Modulation of Inflammation by Plant-Derived Nutraceuticals in Tendinitis

Abstract

Tendinitis (tendinopathy) is a pro-inflammatory and painful tendon disease commonly linked with mechanical overuse and associated injuries, drug abuse, and lifestyle factors (including poor diet and physical inactivity) that causes significant healthcare expenditures due to its high incidence. Nuclear factor kappa B (NF-κB) is one of the major pro-inflammatory transcription factors, along with other inflammation signaling pathways, triggered by a variety of stimuli, including cytokines, endotoxins, physical and chemical stressors, hypoxia, and other pro-inflammatory factors. Their activation is known to regulate the expression of a multitude of genes involved in inflammation, degradation, and cell death. The pathogenesis of tendinitis is still poorly understood, whereas efficient and sustainable treatment is missing. Targeting drug suppression of the key inflammatory regulators represents an effective strategy for tendinitis therapy, but requires a comprehensive understanding of their principles of action. Conventional monotherapies are often ineffective and associated with severe side effects in patients. Therefore, agents that modulate multiple cellular targets represent therapeutic treatment potential. Plant-derived nutraceuticals have been shown to act as multi-targeting agents against tendinitis via various anti-oxidant and anti-inflammatory mechanisms, whereat they were able to specifically modulate numerous signaling pathways, including NF-κB, p38/MAPK, JNK/STAT3, and PI3K/Akt, thus down-regulating inflammatory processes. This review discusses the utility of herbal nutraceuticals that have demonstrated safety and tolerability as anti-inflammatory agents for the prevention and treatment of tendinitis through the suppression of catabolic signaling pathways. Limitations associated with the use of nutraceuticals are also described.

β1-Integrin plays a major role in resveratrol-mediated anti-invasion effects in the CRC microenvironment

“…Here, we found that NF-κB knockdown led to a decreased inflammatory spread and invasion capacity in both CRC cell lines HCT116 and RKO, whereby resveratrol treatment of NF-κB down-regulated CRC cells significantly enhanced their ability to act in a synergistic, powerful anti-inflammatory way. Based on this finding, it is worth considering the potential of resveratrol in the future with regard to the treatment of cancer and other chronic inflammatory diseases such as rheumatoid arthritis, where NF-κB activation also plays a crucial role or Crohn's disease, where dysregulation of NF-κB, physiologically necessary for intestinal homeostasis, triggers an inflammatory cascade (Nissim-Eliraz et al, 2021;Mueller et al, 2022). The fact that integrin receptors physiologically occur and are necessary in the embryonic development is also exploited by malignant cancer cells in the event of disease, thus for treatment of hepatocellular carcinoma, reduction of α2-, β1-, and β3-integrin expression has been proposed as a possible option (Relja et al, 2011).…”

“…Resveratrol has also been announced to make use of integrins as both, surface receptors and signaling molecules, for exerting its anti-tumor effects (Lin et al, 2006;Belleri et al, 2008;Varoni et al, 2016). Integrin families are heterodimeric cell adhesion and signaling molecules that play a central role as signal transducers in the interaction between cells and extracellular matrix (Shakibaei et al, 1997;Shakibaei, 1998;Shakibaei and Merker, 1999;Mueller et al, 2022), thus display a crucial role in the differentiation and function of cells in healthy tissues (Carter et al, 1990;Chen, 1990;Shakibaei, 1995). Moreover, these specific compounds are remarkably up-regulated in cancer cells, what is associated with increased risk for tumor migration and metastasis (Huang et al, 2021).…”

“…After 1 day, the glass slides were removed from well-plates and washed with Hank's salt solution three times, ensuring that only CRC cells were left for immunolabelling. Then, CRC-glass plates were fixated in methanol for 30 min and prepared for immunofluorescence microscopy as described in detail before (Brockmueller et al, 2022;Mueller et al, 2022). In the present work, CRC cells were immunolabeled with E-cadherin-, NF-κBpaxillin-or slug-antibodies.…”

“…Then, the clean CRC-alginate balls were dissolved in sodium citrate (55 mM) for 30 min to isolate CRC cells which were resuspended in lysis buffer as described before (Brockmueller et al, 2022). After 30 min of centrifugation, the liquid supernatant was kept frozen (−80 °C) and samples were further processed with a Bio-Rad (Munich, Germany) transblot apparatus for densitometric evaluation with Bio-Rad Quantity One analysis software as explained in detail in our earlier work (Brockmueller et al, 2022;Mueller et al, 2022). In the current study, the beforementioned antibodies were used in 1: 10.000 dilution and β-actin served as loading control.…”

Wistin Exerts an Anti-Inflammatory Effect via Nuclear Factor-κB and p38 Signaling Pathways in Lipopolysaccharide-Stimulated RAW264.7 Cells

“…Current anti-inflammatory disease treatments (non-steroidal anti-inflammatory drugs and glucocorticoids) have many side effects, including tissue damage, cardiovascular problems, and liver complications. As plant-derived drugs have been reported to have fewer toxic effects, it has been suggested that they could be potential modulators of inflammation [ 22 , 23 ]. Human papillomavirus (HPV) infection can cause chronic inflammation due to the release of pro-inflammatory cytokines [ 24 , 25 ].…”