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https://www.readbyqxmd.com/read/28724258/lldt-288-a-novel-triptolide-analogue-exhibits-potent-antitumor-activity-in-vitro-and-in-vivo
#1
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...
July 15, 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
#2
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
#3
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
#4
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...
July 3, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28533220/triptolide-assisted-phosphorylation-of-p53-suppresses-inflammation-induced-nf-%C3%AE%C2%BAb-survival-pathways-in-cancer-cells
#15
Li Zheng, Jia Jia, Huifang Dai, Lei Wan, Jian Liu, Lin Hu, Mian Zhou, Michael Qiu, Xufeng Chen, Lufen Chang, Jae Y Kim, Karen Reckamp, Dan J Raz, Zongping Xia, Binghui Shen
Chronic inflammation plays important roles in cancer initiation and progression. Resolving chronic inflammation or blocking inflammatory signal transduction may prevent cancer development. Here, we report that the combined low-dose use of two anti-inflammatory drugs, aspirin and triptolide, reduces spontaneous lung cancer incidence from 70% to 10% in a mouse model. Subsequent studies reveal that such treatment has little effect in resolving chronic inflammatory conditions in the lung, but it significantly blocks NF-κB-mediated expression of proliferation and survival genes in cancer cells...
May 22, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28523535/self-protection-against-triptolide-induced-toxicity-in-human-hepatic-cells-via-nrf2-are-nqo1-pathway
#16
Ling-Ling Zhou, Cong Zhou, Xiao-Wen Liang, Zhe Feng, Zhang-Pu Liu, Hao-Lu Wang, Xue-Ping Zhou
OBJECTIVE: To find the signaling pathway of triptolide (TP)-induced liver injury and to reveal whether NF-E2-related factor 2 (Nrf2) plays an important role in cellular self-protection. METHODS: The L-02 and HepG2 cells were cultured and treated with various concentrations of TP. The cell viability was observed, and the cell medium was collected for detecting the aspartate aminotransferase (ALT), alanine aminotransferase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and L-glutathione production (GSH) levels...
May 18, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28509400/glycyrrhetinic-acid-accelerates-the-clearance-of-triptolide-through-p-gp-in-vitro
#17
Zhihua Li, Miao Yan, Lingjuan Cao, Pingfei Fang, Zhaohui Guo, Zhenyan Hou, Bikui Zhang
Triptolide (TP) is an active ingredient isolated from Tripterygium wilfordii Hook. f. (TWHF), which is a traditional herbal medicine widely used for the treatment of rheumatoid arthritis and autoimmune disease in the clinic. However, its adverse reactions of hepatotoxicity and nephrotoxicity have been frequently reported which limited its clinical application. The aim of this study was to investigate the mechanism of glycyrrhetinic acid (GA) effecting on the elimination of TP in HK-2 cells and the role of the efflux transporters of P-gp and multidrug resistance-associated proteins (MRPs) in this process...
May 16, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28480392/effect-of-triptolide-on-proliferation-and-apoptosis-of-angiotensin-ii-induced-cardiac-fibroblasts-in-vitro-a-preliminary-study
#18
COMPARATIVE STUDY
Mao Liu, James Yeh, Yin Huang, Alfredo Redondo, Jianting Ke, Jierong Yao, Guangyi Tan, Wenyi Tang, Jian Chen
BACKGROUND: The effect of triptolide (TPL) on cardiac fibroblasts (CFbs) and cardiac fibrosis remain unknown till now. This study was conducted to explore the effects of TPL on proliferation and apoptosis of angiotensin II (Ang II)-induced CFbs. MATERIALS AND METHODS: Ang II was used to promote proliferation of CFbs. Two dosages of TPL (10ng/ml and 100ng/ml) were chosen. MTT assay was used to detect cell survival rate in vitro. Flow cytometer was performed to analyze apoptosis of CFbs...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28471052/supplementation-with-triptolide-increases-resistance-to-environmental-stressors-and-lifespan-in-c-elegans
#19
Sung-Jin Kim, Sun-Mi Beak, Sang-Kyu Park
Triptolide is a major active compound found in Tripterygium wilfordii., also known as Thunder God Vine. Triptolide has been shown to have anti-inflammatory and anticancer activities. In this study, we examined the effect of dietary supplementation with triptolide on response to environmental stressors and lifespan in vivo using Caenorhabditis elegans as a model system. Treatment with 50 mg/L of triptolide in the growth media increased resistance to oxidative stress and reduced the generation of intracellular reactive oxygen species...
June 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28460475/triptolide-suppresses-the-in-vitro-and-in-vivo-growth-of-lung-cancer-cells-by-targeting-hyaluronan-cd44-rhamm-signaling
#20
Jung Min Song, Kalkidan Molla, Arunkumar Anandharaj, Ingrid Cornax, M Gerard O Sullivan, Ameya R Kirtane, Jayanth Panyam, Fekadu Kassie
Higher levels of hyaluronan (HA) and its receptors CD44 and RHAMM have been associated with poor prognosis and metastasis in NSCLC. In the current study, our goal was to define, using cellular and orthotopic lung tumor models, the role of HA-CD44/RHAMM signaling in lung carcinogenesis and to assess the potential of triptolide to block HA-CD44/RHAMM signaling and thereby suppress the development and progression of lung cancer. Triptolide reduced the viability of five non-small cell lung cancer (NSCLC) cells, the proliferation and self-renewal of pulmospheres, and levels of HA synthase 2 (HAS2), HAS3, HA, CD44, RHAMM, EGFR, Akt and ERK, but increased the cleavage of caspase 3 and PARP...
April 18, 2017: Oncotarget
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