Bromelain Extract Exerts Antiarthritic Effects via Chondroprotection and the Suppression of TNF-α–Induced NF-κB and MAPK Signaling

Pothacharoen, Peraphan; Chaiwongsa, Rujirek; Chanmee, Theerawut; Insuan, Orapin; Wongwichai, Thanchanok; Janchai, Phornpimon; Vaithanomsat, Pilanee

doi:10.3390/plants10112273

Cited by 14 publications

(10 citation statements)

References 50 publications

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“…3). 32,33 One proposed mechanism is through its ability to inhibit platelet aggregation. Platelet aggregation plays a key role in the formation of blood clots, which can lead to cardiovascular diseases such as heart attack and stroke.…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

Bromelain: a review of its mechanisms, pharmacological effects and potential applications

Kumar¹,

Mangla²,

Javed³

et al. 2023

Food Funct.

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Section: Cardiovascular Diseasesmentioning

confidence: 99%

Bromelain: a review of its mechanisms, pharmacological effects and potential applications

Kumar¹,

Mangla²,

Javed³

et al. 2023

Food Funct.

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“…However, the OVT pretreatment repressed the phosphorylation of these proteins, which reflected that the OVT inhibited the activation of NF-κB and MAPK pathways and then resulted in a reduction in the expression of pro-inflammatory cytokines (IL-8, IL-6, IL-1β) and attenuated the inflammatory response. TNF-α, LPS, and other stimulatory signals can trigger NF-κB and MAPK pathways, which primarily control the cytokine secretion and leukocyte recruitment. , Blocking the activation of NF-κB and MAPK pathways may restrain the inflammatory response, which has been demonstrated in vitro and in vivo . ,, In the present study, the NF-κB pathway was inhibited using a p65 inhibitor (which inhibits nuclear translocation of NF-κB p65 but does not affect IκB degradation). ERK, p38, and JNK inhibitors were able to suppress the expression of each of the three subfamilies of MAPK pathways.…”

Section: Discussionmentioning

confidence: 66%

Ovotransferrin Inhibits TNF-α Induced Inflammatory Response in Gastric Epithelial Cells via MAPK and NF-κB Pathway

Huang

Chen

Yao

et al. 2023

J. Agric. Food Chem.

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Ovotransferrin (OVT) has been confirmed to have anti-inflammatory activity. However, its effect and mechanism on gastric inflammation are unclear. In this study, the effect and mechanism of the OVT on the tumor necrosis factor-α (TNF-α) induced inflammatory response in gastric epithelial cells (GES-1) were investigated. The enzyme linked immunosorbent assay (ELISA) was used to determine the levels of inflammation cytokines, followed by RNA sequencing to explore the potential pathways of its anti-inflammatory effect, and then it was validated by Western blotting and pathways inhibitors. Results showed that the OVT at concentrations of 50–400 μg/mL displayed nontoxicity against GES-1 cells. Additionally, 100 μg/mL of OVT obviously reduced the secretion of interleukin (IL)-8, IL-6, and TNF-α by 63.02% (630.09/1703.98), 35.53% (935.81/1451.43), and 36.19% (964.60/1511.63), respectively. The results of RNA sequencing exhibited that the OVT significantly influences the activation of mitogen-activated protein kinase (MAPK) and the nuclear factor kappa-light-chain enhancer of activated B cell (NF-κB) pathways, which was verified by the levels of p-IKK, p-IκB, p-P65, p-ERK, p-JNK, and p-P38 protein. IL-8 contents released by GES-1 cells after incubation with inhibitors of NF-κB and MAPK pathways further confirmed that OVT hindered activation of these two pathways. Collectively, these results suggested that OVT was a natural protein with the potential to treat gastric inflammation.

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“…As the core transcription factor in NF-κB signaling pathway, NF-κB exists in the cytoplasm as an inactive form of trimer with its subunits p65, p50, and inhibitor of NF-κB (IκB) in the resting state. On stimulation, IκB kinase phosphorylates and ubiquitinates IκBα, releasing NF-κB into the nucleus; among the subunits, p65 is the most predominant active form [ 62 ]. The activation of NF-κB pathway initiates the transcription of its downstream proinflammatory factors, such as TNF-α, IL-1β, and IL-6, inducing inflammatory response and pain.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-κb signaling pathway

Yao

Ren

Huang

et al. 2022

J Neuroinflammation

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Background Local neuroinflammation secondary to spinal nerve compression in lumbar disk herniation (LDH) is a key driver contributing to neuropathic pain. Manual therapy (MT), a widely used nonsurgical therapy, can relieve LDH-mediated pain by reducing inflammation. MT has attracted extensive attention; however, its mechanism remains poorly understood. MicroRNAs (miRNAs) are important regulators of pain signaling transduction, but are rarely reported in the chronic compression of dorsal root ganglia (CCD) model, and further investigation is needed to decipher whether they mediate anti-inflammatory and analgesic effects of MT. Methods We used a combination of in vivo behavioral and molecular techniques to study MT intervention mechanisms. Neuropathic pain was induced in a CCD rat model and MT intervention was performed according to standard procedures. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokine levels in dorsal root ganglia (DRG). Small RNA sequencing, immunofluorescence, Western blot, and qRT-PCR were performed to screen miRNAs and their target genes and determine core factors in the pathway possibly regulated by miRNA-mediated target gene in DRG of MT-treated CCD rats. Results Compared with naive rats, small RNA sequencing detected 22 differentially expressed miRNAs in DRG of CCD rats, and compared with CCD rats, MT-treated rats presented 19 differentially expressed miRNAs, which were functionally associated with nerve injury and inflammation. Among these, miR-547-3p was screened as a key miRNA mediating neuroinflammation and participating in neuropathic pain. We confirmed in vitro that its function is achieved by directly regulating its target gene Map4k4. Intrathecal injection of miR-547-3p agomir or MT intervention significantly reduced Map4k4 expression and the expression and phosphorylation of IκBα and p65 in the NF-κB pathway, thus reducing the inflammatory cytokine levels and exerting an analgesic effect, whereas intrathecal injection of miR-547-3p antagomir led to opposite effects. Conclusions In rats, CCD-induced neuropathic pain leads to variation in miRNA expression in DRG, and MT can intervene the transcription and translation of inflammation-related genes through miRNAs to improve neuroinflammation and alleviate neuropathic pain. MiR-547-3p may be a key target of MT for anti-inflammatory and analgesia effects, which is achieved by mediating the Map4k4/NF-κB pathway to regulate downstream inflammatory cytokines.

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Bromelain Extract Exerts Antiarthritic Effects via Chondroprotection and the Suppression of TNF-α–Induced NF-κB and MAPK Signaling

Cited by 14 publications

References 50 publications

Bromelain: a review of its mechanisms, pharmacological effects and potential applications

Bromelain: a review of its mechanisms, pharmacological effects and potential applications

Ovotransferrin Inhibits TNF-α Induced Inflammatory Response in Gastric Epithelial Cells via MAPK and NF-κB Pathway

Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-κb signaling pathway

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