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Journals / Research in Agricultural Sciences / 2026 / Volume: 55 Issue: 2

Walnut Seed Coat (Juglans regia L.), a Plant Effective in Human Health: Antioxidant Activity and in Rats Nephroprotective Effect

İnsan Sağlığında Etkili Bir Bitki Ceviz Tohumu Kabuğu (Juglans regia L.): Antioksidan Aktivitesi ve Sıçanlarda Nefroprotektif Etkisi

Esra Palabıyık(ATATURK UNIVERSITY)0000-0002-3066-1921
Handan Uğuz(ATATURK UNIVERSITY)0000-0001-5444-1459
Hakan Aşkın(ATATURK UNIVERSITY)0000-0003-3248-759X
Seda Aşkın(ATATURK UNIVERSITY)0000-0001-6133-9065
Hülya Akıncıoğlu(AGRI IBRAHIM CECEN UNIVERSITY)0000-0001-5453-0953
Pages
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Publication Date
2024-05-29
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Based on these results, it was clearly determined that E-WSC has significant antioxidant activity due to its bioactive components, has an inhibitory effect on AChE and BChE enzymes, and has a protective effect against oxidative stress by improving hyperlipidemia-related kidney damage.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:In the study, the seed coat (WSC) of Posof (Ardahan/Türkiye) walnuts was extracted to determine their phytochemical components and antioxidant capacities.
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Key Findings & Data:Additionally, antioxidant enzyme activity parameters were measured in the kidney tissues of Triton WR-1339-induced hyperlipidemic rats.
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Conclusion & Impact:Based on these results, it was clearly determined that E-WSC has significant antioxidant activity due to its bioactive components, has an inhibitory effect on AChE and BChE enzymes, and has a protective effect against oxidative stress by improving hyperlipidemia-related kidney damage.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Antioxidant activity · kidney · oxidative stress

Abstract

In the study, the seed coat (WSC) of Posof (Ardahan/Türkiye) walnuts was extracted to determine their phytochemical components and antioxidant capacities. The effects of bioactive components in the ethanol extract of WSC (E-WSC) on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors were investigated. Additionally, antioxidant enzyme activity parameters were measured in the kidney tissues of Triton WR-1339-induced hyperlipidemic rats. Bioactive compounds in WSC were identified by GC-MS system. The antioxidant properties of WSC were measured using Fe+3, Cu+2 and Fe+3-2,4,6-tripyridyl-s-triazine (TPTZ) reducing agent, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'- azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activities. In this analysis, using 30 male Wistar rats (300 ± 30 g) randomly divided into five groups were treated as follows; K1: Healthy control group, K2: E-WSC (150 mg) o.d., K3: E-WSC (300 mg) o.d., K4: Hyperlipidemic group i.p., K5: Hyperlipidemic group i.p. + E-WSC (300 mg) o.d. Superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) analyzes were performed in kidney tissues. Based on these results, it was clearly determined that E-WSC has significant antioxidant activity due to its bioactive components, has an inhibitory effect on AChE and BChE enzymes, and has a protective effect against oxidative stress by improving hyperlipidemia-related kidney damage.

Özet

Çalışmada, Posof (Ardahan/Türkiye) cevizlerinin tohum kabuğu (WSC), fitokimyasal bileşenlerinin ve antioksidan kapasitelerinin belirlenmesi için ekstrakte edilmiştir. WSC'nin (E-WSC) etanol ekstraktındaki biyoaktif bileşenlerin asetilkolinesteraz (AChE) ve butirilkolinesteraz (BChE) inhibitörleri üzerindeki etkileri araştırılmıştır. Ayrıca Triton WR-1339 ile indüklenen hiperlipidemik sıçanların böbrek dokularında antioksidan enzim aktivite parametreleri ölçülmüştür. WSC'deki biyoaktif bileşikler GC-MS sistemi ile tanımlanmıştır. WSC’nin antioksidan özellikleri, Fe+3, Cu+2 ve Fe+3-2,4,6-tripiridil-s-triazin (TPTZ) indirgeyici ajan, 1,1-difenil-2-pikrilhidrazil (DPPH) ve 2,2'- azino-bis (3-etilbenzotiyazolin-6-sülfonik asit) (ABTS) temizleme aktiviteleri kullanılarak ölçülmüştür. 30 adet erkek Wistar sıçanı (300 ± 30 g) kullanılarak yapılan bu analizde, rastgele beş gruba ayrılan sıçanlara aşağıdaki gibi uygulama yapılmıştır; K1: Sağlıklı kontrol grubu, K2: E-WSC (150 mg) o.d., K3: E-WSC (300 mg) o.d., K4: Hiperlipidemik grup i.p., K5: Hiperlipidemik grup i.p. + E-WSC (300 mg) o.d. Böbrek dokularında Süperoksit dismutaz (SOD), katalaz (CAT) ve malondialdehit (MDA) analizleri yapılmıştır. Bu sonuçlara göre E-WSC'nin biyoaktif bileşenlerine bağlı olarak önemli antioksidan aktiviteye sahip olduğu, AChE ve BChE enzimleri üzerinde inhibitör etkiye sahip olduğu ve hiperlipidemiye bağlı böbrek hasarını iyileştirerek oksidatif strese karşı koruyucu etkiye sahip olduğu açıkça belirlenmiştir.

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Cite This Article

Palabıyık, E., Uğuz, H., Aşkın, H., Aşkın, S., Akıncıoğlu, H. (2024). Walnut Seed Coat (Juglans regia L.), a Plant Effective in Human Health: Antioxidant Activity and in Rats Nephroprotective Effect. Research in Agricultural Sciences, Volume: 55 Issue: 2. https://doi.org/10.17097/agricultureatauni.1418238

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References (120)

  1. Abdallah, A. A., Nasr El-Deen, N. A., Abd El-Aziz, H. I. & Neamat-Allah, A. N. (2020). Effect of the aqueous root extract of Curcuma longa L.(turmeric) against thermally oxidized oil-induced hematological, biochemical, and histopathological alterations. Comparative Clinical Pathology, 29, 837–845.
  2. Abu-Raghif, A. R., Sahib, H. B. & Abb as, S. N. (2015). Anti-hyperlipidemic effect of Vitex agnus castus Extracts in Mice. Int. J. Pharm. Sci. Rev. Res, 35, 120–125.
  3. Achan, J., Talisuna, A. O., Erhart, A., Yeka, A., Tibenderana, J. K., Baliraine, F. N. & D'Alessandro, U. (2011). Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malaria journal, 10(1), 1–12.
  4. Acquaviva, R., D’Angeli, F., Malfa, G. A., Ronsisvalle, S., Garozzo, A., Stivala, A. & Genovese, C. (2021).
  5. Antibacterial and anti-biofilm activities of walnut pellicle extract (Juglans regia L.) against coagulase-negative staphylococci. Natural product research, 35(12), 2076—2081.
  6. Adisakwattana, S., Pongsuwan, J., Wungcharoen, C. & Yibchok-anun, S. (2013). In vitro effects of cinnamic acid derivatives on protein tyrosine phosphatase 1B. Journal of Enzyme Inhibition and Medicinal Chemistry, 28(5), 1067–1072.
  7. Ahmad, N., Wee, C. E., Wai, L. K., Zin, N. M. & Azmi, F. (2021). Biomimetic amphiphilic chitosan nanoparticles: Synthesis, characterization and antimicrobial activity. Carbohydrate Polymers, 254, 117299.
  8. Alasalvar, C. & Bolling, B. W. (2015). Review of nut phytochemicals, fat-soluble bioactives, antioxidant components and health effects. British Journal of Nutrition, 113(52), 568–578.
  9. Alissa, E. M. & Ferns, G. A. (2017). Dietary fruits and vegetables and cardiovascular diseases risk. Critical Reviews in Food Science and Nutrition, 57(9), 1950–1962.
  10. Apak, R., Güçlü, K., Özyürek, M., Esin Karademir, S. & Erçağ, E. (2006). The cupric ion reducing antioxidant capacity and polyphenolic content of some herbal teas. International Journal of Food Sciences and Nutrition, 57(5-6), 292–304.
  11. Artunc, T., Menzek, A., Taslimi, P., Gulcin, I., Kazaz, C. & Sahin, E. (2020). Synthesis and antioxidant activities of phenol derivatives from 1, 6-bis (dimethoxyphenyl) hexane-1, 6-dione. Bioorganic Chemistry, 100, 103884.
  12. Attia, A. A., El-Samad, L. M. & Zaghloul, N. (2020). Effects of protein extract from the housefly larvae (Musca domestica vicina) on the hyperlipidemic mice induced by Triton WR-1339.
  13. Aune, D., Keum, N., Giovannucci, E., Fadnes, L. T., Boffetta, P., Greenwood, D. C. & Norat, T. (2016). Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies. BMC Medicine, 14(1), 1–14.
  14. Balaydın, H. T., Gülçin, İ., Menzek, A., Göksu, S. & Şahin, E. (2010). Synthesis and antioxidant properties of diphenylmethane derivative bromophenols including a natural product. Journal of Enzyme Inhibition and Medicinal Chemistry, 25(5), 685–695.
  15. Baldissera, M. D., Souza, C. F., Grando, T. H., Doleski, P. H., Boligon, A. A., Stefani, L. M. & Monteiro, S. G. (2017). Hypolipidemic effect of β-caryophyllene to treat hyperlipidemic rats. Naunyn-Schmiedeberg's Archives of Pharmacology, 390, 215–223.
  16. Bayrak, S., Öztürk, C., Demir, Y., Alım, Z. & Küfrevioglu, Ö. İ. (2020). Purification of polyphenol oxidase from potato and investigation of the inhibitory effects of phenolic acids on enzyme activity. Protein and Peptide Letters, 27(3), 187–192.
  17. Beigh, S., Rashid, H., Sharma, S., Parvez, S. & Raisuddin, S. (2017). Bleomycin-induced pulmonary toxicopathological changes in rats and its prevention by walnut extract. Biomedicine & Pharmacotherapy, 94, 418–429.
  18. Bernard, A., Lheureux, F. & Dirlewanger, E. (2018). Walnut: past and future of genetic improvement. Tree Genet Genomes 14 (1): 1.
  19. Bertges, L. C., Mourão Jr, C. A., Souza, J. B. & Cardoso, V. A. C. (2011). Hyperlipidemia induced by Triton WR1339 (Tyloxapol) in Wistar rats. Braz J Med Sci Health, 1, 32–4.
  20. Beyegue, C. N., Ngangoum, R. C., Kuate, D., Ngondi, J. L. & Oben, J. E. (2012). Effect of Guibourtia tessmannii extracts on blood lipids and oxidative stress markers in triton WR 1339 and high fat diet induced hyperlipidemic rats. Biology and Medicine, 4(1), 1–10.
  21. Bjørklund, G. & Chirumbolo, S. (2017). Role of oxidative stress and antioxidants in daily nutrition and human health. Nutrition, 33, 311–321.
  22. Blois, M. S. (1958). Antioxidant determinations by the use of a stable free radical. Nature, 181(4617), 1199–1200. Bursal, E., Aras, A., Kılıç, Ö., Taslimi, P., Gören, A. C. & Gülçin, İ. (2019). Phytochemical content, antioxidant activity, and enzyme inhibition effect of Salvia eriophora Boiss. & Kotschy against acetylcholinesterase, α‐amylase, butyrylcholinesterase, and α‐glycosidase enzymes. Journal of Food Biochemistry, 43(3), e12776.
  23. Cakmak, K. C. & Gülçin, İ. (2019). Anticholinergic and antioxidant activities of usnic acid-an activity-structure insight. Toxicology Reports, 6, 1273–1280.
  24. Cassidy, L., Fernandez, F., Johnson, J. B., Naiker, M., Owoola, A. G. & Broszczak, D. A. (2020). Oxidative stress in alzheimer’s disease: A review on emergent natural polyphenolic therapeutics. Complementary Therapies in Medicine, 49, 102294.
  25. Ceylan, H., Demir, Y. & Beydemir, Ş. (2019). Inhibitory effects of usnic and carnosic acid on some metabolic enzymes: an in vitro study. Protein and Peptide Letters, 26(5), 364–370.
  26. Cheignon, C., Tomas, M., Bonnefont-Rousselot, D., Faller, P., Hureau, C. & Collin, F. (2018). Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biology, 14, 450–64.
  27. Chen, X., Guo, C. & Kong, J. (2012). Oxidative stress in neurodegenerative diseases. Neural Regeneration Research, 7(5), 376.
  28. Chien, S. C., Chen, P. S., Huang, Y. H., Tang, S. C., Li, Y. H. & Yeh, H. I. (2019). 2019 Taiwan Society of Lipids and Atherosclerosis expert consensus statement on statin intolerance. Journal of the Formosan Medical Association, 118(10), 1385–1392.
  29. Chiu, C. Y., Yen, T. E., Liu, S. H. & Chiang, M. T. (2019). Comparative effects and mechanisms of chitosan and its derivatives on hypercholesterolemia in high-fat diet-fed rats. International Journal of Molecular Sciences, 21(1), 92.
  30. Choi, Y., Abdelmegeed, M. A. & Song, B. J. (2016). Preventive effects of dietary walnuts on high-fat-induced hepatic fat accumulation, oxidative stress and apoptosis in mice. The Journal of Nutritional Biochemistry, 38, 70–80.
  31. Cicero, A. F. & Colletti, A. (2016). Combinations of phytomedicines with different lipid lowering activity for dyslipidemia management: the available clinical data. Phytomedicine, 23(11), 1113–1118.
  32. Cinar, I., Sirin, B., Aydin, P., Toktay, E., Cadirci, E., Halici, I. & Halici, Z. (2019). Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life Sciences, 221, 327–334.
  33. Cintesun, S., Ozman, Z., Kocyigit, A., Mansuroglu, B. & Kocacaliskan, I. (2023). Effects of walnut (Juglans regia L.) kernel extract and juglone on dopamine levels and oxidative stress in rats. Food Bioscience, 51, 102327.
  34. Cosmulescu, S., Trandafir, I., Nour, V. & Botu, M. (2015). Total phenolic, flavonoid distribution and antioxidant capacity in skin, pulp and fruit extracts of plum cultivars. Journal of Food Biochemistry, 39(1), 64–69.
  35. Çakmakçı, S., Topdaş, E. F., Kalın, P., Han, H., Şekerci, P., P. Köse, L. & Gülçin, İ. (2015). Antioxidant capacity and functionality of oleaster (Elaeagnus angustifolia L.) flour and crust in a new kind of fruity ice cream. International Journal of Food Science & Technology, 50(2), 472–481.
  36. Da Rocha, J. T., Sperança, A., Nogueira, C. W. & Zeni, G. (2009). Hypolipidaemic activity of orally administered diphenyl diselenide in Triton WR-1339-induced hyperlipidaemia in mice. Journal of Pharmacy and Pharmacology, 61(12), 1673–1679.
  37. de Almeida Lima, G. D., Rodrigues, M. P., de Oliveira Mendes, T. A., Moreira, G. A., Siqueira, R. P., da Silva, A. M. & Teixeira, R. R. (2018). Synthesis and antimetastatic activity evaluation of cinnamic acid derivatives containing 1, 2, 3-triazolic portions. Toxicology in Vitro, 53, 1–9.
  38. De Sousa, J. A., De Sousa, J. T., Boaretto, F. B. M., Salvi, J. D. O., Fachini, J., Da Silva, J. B. & Picada, J. N. (2019). Anti-hyperlipidemic effects of Campomanesia xanthocarpa aqueous extract and its modulation on oxidative stress and genomic instability in Wistar rats. Journal of Toxicology and Environmental Health, Part A, 82(18), 1009–1018.
  39. Demir, Y., Özaslan, M. S., Duran, H. E., Küfrevioğlu, Ö. İ. & Beydemir, Ş. (2019). Inhibition effects of quinones on aldose reductase: antidiabetic properties. Environmental toxicology and pharmacology, 70, 103195.
  40. Di Mauro, M. D., Fava, G., Spampinato, M., Aleo, D., Melilli, B., Saita, M. G. & D’Antona, N. (2019). Polyphenolic fraction from olive mill wastewater: Scale-up and in vitro studies for ophthalmic nutraceutical applications. Antioxidants, 8(10), 462.
  41. Dicpinigaitis, P. V., Morice, A. H., Birring, S. S., McGarvey, L., Smith, J. A., Canning, B. J. & Page, C. P. (2014). Antitussive drugs–past, present, and future. Pharmacological Reviews, 66(2), 468–512.
  42. Ellman, G. L., Courtney, K. D., Andres Jr, V. & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7(2), 88–95.
  43. Fernández-Agulló, A., Pereira, E., Freire, M. S., Valentão, P., Andrade, P. B., González-Álvarez, J. & Pereira, J. A. (2013). Influence of solvent on the antioxidant and antimicrobial properties of walnut (Juglans regia L.) green husk extracts. Industrial Crops and Products, 42, 126–132.
  44. Fraga, C. G., Croft, K. D., Kennedy, D. O. & Tomás-Barberán, F. A. (2019). The effects of polyphenols and other bioactives on human health. Food & Function, 10(2), 514–528.
  45. Gaschler, M. M. & Stockwell, B. R. (2017). Lipid peroxidation in cell death. Biochemical and Biophysical Research Communications, 482(3), 419–425.
  46. Gella, A. & Durany, N. (2009). Oxidative stress in Alzheimer disease. Cell Adhesion & Migration, 3(1), 88–93.
  47. Gießel, J. M., Loesche, A., Hoenke, S. & Csuk, R. (2019). In search of new cinnamic acid derived flavours and fragrances. Results in Chemistry,1, 100010.
  48. Göçer, H. & Gülçin, İ. (2011). Caffeic acid phenethyl ester (CAPE): correlation of structure and antioxidant properties. International journal of Food Sciences and Nutrition, 62(8), 821–825.
  49. Gulcin, I., Kaya, R., Goren, A. C., Akincioglu, H., Topal, M., Bingol, Z. & Alwasel, S. (2019). Anticholinergic, antidiabetic and antioxidant activities of cinnamon (Cinnamomum verum) bark extracts: Polyphenol contents analysis by LC-MS/MS. International Journal of Food Properties, 22(1), 1511–1526.
  50. Gulcin, I., Kirecci, E., Akkemik, E., Topal, F. & Hisar, O. (2010). Antioxidant, antibacterial, and anticandidal activities of an aquatic plant: duckweed (Lemna minor L. Lemnaceae). Turkish Journal of Biology, 34(2), 175–188.
  51. Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Archives of toxicology, 94(3), 651–715.
  52. Gülçin, I. L., Beydemir, Ş., Topal, F., Gagua, N., Bakuridze, A., Bayram, R. & Gepdiremen, A. (2012). Apoptotic, antioxidant and antiradical effects of majdine and isomajdine from Vinca herbacea Waldst. and kit. Journal of Enzyme Inhibition and Medicinal Chemistry, 27(4), 587–594.
  53. Gülçin, İ. & Daştan, A. (2007). Synthesis of dimeric phenol derivatives and determination of in vitro antioxidant and radical scavenging activities. Journal of Enzyme Inhibition and Medicinal Chemistry, 22(6), 685–695. Gülçin, İ., Gören, A. C., Taslimi, P., Alwasel, S. H., Kılıc, O. & Bursal, E. (2020). Anticholinergic, antidiabetic and antioxidant activities of Anatolian pennyroyal (Mentha pulegium)-analysis of its polyphenol contents by LC-MS/MS. Biocatalysis and Agricultural Biotechnology, 23, 101441.
  54. Gülçin, Ý., Elias, R., Gepdiremen, A., Boyer, L. & Köksal, E. (2007). A comparative study on the antioxidant activity of fringe tree (Chionanthus virginicus L.) extracts. African Journal of Biotechnology, 6(4). 410–418.
  55. Hadi, M. Y., Mohammed, G. J. & Hameed, I. H. (2016). Analysis of bioactive chemical compounds of Nigella sativa using gas chromatography-mass spectrometry. Journal of Pharmacognosy and Phytotherapy, 8(2), 8–24. Haider, S., Batool, Z., Ahmad, S., Siddiqui, R. A. & Haleem, D. J. (2018). Walnut supplementation reverses the scopolamine-induced memory impairment by restoration of cholinergic function via mitigating oxidative stress in rats: a potential therapeutic intervention for age related neurodegenerative disorders. Metabolic Brain Disease, 33, 39–51.
  56. Han, H., Yilmaz, H. & Gulcin, I. (2018). Antioxidant activity of flaxseed (Linum usitatissimum L.) shell and analysis of its polyphenol contents by LC-MS/MS.
  57. Harada, H., Yamashita, U., Kurihara, H., Fukushi, E., Kawabata, J. & Kamei, Y. (2002). Antitumor activity of palmitic acid found as a selective cytotoxic substance in a marine red alga. Anticancer Research, 22(5), 2587–2590. Hashem, M. A., Abd-Allah, N. A., Mahmoud, E. A., Amer, S. A. & Alkafafy, M. (2021). A preliminary study on the effect of psyllium husk ethanolic extract on hyperlipidemia, hyperglycemia, and oxidative stress induced by triton X-100 injection in rats. Biology, 10(4), 335.
  58. Hawking, Z. L. (2016). Alzheimer's disease: the role of mitochondrial dysfunction and potential new therapies. Bioscience Horizons: The International Journal of Student Research, 9, hzw014.
  59. Hazli, U. H. A. M., Abdul-Aziz, A., Mat-Junit, S., Chee, C. F. & Kong, K. W. (2019). Solid-liquid extraction of bioactive compounds with antioxidant potential from Alternanthera sesillis (red) and identification of the polyphenols using UHPLC-QqQ-MS/MS. Food Research International, 115, 241–250.
  60. Hever, J. & Cronise, R. J. (2017). Plant-based nutrition for healthcare professionals: implementing diet as a primary modality in the prevention and treatment of chronic disease. Journal of Geriatric Cardiology: JGC, 14(5), 355.
  61. Imamura, F., Fretts, A., Marklund, M., Ardisson Korat, A. V., Yang, W. S., Lankinen, M. & Fatty Acids and Outcomes Research Consortium (FORCE). (2018). Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: a pooled analysis of prospective cohort studies. PLoS Medicine, 15(10), e1002670.
  62. Jahanban-Esfahlan, A., Ostadrahimi, A., Tabibiazar, M. & Amarowicz, R. (2019). A comparative review on the extraction, antioxidant content and antioxidant potential of different parts of walnut (Juglans regia L.) fruit and tree. Molecules, 24(11), 2133.
  63. Johnson, T. O., Odoh, K. D., Nwonuma, C. O., Akinsanmi, A. O. & Adegboyega, A. E. (2020). Biochemical evaluation and molecular docking assessment of the anti-inflammatory potential of Phyllanthus nivosus leaf against ulcerative colitis. Heliyon, 6(5).
  64. Kmiecik, D., Korczak, J., Rudzińska, M., Kobus-Cisowska, J., Gramza-Michałowska, A. & Hęś, M. (2011). β-Sitosterol and campesterol stabilisation by natural and synthetic antioxidants during heating. Food Chemistry, 128(4), 937–942.
  65. Kosalec, I., Cvek, J. & Tomic, S. (2009). Contaminants of medicinal herbs and herbal products. Arhiv za Higijenu Rada i Toksikologiju, 60(4), 485.
  66. Kovesdy, C. P., Furth, S., Zoccali, C. & World Kidney Day Steering Committee. (2017). Obesity and kidney disease: hidden consequences of the epidemic. Physiology International, 104(1), 1-14.
  67. Köse, L. P., Gülcin, I., Gören, A. C., Namiesnik, J., Martinez-Ayala, A. L. & Gorinstein, S. (2015). LC–MS/MS analysis, antioxidant and anticholinergic properties of galanga (Alpinia officinarum Hance) rhizomes. Industrial Crops and Products, 74, 712–721.
  68. Kumar, G., Srivastava, A., Sharma, S. K. & Gupta, Y. K. (2013). The hypolipidemic activity of Ayurvedic medicine, Arogyavardhini vati in Triton WR-1339-induced hyperlipidemic rats: a comparison with fenofibrate. Journal of Ayurveda and integrative medicine, 4(3), 165.
  69. Lan, J. S., Hou, J. W., Liu, Y., Ding, Y., Zhang, Y., Li, L. & Zhang, T. (2017). Design, synthesis and evaluation of novel cinnamic acid derivatives bearing N-benzyl pyridinium moiety as multifunctional cholinesterase inhibitors for Alzheimer’s disease. Journal of Enzyme Inhibition and Medicinal Chemistry, 32(1), 776–788.
  70. Lateef, M., Iqbal, L., Fatima, N., Siddiqui, K., Afza, N., Zia-ul-Haq, M. & Ahmad, M. (2012). Evaluation of antioxidant and urease inhibition activities of roots of Glycyrrhiza glabra. Pakistan Journal of Pharmaceutical Sciences, 25(1), 99–102.
  71. Lezi, E. & Swerdlow, R. H. (2012). Mitochondria in neurodegeneration. Advances in Mitochondrial Medicine, 269–286.
  72. Li, W., Rong, Y., Wang, J., Li, T. & Wang, Z. (2020). MnO2 switch-bridged DNA walker for ultrasensitive sensing of cholinesterase activity and organophosphorus pesticides. Biosensors and Bioelectronics, 169, 112605. Limmongkon, A., Janhom, P., Amthong, A., Kawpanuk, M., Nopprang, P., Poohadsuan, J. & Boonsong, T. (2017). Antioxidant activity, total phenolic, and resveratrol content in five cultivars of peanut sprouts. Asian Pacific Journal of Tropical Biomedicine, 7(4), 332–338. Luo, X., Su, P. & Zhang, W. (2015). Advances in microalgae-derived phytosterols for functional food and pharmaceutical applications. Marine Drugs, 13(7), 4231—4254.
  73. Mathew, B., Parambi, D. G., Mathew, G. E., Uddin, M. S., Inasu, S. T., Kim, H. & Carradori, S. (2019). Emerging therapeutic potentials of dual‐acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases. Archiv der Pharmazie, 352(11), 1900177.
  74. Mensink, R. P. & World Health Organization. (2016). Effects of saturated fatty acids on serum lipids and lipoproteins: a systematic review and regression analysis.
  75. Mo, H., Jeter, R., Bachmann, A., Yount, S. T., Shen, C. L. & Yeganehjoo, H. (2019). The potential of isoprenoids in adjuvant cancer therapy to reduce adverse effects of statins. Frontiers in Pharmacology, 9, 1515.
  76. Monguchi, T., Hara, T., Hasokawa, M., Nakajima, H., Mori, K., Toh, R. & Shinohara, M. (2017). Excessive intake of trans fatty acid accelerates atherosclerosis through promoting inflammation and oxidative stress in a mouse model of hyperlipidemia. Journal of Cardiology, 70(2), 121–127.
  77. Mozaffarian, D., Micha, R. & Wallace, S. (2010). Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Medicine, 7(3), e1000252.
  78. Mutlu, M., Bingol, Z., Uc, E. M., Köksal, E., Goren, A. C., Alwasel, S. H. & Gulcin, İ. (2023). Comprehensive metabolite profiling of cinnamon (Cinnamomum zeylanicum) leaf oil using LC-HR/MS, GC/MS, and GC-FID: Determination of antiglaucoma, antioxidant, anticholinergic, and antidiabetic profiles. Life, 13(1), 136.
  79. Nazarudin, M. F., Isha, A., Mastuki, S. N., Ain, N. M., Mohd Ikhsan, N. F., Abidin, A. Z. & Aliyu-Paiko, M. (2020). Chemical composition and evaluation of the α-glucosidase inhibitory and cytotoxic properties of marine algae Ulva intestinalis, Halimeda macroloba, and Sargassum ilicifolium. Evidence-based Complementary and Alternative Medicine, 2020.
  80. Nelson, R. H. (2013). Hyperlipidemia as a risk factor for cardiovascular disease. Primary Care: Clinics in Office Practice, 40(1), 195–211.
  81. Nie, C., Zhang, F., Ma, X., Guo, R., Zhou, S., Zhao, L. & Wang, Z. (2018). Determination of quality markers of Xuezhiling tablet for hyperlipidemia treatment. Phytomedicine, 44, 231–238.
  82. Nijhawan, P., Arora, S. & Behl, T. (2019). Intricate role of oxidative stress in the progression of obesity. Obesity Medicine, 15, 100125.
  83. Nunes, X. P., Silva, F. S., Almeida, J. R. G. D. S., Barbosa Filho, J. M., de Lima, J. T., de Araújo Ribeiro, L. A. & Júnior, L. J. Q. (2012). Biological Oxidations and Antioxidant Activity of Natural Products (pp. 1–20). New York: INTECH Open Access Publisher.
  84. Oketch-Rabah, H. A., Marles, R. J., Jordan, S. A. & Dog, T. L. (2019). United States pharmacopeia safety review of Willow Bark. Planta Medica, 85(16), 1192–1202.
  85. Oyaizu, M. (1986). Studies on product of browning reaction prepared from glucose amine. Jpn. J. Nutr., 44, 307–315.
  86. Palabıyık, E., Sulumer, A. N., Uguz, H., Avcı, B., Askın, S., Askın, H. & Demir, Y. (2023). Assessment of hypolipidemic and anti‐inflammatory properties of walnut (Juglans regia) seed coat extract and modulates some metabolic enzymes activity in triton WR‐1339‐induced hyperlipidemia in rat kidney, liver, and heart. Journal of Molecular Recognition, 36(3), e3004.
  87. Palabiyik, E., Aşkın, S. & Aşkın, H. (2022). Effect of Walnut Seed Skin Against Main Organ Damage Caused by Hyperlipidemia. Avrupa Bilim ve Teknoloji Dergisi, 34, 652–656.
  88. Pei, D. & Lu, X. Z. (2011). Walnut germplasm resources in China. China For. Publ. House, Beijing, China. Ramsay, R. R., Majekova, M., Medina, M. & Valoti, M. (2016). Key targets for multi-target ligands designed to combat neurodegeneration. Frontiers in Neuroscience, 10, 375.
  89. Rasera, G. B., Hilkner, M. H., de Alencar, S. M. & de Castro, R. J. S. (2019). Biologically active compounds from white and black mustard grains: an optimization study for recovery and identification of phenolic antioxidants. Industrial Crops and Products, 135, 294–300.
  90. Ravanbakhsh, A., Mahdavi, M., Jalilzade-Amin, G., Javadi, S., Maham, M., Mohammadnejad, D. & Rashidi, M. R. (2016). Acute and subchronic toxicity study of the median septum of Juglans regia in Wistar rats. Advanced Pharmaceutical Bulletin, 6(4), 541. Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M. & Rice-Evans, C. (1999). Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology and Medicine, 26(9-10), 1231–1237. Ros, E., Izquierdo-Pulido, M. & Sala-Vila, A. (2018). Beneficial effects of walnut consumption on human health: Role of micronutrients. Current Opinion in Clinical Nutrition & Metabolic Care, 21(6), 498–504.
  91. Rusu, M. E., Fizesan, I., Pop, A., Mocan, A., Gheldiu, A. M., Babota, M. & Popa, D. S. (2020). Walnut (Juglans regia L.) septum: Assessment of bioactive molecules and in vitro biological effects. Molecules, 25(9), 2187.
  92. Rusu, M. E., Simedrea, R., Gheldiu, A. M., Mocan, A., Vlase, L., Popa, D. S. & Ferreira, I. C. (2019). Benefits of tree nut consumption on aging and age-related diseases: Mechanisms of actions. Trends in Food Science & Technology, 88, 104–120.
  93. Sanches, N. R., Garcia Cortez, D. A., Schiavini, M. S., Nakamura, C. V. & Dias Filho, B. P. (2005). An evaluation of antibacterial activities of Psidium guajava (L.). Brazilian Archives of Biology and Technology, 48, 429–436.
  94. Sehitoglu, M. H., Han, H., Kalin, P., Gülçin, İ., Ozkan, A. & Aboul-Enein, H. Y. (2015). Pistachio (Pistacia vera L.) gum: A potent inhibitor of reactive oxygen species. Journal of Enzyme Inhibition and Medicinal Chemistry, 30(2), 264–269.
  95. Shahidi, F. & Ambigaipalan, P. (2015). Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects–A review. Journal of Functional Foods, 18, 820–897. Shattat, G. F. (2015). A review article on hyperlipidemia: types, treatments and new drug targets. Biomedical and Pharmacology Journal, 7(1), 399–409.
  96. Sheikha, G. A., Bkhaitan, M. M., Kalloush, H., Hamadneh, L., Khalaf, R. A., Al-Qirim, T., & Al-Hiari, Y. (2018). Synthesis of Novel Benzimidazole-2-car boxamide Derivatives and in Vivo Antihyperlipidemic Activity Evaluation. Chemical and Pharmaceutical Bulletin, 66(4), 423–426.
  97. Silinsin, M. & Bursal, E. (2018). UHPLC-MS/MS phenolic profiling and in vitro antioxidant activities of Inula graveolens (L.) Desf. Natural Product Research, 32(12), 1467–1471.
  98. Soccol, C. R., Da Costa, E. S. F., Letti, L. A. J., Karp, S. G., Woiciechowski, A. L. & de Souza Vandenberghe, L. P. (2017). Recent developments and innovations in solid state fermentation. Biotechnology Research and Innovation, 1(1), 52–71.
  99. Sujayev, A., Garibov, E., Taslimi, P., Gulçin, İ., Gojayeva, S., Farzaliyev, V. & Supuran, C. T. (2016). Synthesis of some tetrahydropyrimidine-5-carboxylates, determination of their metal chelating effects and inhibition profiles against acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 1531–1539.
  100. Sun, B., Yan, H., Li, C., Yin, L., Li, F., Zhou, L. & Han, X. (2020). Beneficial effects of walnut (Juglans regia L.) oil-derived polyunsaturated fatty acid prevent a prooxidant status and hyperlipidemia in pregnant rats with diabetes. Nutrition & Metabolism, 17(1), 1–11.
  101. Sun, Y., Qi, G., Li, D., Meng, H., Zhu, Z., Zhao, Y. & Zhang, X. (2019). Walnut (Juglans regia L.) kernel extracts protect against isoproterenol-induced myocardial infarction in rats. Rejuvenation Research, 22(4), 306–312.
  102. Surya, S., Kumar, R. A., Carla, B. & Sunil, C. (2017). Antihyperlipidemic effect of Ficus dalhousiae miq. stem bark on Triton WR-1339 and high fat diet-induced hyperlipidemic rats. Bulletin of Faculty of Pharmacy, Cairo University, 55(1), 73–77.
  103. Sweidan, K., Sheikha, G. A., Shattat, G., Al-qirim, T. & Bkhaitan, M. (2022). Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats. Brazilian Journal of Pharmaceutical Sciences, 58.
  104. Taslimi, P., Köksal, E., Gören, A. C., Bursal, E., Aras, A., Kılıç, Ö. & Gülçin, İ. (2020). Anti-Alzheimer, antidiabetic and antioxidant potential of Satureja cuneifolia and analysis of its phenolic contents by LC-MS/MS. Arabian journal of Chemistry, 13(3), 4528–4537.
  105. Tohma, H., Altay, A., Köksal, E., Gören, A. C. & Gülçin, İ. (2019). Measurement of anticancer, antidiabetic and anticholinergic properties of sumac (Rhus coriaria): analysis of its phenolic compounds by LC–MS/MS. Journal of Food Measurement and Characterization, 13, 1607–1619.
  106. Tohma, H., Köksal, E., Kılıç, Ö., Alan, Y., Yılmaz, M. A., Gülçin, I. & Alwasel, S. H. (2016). RP-HPLC/MS/MS analysis of the phenolic compounds, antioxidant and antimicrobial activities of Salvia L. species. Antioxidants, 5(4), 38.
  107. Tooulia, K. K., Theodosis‐Nobelos, P. & Rekka, E. A. (2015). Thiomorpholine derivatives with hypolipidemic and antioxidant activity. Archiv der Pharmazie, 348(9), 629–634.
  108. Türkan, F., Atalar, M. N., Aras, A., Gülçin, İ. & Bursal, E. (2020). ICP-MS and HPLC analyses, enzyme inhibition and antioxidant potential of Achillea schischkinii Sosn. Bioorganic Chemistry, 94, 103333.
  109. Venkadeswaran, K., Muralidharan, A. R., Annadurai, T., Ruban, V. V., Sundararajan, M., Anandhi, R. & Geraldine, P. (2014). Antihypercholesterolemic and antioxidative potential of an extract of the plant, Piper betle, and its active constituent, eugenol, in triton WR-1339-induced hypercholesterolemia in experimental rats. Evidence-Based Complementary and Alternative Medicine, 2014.
  110. Vieira, V., Pereira, C., Abreu, R. M., Calhelha, R. C., Alves, M. J., Coutinho, J. A. & Ferreira, I. C. (2020). Hydroethanolic extract of Juglans regia L. green husks: A source of bioactive phytochemicals. Food and Chemical Toxicology, 137, 111189.
  111. von Holtz, R. L., Fink, C. S. & Awad, A. B. (1998). β‐sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells.
  112. Winklhofer-Roob, B. M., Faustmann, G. & Roob, J. M. (2017). Low-density lipoprotein oxidation biomarkers in human health and disease and effects of bioactive compounds. Free Radical Biology and Medicine, 111, 38–86.
  113. Xu, Y., Wang, F., Guo, H., Wang, S., Ni, S., Zhou, Y. & Wang, Y. (2019). Antitussive and anti-inflammatory dual-active agents developed from natural product lead compound 1-methylhydantoin. Molecules, 24(13), 2355.
  114. Yang, X., Li, Y., Li, Y., Ren, X., Zhang, X., Hu, D. & Shang, H. (2017). Oxidative stress-mediated atherosclerosis: mechanisms and therapies. Frontiers in Physiology, 8, 600.
  115. Yu, Z., Xu, H., Yu, X., Sui, D. & Lin, G. (2017). Hypolipidemic effects of total flavonoide extracted from the leaves of Actinidiakolomikta in rats fed a high-fat diet. Iranian Journal of Basic Medical Sciences, 20(10), 1141.
  116. Zarzecki, M. S., Araujo, S. M., Bortolotto, V. C., de Paula, M. T., Jesse, C. R. & Prigol, M. (2014). Hypolipidemic action of chrysin on Triton WR-1339-induced hyperlipidemia in female C57BL/6 mice. Toxicology Reports, 1, 200–208.
  117. Zhang, S., Wang, S., Huang, J., Lai, X., Du, Y., Liu, X. & Yang, G. (2016). High-specificity quantification method for almond-by-products, based on differential proteomic analysis. Food Chemistry, 194, 522–528.
  118. Zhao, L., Huang, Y., Adeleye, A. S. & Keller, A. A. (2017). Metabolomics reveals Cu (OH) 2 nanopesticide-activated anti-oxidative pathways and decreased beneficial antioxidants in spinach leaves. Environmental Science & Technology, 51(17), 10184–10194.
  119. Zong-liang, L., Zhi-min, X., Wen-rong, K. & Shui-ping, Z. (2006). Advance in basic and clinical research of Xuezhikang capsule. Chinese journal of integrative Medicine, 12(2), 85–93.
  120. Beyegue, C. N., Ngangoum, R. C., Kuate, D., Ngondi, J. L. & Oben, J. E. (2012). Effect of Guibourtia tessmannii extracts on blood lipids and oxidative stress markers in triton WR 1339 and high fat diet induced hyperlipidemic rats. Biology and Medicine, 4(1), 1–10.