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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

The Protective Role of Grape Seed in Obesity and Lipid Profile: An Updated Narrative Overview of Preclinical and Clinical Studies

Author(s): Marjan Talebi, Hadi Esmaeeli, Selen İlgün, Mohsen Talebi, Tahereh Farkhondeh, Gaurav Mishra and Saeed Samarghandian*

Volume 23, Issue 1, 2023

Published on: 13 September, 2022

Page: [46 - 62] Pages: 17

DOI: 10.2174/1871530322666220630091859

Price: $65

Abstract

Obesity and dyslipidemia are common disorders universally. According to the acquired outcomes of recent studies, dietary supplementations which have great content of phenolic compounds exert protective effects against obesity and dyslipidemia. Grape [Vitis vinifera] seeds are considered attractive sources of phenolic compounds with anti-oxidative stress and anti-inflammatory effects. There are also various experimental studies describing hepatoprotective, neuroprotective, anti-aging, cardioprotective, and anti-carcinogenic effects of polyphenols isolated from grape seed, highlighting the therapeutic and biological aspects of proanthocyanidins. The present review article first discusses pharmacological, botanical, toxicological, and phytochemical characteristics of Vitis vinifera seeds and afterward designates the protective properties which are attributed to the intake of grape seeds in obesity and hyperlipidemia. Overall valuable and updated findings of this study display that polyphenol of grape seeds has meaningful impacts on the regulation of lipid profile levels and management of obesity.

Keywords: Obesity, dyslipidemia, vitis vinifera, grape seed, proanthocyanidins, hyperlipidemia, adipocyte, natural products.

Graphical Abstract

[1]
Hruby, A.; Hu, F.B. The epidemiology of obesity: A big picture. PharmacoEconomics, 2015, 33(7), 673-689.
[http://dx.doi.org/10.1007/s40273-014-0243-x] [PMID: 25471927]
[2]
Fruh, S.M. Obesity: Risk factors, complications, and strategies for sustainable long-term weight management. J. Am. Assoc. Nurse Pract., 2017, 29(S1), S3-S14.
[http://dx.doi.org/10.1002/2327-6924.12510] [PMID: 29024553]
[3]
Nammi, S.; Koka, S.; Chinnala, K.M.; Boini, K.M. Obesity: An overview on its current perspectives and treatment options. Nutr. J., 2004, 3(1), 3.
[http://dx.doi.org/10.1186/1475-2891-3-3] [PMID: 15084221]
[4]
[5]
Talebi, M.; Talebi, M.; Farkhondeh, T.; Simal-Gandara, J.; Kopustinskiene, M.D.; Bernatoniene, J.; Pourbagher-Shahri, A.M.; Samarghandian, S. Promising protective effects of chrysin in cardiometabolic diseases. Curr. Drug Targets, 2021, 23(5), 458-470.
[PMID: 34636295]
[6]
Tripathy, J.P.; Thakur, J.S.; Jeet, G.; Chawla, S.; Jain, S.; Pal, A.; Prasad, R. Burden and risk factors of dyslipidemia-results from a STEPS survey in Punjab India. Diabetes Metab. Syndr., 2017, 11(Suppl. 1), S21-S27.
[http://dx.doi.org/10.1016/j.dsx.2016.08.015] [PMID: 27595388]
[7]
Wang, N.; Fulcher, J.; Abeysuriya, N.; Park, L.; Kumar, S.; Di Tanna, G.L.; Wilcox, I.; Keech, A.; Rodgers, A.; Lal, S. Intensive LDL cholesterol-lowering treatment beyond current recommendations for the prevention of major vascular events: A systematic review and meta-analysis of randomised trials including 327 037 participants. Lancet Diabetes Endocrinol., 2020, 8(1), 36-49.
[http://dx.doi.org/10.1016/S2213-8587(19)30388-2] [PMID: 31862150]
[8]
Samarghandian, S.; Farkhondeh, T.; Samini, F. A review on possible therapeutic effect of nigella sativa and thymoquinone in neurodegenerative diseases. CNS Neurol. Disord. Drug Targets, 2018, 17(6), 412-420.
[http://dx.doi.org/10.2174/1871527317666180702101455] [http://dx.doi.org/10.1080/14737175.2021.1923479] [PMID: 33910446]
[9]
Gupta, N.K.; Dixit, V.K. Absorption enhancement of grape seed polyphenols by complexation with phosphatidyl choline. Drug Deliv., 2011, 18(5), 312-319.
[http://dx.doi.org/10.3109/10717544.2010.544691]
[10]
Talebi, M.; Zarshenas, M.M.; Yazdani, E.; Moein, M. Preparation and evaluation of possible antioxidant activities of Rose traditional tablet”[Qurs-e-Vard]” a selected Traditional Persian Medicine [TPM] formulation via various procedures. Curr. Drug Discov. Technol., 2020, 2020
[PMID: 32990537]
[11]
Rhee, E-J.; Kim, H.C.; Kim, J.H.; Lee, E.Y.; Kim, B.J.; Kim, E.M. 2018 Guidelines for the management of dyslipidemia. Korean J. Intern. Med., 2019, 34(4), 723-771.
[12]
Samarghandian, S.; Borji, A.; Afshari, R.; Delkhosh, M.B.; Gholami, A. The effect of lead acetate on oxidative stress and antioxidant status in rat bronchoalveolar lavage fluid and lung tissue. Toxicology mechanisms and methods, 2013 Jul 1;23(6), 432-436.
[http://dx.doi.org/10.1186/s12993-022-00187-3] [PMID: 35093121]
[13]
Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; Supuran, C.T.; Banach, M.; Rollinger, J.M. Natural products in drug discovery: Advances and opportunities. Nat. Rev. Drug Discov., 2021, 20(3), 200-216.
[http://dx.doi.org/10.1038/s41573-020-00114-z] [PMID: 33510482]
[14]
Gadde, K.M.; Martin, C.K.; Berthoud, H-R.; Heymsfield, S.B. Obesity: Pathophysiology and management. J. Am. Coll. Cardiol., 2018, 71(1), 69-84.
[http://dx.doi.org/10.1016/j.jacc.2017.11.011] [PMID: 29301630]
[15]
Hardie, W.J.; O’brien, T.P.; Jaudzems, V.G. Morphology, anatomy and development of the pericarp after anthesis in grape, Vitis vinifera L. Aust. J. Grape Wine Res., 1996, 2(2), 97-142.
[http://dx.doi.org/10.1111/j.1755-0238.1996.tb00101.x]
[16]
Jiang, H-E.; Zhang, Y-B.; Li, X.; Yao, Y-F.; Ferguson, D.K.; Lü, E-G. Evidence for early viticulture in China: proof of a grapevine (Vitis vinifera L., Vitaceae) in the Yanghai Tombs, Xinjiang. J. Archaeol. Sci., 2009, 36(7), 1458-1465.
[http://dx.doi.org/10.1016/j.jas.2009.02.010]
[17]
Ma, Z-Y.; Nie, Z-L.; Ren, C.; Liu, X-Q.; Zimmer, E.A.; Wen, J. Phylogenomic relationships and character evolution of the grape family (Vitaceae). Mol. Phylogenet. Evol., 2021, 154, 106948.
[http://dx.doi.org/10.1016/j.ympev.2020.106948] [PMID: 32866616]
[18]
Reisch, B.I.; Owens, C.L.; Cousins, P.S. Grape. In: Fruit breeding; Springer, 2012; pp. 225-262.
[http://dx.doi.org/10.1007/978-1-4419-0763-9_7]
[19]
Kamrani Rad, S.Z.; Javadi, B.; Hayes, A.W.; Karim, I. G. Potential angiotensin converting enzyme (ACE) inhibitors from Iranian traditional plants described by Avicenna’s Canon of Medicine. Avicenna J. Phytomed., 2019, 9(4), 291-309.
[PMID: 31309069]
[20]
Inoue, M.; Craker, L.E. Medicinal and aromatic plants uses and functions. In: Horticulture: Plants for People and Places;; Dixon, G.; Aldous, D.Eds Springer: Dordrecht, 2014; 2, pp. 645-69.
[21]
Ahmadi, L.; El-Kubbe, A.; Roney, K.S. Potential cardio-protective effects of green grape juice: A review. Curr. Nutr. Food Sci., 2019, 15(3), 202-207.
[http://dx.doi.org/10.2174/1573401313666170905160818]
[22]
Fia, G.; Bucalossi, G.; Proserpio, C.; Vincenzi, S. Unripe grapes: An overview of the composition, traditional and innovative applications, and extraction methods of a promising waste of viticulture. Aust. J. Grape Wine Res., 2022, 28(1), 8-26.
[23]
The effects of unripe grape juice on lipid profile improvement. Cholesterol, 2012, 2012, 890262.
[24]
Badet, C. Antibacterial activity of grape (Vitis vinifera, Vitis rotundifolia) seeds.Nuts and Seeds in Health and Disease Prevention; Preedy, V.R.; Watson, R.R.; Patel, V.B., Eds.; Elsevier: Amsterdam, Netherlands, 2011, pp. 545-552.
[25]
Haseeb, S.; Alexander, B.; Santi, R.L.; Liprandi, A.S.; Baranchuk, A. What’s in wine? A clinician’s perspective. Trends Cardiovasc. Med., 2019, 29(2), 97-106.
[26]
Martin, M.E.; Grao-Cruces, E.; Millan-Linares, M.C.; Montserrat-de la Paz, S. Grape (Vitis vinifera L.) seed oil: A Functional food from the winemaking industry. Foods, 2020, 9(10), 1360.
[http://dx.doi.org/10.3390/foods9101360] [PMID: 32992712]
[27]
Altinok, E.; Kurultay, S.; Boluk, E.; Atik, D.S.; Kopuk, B.; Gunes, R. Investigation of using possibility of grape pomace in wafer sheet for wheat flour substitution. Int. J. Food Sci. Technol., 2022, 57(6), 3634-3642.
[http://dx.doi.org/10.1111/ijfs.15687]
[28]
Altınok, E.; Kurultay, S.; Konar, N.; Toker, O.S.; Kopuk, B.; Gunes, R. Utilising grape juice processing by-products as bulking and colouring agent in white chocolate. Int. J. Food Sci. Technol., 2022, 57(7), 4119-4128.
[http://dx.doi.org/10.1111/ijfs.15728]
[29]
Carullo, G.; Spizzirri, U.G.; Montopoli, M.; Cocetta, V.; Armentano, B.; Tinazzi, M. Milk kefir enriched with inulin-grafted seed extract from white wine pomace: Chemical characterisation, antioxidant profile and in vitro gastrointestinal digestion. Int. J. Food Sci. Technol., 2022, 57(7), 4086-4095.
[http://dx.doi.org/10.1111/ijfs.15724]
[30]
Tremlova, B.; Havlova, L.; Benes, P.; Zemancova, J.; Buchtova, H.; Tesikova, K. Vegetarian “Sausages” with the addition of grape flour. Appl. Sci., 2022, 12(4), 2189.
[http://dx.doi.org/10.3390/app12042189]
[31]
Devesa-Rey, R.; Vecino, X.; Varela-Alende, J.L.; Barral, M.T.; Cruz, J.M.; Moldes, A.B. Valorization of winery waste vs. the costs of not recycling. Waste Manag., 2011, 31(11), 2327-2335.
[32]
Unterkofler, J.; Muhlack, R.A.; Jeffery, D.W. Processes and purposes of extraction of grape components during winemaking: Current state and perspectives. Appl. Microbiol. Biotechnol., 2020, 104(11), 4737-4755.
[http://dx.doi.org/10.1007/s00253-020-10558-3]
[33]
Ky, I.; Lorrain, B.; Kolbas, N.; Crozier, A.; Teissedre, P.L. Wine by-products: Phenolic characterization and antioxidant activity evaluation of grapes and grape pomaces from six different French grape varieties. Molecules, 2014, 19(1), 482-506.
[http://dx.doi.org/10.3390/molecules19010482]
[34]
Rousserie, P.; Rabot, A.; Geny-Denis, L. From flavanols biosynthesis to wine tannins: What place for grape seeds? J. Agric. Food Chem., 2019, 67(5), 1325-1343.
[http://dx.doi.org/10.1021/acs.jafc.8b05768] [PMID: 30632368]
[35]
Bordiga, M.; Meudec, E.; Williams, P.; Montella, R.; Travaglia, F.; Arlorio, M.; Coïsson, J.D.; Doco, T. The impact of distillation process on the chemical composition and potential prebiotic activity of different oligosaccharidic fractions extracted from grape seeds. Food Chem., 2019, 285(285), 423-430.
[http://dx.doi.org/10.1016/j.foodchem.2019.01.175] [PMID: 30797366]
[36]
Antoniolli, A.; Fontana, A.R.; Piccoli, P.; Bottini, R. Characterization of polyphenols and evaluation of antioxidant capacity in grape pomace of the cv. Malbec. Food Chem., 2015, 178(178), 172-178.
[http://dx.doi.org/10.1016/j.foodchem.2015.01.082] [PMID: 25704698]
[37]
Guaita, M.; Bosso, A. Polyphenolic characterization of grape skins and seeds of four Italian red cultivars at harvest and after fermentative maceration. Foods, 2019, 8(9), 395.
[http://dx.doi.org/10.3390/foods8090395] [PMID: 31500205]
[38]
Gong, P.; Wang, P.; Pi, S.; Guo, Y.; Pei, S.; Yang, W.; Chang, X.; Wang, L.; Chen, F. Proanthocyanidins protect against cadmium-induced diabetic nephropathy through p38 MAPK and Keap1/Nrf2 signaling pathways. Front. Pharmacol., 2022, 12, 801048.
[http://dx.doi.org/10.3389/fphar.2021.801048] [PMID: 35046823]
[39]
Qian, Y.; Sun, Y.; Chen, Y.; Mao, Z.; Shi, Y.; Wu, D.; Gu, B.; Liu, Z.; Zhang, Q. Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma. Pharm. Biol., 2022, 60(1), 347-358.
[http://dx.doi.org/10.1080/13880209.2022.2032205] [PMID: 35171066]
[40]
Magrone, T.; Jirillo, E.; Magrone, M.; Russo, M.A.; Romita, P.; Massari, F.; Foti, C. Red grape polyphenol oral administration improves immune response in women affected by nickel-mediated allergic contact dermatitis. Endocr. Metab. Immune Disord. Drug Targets, 2021, 21(2), 374-384.
[http://dx.doi.org/10.2174/1871530320666200313152648] [PMID: 32167433]
[41]
Sheng, K.; Yang, J.; Xu, Y.; Kong, X.; Wang, J.; Wang, Y. Alleviation effects of grape seed proanthocyanidin extract on inflammation and oxidative stress in a D-galactose-induced aging mouse model by modulating the gut microbiota. Food Funct., 2022, 13(3), 1348-1359.
[http://dx.doi.org/10.1039/D1FO03396D] [PMID: 35043135]
[42]
Wu, Y.; Mo, R.; Zhang, M.; Zhou, W.; Li, D. Grape seed proanthocyanidin alleviates intestinal inflammation through gut microbiota-bile acid crosstalk in mice. Front. Nutr., 2022, 8, 786682.
[http://dx.doi.org/10.3389/fnut.2021.786682] [PMID: 35155513]
[43]
Chen, J.; Chen, Y.; Zheng, Y.; Zhao, J.; Yu, H.; Zhu, J. Relationship between neuroprotective effects and structure of procyanidins. Molecules, 2022, 27(7), 2308.
[http://dx.doi.org/10.3390/molecules27072308] [PMID: 35408708]
[44]
Mahdipour, R.; Ebrahimzadeh-Bideskan, A.; Hosseini, M.; Shahba, S.; Lombardi, G.; Malvandi, A.M.; Mohammadipour, A. The benefits of grape seed extract in neurological disorders and brain aging. Nutr. Neurosci., 2022, 1-15.
[http://dx.doi.org/10.1080/1028415X.2022.2051954] [PMID: 35343876]
[45]
Tao, K.; Guo, L.; Hu, X.; Fitzgerald, C.; Rouzard, K.; Healy, J. Encapsulated activated grape seed extract: A novel formulation with anti-aging, skin-brightening, and hydration properties. Cosmetics, 2022, 9(1), 4.
[http://dx.doi.org/10.3390/cosmetics9010004]
[46]
Li, C.; Zhang, L.; Liu, C.; He, X.; Chen, M.; Chen, J. Lipophilic grape seed proanthocyanidin exerts anti-cervical cancer effects in HeLa Cells and a HeLa-derived xenograft zebrafish model. Antioxidants, 2022, 11(2), 422.
[http://dx.doi.org/10.3390/antiox11020422] [PMID: 35204304]
[47]
Sun, T.; Chen, Q.Y.; Wu, L.J.; Yao, X.M.; Sun, X.J. Antitumor and antimetastatic activities of grape skin polyphenols in a murine model of breast cancer. Food Chem. Toxicol., 2012, 50(10), 3462-3467.
[http://dx.doi.org/10.1016/j.fct.2012.07.037]
[48]
Zheng, W.; Feng, Y.; Bai, Y.; Feng, Z.; Yang, X.; Dang, B. Proanthocyanidins extracted from grape seeds inhibit the growth of hepatocellular carcinoma cells and induce apoptosis through the MAPK/AKT pathway. Food Biosci., 2022, 45, 101337.
[http://dx.doi.org/10.1016/j.fbio.2021.101337]
[49]
Xagoraris, M.; Oikonomou, I.; Daferera, D.; Kanakis, C.; Lappa, I.K.; Giotis, C. Quality evaluation of winery by-products from ionian islands grape varieties in the concept of circular bioeconomy. Sustainability, 2021, 13(10), 5454.
[http://dx.doi.org/10.3390/su13105454]
[50]
Rodríguez-Pérez. C; García-Villanova, B; Guerra-Hernández, E; Verardo, V. Grape seeds proanthocyanidins: An overview of in vivo bioactivity in animal models. Nutrients, 2019, 11(10), 2435.
[51]
Gabetta, B.; Fuzzati, N.; Griffini, A.; Lolla, E.; Pace, R.; Ruffilli, T.; Peterlongo, F. Characterization of proanthocyanidins from grape seeds. Fitoterapia, 2000, 71(2), 162-175.
[http://dx.doi.org/10.1016/S0367-326X(99)00161-6] [PMID: 10727813]
[52]
Monagas, M. Gómez-Cordovés, C.; Bartolomé, B.; Laureano, O.; Ricardo da Silva, J.M. Monomeric, oligomeric, and polymeric flavan-3-ol composition of wines and grapes from Vitis vinifera L. Cv. Graciano, Tempranillo, and Cabernet Sauvignon. J. Agric. Food Chem., 2003, 51(22), 6475-6481.
[53]
Wang, E.H.; Yu, Z.L.; Bu, Y.J.; Xu, P.W.; Xi, J.Y.; Liang, H.Y. Grape seed proanthocyanidin extract alleviates high-fat diet induced testicular toxicity in rats. RSC Advances, 2019, 9(21), 11842-11850.
[http://dx.doi.org/10.1039/C9RA01017C] [PMID: 35517006]
[54]
Blackford, C.L.; Trengove, R.D.; Boss, P.K. Exploring the influence of grape tissues on the concentration of wine volatile compounds. Aust. J. Grape Wine Res., 2022, 28(2), 218-231.
[http://dx.doi.org/10.1111/ajgw.12524]
[55]
Gourineni, V.; Shay, N.F.; Chung, S.; Sandhu, A.K.; Gu, L. Muscadine grape (Vitis rotundifolia) and wine phytochemicals prevented obesity-associated metabolic complications in C57BL/6J mice. J. Agric. Food Chem., 2012, 60(31), 7674-7681.
[http://dx.doi.org/10.1021/jf3013663] [PMID: 22788667]
[56]
Samarghandian, S; Borji, A; Hidar Tabasi, S. Effects of Cichorium intybus linn on blood glucose, lipid constituents and selected oxidative stress parameters in streptozotocin-induced diabetic rats. Cardiovas. Haematologic. Disorders-Drug Targets (Formerly Current Drug Targets Cardiovascular & Hematological Disorders)., 2013, 13(3), 231-236.
[57]
Ono, M.; Yamamoto, M.; Masuoka, C.; Ito, Y.; Yamashita, M.; Nohara, T. Diterpenes from the fruits of Vitex rotundifolia. J. Nat. Prod., 1999, 62(11), 1532-1537.
[http://dx.doi.org/10.1021/np990204x] [PMID: 10579867]
[58]
Sandhu, A.K.; Gu, L. Antioxidant capacity, phenolic content, and profiling of phenolic compounds in the seeds, skin, and pulp of Vitis rotundifolia (Muscadine Grapes) As determined by HPLC-DAD-ESI-MS(n). J. Agric. Food Chem., 2010, 58(8), 4681-4692.
[http://dx.doi.org/10.1021/jf904211q] [PMID: 20334341]
[59]
Amico, V.; Barresi, V.; Chillemi, R.; Condorelli, D.F.; Sciuto, S.; Spatafora, C. Bioassay-guided isolation of antiproliferative compounds from grape (Vitis vinifera) stems. Nat. Prod. Commun., 2009, 4(1), 27-34.
[60]
Chiou, A.; Panagopoulou, E.A.; Gatzali, F.; De Marchi, S.; Karathanos, V.T. Anthocyanins content and antioxidant capacity of Corinthian currants (Vitis vinifera L., var. Apyrena). Food Chem., 2014, 146, 157-165.
[http://dx.doi.org/10.1016/j.foodchem.2013.09.062] [PMID: 24176327]
[61]
Nassiri-Asl, M.; Hosseinzadeh, H. Review of the pharmacological effects of Vitis vinifera (Grape) and its bioactive constituents: An update. Phytother. Res., 2016, 30(9), 1392-1403.
[http://dx.doi.org/10.1002/ptr.5644] [PMID: 27196869]
[62]
Gibis, M.; Ruedt, C.; Weiss, J. In vitro release of grape-seed polyphenols encapsulated from uncoated and chitosan-coated liposomes. Food Res. Int., 2016, 88(Pt A), 105-113.
[http://dx.doi.org/10.1016/j.foodres.2016.02.010] [PMID: 28847389]
[63]
Castellani, S.; Trapani, A.; Spagnoletta, A.; di Toma, L.; Magrone, T.; Di Gioia, S.; Mandracchia, D.; Trapani, G.; Jirillo, E.; Conese, M. Nanoparticle delivery of grape seed-derived proanthocyanidins to airway epithelial cells dampens oxidative stress and inflammation. J. Transl. Med., 2018, 16(1), 140.
[http://dx.doi.org/10.1186/s12967-018-1509-4] [PMID: 29792199]
[64]
Unusan, N. Proanthocyanidins in grape seeds: An updated review of their health benefits and potential uses in the food industry. J. Funct. Foods, 2020, 67, 103861.
[http://dx.doi.org/10.1016/j.jff.2020.103861]
[65]
Akaberi, M.; Hosseinzadeh, H. Grapes (Vitis vinifera) as a potential candidate for the therapy of the metabolic syndrome. Phytother. Res., 2016, 30(4), 540-556.
[66]
Escobar-Martínez. I.; Arreaza-Gil, V.; Muguerza, B.; Arola-Arnal, A.; Bravo, F.I.; Torres-Fuentes, C.; Suárez, M. Administration time significantly affects plasma bioavailability of grape seed proanthocyanidins extract in healthy and obese fischer 344 Rats. Mol. Nutr. Food Res., 2022, 66(3), e2100552.
[http://dx.doi.org/10.1002/mnfr.202100552] [PMID: 34851030]
[67]
Stein, J.H.; McBride, P.E. Should advanced lipoprotein testing be used in clinical practice? Nat. Clin. Pract. Cardiovasc. Med., 2006, 3(12), 640-641.
[http://dx.doi.org/10.1038/ncpcardio0719] [PMID: 17122792]
[68]
Pollex, R.L.; Hegele, R.A. Genetic determinants of the metabolic syndrome. Nat. Clin. Pract. Cardiovasc. Med., 2006, 3(9), 482-489.
[http://dx.doi.org/10.1038/ncpcardio0638] [PMID: 16932765]
[69]
Yao, Y.S.; Li, T.D.; Zeng, Z.H. Mechanisms underlying direct actions of hyperlipidemia on myocardium: An updated review. Lipids Health Dis., 2020, 19(1), 23.
[http://dx.doi.org/10.1186/s12944-019-1171-8] [PMID: 32035485]
[70]
Roshanravan, B.; Yousefizadeh, S.; Apaydin Yildirim, B.; Farkhondeh, T.; Amirabadizadeh, A.; Ashrafizadeh, M.; Talebi, M.; Samarghandian, S. The effects of Berberis vulgaris L. and Berberis aristata L. in metabolic syndrome patients: A systematic and meta-analysis study. Arch. Physiol. Biochem., 2020, 1-12.
[http://dx.doi.org/10.1080/13813455.2020.1828482] [PMID: 33040642]
[71]
Brautbar, A.; Ballantyne, C.M. Pharmacological strategies for lowering LDL cholesterol: Statins and beyond. Nat. Rev. Cardiol., 2011, 8(5), 253-265.
[http://dx.doi.org/10.1038/nrcardio.2011.2] [PMID: 21321561]
[72]
Last, A.R.; Ference, J.D.; Falleroni, J. Pharmacologic treatment of hyperlipidemia. Am. Fam. Physician, 2011, 84(5), 551-558.
[73]
Mach, F.; Baigent, C.; Catapano, A.L.; Koskinas, K.C.; Casula, M.; Badimon, L.; Chapman, M.J.; De Backer, G.G.; Delgado, V.; Ference, B.A.; Graham, I.M.; Halliday, A.; Landmesser, U.; Mihaylova, B.; Pedersen, T.R.; Riccardi, G.; Richter, D.J.; Sabatine, M.S.; Taskinen, M.R.; Tokgozoglu, L.; Wiklund, O. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur. Heart J., 2020, 41(1), 111-188.
[http://dx.doi.org/10.1093/eurheartj/ehz455] [PMID: 31504418]
[74]
Bahmani, M.; Mirhoseini, M.; Shirzad, H.; Sedighi, M.; Shahinfard, N.; Rafieian-Kopaei, M. A review on promising natural agents effective on hyperlipidemia. J. Evid. Based Complementary Altern. Med., 2015, 20(3), 228-238.
[http://dx.doi.org/10.1177/2156587214568457] [PMID: 25633423]
[75]
Rouhi-Boroujeni, H.; Rouhi-Boroujeni, H.; Heidarian, E.; Mohammadizadeh, F.; Rafieian-Kopaei, M. Herbs with anti-lipid effects and their interactions with statins as a chemical anti- hyperlipidemia group drugs: A systematic review. ARYA Atheroscler., 2015, 11(4), 244-251.
[PMID: 26478732]
[76]
Cicero, A.F.G.; Fogacci, F.; Stoian, A.P.; Vrablik, M.; Al Rasadi, K.; Banach, M. Nutraceuticals in the management of dyslipidemia: Which, when, and for whom? could nutraceuticals help low-risk individuals with non-optimal lipid levels? Curr. Atheroscler. Rep., 2021, 23(10), 57.
[77]
Ji, X.; Shi, S.; Liu, B.; Shan, M.; Tang, D.; Zhang, W.; Zhang, Y.; Zhang, L.; Zhang, H.; Lu, C.; Wang, Y. Bioactive compounds from herbal medicines to manage dyslipidemia. Biomed. Pharmacother., 2019, 118, 109338.
[http://dx.doi.org/10.1016/j.biopha.2019.109338] [PMID: 31545238]
[78]
Wall-Medrano, A.; de la Rosa, L.A. Vázquez-Flores, A.A.; Mercado-Mercado, G.; González-Arellanes, R.; López-Díaz, J.A.; González-Córdova, A.F.; González-Aguilar, G.A.; Vallejo-Cordoba, B.; Molina-Corral, F.J. Lipidomic and antioxidant response to grape seed, corn and coconut oils in healthy wistar rats. Nutrients, 2017, 9(1), E82.
[http://dx.doi.org/10.3390/nu9010082] [PMID: 28117688]
[79]
Thiruchenduran, M.; Vijayan, N.A.; Sawaminathan, J.K.; Devaraj, S.N. Protective effect of grape seed proanthocyanidins against cholesterol cholic acid diet-induced hypercholesterolemia in rats. Cardiovasc. Pathol., 2011, 20(6), 361-368.
[http://dx.doi.org/10.1016/j.carpath.2010.09.002]
[80]
Yin, M.; Zhang, P.; Yu, F.; Zhang, Z.; Cai, Q.; Lu, W. Grape seed procyanidin B2 ameliorates hepatic lipid metabolism disorders in db/db mice. Mol. Med. Rep., 2017, 16(3), 2844-2850.
[81]
Samarghandian, S.; Azimi-Nezhad, M.; Mehrad-Majd, H.; Mirhafez, S.R. Thymoquinone ameliorates acute renal failure in gentamicin-treated adult male rats. Pharmacology, 2015, 96(3-4), 112-117.
[http://dx.doi.org/10.3390/molecules25215218] [PMID: 33182462]
[82]
Upadhyay, J.; Farr, O.; Perakakis, N.; Ghaly, W.; Mantzoros, C. Obesity as a disease. Med. Clin. North Am., 2018, 102(1), 13-33.
[http://dx.doi.org/10.1016/j.mcna.2017.08.004] [PMID: 29156181]
[83]
Vogels, N.; Nijs, I.M.T.; Westerterp-Plantenga, M.S. The effect of grape-seed extract on 24 h energy intake in humans. Eur. J. Clin. Nutr., 2004, 58(4), 667-673.
[http://dx.doi.org/10.1038/sj.ejcn.1601863] [PMID: 15042136]
[84]
Stuby, J.; Gravestock, I.; Wolfram, E.; Pichierri, G.; Steurer, J.; Burgstaller, J.M. Appetite-suppressing and satiety-increasing bioactive phytochemicals: A systematic review. Nutrients, 2019, 11(9), E2238.
[http://dx.doi.org/10.3390/nu11092238] [PMID: 31533291]
[85]
Neeland, I.J.; Ross, R.; Després, J-P.; Matsuzawa, Y.; Yamashita, S.; Shai, I.; Seidell, J.; Magni, P.; Santos, R.D.; Arsenault, B.; Cuevas, A.; Hu, F.B.; Griffin, B.; Zambon, A.; Barter, P.; Fruchart, J.C.; Eckel, R.H. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: A position statement. Lancet Diabetes Endocrinol., 2019, 7(9), 715-725.
[http://dx.doi.org/10.1016/S2213-8587(19)30084-1] [PMID: 31301983]
[86]
Farkhondeh, T.; Amirabadizadeh, A.; Aramjoo, H.; Llorens, S.; Roshanravan, B.; Saeedi, F.; Talebi, M.; Shakibaei, M.; Samarghandian, S. Impact of metformin on cancer biomarkers in non-diabetic cancer patients: A systematic review and meta-analysis of clinical trials. Curr. Oncol., 2021, 28(2), 1412-1423.
[http://dx.doi.org/10.3390/curroncol28020134] [PMID: 33917520]
[87]
Heymsfield, S.B.; Wadden, T.A. Mechanisms, pathophysiology, and management of obesity. N. Engl. J. Med., 2017, 376(3), 254-266.
[http://dx.doi.org/10.1056/NEJMra1514009] [PMID: 28099824]
[88]
Talebi, M. Farkhondeh, T.; Mishra, G.; İlgün, S.; Samarghandian, S. New insights into the role of the Nrf2 signaling pathway in green tea catechin applications. Phytother. Res., 2021, 35(6), 3078-3112.
[http://dx.doi.org/10.1002/ptr.7033]
[89]
Singh, M.; Thrimawithana, T.; Shukla, R.; Adhikari, B. Managing obesity through natural polyphenols: A review. Futur Foods, 2020, 1–2, 100002.
[http://dx.doi.org/10.1016/j.fufo.2020.100002]
[90]
Cardel, M.I.; Jastreboff, A.M.; Kelly, A.S. Treatment of adolescent obesity in 2020. JAMA, 2019, 322(17), 1707-1708.
[http://dx.doi.org/10.1001/jama.2019.14725] [PMID: 31566652]
[91]
Stefan, N. Causes, consequences, and treatment of metabolically unhealthy fat distribution. Lancet Diabetes Endocrinol., 2020, 8(7), 616-627.
[http://dx.doi.org/10.1016/S2213-8587(20)30110-8] [PMID: 32559477]
[92]
Toubal, A.; Treuter, E.; Clément, K.; Venteclef, N. Genomic and epigenomic regulation of adipose tissue inflammation in obesity. Trends Endocrinol. Metab., 2013, 24(12), 625-634.
[http://dx.doi.org/10.1016/j.tem.2013.09.006] [PMID: 24169451]
[93]
Wijayatunga, N.N.; Dhurandhar, E.J. Normal weight obesity and unaddressed cardiometabolic health risk-a narrative review. Int. J. Obes., 2021, 45(10), 2141-2155.
[94]
Abdel-Kawi, S.H.; Hashem, K.S.; Abd-Allah, S. Mechanism of diethylhexylphthalate (DEHP) induced testicular damage and of grape seed extract-induced protection in the rat. Food Chem. Toxicol., 2016, 90, 64-75.
[http://dx.doi.org/10.1016/j.fct.2016.02.003] [PMID: 26854921]
[95]
Pourbagher-Shahri, A.M.; Farkhondeh, T.; Talebi, M.; Kopustinskiene, D.M.; Samarghandian, S.; Bernatoniene, J. An overview of NO signaling pathways in aging. Molecules, 2021, 26(15), 4533.
[http://dx.doi.org/10.3390/molecules26154533] [PMID: 34361685]
[96]
Talebi, M.; Talebi, M.; Kakouri, E.; Farkhondeh, T.; Pourbagher-Shahri, A.M.; Tarantilis, P.A.; Samarghandian, S. Tantalizing role of p53 molecular pathways and its coherent medications in neurodegenerative diseases. Int. J. Biol. Macromol., 2021, 172, 93-103.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.01.042] [PMID: 33440210]
[97]
Coppack, S.W. Pro-inflammatory cytokines and adipose tissue. Proc. Nutr. Soc., 2001, 60(3), 349-356.
[http://dx.doi.org/10.1079/PNS2001110] [PMID: 11681809]
[98]
Smith, C.C.T.; Mocanu, M.M.; Davidson, S.M.; Wynne, A.M.; Simpkin, J.C.; Yellon, D.M. Leptin, the obesity-associated hormone, exhibits direct cardioprotective effects. Br. J. Pharmacol., 2006, 149(1), 5-13.
[http://dx.doi.org/10.1038/sj.bjp.0706834] [PMID: 16847434]
[99]
Boccellino, M.; D’Angelo, S. Anti-obesity effects of polyphenol intake: Current status and future possibilities. Int. J. Mol. Sci., 2020, 21(16), 5642.
[http://dx.doi.org/10.3390/ijms21165642] [PMID: 32781724]
[100]
Llaha, F.; Zamora-Ros, R. The effects of polyphenol supplementation in addition to calorie restricted diets and/or physical activity on body composition parameters: A systematic review of randomized trials. Front. Nutr., 2020, 7(84), 84.
[http://dx.doi.org/10.3389/fnut.2020.00084] [PMID: 32582757]
[101]
Sun, N-N.; Wu, T-Y.; Chau, C-F. Natural dietary and herbal products in anti-obesity treatment. Molecules, 2016, 21(10), 1351.
[http://dx.doi.org/10.3390/molecules21101351] [PMID: 27727194]
[102]
Konstantinidi, M.; Koutelidakis, A.E. Functional foods and bioactive compounds: A review of its possible role on weight management and obesity’s metabolic consequences. Medicines (Basel), 2019, 6(3), 94.
[http://dx.doi.org/10.3390/medicines6030094] [PMID: 31505825]
[103]
Karri, S.; Sharma, S.; Hatware, K.; Patil, K. Natural anti-obesity agents and their therapeutic role in management of obesity: A future trend perspective. Biomed. Pharmacother., 2019, 110, 224-238.
[http://dx.doi.org/10.1016/j.biopha.2018.11.076] [PMID: 30481727]
[104]
Firouzi, S.; Malekahmadi, M.; Ghayour-Mobarhan, M.; Ferns, G.; Rahimi, H.R. Barberry in the treatment of obesity and metabolic syndrome: Possible mechanisms of action. Diabetes Metab. Syndr. Obes., 2018, 11, 699-705.
[http://dx.doi.org/10.2147/DMSO.S181572] [PMID: 30519065]
[105]
Nijhawan, P.; Behl, T. Nutraceuticals in the management of obesity. Obes. Med., 2020, 17, 100168.
[http://dx.doi.org/10.1016/j.obmed.2019.100168]
[106]
Venkatakrishnan, K.; Chiu, H-F.; Wang, C-K. Extensive review of popular functional foods and nutraceuticals against obesity and its related complications with a special focus on randomized clinical trials. Food Funct., 2019, 10(5), 2313-2329.
[http://dx.doi.org/10.1039/C9FO00293F] [PMID: 31041963]
[107]
Sharifi-Rad, J.; Rodrigues, C.F.; Sharopov, F.; Docea, A.O.; Can Karaca, A.; Sharifi-Rad, M. Kahveci Karıncaoglu, D.; Gülseren, G.; Şenol, E.; Demircan, E.; Taheri, Y.; Suleria, H.A.R.; Özçelik, B.; Nur Kasapoğlu, K.; Gültekin-Özgüven, M.; Daşkaya-Dikmen, C.; Cho, W.C.; Martins, N.; Calina, D. Diet, lifestyle and cardiovascular diseases: Linking pathophysiology to cardioprotective effects of natural bioactive compounds. Int. J. Environ. Res. Public Health, 2020, 17(7), E2326.
[http://dx.doi.org/10.3390/ijerph17072326] [PMID: 32235611]
[108]
Schini-Kerth, V.B. Étienne-Selloum, N.; Chataigneau, T.; Auger, C. Vascular protection by natural product-derived polyphenols: In vitro and in vivo evidence. Planta Med., 2011, 77(11), 1161-1167.
[http://dx.doi.org/10.1055/s-0030-1250737] [PMID: 21267812]
[109]
Aragonès, G.; Ardid-Ruiz, A.; Ibars, M. Suárez, M.; Bladé, C. Modulation of leptin resistance by food compounds. Mol. Nutr. Food Res., 2016, 60(8), 1789-1803.
[http://dx.doi.org/10.1002/mnfr.201500964] [PMID: 26842874]
[110]
Ardid-Ruiz, A.; Harazin, A.; Barna, L.; Walter, F.R.; Bladé, C. Suárez, M.; Deli, M.A.; Aragonès, G. The effects of Vitis vinifera L. phenolic compounds on a blood-brain barrier culture model: Expression of leptin receptors and protection against cytokine-induced damage. J. Ethnopharmacol., 2020, 247, 112253.
[http://dx.doi.org/10.1016/j.jep.2019.112253] [PMID: 31562952]
[111]
Campos-Bedolla, P.; Walter, F.R.; Veszelka, S.; Deli, M.A. Role of the blood-brain barrier in the nutrition of the central nervous system. Arch. Med. Res., 2014, 45(8), 610-638.
[http://dx.doi.org/10.1016/j.arcmed.2014.11.018] [PMID: 25481827]
[112]
da Costa, G.F.; Santos, I.B.; de Bem, G.F.; Cordeiro, V.S.C.; da Costa, C.A.; de Carvalho, L.C.R.M.; Ognibene, D.T.; Resende, A.C.; de Moura, R.S. The beneficial effect of anthocyanidin‐rich Vitis vinifera L. grape skin extract on metabolic changes induced by high‐fat diet in mice involves antiinflammatory and antioxidant actions. Phytother. Res., 2017, 31(10), 1621-1632.
[http://dx.doi.org/10.1002/ptr.5898] [PMID: 28840618]
[113]
Pourbagher-Shahri, A.M.; Farkhondeh, T.; Ashrafizadeh, M.; Talebi, M.; Samargahndian, S. Curcumin and cardiovascular diseases: Focus on cellular targets and cascades. Biomed. Pharmacother., 2021, 136, 111214.
[http://dx.doi.org/10.1016/j.biopha.2020.111214] [PMID: 33450488]
[114]
Shulman, G.I. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N. Engl. J. Med., 2014, 371(12), 1131-1141.
[http://dx.doi.org/10.1056/NEJMra1011035] [PMID: 25229917]
[115]
Mahanna, M.; Millan-Linares, M.C.; Grao-Cruces, E.; Claro, C.; Toscano, R.; Rodriguez-Martin, N.M. Resveratrol-enriched grape seed oil (Vitis vinifera L.) protects from white fat dysfunction in obese mice. J. Funct. Foods, 2019, 62, 103546.
[http://dx.doi.org/10.1016/j.jff.2019.103546]
[116]
Serrano, J. Casanova-Martí, À.; Gil-Cardoso, K.; Blay, M.T.; Terra, X.; Pinent, M.; Ardévol, A. Acutely administered grape-seed proanthocyanidin extract acts as a satiating agent. Food Funct., 2016, 7(1), 483-490.
[http://dx.doi.org/10.1039/C5FO00892A] [PMID: 26514231]
[117]
Downing, L.E.; Edgar, D.; Ellison, P.A.; Ricketts, M.L. Mechanistic insight into nuclear receptor-mediated regulation of bile acid metabolism and lipid homeostasis by grape seed procyanidin extract (GSPE). Cell Biochem. Funct., 2017, 35(1), 12-32.
[http://dx.doi.org/10.1002/cbf.3247] [PMID: 28083965]
[118]
Pajuelo, D. Díaz, S.; Quesada, H.; Fernández-Iglesias, A.; Mulero, M.; Arola-Arnal, A.; Salvadó, M.J.; Bladé, C.; Arola, L. Acute administration of grape seed proanthocyanidin extract modulates energetic metabolism in skeletal muscle and BAT mitochondria. J. Agric. Food Chem., 2011, 59(8), 4279-4287.
[http://dx.doi.org/10.1021/jf200322x] [PMID: 21401106]
[119]
Caimari, A. Mariné-Casadó, R.; Boqué, N.; Crescenti, A.; Arola, L.; Del Bas, J.M. Maternal intake of grape seed procyanidins during lactation induces insulin resistance and an adiponectin resistance-like phenotype in rat offspring. Sci. Rep., 2017, 7(1), 12573.
[http://dx.doi.org/10.1038/s41598-017-12597-9] [PMID: 28974704]
[120]
Yazıcı D.; Sezer, H. Insulin resistance, obesity and lipotoxicity. Adv. Exp. Med. Biol., 2017, 960, 277-304.
[http://dx.doi.org/10.1007/978-3-319-48382-5_12] [PMID: 28585204]
[121]
Crescenti, A.; del Bas, J.M.; Arola-Arnal, A.; Oms-Oliu, G.; Arola, L.; Caimari, A. Grape seed procyanidins administered at physiological doses to rats during pregnancy and lactation promote lipid oxidation and up-regulate AMPK in the muscle of male offspring in adulthood. J. Nutr. Biochem., 2015, 26(9), 912-920.
[http://dx.doi.org/10.1016/j.jnutbio.2015.03.003] [PMID: 26007288]
[122]
Baselga-Escudero, L.; Pascual-Serrano, A.; Ribas-Latre, A.; Casanova, E. Salvadó, M.J.; Arola, L.; Arola-Arnal, A.; Bladé, C. Long-term supplementation with a low dose of proanthocyanidins normalized liver miR-33a and miR-122 levels in high-fat diet-induced obese rats. Nutr. Res., 2015, 35(4), 337-345.
[http://dx.doi.org/10.1016/j.nutres.2015.02.008] [PMID: 25769350]
[123]
Wei, S.; Zheng, Y.; Zhang, M.; Zheng, H.; Yan, P. Grape seed procyanidin extract inhibits adipogenesis and stimulates lipolysis of porcine adipocytes in vitro. J. Anim. Sci., 2018, 96(7), 2753-2762.
[http://dx.doi.org/10.1093/jas/sky158] [PMID: 29701782]
[124]
Nagpal, R.; Newman, T.M.; Wang, S.; Jain, S.; Lovato, J.F.; Yadav, H. Obesity-linked gut microbiome dysbiosis associated with derangements in gut permeability and intestinal cellular homeostasis independent of diet. J. Diabetes Res., 2018, 2018, 3462092.
[http://dx.doi.org/10.1155/2018/3462092] [PMID: 30250849]
[125]
Hernández-García. J.; Navas-Carrillo, D.; Orenes-Piñero, E. Alterations of circadian rhythms and their impact on obesity, metabolic syndrome and cardiovascular diseases. Crit. Rev. Food Sci. Nutr., 2020, 60(6), 1038-1047.
[http://dx.doi.org/10.1080/10408398.2018.1556579] [PMID: 30633544]
[126]
Meyhöfer, S.; Wilms, B.; Oster, H.; Schmid, S.M. Importance of sleep and circadian rhythm for energy metabolism. Internist (Berl.), 2019, 60(2), 122-127.
[PMID: 30645664]
[127]
Vinson, J.A.; Mandarano, M.A.; Shuta, D.L.; Bagchi, M.; Bagchi, D. Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model. Mol. Cell. Biochem., 2002, 240(1-2), 99-103.
[http://dx.doi.org/10.1023/A:1020611925819] [PMID: 12487376]
[128]
Del Bas, J.M. Fernández-Larrea, J.; Blay, M.; Ardèvol, A.; Salvadó, M.J.; Arola, L.; Bladé, C. Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats. FASEB J., 2005, 19(3), 479-481.
[http://dx.doi.org/10.1096/fj.04-3095fje] [PMID: 15637110]
[129]
Park, S.H.; Park, T.S.; Cha, Y.S. Grape seed extract (Vitis vinifera) partially reverses high fat diet-induced obesity in C57BL/6J mice. Nutr. Res. Pract., 2008, 2(4), 227-233.
[http://dx.doi.org/10.4162/nrp.2008.2.4.227] [PMID: 20016723]
[130]
Terra, X.; Montagut, G.; Bustos, M.; Llopiz, N.; Ardèvol, A.; Bladé, C. Fernández-Larrea, J.; Pujadas, G.; Salvadó, J.; Arola, L.; Blay, M. Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J. Nutr. Biochem., 2009, 20(3), 210-218.
[http://dx.doi.org/10.1016/j.jnutbio.2008.02.005] [PMID: 18602813]
[131]
Quesada, H.; del Bas, J.M.; Pajuelo, D. Díaz, S.; Fernandez-Larrea, J.; Pinent, M.; Arola, L.; Salvadó, M.J.; Bladé, C. Grape seed proanthocyanidins correct dyslipidemia associated with a high-fat diet in rats and repress genes controlling lipogenesis and VLDL assembling in liver. Int. J. Obes., 2009, 33(9), 1007-1012.
[http://dx.doi.org/10.1038/ijo.2009.136] [PMID: 19581912]
[132]
Terra, X.; Pallarés, V.; Ardèvol, A.; Bladé, C. Fernández-Larrea, J.; Pujadas, G.; Salvadó, J.; Arola, L.; Blay, M. Modulatory effect of grape-seed procyanidins on local and systemic inflammation in diet-induced obesity rats. J. Nutr. Biochem., 2011, 22(4), 380-387.
[http://dx.doi.org/10.1016/j.jnutbio.2010.03.006] [PMID: 20655715]
[133]
Asadi, F.; Shahriari, A.; Chahardah-Cheric, M. Effect of long-term optional ingestion of canola oil, grape seed oil, corn oil and yogurt butter on serum, muscle and liver cholesterol status in rats. Food Chem. Toxicol., 2010, 48(8-9), 2454-2457.
[http://dx.doi.org/10.1016/j.fct.2010.06.012] [PMID: 20542074]
[134]
Charradi, K.; Sebai, H.; Elkahoui, S.; Ben Hassine, F.; Limam, F.; Aouani, E. Grape seed extract alleviates high-fat diet-induced obesity and heart dysfunction by preventing cardiac siderosis. Cardiovasc. Toxicol., 2011, 11(1), 28-37.
[http://dx.doi.org/10.1007/s12012-010-9101-z] [PMID: 21234706]
[135]
Goodrich, K.M.; Fundaro, G.; Griffin, L.E.; Grant, A.; Hulver, M.W.; Ponder, M.A.; Neilson, A.P. Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: A secondary analysis of healthy Wistar Furth rats. Nutr. Res., 2012, 32(10), 787-794.
[http://dx.doi.org/10.1016/j.nutres.2012.09.004] [PMID: 23146776]
[136]
Fernández-Iglesias. A.; Pajuelo, D.; Quesada, H.; Díaz, S.; Bladé, C.; Arola, L.; Salvadó, M.J.; Mulero, M. Grape seed proanthocyanidin extract improves the hepatic glutathione metabolism in obese Zucker rats. Mol. Nutr. Food Res., 2014, 58(4), 727-737.
[http://dx.doi.org/10.1002/mnfr.201300455] [PMID: 24338985]
[137]
Jhun, J.Y.; Moon, S.J.; Yoon, B.Y.; Byun, J.K.; Kim, E.K.; Yang, E.J.; Ju, J.H.; Hong, Y.S.; Min, J.K.; Park, S.H.; Kim, H.Y.; Cho, M.L. Grape seed proanthocyanidin extract-mediated regulation of STAT3 proteins contributes to Treg differentiation and attenuates inflammation in a murine model of obesity-associated arthritis. PLoS One, 2013, 8(11), e78843.
[http://dx.doi.org/10.1371/journal.pone.0078843] [PMID: 24223854]
[138]
Satyam, S.M.; Bairy, L.K.; Pirasanthan, R. Influence of grape seed extract and zinc containing multivitamin-mineral nutritional food supplement on lipid profile in normal and diet-induced hypercholesterolemic rats. J. Clin. Diagn. Res., 2014, 8(12), HC12-HC15.
[http://dx.doi.org/10.7860/JCDR/2014/10095.5282] [PMID: 25653967]
[139]
Kim, H.; Bartley, G.E.; Arvik, T.; Lipson, R.; Nah, S.Y.; Seo, K.; Yokoyama, W. Dietary supplementation of chardonnay grape seed flour reduces plasma cholesterol concentration, hepatic steatosis, and abdominal fat content in high-fat diet-induced obese hamsters. J. Agric. Food Chem., 2014, 62(8), 1919-1925.
[http://dx.doi.org/10.1021/jf404832s] [PMID: 24517872]
[140]
Javadi, S.; Eftekhari, A.; Farshid, A.A. The effects of grape seed oil on histopathological changes of the pancreas, liver and plasma lipids in streptozotocin induced diabetic rats. Majallah-i Pizishki-i Urumiyyah, 2014, 25(7), 605-615.
[141]
Madi Almajwal, A.; Farouk Elsadek, M. Lipid-lowering and hepatoprotective effects of Vitis vinifera dried seeds on paracetamol-induced hepatotoxicity in rats. Nutr. Res. Pract., 2015, 9(1), 37-42.
[http://dx.doi.org/10.4162/nrp.2015.9.1.37] [PMID: 25671066]
[142]
Margalef, M.; Pons, Z.; Iglesias-Carres, L.; Bravo, F.I.; Muguerza, B.; Arola-Arnal, A. Lack of tissue accumulation of grape seed flavanols after daily long-term administration in healthy and cafeteria-diet obese rats. J. Agric. Food Chem., 2015, 63(45), 9996-10003.
[http://dx.doi.org/10.1021/acs.jafc.5b03856] [PMID: 26496863]
[143]
Kim, H.; Kim, D.H.; Seo, K.H.; Chon, J.W.; Nah, S.Y.; Bartley, G.E.; Arvik, T.; Lipson, R.; Yokoyama, W. Modulation of the intestinal microbiota is associated with lower plasma cholesterol and weight gain in hamsters fed chardonnay grape seed flour. J. Agric. Food Chem., 2015, 63(5), 1460-1467.
[http://dx.doi.org/10.1021/jf5026373] [PMID: 25598538]
[144]
Charradi, K.; Mahmoudi, M.; Bedhiafi, T.; Kadri, S.; Elkahoui, S.; Limam, F.; Aouani, E. Dietary supplementation of grape seed and skin flour mitigates brain oxidative damage induced by a high-fat diet in rat: Gender dependency. Biomed. Pharmacother., 2017, 87, 519-526.
[http://dx.doi.org/10.1016/j.biopha.2017.01.015] [PMID: 28076832]
[145]
Seo, K-H.; Bartley, G.E.; Tam, C.; Kim, H-S.; Kim, D-H.; Chon, J-W.; Kim, H.; Yokoyama, W. Chardonnay grape seed flour ameliorates hepatic steatosis and insulin resistance via altered hepatic gene expression for oxidative stress, inflammation, and lipid and ceramide synthesis in diet-induced obese mice. PLoS One, 2016, 11(12), e0167680-e0167680.
[http://dx.doi.org/10.1371/journal.pone.0167680] [PMID: 27977712]
[146]
El-Desouky, W.; Hanafi, A.; Abbas, M.M. Radioprotective effect of green tea and grape seed extracts mixture on gamma irradiation induced immune suppression in male albino rats. Int. J. Radiat. Biol., 2017, 93(4), 433-439.
[http://dx.doi.org/10.1080/09553002.2016.1254834] [PMID: 27813697]
[147]
Salmabadi, Z.; Mohseni Kouchesfahani, H.; Parivar, K.; Karimzadeh, L. Effect of grape seed extract on lipid profile and expression of interleukin-6 in polycystic ovarian syndrome wistar rat model. Int. J. Fertil. Steril., 2017, 11(3), 176-183.
[PMID: 28868839]
[148]
Serrano, J. Casanova-Martí, À.; Blay, M.; Terra, X.; Ardévol, A.; Pinent, M. Defining conditions for optimal inhibition of food intake in rats by a grape-seed derived proanthocyanidin extract. Nutrients, 2016, 8(10), E652.
[http://dx.doi.org/10.3390/nu8100652] [PMID: 27775601]
[149]
Griffin, L.E.; Witrick, K.A.; Klotz, C.; Dorenkott, M.R.; Goodrich, K.M.; Fundaro, G.; McMillan, R.P.; Hulver, M.W.; Ponder, M.A.; Neilson, A.P. Alterations to metabolically active bacteria in the mucosa of the small intestine predict anti-obesity and anti-diabetic activities of grape seed extract in mice. Food Funct., 2017, 8(10), 3510-3522.
[http://dx.doi.org/10.1039/C7FO01236E] [PMID: 28875188]
[150]
El Ayed, M.; Kadri, S.; Smine, S.; Elkahoui, S.; Limam, F.; Aouani, E. Protective effects of grape seed and skin extract against high-fat-diet-induced lipotoxicity in rat lung. Lipids Health Dis., 2017, 16(1), 174.
[http://dx.doi.org/10.1186/s12944-017-0561-z] [PMID: 28903761]
[151]
Bedhiafi, T.; Charradi, K.; Azaiz, M.B.; Mahmoudi, M.; Msakni, I.; Jebari, K.; Bouziani, A.; Limam, F.; Aouani, E. Supplementation of grape seed and skin extract to orlistat therapy prevents high-fat diet-induced murine spleen lipotoxicity. Appl. Physiol. Nutr. Metab., 2018, 43(8), 782-794.
[http://dx.doi.org/10.1139/apnm-2017-0743] [PMID: 29514007]
[152]
Cho, Y.J.; Lee, H.G.; Seo, K.H.; Yokoyama, W.; Kim, H. Antiobesity effect of prebiotic polyphenol-rich grape seed flour supplemented with probiotic kefir-derived lactic acid bacteria. J. Agric. Food Chem., 2018, 66(47), 12498-12511.
[http://dx.doi.org/10.1021/acs.jafc.8b03720] [PMID: 30392364]
[153]
Mahmoudi, M.; Charradi, K.; Limam, F.; Aouani, E. Grape seed and skin extract as an adjunct to xenical therapy reduces obesity, brain lipotoxicity and oxidative stress in high fat diet fed rats. Obes. Res. Clin. Pract., 2018, 12(Suppl. 2), 115-126.
[http://dx.doi.org/10.1016/j.orcp.2016.04.006] [PMID: 27161420]
[154]
El Ayed, M.; Kadri, S.; Mabrouk, M.; Aouani, E.; Elkahoui, S. Protective effect of grape seed and skin extract against high-fat diet-induced dyshomeostasis of energetic metabolism in rat lung. Lipids Health Dis., 2018, 17(1), 109.
[http://dx.doi.org/10.1186/s12944-018-0754-0] [PMID: 29747667]
[155]
Rameshrad, M.; Razavi, B.M.; Imenshahidi, M.; Hosseinzadeh, H. Vitis vinifera (grape) seed extract and resveratrol alleviate bisphenol-A-induced metabolic syndrome: Biochemical and molecular evidences. Phytother. Res., 2019, 33(3), 832-844.
[156]
González-Quilen. C.; Gil-Cardoso, K.; Ginés, I.; Beltrán-Debón, R.; Pinent, M.; Ardévol, A.; Terra, X.; Blay, M.T. Grape-seed proanthocyanidins are able to reverse intestinal dysfunction and metabolic endotoxemia induced by a cafeteria diet in wistar rats. Nutrients, 2019, 11(5), E979.
[http://dx.doi.org/10.3390/nu11050979] [PMID: 31035432]
[157]
Shi, Y.; Jia, M.; Xu, L.; Fang, Z.; Wu, W.; Zhang, Q. MiR-96 and autophagy are involved in the beneficial effect of grape seed proanthocyanidins against high-fat-diet-induced dyslipidemia in mice. Phytother. Res., 2019, 33(4), 1222-1232.
[158]
Wu, Y.; Ma, N.; Song, P.; He, T.; Levesque, C.; Bai, Y.; Zhang, A.; Ma, X. Grape seed proanthocyanidin affects lipid metabolism via changing gut microflora and enhancing propionate production in weaned pigs. J. Nutr., 2019, 149(9), 1523-1532.
[http://dx.doi.org/10.1093/jn/nxz102] [PMID: 31175811]
[159]
Zhou, F.; Yin, M.; Liu, Y.; Han, X.; Guo, J.; Ren, C. Grape seed flour intake decreases adiposity gain in high-fat-diet induced obese mice by activating thermogenesis. J. Funct. Foods, 2019, 62, 103509.
[http://dx.doi.org/10.1016/j.jff.2019.103509]
[160]
Du, H.; Wang, Q.; Li, T.; Ren, D.; Yang, X. Grape seed proanthocyanidins reduced the overweight of C57BL/6J mice through modulating adipose thermogenesis and gut microbiota. Food Funct., 2021, 12(18), 8467-8477.
[http://dx.doi.org/10.1039/D1FO01361K] [PMID: 34296715]
[161]
Preuss, H.G.; Wallerstedt, D.; Talpur, N.; Tutuncuoglu, S.O.; Echard, B.; Myers, A.; Bui, M.; Bagchi, D. Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: A pilot study. J. Med., 2000, 31(5-6), 227-246.
[PMID: 11508317]
[162]
Vigna, G.B.; Costantini, F.; Aldini, G.; Carini, M.; Catapano, A.; Schena, F.; Tangerini, A.; Zanca, R.; Bombardelli, E.; Morazzoni, P.; Mezzetti, A.; Fellin, R.; Maffei Facino, R. Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers. Metabolism, 2003, 52(10), 1250-1257.
[http://dx.doi.org/10.1016/S0026-0495(03)00192-6] [PMID: 14564675]
[163]
Sano, A.; Uchida, R.; Saito, M.; Shioya, N.; Komori, Y.; Tho, Y.; Hashizume, N. Beneficial effects of grape seed extract on malondialdehyde-modified LDL. J. Nutr. Sci. Vitaminol. (Tokyo), 2007, 53(2), 174-182.
[http://dx.doi.org/10.3177/jnsv.53.174] [PMID: 17616006]
[164]
Kar, P.; Laight, D.; Rooprai, H.K.; Shaw, K.M.; Cummings, M. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: A double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabet. Med., 2009, 26(5), 526-531.
[http://dx.doi.org/10.1111/j.1464-5491.2009.02727.x] [PMID: 19646193]
[165]
De Groote, D.; Van Belleghem, K.; Devière, J.; Van Brussel, W.; Mukaneza, A.; Amininejad, L. Effect of the intake of resveratrol, resveratrol phosphate, and catechin-rich grape seed extract on markers of oxidative stress and gene expression in adult obese subjects. Ann. Nutr. Metab., 2012, 61(1), 15-24.
[http://dx.doi.org/10.1159/000338634] [PMID: 22776850]
[166]
Effect of supplementation with grape seed extract (Vitis vinifera) on serum lipid profiles in patient with type 2 diabetes. Majallah-i Ghudad-i Darun/Riz va Mitabulism-i Iran, 2013, 15(1), 59-66.
[167]
Irandoost, P.; Ebrahimi-Mameghani, M.; Pirouzpanah, S. Does grape seed oil improve inflammation and insulin resistance in overweight or obese women? Int. J. Food Sci. Nutr., 2013, 64(6), 706-710.
[http://dx.doi.org/10.3109/09637486.2013.775228] [PMID: 23506314]
[168]
Razavi, S.M.; Gholamin, S.; Eskandari, A.; Mohsenian, N.; Ghorbanihaghjo, A.; Delazar, A.; Rashtchizadeh, N.; Keshtkar-Jahromi, M.; Argani, H. Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia. J. Med. Food, 2013, 16(3), 255-258.
[http://dx.doi.org/10.1089/jmf.2012.2408] [PMID: 23437789]
[169]
Zolfi, H.R. The effect of grape seed (Vitis vinifera L.) extract supplementation on lipid profile and high-sensitivity C-reactive protein levels after aerobic exercise in non-athlete males. Feyz J. Kashan Univ. Med. Sci., 2015, 19(3), 204-213.
[170]
Saedmocheshi, S.; Almori, M.R.; Saedmocheshi, L. Interactive effect of grape seed extract along with aerobic activity on lipid profile in inactive obese women aged over 60 years sanandaj. Iran J. Diabetes Lipid Disord., 2015, 14(4), 273-278.
[171]
Taghizadeh, M.; Malekian, E.; Memarzadeh, M.R.; Mohammadi, A.A.; Asemi, Z. Grape seed extract supplementation and the effects on the biomarkers of oxidative stress and metabolic profiles in female volleyball players: A randomized, double-blind, placebo-controlled clinical trial. Iran. Red Crescent Med. J., 2016, 18(9), e31314.
[http://dx.doi.org/10.5812/ircmj.31314] [PMID: 28144458]
[172]
Argani, H.; Ghorbanihaghjo, A.; Vatankhahan, H.; Rashtchizadeh, N.; Raeisi, S.; Ilghami, H. The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia. Sao Paulo Med. J., 2016, 134(3), 234-239.
[http://dx.doi.org/10.1590/1516-3180.2015.01702312] [PMID: 27191247]
[173]
Parandoosh, M.; Yousefi, R.; Khorsandi, H.; Nikpayam, O.; Saidpour, A.; Babaei, H. The effects of grape seed extract (Vitis vinifera) supplement on inflammatory markers, neuropeptide Y, anthropometric measures, and appetite in obese or overweight individuals: A randomized clinical trial. Phytother. Res., 2020, 34(2), 379-387.
[http://dx.doi.org/10.1002/ptr.6529] [PMID: 31713941]
[174]
Ebrahimi-Mameghani, M.; Irandoost, P.; Pourmoradian, S. The effects of grape seed oil on the cardiovascular risk factors in overweight and obese women: A double-blind randomized clinical trial. Curr. Top. Nutraceutical Res., 2020, 18(3), 221-226.
[175]
Yousefi, R.; Parandoosh, M.; Khorsandi, H.; Hosseinzadeh, N.; Madani Tonekaboni, M.; Saidpour, A.; Babaei, H.; Ghorbani, A. Grape seed extract supplementation along with a restricted-calorie diet improves cardiovascular risk factors in obese or overweight adult individuals: A randomized, placebo-controlled trial. Phytother. Res., 2021, 35(2), 987-995.
[http://dx.doi.org/10.1002/ptr.6859] [PMID: 33044768]

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Request history8.2.27PHP Version1.27sRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
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      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
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      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
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      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
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      • 7: 51271683
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      • 11: 51271683
      • 12: 51271683
      • 13: 51271683
      • 14: 51271683
      • 15: 51271683
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
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      7.74msalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 59 limit 1
      1.19msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
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      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=59) and sj.journal_id!=59 group by `j`.`nid`) as `aggregate_table`
      1.95msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=59) and sj.journal_id!=59 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.69msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=59) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      29.2msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=59) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      48.38msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '124903'
      22.12msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 124903
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '124903'
      57.29msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 124903
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '124903' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      23.18msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 124903
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      370μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      720μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 59 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      261msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 59 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      230msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 59 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      39.63msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 124903 limit 1
      15.19msalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 124903
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 124903 and content_type = 'article' order by status desc limit 1
      850μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 206517 limit 1
      3.24msalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 206517
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      680μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'EMIDDT' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      2.22msalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: EMIDDT
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '124903' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      6.7msalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '12060' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      580μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3337' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      590μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3337) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3337) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3337)
      80.27msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12060) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12060) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12060)
      1.6msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 124903) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 124903) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51271683 and j.to_ip >=51271683 )) and ((j.from_date <= 1740774490 and j.to_date >= 1740774490 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 124903)
      910μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '46' and is_uploaded = 1 and issue_id = 12060 order by cast(first_page as SIGNED) desc limit 1
      940μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 46
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '62' and is_uploaded = 1 and issue_id = 12060 order by cast(first_page as SIGNED) asc limit 1
      1.19msalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 62
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      250μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      1.59msalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 124903 limit 1
      5.05msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 124903
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 59 and `b`.`banner_from_date` <= 1740774490 and `b`.`banner_to_date` >= 1740774490 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      3.03msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 59
      • 3: 1740774490
      • 4: 1740774490
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 59 and `b`.`banner_from_date` <= 1740774490 and `b`.`banner_to_date` >= 1740774490 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      2.15msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 59
      • 3: 1740774490
      • 4: 1740774490
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='37509cb4cf7f098c0d4f6785e79011a9'
      460μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:291
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-28 20:28:10GET/article/124903414361