via the mitochondrial pathway...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29523159/c-myc-dependent-repression-of-two-oncogenic-mirna-clusters-contributes-to-triptolide-induced-cell-death-in-hepatocellular-carcinoma-cells
#19
Shu-Guang Li, Qian-Wei Shi, Ling-Yan Yuan, Li-Ping Qin, Yan Wang, Yu-Qing Miao, Zhe Chen, Chang-Quan Ling, Wen-Xing Qin
BACKGROUND: Triptolide is a structurally unique diterpene triepoxide with potent antitumor activity. However,the effect and mechanism of triptolide on hepatocellular carcinoma (HCC) is not well studied. METHODS: Cells were treated with triptolide, and the anti-HCC activity of triptolide was evaluated using flow cytometry, western blot, and xenograft studies. MicroRNA microarray and quantitative reverse-transcription polymerase chain reaction was used to identify differential microRNAs induced by triptolide...
March 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29516693/-involvement-of-pi-3-k-akt-mtor-signaling-in-protective-effects-of-moxibustion-for-premature-ovarian-failure-in-rats
#20
Cai-Rong Zhang, Ji-Li Deng, Wei-Na Zhu, Ming-Xing Miao, Wei-Wei Shen, Sheng-Jun Cao, Yong Tang
OBJECTIVE: To study the protective effect of moxibustion for tripterygium-induced premature ovarian failure (POF) and its underlying mechanisms in rats. METHODS: Forty-five female SD rats were randomly divided into normal control, POF model and moxibustion groups ( n =15/group). The POF model was induced by intragastric administration of Triptolide (40 mg/kg), once daily for 6 weeks. From the 4th week after modeling, moxibustion was given at "Guanyuan" (CV 4) and bilateral "Sanyinjiao" (SP 6) for 10 min, once daily for 3 weeks...
February 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
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