Natural Kaempferol Delays Parkinson’s Sym... - Cure Parkinson's

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Natural Kaempferol Delays Parkinson’s Symptoms in Fruit Fly Model

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Natural Kaempferol Delays Parkinson’s Symptoms in Fruit Fly Model 2020

"The natural compound kaempferol — which acts as a potent antioxidant — can reduce the physical and behavioral symptoms of Parkinson’s in a fruit fly model of the disease.

According to the researchers, this molecule may exert its protective effects by blocking the aggregation, or clumping, of a protein called alpha-synuclein, which is one key culprit behind Parkinson’s development."

17 Replies

Kaempferol alleviates LD-mitochondrial damage by promoting autophagy: Implications in Parkinson's disease 2021


Emerging evidence indicates that unexpected lipid droplet (LD) deposition and peroxidation can accelerate organelle stress and plays a crucial role in the pathogenesis of neurodegenerative diseases (NDDs). In our previous study, we confirmed that kaempferol (Ka), a natural flavonoid small molecule, exhibited neuroprotective effects on mice with LPS-induced Parkinson's disease (PD). In addition, previous studies have shown that autophagy plays an important role in the regulation of cellular LD deposition. In the current study, we showed that Ka protected against TH+ neuronal loss and behavioral deficits in MPTP/p-induced PD mice, accompanied by reduced lipid oxidative stress in the substantia nigra pars compacta (SNpc). In cultured neuronal cells, Ka exhibited a relatively safe concentration range and significantly suppressed LD accumulation and cellular apoptosis induced by MPP+. Further study indicated that the protective effect of Ka was dependent on autophagy, specifically lipophagy. Critically, Ka promoted autophagy to mediate LD degradation in lysosomes, which then alleviated lipid deposition and peroxidation and the resulting mitochondrial damage, consequently reducing neuronal death. Furthermore, AAV-shAtg5-mediated Atg5 knockdown abolished the neuroprotective effects of Ka against lipid oxidation in PD mice. This work demonstrates that Ka prevents dopaminergic neuronal degeneration in PD via the inhibition of lipid peroxidation-mediated mitochondrial damage by promoting lipophagy and provides a potential novel therapeutic strategy for PD and related NDDs."

Invalid study due to pretreatment:

"Control mice received saline and probenecid

injection. In the MPTP + Ka-treated group, mice received Ka (50 mg/kg,

a single injection/day during experiments, Jingzhu Biotechnology,

Nanjing, China) intraperitoneally (i.p.) daily 3 d prior to treatment with

MPTP and over the 5 MPTP injection weeks"

Bolt – I do not have the time and the energy to check whether the studies you have cited in the succeeding comments engage in pretreatment or posttreatment with the test substance. Perhaps you would like to do so.

This is a Flavonol, similar to quercetin and Fisetin:

Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro 2021


Aggregation of α-synuclein (α-Syn) is implicated in the pathogenesis of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Therefore, the removal of α-Syn aggregation could lead to the development of many new therapeutic agents for neurodegenerative diseases. In the present study, we succeeded in generating a new α-Syn stably expressing cell line using a piggyBac transposon system to investigate the neuroprotective effect of the flavonoid kaempferol on α-Syn toxicity. We found that kaempferol provided significant protection against α-Syn-related neurotoxicity. Furthermore, kaempferol induced autophagy through an increase in the biogenesis of lysosomes by inducing the expression of transcription factor EB and reducing the accumulation of α-Syn; thus, kaempferol prevented neuronal cell death. Moreover, kaempferol directly blocked the amyloid fibril formation of α-Syn. These results support the therapeutic potential of kaempferol in diseases such as synucleinopathies that are characterized by α-Syn aggregates."

Kaempferol attenuates neuroinflammation and blood brain barrier dysfunction to improve neurological deficits in cerebral ischemia/reperfusion rats 2019

" Abstract

Kaempferol has been reported to act as an anti-inflammatory agent in LPS-induced neuroinflammation in vitro and in vivo, but its role in the inflammation after cerebral ischemia/reperfusion (I/R) is unclear. The present study was to investigate the effect of kaempferol on inflammation in ischemic brain tissue and explore its mechanisms in cerebral I/R rats. Cerebral I/R rat model was established by middle cerebral artery occlusion for 60 min and following reperfusion. Kaempferol at doses of 25, 50 and 100 mg/kg was administered for 7 days after cerebral I/R. Kaempferol treatment significantly reduced cerebral infarct volume, attenuated inflammation and blood-brain barrier (BBB) disruption after cerebral I/R, thus improved neurological outcomes at the day 7 after cerebral I/R. Furthermore, the results also showed kaempferol treatment decreased the phosphorylation and nuclear transposition of transcription factor NF-κB p65, thus inhibited expression of various pro-inflammatory proteins. In conclusion, kaempferol attenuates neuroinflammation and blood brain barrier dysfunction to improve neurological deficits in cerebral I/R rats, its mechanism is related to NF-κB pathway."

Intestinal absorption and neuroprotective effects of kaempferol-3-O-rutinoside 2017


Kaempferol-3-O-rutinoside (K3R) has been proven to have biological activities for the prevention and treatment of central nervous system (CNS) diseases. However, the details of its absorption from the gastrointestinal tract and transport across the blood–brain barrier (BBB) are not clear. Therefore, to provide a basis for its efficacy, we explored its intestinal absorption with Caco-2 monolayer cells, rat orthotopic intestinal perfusion, its transport across a BBB model based on bEnd.3 monolayer cells and its pharmacological effects on PC12 cells in terms of neuropathy. The results indicated that the transport of K3R is concentration dependent; moreover, the apparent permeability coefficient (Papp) of K3R lacked directionality, and the efflux rate after adding P-glycoprotein inhibitor did not show a significant change. K3R was found to be completely absorbed in the intestines of rats, and the absorption process follows the first-order kinetics. K3R can pass through the BBB with passive diffusion. The neuroprotective effects of K3R were related to stabilization of the mitochondrial membrane and a decrease in reactive oxygen species. These results demonstrated that K3R can be absorbed in a relatively moderate ratio in the gastrointestinal tract and transported to the brain. Thus, K3R may be a potent drug for the prevention and treatment of neurodegenerative diseases such as Parkinson's disease."


The Pharmacological Action of Kaempferol in Central Nervous System Diseases: A Review 2021

"Kaempferol (KPF) is a flavonoid antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary KPF in reducing the risk of chronic diseases, especially cancer. Nevertheless, little is known about the cellular and molecular mechanisms underlying KPF actions in the central nervous system (CNS). Also, the relationship between KPF structural properties and their glycosylation and the biological benefits of these compounds is unclear. The aim of this study was to review studies published in the PubMed database during the last 10 years (2010–2020), considering only experimental articles that addressed the isolated cell effect of KPF (C15H10O6) and its derivatives in neurological diseases such as Alzheimer's disease, Parkinson, ischemia stroke, epilepsy, major depressive disorder, anxiety disorders, neuropathic pain, and glioblastoma. 27 publications were included in the present review, which presented recent advances in the effects of KPF on the nervous system. KPF has presented a multipotential neuroprotective action through the modulation of several proinflammatory signaling pathways such as the nuclear factor kappa B (NF-kB), p38 mitogen-activated protein kinases (p38MAPK), serine/threonine kinase (AKT), and β-catenin cascade. In addition, there are different biological benefits and pharmacokinetic behaviors between KPF aglycone and its glycosides. The antioxidant nature of KPF was observed in all neurological diseases through MMP2, MMP3, and MMP9 metalloproteinase inhibition; reactive oxygen species generation inhibition; endogenous antioxidants modulation as superoxide dismutase and glutathione; formation and aggregation of beta-amyloid (β-A) protein inhibition; and brain protective action through the modulation of brain-derived neurotrophic factor (BDNF), important for neural plasticity. In conclusion, we suggest that KPF and some glycosylated derivatives (KPF-3-O-rhamnoside, KPF-3-O-glucoside, KPF-7-O-rutinoside, and KPF-4′-methyl ether) have a multipotential neuroprotective action in CNS diseases, and further studies may make the KPF effect mechanisms in those pathologies clearer. Future in vivo studies are needed to clarify the mechanism of KPF action in CNS diseases as well as the impact of glycosylation on KPF bioactivity."

Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice via inhibiting HMGB1 release and down-regulating TLR4/MyD88 pathway

Citrus Polyphenols in Brain Health and Disease: Current Perspectives 2021

Recent progress regarding kaempferol for the treatment of various diseases (Review)

"KP has neuroprotective effects in Parkinson's disease (PD) 2019

PD is the second most common disorder of the central nervous system (173). Its pathological features are the loss of dopaminergic neurons and the formation of cytoplasmic inclusions in the substantia nigra (SN). When PD is present, ~80% of striatal dopamine is lost and damage to the terminal region may preempt the loss of cell bodies in SN (174).

Han et al (175) hypothesized that inflammasomes are associated with immune homeostasis and their dysregulation leads to neurodegenerative disorders. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is involved in PD. KP inhibits NLRP3 inflammasome activation, leading to reduced NLRP3 protein expression and deactivation of the NLRP3 inflammasome in order to promote macroautophagy/autophagy in microglia.

Li and Pu (176) indicated that pre-intake of KP markedly improved 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine and dihydroxy-phenyl acetic acid (DOPAC) depletion in the striatum, and also reduced the DOPAC/dopamine ratio and the MPTP-induced loss of tyrosine hydroxylase-positive neurons in mouse SN. KP has a neuroprotective effect in mice with MPTP-induced PD, which may contribute to its anti-oxidant capacity to scavenge free radicals and lead to the survival of more dopamine neurons.

In previous studies, KP 3-O-rutinoside and anhydrosafflor yellow B, as the compounds isolated from SSFE, a standardized safflower flavonoid extract, have been demonstrated to reduce the levels of ROS, which are induced by hydrogen peroxide and restore tyrosine hydroxylase activity in PC12 cells (177). Ren et al (178) indicated that KP 3-O-rutinoside and dehydrin flavonoid B inhibited microtubule instability and reduced the cell volume. In addition, SSFE, in the form of pills, may inhibit astrocyte proliferation and improve the neurological behavior in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. In a study using a magnetic resonance imaging-based, tracer-based approach, 6-OHDA was indicated to alter diffusion parameters of endothelial cells, including reduced bowing and clearance rate constants and increased elimination half-life of the tracer in the SN with 6-OHDA-induced lesions. These results indicated that flavonoids may be potential anti-PD medicines.

KP prevents Alzheimer's disease (AD)

Studies have indicated that the abnormal production of various proteins and high concentrations of glutamate may lead to excessive ROS production in cells, resulting in neurotoxicity and neuronal death (179). Yang et al (180) examined the neuroprotective effects of KP in glutamate-treated HT22 hippocampal neuronal cells. Lactate dehydrogenase assays and fluorescein-5-isothiocyanate-connexin V/propidium iodide double staining procedures were subsequently used to confirm the protective effect of KP on HT22 cells. These results also indicated that KP protects nerves by regulating the expression levels of apoptosis-associated proteins, including Bcl-2, Bid, apoptosis-inducing factor and MAPK.

AD is characterized by the accumulation and deposition of β-amyloid peptides, leading to progressive neuronal damage and cell loss. Among several hypotheses, oxidative stress may be a mechanism that leads to neurodegeneration. To date, there is no cure for AD, but the use of natural anti-oxidants may delay the pathogenesis of the disease. These results suggest that KP may serve as a useful drug for the prevention and treatment of neurodegenerative diseases, including AD."

Kaempferol induces ROS-dependent apoptosis in pancreatic cancer cells via TGM2-mediated Akt/mTOR signaling 2021

"Kaempferol effectively suppressed pancreatic cancer in vitro and in vivo. Kaempferol promoted apoptosis in vitro by increasing ROS generation, which was involved in Akt/mTOR signaling. TGM2 levels were significantly increased in PDAC tissues compared with normal tissues, and high TGM2 expression was positively correlated with poor prognosis in pancreatic cancer patients. Decreased TGM2 mRNA and protein levels were observed in the cells after treatment with kaempferol. Additionally, TGM2 overexpression downregulated ROS production and inhibited the abovementioned apoptotic signaling pathway."

What foods contain kaempferol?

Common foods that contain kaempferol include: apples, grapes, tomatoes, green tea, potatoes, onions, broccoli, Brussels sprouts, squash, cucumbers, lettuce, green beans, peaches, blackberries, raspberries, and spinach.

This stuff is not cheap!

in reply to Bolt_Upright

in Brocoli (Brassica oleracea ), 100 mg·kg-1 of Kaempferol

Bolt_Upright profile image
Bolt_Upright in reply to

That is excellent information! I need to eat more broccoli!

"kaempferol's bioavailability was reported to very low, as low as 2%"

You are right! Squeezed juice of broccoli, apple and orange with a little ginger and turmeric is a pure delight !

your posts are GREAT! keep it up! thanks!

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