**9. Whey protein hydrolysate downregulate inflammation-related genes**

Bioactive peptides with anti-inflammatory effects, as well as amino acids, are used in dairy protein hydrolysates [98]. After the consumption of milk or yogurt, postprandial mRNA levels of inflammatory markers were shown to be lower in an acute clinical trial [99]. These findings indicate that dairy nutrients, as shown in mice, may control the transcriptome [100]. Low-grade systemic inflammation has been related to endothelial dysfunction and the progression of atherosclerosis in obese and/or T2D people [101]. Reduced nitric oxide (NO) supply and hence endothelial nitric oxide synthase (eNOS) activity characterize endothelial dysfunction. The research showed that lower the availability of NO, enhances the invasion

of macrophages linked to adhering molecules like vascular cellular adhesion molecule (VCAM)–1, along with the discharge of proinflammatory cytokines like interleukins (ILs) and tumor necrosis factor (TNF–α) [102]. Antioxidant enzymes including superoxide dismutases (SOD) may even deactivate reactive oxygen species (ROS) that are connected to endothelial dysfunction [103]. Endothelial cells play an important role in inflammation. Dairy products' special protein and amino acid composition can influence cytokine gene expression and development. However, mechanistic experiments comparing various dairy protein compounds are rare [104]. Whey proteins and their chief amino acids, BCAAs, shown an increased anti-inflammatory capacity compared to other proteins.

Whey protein hydrolysate and BCAA have anti-inflammatory properties by lowering TNF and VCAM-1 expression and thereby attenuating TNF-α induced gene expression. Similarly, whey proteins were found to have an anti-inflammatory impact in Caco-2 intestinal cells by lowering IL-8 production [105]. Whey proteins' protective effects may be regulated by BCAAs. In HUVECs, BCAAs reduced the inflammatory reaction caused by TNF. In obese mice, induction of BCAAs, particularly leucine, reduced the appearance of genes involved in inflammation in the adipose tissue and liver, as well as macrophage infiltration [106].

In a rodent model of endothelial dysfunction, glutamine reduced the levels of circulating inflammatory markers (IL-6, IL-1, MIP-1, GM-CSF, MIP-2, IFN, and E-selectin) [107]. SOD2 expression is influenced by whey proteins and amino acids in the absence of TNF stimulation. WPH have been shown in to reduce inflammatory responses by constraining the nuclear factor κB (NF-κB) pathway [108]. Furthermore, glutamine, leucine, and proline have the ability to block the NF-κB pathway [109]. NF-κB is a transcription factor that controls the transcription of several inflammatory genes when it is triggered by proinflammatory signals like TNFα. TNF, VCAM-1, and SOD2 are among the genes controlled by NF-κB [110], and these were the genes most affected by whey protein combinations in this study. As a result, it is established that by a route of NF-κB pathway, clear reduction in TNFlinked appearance of genes for inflammation through hydro-lysates and BCAAs of whey proteins could be achieved. Whey protein isolate, caseins, and WPC are entire proteins that can require other pathways. Autophagy, for example, has an effect on the functionality of mitochondria and oxidative stress, and that could be stimulated by proteins [111, 112].
