Protective Effect Of Kaempferol Research Articles

Kaempferol ameliorated alcoholic liver disease through inhibiting hepatic bile acid synthesis by targeting intestinal FXR-FGF15 signaling

BackgroundAlcoholic liver disease (ALD) is characterized by the disturbance of bile acids homeostasis, which further deteriorates ALD. Bile acid metabolism and its related signal molecules have become new therapeutic targets for alcoholic liver disease. This study aimed to investigate the impact of kaempferol (KAE) on ALD and elucidate its underlying mechanisms. MethodsC57BL/6 N mice were utilized to establish Binge-on-Chronic alcohol exposure mice model. KAE was administered as an interventional drug to chronic alcohol-fed mice for four weeks to assess its effects on liver damage and bile acid metabolism. And Z-Guggulsterone (Z-Gu), a global FXR inhibitor, was used to investigate the impact of intestinal FXR-FGF15 signal in ALD mice. Additionally, intestinal epithelial cells were exposed to alcohol or specific bile acid to induce the damage of FXR activity in vitro. The dual luciferase activity assay was employed to ascertain the interplay between KAE and FXR activity. ResultsThe results indicated that KAE treatment exhibited a significant hepatoprotective effect against chronic alcohol-fed mice. Accompanied by the intestinal FXR activation, the administration of KAE suppressed hepatic bile acid synthesis and promoted intestinal bile acid excretion in chronic ALD mice. And the notable alterations in total bile acid levels and composition were observed in mice after chronic alcohol feeding, which were reversed by KAE supplementation. And more, the protective effects of KAE on ALD mice were deprived by the inhibition of intestinal FXR activation. In vitro experiments demonstrated that KAE effectively activated FXR-FGF15 signaling, mitigated the damage to FXR activity in intestinal epithelial cells caused by alcohol or specific bile acids. Additionally, luciferase activity assays revealed that KAE directly promoted FXR expression, thereby enhancing FXR activity. ConclusionKAE treatment inhibited hepatic bile acids synthesis, maintained bile acids homeostasis in ALD mice by directly activating intestinal FXR-FGF15 signaling, which effectively alleviated liver injury induced by chronic alcohol consumption.

Protective effect of kaempferol against cognitive and neurological disturbances induced by d-galactose and aluminum chloride in mice

Protective effect of kaempferol against cognitive and neurological disturbances induced by d-galactose and aluminum chloride in mice

Kaemperfol Protects Dopaminergic Neurons by Promoting mTOR-Mediated Autophagy in Parkinson's Disease Models.

We previously showed that kaempferol (KAE) could exert neuroprotective effects against PD. It has been demonstrated that abnormal autophagy plays a key role in the development of PD. Mitochondrial dysfunction, involved in the development of PD, can damage dopaminergic neurons. Whether the protective effects of KAE were exerted via regulating autophagy remains largely undefined, however. This study aimed to investigate whether KAE could protect dopaminergic neurons via autophagy and the underlying mechanisms using a MPTP/MPP+-stimulated PD model. Cell viability was detected by cell counting kit-8 (CCK-8) assay, and protein levels of autophagy mediators along with mTOR signaling pathway molecules were investigated by immunohistochemistry and Western blot analyses. The results showed that KAE could ameliorate the behavioral impairments of mice, reduce the loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta, and reduce α-synuclein (α-syn) levels. Furthermore, KAE upregulated levels of autophagy effector protein of Beclin-1 and autophagy microtubule associated protein of light chain 3 (LC3) in the substantia nigra (SN) while rescuing mitochondrial integrity, and downregulated levels of ubiquitin binding protein p62 and cleaved caspase-3, probably by decreasing the mammalian target of rapamycin (mTOR) signaling pathway. Further in vitro experiments demonstrated similar results. In conclusion, KAE exerts neuroprotective effects against PD potentially by promoting autophagy via inhibiting the mTOR signaling pathway.

A comprehensive and mechanistic review on protective effects of kaempferol against natural and chemical toxins: Role of NF-κB inhibition and Nrf2 activation.

Different toxins, including chemicals and natural, can be entered from various routes and influence human health. Herbal medicines and their active components can attenuate the toxicity of agents via multiple mechanisms. For example, kaempferol, as a flavonoid, can be found in fruits and vegetables, and has an essential role in improving disorders such as cardiovascular disorders, neurological diseases, cancer, pain, and inflammation situations. The beneficial effects of kaempferol may be related to the inhibition of oxidative stress, attenuation of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear factor ĸB (NF-ĸB) as well as the modulation of apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways. This flavonoid boasts a wide spectrum of toxin targeting effects in tissue fibrosis, inflammation, and oxidative stress thus shows promising protective effects against natural and chemical toxin induced hepatotoxicity, nephrotoxicity, cardiotoxicity, neurotoxicity, lung, and intestinal in the in vitro and in vivo setting. The most remarkable aspect of kaempferol is that it does not focus its efforts on just one organ or one molecular pathway. Although its significance as a treatment option remains questionable and requires more clinical studies, it seems to be a low-risk therapeutic option. It is crucial to emphasize that kaempferol's poor bioavailability is a significant barrier to its use as a therapeutic option. Nanotechnology can be a promising way to overcome this challenge, reviving optimism in using kaempferol as a viable treatment agent against toxin-induced disorders.

Protective effect of Kaempferol on endothelial cell injury in glucocorticoid induced osteonecrosis of the femoral head

To explore the effect of Kaempferol on bone microvascular endothelial cells (BMECs) in glucocorticoid induced osteonecrosis of the femoral head (GIONFH) in vitro. BMECs were isolated from cancellous bone of femoral head or femoral neck donated voluntarily by patients with femoral neck fracture. BMECs were identified by von Willebrand factor and CD31 immunofluorescence staining and tube formation assay. The cell counting kit 8 (CCK-8) assay was used to screen the optimal concentration and the time point of dexamethasone (Dex) to inhibit the cell activity and the optimal concentration of Kaempferol to improve the inhibition of Dex. Then the BMECs were divided into 4 groups, namely, the cell group (group A), the cells treated with optimal concentration of Dex group (group B), the cells treated with optimal concentration of Dex+1 μmol/L Kaempferol group (group C), and the cells treated with optimal concentration of Dex+5 μmol/L Kaempferol group (group D). EdU assay, in vitro tube formation assay, TUNEL staining assay, Annexin Ⅴ/propidium iodide (PI) staining assay, Transwell migration assay, scratch healing assay, and Western blot assay were used to detect the effect of Kaempferol on the proliferation, tube formation, apoptosis, migration, and protein expression of BMECs treated with Dex. The cultured cells were identified as BMECs. CCK-8 assay showed that the optimal concentration and the time point of Dex to inhibit cell activity was 300 μmol/L for 24 hours, and the optimal concentration of Kaempferol to improve the inhibitory activity of Dex was 1 μmol/L. EdU and tube formation assays showed that the cell proliferation rate, tube length, and number of branch points were significantly lower in groups B-D than in group A, and in groups B and D than in group C ( P<0.05). TUNEL and Annexin V/PI staining assays showed that the rates of TUNEL positive cells and apoptotic cells were significantly higher in groups B-D than in group A, and in groups B and D than in group C ( P<0.05). Scratch healing assay and Transwell migration assay showed that the scratch healing rate and the number of migration cells were significantly lower in groups B-D than in group A, and in groups B and D than in group C ( P<0.05). Western blot assay demonstrated that the relative expressions of Cleaved Caspase-3 and Bax proteins were significantly higher in groups B-D than in group A, and in groups B and D than in group C ( P<0.05); the relative expressions of matrix metalloproteinase 2, Cyclin D1, Cyclin E1, VEGFA, and Bcl2 proteins were significantly lower in groups B-D than in group A, and in groups B and D than in group C ( P<0.05). Kaempferol can alleviate the damage and dysfunction of BMECs in GIONFH.

Possible radioprotection of submandibular glands in gamma-irradiated rats using kaempferol: a histopathological and immunohistochemical study

Background and purpose Salivary gland damage remains a problem despite advances in radiotherapy schedules for head and neck cancer. Kaempferol, a natural flavonoid, found in several fruits and vegetables, is a good antioxidant. This study was designed to evaluate the possible protective effects of kaempferol on submandibular glands (SMGs) of rats exposed to fractionated gamma irradiation. Materials and methods Twenty-four male adult Wistar albino rats were included in this study and assigned to three groups (n = 8). Rats in group K received kaempferol orally in five doses at a dose of 10 mg/kg/2 days for 10 days. Meanwhile, rats in group R were subjected to fractionated whole-body gamma irradiation at a dose of 2 Gy/5 days/week for 2 weeks (20 Gy), and the KR group received kaempferol as group K and then was subjected to a fractionated whole-body gamma irradiation as group R. SMG samples were collected on days 1 and 7 after the last radiation session; and processed for histopathological and immunohistochemical investigations. Results The SMGs of group R showed focal atrophy and degeneration. Acini showed vacuolization and had pyknotic hyperchromatic nuclei. Striated ducts degenerated, shrunken, and were surrounded by empty spaces. The percentage of areas covered by cyclooxygenase-2 (COX-2) significantly increased, whereas the percentage of areas covered by proliferating cell nuclear antigen (PCNA) significantly decreased compared with those in group K. Cotreatment with kaempferol (group KR) partially preserved normal gland architecture where acinar vacuolation and degeneration were almost absent; however, some ducts degenerated. A significant decrease in the percentage of areas covered by COX-2 and a significant increase in the percentage of areas covered by PCNA were observed compared with those in group R. Conclusions Kaempferol has a possible radioprotective effect on the SMGs of rats exposed to fractionated gamma irradiation.

Protective Effect of Kaempferol and Its Nanoparticles on 5-Fluorouracil-Induced Cardiotoxicity in Rats.

Background Fluorouracil (5-FU) is the third most common chemotherapeutic agent used in the treatment of solid tumors. 5-FU-associated cardiotoxicity ranks the second causes of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Kaempferol (KPF), a common flavonoid, possessing anti-inflammatory, antiapoptotic, antioxidative properties, and its protective effects on cardiovascular disease has been reported in various studies. The current study is aimed at appraising the effect of KPF and KPF nanoparticles (NPs) on 5-FU-induced cardiotoxicity in rats. Methods Thirty Male Wistar rats were divided into five groups as follows: control, 5-FU, 5-FU+10 mg/kg vitamin C, 5-FU+ 1 mg/kg KPF, and 5-FU+ 1 mg/kg KPF-NPs. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-FU (100 mg/kg). The control group received normal saline, and the treatment groups received KPF and KPF-NPs with an intraperitoneal injection for 14 days. Each heart histopathological lesions were given a score of 0 to 3 in compliance with the articles for statistical analysis. Results 5-FU resulted in a significant cardiotoxicity represented by an increase in cardiac enzymes, MDA (malondialdehyde) levels, COX-2 (cyclooxygenase-2) expression, and histopathological degenerations. 5-FU treatment also decreased body weight, TAC (total antioxidant capacity) values, VEGF (vascular endothelial growth factor) expression, blood cells, and hemoglobin (Hb) levels. Treatment with KPF and KPF-NPs reduced oxidative stress, cardiac enzymes, COX-2 expression, and VEGF expression. The number of blood cells, Hb levels, and histopathological degenerations, in cardiac tissue also body weight of animals, increased, followed by treatment with KPF and KPF-NPs. Conclusion Our results demonstrated that treatment with KPF and KPF-NPs significantly improved cardiotoxicity induced by 5-FU in rats.

Protective Effect of Kaempferol against Hydrogen Peroxide-Induced Oxidative Damage in HUVECs Cell Line

Protective Effect of Kaempferol against Hydrogen Peroxide-Induced Oxidative Damage in HUVECs Cell Line

Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K/AKT/Nrf2 pathway

Context The effect of kaempferol, a regulator of oestrogen receptors, on atherosclerosis (AS) and the underlying mechanism is elusive. Objective To explore the effect and mechanism of kaempferol on AS. Methods and materials In vivo, C57BL/6 and apolipoprotein E (APOE)–/– mice were randomly categorized into six groups (C57BL/6: control, ovariectomy (OVX), high-fat diet (HFD); APOE–/–: OVX-HFD, OVX-HFD + kaempferol (50 mg/kg) and OVX-HFD + kaempferol (100 mg/kg) and administered with kaempferol for 16 weeks, intragastrically. Oil-Red and haematoxylin–eosin (HE) staining were employed to examine the effect of kaempferol. In vitro, human aortic endothelial cells (HAECs) were pre-treated with or without kaempferol (5, 10 or 20 μM), followed by administration with kaempferol and oxidized low-density lipoprotein (ox-LDL) (200 μg/mL). The effect of kaempferol was evaluated using flow cytometry, and TdT-mediated dUTP Nick-End Labelling (TUNEL). Results In vivo, kaempferol (50 and 100 mg/kg) normalized the morphology of blood vessels and lipid levels and suppressed inflammation and apoptosis. It also activated the G protein-coupled oestrogen receptor (GPER) and PI3K/AKT/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. In vitro, ox-LDL (200 μg/mL) reduced the cell viability to 50% (IC50). Kaempferol (5, 10 or 20 μM) induced-GPER activation increased cell viability to nearly 10%, 19.8%, 30%, and the decreased cellular reactive oxygen species (ROS) generation (16.7%, 25.6%, 31.1%), respectively, consequently attenuating postmenopausal AS. However, the protective effects of kaempferol were blocked through co-treatment with si-GPER. Conclusions The beneficial effects of kaempferol against postmenopausal AS are associated with the PI3K/AKT/Nrf2 pathways, mediated by the activation of GPER.

Protective effects of kaempferol, quercetin, and its glycosides on amyloid beta-induced neurotoxicity in C6 glial cell

알츠하이머 질환(Alzheimer’s disease)은 대표적인 신경퇴행성 질환이며, 뇌 내 amyloid beta (Aβ) 축적에 의한 산화적 스트레스 및 염증반응은 대표적인 AD의 원인으로 알려져 있다. 본 연구에서는 kaempferol (K), kaempferol-3-O-glucoside (KG), quercetin (Q) 및 quercetin-3-β-D-glucoside (QG)와 같은 4가지 flavonoids 의 C6 신경교세포에서 Aβ로 인한 신경독성으로부터의 보호 효능을 살펴보고자 하였다. C6 신경교세포에 Aβ를 처리하였을 때세포 생존율이 감소한 반면, 4가지 flavonoids 중에서 Q와 QG의 처리 시 세포 생존율 증가를 통해 신경교세포 보호 효과를 확인하였다. 또한, Aβ를 처리한 control군의 경우 reactive oxygen species (ROS) 생성을 유도한 반면, flavonoids의 처리 시 ROS생성이 감소하였다. 특히 Aβ를 처리한 control군은 133.39%의 ROS 생성을 나타내었으며, 1 μM의 KG와 QG를 각각 처리시107.44, 113.10%의 수치를 나타내어 ROS 생성 감소를 확인하였다. Flavonoids의 Aβ에 대한 신경교세포 보호 기전을 확인하기 위해 염증 관련 단백질 발현을 측정하였다. Aβ로 신경독성이 유도된 control군은 염증 관련 단백질 발현이 증가하였다. 그러나, flavonoids를 처리한 군의 경우 염증 매개 인자인 inducible nitric oxide synthase, cyclooxygenase-2 and interleukin-1β의 발현 감소를 확인하였다. 특히, KG와 QG를 처리한 군은 aglycone 형태인 K와 Q를 처리한 군에 비해 효과적으로 염증매개 인자 발현을 감소시켰다. 본 연구는 flavonoids의 일종인K, Q와 그 배당체인 KG, QG의 Aβ로 신경독성이 유도된 신경교세포에서 산화적 스트레스 및 염증반응 조절을 통한 보호 효과를 나타냄을 알 수 있었으며, 이들 생리활성성분은 AD 예방 및 치료 소재로써의 가능성이 있을 것으로 사료된다.

Protective Effect of Kaempferol on LPS-Induced Inflammation and Barrier Dysfunction in a Coculture Model of Intestinal Epithelial Cells and Intestinal Microvascular Endothelial Cells.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of intestinal mucosa and submucosa, characterized by the disruption of the intestinal epithelial barrier, increased production of inflammatory mediators, and excessive tissue injury. Intestinal epithelial cells, as well as microvascular endothelial cells, play important roles in IBD. To study the potential effects of kaempferol in IBD progress, we established a novel epithelial-endothelial cells coculture model to investigate the intestinal inflammation and barrier function. Data demonstrated an obvious increased transepithelial electrical resistance (TEER) (1222 ± 60.40 Ω cm2 vs 1371 ± 38.77 Ω cm2), decreased flux of FITC (180.8 ± 20.06 μg/mL vs 136.7 ± 14.78 μg/mL), and up-regulated occludin and claudin-2 expression in Caco-2 that was specifically cocultured with endothelial cells. Meanwhile, 80 μM kaempferol alleviated the drop of TEER, the increase of FITC flux, and the overexpression of interleukin-8 (IL-8) induced by 1 μg/mL lipopolysaccharide (LPS). Additionally, kaempferol also ameliorated the LPS-induced decrease of protein expression of zonula occludens-1 (ZO-1), occludin, and claudin-2, together with the inhibited protein expressions of the phosphorylation level of NF-κB and I-κB induced by LPS. Our results suggest that kaempferol alleviates the IL-8 secretion and barrier dysfunction of the Caco-2 monolayer in the LPS-induced epithelial-endothelial coculture model via inhibiting the NF-κB signaling pathway activation.

The protective effect of kaempferol on heart via the regulation of Nrf2, NF-κβ, and PI3K/Akt/GSK-3β signaling pathways in isoproterenol-induced heart failure in diabetic rats.

This study was designed to delineate the effect of kaempferol (KF) on heart failure (HF) in diabetic rats. Streptozotocin-induced male diabetic rats received KF orally at 10 and 20 mg/kg for 42 consecutive days. In last 2 days of the experimental period, isoproterenol was subcutaneously injected at 85 mg/kg to induce HF. The hearts were processed for hemodynamic, biochemical, molecular, and histological investigations. Systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were elevated in KF-treated HF-induced diabetic rats. Moreover, KF treatment resulted in decreased fasting blood glucose and glycosylated hemoglobin levels with increased serum insulin levels. Besides, serum cardiac injury markers like troponin-I, creatine kinase-muscle/brain, lactate dehydrogenase, and brain natriuretic peptide levels were significantly reduced in KF treatment. KF treatment has shown decrease in cardiac heme oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf-2), and γ-glutamylcysteine synthetase with increased Keap1 mRNA levels. The cardioprotection of KF was improved by inhibition of apoptosis via blocking phosphorylation of Akt/glycogen synthase kinase (GSK)-3β and p38 mitogen-activated protein-kinase/extracellular signal-regulated kinases signaling pathways in HF-induced diabetic rats. Moreover, reduced cardiac apoptosis in KF treatment was confirmed by decreased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, histopathological changes in HF-induced diabetic rats. Therefore, the cardioprotective effect of KF is attributed to the regulation of Nrf2, nuclear factor kappa-light-chain-enhancer of activated B cells, and Akt/GSK-3β signaling pathways in HF-induced diabetic rats.

Kaempferol protects mice from d-GalN/LPS-induced acute liver failure by regulating the ER stress-Grp78-CHOP signaling pathway

Kaempferol is a flavonoid compound that has many functions, such as anti-inflammation and antioxidation. Acute liver failure (ALF) is a life-threatening illness accompanied by serious inflammation and extensive hepatocyte apoptosis. The aim of this study was to examine the therapeutic potential of kaempferol and its mechanism in ALF. In a murine ALF model induced by d-galactosamine (d-GalN, 700 mg/kg) / lipopolysaccharide (LPS, 10 μg/kg), mice were pretreated with kaempferol at 2 h before d-GalN/LPS administration and then sacrificed 6 h after d-GalN/LPS injection. Lethality, liver damage, endoplasmic reticulum(ER) stress, hepatocyte viability and apoptosis were evaluated. Whether pretreatment of kaempferol protected hepatocytes from ER stress-induced apoptosis was detected in vitro. Pretreatment of kaempferol decreased lethality, prolonged the survival time and significantly protected against liver injury, which was indicated by decreased transaminase levels and the well-preserved liver structure. The protective effect of kaempferol on the ALF mouse model was achieved by inhibiting hepatocyte apoptosis. Moreover, pretreatment of kaempferol increased the expression of glucose-regulated/binding immunoglobulin protein 78 (Grp78), decreased the expression of C/EBP-homologous protein (CHOP), and protected hepatocytes from ER stress-induced apoptosis in vitro. Our results showed that pretreatment of Grp78 siRNA partially negated the hepatic protection from kaempferol and reversed the inhibition of CHOP protein expression in d-GalN/LPS-induced ALF mice. In conclusion, kaempferol inhibits hepatocyte apoptosis to protect mice from liver failure by regulating the ER stress-Grp78-CHOP signaling pathway. Therefore, kaempferol may be used to treat ALF.

A neuroprotective role of kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3β-Nrf2 signaling pathway

Chlorpyrifos (CPF) is an agricultural pesticide and a potential food contaminant, which causes neurotoxicity. Here, we aimed at exploring the link between the repeated exposure to CPF and memory dysfunction in rats and the possible protective effect of kaempferol, a flavonoid with appreciable antioxidant and anti-inflammatory activities. Rats were divided into: Control group (received drug vehicles for 14 days); CPF-treated group (received subcutaneous 18 mg/kg BW of CPF daily for 14 days and CPF + Kaempferol treated group (received the same CPF dose +21 mg/kg BW of Kaempferol intraperitoneally for 14 days. On the 14th day, Y-maze and novel target recognition behavioral tests were employed to evaluate memory deficits. 24 h after the last dose of CPF, animals were sacrificed, and brain tissues were used for the determination of oxidative stress biomarkers and gene expression levels of GSK3β and Nrf2. The results revealed that CPF-treated rats suffered from severe deterioration of spatial and non-spatial memory functions with low activities of antioxidant enzymes and acetylcholinesterase (AChE). The administration of kaempferol significantly protected against CPF-induced neuronal damage, increased the activities of antioxidant enzymes and AChE and induced a better performance in the behavioral tests. The protective effect of kaempferol was mediated through the inhibition of GSK3β gene expression and the induction of Nrf2 expression in the brain tissues. In conclusion, the repeated exposure to CPF is associated with oxidative stress and memory deficits in rats. However, kaempferol administration effectively alleviated CPF- induced brain toxicity, possibly through the modulation of GSK3β-Nrf2 signaling pathway.

Protective Effect of Kaempferol on Biochemical and Histopathological Changes in Mercuric Chloride Induced Nephrotoxicity in Experimental Rats

The present study was aimed at assessing therapeutic implications of kaempferol on histopathological and ultra structural changes against mercuric chloride (HgCl2)-induced nephrotoxicity in animal model. The oral effective dose of kaempferol (100 mg/kg body weight) was given once a day until the end of the study (45 days post-induction of nephrotoxicity) to HgCl2 -induced nephrotoxicity in albino rats. At the end of the experimental period, urinary marker enzymes, lipid profile, histopathological and electron microscopical studies were assessed in control and experimental animals. HgCl2 - intoxication showed altered levels of lipid profiles, a significant decline in urinary marker enzymes in renal cells and damage in renal tissues which signpost the HgCl2 -induced nephrotoxicity. The treatment with flavonoid, kaempferol normalized the altered levels of urinary marker enzymes, lipid parameters, histopathological as wells as electron microscopical changes caused by HgCl2. It is concluded from the present study that kaempferol may play a significant role in the management of nephrotoxicity. However, further studies need to be conducted to find out the molecular aspects of nephro-protective role of kaempferol to ascertain its potential.

Protective Effect of Kaempferol on Cultured Neuroglial Cells Damaged by Induction of Ischemia-like Condition

Protective Effect of Kaempferol on Cultured Neuroglial Cells Damaged by Induction of Ischemia-like Condition

Protective effect of kaempferol, a flavonoid widely present in varieties of edible plants, on IL-1β-induced inflammatory response via inhibiting MAPK, Akt, and NF-κB signalling in SW982 cells

Effects and mechanisms of kaempferol, identified in a wide variety of dietary sources, on the expression of interleukin (IL)-6, IL-8, matrix metallo proteinase (MMP)-1, and cyclooxygenase (COX)-2 were evaluated in IL-1β-induced SW982 cells. The cells were pretreated with kaempferol of various concentrations (2, 10 and 50 µmol/L) followed by IL-1β (10 ng/mL) stimulation. Kaempferol significantly suppressed mRNA and protein levels of IL-6, IL-8, MMP-1, and COX-2 induced by IL-1β. Kaempferol also inhibited mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) phosphorylation and decreased IκB-α degradation and p65 protein translocation into the nucleus. Moreover, adenosine monophosphate-activated protein kinase (AMPK) does not contribute to the anti-inflammatory effects in SW982 cells, although its phosphorylation is significantly increased by kaempferol. These results indicate that kaempferol may have an anti-inflammatory effect by inhibiting expression of IL-6, IL-8, MMP-1 and COX-2 via suppressing MAPK, Akt, and nuclear factor (NF)-κB signalling but not activating AMPK signalling.

Protective Role of Kaempferol Against Acrylamide Intoxication

Background: In present scenario Acrylamide (A) concentration in starchy food processed at high temperatures have become very serious health problems. It is also used in industries and research chemical and potent toxic to experimental animals as well as humans. The present study was carried out to investigate protective effects of Kaempferol (KPF) against A-induced toxicity in rats. KPF is a natural flavonol, found in tea, strawberries, broccoli, cabbage, beans, grapes, tomato and plant products used in traditional medicine such as ginkgo biloba, Moringa oleifera and propolis. Methods: A (38.27 mg/kg, p.o.) was administered to female Wistar rats for 10 consecutive days followed by therapy of KPF for 3 days at different doses (5, 10, 20, 40 mg/kg, p.o.). Results: Activities of transaminases (aspartate aminotransferase/alanine aminotransferase), urea, creatinine and lipid profile were significantly rise whereas decline in haemoglobin after A administration. A significant elevation of LPO were observed with concomitant depleted activities of SOD, CAT and GSH in toxicant treated group. Significant reduction was found in the activity of AChE in brain. Therapy of KPF showed its protective effect on biochemical and histopathological observation at all the doses in a dose dependent manner. Conclusion: The protective effect of KPF was observed against A-induced toxicity.

Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells

The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction.

Protective effects of kaempferol against cardiac sinus node dysfunction via CaMKII deoxidization.

Kaempferol exerts cardioprotective actions through incompletely understood mechanisms. This study investigated the molecular mechanisms underlying the cardioprotective effects of kaempferol in sinus node dysfunction (SND) heart. Here, we demonstrate that angiotensin II (Ang II) infusion causes SND through oxidized calmodulin kinase II (CaMKII). In contrast to this, kaempferol protects sinus node against Ang II-induced SND. Ang II evoked apoptosis with caspase-3 activation in sinus nodal cells. However, kaempferol lowered the CaMKII oxidization and the sinus nodal cell death. To block the CaMKII oxidization, gene of p47phox, a cytosolic subunit of NADPH oxidase, was deleted using Cas9 KO plasmid. In the absence of p47phox, sinus nodal cells were highly resistance to Ang II-induced apoptosis, suggesting that oxidized-CaMKII contributed to sinus nodal cell death. In Langendorff heart from Ang II infused mice, kaempferol preserved normal impulse formation at right atrium. These data suggested that kaempferol protects sinus node via inhibition of CaMKII oxidization and may be useful for preventing SND in high risk patients.