A synthetic diosgenin primary amine derivative attenuates LPS-stimulated inflammation via inhibition of NF-κB and JNK MAPK signaling in microglial BV2 cells

Cai, Bangrong; Seong, Kyung-Joo; Bae, Sun-Woong; Chun, Changbum; Kim, Wonjae; Jung, Ji‐Yeon

doi:10.1016/j.intimp.2018.05.021

Cited by 41 publications

(20 citation statements)

References 39 publications

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“…The MAPK family, which includes ERK1/2, JNK, and p38 MAPK, is thought to play pivotal roles in modulating pro-inflammatory mediators and cell migration in various cell types including microglial cells [20][21][22][23]26,27]. Therefore, we aimed to evaluate whether MAPK pathways were associated with anti-inflammatory and anti-migratory activities of HSR1101 in BV2 cells.…”

Section: Effect Of Hsr1101 On Mapk Phosphorylation In Lps-treated Bv2mentioning

confidence: 99%

Anti-Inflammatory and Anti-Migratory Activities of Isoquinoline-1-Carboxamide Derivatives in LPS-Treated BV2 Microglial Cells via Inhibition of MAPKs/NF-κB Pathway

Thu

Bui

Sim

et al. 2020

IJMS

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Eleven novel isoquinoline-1-carboxamides (HSR1101~1111) were synthesized and evaluated for their effects on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators and cell migration in BV2 microglial cells. Three compounds (HSR1101~1103) exhibited the most potent suppression of LPS-induced pro-inflammatory mediators, including interleukin (IL)-6, tumor necrosis factor-alpha, and nitric oxide (NO), without significant cytotoxicity. Among them, only N-(2-hydroxyphenyl) isoquinoline-1-carboxamide (HSR1101) was found to reverse LPS-suppressed anti-inflammatory cytokine IL-10, so it was selected for further characterization. HSR1101 attenuated LPS-induced expression of inducible NO synthase and cyclooxygenase-2. Particularly, HSR1101 abated LPS-induced nuclear translocation of NF-κB through inhibition of IκB phosphorylation. Furthermore, HSR1101 inhibited LPS-induced cell migration and phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 MAPK. The specific MAPK inhibitors, U0126, SP600125, and SB203580, suppressed LPS-stimulated pro-inflammatory mediators, cell migration, and NF-κB nuclear translocation, indicating that MAPKs may be the upstream kinase of NF-κB signaling. Collectively, these results demonstrate that HSR1101 is a potent and promising compound suppressing LPS-induced inflammation and cell migration in BV2 microglial cells, and that inhibition of the MAPKs/NF-κB pathway mediates its anti-inflammatory and anti-migratory effects. Based on our findings, HSR1101 may have beneficial impacts on various neurodegenerative disorders associated with neuroinflammation and microglial activation.

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Section: Effect Of Hsr1101 On Mapk Phosphorylation In Lps-treated Bv2mentioning

confidence: 99%

Anti-Inflammatory and Anti-Migratory Activities of Isoquinoline-1-Carboxamide Derivatives in LPS-Treated BV2 Microglial Cells via Inhibition of MAPKs/NF-κB Pathway

Thu

Bui

Sim

et al. 2020

IJMS

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“…Third, DGfatty acid derivatives with a hydrophobic moiety have been designed and prepared based on DG 3-caproate, also known as caprospinol, a naturally occurring compound in Gynura japonica that can protect neuronal cells from Aβ1-42 neurotoxicity [56]. Additionally, a series of DG derivatives with hydrophilic moieties such as PEG oligomers [28] and polyamines [57] have been synthesized to improve its solubility and biological activity (Compound 7). Fourth, DG-drug conjugates including DG moieties have been covalently linked to other therapeutic agents directly or via a linkage, forming codrugs with enhanced physicochemical, biopharmaceutical, and drug delivery properties (Compounds 8 and 9) [58,59].…”

Section: Semisynthetic Derivatives Of Diosgenin Against Neurological mentioning

confidence: 99%

“…Recently, we reported that DG derivatives carrying primary amine (Compound 7, DGP) or the amino acid Larginine (Compound 4, Arg-DG) at the C3 show a significant increase in aqueous solubility and anti-inflammatory activity in LPS-induced BV2 cells compared to DG. The possible mechanisms of both derivatives involve the inhibition of NF-κB activation and JNK/MAPK signaling [57,84]. Arg-DG can also rescue hippocampal neurogenesis and cognitive function impaired by LPS via the inhibition of microglial overactivation, the expression of the TLR4 receptor and downstream signaling of NF-κB and JNK/MAPK, and the ultimate suppression of proinflammatory cytokines.…”

Section: Pharmacological Activity and Mechanism Of Diosgenin And Its mentioning

confidence: 99%

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Cai

Zhang

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Diosgenin (DG), a well-known steroidal sapogenin, is present abundantly in medicinal herbs such as Dioscorea rhizome, Dioscorea villosa, Trigonella foenum-graecum, Smilax China, and Rhizoma polgonati. DG is utilized as a major starting material for the production of steroidal drugs in the pharmaceutical industry. Due to its wide range of pharmacological activities and medicinal properties, it has been used in the treatment of cancers, hyperlipidemia, inflammation, and infections. Numerous studies have reported that DG is useful in the prevention and treatment of neurological diseases. Its therapeutic mechanisms are based on the mediation of different signaling pathways, and targeting these pathways might lead to the development of effective therapeutic agents for neurological diseases. The present review mainly summarizes recent progress using DG and its derivatives as therapeutic agents for multiple neurological disorders along with their various mechanisms in the central nervous system. In particular, those related to therapeutic efficacy for Parkinson’s disease, Alzheimer’s disease, brain injury, neuroinflammation, and ischemia are discussed. This review article also critically evaluates existing limitations associated with the solubility and bioavailability of DG and discusses imperatives for translational clinical research. It briefly recapitulates recent advances in structural modification and novel formulations to increase the therapeutic efficacy and brain levels of DG. In the present review, databases of PubMed, Web of Science, and Scopus were used for studies of DG and its derivatives in the treatment of central nervous system diseases published in English until December 10, 2019. Three independent researchers examined articles for eligibility. A total of 150 articles were screened from the above scientific literature databases. Finally, a total of 46 articles were extracted and included in this review. Keywords related to glioma, ischemia, memory, aging, cognitive impairment, Alzheimer, Parkinson, and neurodegenerative disorders were searched in the databases based on DG and its derivatives.

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“…p65 is a subunit of NF-κB with p50 and is phosphorylated by various stimuli. Phosphorylated p65 translocated into the nucleus and then it binds to the promotor region and produces various inflammatory mediators resulting in asthmatic responses ( Cai et al, 2018 ). AP-1 also is considered as a major activator of inflammatory genes.…”

Section: Discussionmentioning

confidence: 99%

Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma

Shin

Park

et al. 2018

Front. Pharmacol.

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Lobeglitazone (LB) is a novel agonist of peroxisome proliferator-activated receptor (PPAR)-α and γ that was developed as a drug to treat diabetes mellitus. We explored the ameliorative effects of LB on allergic asthma using a murine model of ovalbumin (OVA)-induced asthma. To boost the immune response of animals, OVA sensitization was performed on days 0 and 14. LB (250 or 500 μg/kg) was administered by oral gavage on days 18 to 23, and the OVA challenge was performed using an ultrasonic nebulizer on days 21 to 23. Plethysmography showed airway hyperresponsiveness (AHR) on day 24. LB treatment effectively decreased inflammatory cell recruitment, T-helper type 2 cytokines in the bronchoalveolar lavage fluid, and immunoglobulin (Ig) E in the serum of the animals with OVA-induced asthma, which was accompanied by a marked reduction in AHR. It also decreased airway inflammation, mucus hypersecretion, phosphorylation of nuclear transcription factor-kappa-B (NF-κB), and expression of activating protein (AP)-1 and mucin 5AC (MUC5AC). Overall, LB effectively attenuated the pathophysiological changes of asthma and its effects appear related to a reduction in the phosphorylation of NF-κB and the expression of AP-1. Thus, our results suggest that LB has a potential to treat allergic asthma.

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A synthetic diosgenin primary amine derivative attenuates LPS-stimulated inflammation via inhibition of NF-κB and JNK MAPK signaling in microglial BV2 cells

Cited by 41 publications

References 39 publications

Anti-Inflammatory and Anti-Migratory Activities of Isoquinoline-1-Carboxamide Derivatives in LPS-Treated BV2 Microglial Cells via Inhibition of MAPKs/NF-κB Pathway

Anti-Inflammatory and Anti-Migratory Activities of Isoquinoline-1-Carboxamide Derivatives in LPS-Treated BV2 Microglial Cells via Inhibition of MAPKs/NF-κB Pathway

Therapeutic Potential of Diosgenin and Its Major Derivatives against Neurological Diseases: Recent Advances

Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma

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