## 4 Discussion
Likewise, smaller molecular weight peptides (2-10 residues) are more soluble and can coordinate efficiently with enzyme active site regions [2]. This trend corresponds well with that described by [PERSON] et al. [6], where peptide fractions from cotton leaf worm (_S. littoralis_) were separated by SEC and RP-HPLC. Fractionation revealed an active peptide with an aromatic, hydrophobic amino acid at the carboxyl terminus, namely phenylalanine, and consisted of a hydrophobic amino acid at the amino terminus, alanine, which showed antihypertensive activity in vitro and in vivo [6]. Fraction F6 was separated into two charged groups, anionic and cationic peptides, which confirmed that the most potent peptides were primarily cationic in nature. The data conferred the cationic pool of peptides withsuperior inhibiting activity towards ACE, \(\alpha\)-amylase, and \(\alpha\)-glucosidase; DPP-IV inhibiting activity, however, decreased after the various stages of fractionation. Cellular inflammation and dysfunction play a crucial role in several disorders, including CVD risk factors, such as hypertensive and hyperglycemic responses. Nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-\(\kappa\)B) is a central regulator of pro-inflammatory mediators and is an essential component linking chronic inflammation and CVD. Thus, regulating NF-\(\kappa\)B is considered a potential therapeutic target for CVD risk factors [30]. Since the monocytogenes-induced NF-\(\kappa\)B pathway is the most dominant host response in macrophage cells, we examined the ability of cricket peptides to inhibit NF-\(\kappa\)B in the RAW 264.7-NF-\(\kappa\)B-luciferase reporter cell line. Our results demonstrated that the cationic peptide fraction inhibited NF-\(\kappa\)B expression in RAW 267.4 cells. This reporter contained a firefly luciferase gene under the control of multimerized NF-\(\kappa\)B responsive pathways, which are commonly used to assess the potency of anti-inflammatory molecules and peptides. During inflammatory scenarios, NF-\(\kappa\)B positively modulates expression levels of several chemokines (e.g., MCP-1), proangiogenic factors, for example, vascular endothelial growth factor (VEGF), and cellular inhibitors of apoptosis [31]. In this study, NF-\(\kappa\)B expression was stimulated by the bacterial cell wall component lipopolysaccharideacharide (LPS), which is known to induce an inflammatory cascade, by activating the TLR4-NF\(\kappa\)B signaling pathway [30]. Cells pre-treated with the cationic fraction demonstrated lower levels of NF-\(\kappa\)B, as compared to LPS alone, verifying that this fraction contained some of the more potent peptides present within CPHD. This observation was further confirmed by the fact that the isolated cationic fractions exhibited proportionate NF-\(\kappa\)B regulation, compared to that of CPHD (Figure 2). Notably, this anti-inflammatory activity was maintained and required a much lower concentration of the cationic peptides (1-10 \(\mathrm{\SIUnitSymbolMicro g}\)/mL vs. 100-500 \(\mathrm{\SIUnitSymbolMicro g}\)/mL, Figure 2). Most food-derived peptides exert anti-inflammatory activities by inhibiting signaling components of either NF-\(\kappa\)B or mitogen-activated protein kinase (MAPK) pathways, the two major pathways were involved in chronic inflammation following uncontrolled signal activation [32]. Similar to the findings of this study, venom from wasp (_Nasonia vitripennis_) dose-dependently inhibited NF-\(\kappa\)B signaling in reporter fibrosarcoma cells [33]. More than half of NF-\(\kappa\)B was suppressed with 6.4 and 12.5 \(\mathrm{\SIUnitSymbolMicro g}\)/mL of wasp venom. In addition to the NF-\(\kappa\)B inhibitory action, the wasp venom also inhibited IL-6 (a pro-inflammatory cytokine) expression in LPS-activated macrophages, as well as, expression of two NF-\(\kappa\)B target genes, \(\mathrm{I}\)\(\mathrm{R}\)\(\mathrm{\SIUnitSymbolMicro g}\) and A20 [33]. In another study, peptide fractions from cricket (_G.