Helenalin from Centipeda minima ameliorates acute hepatic injury by protecting mitochondria function, activating Nrf2 pathway and inhibiting NF-κB activation

Li, Yan; Zeng, Yanwu; Huang, Quanfang; Song, Wen; Wei, Yuansong; Chen, Ya; Zhang, Xiaolin; Bai, Facheng; Lu, Zhaojun; Wei, Jinbin; Lin, Xiaobo

doi:10.1016/j.biopha.2019.109435

Cited by 25 publications

(23 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…is an annual small herb commonly found in Asia for alleviating headaches, infection, and respiratory discomfort. In previous studies, its extract (CME) has been found to be possess antiinflammatory (40), anti-angiogenic (41), and anti-cancer (13, 17) effects, through by inhibition of NF-κB and activation of Nrf2 (42), however its effects on TNBC had yet to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

et al. 2020

View full text Add to dashboard Cite

Breast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Among the subtypes of breast cancer, triple negative breast cancer (TNBC) is the most aggressive and carries the poorest prognosis, largest recurrence, and lowest survival rate. Major treatment options for TNBC patients are mainly constrained to chemotherapy, which can be accompanied by severe side effects. Therefore, development of novel and effective anti-cancer drugs for the treatment of TNBC are urgently required. Centipeda minima is a well-known traditional Chinese herbal medicine that has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. Recent studies have shown that Centipeda minima exhibited efficacy against certain cancers, however, to date, no studies have been conducted on its effects in breast cancer. Here, we aimed to investigate the anti-cancer activity of the total extract of Centipeda minima (CME), and its underlying mechanism, in TNBC. In MDA-MB-231, we found that CME could significantly reduce cell viability and proliferation, induce apoptosis and inhibit cancer cell migration and invasion, in a dose and time-dependent manner. We showed that CME may potentially act via inhibition of multiple signaling pathways, including the EGFR, PI3K/AKT/mTOR, NF-κB, and STAT3 pathways. Treatment with CME also led to in vitro downregulation of MMP-9 activity and inhibition of metastasis. Further, we demonstrated that CME could significantly reduce tumor burden in MDA-MB-231 xenograft mice, without any appreciable side effects. Based on our findings, CME is a promising candidate for development as a therapeutic with high efficacy against TNBC.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

et al. 2020

View full text Add to dashboard Cite

show abstract

“…[64] We focusedo n the antioxidant anda nti-inflammatory activity associated with Keap1/Nrf2 pathway,w hich pseudoguaianolides are also known to activate. [20] Kelch-like ECH-associated protein 1 (Keap1), as the cytoplasmic repressor of nuclear factor erythroid-2-related factor (Nrf2), is the protein with the most cysteines (27 residues)i nt he proteome, several of which are readily alkylated by electrophiles to induce Nrf2 nuclear translocation. [65][66][67] Further,many oxidative stress related genes are regulated by Nrf2.…”

Section: Scheme4a) Synthesis Of Isomeric Scaffolds B)mentioning

confidence: 99%

“…Pseudoguaianolide natural products (helenalin, [12][13][14][15] aromaticin, [16] mexicanin, [17] and many others, Figure 2A)e xhibit potent bioactivities where their enone and exomethylenelactone Michael acceptors act as covalentm odifiers of biological cysteiner esidues. [18][19][20][21][22][23][24][25][26][27][28][29] For example, helenalin is known to inhibit NF-kBp 65, [22,27,29] C/EBPb isoform selectively, [18,19] and c-Myb. [21] Of direct relevance to this report,h elenalin hasb een shownt oa ctivate Nrf2.…”

Section: Introductionmentioning

confidence: 99%

“…[21] Of direct relevance to this report,h elenalin hasb een shownt oa ctivate Nrf2. [20] Other sesquiterpene lactones (pseudoguaianolide, guaianolides,a nd beyond) and semisynthetic analogues have also shown promising biological activities. [30][31][32][33][34][35][36] As such, the (pseudo)guaianolide family and their analogues have been implicated as leads in drug development.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Function‐Oriented and Modular (+/−)‐cis‐Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF‐κB Inhibitors

Emmetiere

Ratnayake

Schares

et al. 2021

Chemistry A European J

View full text Add to dashboard Cite

Described herein is af unction-oriented synthesis route and biological evaluation of pseudoguaianolide analogues. The 10-step synthetic route developed retains the topological complexity of the natural product, installs functional handles for late-stage diversification, and forges the key bioactive Michael acceptors early in the synthesis. The analogues were found to be low-micromolar Nrf2 activators and micromolar NF-kBi nhibitors and dependent on the local environment of the Michael acceptor moieties.

show abstract

“…Helenalin is a pseudoguaianolide natural product with numerous pharmacological activities against inflammation [ 17 ], oxidative stress [ 18 ], and cancers [ 19 ]. A series of cellular experiments have shown that helenalin is toxic to tumor cells, but not to normal cells, indicating that helenalin may be effective as a low-level toxicant for prostate cancer [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Helenalin Facilitates Reactive Oxygen Species-Mediated Apoptosis and Cell Cycle Arrest by Targeting Thioredoxin Reductase-1 in Human Prostate Cancer Cells

Yang

Zhang

et al. 2021

Med Sci Monit

View full text Add to dashboard Cite

Background Helenalin is a pseudoguaianolide natural product with anti-cancer activities. This study investigated the underlying mechanism of the anti-prostate cancer effects of helenalin in vitro. Material/Methods CCK-8 assay was performed to detect the optimal concentrations of helenalin in DU145 and PC-3 cells. After exposure to helenalin and/or reactive oxygen species (ROS) inhibitor, ROS production was assessed by DCFH-DA staining. Thioredoxin reductase-1 (TrxR1) expression was detected by RT-qPCR and western blot. Moreover, apoptosis and cell cycle were evaluated by flow cytometry. Following TrxR1 knockdown or overexpression, TrxR1 expression, ROS generation, apoptosis, cell cycle, migration, and invasion were examined in cells co-treated with helenalin. Results Helenalin distinctly repressed the viability of prostate cancer cells in a concentration-dependent manner. We chose 8 μM and 4 μM as the optimal concentrations of helenalin for DU145 and PC-3 cells, respectively. Helenalin treatment markedly triggered ROS production and lowered TrxR1 expression, which was ameliorated by ROS inhibitor. Exposure to helenalin facilitated apoptosis as well as G0/G1 cell cycle arrest, which was reversed by ROS inhibitor. Helenalin relieved the inhibitory effect of TrxR1 on ROS production. Furthermore, helenalin ameliorated the decrease in apoptosis rate and the shortening of G0/G1 phase as well as the increase in migration and invasion induced by TrxR1 overexpression. Conclusions Our findings revealed that helenalin accelerated ROS-mediated apoptosis and cell cycle arrest via targeting TrxR1 in human prostate cancer cells.

show abstract

Helenalin from Centipeda minima ameliorates acute hepatic injury by protecting mitochondria function, activating Nrf2 pathway and inhibiting NF-κB activation

Cited by 25 publications

References 34 publications

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways

Function‐Oriented and Modular (+/−)‐cis‐Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF‐κB Inhibitors

Helenalin Facilitates Reactive Oxygen Species-Mediated Apoptosis and Cell Cycle Arrest by Targeting Thioredoxin Reductase-1 in Human Prostate Cancer Cells

Contact Info

Product

Resources

About