CP markedly decreased carbachol-induced contraction of detrusor strips (p < 0.01), which was prevented by the high-dose DMF treatment (p < 0.05)...Additionally, combination of different concentrations of CP and DMF exhibited a potent synergistic cytotoxic effect in SH-SY5Y cells. DMF improved CP-induced acute cystitis by partially suppressing oxidative stress and inflammation, while also enhancing the cytotoxic effects of CP.

Targeting these molecules could offer therapeutic potential in attenuating atherosclerosis-related complications. Not applicable.

In both in vivo and in vitro experiments, TFL activated the Nrf2/HO-1 signalling pathway, promoting the expression of antioxidant enzymes and thereby ameliorating CDDP-induced oxidative stress, mitochondrial dysfunction and renal cell apoptosis.

P2, N=30, Recruiting, Medical University of Lodz

Dr. Imitola has a non-compensated relationship as a Committee Member with International Society for Stem Cell Research that is relevant to AAN interests or activities.

P=N/A, N=20, Not yet recruiting, Biogen | Initiation date: Oct 2024 --> Oct 2026

On the 8th day, mice were euthanized with ketamine/xylazine, and serum factors, oxidative stress markers, apoptosis index, and inflammatory markers were measured...Furthermore, PQ decreased hepatic total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase. However, DMF reduced the harmful effects caused by the imbalance in the oxidant and antioxidant system and histopathological damage in PQ-poisoned mice and improved the damage caused by inflammation and apoptosis.

Moreover, SP downregulated APAP-induced high-mobility group box 1 (HMGB1) and toll-like receptor 4 (TLR4) expression, inhibited nuclear factor kappa-B (NF-κB) and MAPK activation. Taken together, our study reveals the protective roles of SP against AILI through the downregulation of NLRP3 expression, and the inhibition of the Nrf2/HMGB1/TLR4/NF-κB signaling pathways.

However, there is limited evidence that EDA is effective against DICM. The findings obtained herein bolster the evidence in DICM by demonstrating prolonged survival and continued preservation of cardiac function and proposing a possible mechanism.

Further mechanistic studies suggested that the protection of UNA on AD C. elegans may be through modulation of the MAPKs/Nrf2/HO-1 pathway. These results highlight the neuroprotective potential of UNA and suggest that UNA may be an effective therapeutic agent for alleviating AD.

NF-κB inhibition enhanced the anti-inflammatory and anti-oxidative effects of anemonin, while Nrf2 knockdown attenuated these effects of anemonin, implying the critical roles of NF-κB and Nrf2. These results indicated that anemonin suppressed sepsis-induced acute lung injury by inhibition of NF-κB and activation of Nrf2/heme oxygenase-1 pathway, suggesting that anemonin might be developed as a new therapeutic agent for the treatment of sepsis-induced ALI.

However, the neuroprotective effect of Std was significantly weakened by Nrf2 inhibitor ML385. These results indicate that Std provides substantial protection against high glucose-induced hippocampal injury by inhibiting the TXNIP/NLRP3 pathways dependent on Nrf2, which may serve as a promising agent for attenuating DACD.

MRN protects against renal inflammation induced by 5-FU, as evidenced by decreased TNF-α and IL-6 levels in the rat kidney mediated by the downregulation of the ERK1/2 and VCAM-1 proteins and decreased NF-κB phosphorylation as shown by Western blotting. These findings support using MRN as a novel and promising treatment for 5-FU-induced nephrotoxicity.

In addition, epicatechin increased the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). We therefore conclude that epicatechin protected EMB-induced liver injury by preventing ferroptosis through activating Nrf2.

P=N/A, N=300, Recruiting, Reata, a wholly owned subsidiary of Biogen | Not yet recruiting --> Recruiting

Knockdowning and blocking JAM3 sensitized cancer cells to ferroptosis inducers RSL3 and erastin, while JAM3 overexpression conferred resistance to these agents. In addition, JAM3 also promoted ovarian cancer cells resistance to chemotherapeutic agent cisplatin in vitro and in vivo by inhibiting ferroptosis...Moreover, JAM3 high expression was associated with poor prognosis in patients with ovarian cancer. Altogether, this study provided novel insights into the molecular mechanisms underlying ferroptosis resistance and identify JAM3 as a potential therapeutic target for combating drug resistance in ovarian cancer.

RRx-001 reduces the viability of HCC cells and induces apoptosis. This effect may be due to the downregulation of CD47 expression and the alteration of the TP53 protein regulatory pathway.

At low 5-10 µM concentrations LCB1353 protects non-small cell lung cancer H1299 cells from ferroptotic death induced by cytotoxic concentrations of RSL3, reducing cell death from 90 % to 5 %. Thus, we suggest that cyclic vinyl sulfones are promising scaffolds for the design of protective molecules for conditions associated with toxic and inflammatory levels of oxidative stress.

Nrf2 deficiency negated the neuroprotective effects of filbertone in MPTP-treated mice. Consequently, our finding suggests that filbertone is a novel therapeutic agent for neurodegenerative diseases, enhancing neuronal resilience through the Nrf2 signaling pathway and upregulation of neurotrophic factors.

P1, N=20, Recruiting, University of Nebraska | Not yet recruiting --> Recruiting

Importantly, the therapeutic potential of DMF in clinical cGVHD has been validated in human data whereby DMF effectively reduces IL-21 production and Tfh cell generation in peripheral blood mononuclear cells from active cGVHD patients and further attenuates xenograft GVHD. Collectively, our findings reveal that DMF potently inhibits cGVHD development by repressing Tfh cell differentiation via Nrf2, paving the way for the treatment of cGVHD in the clinic.

The ABC subtype was also associated with lower white blood cell counts and more frequent chemotherapy courses than the GCB subtype. These findings suggest that nuclear Nrf2 could be a biomarker for DLBCL clinical diagnosis.

Nrf2 inhibitor Brusatol inhibited the activation of Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase 1 (NQO-1) caused by esculetin and abolished its protection effect. Esculetin protected cerebral neurons from ischemia-reperfusion injury by inhibiting NF-κB and Nrf2/HO-1/NQO-1 activation.

P1, N=12, Recruiting, Reata, a wholly owned subsidiary of Biogen | Not yet recruiting --> Recruiting

P2, N=53, Completed, EpicentRx, Inc. | Phase classification: P2a --> P2

P3, N=292, Active, not recruiting, EpicentRx, Inc. | Recruiting --> Active, not recruiting

P=N/A, N=20, Recruiting, Reata, a wholly owned subsidiary of Biogen | Not yet recruiting --> Recruiting

Moreover, there was an elevation in the activity of anti-oxidative enzymes, specifically SOD and GSH (P<0.05), coupled with an enhanced expression of Nrf2 and HO-1 in the diabetic group (P<0.01). The study findings demonstrate that TFST can suppress oxidative stress by modulating the Nrf2 pathway and up-regulating HO-1 activity, thereby ameliorating diabetes-induced acute lung injury.

P=N/A, N=20, Not yet recruiting, Reata, a wholly owned subsidiary of Biogen

Additionally, the suppression of ALDH2 on IL-6 and TNF-α levels and promotion of it on OCN and RUNX2 expression in PDLSC model of periodontitis was further intensified by ferrostatin-1, but reversed by FIN56. ALDH2 may alleviate inflammation and facilitate osteogenic differentiation of PDLSC in periodontitis by hindering ferroptosis via activating Nrf2, suggesting it to be a promising candidate for treating periodontitis.

Quercetin showed preventive effects by reducing these markers, acting through modulation of the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway. This anti-inflammatory effect, complementary to the antioxidant effects of quercetin, provides a multifaceted approach to cell protection that is important for developing therapeutic strategies against ischemia-reperfusion injury and could be helpful in preventive strategies against ischemia-reperfusion.

P=N/A, N=300, Not yet recruiting, Reata, a wholly owned subsidiary of Biogen

P=N/A, N=10500, Active, not recruiting, Biogen | Not yet recruiting --> Active, not recruiting

P1, N=12, Not yet recruiting, Reata, a wholly owned subsidiary of Biogen

P1/2, N=52, Active, not recruiting, Golden Biotechnology Corporation | Trial completion date: Mar 2024 --> Dec 2024

Praelolide markedly alleviated synovial inflammation and bone destruction in CIA mice by enhancing catalase activity and activating the Nrf2 pathway to reduce disease-related ROS accumulation, highlighting praelolide as a promising candidate for multitarget treatment of RA.

P3, N=102, Completed, Biogen | Recruiting --> Completed

We verified that the anti-inflammatory effect of Lico A is associated with the activation of the Nrf2/HO-1 axis. These results indicated that Lico A could provide a protective role in A. fumigatus keratitis through its anti-inflammatory and antifungal activities.

In summary, our findings suggest that bufalin exerts anti-inflammatory and antioxidant actions in NaT-SAP rats by inhibiting NF-κB and activating the Keap1-Nrf2/HO-1 pathway. This study represents the inaugural application of bufalin in NaT-induced SAP rats, indicating its potential as an effective therapeutic agent for SAP patients.

4-HC treatment significantly decreased lung oxidative stress, inflammatory cell infiltration, and IgE levels. According to our findings, we imply that 4-HC may be utilized as an anti-asthmatic agent through the upregulation of Nrf2/GPx4 signaling pathway.

Besides the intracellular NADH oxidation in the presence of 1, the induced oxidative stress also led to a decrease of NAD+, resulting in depletion of both NAD+/NADH coenzymes. The discussed findings provide new insight into the biochemical effects of catalytic anticancer compounds that induce cell death via a redox-mediated mode of action.

This suggests that it has the potential to be used as a therapeutic agent for reducing dental pulp inflammation. These findings support the need to further explore Asiatic acid as a promising intervention for maintaining dental pulp health.