Molecular Cascade of Neolignan as A Natural Anti-Diabetics Agent: A Bioinformatics Approach http://www.doi.org/10.26538/tjnpr/v7i11.23
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Abstract
Neolignan, a biosynthesis product of the shikimate pathway in plants, has previously shown in vitro anti-diabetic activity. This study was designed to identify neolignan's multiple molecular targets and its molecular cascade for inhibiting diabetes. The researchers mined online databases for genes related to diabetes and hyperglycemia, as well as genes affected by neolignan. The Venn diagram result of these genes was further utilized to figure out a network of protein-protein interaction and gene clustering.
In summary, the study identified proteins targeted by neolignan, which include IGFR-1, EGFR, the inflammatory cytokine TNF-α, the chaperone protein Hsp90, as well as various downstream signaling molecules such as MAPK8, SCR, PI3K, and JAK1. These proteins work in concert during neolignan treatment to support its anti-diabetic activity. This research provides an initial glimpse into the molecular mechanisms of neolignan in diabetes treatment.
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Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol. 2018; 14(2): 88-98.
Zhao C, Chen J, Shao J, Shen J, Li K, Gu W, Li S, Fan J. Neolignan Constituents with Potential Beneficial Effects in Prevention of Type 2 Diabetes from Viburnum fordiae Hance Fruits. Journal of agricultural and food chemistry. 2018; 66(40): 10421-10430.
Abdul M, Khan B, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes–global burden of disease and forecasted trends. Epidemiol. Glob. Health 2020; 10(1): 107-111.
Wang S, Ding L, Ji H, Xu Z, Liu Q, Zheng Y. The Role of p38 MAPK in the Development of Diabetic Cardiomyopathy. Int. J. Mol. Sci. 2016; 17(7): 1037-1051.
Yaribeygi H, Sathyapalan T, Atkin SL, Sahebkar A. Molecular mechanisms linking oxidative stress and diabetes mellitus. Oxidative medicine and cellular longevity. 2020; 2020: 1-13.
F. F. Jubaidi, S. Zainalabidin, I. S. Taib, Z. Abdul Hamid, N. N. Mohamad Anuar, J. Jalil, N. A. Mohd Nor, S. B. Budin. The Role of PKC-MAPK Signalling Pathways in the Development of Hyperglycemia-Induced Cardiovascular Complications. Int. J. Mol. Sci. 2022; 23(15): 8582.
M. Dunlop. Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int. Suppl. 2000; 58: S3-12.
J. Shi, J. Fan, Q. Su, Z. Yang. Cytokines and Abnormal Glucose and Lipid Metabolism. Front. Endocrinol. (Lausanne). 2019; 10(1): 703
L. Wang, H. L. Wang, T. T. Liu, H. Y. Lan. Regulation of plant responses to salt stress. Int. J. Mol. Sci. 2021; 22(9): 4609.
C. Iacobini, M. Vitale, J. Haxhi, C. Pesce, G. Pugliese, S. Menini. Mutual regulation between redox and hypoxia-inducible factors in cardiovascular and renal complications of diabetes. Antioxidants 2022; 11(11): 2183.
Singh R, Kaur N, Kishore L, Gupta GK. Management of diabetic complications: a chemical constituents based approach. Journal of Ethnopharmacology. 2013; 150(1):51-70.
Chaudhury, C. Duvoor, V. S. Reddy Dendi, S. Kraleti, A. Chada, R. Ravilla, A. Marco, N. S. Shekhawat, M. T. Montales, K. Kuriakose, et al., Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Front. Endocrinol. (Lausanne). 2017; 8:6.
G. Roglic. WHO Global report on diabetes: A summary. Int. J. Noncommunicable Dis. 2016; 1(1):3.
J. da Rocha Fernandes, K. Ogurtsova, U. Linnenkamp, L. Guariguata, T. Seuring, P. Zhang, D. Cavan, L. E. Makaroff. IDF Diabetes Atlas estimates of 2014 global health expenditures on diabetes. Diabetes Res. Clin. Pract. 2016; 117:48-54.
M. Ekor. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Neurol. 2014; 4(1):1777.
C. G. Yedjou, J. Grigsby, A. Mbemi, D. Nelson, B. Mildort, L. Latinwo, P. B. Tchounwou. The management of diabetes mellitus using medicinal plants and vitamins. Int. J. Mol. Sci. 2023; 24(10):9085.
M. L. Willcox, C. Elugbaju, M. Al-Anbaki, M. Lown, B. Graz. Effectiveness of medicinal plants for glycaemic control in type 2 diabetes: an overview of meta-analyses of clinical trials. Front. Pharmacol. 2021; 12(1):777561.
H. Choudhury, M. Pandey, C. K. Hua, C. S. Mun, J. K. Jing, L. Kong, L. Y. Ern, N. A. Ashraf, S. W. Kit, T. S. Yee, Picika, M.R., Gorain, B., Kesharwari., An update on natural compounds in the remedy of diabetes mellitus: A systematic review. J. Tradit. Complement. Med. 2018; 8(3):361.
C. Zhao, J. Chen, J. Shao, J. Shen, X. Xu, K. Li, W. Gu, M. Zhao. Isolation of neolignan and phenolic glycosides from the branches of Viburnum macrocephalum f. keteleeri and their α-glucosidase inhibitory activity. J. Fan, Holzforschung 2018; 72(12):1017.
Y. S. Hartini, D. Setyaningsih. α-amylase and a-glucosidase inhibitory effects of four piper species and GC-MS analysis of Piper crocatum. Biodiversitas 2023; 24(2): 1313-1319
M. D. Goncalves, A. Farooki. Management of phosphatidylinositol-3-kinase inhibitor-associated hyperglycemia. Integr. Cancer Ther. 2022; 21.
Cheng ZB, Lu X, Bao JM, Han QH, Dong Z, Tang GH, Gan LS, Luo HB, Yin S. (±)-Torreyunlignans A−D, Rare 8−9′ Linked Neolignan Enantiomers as Phosphodiesterase-9A Inhibitors from Torreya yunnanensis. J. Nat. Prod. 2014; 77(12): 2651-2657.
Bastos RG, Rodrigues SdO, Marques LA, Oliveira CM, Salles BCC, Zanatta AC, Rocha FD, Vilegas W, Pagnossa JP, Paula FBdA, Silva GA, Batiha GE, Sarah SS, Aggad, Alotaibi BS, Yousef FM, Silva MA. Eugenia sonderiana O. Berg leaves: Phytochemical characterization, evaluation of in vitro and in vivo antidiabetic effects, and structure-activity correlation. Biomedicine & Pharmacotherapy. 2023; 165: 115126.
Peng X, Wang J, Peng W, Wu FX, Pan Y. Protein-protein interactions: detection, reliability, assessment and applications. Briefings in Bioinformatics. 2017; 18(5): 798-819.
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8(4): 1-7.
Lin CY, Chin CH, Wu HH, Chen SH, Ho CW, Ko MT. Hubba: hub objects analyzer - a framework of interactome hubs identification for network biology. 2008; 36(2): 438-443.
Tan DC, Kassim NK, Ismail IS, Hamid M, Bustamam MSA. Identification of Antidiabetic Metabolites from Paederia foetida L. Twigs by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Study. BioMed Research International. 2019; 2019.
Arif R, Ahmad S, Mustafa G, Mahrosh HS, Ali M, ul-Qamar MT, Dar HR. Molecular Docking and Simulation Studies of Antidiabetic Agents Devised from Hypoglycemic Polypeptide-P of Momordica charantia. BioMed Res. Int. 2021; 2021.
Swilam N, Nawwar MAM, Radwam RA, Mostafa ES. Antidiabetic Activity and In Silico Molecular Docking of Polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation of Undescribed Acylated Flavonol Diglucoside. Plants. 2022; 11(452): 1-27.
Schultze SM, Hemmings BA, Niessen M, Tschopp O. PI3K/AKT, MAPK, AMPK signalling: protein kinases in glucose homeostasis. Expert Reviews in Molecular Medicine. 2012; 14(e1): 1-21.
He X, Gao F, Hou J, Li T, Tan J, Wang C, Liu X, Wang M, Liu H, Chen Y, Yu Z, Yang M. Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus. J. Biol. Chem. 2021; 297(2): 1-11.
Mantravadi S, George M, Brensinger C, Du M, Baker JF, Ogdie A. Impact of tumor necrosis factor inhibitors and methotrexate on diabetes mellitus among patients with inflammatory arthritis. BMC Rheumatology. 2020; 4(39): 1-10.
Saxena M, Ali D, Modi DR, Almarzoug MH, Hussain SA, Manohrdas S. Association of TNF-α gene expression and release in response to anti-diabetic drugs from human adipocytes in vitro. Diabetes, Metabolic Syndrome and Obesity. 2020; 13: 2633-2640.
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, & Olson AJ. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009; 30(16): 2785-2791.
Santos-Martins D, Solis-Vasquez LAF, Tillack MF, Sanner A, Koch S, Forli. Accelerating AutoDock4 with GPUs and gradient-based local search. J. Chem. Theory Comput. 2021; 17(2): 1060.
Zhong H, Wang Z, Wang X, Liu H, Li D, Liu H, Yao X, Hou T. Importance of a crystalline water network in docking-based virtual screening: a case study of BRD4. Phys. Chem. Chem. Phys. 2019; 21(45): 25276.
Thirone ACP, JeBailey L, Bilan PJ, Klip A. Opposite effect of JAK2 on insulin-dependent activation of mitogen-activated protein kinases and Akt in muscle cells: possible target to ameliorate insulin resistance. Diabetes. 2006; 55(4): 942
Cong LN, Chen H, Li Y, Zhou L, McGibbon MA, Taylor SI, Quon MJ. Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells. Mol. Endocrinol. 1997; 11(13): 1881.
Yan Y, Ma L, Zhou X, Ponnusamy M, Tang J, Zhuang MA, Tolbert E, Bayliss G, Bai J, Zhuang S. Src inhibition blocks renal interstitial fibroblast activation and ameliorates renal fibrosis. Kidney Int. 2016; 89(1): 68-81.
Zheng T, Wang HY, Chen Y, Chen X, Wu ZL, Hu QY, Sun H. Src activation aggravates podocyte injury in diabetic nephropathy via suppression of FUNDC1-mediated mitophagy. Front Pharmacol. 2022; 13: 897046.
Rivero-González A, Martín-Izquierdo E, Marín-Delgado C, Rodríguez-Muñoz A, Navarro-González JF. Cytokines in diabetes and diabetic complications. Cytokine Eff. Funct. Tissues 2017; 119.
Kasprzak A. Insulin-like growth factor 1 (IGF-1) signaling in glucose metabolism in colorectal cancer. Int. J. Mol. Sci. 2021; 22(12): 6434.
K. Rehman, M.S.H. Akash. Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked?. J. Biomedical Science. 2016; 23:87
Sheng L, Bayliss G, Zhuang S. Epidermal growth factor receptor: A potential therapeutic target for diabetic kidney disease. Front. Pharmacol. 2021; 11(1): 598910
Ding X, Meng C, Dong H, Zhang S, Zhou H, Tan W, Huang L, He A, Li J, Huang J, LI W, Zou F, Zou M.C., Extracellular Hsp90α, which participates in vascular inflammation, is a novel serum predictor of atherosclerosis in type 2 diabetes. BMJ Open Diabetes Res. Care 2022; 10(1): e002579.
Cerychova R, Pavlinkova G. HIF-1α is required for the development of the sympathetic nervous system. Front. Endocrinol. (Lausanne). 2018; 116(27): 13414.
Gurzov EN, Stanley WJ, Pappas EG, Thomas HE, Gough DJ. The JAK/STAT pathway in obesity and diabetes. FEBS J. 2016; 283(16): 3002.
Bengal E, Aviram S, Hayek T. p38 MAPK in glucose metabolism of skeletal muscle: beneficial or harmful?. Int. J. Mol. Sci. 2020; 21(18): 6480.
Osawa H, Yamada K, Tabara Y, Ochi M, Onuma H, Nishida W, Shimizu I, Kawamoto R, Fujii Y, Miki T, Ohashi J, Makino H., The G/G genotype of a single nucleotide polymorphism at–1066 of c‐Jun N‐terminal kinase 1 gene (MAPK8) does not affect type 2 diabetes susceptibility despite the specific binding of AP2α. Clin. Endocrinol. (Oxf). 2008; 69(1): 36-44.
Dorotea D, Jiang S, Pak ES, Son JB, Choi HG, Ahn SM, Ha H. Pan-Src kinase inhibitor treatment attenuates diabetic kidney injury via inhibition of Fyn kinase-mediated endoplasmic reticulum stress. Exp. Mol. Med. 2022; 54(8): 1086.
Jaeschke A, Rincón M, Doran B, Reilly J, Neuberg D, Greiner DL, Shultz LD, Rossini AA, Flavell RA, Davis RJ. Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes. Proc. Natl. Acad. Sci. U. S. A. 2005; 102(19): 6931.
Zhang Y, Lin C, Chen R, Luo L, Huang J, Liu H, Chen W, Xu J, Yu H, Ding Y. Polyunsaturated fatty acid intake and incidence of type 2 diabetes in adults: a dose response meta-analysis of cohort studies. Diabetol. Metab. Syndr. 2022; 14(1): 34.
García-Pastor C, Benito-Martínez S, Moreno-Manzano V, Fernández-Martínez AB, Lucio-Cazaña FJ. Mechanism and Consequences of The Impaired Hif-1α Response to Hypoxia in Human Proximal Tubular HK-2 Cells Exposed to High Glucose. Sci. Rep. 2019; 9(1): 15868.
Gunton JE. Hypoxia-inducible factors and diabetes. J. Clin. Invest. 2020; 130(10): 5063.