Triptolide inhibits the inflammatory activities of neutrophils to ameliorate chronic arthritis

Huang, Guangrui; Yuan, Kai; Zhu, Qingqing; Zhang, Shan; Lu, Qing‐Yi; Zhu, Mengmeng; Sheng, Honghao; Yu, Renqiang; Luo, Guangbin; Xu, Anlong

doi:10.1016/j.molimm.2018.06.012

Cited by 45 publications

(24 citation statements)

References 44 publications

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“…Triptolide (T10) is a monomeric component isolated from a Chinese herb, Tripterygium wilfordii Hook F , which is characterized by anti-inflammatory and anticancer activity [9, 10]. Additionally, it suppresses disturbances produced by cell-autonomous mechanisms in PD, such as aggregation of α Syn and disruption of the autophagy-lysosome system [11].…”

Section: Introductionmentioning

confidence: 99%

Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway

Feng

Zheng

Zhang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Evidence suggests that various forms of α-synuclein- (αSyn-) mediated microglial activation are associated with the progression of Parkinson’s disease. MicroRNA-155-5p (miR155-5p) is one of the most important microRNAs and enables a robust inflammatory response. Triptolide (T10) is a natural anti-inflammatory component, isolated from a traditional Chinese herb. The objective of the current study was to identify the role and potential regulatory mechanism of T10 in αSyn-induced microglial activation via the miR155-5p mediated SHIP1 signaling pathway. Mouse primary microglia were exposed to monomers, oligomers, and preformed fibrils (PFFs) of human wild-type αSyn, respectively. The expressions of TNFα and IL-1β, measured by enzyme-linked immunosorbent assay (ELISA) and qPCR, demonstrated that PFFs initiated the strongest immunogenicity in microglia. Application of inhibitors of toll-like receptor (TLR) 1/2, TLR4, and TLR9 indicated that PFFs activated microglia mainly via the NF-κB pathway by binding TLR1/2 and TLR4. Treatment with T10 significantly suppressed PFF-induced microglial activation and attenuated the release of proinflammatory cytokines including TNFα and IL-1β. Levels of IRAK1, TRAF6, IKKα/β, p-IKKα/β, NF-κB, p-NF-κB, PI3K, p-PI3K, t-Akt, p-Akt and SHIP1 were measured via Western blot. Levels of miR155-5p were measured by qPCR. The results demonstrated that SHIP1 acted as a downstream target molecule of miR155-5p. Treatment with T10 did not alter the expression of IRAK1 and TRAF6, but significantly decreased the expression of miR155-5p, resulting in upregulation of SHIP1 and repression of NF-κB activity, suggesting inhibition of inflammation and microglial activation. The protective effects of T10 were abolished by the use of SHIP1 siRNA and its inhibitor, 3AC, and miR155-5p mimics. In conclusion, our results demonstrated that treatment with T10 suppressed microglial activation and attenuated the release of proinflammatory cytokines by suppressing NF-κB activity via targeting the miR155-5p/SHIP1 pathway in PFFs-induced microglial activation.

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Section: Introductionmentioning

confidence: 99%

Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway

Feng

Zheng

Zhang

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Up to now, a number of studies have demonstrated that triptolide has anti-RA effect. Triptolide can alleviate RA by downregulating neutrophil inflammatory functions effectively (Fan et al., 2016; Zhang et al., 2017; Huang et al., 2018). In recent years, triptolide is mainly used for oral and parenteral administration, but it is usually detected in organs rapidly after administration and excreted via urinary, fecal, and biliary routes (Gong et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

Cubic and hexagonal liquid crystals as drug carriers for the transdermal delivery of triptolide

et al. 2019

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The purpose of this study was to develop and evaluate triptolide-loaded cubic and hexagonal liquid crystals for transdermal drug delivery systems (TDDSs). We prepared and characterized triptolide-loaded lyotropic liquid crystals and evaluated for their percutaneous permeation properties in vitro and in vivo . We then used the adjuvant arthritic rat model and HaCaT cells to analyze the pharmacodynamics and conduct cell-stimulating studies of these liquid crystals. The optimized preparations were identified as cubic and hexagonal phase structures, respectively. Moreover, the in vitro percutaneous penetration studies demonstrated that compared to the homemade triptolide gel, cubic and hexagonal liquid crystals could significantly increase the percutaneous cumulative penetration of drugs within 48 h. Besides, the results of skin-blood synchronous microdialysis showed that the triptolide concentration in skin was higher than that in blood, and the cubic and hexagonal liquid crystals significantly increased the bioavailability of triptolide. Triptolide-loaded cubic and hexagonal liquid crystals presented excellent anti-arthritic effects, alleviating paw swelling and inhibiting inflammation by downregulating the levels of TNF-α and IL-1β. In vitro cell-stimulating studies displayed that triptolide-loaded cubic and hexagonal liquid crystals exhibited no obvious toxicity, which exhibited that triptolide-loaded cubic and hexagonal liquid crystals were remarkable biocompatibility. Collectively, triptolide-loaded cubic and hexagonal liquid crystals represented a promising candidate for rheumatoid arthritis therapy.

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“…TPL, because of its high content and strong physiological activity in Tripterygium wilfordii HOOK. F, has been widely studied in anti-tumor, im-munomodulation, anti-inflammatory, 16,17) and other aspects. Interestingly, in the early literature, TPL was the target of attenuation and enhancement in the combined effects research.…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment with Triptolide and Tyrosine Kinase Inhibitors Synergistically Enhances Apoptosis in Non-small Cell Lung Cancer H1975 Cells but Not H1299 Cells through EGFR/Akt Pathway

Tong

Jiang

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Lung cancer is one of the most common malignant cancers in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a second-or third-line therapy for mutated non-small cell lung cancer (NSCLC). It usually becomes drug resistance after a period of treatment. Triptolide (TPL) is an epoxy diterpenoid lactone compound extracted from Tripterygium wilfordii HOOK. F. and many studies demonstrated that TPL has a synergistic effect when combined with chemotherapy drugs. In this research, we plan to evaluate the combined effect of TPL and EGFR-TKIs (Gefitinib, Erlotinib, and Icotinib) and investigate the possible mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to detect the cell viabilities, combined effect was evaluated by Combination Index. Molecular docking study was used to predict the binding ability of TPL. The expression of proteins was detected by Western blot. MTT results showed TPL had synergistic effect with three EGFR-TKIs at different concentrations on H1975 cells but not on H1299 cells. Molecular docking study demonstrated that TPL with T790M/ L858R EGFR can form a more stable compound than that with wild type EGFR. Western blot results showed TPL inhibited the EGFR/Akt pathway and increased the expression of Bax and the ratio of Bax and Bcl-2 in H1975 cells. In conclusion, TPL had synergistic effect with three EGFR-TKIs on H1975 cells but not on H1299 cells, which may be due to the binding ability of TPL and different-type EGFR. The synergistic effect of TPL on H1975 cells may be partly related to the inhibition of the EGFR/Akt pathway.

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Triptolide inhibits the inflammatory activities of neutrophils to ameliorate chronic arthritis

Cited by 45 publications

References 44 publications

Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway

Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway

Cubic and hexagonal liquid crystals as drug carriers for the transdermal delivery of triptolide

Combined Treatment with Triptolide and Tyrosine Kinase Inhibitors Synergistically Enhances Apoptosis in Non-small Cell Lung Cancer H1975 Cells but Not H1299 Cells through EGFR/Akt Pathway

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