Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis

Abstract

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.

Annexin A1 (Ac2-26)-dependent Fpr2 receptor alleviates sepsis-induced acute kidney injury by inhibiting inflammation and apoptosis in vivo and in vitro

“…2 C). In addition, previous studies reported that ANXA1 (Ac2-26) inhibits inflammatory responses through Fpr2 in LPS-induced uveitis in rats [ 39 ]. The data showed that WRW4 reversed the negative regulation of inflammatory cytokines and kidney tissue injury by ANXA1 while significantly promoting the phosphorylation of PI3K and AKT and increasing the levels of NF-κB in CLP-induced mice (Fig.…”

“…The inflammatory response induced by LPS through the production and release of a large amount of proinflammatory cytokines, such as TNF-α, IL-2, and IL-6, eventually leads to renal tubular epithelial cell damage and SI-AKI [ 40 ]. It has been shown that ANXA1 (Ac2-26) reduces the production of proinflammatory cytokines, such as TNF-α, IL-1β and IL-6, in LPS-induced uveitis [ 39 ]. In addition, ANXA1 (Ac2-26) has become an effective anti-inflammatory therapeutic target based on its ability to reduce inflammatory responses in vitro and in vivo and has organ-protective effects [ 22 ].…”

“…Zhao et al found that glycyrrhizic acid alleviates SI-AKI by inhibiting apoptosis in kidney tissue [ 48 ]. ANXA1 has been shown to have multiple biological activities, including carcinogenesis, cell proliferation, apoptosis, metastasis, and anti-inflammation [ 39 ]. Overexpression of ANXA1 inhibits PI3K/AKT phosphorylation, thereby reducing the activity of caspase-3 and upregulating Bcl-2 expression levels, leading to anti-apoptosis in human bronchial epithelial cells [ 49 ].…”

Biological activities of peptides obtained by pepsin hydrolysis of fishery products

“…A controlled inflammatory response is beneficial; however, excessive or uncontrolled inflammation and oxidative stress are known to promote the onset of chronic human diseases such as diabetes, obesity, cardiovascular disease, cancer, respiratory disorders, atherosclerosis and neurodegenerative diseases [97,98]. For this reason, the use of synthetic anti-inflammatories has been necessary, which allows controlling the overproduction of inflammatory mediators and the overresponse of enzymes involved in the inflammatory process [99]; nevertheless, prolonged use of these medications has negative consequences for the organism [100]. That is why there is currently a growing interest in finding anti-inflammatory compounds of natural origin, which do not have secondary effects on the body.…”