XJP-1

Angioedema is nonpitting swelling that involves the deeper subcutaneous and submucosal layers of tissue. Angioedema can be classified as histaminergic, bradykinin mediated, or idiopathic in etiology. Bradykinin-mediated angioedema presents without urticaria, whereas histaminergic angioedema is usually associated with urticaria (i.e., chronic spontaneous urticaria and angioedema) but manifests with isolated angioedema in ∼20% of patients and clinically overlaps with idiopathic angioedema. Bradykinin-mediated angioedema most commonly occurs in hereditary angioedema (HAE) with or without C1-esterase inhibitor (C1-INH) (HAE-C1INH) deficiency, acquired C1-INH deficiency, and angiotensin-converting enzyme (ACE) inhibitor angioedema. HAE is a life-threatening genetic autosomal dominant disorder most commonly due to a mutation in the serpin family G member 1 (SERPING1) gene, which leads to a deficiency in C1-INH, although multiple new genetic mutations have also been described in HAE with normal C1-INH (HAE‐nl-C1INH) level. Clinically, patients have edema that can lead to life-threatening laryngeal edema and asphyxiation. HAE‐nl-C1INH describes patients with similar symptoms to those with HAE‐C1INH deficiency but have normal C1-INH function and are distinguished by various genetic mutations and a family history of angioedema. Acquired C1-INH deficiency also mimics HAE with symptoms but is due to circulating anti-idiotypic antibodies, leading to either C1-INH consumption or inactivation. Patients are often diagnosed with underlying malignant, lymphoproliferative, or autoimmune disorders. ACE-inhibitor angioedema classically presents with facial, tongue, and oral cavity swelling not associated with pruritus accompanied by normal laboratory studies. Treatment involves stopping the ACE inhibitor though recurrence can occur for a few weeks to months after discontinuation. Idiopathic angioedema is the largest category and is diagnosed when patients experience angioedema without an identifiable etiology with nl-C1INH function and no family history of angioedema. Idiopathic angioedema is further characterized into histaminergic or nonhistaminergic angioedema, depending on the response to high-dose antihistamines. Given the considerable impact of angioedema, physicians and patients must collaborate to craft personalized management strategies. For those with HAE, short- and long-term prophylaxis and on-demand therapy must be considered.

Angiotensin-I Converting Enzyme (ACE, EC 3.4.15.1) plays an essential role in controlling blood pressure. In this research, ACE inhibitors extracted from Arthrospira platensis thermolysin protease were provided using various chromatographic techniques, including reversed-phase high-performance liquid chromatography (RP-HPLC) and strong cation exchange chromatography (SCX). The amino acid sequence was determined by liquid-chromatography-tandem mass spectrometry (LC-MS/MS) and identified using two independent approaches: database-assisted identification and de novo sequencing. FY11 (FSESSAPEQHY) and IR5 (ILLYR) were established with the m/z 1281.54 and 677.37, respectively. The IC₅₀ of IR5 from triplicate experiments was lower than FY11, with the value 10.54 ± 1.38 µM. IR5 was regarded as a non-competitive ACE inhibitor, with the docking interaction energy of - 106.842 kJ/mol. Docking results revealed that the interaction between ACE and peptide existed outside the ACE active site, excluding Arg 522, one of the Cl₂ binding sites. Notably, the content of IR5 in 2 mg of crude thermolysin digest was determined to be 2.42 µg/mg using LC-MS/MS quantification. Based on all these features, Arthrospira peptides can be considered to be a potentially promising antihypertensive agent.