Inhibition of nuclear factor kappa B as a mechanism of Danshensu during Toll-like receptor 2-triggered inflammation in macrophages

Ye, Tingting; Xiong, Difeifei; Li, Yufei; Shouliang, Gong; Zhang, Luquan; Li, Bailing; Pan, Jianyang; Qian, Jing; Qu, Haibin

doi:10.1016/j.intimp.2020.106419

Cited by 13 publications

(4 citation statements)

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“…Danshen is traditionally used to treat cardiac (heart) and vascular (blood vessel) disorders such as atherosclerosis or blood clotting abnormalities 27 . In line with our data, Danshen has been shown to inhibit IL-6 production in macrophages 28,29 . Protocatechuic acid (PCA) and Protocatechuic aldehyde (PA) are phenolic acids found in many plants including green tea, rapeseed and Danshen.…”

Section: Discussionsupporting

confidence: 91%

An In Vitro Study Determining the anti-inflammatory activities of sinapinic acid-containing extracts generated from Irish rapeseed meal

Quinn

Scott

Finn

et al. 2020

MRAJ

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Sinapinic acid (SA) has been shown to possess various bioactive properties including anti-diabetic, anti-inflammatory and histone deacetylase inhibitory activities. However, the amount obtained from our diet is insufficient to produce beneficial effects on health. Therefore, isolating this bioactive phenolic from a natural source, such as rapeseed meal, could generate extracts containing concentrated amounts of SA which could be consumed as a functional food ingredient to prevent health-related disease, particularly inflammation. Inflammation is a multi-faceted pathology, which plays a role in numerous diseases including cardiovascular disease, diabetes, arthritis and cancer. Current therapies such as non-steroidal anti-inflammatories (NSAIDs) are associated with various adverse side effects, with the result being an increase in research aiming to identify natural compounds which possess anti-inflammatory activity. In this work, an in vitro study assessed the anti-inflammatory activities of two sinapinic acid-containing extracts on human-derived peripheral blood mononuclear cells (PBMCs). Both extracts were found to significantly reduce the levels of key pro-inflammatory cytokines including TNF-alpha, IL-12 and IL-6. Importantly, these extracts were found to be more potent than commercial SA in terms of their anti-inflammatory activities. Results demonstrate the potential of these extracts as anti-inflammatory agents.

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Section: Discussionsupporting

confidence: 91%

An In Vitro Study Determining the anti-inflammatory activities of sinapinic acid-containing extracts generated from Irish rapeseed meal

Quinn

Scott

Finn

et al. 2020

MRAJ

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“…In addition, DSS has anti-tumor activity in B16F10 melanoma by inhibiting angiogenesis and tumor cell invasion (Zhang 2010 ). Recently, DSS has been reported to have anti-immune activity (Ye 2020 ; Guan 2015 ), which attracted us to focus on its role in OA progression. Interestingly, we found that DSS treatment significantly decreased IL-1β-enhanced expression of IL-6, COX-2, TNF-α, and iNOS in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…Danshensu (DSS) is a bioactive agent isolated from an edible traditional Chinese medicine salvia miltiorrhiza (dan shen) (Cao 2019 ). DSS has been reported to have an anti-inflammatory effect involving TLR2 (Toll-like receptor 2) and macrophages through the NF-κB signaling pathway (Ye 2020 ). In addition, DSS can also significantly ameliorate colon inflammation in dextran sulfate sodium-induced colitis (Wen 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway

Zhang

et al. 2021

Mol Med

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Purpose Osteoarthritis (OA) is the most common inflammatory disease associated with pain and cartilage destruction. Interleukin (IL)-1β is widely used to induce inflammatory response in OA models. This study aimed to explore the role of Danshensu (DSS) in IL-1β-induced inflammatory responses in OA. Methods IL-1β was used to induce chondrocyte inflammation. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. IL-6, COX-2, TNF-α, and iNOS mRNA levels were detected by qRT-PCR. MMP3, MMP13, ADAMTS4, ADAMTS5, Aggrecan, Collagen, p-IκBα, and p-p65 protein levels were detected by Western blot. An OA mouse model was established by surgical destabilization of the medial meniscus (DMM), and the Osteoarthritis Research Society International (OARSI) score was evaluated by H&E staining. Results DSS did not affect the levels of inflammatory indicators including IL-6, COX-2, TNF-α, iNOS, PEG2, and NO but suppressed COX-2 and iNOS protein expression in IL-1β treated chondrocytes. In addition, DSS downregulated IL-1β-enhanced expression of MMP3, MMP13, ADAMTS4, and ADAMTS5 and upregulated aggrecan and collagen expression. Moreover, DSS significantly inhibited IL-1β-induced phosphorylation of p-IκBα and p-p65 in a dose-dependent manner in chondrocytes, suggesting it plays a role in the NF-κB signaling pathway. Furthermore, DSS significantly reduced DMM-induced cartilage OARSI score in mice, further demonstrating its protective role in OA progression in vivo. Conclusions Our study revealed the protective role of DSS in OA, suggesting that DSS might act as a potential treatment for OA.

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“…The phenolic acids have been widely reported for AS treatment. Tanshinol has a pronounced anti-inflammatory effect involving TLR2 and macrophages through the NF- κ B signaling pathway, which supports the novel application of DSS in the treatment of relevant diseases including AS and ischemic or ischemic/perfusion injury of the heart and brain [ 38 ]. Chlorogenic acid mitigates ox-LDL-induced endothelial oxidative stress and mitochondrial dysfunction by activating SIRT1 and modulating the AMPK/PGC-1 signaling pathway [ 39 ].…”

Section: Discussionmentioning

confidence: 87%

Guanxinning Tablet Attenuates Coronary Atherosclerosis via Regulating the Gut Microbiota and Their Metabolites in Tibetan Minipigs Induced by a High-Fat Diet

Yang

Shen

et al. 2022

Journal of Immunology Research

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Coronary atherosclerosis (CA) is a chronic and evolving inflammatory disease characterized by the build-up of atherosclerotic plaque in the wall of coronary arteries. Guanxinning tablet (GXNT) is a novel Chinese medicine formula, which has been clinically used to treat coronary heart disease for many years. However, the potential mechanism for treating CA remains unclear. Thus, the study was aimed at investigating the therapeutic effect of GXNT on CA and further explore the underlying mechanisms from the perspective of gut microbiota. Following the establishment of a CA model in Tibetan minipigs, GXNT was orally administrated. We simultaneously detected blood lipid levels, observed ventricular function using ultrasound examination, measured platelet aggregation, and checked changes in inflammatory factors, oxidative stress factors, and vascular endothelial injury-related indexes applying ELISA assays. Histopathological changes of coronary artery tissue were subsequently evaluated using Sudan IV staining, HE staining, Oil red “O” staining, and immunohistochemistry assays. Finally, alterations of the gut microbiota and microbial metabolites were detected using metagenomic sequencing and targeted metabolomics, respectively. The results have suggested that GXNT could regulate dyslipidemia, improve heart function, and inhibit the levels of ox-LDL, CRP, TNF-α, IL-1β, SOD, MDA, vWF, and ET-1, as well as platelet aggregation. Additionally, histopathological findings revealed that GXNT could reduce lipid deposition, alleviate AS lesions, and restrain the expressions of NF-κB, TNF-α, and MMP-9. Furthermore, the composition of the gut microbiota was altered. Specifically, GXNT could upregulate the relative abundance of Prevotellaceae and Prevotella and downregulate the abundance of Proteobacteria, Enterobacteriaceae, and Escherichia. As for microbial metabolites, GXNT could increase fecal propionic acid, butyric acid, and LCA-3S and decrease fecal TMA-related metabolites, CDCA, and serum TMAO. In sum, the results showed that GXNT had a satisfactory anti-CA effect, and the mechanism was closely associated with modulating gut microbiota and related metabolites.

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Inhibition of nuclear factor kappa B as a mechanism of Danshensu during Toll-like receptor 2-triggered inflammation in macrophages

Cited by 13 publications

References 55 publications

An In Vitro Study Determining the anti-inflammatory activities of sinapinic acid-containing extracts generated from Irish rapeseed meal

An In Vitro Study Determining the anti-inflammatory activities of sinapinic acid-containing extracts generated from Irish rapeseed meal

Danshensu inhibits the IL-1β-induced inflammatory response in chondrocytes and osteoarthritis possibly via suppressing NF-κB signaling pathway

Guanxinning Tablet Attenuates Coronary Atherosclerosis via Regulating the Gut Microbiota and Their Metabolites in Tibetan Minipigs Induced by a High-Fat Diet

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