Parthenolide, a feverfew-derived phytochemical, ameliorates obesity and obesity-induced inflammatory responses via the Nrf2/Keap1 pathway

Kim, Chae Young; Kang, Bobin; Suh, Hyung Joo; Hyun-Min, Choi

doi:10.1016/j.phrs.2019.104259

Cited by 41 publications

(17 citation statements)

References 36 publications

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“…Moreover, Shin S. et al demonstrated that treatment with CDDO imidazolide, a potent Nrf2 activator, could prevent high-fat diet-induced increases in body weight, adipose mass, and hepatic lipid accumulation via increasing oxygen consumption and energy expenditure, and decreasing food intake in wild-type mice, but not in Nrf2-disrupted mice, which indicates that activation of the Nrf2 pathway prevents obesity [84]. Lastly, parthenolide and epigallocatechin 3-gallate can inhibit obesity and obesity-induced inflammatory responses via Nrf2/Keap1 signaling under high-fat diet conditions [90,91].…”

Section: The Role Of Nrf2 In Obesitymentioning

confidence: 99%

“…Due to the crucial role of anti-inflammatory and antioxidant defense played by the Nrf2 pathway in metabolic homeostasis, there are numerous studies performed to investigate the effect and mechanisms of the Nrf2 pathway in obesity and insulin resistance. In animal models, two different approaches have been frequently used to investigate the regulation of Nrf2: genetic manipulation such as Nrf2 Knockout (KO) or Keap1 Knockdown (KD) mice and administration of Nrf2 pharmacological activators [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ]. Nrf2 KO mice lack constitutive expression of Nrf2 and hence, exhibit an inability to induce cytoprotective genes under oxidative stress.…”

Section: The Role Of Nrf2 Pathway In Obesity and Insulin Resistancmentioning

confidence: 99%

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The Role of the Nrf2 Signaling in Obesity and Insulin Resistance

Eguchi

Lau

et al. 2020

IJMS

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Obesity, a metabolic disorder characterized by excessive accumulation of adipose tissue, has globally become an increasingly prevalent disease. Extensive studies have been conducted to elucidate the underlying mechanism of the development of obesity. In particular, the close association of inflammation and oxidative stress with obesity has become increasingly evident. Obesity has been shown to exhibit augmented levels of circulating proinflammatory cytokines, which have been associated with the activation of pathways linked with inflammation-induced insulin resistance, a major pathological component of obesity and several other metabolic disorders. Oxidative stress, in addition to its role in stimulating adipose differentiation, which directly triggers obesity, is considered to feed into this pathway, further aggravating insulin resistance. Nuclear factor E2 related factor 2 (Nrf2) is a basic leucine zipper transcription factor that is activated in response to inflammation and oxidative stress, and responds by increasing antioxidant transcription levels. Therefore, Nrf2 has emerged as a critical new target for combating insulin resistance and subsequently, obesity. However, the effects of Nrf2 on insulin resistance and obesity are controversial. This review focuses on the current state of research on the interplay of inflammation and oxidative stress in obesity, the role of the Nrf2 pathway in obesity and insulin resistance, and the potential use of Nrf2 activators for the treatment of insulin resistance.

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Section: The Role Of Nrf2 In Obesitymentioning

confidence: 99%

Section: The Role Of Nrf2 Pathway In Obesity and Insulin Resistancmentioning

confidence: 99%

The Role of the Nrf2 Signaling in Obesity and Insulin Resistance

Eguchi

Lau

et al. 2020

IJMS

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“…Decreased SOD and GSH-Px in combination with increased MDA levels are closely associated with oxidative stress ( 38 ). PAR has been shown to regulate obesity-induced inflammatory/oxidant responses and proposed as an effective agent for the treatment of obesity-related diseases ( 39 ). In agreement with these previous findings, PAR-treated MAFLD model mice in the present study displayed decreased TNF-α, IL-1β, IL-6 and MDA levels, together with elevated SOD and GSH-Px activities.…”

Section: Discussionmentioning

confidence: 99%

Parthenolide plays a protective role in the liver of mice with metabolic dysfunction‑associated fatty liver disease through the activation of the HIPPO pathway

Wang

Liu

2021

Mol Med Rep

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Metabolic dysfunction-associated fatty liver disease (MAFLD) is a serious threat to human health. Parthenolide (PAR) displays several important pharmacological activities, including the promotion of liver function recovery during hepatitis. The aim of the present study was to assess the effect of PAR on MAFLD in a mouse model. Body weight, liver to body weight ratios, histological score, alanine transaminase, aspartate transaminase, total cholesterol and triglyceride levels were determined to evaluate liver injury. Liver hydroxyproline concentrations were also assessed. The expression levels of lipid metabolism-related genes (sterol regulatory element binding protein-1c, fatty acid synthase, acetyl CoA carboxylase 1, stearoyl CoA desaturase 1 and carbohydrate response element-binding protein, peroxisome proliferator-activated receptor α, carnitine palmitoyl transferase 1α and acyl-CoA dehydrogenase short chain), liver fibrosis-associated genes (α-smooth muscle actin, tissue inhibitor of metalloproteinase 1 and TGF-β1), pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and oxidative stress-associated enzymes (malondialdehyde, superoxide dismutase and glutathione peroxidase) were measured in mice with MAFLD. The expression levels of genes associated with the HIPPO pathway were also measured.In vivo experiments using a specific inhibitor of HIPPO signalling were performed to verify the role of this pathway in the effects of PAR. PAR exerted beneficial effects on liver injury, lipid metabolism, fibrosis, inflammation and oxidative stress in mice with MAFLD, which was mediated by activation of the HIPPO pathway.

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“…Several plant-derived small molecules have been identified as potential inhibitors of the NF-κB pathway. PTL, a major sesquiterpene lactone derived from feverfew, has been reported to be a potent inhibitor of NF-κB, through the interference in a common step of the NF-κB activation pathway [ 15 , 16 ]. In the present study, we examined the effects of PTL on changes in cell viability and in vitro osteoblastic activity in hPDCs.…”

Section: Discussionmentioning

confidence: 99%

“…Parthenolide (PTL), isolated from the Mexican Indian Asteraceae family plants, induces apoptosis in several cell types, by inhibiting the nuclear factor-kappa B (NF-κB) signaling pathway [15,16]. Because the downstream signaling events of inflammatory cytokines include the activation of NF-κB, PTL may potentially serve as a novel treatment for inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Parthenolide Has Negative Effects on In Vitro Enhanced Osteogenic Phenotypes by Inflammatory Cytokine TNF-α via Inhibiting JNK Signaling

Park

Kang

Hwang

et al. 2020

IJMS

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Nuclear factor kappa B (NF-κB) regulates inflammatory gene expression and represents a likely target for novel disease treatment approaches, including skeletal disorders. Several plant-derived sesquiterpene lactones can inhibit the activation of NF-κB. Parthenolide (PTL) is an abundant sesquiterpene lactone, found in Mexican Indian Asteraceae family plants, with reported anti-inflammatory activity, through the inhibition of a common step in the NF-κB activation pathway. This study examined the effects of PTL on the enhanced, in vitro, osteogenic phenotypes of human periosteum-derived cells (hPDCs), mediated by the inflammatory cytokine tumor necrosis factor (TNF)-α. PTL had no significant effects on hPDC viability or osteoblastic activities, whereas TNF-α had positive effects on the in vitro osteoblastic differentiation of hPDCs. c-Jun N-terminal kinase (JNK) signaling played an important role in the enhanced osteoblastic differentiation of TNF-α-treated hPDCs. Treatment with 1 µM PTL did not affect TNF-α-treated hPDCs; however, 5 and 10 µM PTL treatment decreased the histochemical detection and activity of alkaline phosphatase (ALP), alizarin red-positive mineralization, and the expression of ALP and osteocalcin mRNA. JNK phosphorylation decreased significantly in TNF-α-treated hPDCs pretreated with PTL. These results suggested that PTL exerts negative effects on the increased osteoblastic differentiation of TNF-α-treated hPDCs by inhibiting JNK signaling.

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Parthenolide, a feverfew-derived phytochemical, ameliorates obesity and obesity-induced inflammatory responses via the Nrf2/Keap1 pathway

Cited by 41 publications

References 36 publications

The Role of the Nrf2 Signaling in Obesity and Insulin Resistance

The Role of the Nrf2 Signaling in Obesity and Insulin Resistance

Parthenolide plays a protective role in the liver of mice with metabolic dysfunction‑associated fatty liver disease through the activation of the HIPPO pathway

Parthenolide Has Negative Effects on In Vitro Enhanced Osteogenic Phenotypes by Inflammatory Cytokine TNF-α via Inhibiting JNK Signaling

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