Triptolide: Medicinal chemistry, chemical biology and clinical progress

Hou, Wenhua; Liu, Bo; Xu, Hongtao

doi:10.1016/j.ejmech.2019.05.032

Cited by 107 publications

(64 citation statements)

References 131 publications

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“…Apart from polyphenols, terpenoids are the second-largest group of active constituents for CAC treatment, among which the typical ones are triptolide, celastrol, and pristimerin. Celastrol is a quinone methide triterpenoid first extracted from the root bark of the Chinese medicine 'Thunder of God Vine' (also known as Tripterygium wilfordii Hook F) in 1936 (Yang et al, 2006;Hou et al, 2019). Pristimerin (a species of quinone methide triterpenoid) and triptolide (a species of diterpenoid triepoxide) are also capable of being isolated from Tripterygium wilfordii Hook F Hou et al, 2019;.…”

Section: Herbal Medicines Based On the Above Active Componentsmentioning

confidence: 99%

“…Celastrol is a quinone methide triterpenoid first extracted from the root bark of the Chinese medicine 'Thunder of God Vine' (also known as Tripterygium wilfordii Hook F) in 1936 (Yang et al, 2006;Hou et al, 2019). Pristimerin (a species of quinone methide triterpenoid) and triptolide (a species of diterpenoid triepoxide) are also capable of being isolated from Tripterygium wilfordii Hook F Hou et al, 2019;. It is surprising that these three components are all active constituents of Tripterygium wilfordii Hook F and that they are also abundant in the Celastraceae and Hippocrateaceae families Venkatesha et al, 2016).…”

Section: Herbal Medicines Based On the Above Active Componentsmentioning

confidence: 99%

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Apoptosis Exerts a Vital Role in the Treatment of Colitis-Associated Cancer by Herbal Medicine

et al. 2020

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Colitis-associated cancer (CAC) is known as inflammatory bowel disease (IBD)-developed colorectal cancer, the pathogenesis of which involves the occurrence of apoptosis. Western drugs clinically applied to CAC are often single-targeted and exert many adverse reactions after long-term administration, so it is urgent to develop new drugs for the treatment of CAC. Herbal medicines commonly have multiple components with multiple targets, and most of them are low-toxicity. Some herbal medicines have been reported to ameliorate CAC through inducing apoptosis, but there is still a lack of systematic review. In this work, we reviewed articles published in Sci Finder, Web of Science, PubMed, Google Scholar, CNKI, and other databases in recent years by setting the keywords as apoptosis in combination with colitis-associated cancer. We summarized the herbal medicine extracts or their compounds that can prevent CAC by modulating apoptosis and analyzed the mechanism of action. The results show the following. (1) Herbal medicines regulate both the mitochondrial apoptosis pathway and death receptor apoptosis pathway. (2) Herbal medicines modulate the above two apoptotic pathways by affecting signal transductions of IL-6/STAT3, MAPK/NF-k B, Oxidative stress, Noncanonical TGF-b1, WNT/b-catenin, and Cell cycle, thereby ameliorating CAC. We conclude that following. (1) Studies on the role of herbal medicine in regulating apoptosis through the Ras/Raf/ERK, WNT/b-catenin, and Cell cycle pathways have not yet been carried out in sufficient depth. (2) The active constituents of reported anti-CAC herbal medicine mainly include polyphenols, terpenoids, and saccharide. Also, we identified other herbal medicines with the constituents mentioned above as their main components, aiming to provide a reference for the clinical use of herbal medicine in the treatment of CAC. (3) New dosage forms can be utilized to elevate the targeting and reduce the toxicity of herbal medicine.

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Section: Herbal Medicines Based On the Above Active Componentsmentioning

confidence: 99%

Section: Herbal Medicines Based On the Above Active Componentsmentioning

confidence: 99%

Apoptosis Exerts a Vital Role in the Treatment of Colitis-Associated Cancer by Herbal Medicine

et al. 2020

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“…TP can also abrogate the growth of colon cancer and induce cell cycle arrest by inhibiting the transcriptional activation of early gene 2 promoter binding factor (E2F) (Oliveira et al, 2015). Besides the immunomodulatory and anti-cancer effects, It has been also reported that TP treatment can protect rat hearts against pressure overload-induced cardiac fibrosis, improve ventricular function (Wen et al, 2013;Zhang et al, 2013;Li et al, 2017) and attenuate cardiac hypertrophy (Ding et al, 2016), even though it may cause acute myocardial damage, such as myocardium denaturation, swelling, and necrosis when administered with high dose (Hou et al, 2019). However, the effects of TP on cell cycle regulators in myocardial hypertrophy and its mechanism are currently poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…Triptolide (TP), the major active component of the Chinese medicinal herb Tripterygium wilfordii Hook F, has been used for the treatment of some inflammatory, autoimmune disorders, such as lupus, nephrotic syndrome, Behçet’s disease, and rheumatoid arthritis, and a variety of cancers ( Pan, 2010 ; Fan et al., 2016 ; Ziaei and Halaby, 2016 ; Hou et al., 2019 ; Noel et al., 2019 ). It has been suggested that TP could downregulate the expression of the retinoblastoma protein (Rb), cyclin A, cyclin B, CDK1, and CDK2; trigger cell cycle arrest in the S phase; and induce apoptosis in the cells involved in human renal cell carcinoma and multiple myeloma ( Li et al., 2011 ; Noel et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Triptolide on Temporal Expression of Cell Cycle Regulators During Cardiac Hypertrophy

Pan

Ding

et al. 2020

Front. Pharmacol.

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Adult mammalian cardiomyocytes may reenter the cell cycle and cause cardiac hypertrophy. Triptolide (TP) can regulate the expressions of various cell cycle regulators in cancer cells. However, its effects on cell cycle regulators during myocardial hypertrophy and mechanism are unclear. This study was designed to explore the profile of cell cycle of cardiomyocytes and the temporal expression of their regulators during cardiac hypertrophy, as well as the effects of TP. The hypertrophy models employed were neonatal rat ventricular myocytes (NRVMs) stimulated with angiotensin II (Ang II) for scheduled times (from 5 min to 48 h) in vitro and mice treated with isoprenaline (Iso) for from 1 to 21 days, respectively. TP was used in vitro at 1 mg/L and in vivo at 10 mg/kg. NRVMs were analyzed using flow cytometry to detect the cell cycle, and the expression levels of mRNA and protein of various cell cycle regulators were determined using realtime PCR and Western blot. It was found NRVM numbers in phases S and G 2 increased, while that in the G 1 phase decreased significantly after Ang II stimulation. The mRNA expression levels of p21 and p27 increased soon after stimulation, and thereafter, mRNA expression levels of all cell cycle factors showed a decreasing trend and reached their lowest levels in 1-3 h, except for cyclin-dependent kinase 1 (CDK1) and CDK4 mRNA. The mRNA expression levels of CDK1, p21, and p27 increased markedly after stimulation with Ang II for 24-48 h. In myocardium tissue, CDK and cyclin expression levels peaked in 3-7 days, followed by a decreasing trend, while those of p21 and p27 mRNA remained at a high level on day 21. Expression levels of all protein were consistent with the results of mRNA in NRVMs or mice. The influence of Ang II or Iso on protein expression was more obvious than that on mRNA. TP treatment effectively prevented the imbalance in the expression of cell cycle regulators in the hypertrophy model group. In Conclusion, an imbalance in the expression of cell cycle regulators occurs during cardiac hypertrophy, and triptolide corrects these abnormal expression levels and attenuates cardiac hypertrophy.

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“…Triptolide is a diterpene triepoxide puri ed from Tripterygium wilfordii Hook F, commonly known as 'lei gong teng' or 'thunder god vine', a medicinal plant whose extracts have been used in traditional Chinese medicine for treating rheumatoid arthritis and other in ammatory diseases [11][12][13][14][15][16]. Recent studies have shown that triptolide kills CRC and other cancer cells in vitro with high potency [17,18].…”

Section: Introductionmentioning

confidence: 99%

Prediction of triptolide targets in colorectal cancer using network pharmacology and molecular docking

Song¹,

Dai²,

Zhang³

et al. 2020

Preprint

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Network pharmacology is an approach that uses bioinformatics to predict and identify multiple drug targets and interactions in disease. Here, we applied network pharmacology to investigate the potential mechanisms of action of triptolide, an active component in the traditional Chinese medicine Tripterygium wilfordii Hook F, in colorectal cancer (CRC). We first searched public databases for genes and proteins known to be associated with CRC, as well as those predicted to be targets of triptolide, and then used Ingenuity Pathway Analysis (IPA) to identify enriched gene pathways and networks. Networks and pathways that overlapped between CRC-associated proteins and triptolide target proteins were then used to predict candidate protein targets of triptolide in CRC. The following proteins were found to be expressed in both CRC-associated networks and triptolide target networks: JUN, FOS, CASP3, BCL2, IFNG, and VEGFA. Docking studies suggested that triptolide can fit in the binding pocket of the four top candidate triptolide target proteins (CASP3, BCL2, VEGFA and IFNG). The overlapping pathways were activation of neuroinflammation signaling, glucocorticoid receptor signaling, T helper (Th) cell differentiation, Th1/Th2 activation, and colorectal cancer metastasis signaling. These results show that network pharmacology can be used to generate hypotheses about how triptolide exerts therapeutic effects in CRC. Network pharmacology may be a useful method for characterizing multi-target drugs in complex diseases.

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Triptolide: Medicinal chemistry, chemical biology and clinical progress

Cited by 107 publications

References 131 publications

Apoptosis Exerts a Vital Role in the Treatment of Colitis-Associated Cancer by Herbal Medicine

Apoptosis Exerts a Vital Role in the Treatment of Colitis-Associated Cancer by Herbal Medicine

Effect of Triptolide on Temporal Expression of Cell Cycle Regulators During Cardiac Hypertrophy

Prediction of triptolide targets in colorectal cancer using network pharmacology and molecular docking

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