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https://www.readbyqxmd.com/read/28801636/inhibition-of-hypoxic-response-decreases-stemness-and-reduces-tumorigenic-signaling-due-to-impaired-assembly-of-hif1-transcription-complex-in-pancreatic-cancer
#1
Olivia McGinn, Vineet K Gupta, Patricia Dauer, Nivedita Arora, Nikita Sharma, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number of hypoxia mediated signaling pathways including cell proliferation, metabolism and cell survival. Previous studies from our laboratory have shown that Minnelide, a water-soluble pro-drug of triptolide (anti-cancer compound), decreases viability of cancer cells in vitro as well as in vivo. However, its mechanism of action remain elusive. In the current study we evaluated the effect of Minnelide, on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782773/triptolide-and-celastrol-loaded-silk-fibroin-nanoparticles-show-synergistic-effect-against-human-pancreatic-cancer-cells
#2
Baoyue Ding, Md Arif Wahid, Zhijun Wang, Chen Xie, Arvind Thakkar, Sunil Prabhu, Jeffrey Wang
Pancreatic cancer is a lethal disease with a dreadful 5-year survival rate of only 5%. In spite of several treatment options, the prognosis still remains extremely poor. Therefore, novel therapy strategies with combinations of drugs are urgently required to combat this fatal disease. Triptolide (TPL) and celastrol (CL), two main compounds in traditional Chinese medicine isolated from Thunder God Vine, have a broad range of bioactivities including anticancer activity. Silk fibroin (SF), a naturally occurring protein with several unique properties, is an ideal carrier material...
August 7, 2017: Nanoscale
https://www.readbyqxmd.com/read/28752968/-effects-of-triptolide-on-the-autophagy-in-synovial-spleen-and-thymus-of-rats-with-adjuvant-arthritis
#3
Lei Wan, Jian Liu, Chuan-Bing Huang, Xiao-Jun Zhang, Ya-Li Wang, Ping-Heng Zhang, Yue Sun, Lei Liu
OBJECTIVE: To determine the effect of triptolide (TP) on the expression of ATG /LC3-Ⅱ Beclin1 in synovial, spleen, and thymusof rats with adjuvant arthritis (AA). METHODS: Rats were divided for four groups: normal control (NC), model control (MC), leflunomide (LEF) treatment, and triptolide (TP)treatment, with 12 rats in each group.The AA model was established through Freund's complete adjuvant (0.1 mL each) injection into the right foot plantar skin to introduce inflammation and 10 days of tail root injection of 0...
July 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28751314/biosynthesis-of-diterpenoids-in-tripterygium-adventitious-root-cultures
#4
Fainmarinat Inabuy, Justin T Fischedick, Iris Lange, Michael Hartmann, Narayanan Srividya, Amber N Parrish, Meimei Xu, Reuben J Peters, Bernd Markus Lange
Adventitious root cultures were developed from Tripterygium regelii Sprague & Takeda and growth conditions optimized for the abundant production of diterpenoids, which can be collected directly from the medium. An analysis of publicly available transcriptome data sets collected with T. regelii roots and root cultures indicated the presence of a large gene family (with 20 members) for terpene synthases (TPSs). Nine candidate diterpene synthase genes were selected for follow-up functional evaluation, of which two belonged to the TPS-c, three to the TPS-e/f and four to the TPS-b subfamily...
July 27, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28743324/atomic-force-microscopy-study-of-the-anti-inflammatory-effects-of-triptolide-on-rheumatoid-arthritis-fibroblast-like-synoviocytes
#5
Zhanhui Su, Han Sun, Man Ao, Chunying Zhao
High-resolution atomic force microscopy (AFM) was used for the in situ evaluation of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of triptolide, based on the morphological and biophysical changes observed in RA-FLS. RA-FLS have been reported to play a primary role in inflammatory bone destruction during the development of RA and thus are regarded as an important target for RA treatment. Triptolide pretreatment significantly inhibited tumor necrosis factor-α-induced expression of the interleukin (IL)-1β, IL-6, and IL-8 genes in MH7A cells...
July 26, 2017: Microscopy and Microanalysis
https://www.readbyqxmd.com/read/28740548/modulation-of-salmonella-tumor-colonization-and-intratumoral-anti-angiogenesis-by-triptolide-and-its-mechanism
#6
Jianxiang Chen, Yiting Qiao, Bo Tang, Guo Chen, Xiufeng Liu, Bingya Yang, Jing Wei, Xiangyu Zhang, Xiawei Cheng, Pan Du, Wenhui Jiang, Qingang Hu, Zi-Chun Hua
The weakened tumour colonization of attenuated Salmonella has severely hampered its clinical development. In this study, we investigated whether an anti-inflammation and antiangiogenesis compound triptolide could improve the efficacy of VNP20009, a highly attenuated Salmonella strain, against mice melanoma. By comparing the effects of conventional VNP20009 monotherapy and a combination therapy that uses both triptolide and VNP20009, we found that triptolide significantly improved the tumour colonization of VNP20009 by reducing the number of infiltrated neutrophils in the melanoma, which led to a larger necrotic area in the melanoma...
2017: Theranostics
https://www.readbyqxmd.com/read/28724258/lldt-288-a-novel-triptolide-analogue-exhibits-potent-antitumor-activity-in-vitro-and-in-vivo
#7
Hongtao Xu, Xiaoting Fan, Guanjun Zhang, Xiaoyu Liu, Zhihong Li, Yuanchao Li, Biao Jiang
(14S)-14β-(1-(2-morpholinoethyl)-1H-indazol-5-ylamino)mthylepitriptolide (LLDT-288) was a novel C14β-heterocycle aminomethyl substituent triptolide analogue, which showed comparable cytotoxicity to triptolide. Here we demonstrated that LLDT-288 displayed broad-spectrum, potent antitumor activity, effectively against drug-resistance cancer cells, and induced apoptosis in vitro, but exerted low toxicity. Moreover, it exhibited a remarkable microsomal stability, and showed no inhibitory effects on different cytochrome P450 isoforms...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28719353/effect-of-triptolide-on-retinal-ganglion-cell-survival-in-an-optic-nerve-crush-model
#8
Y-F Li, Y-F Zou, X-F Chen, W Zhang
Optic nerve crush model could be used to investigate the mechanism of neuronal survival and axonal regeneration in central nervous system. Triptolide, a Chinese herb extract with anti-inflammatory and immunosuppressive activities, has shown neuron protective functions in nervous system. In this study, we investigated the changes in retinal ganglion cell survival and axonal regeneration after administration of triptolide in optic nerve crush model. Triptolide treatment tended to promote retinal ganglion cell survival rather than optic nerve regeneration as well as inhibit the expression of tumor necrosis factor-α and activation of nuclear factor-kappa B...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28695984/triptolide-prevents-extracellular-matrix-accumulation-in-experimental-diabetic-kidney-disease-by-targeting-microrna-137-notch1-pathway
#9
Fei Han, Shanshan Wang, Yunpeng Chang, Chunjun Li, Juhong Yang, Zhe Han, Baocheng Chang, Bei Sun, Liming Chen
MicroRNAs (miRNAs) are involved in multiple biological functions via suppressing target genes. Triptolide is a monomeric compound isolated from a traditional Chinese herb, which exerts protective roles in many kinds of glomerular diseases. However, our understanding of the triptolide effect on miRNAome is still limited. In this study, we found that triptolide significantly decreased albuminuria and improved glomerulosclerosis in rats with diabetic kidney disease (DKD). And triptolide also inhibited extracellular matrix (ECM) protein accumulation and the notch1 pathway activation under diabetic conditions...
July 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28677733/sulforaphane-inhibits-the-interferon-%C3%AE-induced-expression-of-mig-ip-10-and-i-tac-in-ins%C3%A2-1-pancreatic-%C3%AE-cells-through-the-downregulation-of-irf-1-stat-1-and-pkb
#10
Yu-Kyoung Park, Mahesh Ramalingam, Shin Kim, Byeong-Churl Jang, Jong Wook Park
Sulforaphane (SFN) is a dietary isothiocyanate abundantly available in cruciferous vegetables and has been shown to possess anti-inflammatory and immunomodulatory activities. Chemokines are important mediators of inflammation and immune responses due to their ability to recruit and activate macrophages and leukocytes. To date, little is known about the SFN-mediated regulation of chemokine expression in pancreatic β-cells. In this study, we investigated the inhibitory effects and mechanisms of SFN on the interferon-γ (IFN-γ)-induced expression of a subset of chemokines, including monokine induced by IFN-γ (MIG), IFN-inducible protein of 10 kDa (IP-10) and IFN-inducible T‑cell alpha chemoattractant (I-TAC), in INS‑1 cells, a rat pancreatic β-cell line...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28672939/triptolide-suppresses-ultraviolet-b-enhanced-sebum-production-by-inhibiting-the-biosynthesis-of-triacylglycerol-in-hamster-sebaceous-glands-in-vivo-and-in-vitro
#11
Takashi Sato, Noriko Akimoto, Aiko Takahashi, Akira Ito
Ultraviolet B (UVB) irradiation causes alterations in cutaneous barrier function, including excessive production of sebum in sebaceous glands, which is associated with the aggravation of acne. This study aimed to evaluate the inhibitory effects of triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, on sebocytic lipogenesis in UVB-irradiated hamster skin in vivo and in vitro. Topical application of triptolide decreased the UVB-enhanced sebum accumulation in the sebaceous glands of hamster skin...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28638477/triptolide-inhibits-the-ar-signaling-pathway-to-suppress-the-proliferation-of-enzalutamide-resistant-prostate-cancer-cells
#12
Yangyang Han, Weiwei Huang, Jiakuan Liu, Dandan Liu, Yangyan Cui, Ruimin Huang, Jun Yan, Ming Lei
Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown...
2017: Theranostics
https://www.readbyqxmd.com/read/28629539/uplc-esi-qtof-ms-based-metabolomics-survey-on-the-toxicity-of-triptolide-and-detoxication-of-licorice
#13
Zhuo Wang, Jian-Qun Liu, Jin-Di Xu, He Zhu, Ming Kong, Guo-Hua Zhang, Su-Min Duan, Xiu-Yang Li, Guang-Fu Li, Li-Fang Liu, Song-Lin Li
Triptolide (TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction (LWE) against such toxicity...
June 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28627592/triptolide-exerts-protective-effects-against-fibrosis-following-ileocolonic-anastomosis-by-mechanisms-involving-the-mir-16-1-hsp70-pathway-in-il-10-deficient-mice
#14
Hong-Wei Hou, Jin-Min Wang, Dong Wang, Rong Wu, Zhen-Ling Ji
Surgeries, particularly ileocecal resection (ICR), are often required in the treatment of Crohn's disease (CD). However, recurrences are common for patients who undergo ICR, and anastomotic fibrosis is the main cause of re-operation. The present study aimed to investigate the therapeutic effects of triptolide (TPL) in ameliorating fibrosis following ileocolonic anastomosis. A model of IL‑10‑/‑ mice undergoing ICR was used to study postsurgical inflammation and fibrosis of anastomosis. For this purpsose, interleukin (IL)‑10‑/‑ mice were randomly divided into 3 groups as follows: the control group, the saline‑treated group subjected to ICR (ST‑ICR) and the TPL‑treated group subjected to ICR (TT‑ICR)...
June 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28614959/the-effects-of-triptolide-on-the-pharmacokinetics-of-sorafenib-in-rats-and-its-potential-mechanism
#15
Xianming Wang, Xin Zhang, Fei Liu, Minghai Wang, Shiyong Qin
CONTEXT: Combining sorafenib with triptolide could inhibit tumour growth with greater efficacy than single-agent treatment. However, their herb-drug interaction remains unknown. OBJECTIVE: This study investigates the herb-drug interaction between triptolide and sorafenib. MATERIALS AND METHODS: The effects of triptolide (10 mg/kg) on the pharmacokinetics of different doses of sorafenib (20, 50 and 100 mg/kg) in rats, and blood samples were collected within 48 h and evaluated using LC-MS/MS...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28608823/production-of-putative-diterpene-carboxylic-acid-intermediates-of-triptolide-in-yeast
#16
Victor Forman, Roberta Callari, Christophe Folly, Harald Heider, Björn Hamberger
The development of medical applications exploiting the broad bioactivities of the diterpene therapeutic triptolide from Tripterygium wilfordii is limited by low extraction yields from the native plant. Furthermore, the extraordinarily high structural complexity prevents an economically attractive enantioselective total synthesis. An alternative production route of triptolide through engineered Saccharomyces cerevisiae (yeast) could provide a sustainable source of triptolide. A potential intermediate in the unknown biosynthetic route to triptolide is the diterpene dehydroabietic acid...
June 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28608490/antiestrogenic-activity-of-triptolide-in-human-breast-cancer-cells-mcf-7-and-immature-female-mouse
#17
Yi Tang, Jun Wang, Jinghua Cheng, Lijun Wang
Preclinical Research To investigate the antiestrogenic activity of triptolide in human breast cancer cell line MCF-7 and immature female C57BL/6 mouse. The effects of triptolide on cell proliferation, cell cycle, and the expression of estrogen receptor alpha (ERα) and progesterone receptor (PR) were examined in MCF-7 cells. In vivo antiestrogenic effects of triptolide were observed after cotreatment of mice with E2 and triptolide for 4 days. Triptolide dose- and time-dependently inhibited cell growth in untreated or E2 -treated MCF-7 cells, which was associated with increased S phase arrest...
June 2017: Drug Development Research
https://www.readbyqxmd.com/read/28572827/protective-effect-of-18%C3%AE-glycyrrhetinic-acid-against-triptolide-induced-hepatotoxicity-in-rats
#18
Guanghua Yang, Lan Wang, Xiuting Yu, Yanfeng Huang, Chang Qu, Zhenbiao Zhang, Dandan Luo, Ji Lin, Lian Zhou, Ziren Su, Xiaojun Zhang, Haiming Chen
Triptolide (TP) is the major active component of Tripterygium wilfordii Hook F (TWHF) and possesses multiple pharmacological effects. However, hepatotoxicity of TP which is one of the toxic properties slows its progression in clinical application. 18β-Glycyrrhetinic acid (GA) is the main bioactive ingredient of Licorice (Glycyrrhiza glabra L.), a herbal medicine famous for its detoxification. This study aims to investigate whether GA possesses protective effect against TP-induced hepatotoxicity in rats. TP interference markedly elevated serum levels of ALT, AST, and ALP, caused evident liver histopathological changes, and elevated hepatic TNF-α, IL-6, IL-1β, and IFN-γ as well as nuclear translocation of NF-κB...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28558869/triptolide-reduces-prostate-size-and-androgen-level-on-testosterone-induced-benign-prostatic-hyperplasia-in-sprague-dawley-rats
#19
Yu-Rong Wang, Yuan Xu, Zhen-Zhou Jiang, Lu-Yong Zhang, Tao Wang
Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg·kg(-1) for 2 weeks, along with the TP injections...
May 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28536529/activation-of-sirt1-fxr-signaling-pathway-attenuates-triptolide-induced-hepatotoxicity-in-rats
#20
Jing Yang, Lixin Sun, Lu Wang, Hozeifa M Hassan, Xuan Wang, Phillip B Hylemon, Tao Wang, Huiping Zhou, Luyong Zhang, Zhenzhou Jiang
Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis...
2017: Frontiers in Pharmacology
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