The Pharmacological Action of Kaempferol in Central Nervous System Diseases: A Review

Santos, Jéssica Silva dos; Cirino, João Pedro Gonçalves; Carvalho, Patrícia de Oliveira; Ortega, Manoela Marques

doi:10.3389/fphar.2020.565700

Cited by 129 publications

(86 citation statements)

References 114 publications

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“…Beneficial effects of kaempferol administration in animal models of Alzheimer’s and Parkinson’s diseases, ischemic stroke, epilepsy, major depressive disorders, and anxiety disorders were recently summarized by Silva dos Santos et al [ 6 ]. Pharmacological research concerning kaempferol glycosides and their action in CNS diseases produced far fewer results.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacological activities of the compounds and their role as the components of human diet are the subject of numerous studies [ 1 , 2 , 3 , 4 , 5 ]. Recently, two review papers summarizing the research on neuroprotective action of kaempferol, quercetin and glycosidic derivatives of the compounds were published [ 6 , 7 ]. Kaempferol 7- O -rhamnosides, however, remain a poorly investigated group of kaempferol derivatives in regard of their neuroprotective potential.…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective Properties of Kempferol Derivatives from Maesa membranacea against Oxidative Stress-Induced Cell Damage: An Association with Cathepsin D Inhibition and PI3K/Akt Activation

Jantas

Malarz

et al. 2021

IJMS

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As components of the human diet with potential health benefits, flavonols are the subject of numerous studies, confirming their antioxidant, free radical scavenging and anti-inflammatory activity. Taking into consideration the postulated pathogenesis of certain CNS dysfunctions characterized by neuronal degradation, flavonols may prevent the decay of neurons in multiple pathways. Leaves of Maesa membranacea yielded several flavonol glycosides including α-rhamnoisorobin (kaempferol 7-O-α-rhamnoside) and kaempferitrin (kaempferol 3,7-di-O-α-rhamnoside). The latter compound was a major constituent of the investigated plant material. Neuroprotective effects of kaempferitrin and α-rhamnoisorobin were tested in vitro using H2O2-, 6-OHDA- and doxorubicin-induced models of SH-SY5Y cell damage. Both undifferentiated and differentiated neuroblastoma cells were used in the experiments. α-Rhamnoisorobin at a concentration range of 1–10 µM demonstrated cytoprotective effects against H2O2-induced cell damage. The compound (at 1–10 µM) was also effective in attenuating 6-OHDA-induced neurotoxicity. In both H2O2- and 6-OHDA-induced cell damage, kaempferitrin, similar to isoquercitrin, demonstrated neuroprotective activity at the highest of the tested concentrations (50 µM). The tested flavonols were not effective in counteracting doxorubicin-induced cytotoxicity. Their caspase-3- and cathepsin D-inhibitory activities appeared to be structure dependent. Inhibition of the PI3-K/Akt pathway abolished the neuroprotective effect of the investigated flavonols.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuroprotective Properties of Kempferol Derivatives from Maesa membranacea against Oxidative Stress-Induced Cell Damage: An Association with Cathepsin D Inhibition and PI3K/Akt Activation

Jantas

Malarz

et al. 2021

IJMS

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“…Kaempferol, which has antioxidant and anti-inflammatory Evidence-Based Complementary and Alternative Medicine properties, may exert its antidepressant effects by increasing the Akt/β-catenin cascade in the prefrontal cortex [63]. In addition, kaempferol reduced the concentrations of inflammatory mediators IL-1β and TNFα in the prefrontal cortex of depressed mice, especially at a dose of 20 mg/kg [64]. Beta-sitosterol shortened the immobility time of depressed mice in forced swimming experiments and regulated the levels of NE, 5-HT and the metabolite 5-HIAA in the brains of mice.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Targets and Mechanism of Xingpi Jieyu Decoction in Depression: A Network Pharmacology Study

Chang

Tian

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Depression is a common mental disease that lacks effective therapeutic drugs with good curative effects and few adverse reactions. Traditional Chinese medicine (TCM) has the advantages of multiple components, multiple channels, and fewer adverse reactions in the treatment of depression. Although Xingpi Jieyu Decoction (XPJYD) demonstrates a good therapeutic effect on depression, the pharmacological mechanism underlying its antidepressant effect is still unclear. Methods. We used a network pharmacology strategy, including the construction and analysis of a complex drug-disease network, to explore the complex mechanism of XPJYD treatment of depression. In addition, molecular docking technology was used to preliminarily study the binding ability of the potential active components and core therapeutic targets of XPJYD. Results. The network pharmacology results showed 42 targets of XPJYD that are involved in depression. PPI network analysis demonstrated that the top 10 core targets were AKT1, VEGFA, MAPK8, FOS, ESR1, NR3C1, IL6, HIF1A, NOS3, and AR. The molecular docking results showed that the binding energies of beta sitosterol with AR, FOS, AKT1, VEGFA, NR3C1, and NOS3 were less than −7.0 kcal·mol−1, indicating a good docking effect. The GO enrichment analysis results showed that the XPJYD antidepression mechanism mainly involves the following biological processes such as apoptotic signaling pathway, cellular response to lipid, inflammatory response, and others. The KEGG analysis results indicated that XPJYD may regulate 13 pathways such as PI3K-Akt signaling pathway and estrogen signaling pathway in the treatment of depression. Conclusions. This study reflects the characteristics of the mechanism of action by which XPJYD treats depression, which includes multiple components, multiple targets, and multiple pathways, and provides a biological basis for further verification and a novel perspective for drug discovery in depression.

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“…Luteolin has broad anti-viral properties [ 327 , 328 , 329 ] and inhibits the entry of the corona virus into host cells [ 237 , 330 , 331 ]. Furthermore, luteolin better penetrates into the brain, inhibits both microglia [ 259 , 332 , 333 , 334 ] and mast cells [ 317 , 335 ], is neuroprotective [ 336 , 337 , 338 , 339 ], and has been reported to reduce neuroinflammation [ 337 , 340 , 341 , 342 ] and cognitive dysfunction [ 61 , 343 , 344 , 345 ], especially brain fog [ 346 ]. In fact, flavonoids were recently shown to improve cerebral cortical oxygenation and cognition in healthy adults.…”

Section: Treatment Approachesmentioning

confidence: 99%

Ways to Address Perinatal Mast Cell Activation and Focal Brain Inflammation, including Response to SARS-CoV-2, in Autism Spectrum Disorder

2021

JPM

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The prevalence of autism spectrum disorder (ASD) continues to increase, but no distinct pathogenesis or effective treatment are known yet. The presence of many comorbidities further complicates matters, making a personalized approach necessary. An increasing number of reports indicate that inflammation of the brain leads to neurodegenerative changes, especially during perinatal life, “short-circuiting the electrical system” in the amygdala that is essential for our ability to feel emotions, but also regulates fear. Inflammation of the brain can result from the stimulation of mast cells—found in all tissues including the brain—by neuropeptides, stress, toxins, and viruses such as SARS-CoV-2, leading to the activation of microglia. These resident brain defenders then release even more inflammatory molecules and stop “pruning” nerve connections, disrupting neuronal connectivity, lowering the fear threshold, and derailing the expression of emotions, as seen in ASD. Many epidemiological studies have reported a strong association between ASD and atopic dermatitis (eczema), asthma, and food allergies/intolerance, all of which involve activated mast cells. Mast cells can be triggered by allergens, neuropeptides, stress, and toxins, leading to disruption of the blood–brain barrier (BBB) and activation of microglia. Moreover, many epidemiological studies have reported a strong association between stress and atopic dermatitis (eczema) during gestation, which involves activated mast cells. Both mast cells and microglia can also be activated by SARS-CoV-2 in affected mothers during pregnancy. We showed increased expression of the proinflammatory cytokine IL-18 and its receptor, but decreased expression of the anti-inflammatory cytokine IL-38 and its receptor IL-36R, only in the amygdala of deceased children with ASD. We further showed that the natural flavonoid luteolin is a potent inhibitor of the activation of both mast cells and microglia, but also blocks SARS-CoV-2 binding to its receptor angiotensin-converting enzyme 2 (ACE2). A treatment approach should be tailored to each individual patient and should address hyperactivity/stress, allergies, or food intolerance, with the introduction of natural molecules or drugs to inhibit mast cells and microglia, such as liposomal luteolin.

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The Pharmacological Action of Kaempferol in Central Nervous System Diseases: A Review

Cited by 129 publications

References 114 publications

Neuroprotective Properties of Kempferol Derivatives from Maesa membranacea against Oxidative Stress-Induced Cell Damage: An Association with Cathepsin D Inhibition and PI3K/Akt Activation

Neuroprotective Properties of Kempferol Derivatives from Maesa membranacea against Oxidative Stress-Induced Cell Damage: An Association with Cathepsin D Inhibition and PI3K/Akt Activation

Therapeutic Targets and Mechanism of Xingpi Jieyu Decoction in Depression: A Network Pharmacology Study

Ways to Address Perinatal Mast Cell Activation and Focal Brain Inflammation, including Response to SARS-CoV-2, in Autism Spectrum Disorder

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