Protective Effect of Tetrahydroquinolines from the Edible Insect Allomyrina dichotoma on LPS-Induced Vascular Inflammatory Responses

The larva of Allomyrina dichotoma (family Scarabaeidae) is an edible insect that is registered in the Korean Food Standards Codex as a food resource. The chemical study on the larvae of A. dichotoma resulted in the isolation of three new tetrahydroquinolines, allomyrinaines A–C (1–3), one new dopamine derivative, allomyrinamide A (4), and four known compounds (5–8). The structures were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) and MS spectroscopic data analysis. Allomyrinaines A–C (1–3) possessed three stereogenic centers at C-2, C-3, and C-4, whose relative configurations were determined by analyses of the coupling constants and the nuclear Overhauser enhancement spectroscopy (NOESY) data, as well as DP4+ calculation. The anti-inflammatory effects of compounds 1–4 were evaluated in human endothelial cells. Allomyrinaines A–C (1–3) could stabilize vascular barrier integrity on lipopolysaccharide (LPS)-induced vascular inflammation via inhibition of the nuclear factor-κB (NF-κB) pathway. The physiologically relevant concentration was confirmed by Q-TOF-MS-based quantitative analysis on allomyrinaines A–C in crude extract. This study suggests that allomyrinaines A–C (1–3) are bioactive constituents of A. dichotoma to treat vascular inflammatory disorder.

[1]  A. Makatsariya,et al.  Septic shock , 2020, Obstetrics, Gynecology and Reproduction.

[2]  Heesoon Lee,et al.  Inhibition of inflammatory mediators and cell migration by 1,2,3,4-tetrahydroquinoline derivatives in LPS-stimulated BV2 microglial cells via suppression of NF-κB and JNK pathway. , 2020, International immunopharmacology.

[3]  Seung-Yoon Park,et al.  Macrophagic Stabilin-1 Restored Disruption of Vascular Integrity Caused by Sepsis , 2018, Thrombosis and Haemostasis.

[4]  Wonhwa Lee,et al.  Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity. , 2017, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[5]  Wonhwa Lee,et al.  Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity , 2017, Scientific Reports.

[6]  Y. H. Kim,et al.  Quinoxaline-, dopamine-, and amino acid-derived metabolites from the edible insect Protaetia brevitarsis seulensis , 2017, Archives of Pharmacal Research.

[7]  Haifeng Zhou,et al.  Antidesmone, a unique tetrahydroquinoline alkaloid, prevents acute lung injury via regulating MAPK and NF‐&kgr;B activities , 2017, International immunopharmacology.

[8]  E. Yun,et al.  Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways , 2016, Nutrients.

[9]  R. Erenler,et al.  Isolation and identification of chemical constituents from Origanum majorana and investigation of antiproliferative and antioxidant activities. , 2016, Journal of the science of food and agriculture.

[10]  Ariel M. Sarotti,et al.  Beyond DP4: an Improved Probability for the Stereochemical Assignment of Isomeric Compounds using Quantum Chemical Calculations of NMR Shifts. , 2015, The Journal of organic chemistry.

[11]  D. Ferreira,et al.  Quinic acid derivatives from Salicornia herbacea alleviate HMGB1-mediated endothelial dysfunction , 2015 .

[12]  이지은,et al.  Hepatoprotective and Anticancer Activities of Allomyrina dichotoma Larvae , 2015 .

[13]  E. Yun,et al.  Effects of solvent fractions of Allomyrina dichotoma larvae through the inhibition of in vitro BACE1 and β‐amyloid(25–35)‐induced toxicity in rat pheochromocytoma PC12 cells , 2014 .

[14]  Ji-Young Kim,et al.  Fatty Acid and Volatile Oil Compositions of Allomyrina dichotoma Larvae , 2012, Preventive nutrition and food science.

[15]  J. Bae Role of high mobility group box 1 in inflammatory disease: Focus on sepsis , 2012, Archives of pharmacal research.

[16]  Seong-Ryul Kim,et al.  Antioxidant activity of various solvent extracts from Allomyrina dichotoma (Arthropoda: Insecta) larvae. , 2010, Journal of photochemistry and photobiology. B, Biology.

[17]  R. Sartor,et al.  Lipopolysaccharide activates innate immune responses in murine intestinal myofibroblasts through multiple signaling pathways. , 2009, American journal of physiology. Gastrointestinal and liver physiology.

[18]  W. Aird Endothelium as a therapeutic target in sepsis. , 2007, Current drug targets.

[19]  Peter A. Ward,et al.  Novel strategies for the treatment of sepsis , 2003, Nature Medicine.

[20]  Jonathan Cohen The immunopathogenesis of sepsis , 2002, Nature.

[21]  P A Ward,et al.  Mechanisms of enhanced lung injury during sepsis. , 1999, The American journal of pathology.

[22]  P. Ward,et al.  Mechanisms of endothelial cell injury in acute inflammation. , 1994, Shock.

[23]  J. Pugin,et al.  Lipopolysaccharide (LPS)-binding protein and soluble CD14 function as accessory molecules for LPS-induced changes in endothelial barrier function, in vitro. , 1994, The Journal of clinical investigation.

[24]  Sanggil Choe,et al.  A grayanotox-9(11)-ene derivative from Rhododendron brachycarpum and its structural assignment via a protocol combining NMR and DP4 plus application. , 2017, Phytochemistry.

[25]  정성현,et al.  장수풍뎅이 유충으로부터 지표성분(Inosine)의 분리 및 정량분석 , 2006 .

[26]  S. Chung,et al.  Isolation and Quantitative Analysis of Inosine as an Index Component from Larva of Allomirina dichotoma , 2006 .

[27]  P. Nawroth,et al.  LPS and Cytokine-Activated Endothelium , 2000, Seminars in thrombosis and hemostasis.