Aging-related diseases (ARDs) are a major global health concern, and the development of effective therapies is urgently needed. Kaempferol, a flavonoid found in several plants, has emerged as a ...promising candidate for ameliorating ARDs. This comprehensive review examines Kaempferol's chemical properties, safety profile, and pharmacokinetics, and highlights its potential therapeutic utility against ARDs. Kaempferol's therapeutic potential is underpinned by its distinctive chemical structure, which confers antioxidative and anti-inflammatory properties. Kaempferol counteracts reactive oxygen species (ROS) and modulates crucial cellular pathways, thereby combating oxidative stress and inflammation, hallmarks of ARDs. Kaempferol's low toxicity and wide safety margins, as demonstrated by preclinical and clinical studies, further substantiate its therapeutic potential. Compelling evidence supports Kaempferol's substantial potential in addressing ARDs through several mechanisms, notably anti-inflammatory, antioxidant, and anti-apoptotic actions. Kaempferol exhibits a versatile neuroprotective effect by modulating various proinflammatory signaling pathways, including NF-kB, p38MAPK, AKT, and the β-catenin cascade. Additionally, it hinders the formation and aggregation of beta-amyloid protein and regulates brain-derived neurotrophic factors. In terms of its anticancer potential, kaempferol acts through diverse pathways, inducing apoptosis, arresting the cell cycle at the G2/M phase, suppressing epithelial-mesenchymal transition (EMT)-related markers, and affecting the phosphoinositide 3-kinase/protein kinase B signaling pathways. Subsequent studies should focus on refining dosage regimens, exploring innovative delivery systems, and conducting comprehensive clinical trials to translate these findings into effective therapeutic applications.
•ARDs major global health issue, need for therapies•Kaempferol promising for ARDs, found in plants•Kaempferol has antioxidative, anti-inflammatory structure.•Counters ROS, fights ARD oxidative stress and inflammation•Low toxicity, safe per studies, good for ARD therapy
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•Review on the mechanism of kaempferol in the treatment of breast cancer.•Developing into preparations can improve the low bioavailability of kaempferol.•Targeted drug delivery system ...may be a new strategy for kaempferol in the treatment of breast cancer.
In the last century, natural compounds have achieved remarkable achievements in the treatment of tumors through chemotherapy. This inspired scientists to continuously explore anticancer agents from natural compounds. Kaempferol is an ordinary natural compound, the most common flavonoid, which is widely existed in vegetables and fruits. It has been reported to have various anticancer activities, including breast cancer, prostate cancer, bladder cancer, cervical cancer, colon cancer, liver cancer, lung cancer, ovarian cancer, leukemia, etc. Meanwhile, we found that there were more reports on breast cancer among these cancers although there are limited clinical studies that have addressed the benefits of kaempferol as an anti-cancer agent for breast cancer treatment. Then we realize that although kaempferol has been reported to have anti-breast cancer effect many times, it is still far from becoming a real anti-breast cancer agent. Therefore, in this review, we talk about the options for improving the anti-breast cancer effect of kaempferol, including various techniques and methods to improve the bioavailability of kaempferol, the idea of combining other compounds to produce synergistic effects, and the possibility of developing kaempferol into a targeted drug delivery system.
•We successfully prepared and evaluated kaempferol–phospholipid complex.•A UHPLC–MS/MS method was developed and fully validated to determine the concentration of KP in vivo.•The comparison of ...bioavailability between kaempferol and kaempferol–phospholipid complex were carried out.
As one of the dietary flavonoids, kaempferol (KP) has been well known to show strong anti-oxidative effect along with other biological properties. However, the oral bioavailability of KP is relatively low due to its poor solubility. In this study, we intended to increase the solubility and bioavailability of KP by preparing kaempferol–phospholipid complex (KP–PC). The KP–PC's physicochemical properties were characterized in terms of infrared spectroscopy (IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), water/n-Octanol solubility and in vitro dissolution. KP–PC exhibited higher solubility and dissolution rate than KP, indicating a significant improvement in hydrophilicity. A UPLC–ESI–MS/MS method was developed and validated for the determination of KP in Sprague-Dawley (SD) rat plasma, so as to investigate the oral bioavailability of KP–PC versus KP. Results showed that Cmax and AUC0–48h of KP from the complex (Cmax: 3.94±0.83μg/mL, AUC0–48h: 57.81±9.43mg/Lh) were higher than that of KP (Cmax: 1.43±0.21μg/mL, AUC0–48h: 13.65±3.12mg/Lh). This research indicated that phospholipid complex (PC) might be one of the suitable approachs to improve the oral bioavailability of KP and other poor-solubility flavonoids.
There has been a rapid increase in the incidence and prevalence of opportunistic bacterial infections. Inappropriate use of current antibiotics has continuously contributed to the emergence of ...resistance to conventional antibiotic therapy. Therefore, the search for natural molecules that are able to combat infections is of great public interest, and many of these compounds with antimicrobial properties can be obtained from phytochemical studies of medicinal plants. In this context, this study reports the isolation and characterization of the flavonoid, kaempferol 7-O-β-D-(6″-O-cumaroyl)-glucopyranoside, from Croton piauhiensis leaves. Additionally, the intrinsic antimicrobial action of the compound and its enhancement against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains were assessed. The minimum inhibitory concentration (MIC) of the compound was determined using broth microdilution assays. To evaluate the modulatory effect of the flavonoid, the MIC of antibiotics amikacin and gentamicin, belonging to the class aminoglycosides was assessed, with and without the compound in sterile microplates. The results of intrinsic antibacterial activity tests revealed that the compound had no antibacterial activity against strains tested at concentrations <1024 μg/mL. The combination of the flavonoid at a concentration of 128 μg/mL with gentamicin presented synergistic effects against S. aureus 10 and E. coli 06, and also reduced the MIC from 16 μg/mL to 4 μg/mL and 8 μg/mL, respectively. Amikacin also showed synergistic effects against S. aureus 10 and E. coli 06. We also observed reduced MIC for both, from 128 μg/mL to 32 μg/mL; however, antagonism for P. aeruginosa increased the MIC from 16 μg/mL to 64 μg/mL. The combination of the flavonoid with the aminoglycosides may be an alternative to potentiate the expected results in treatment against S. aureus and E. coli, since their association leads to a synergistic effect, reducing the MIC of these drugs and decreasing the dose necessary for therapeutic success.
•The combination of the kaempferol enhanced the antibiotic activity of the amikacin.•The combination of the kaempferol enhanced the antibiotic activity of the gentamicin.•Both combinations decreased the dose necessary for therapeutical success of the antibiotics.
Our previous reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent in vitro antioxidant capacities as well as inhibitory ...activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including mainly ellagic acid, kaempferol and their derivatives. Nevertheless, few in vivo studies on antidiabetic activities of these phenolics were conducted. The present study investigated hypoglycemic effects with normal and diabetic rats being administrated orally without or with ECE at 200 and 800 mg/kg for 15 days. In normal rats, no significant differences were exhibited after ECE administration in body weight, fasting blood glucose level, levels of cholesterol, triglyceride, LDL and AST in serum, organ indexes, and levels of GSH and MDA in organs. In diabetic rats, the fasting blood glucose level, indexes of heart and liver, and levels of cholesterol and triglyceride in serum and MDA in heart tissue were significantly decreased. Moreover, HDL levels in serum and SOD activities in the four organs of diabetic rats were significantly improved after ECE administration at 800 mg/kg. Thus, in addition to inhibiting α-glucosidase, α-amylase and protein glycation reported previously, oak cups might contain novel dietary phytonutrients in preventing abnormal changes in blood glucose and lipid profile and attenuating oxidant stress in vivo. The results also implied that it is ellagic acid, kaempferol and their derivatives enriched in ECE that might play vital roles in managing type 1 as well as type 2 diabetes.
•Apple MdUGT75B1 and MdUGT71B1 were identified as key UGTs in flavonol biosynthesis.•MdUGT75B1 was flavonol-specific UGT with UDP-Gal preference.•MdUGT71B1 exhibited UDP-Glc preference toward broader ...flavonoid substrates.
Apple is rich in flavonol glycosides, which are believed to contribute to putative health benefits associated with apple consumption. Glycosylation, catalyzed by uridine diphospho-glycosyltransferases (UGTs), is the last step in flavonol biosynthesis, which confers molecular stability and solubility to the flavonol. In the present study, the involvement of two UGTs, MdUGT75B1 and MdUGT71B1, in flavonol biosynthesis in apple was investigated. The major flavonols are quercetin 3-O-glycosides, and UV-B and blue light treatment significantly enhanced the accumulation of quercetin 3-O-galactoside, quercetin 3-O-glucoside, and kaempferol 3-O-galactoside. Transcript levels of MdUGT75B1 and MdUGT71B1 in fruit subjected to different treatments were correlated well with flavonol accumulation. MdUGT75B1 showed flavonol-specific activity with a preference for UDP-galactose as the sugar donor, while MdUGT71B1 using UDP-glucose exhibited a wider substrate acceptance. Thus, MdUGT75B1 and MdUGT71B1 are key UGTs involved in flavonol biosynthesis and may have important roles in regulating accumulation of these health-promoting bioactive compounds in apple.
Alzheimer's disease (AD) is the most common type of dementia and seriously affects human life and health. Kaempferol (KMP) is a common flavonoid, that is mainly derived from the rhizomes of ...Kaempferol galanga L. and is widely found in various fruits and vegetables. Previous studies have suggested that KMP has multiple pharmacological activities. However, the anti-AD mechanism of KMP has not been elucidated.
This systematic review aims to summarize the existing preclinical experiments on KMP, further confirm the therapeutic effect of KMP in an AD model, and summarize the possible mechanism by which KMP exerts anti-AD effects. Electronic databases, including PubMed, China National Knowledge Infrastructure (CNKI), Baidu Academic, and Wanfang, were searched using the keywords of ‘Kaempferol,’ ‘KMP,’ ‘pharmacology,’ and ‘Alzheimer’s disease’.
We evaluated the reliability of the 12 included studies, and the results showed that the anti-AD mechanism of KMP was reliable and that the prospect of KMP in the treatment of cognitive impairment was promising. We comprehensively assessed the neuroprotective effects of KMP in in vivo and in vitro models of AD. These studies shown that KMP ameliorated AD through several mechanisms, including its antioxidant, anti-inflammatory, anti-apoptotic, and anti-acetylcholinesterase effects.
KMP may exert anti-AD effects through various mechanisms and is a potential drug with broad prospects for the treatment of AD.
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•Kaempferol (KMP) is a flavonoid derived from Kaempferol galanga L. with potential neuroprotective effects.•12 articles were reviewed for KMP in the treatment of AD.•KMP provided novel multi-mechanistic AD therapeutic strategy.
Context: Cassia alata Linn. syn. Senna alata (L.) Roxb. (Caesalpiniaceae) is used for treating various disease conditions including diabetes but its mechanism(s) of action and active principles ...remain to be elucidated.
Objective: The antidiabetic principles were identified using an in vitro α-glucosidase inhibition study.
Materials and methods: The methanol extract of leaves of C. alata, which showed potent α-glucosidase inhibitory activity (IC50, 63.75 ± 12.81 µg/ml), was fractionated. Active fractions were taken for further analysis by a variety of techniques including HPLC and Combiflash chromatography. The identity of the isolated compounds was established by spectroscopic analysis while their potential antidiabetic activity was assessed by in vitro enzyme inhibition studies.
Results: The α-glucosidase inhibitory effect of the crude extract was far better than the standard clinically used drug, acarbose (IC50, 107.31 ± 12.31 µg/ml). A subsequent fractionation of the crude extract was made using solvents of ascending polarity (petroleum ether, chloroform, ethyl acetate, n-butanol and water). The ethyl acetate (IC50, 2.95 ± 0.47 µg/ml) and n-butanol (IC50, 25.80 ± 2.01 µg/ml) fractions which contained predominantly kaempferol (56.7 ± 7.7 µM) and kaempferol 3-O-gentiobioside (50.0 ± 8.5 µM), respectively, displayed the highest carbohydrate enzyme inhibitory effect.
Discussion: One of the possible antidiabetic mechanisms of action of C. alata is by inhibiting carbohydrate digestion. This is the first report on α-glucosidase activity of kaempferol 3-O-gentiobioside.
Conclusion: Considering the activity profile of the crude extract and isolated bioactive compounds, further in vivo and clinical studies on C. alata extracts and compounds are well merited.
Kaempferol is a major flavonoid found in natural plant extracts; it shows great potential in anti-inflammatory and anti-cancer medicine. However, the underlying mechanism of the protective action of ...kaempferol on the gut-vascular barrier (GVB) and the active sites preventing intestinal micro-angiogenesis has not been reported. The purpose of our study is to investigate the protective effect of kaempferol on the barrier damage induced by lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α), and its mechanism of protective action on intestinal micro-angiogenesis. Our data showed that the combination of LPS and TNF-α activates the inflammatory response of the rat intestinal microvascular endothelial cells (RIMVECs), leading to overexpression of vascular endothelial growth factors (VEGFs). Also, the permeability of GVB and transepithelial electrical resistance (TEER) constructed by Transwell and the tubular structure of RIMVEC were significantly affected. Kaempferol (25, 50, and 100 μM) decreased the inflammatory factor secretion and GVB permeability, down-regulated the expression of VEGFs, p-Akt, and hypoxia-inducible factor-1alpha (HIF-1α). It also alleviated the abnormal expression of tight junction proteins (TJs). Moreover, kaempferol may prevents intestinal angiogenesis in the presence of Akt inhibitor (MK-2206 2HCl) by regulating tube formation and downstream signaling of the VEGF/Akt pathways. In addition, the wound healing test showed that kaempferol had a similar effect in the presence of p38 inhibitor (SB203580), which intuitively restrained the migration of RIMVECs and reduced the p38 MAPK signaling. Our results demonstrated that kaempferol exhibits significant anti-inflammatory effects in LPS and TNF-α induced inflammatory environments. Kaempferol prevents intestinal angiogenesis by impeding the tube formation and migration of RIMVECs. It also suppresses the expression of angiogenesis-related signals, thereby protecting the GVB.
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•LPS and TNF-α induce the inflammatory injury and angiogenesis of RIMVECs.•Angiogenesis-related factors, cell migration, and tube formation analysis show the antiangiogenic potential of kaempferol.•Kaempferol protects the integrity of the gut-vascular barrier.•Downregulation of VEGF/Akt/p38 signaling is an effective pathway for kaempferol to prevent angiogenesis.
Kaempferol is a natural antioxidant present in vegetables and fruits used in human nutrition. In previous work, we showed that intraperitoneal (i.p.) kaempferol administration strongly protects ...against striatum neurodegeneration induced by i.p. injections of 3-nitropropionic acid (NPA), an animal model of Huntington's disease. Recently, we have shown that reactive A1 astrocytes generation is an early event in the neurodegeneration induced by NPA i.p. injections. In the present work, we have experimentally evaluated the hypothesis that kaempferol protects both against the activation of complement C3 protein and the generation of reactive A1 astrocytes in rat brain striatum and hippocampus. To this end, we have administered NPA and kaempferol i.p. injections to adult Wistar rats following the protocol described in previous work. Kaempferol administration prevents proteolytic activation of complement C3 protein and generation of reactive A1 astrocytes NPA-induced in the striatum and hippocampus. Also, it blocked the NPA-induced increase of NF-κB expression and enhanced secretion of cytokines IL-1α, TNFα, and C1q, which have been linked to the generation of reactive A1 astrocytes. In addition, kaempferol administration prevented the enhanced production of amyloid β peptides in the striatum and hippocampus, a novel finding in NPA-induced brain degeneration found in this work.
•Kaempferol prevents the NPA-induced complement C3 protein activation in rat brain.•Kaempferol protects against reactive A1 astrocytes induction by NPA in rat brain.•Kaempferol blocks the NPA-induced increase of IL-1α, TNFα and C1q in rat brain.•Kaempferol prevents the NPA-induced NF-κB expression in striatum and hippocampus.•Kaempferol blocks NPA-induced amyloid β peptides production in striatum and hippocampus.
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