生物活性

• 描述Maleic Acid is a Glutamate Decarboxylase (GAD) inhibitor of E. coli and L. monocytogenes^[3]. Maleic acid affected the extracellular GABA levels while it did not affect the intracellular ones. Maleic acid had a major impact mainly on GadD2 activity as also shown in cell lysates. Furthermore, it was demonstrated that maleic acid is able to partly remove biofilms of L. monocytogenes. Maleic acid is able to inhibit the GAD of L. monocytogenes significantly enhancing its sensitivity to acidic conditions and together with its ability to remove biofilms^[4]. Maleic acid induced concentration-dependent and time-dependent cell death shown by increased lactate dehydrogenase release as well as ethidium homodimer and calcein acetoxymethyl ester staining. MA (Maleic acid) toxicity was critically dependent on calcium levels in culture medium and blocked by the extra- and intracellular calcium chelators EGTA and BAPTA-AM respectively. Moreover, MA-induced cell death was associated with activation of calcium-dependent calpain proteases^[5]. MA induced proteinuria, an increase in urinary excretion of N-acetyl-β-d-glucosaminidase, and a decrease in plasma glutathione peroxidase activity, renal blood flow, and oxygenation and perfusion of renal cortex. Moreover, MA impaired mitochondrial bioenergetics associated to complex I, mitochondrial membrane potential and respiratory control index and increased the mitochondrial production of hydrogen peroxide^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02731287	Hemangioma	Phase 2	Completed	-	Spain ... more >> Hospital de la Santa Creu i Sant Pau Barcelona, Spain, 08025 Hospital Virgen del Rocío Sevilla, Spain, 41013 Collapse <<
  NCT01873131	Hemangioma	Not Applicable	Recruiting	December 2020	United States, Massachusetts ... more >> Massachusetts General Hospital Recruiting Boston, Massachusetts, United States, 02114 Contact: Thanh Nga T Tran, MD PhD    617-724-4937    ttran2@partners.org    Contact: Ray H Jalian, MD    617 724-4937    hjalian@partners.org    Principal Investigator: R. Rox Anderson, MD          Sub-Investigator: Thanh Nga T Tran, MD PhD          Sub-Investigator: Kelly Stankiewicz, MD          Sub-Investigator: Ray H Jalian, MD Collapse <<
  NCT02207621	Ocular Hypertension ... more >> Open-angle Glaucoma Collapse <<	Phase 3	Completed	-	United States, New Jersey ... more >> Aerie Pharmaceuticals Bedminster, New Jersey, United States, 07921 Collapse <<

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• 参考文献

• [1] El-Sakhawy F, Kassem H, et al. Phytochemical investigation of the bioactive extracts of the leaves of Ficus cyathistipula Warb. Z Naturforsch C. 2016;71(5-6):141-54.

  [2] El Sayed AM, Ezzat SM, Sabry OM. A new antibacterial lupane ester from the seeds of Acokanthera oppositifolia Lam. Nat Prod Res. 2016 Apr 4:1-6.

  [3] Fonda ML. Glutamate decarboxylase. Substrate specificity and inhibition by carboxylic acids. Biochemistry. 1972 Mar 28;11(7):1304-9

  [4] Paudyal R, Barnes RH, Karatzas KAG. A novel approach in acidic disinfection through inhibition of acid resistance mechanisms; Maleic acid-mediated inhibition of glutamate decarboxylase activity enhances acid sensitivity of Listeria monocytogenes. Food Microbiol. 2018 Feb;69:96-104

  [5] Tuncel AT, Ruppert T, Wang BT, Okun JG, Kölker S, Morath MA, Sauer SW. Maleic Acid--but Not Structurally Related Methylmalonic Acid--Interrupts Energy Metabolism by Impaired Calcium Homeostasis. PLoS One. 2015 Jun 18;10(6):e0128770

  [6] Briones-Herrera A, Avila-Rojas SH, Aparicio-Trejo OE, Cristóbal M, León-Contreras JC, Hernández-Pando R, Pinzón E, Pedraza-Chaverri J, Sánchez-Lozada LG, Tapia E. Sulforaphane prevents maleic acid-induced nephropathy by modulating renal hemodynamics, mitochondrial bioenergetics and oxidative stress. Food Chem Toxicol. 2018 May;115:185-197

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