- Please check and comment entries here.
Anthocyanins and Chronic Diseases
Anthocyanins constitute a subclass of flavonoids with more than 700 structurally different anthocyanin derivatives of 27 aglycons identified. Anthocyanins are glucosides of the anthocyanidins (precursors of anthocyanins), which are derivatives via the phenylpropanoid pathway. Due to their multiple phenyl groups, anthocyanins are rarely found as aglycons (anthocyanidins).
Inflammation affects a wide variety of physiological and pathological processes. This condition is an essential component of immune surveillance and host defense. Although the pathological aspects of numerous mechanisms of inflammation are well recognized, their physiological functions are mostly unexplained.
Low-grade chronic inflammation (LGCI) is a pathological feature of a wide range of chronic conditions. LGCI is characterized by elevated concentrations of inflammatory markers in the absence of any overt symptoms. However, this condition has not yet been consistently defined or measured. Although there is likely a genetic predisposition, many other triggers can impact the inflammatory process. Some exogenous and endogenous factors such as smoking, air pollution, silica dust, recurrent episodes of acute inflammation, persistent infections, autoimmune disorders, and overweight or obesity have been identified. Several triggers including overproduction of reactive oxygen species (ROS) and advanced glycation end products (AGEs), mitochondrial dysfunction, renin–angiotensin system (RAS) deregulation, hormonal changes, uric acid (urate) crystals, oxidized lipoproteins, homocysteine, visceral adiposity, an imbalance in the gut microbiota, and accumulation of cell debris due to defective autophagy also play a significant role .
In recent years LGCI has been shown to contribute to most if not all chronic diseases typical of age-related decline of many functional systems in the older population. This phenomenon has been termed “inflamm-aging” . LGI has also been given the name “metaflammation” (an inflammation of metabolic tissue), which originates from metabolic cells in response to excess nutrients . There is a general lack of sensitive and specific biomarkers of low-grade chronic inflammation that can be used in human trials. In humans, the most well-accepted markers of systemic inflammation are a number of circulating pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8). To date, high-sensitivity C-reactive protein (hsCRP), fibrinogen, and such cellular biomarkers like the white blood cell and platelet counts have also been used to assess LGCI .
Current research provides links among the change in inflammatory profile and the risk of a number of chronic conditions, including metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), cancer, cardiovascular, and neurodegenerative disease .
Inflammation and oxidative stress act as cooperative and synergistic partners in the pathogenesis of a wide variety of diseases, elevating adverse chronic diseases’ risk factors levels . As an example, misdirected oxidative stress in various tissues potentiates inflammatory responses and inciting target organ damage . Oxidative stress occurs when an organism accumulates more ROS than can be eliminated by antioxidant defense mechanisms. The accumulation of ROS and free radicals in a cell affects many important compounds, such as lipids, proteins, DNA, carbohydrates, and enzymes, and can result in cell damage . In healthy humans, cells defend themselves against ROS-related damage through antioxidants that prevent or counterbalance oxidation even at low concentrations. The ROS and antioxidant protection against free radical tissue injury are in balance . It has been reported that impaired oxidant—antioxidant status is involved in the etiopathogenesis of various complications .
Dietary factors are involved in regulating the inflammatory state and activating the endogenous antioxidant defenses. Protective dietary compounds such as polyphenols, which are consumed together with a human diet, may be beneficial in attenuating the potentially harmful risk factors of chronic diseases. Among them, anthocyanins are emerging potential agents for counteracting the onset and progression of numerous non-communicable diseases such as neurodegenerative, cardiovascular, and metabolic diseases and cancer. They have been shown to stimulate immunomodulatory and antioxidant effects, thereby blunting the cooperative and synergistic deleterious effects of oxidative stress and pro-inflammatory cytokines and may, therefore, provide protection against chronic diseases . Their anti-inflammatory activity has been widely investigated by many authors. In the query performed in the ClinicalTrials.gov database in May 2021, the keyword “anthocyanin” has identified 145 clinical studies in which anthocyanins were registered.
2. Anthocyanins and Their Antioxidant and Anti-Inflammatory Activity
Anthocyanins and their metabolites, which are found in food, possess many biochemical properties, but the best-investigated effect is their antioxidants . These substances can be mediated by inhibition of both the activity and production of various pro-inflammatory important substances and enzymes, such as TNF-α, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and lipoxygenase (LOX). They are also known for upregulating the production of glutamate-cysteine ligase (GCL) and of glutamate-cysteine ligase modifier subunit (GCLM), and consequently, the levels of reduced glutathione (GSH), in activated microglial cells . Of natural substances, anthocyanins have been suggested to play an important role in the suppression of inflammation also by inhibition of nuclear factor-kappa B cells (NF-κB) activation, which, in turn, is responsible for the control of transcription of DNA, cytokine production, and cell survival . For example, cyanidin-3-glucoside, major anthocyanin of black rice ( Oryza sativa L.), inhibited nuclear translocation of NF-κB p50 and p65 signaling in a 5-Fluoruracil-induced oral mucositis rat model and in oral keratinocyte culture . Another investigator showed that malvidin-3-glucoside, found in rabbiteye blueberry ( Vaccinium ashei ), also suppressed TNFα in human umbilical vein endothelial cells by inhibiting nuclear translocation of p65 of NF-κB . Treatment with cyanidin-3- O -sophoroside and cyanidin-3- O -sambubioside from black peanut ameliorated UV-irradiated oxidative injury through the action of the nuclear factor erythroid 2-related factor 2 (Nrf2) by interaction with the NF-κB signaling pathway in human keratinocyte cells (HaCaT cells) and mice skin . This finding suggested that anthocyanins from black peanut skin might regulate oxidative stress and the suppression of cell apoptosis and might be used as a potential protective agent against UV-B-induced skin damage.
|Disorder/Substances||In Vitro or In Vivo Model||Mode of Action||References|
|Adipose Tissue Inflammation|
|Delta-tocotrienol, (DT3), and tart cherry anthocyanins (TCA)||3T3-L1 adipocytes||↓||IL-6 secretion and expression from adipocytes
Down-regulation of Mip2, and COX-2 mediated via the NFkB
|Harlan et al.
|cyanidin-3-O-glucoside||Murine 3T3-L1 hypertrophic adipocytes||Modulating the expression of the PPAR-ɣ,
Inhibiting the inflammatory pathway modulated by NF-κB
|Molonia et al. |
|Pulmonary Artery Hypertension|
|Cyanidin-3-O-β-glucoside||Transforming growth factor-β1 (TGF-β1)-mediated human pulmonary arterial smooth muscle cells (SMCs),
Pulmonary artery hypertension (PAH) rats
|IL-6, TNF-α and IL-10
Suppressive effect on PAH progression
|Ouyang et al.
|Padus racemose Anthocyanins||H2 O2 -induced rat insulinoma (INS-1) pancreatic cells damage||inhibiting the activation of p38 MAPK and NF-κB||Liu et al.
|Hypercholestrolemia and Hepatic Inflammation|
|Black Raspberry (Rubus occidentalis)||Rats fed high-fat and high-choline diets||↓
|cecal TMA and serum oxidized TMAO,
mRNA expression of pro-inflammatory genes including NF-κB, IL-1β, IL-6, COX-2
protein expression of NF-κB and COX-2 in liver tissue
|Lim et al.
|rice bran, cyanidin 3-glucoside||Human prostatic cancer (PC3) cells||↓
|expression of Smad/Snail signaling molecules
expression of cell surface protein, E-cadherin
Inhibited matrix metalloproteinase-9 and NF-κB Mediating Snail/E-cadherin expression
|Vitis coignetiae Pulliat (Meoru in Korea)||MCF-7 Human Breast Cancer Cells||↑||Inhibiting Akt and NF-κB activity
Cisplatin (anti-cancer drug) sensitivity
et al. 
|Dark Sweet Cherry (Prunus avium)||MDA-MB-453 breast cancer cells and athymic mice xenografted with MDA-MB-453 breast cancer cells||↑||Bax/Bcl-2 ratio
Activation of MAPKs ERK1/2 and p38
Down-regulation of total oncogenic and stress-related Akt
|Layosa et al.
Noratto et al.
|Vitis coignetiae Pulliat (Meoru in Korea)||Hep3B Human Hepatocellular Carcinoma Cells||Inhibition of the activation NF-κB and suppressed the NF-κB-regulated proteins,
Inhibition of proliferation, invasion, and angiogenesis
|Kim et al.
|Dried acai berries extract (Euterpe oleracea)||Ethanol-induced gastric ulcer in rats||↑
|GSH content and GST and CAT activity
MPO activity, TNF-a
|Cury et al.
|Hibiscus sabdariffa L. (Malvaceae)||Streptozotocin-induced Alzheimer’s disease in mice||↓
|TNF-α, IL-6, and IL-1β
Elevated MDA and MPO
Reverse up-regulation in the amyloidogenic pathway
|El-Shiekh et al.
|Delphinidin||Alzheimer’s disease model in rats||↓
|AChE, APP, and Aβ
ROS overproduction in hippocampus
|Heysieattalab et al.
|Portugal Blueberries (Vaccinium corymbosum L)||Mouse microglia N9 cell line||↓
|Suppression of NF-kB and STAT1
NO, PGE2, COX-2
Intracellular Production of ROS
|Serra et al.
|Cyanidin-3-O-glucoside||High glucose-induced lens epithelial cell (SRA01/04)||Inhibition SRA01/04 cell apoptosis
Regulation of the Bcl-2/Bax ratio
Suppression of NF-κB activation and subsequent Cox-2 expression
|Song et al.
The entry is from 10.3390/molecules26144380
- Custodero, C.; Mankowski, R.T.; Lee, S.A.; Chen, Z.; Wu, S.; Manini, T.M.; Echeverri, J.H.; Sabbà, C.; Beavers, D.P.; Cauley, J.A.; et al. Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in mid-dle-age and older adults: A systematic review and meta-analysis. Ageing Res. Rev. 2018, 46, 42–59.
- Hutchinson, A.N.; Tingö, L.; Brummer, R.J. The Potential Effects of Probiotics and ω-3 Fatty Acids on Chronic Low-Grade In-flammation. Nutrients 2020, 12, 2402.
- Calder, P.; Bosco, N.; Bourdet-Sicard, R.; Capuron, L.; Delzenne, N.; Doré, J.; Franceschi, C.; Lehtinen, M.J.; Recker, T.; Salvioli, S.; et al. Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition. Ageing Res. Rev. 2017, 40, 95–119.
- Power Guerra, N.; Müller, L.; Pilz, K.; Glatzel, A.; Jenderny, D.; Janowitz, D.; Vollmar, B.; Kuhla, A. Dietary-Induced Low-Grade Inflammation in the Liver. Biomedicines 2020, 8, 587.
- Bonaccio, M.; Pounis, G.; Cerletti, C.; Donati, M.B.; Iacoviello, L.; De Gaetano, G.; on behalf of the MOLI-SANI Study Investigators. Mediterranean diet, dietary polyphenols and low grade inflammation: Results from the MOLI-SANI study. Br. J. Clin. Pharmacol. 2016, 83, 107–113.
- Barbaresko, J.; Koch, M.; Schulze, M.B.; Nöthlings, U. Dietary pattern analysis and biomarkers of low-grade inflammation: A systematic literature review. Nutr. Rev. 2013, 71, 511–527.
- Sproston, N.R.; Ashworth, J.J. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front. Immunol. 2018, 9, 754.
- Żelechowska, P.; Agier, J.; Kozłowska, E.; Brzezińska-Błaszczyk, E.; Żelechowska, P.; Agier, J.; Kozłowska, E.; Brzezińska-Błaszczyk, E. Mast cells participate in chronic low-grade inflammation within adipose tissue. Obes. Rev. 2018, 19, 686–697.
- Bakkar, N.Z.; Dwaib, H.S.; Fares, S.; Eid, A.H.; Al-Dhaheri, Y.; El-Yazbi, A.F. Cardiac Autonomic Neuropathy: A Progressive Consequence of Chronic Low-Grade Inflammation in Type 2 Di-abetes and Related Metabolic Disorders. Int. J. Mol. Sci. 2020, 21, 9005.
- Corrêa, T.A.F.; Quintanilha, B.J.; Norde, M.M.; Pinhel, M.A.D.S.; Nonino, C.B.; Rogero, M.M. Nutritional genomics, inflammation and obesity. Arch. Endocrinol. Metab. 2020, 64, 205–222.
- Lund, M.A.V.; Thostrup, A.H.; Frithioff-Bøjsøe, C.; Lausten-Thomsen, U.; Hedley, P.L.; Pedersen, O.; Christiansen, M.; Hansen, T.; Holm, J.-C. Low-grade inflammation independently associates with cardiometabolic risk in children with overweight/obesity. Nutr. Metab. Cardiovasc. Dis. 2020, 30, 1544–1553.
- Lüscher, T.F. Cardio-oncology: Low-grade inflammation as a common pathway of cancer and cardiovascular disease. Eur. Heart J. 2019, 40, 3871–3874.
- Singh, N.; Baby, D.; Rajguru, J.P.; Patil, P.B.; Thakkannavar, S.S.; Pujari, V.B. Inflammation and cancer. Ann. Afr. Med. 2019, 18, 121–126.
- Crowley, S.D. The Cooperative Roles of Inflammation and Oxidative Stress in the Pathogenesis of Hypertension. Antioxidants Redox Signal. 2014, 20, 102–120.
- Pizzino, G.; Irrera, N.; Cucinotta, M.; Pallio, G.; Mannino, F.; Arcoraci, V.; Squadrito, F.; Altavilla, D.; Bitto, A. Oxidative Stress: Harms and Benefits for Human Health. Oxid. Med. Cell. Longev. 2017, 2017, 8416763.
- Tena, N.; Martín, J.; Asuero, A.G. State of the Art of Anthocyanins: Antioxidant Activity, Sources, Bioavailability, and Therapeutic Effect in Human Health. Antioxidants 2020, 9, 451.
- Wojsiat, J.; Zoltowska, K.M.; Laskowska-Kaszub, K.; Wojda, U. Oxidant/Antioxidant Imbalance in Alzheimer’s Disease: Therapeutic and Diagnostic Prospects. Oxidative Med. Cell. Longev. 2018, 2018, 1–16.
- Arroyave-Ospina, J.C.; Wu, Z.; Geng, Y.; Moshage, H. Role of Oxidative Stress in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Implications for Prevention and Therapy. Antioxidants 2021, 10, 174.
- Spahis, S.; Borys, J.-M.; Levy, E. Metabolic Syndrome as a Multifaceted Risk Factor for Oxidative Stress. Antioxid. Redox Signal. 2017, 26, 445–461.
- Rosario, V.A.D.; Chang, C.; Spencer, J.; Alahakone, T.; Roodenrys, S.; Francois, M.; Weston-Green, K.; Hölzel, N.; Nichols, D.S.; Kent, K.; et al. Anthocyanins attenuate vascular and inflammatory responses to a high fat high energy meal challenge in overweight older adults: A cross-over, randomized, double-blind clinical trial. Clin. Nutr. 2021, 40, 879–889.
- Smeriglio, A.; Barreca, D.; Bellocco, E.; Trombetta, D. Chemistry, Pharmacology and Health Benefits of Anthocyanins. Phytother. Res. 2016, 30, 1265–1286.
- Wang, Y.; Qian, J.; Cao, J.; Wang, D.; Liu, C.; Yang, R.; Li, X.; Sun, C. Antioxidant Capacity, Anticancer Ability and Flavonoids Composition of 35 Citrus (Citrus reticulata Blanco) Varieties. Molecules 2017, 22, 1114.
- Wen, L.; Zhao, Y.; Jiang, Y.; Yu, L.; Zeng, X.; Yang, J.; Tian, M.; Liu, H.; Yang, B. Identification of a flavonoid C-glycoside as potent antioxidant. Free Radic. Biol. Med. 2017, 110, 92–101.
- Kšonžeková, P.; Mariychuk, R.; Eliasová, A.; Mudroňová, D.; Csank, T.; Király, J.; Marcinčáková, D.; Pistl, J.; Tkáciková, L. In vitro study of biological activities of anthocyanin-rich berry extracts on porcine intestinal epithelial cells. J. Sci. Food Agric. 2016, 96, 1093–1100.
- Serra, D.; Henriques, J.F.; Serra, T.; Bento Silva, A.; Bronze, M.R.; Dinis, T.C.P.; Almeida, L.M. An Anthocyanin-Rich Extract Obtained from Portuguese Blueberries Maintains Its Efficacy in Reducing Microglia-Driven Neuroinflammation after Simulated Digestion. Nutrients 2020, 12, 3670.
- Yousuf, B.; Gul, K.; Wani, A.A.; Singh, P. Health Benefits of Anthocyanins and Their Encapsulation for Potential Use in Food Systems: A Review. Crit. Rev. Food Sci. Nutr. 2016, 56, 2223–2230.
- Jurikova, T.; Mlcek, J.; Skrovankova, S.; Sumczynski, D.; Sochor, J.; Hlavacova, I.; Snopek, L.; Orsavová, J. Fruits of Black Chokeberry Aronia melanocarpa in the Prevention of Chronic Diseases. Molecules 2017, 22, 944.
- Song, X.L.; Li, M.-J.; Liu, Q.; Hu, Z.-X.; Xu, Z.-Y.; Li, J.-H.; Zheng, W.-L.; Huang, X.-M.; Xiao, F.; Cui, Y.-H.; et al. Cyanidin-3-O-glucoside Protects Lens Epithelial Cells against High Glucose-Induced Apoptosis and Prevents Cataract Formation via Suppressing NF-κB Activation and Cox-2 Expression. J. Agric. Food Chem. 2020, 68, 8286–8294.
- Tancharoen, S.; Shakya, P.; Narkpinit, S.; Dararat, P.; Kikuchi, K. Anthocyanins Extracted from Oryza sativa L. Prevent Fluorouracil-Induced Nuclear Factor-κB Activation in Oral Mucositis: In Vitro and In Vivo Studies. Int. J. Mol. Sci. 2018, 19, 2981.
- Huang, W.-Y.; Liu, Y.-M.; Wang, J.; Wang, X.-N.; Li, C. Anti-Inflammatory Effect of the Blueberry Anthocyanins Malvidin-3-Glucoside and Malvidin-3-Galactoside in Endothelial Cells. Molecules 2014, 19, 12827–12841.
- Li, K.; Zhang, M.; Chen, H.; Peng, J.; Jiang, F.; Shi, X.; Bai, Y.; Jian, M.; Jia, Y. Anthocyanins from black peanut skin protect against UV-B induced keratinocyte cell and skin oxidative damage through activating Nrf 2 signaling. Food Funct. 2019, 10, 6815–6828.
- Kumar, S.; Pandey, A.K. Chemistry and Biological Activities of Flavonoids: An Overview. Sci. World J. 2013, 2013, 1–16.
- Farzaei, M.H.; Singh, A.K.; Kumar, R.; Croley, C.R.; Pandey, A.K.; Coy-Barrera, E.; Patra, J.K.; Das, G.; Kerry, R.G.; Annunziata, G.; et al. Targeting Inflammation by Flavonoids: Novel Therapeutic Strategy for Metabolic Disorders. Int. J. Mol. Sci. 2019, 20, 4957.
- Wen, L.; Jiang, Y.; Yang, J.; Zhao, Y.; Tian, M.; Yang, B. Structure, bioactivity, and synthesis of methylated flavonoids. Ann. N. Y. Acad. Sci. 2017, 1398, 120–129.
- Kozłowska, A.; Szostak-Węgierek, D. Plant Flavonoids in Health, Prevention, and Treatment of Chronic Diseases. In Nutritional Antioxidant Therapies: Treatments and Perspectives; Al-Gubory, K.H., Laher, I., Eds.; Springer International Publishing: Cham, Switzerland, 2017; pp. 347–376.
- Harlan, L.; Mena, L.; Ramalingam, L.; Jayarathne, S.; Shen, C.-L.; Moustaid-Moussa, N. Mechanisms Mediating Anti-Inflammatory Effects of Delta-Tocotrienol and Tart Cherry Anthocyanins in 3T3-L1 Adipocytes. Nutrients 2020, 12, 3356.
- Molonia, M.S.; Occhiuto, C.; Muscarà, C.; Speciale, A.; Bashllari, R.; Villarroya, F.; Saija, A.; Cimino, F.; Cristani, M. Cyanidin-3-O-glucoside restores insulin signaling and reduces inflammation in hypertrophic adipocytes. Arch. Biochem. Biophys. 2020, 691, 108488.
- Ouyang, S.; Chen, W.; Gaofeng, Z.; Changcheng, L.; Guoping, T.; Minyan, Z.; Yang, L.; Min, Y.; Luo, J. Cyanidin-3-O-β-glucoside protects against pulmonary artery hypertension induced by monocrotaline via the TGF-β1/p38 MAPK/CREB signaling pathway. Mol. Med. Rep. 2021, 23, 1–12.
- Liu, J.; Tian, S.; Xin, C.; Liu, J.; Wang, Q.; He, Y.; Liu, M.; Fu, M.; Yang, Y.; Cao, X. The Identification of Anthocyanins from Padus racemosa and Its Protective Effects on H2O2-Induced INS-1 Cells Damage and STZ-Induced Diabetes Mice. Chem. Biodivers. 2020, 17, e2000382.
- Lim, T.; Ryu, J.; Lee, K.; Park, S.Y.; Hwang, K.T. Protective Effects of Black Raspberry (Rubus occidentalis) Extract against Hypercholesterolemia and Hepatic Inflammation in Rats Fed High-Fat and High-Choline Diets. Nutrients 2020, 12, 2448.
- Jongsomchai, K.; Leardkamolkarn, V.; Mahatheeranont, S. A rice bran phytochemical, cyanidin 3-glucoside, inhibits the progression of PC3 prostate cancer cell. Anat. Cell Biol. 2020, 53, 481–492.
- Paramanantham, A.; Kim, M.J.; Jung, E.J.; Kim, H.J.; Chang, S.-H.; Jung, J.-M.; Hong, S.C.; Shin, S.C.; Kim, G.S.; Lee, W.S. Anthocyanins Isolated from Vitis coignetiae Pulliat Enhances Cisplatin Sensitivity in MCF-7 Human Breast Cancer Cells through Inhibition of Akt and NF-κB Activation. Molecules 2020, 25, 3623.
- Layosa, M.A.A.; Lage, N.N.; Chew, B.P.; Atienza, L.; Mertens-Talcott, S.; Talcott, S.; Noratto, G.D. Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Down-regulation. Nutr. Cancer 2020, 1–13.
- Noratto, G.; Layosa, M.A.; Lage, N.N.; Atienza, L.; Ivanov, I.; Mertens-Talcott, S.U.; Chew, B.P. Antitumor potential of dark sweet cherry sweet (Prunus avium) phenolics in suppressing xenograft tumor growth of MDA-MB-453 breast cancer cells. J. Nutr. Biochem. 2020, 84, 108437.
- Kim, M.J.; Paramanantham, A.; Lee, W.S.; Yun, J.W.; Chang, S.H.; Kim, D.C.; Park, H.S.; Choi, Y.H.; Kim, G.S.; Ryu, C.H.; et al. Anthocyanins Derived from Vitis coignetiae Pulliat Contributes Anti-Cancer Effects by Suppressing NF-κB Pathways in Hep3B Human Hepatocellular Carcinoma Cells and In Vivo. Molecules 2020, 25, 5445.
- Cury, B.J.; Boeing, T.; Somensi, L.B.; Mariano, L.N.B.; de Andrade, S.F.; Breviglieri, E.; Klein-Junior, L.C.; de Souza, P.; da Silva, L.M. Açaí berries (Euterpe oleracea Mart.) dried extract improves ethanol-induced ulcer in rats. J. Pharm. Pharmacol. 2020, 72, 1239–1244.
- El-Shiekh, R.A.; Ashour, R.M.; El-Haleim, E.A.A.; Ahmed, K.A.; Abdel-Sattar, E. Hibiscus sabdariffa L.: A potent natural neuroprotective agent for the prevention of streptozoto-cin-induced Alzheimer’s disease in mice. Biomed. Pharmacother. 2020, 128, 110303.
- Heysieattalab, S.; Sadeghi, L. Effects of Delphinidin on Pathophysiological Signs of Nucleus Basalis of Meynert Lesioned Rats as Animal Model of Alzheimer Disease. Neurochem. Res. 2020, 45, 1636–1646.