Olive-Derived Hydroxytyrosol Shows Anti-inflammatory Effect without Gastric Damage in Rats

Yonezawa, Yutaka; Kihara, Tohru; Ibi, Kanata; Senshu, Masanori; Nejishima, Hiroaki; Takeda, Yohei; Imai, Kunitoshi; Ogawa, Hideoki

doi:10.1248/bpb.b18-00979

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…HT-29 intestinal cells 1-5 µg/mL Induction of apoptosis through COX-2 suppression and AMPK activation [122] Oleuropein showed an inhibitory effect against COX-2 over-expression in different tumor cell lines [130], but the most studied EVOO phenolic compound is undoubtedly its derivative HT. It was shown, for instance, that LPS-induced expression of COX-2 and thus PGE2 production were inhibited by HT pretreatment in human and mouse granulocytes, macrophages, and monocytes [66,100,[124][125][126][127]. Among the mechanisms involved in COX-2 suppression by HT, as well as by EVOO polyphenols extracts, the inhibition of NF-κB following MAPKs modulation is the most recognized [107].…”

Section: Inhibition Of Cox-2 and Prostaglandinsmentioning

confidence: 99%

“…Among the mechanisms involved in COX-2 suppression by HT, as well as by EVOO polyphenols extracts, the inhibition of NF-κB following MAPKs modulation is the most recognized [107]. In vivo, it was observed that HT suppressed COX-2-induced inflammation and PGE2 production in a carrageenan-induced rat paw edema model, although the efficacy was less than that of celecoxib and indomethacin [124]. The same outcome was observed in diet-dextran sodium sulfate (DSS) mice which developed chronic colitis, where olive oil supplemented with HT or with phenolic extracts (850 ppm), given to enrich normal diet, resulted to be more efficacious than olive oil in down regulating cytokines release like TNF-α, MAPKs, and NF-κB pathway activation and consequently iNOS and COX-2 expression [125,126].…”

Section: Inhibition Of Cox-2 and Prostaglandinsmentioning

confidence: 99%

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Extra Virgin Olive Oil Polyphenols: Modulation of Cellular Pathways Related to Oxidant Species and Inflammation in Aging

Serreli

Deiana

2020

Cells

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The olive-oil-centered Mediterranean diet has been associated with extended life expectancy and a reduction in the risk of age-related degenerative diseases. Extra virgin olive oil (EVOO) itself has been proposed to promote a “successful aging”, being able to virtually modulate all the features of the aging process, because of its great monounsaturated fatty acids content and its minor bioactive compounds, the polyphenols above all. Polyphenols are mostly antioxidant and anti-inflammatory compounds, able to modulate abnormal cellular signaling induced by pro-inflammatory stimuli and oxidative stress, as that related to NF-E2-related factor 2 (Nrf-2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which have been identified as important modulators of age-related disorders and aging itself. This review summarizes existing literature about the interaction between EVOO polyphenols and NF-κB and Nrf-2 signaling pathways. Reported studies show the ability of EVOO phenolics, mainly hydroxytyrosol and tyrosol, to activate Nrf-2 signaling, inducing a cellular defense response and to prevent NF-κB activation, thus suppressing the induction of a pro-inflammatory phenotype. Literature data, although not exhaustive, indicate as a whole that EVOO polyphenols may significantly help to modulate the aging process, so tightly connected to oxidative stress and chronic inflammation.

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Section: Inhibition Of Cox-2 and Prostaglandinsmentioning

confidence: 99%

Section: Inhibition Of Cox-2 and Prostaglandinsmentioning

confidence: 99%

Extra Virgin Olive Oil Polyphenols: Modulation of Cellular Pathways Related to Oxidant Species and Inflammation in Aging

Serreli

Deiana

2020

Cells

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“…COX-1, COX-2, and 12-LOX upregulation during inflammatory processes plays an essential role in inflammatory signaling pathways ( Gunaydin & Bilge, 2018 ). Control over inflammation is required to avoid excessive damage from the exaggerated immune response or conversion to chronic illness ( Yonezawa et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Mycophenolate suppresses inflammation by inhibiting prostaglandin synthases: a study of molecular and experimental drug repurposing

Al-Hizab

Kandeel

2021

PeerJ

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Mycophenolate mofetil is an established anti-proliferative and immune-suppressive agent that minimizes the proliferation of inflammatory cells by interfering with nucleic acid synthesis. Herein, we report our discovery of the prostaglandin inhibiting properties of MMF, which offers new applications for the drug in the treatment of inflammatory diseases. The estimated values of IC50MMFCOX-1, IC50MMFCOX-2, and IC50MMF5-LOX were 5.53, 0.19, and 4.47 µM, respectively. In contrast, mycophenolic acid (MPA) showed slightly stronger inhibition: IC50MPACOX-1, IC50MPACOX-2, and IC50MPA5-LOX were 4.62, 0.14, and 4.49 µM, respectively. These results indicate that MMF and MPA are, respectively, 28.6 and 33 times more selective for cyclooxygenase-2 than for cyclooxygenase-1, which implies that MMF would have less impact on the gastric mucosa than most nonselective, nonsteroidal anti-inflammatory drugs. Furthermore, MMF provided dose-dependent relief of acute inflammation in the carrageenan-induced rat paw edema test, with results comparable to those of celecoxib and indomethacin. Molecular dynamics simulations indicated that the MMF bond with COX-2 was stable, as evidenced by a low root-mean-square deviation of atomic positions, complementary per-residue root-mean-square fluctuation, and 0–4 hydrogen bonds during the 50-ns simulation time. Therefore, MMF provides immune-suppressing, cyclooxygenase-inhibiting, and inflammation-relieving properties. Our results indicate that MMF can be 1) repositioned for inflammation treatment without the need for further expensive clinical trials, 2) used for local acute inflammations, and 3) used as a sparing agent for other steroid and non-steroid anti-inflammatory medications, especially in topical applications.

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“…12,18 HT was found to inhibit the development of inflammatory cascade following LPS and carrageenan injection through downregulating the levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) and other inflammatory mediators, namely inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) along with their products including nitric oxide (NO) and prostaglandin E2 (PGE2), and nuclear factor kappa-B (NF-κB). 16,19…”

Section: Introductionmentioning

confidence: 99%

Hydroxytyrosol ameliorates oxidative challenge and inflammatory response associated with lipopolysaccharide-mediated sepsis in mice

Alblihed

2020

Hum Exp Toxicol

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Hydroxytyrosol (HT) is among the main bioactive ingredients isolated from olive tree with a variety of biological and pharmacological activities. In the current study, the antioxidative and anti-inflammatory activities of HT were distinguished in the splenic tissue following lipopolysaccharide (LPS)-mediated septic response. Thirty-five Swiss mice were divided into five groups (n = 7): control, HT (40 mg/kg), LPS (10 mg/kg), HT 20 mg+LPS and HT 40 mg+LPS. HT was administered for 10 days, while a single LPS dose was applied. The obtained findings demonstrate that HT administration enhanced the survival rate and decreased lactate dehydrogenase level in LPS-challenged mice. Treatment with HT inhibited the incidence of oxidative damage in splenic tissue through decreasing lipoperoxidation and increasing antioxidant molecules, namely glutathione, superoxide dismutase and catalase. HT also decreased total leukocytes count, C-reactive protein, monocyte chemoattractant protein-1, and myeloperoxidase levels. Additionally, HT suppressed the production levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6. Moreover, mRNA expression of inducible nitric oxide synthase and nitric oxide production were increased after HT administration. Furthermore, HT supplementation resulted in a downregulation of p38 mitogen-activated protein kinase, inhibited the activation of the nuclear factor kappa-B from the nucleus to the cytoplasm, and attenuated infiltration of activated immune cells and tissue injury following LPS injection. Collectively, these findings demonstrate the antioxidative and anti-inflammatory properties of HT against LPS-mediated inflammation and sepsis. Therefore, HT could be applied as an alternative anti-inflammatory agent to minimize or prevent the development of systemic inflammatory response associated with septic shock.

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Olive-Derived Hydroxytyrosol Shows Anti-inflammatory Effect without Gastric Damage in Rats

Cited by 12 publications

References 30 publications

Extra Virgin Olive Oil Polyphenols: Modulation of Cellular Pathways Related to Oxidant Species and Inflammation in Aging

Extra Virgin Olive Oil Polyphenols: Modulation of Cellular Pathways Related to Oxidant Species and Inflammation in Aging

Mycophenolate suppresses inflammation by inhibiting prostaglandin synthases: a study of molecular and experimental drug repurposing

Hydroxytyrosol ameliorates oxidative challenge and inflammatory response associated with lipopolysaccharide-mediated sepsis in mice

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