Author(s): Boburbek Yuldoshev, Nurali Ergashev, Esokhon Komilov, Yulduz Rakhmatillayeva, Donyor Siddiqov, Nozim Shodiev, Muzaffar Asrarov, Gulnazira Abdulkhakova

Email(s): yuldoshevboburbek10@gmail.com , nuraliergashev79@gmail.com

DOI: 10.52711/0974-360X.2026.00577   

Address: Boburbek Yuldoshev1, Nurali Ergashev2, Esokhon Komilov3, Yulduz Rakhmatillayeva4, Donyor Siddiqov5, Nozim Shodiev6, Muzaffar Asrarov7, Gulnazira Abdulkhakova8
1PhD Student of the Institute of Biophysics and Biochemistry at the National University of Uzbekistan, Tashkent, Republic of Uzbekistan.
2DSc of the Institute of Biophysics and Biochemistry at the National University of Uzbekistan, Tashkent, Republic of Uzbekistan.
3PhD in the Institute of Biophysics and Biochemistry at the National University of Uzbekistan, Tashkent, Republic of Uzbekistan.
4Master’s Student of Karshi State University, Karshi, Republic of Uzbekistan.
5PhD in S.Yu.Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan.
6PhD Student of the University of Debrecen, Hungary.
7Professor of the Institute of Biophysics and Biochemistry at the National University of Uzbekistan, Tashkent, Republic of Uzbekistan.
8PhD Student of the Institute of Biophysics

Published In:   Volume - 19,      Issue - 9,     Year - 2026


ABSTRACT:
Oxidative stress (OS) is a pathological state that develops when there is a disequilibrium between the generation and accumulation of reactive oxygen species (ROS) in cells and tissues and the capacity of biological systems to detoxify these reactive intermediates. Free radicals, mainly formed from unsaturated fatty acids during lipid peroxidation, act as secondary messengers in oxidative and electrophilic stress responses by transmitting electrophilic signals. They also influence vital cellular pathways, including autophagy, proliferation, and apoptosis. Considering the harmful consequences of OS, the present study examined the effect of the flavonoid kaempferol on malondialdehyde (MDA) formation and the activities of major antioxidant enzymes—catalase, glutathione peroxidase (GPx), and glutathione reductase (GR)—in rat brain tissue homogenates exposed to oxidative stress. Moreover, the in vivo impact of kaempferol and its glycosides (kaempferol-7-O-rhamnoside, kaempferitrin, and afzelin) on NADH dehydrogenase activity in rat brain mitochondria was also evaluated. The findings revealed that kaempferol exhibited potent antioxidant activity under OS conditions. It significantly enhanced GPx and GR activities while lowering MDA levels, a key lipid peroxidation byproduct that accumulates during oxidative stress. Kaempferol also restored catalase activity, which was markedly reduced under OS. Specifically, kaempferol decreased MDA accumulation by 1.61-fold and increased catalase activity by 3.3-fold. Additionally, GPx and GR activities, which had been substantially reduced by OS, were recovered to 77.16% and 63.13% of control levels, respectively. Kaempferol also showed strong inhibitory effects on mitochondrial NADH dehydrogenase activity, achieving complete inhibition at 50 µM. Its glycosides exhibited lower but significant inhibition, with kaempferol-7-O-rhamnoside reducing activity by 84.34 ± 0.96%, kaempferitrin by 61.58±1.9%, and afzelin by 47.64±1.6%. The overall order of inhibitory potency was: kaempferol > kaempferol-7-O-rhamnoside > kaempferitrin > afzelin.


Cite this article:
Boburbek Yuldoshev, Nurali Ergashev, Esokhon Komilov, Yulduz Rakhmatillayeva, Donyor Siddiqov, Nozim Shodiev, Muzaffar Asrarov, Gulnazira Abdulkhakova. The effects of Kaempferol and its Glycosides on MDA Formation and the Activity of some Enzymes in In Vitro and In Vivo studies. Research Journal Pharmacy and Technology. 2026;19(9):4117-5. doi: 10.52711/0974-360X.2026.00577

Cite(Electronic):
Boburbek Yuldoshev, Nurali Ergashev, Esokhon Komilov, Yulduz Rakhmatillayeva, Donyor Siddiqov, Nozim Shodiev, Muzaffar Asrarov, Gulnazira Abdulkhakova. The effects of Kaempferol and its Glycosides on MDA Formation and the Activity of some Enzymes in In Vitro and In Vivo studies. Research Journal Pharmacy and Technology. 2026;19(9):4117-5. doi: 10.52711/0974-360X.2026.00577   Available on: https://rjptonline.org/AbstractView.aspx?PID=2026-19-9-23


REFERENCES:
1.    Jomova K, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Valko M. Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Archives of Toxicology. 2024; 98(5): 1323-67.
2.    Juan CA, Pérez de la Lastra JM, Plou FJ, Pérez-Lebeña E. The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies. International Journal of Molecular Sciences. 2021; 22(9).
3.    Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Archives of Toxicology. 2023; 97(10): 2499-574.
4.    Reddy VP. Oxidative Stress in Health and Disease. Biomedicines. 2023; 11(11).
5.    Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. The Lancet Neurology. 2011; 10(9): 819-28.
6.    Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999; 53(9): 1937-42.
7.    Shoeb M, Ansari NH, Srivastava SK, Ramana KV. 4-Hydroxynonenal in the pathogenesis and progression of human diseases. Current Medicinal Chemistry. 2014; 21(2): 230-7.
8.    Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? Journal of Alzheimer's disease: JAD. 2005; 7(1): 63-80.
9.    Faiq MA, Sengupta T, Nath M, Velpandian T, Saluja D, Dada R, et al. Ocular manifestations of central insulin resistance. Neural regeneration research. 2023;18(5):1139-46.
10.    González A, Calfío C, Churruca M, Maccioni RB. Glucose metabolism and AD: evidence for a potential diabetes type 3. Alzheimer's Research and Therapy. 2022; 14(1): 56.
11.    Kandimalla R, Thirumala V, Reddy PH. Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal. Biochimica et biophysica acta Molecular basis of disease. 2017; 1863(5): 1078-89.
12.    Kroner Z. The relationship between Alzheimer's disease and diabetes: Type 3 diabetes? Alternative medicine review : A Journal Of Clinical Therapeutic. 2009; 14(4): 373-9.
13.    Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease. Biochimica et biophysica acta Molecular basis of disease. 2017; 1863(5): 1037-45.
14.    Stanciu GD, Bild V, Ababei DC, Rusu RN, Cobzaru A, Paduraru L, et al. Link Between Diabetes and Alzheimer's Disease due to the Shared Amyloid Aggregation and Deposition Involving both Neurodegenerative Changes and Neurovascular Damages. Journal of Clinical Medicine. 2020; 9(6).
15.    Mortezaee K. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and liver fibrosis: A review. Cell biochemistry and function. 2018; 36(6): 292-302.
16.    Halliwell B, Gutteridge J. Free Radicals in Biology and Medicine2015.
17.    Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian journal of clinical biochemistry: IJCB. 2015; 30(1): 11-26.
18.    Fialkow L, Wang Y, Downey GP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free radical biology and medicine. 2007; 42(2): 153-64.
19.    Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clinical interventions in aging. 2018; 13: 757-72.
20.    Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. The international journal of biochemistry and cell biology. 2007; 39(1): 44-84.
21.    Wu JQ, Kosten TR, Zhang XY. Free radicals, antioxidant defense systems, and schizophrenia. Progress in neuro-psychopharmacology and biological psychiatry. 2013; 46: 200-6.
22.    Zhang J, Hu J, Sang W, Wang J, Yan Q. Peroxynitrite (ONOO(-)) Redox Signaling Molecule-Responsive Polymersomes. ACS macro letters. 2016; 5(8): 919-24.
23.    Halliwell B. Reactive oxygen species (ROS), oxygen radicals and antioxidants: Where are we now, where is the field going and where should we go? Biochemical and biophysical research communications. 2022; 633: 17-9.
24.    Ji T, Zheng L, Wu J, Duan M, Liu Q, Liu P, et al. The thioesterase APT1 is a bidirectional-adjustment redox sensor. Nature communications. 2023; 14(1): 2807.
25.    Mates JM, Pérez-Gómez C, Núñez de Castro I. Antioxidant enzymes and human diseases. Clinical biochemistry. 1999; 32(8): 595-603.
26.    Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine. 2018; 54(4): 287-93.
27.    Cheng J, Wang F, Yu DF, Wu PF, Chen JG. The cytotoxic mechanism of malondialdehyde and protective effect of carnosine via protein cross-linking/mitochondrial dysfunction/reactive oxygen species/MAPK pathway in neurons. European Journal of Pharmacology. 2011; 650(1): 184-94.
28.    Narayanankutty A, Job JT, Narayanankutty V. Glutathione, an Antioxidant Tripeptide: Dual Roles in Carcinogenesis and Chemoprevention. Current protein and peptide science. 2019; 20(9): 907-17.
29.    Corso CR, Acco A. Glutathione system in animal model of solid tumors: From regulation to therapeutic target. Critical reviews in oncology/hematology. 2018; 128: 43-57.
30.    Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free radical biology and medicine. 2016; 95: 27-42.
31.    Handy DE, Loscalzo J. The role of glutathione peroxidase-1 in health and disease. Free radical biology and medicine. 2022; 188: 146-61.
32.    Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigó R, et al. Characterization of mammalian selenoproteomes. Science (New York, NY). 2003; 300(5624): 1439-43.
33.    Wagner AH, Kautz O, Fricke K, Zerr-Fouineau M, Demicheva E, Güldenzoph B, et al. Upregulation of glutathione peroxidase offsets stretch-induced proatherogenic gene expression in human endothelial cells. Arteriosclerosis, thrombosis, and vascular biology. 2009; 29(11): 1894-901.
34.    Guo Z, Ran Q, Roberts LJ, 2nd, Zhou L, Richardson A, Sharan C, et al. Suppression of atherogenesis by overexpression of glutathione peroxidase-4 in apolipoprotein E-deficient mice. Free radical biology and medicine. 2008; 44(3): 343-52.
35.    Lee SE, Park YS. The Emerging Roles of Antioxidant Enzymes by Dietary Phytochemicals in Vascular Diseases. Life (Basel, Switzerland). 2021; 11(3).
36.    Shingu M, Yoshioka K, Nobunaga M, Yoshida K. Human vascular smooth muscle cells and endothelial cells lack catalase activity and are susceptible to hydrogen peroxide. Inflammation. 1985; 9(3): 309-20.
37.    van den Bosch H, Schutgens RB, Wanders RJ, Tager JM. Biochemistry of peroxisomes. Annual review of biochemistry. 1992; 61: 157-97.
38.    Dubick MA, Keen CL, DiSilvestro RA, Eskelson CD, Ireton J, Hunter GC. Antioxidant enzyme activity in human abdominal aortic aneurysmal and occlusive disease. Proceedings of the Society for Experimental Biology and Medicine Society for Experimental Biology and Medicine (New York, NY). 1999; 220(1): 39-45.
39.    Ramos-Mozo P, Madrigal-Matute J, Martinez-Pinna R, Blanco-Colio LM, Lopez JA, Camafeita E, et al. Proteomic analysis of polymorphonuclear neutrophils identifies catalase as a novel biomarker of abdominal aortic aneurysm: potential implication of oxidative stress in abdominal aortic aneurysm progression. Arteriosclerosis, thrombosis, and vascular biology. 2011; 31(12): 3011-9.
40.    Wang W, Wang YR, Chen J, Chen YJ, Wang ZX, Geng M, et al. Pterostilbene Attenuates Experimental Atherosclerosis through Restoring Catalase-Mediated Redox Balance in Vascular Smooth Muscle Cells. Journal of agricultural and food chemistry. 2019;67(46):12752-60.
41.    Kerscher S, Dröse S, Zickermann V, Brandt U. The three families of respiratory NADH dehydrogenases. Results and problems in cell differentiation. 2008;45:185-222.
42.    Herrmann JM, Riemer J. Apoptosis inducing factor and mitochondrial NADH dehydrogenases: redox-controlled gear boxes to switch between mitochondrial biogenesis and cell death. Biological chemistry. 2021; 402(3): 289-97.
43.    Saladi S, Boos F, Poglitsch M, Meyer H, Sommer F, Mühlhaus T, et al. The NADH Dehydrogenase Nde1 Executes Cell Death after Integrating Signals from Metabolism and Proteostasis on the Mitochondrial Surface. Molecular cell. 2020; 77(1): 189-202.e6.
44.    Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017; 2017: 8416763.
45.    Huccetogullari D, Luo ZW, Lee SY. Metabolic engineering of microorganisms for production of aromatic compounds. Microbial cell factories. 2019; 18(1): 41.
46.    Yonekura-Sakakibara K, Higashi Y, Nakabayashi R. The Origin and Evolution of Plant Flavonoid Metabolism. Frontiers in Plant Science. 2019; 10: 943.
47.    Kumar S, Mishra A, Pandey AK. Antioxidant mediated protective effect of Parthenium hysterophorus against oxidative damage using in vitro models. BMC complementary and alternative medicine. 2013; 13: 120.
48.    Mishra A, Kumar S, Pandey AK. Scientific validation of the medicinal efficacy of Tinospora cordifolia. TheScientificWorldJournal. 2013; 2013: 292934.
49.    Pandey AK, Mishra AK, Mishra A. Antifungal and antioxidative potential of oil and extracts derived from leaves of Indian spice plant Cinnamomum tamala. Cellular and molecular biology (Noisy-le-Grand, France). 2012; 58(1): 142-7.
50.    Imran M, Rauf A, Shah ZA, Saeed F, Imran A, Arshad MU, et al. Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review. Phytotherapy research: PTR. 2019; 33(2): 263-75.
51.    Ren J, Lu Y, Qian Y, Chen B, Wu T, Ji G. Recent progress regarding kaempferol for the treatment of various diseases. Experimental and therapeutic medicine. 2019; 18(4): 2759-76.
52.    Guo Z, Liao Z, Huang L, Liu D, Yin D, He M. Kaempferol protects cardiomyocytes against anoxia/reoxygenation injury via mitochondrial pathway mediated by SIRT1. European journal of pharmacology. 2015; 761: 245-53.
53.    López-Sánchez C, Lagoa R, Poejo J, García-López V, García-Martínez V, Gutierrez-Merino C. An Update of Kaempferol Protection against Brain Damage Induced by Ischemia-Reperfusion and by 3-Nitropropionic Acid. Molecules. 2024; 29(4).
54.    Zhang N, Xu H, Wang Y, Yao Y, Liu G, Lei X, et al. Protective mechanism of kaempferol against Aβ(25-35)-mediated apoptosis of pheochromocytoma (PC-12) cells through the ER/ERK/MAPK signalling pathway. Archives of Medical Science: AMS. 2021; 17(2): 406-16.
55.    Ramkumar KM, Vijayakumar RS, Vanitha P, Suganya N, Manjula C, Rajaguru P, et al. Protective effect of gallic acid on alloxan-induced oxidative stress and osmotic fragility in rats. Human and experimental toxicology. 2014; 33(6): 638-49.
56.    Орёл НМ, Новиков ДА, Кукулянская ТА, Губич ОИ, Зырянова ТН, Корик ЕО, et al. Практикум по биохимии: пособие/сост.: НМ Орёл [и др.]. 2015.
57.    Popov SS, Shulgin KK, Pashkov AN, Agarkov AA. The effect of melaxen on the activity of caspases and the glutathione antioxidant system in toxic liver injury. Acta naturae. 2014; 6(2): 110-8.
58.    Lu Z, Hu Y, Wang Y, Zhang T, Long J, Liu J. Topological reorganizations of mitochondria isolated from rat brain after 72 hours of paradoxical sleep deprivation, revealed by electron cryo-tomography. American Journal of Physiology-Cell Physiology. 2021; 321(1): C17-C25.
59.    Watters C. A one-step biuret assay for protein in the presence of detergent. Analytical biochemistry. 1978;88(2):695-8.
60.    Shukolyukov S. Oxidation of pyridinnucleotides by bovine retinal rod outer segments. Journal of Evolutionary Biochemistry and Physiology. 1970; 6: 504-10.
61.    Huo H, Zhang A, Shi Y, Zhuo Y, Nan C, Yan D, et al. Kaempferol Plays a Neuroprotection Role by Alleviating Oxidative Stress via AKT/Nrf2/HO-1 Pathway and Inhibiting Apoptosis in Intracerebral Hemorrhage. Neurochemical research. 2025; 50(5): 291.
62.    Wang J, Mao J, Wang R, Li S, Wu B, Yuan Y. Kaempferol Protects Against Cerebral Ischemia Reperfusion Injury Through Intervening Oxidative and Inflammatory Stress Induced Apoptosis. Frontiers in pharmacology. 2020; 11: 424.
63.    Silva Dos Santos J, Gonçalves Cirino JP, de Oliveira Carvalho P, Ortega MM. The Pharmacological Action of Kaempferol in Central Nervous System Diseases: A Review. Frontiers in Pharmacology. 2020; 11: 565700.
64.    Akefe IO, Ayo JO, Sinkalu VO. Kaempferol and zinc gluconate mitigate neurobehavioral deficits and oxidative stress induced by noise exposure in Wistar rats. PloS one. 2020; 15(7): e0236251.
65.    Wang Y, Chen C, Li Y, Li R, Wang J, Wu C, et al. Kaempferol inhibits oxidative stress and reduces macrophage pyroptosis by activating the NRF2 signaling pathway. PLoS One. 2025;20(6):e0325189.
66.    Du W, An Y, He X, Zhang D, He W. Protection of Kaempferol on Oxidative Stress-Induced Retinal Pigment Epithelial Cell Damage. Oxidative medicine and cellular longevity. 2018; 2018: 1610751.
67.    Hussein RM, Mohamed WR, Omar HA. A neuroprotective role of kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3β-Nrf2 signaling pathway. Pesticide biochemistry and physiology. 2018; 152: 29-37.
68.    Cui Y, Zhao S, Wu Z, Dai P, Zhou B. Mitochondrial release of the NADH dehydrogenase Ndi1 induces apoptosis in yeast. Molecular biology of the cell. 2012; 23(22): 4373-82.
69.    Vera A-V, Laszlo T. The role of mitochondrial dehydrogenases in the generation of oxidative stress. Neurochemistry International. 2013; 62(5): 757-63.
70.    Yang C, Yang W, He Z, Guo J, Yang X, Wang R, et al. Kaempferol Alleviates Oxidative Stress and Apoptosis Through Mitochondria-dependent Pathway During Lung Ischemia-Reperfusion Injury. Frontiers in Pharmacology. 2021; 12: 624402.

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