Inhibition of Lipopolysaccharide-Induced Inflammatory and Oxidative Responses by <i>Trans</i>-cinnamaldehyde in C2C12 Myoblasts

Park, Cheol; Lee, Hyesook; Molagoda, Ilandarage Menu Neelaka; Jeong, Jin‐Woo; Jin, Cheng‐Yun; Kim, Gi‐Young; Choi, Sung Hyun; Hong, Su‐Hyun; Choi, Yung Hyun

doi:10.7150/ijms.59169

Cited by 26 publications

(20 citation statements)

References 69 publications

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“…In the docking analysis of the metabolites against COX-2, the compounds were bound to various active sites that probably inhibit specific enzymatic activities of COX-2. In particular, the smaller flavonol aglycone 2 bound strongly to the NSAID-binding site situated at the middle of a narrow tunnel, while the larger glycosylated , flavonols 5 and 3 preferred binding at the peroxidase binding site and at the hydrophilic side chain, an entry to the cyclooxygenase tunnel. The various mechanisms of attachment at different catalytic sites of flavonols 1 – 5 suggest a potentially strong COX-2-inhibitory activity of the fraction, which corroborates with the in vitro data.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba

et al. 2023

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Pathologic hyperreactive inflammatory responses occur when there is excessive activation of a proinflammatory NF-κB pathway and a reduced cytoprotective NRF2 cascade. The noncytotoxic, highly selective COX-2 inhibitory flavonol-enriched butanol fraction (UaB) from Uvaria alba (U. alba) was investigated for its inflammatory modulating potential by targeting NF-κB activation and NRF2 activity. Enzyme-linked immunosorbent assay was initially performed to measure levels of proinflammatory mediators [nitric oxide (NO), prostaglandin E2, and reactive oxygen species (ROS)] and cytokines [tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6], followed by reverse transcription-polymerase chain reaction and western blotting to determine mRNA and protein expression, respectively. Using immunofluorescence staining combined with western blot analysis, the activation of NF-κB was further investigated. NRF2 activity was also measured using a luciferase reporter assay. UaB abrogated protein and mRNA expressions of inducible nitric oxide synthase (iNOS), COX-2, TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages, thereby suppressing the production of proinflammatory mediators and cytokines. This was further validated when a concentration-dependent decrease in NO and ROS production was observed in zebrafish (Danio rerio) larvae. UaB also increased NRF2 activity in HaCaT/ARE cell line and attenuated NF-κB activation by inhibiting the nuclear translocation of transcription factor p65 in RAW 264.7 macrophages. Nontargeted LC–MS analysis of UaB revealed the presence of the flavonols quercitrin (1), quercetin (2), rutin (3), kaempferol (4), and kaempferol 3-O-rutinoside (5). Molecular docking indicates that major flavonol aglycones have high affinity toward COX-2 NSAID-binding sites, TNF-α, and TNF-α converting enzyme, while the glycosylated flavonoids showed strong binding toward iNOS and IKKall possessing dynamic stability when performing molecular dynamics simulations at 140 ns. This is the first report to have elucidated the mechanistic anti-inflammatory potential of the Philippine endemic plant U. alba.

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Section: Discussionmentioning

confidence: 99%

Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba

et al. 2023

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“…In this study, we demonstrated that AN07 protected myotubes against LPS-induced atrophy by regulating protein synthesis and degradation signaling, attenuating inflammatory and oxidative stress signaling, and improving mitochondrial function. The balance between Noxs-induced ROS production and SODs-induced ROS reduction controls the cellular redox homeostasis, which plays a critical role in oxidative-stress-induced skeletal muscle atrophy [ 22 , 24 , 40 ]. Previous studies have shown that upregulation of Noxs protein expression participate in LPS-induced inflammatory responses and ROS production [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…The balance between Noxs-induced ROS production and SODs-induced ROS reduction controls the cellular redox homeostasis, which plays a critical role in oxidative-stress-induced skeletal muscle atrophy [ 22 , 24 , 40 ]. Previous studies have shown that upregulation of Noxs protein expression participate in LPS-induced inflammatory responses and ROS production [ 40 , 41 ]. Nox4 is one of the major contributors of ROS generation in skeletal muscle [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of the Chalcone-Based Derivative AN07 on Inflammation-Associated Myotube Atrophy Induced by Lipopolysaccharide

Fang

Lin

Chang

et al. 2022

IJMS

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Inflammation is a major cause of skeletal muscle atrophy in various diseases. 2-Hydroxy-4′-methoxychalcone (AN07) is a chalcone-based peroxisome-proliferator-activated receptor gamma (PPARγ) agonist with various effects, such as antiatherosclerosis, anti-inflammation, antioxidative stress, and neuroprotection. In this study, we examined the effects of AN07 on protein homeostasis pathway and mitochondrial function in inflammation-associated myotube atrophy induced by lipopolysaccharides (LPS). We found that AN07 significantly attenuated NF-κB activation, inflammatory factors (TNF-α, IL-1β, COX-2, and PGE2), Nox4 expression, and reactive oxygen species levels in LPS-treated C2C12 myotubes. Moreover, AN07 increased SOD2 expression and improved mitochondrial function, including mitochondrial membrane potential and mitochondrial oxygen consumption rate. We also demonstrated that AN07 attenuated LPS-induced reduction of myotube diameter, MyHC expression, and IGF-1/IGF-1R/p-Akt-mediated protein synthesis signaling. Additionally, AN07 downregulated LPS-induced autophagy–lysosomal protein degradation molecules (LC3-II/LC3-I and degraded p62) and ubiquitin–proteasome protein degradation molecules (n-FoxO1a/MuRF1/atrogin-1). However, the regulatory effects of AN07 on protein synthesis and degradation signaling were inhibited by the IGF-1R inhibitor AG1024 and the PI3K inhibitor wortmannin. In addition, the PPARγ antagonist GW9662 attenuated the effects of AN07 against LPS-induced inflammation, oxidation, and protein catabolism. In conclusion, our findings suggest that AN07 possesses protective effects on inflammation-induced myotube atrophy and mitochondrial dysfunction.

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“…The main constituents of CCT are terpenoids, phenylpropanoids, and glycosides, and modern studies have confirmed that CCT possesses a wide range of pharmacological effects, including antiinflammatory and analgesic effects (Zhang et al, 2019). Trans-cinnamaldehyde, a bioactive component found in CCT, exhibited good anti-inflammatory effects in a lipopolysaccharide-induced zebrafish inflammation model and rat experiments (Lee and Lim, 2021;Park et al, 2021). Lycium barbarum polysaccharides, which are the active component of LyC, exerted protective effects against ovarian injury in rats by reducing oxidative stress and activating the Nrf2/ARE-signaling pathway (Yang et al, 2017).…”

Section: Modern Pharmacology and Dysmenorrheamentioning

confidence: 99%

“…Research has shown that the main active constituents of PL are monoterpene glucosides, which possess antioxidant and anti-inflammatory effects (Li et al, 2021). In particular, paeoniflorin, which is one of the monoterpene glucosides and a major active compound of PL, improves endometrial receptivity by inducing the expression of leukemia inhibitory factors, thereby enhancing the embryo implantation rate (Park et al, 2021). PL may also provide beneficial effects towards ovarian function and oocyte quality, possibly by stimulating ovarian angiogenesis and follicular development (Park et al, 2020).…”

Section: Modern Pharmacology and Dysmenorrheamentioning

confidence: 99%

Ethnopharmacological Survey of Traditional Chinese Medicine Pharmacy Prescriptions for Dysmenorrhea

Su¹,

Su²,

Ko³

et al. 2021

Front. Pharmacol.

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Chinese herbal medicines have long been used for the treatment of dysmenorrhea. The treatment experiences of traditional Chinese medicine (TCM) pharmacies passed down through generations have contributed to a wealth of prescriptions for dysmenorrhea that have achieved significant therapeutic effects in countless Taiwanese women. Therefore, surveying and analyzing these prescriptions may enable us to elucidate the core medication combinations used in TCM prescriptions for dysmenorrhea. In the present study, a field investigation was conducted on various TCM pharmacies in Taiwan. A total of 96 TCM pharmacies were sampled, and 99 prescriptions for dysmenorrhea containing 77 different medicinal materials were collected. Compositae (8%) was the most common botanical source of the medicinal materials, and the predominant TCM property and flavor of the materials were warm (45%) and sweet (73%), respectively. The blood-activating and stasis-dispelling effect (23%) and the qi-tonifying effect (23%) were the most prevalent traditional effects, and the modern pharmacological effects most commonly found in the materials were anti-inflammatory (73%), antitumor (59%), and analgesic (12%) effects. Network analysis of the 77 medicinal materials used in the prescriptions, which was performed using the Traditional Chinese Medicine Inheritance Support System, yielded seven core medicinal materials and the corresponding network diagram. The seven core medicinal materials ranked in order of relative frequency of citation (RFC) were Angelica sinensis (Oliv.) Diels (Dang Gui), Ligusticum chuanxiong Hort (Chuan Qiong), Rehmannia glutinosa Libosch (Di Huang), Paeonia lactiflora Pall (Bai Shao), Hedysarum polybotrys Hand.-Mazz (Hong Qi), Lycium chinense Mill (Gou Qi Zi), and Cinnamomum cassia (L.). J. Presl (Gui Zhi). A total of 58 combinations, each consisting of two to five of the seven medicinal materials and 107 association rules among the materials, were identified. This study provides a record of valuable knowledge on TCM pharmacy prescriptions for dysmenorrhea. The rich medicinal knowledge of TCM pharmacies in Taiwan is worthy of further exploration, and the results of this study can serve as a basis for future pharmacological research and the development of naturally derived medications for dysmenorrhea.

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Inhibition of Lipopolysaccharide-Induced Inflammatory and Oxidative Responses by Trans-cinnamaldehyde in C2C12 Myoblasts

Cited by 26 publications

References 69 publications

Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba

Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba

Protective Effects of the Chalcone-Based Derivative AN07 on Inflammation-Associated Myotube Atrophy Induced by Lipopolysaccharide

Ethnopharmacological Survey of Traditional Chinese Medicine Pharmacy Prescriptions for Dysmenorrhea

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