||1. Kaempferol activates LXR-β and suppresses SREBP-1 to enhance symptoms in metabolic syndrome.|
2. Kaempferol exerts a potent inhibitory effect on in vitro bone resorption.
3. Kaempferol has anti-inflammatory action, can prevent and treat inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis.
4. Kaempferol has therapeutic potential for the prevention and treatment of thrombovascular diseases, can enhance relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization.
5. Kaempferol can inhibit cancer cell invasion through blocking the PKCδ/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity, may act as a therapeutic potential candidate for cancer metastasis.
6. Kaempferol is an autophagic enhancer, has a more general protection in Parkinson's disease, can mediate antiapoptotic and antioxidant effects is the enhancement of mitochondrial turnover by autophagy.
|Free Radic Biol Med. 2015 Jun;83:41-53. |
|Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation.[Pubmed: 25645952]|
|Reactive oxygen species (ROS) generated upon collagen stimulation act as second messengers to propagate various platelet-activating events. Among the ROS-generating enzymes, NADPH oxidase (NOX) plays a prominent role in platelet activation. Thus, NOX has been suggested as a novel target for anti-platelet drug development. Although Kaempferol has been identified as a NOX inhibitor, the influence of Kaempferol on the activation of platelets and the underlying mechanism have never been investigated. Here, we studied the effects of Kaempferol on NOX activation, ROS-dependent signaling pathways, and functional responses in collagen-stimulated platelets. |
METHODS AND RESULTS:
Superoxide anion generation stimulated by collagen was significantly inhibited by Kaempferol in a concentration-dependent manner. More importantly, Kaempferol directly bound p47(phox), a major regulatory subunit of NOX, and significantly inhibited collagen-induced phosphorylation of p47(phox) and NOX activation. In accordance with the inhibition of NOX, ROS-dependent inactivation of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) was potently protected by Kaempferol. Subsequently, the specific tyrosine phosphorylation of key components (Syk, Vav1, Btk, and PLCγ2) of collagen receptor signaling pathways was suppressed by Kaempferol. Kaempferol also attenuated downstream responses, including cytosolic calcium elevation, P-selectin surface exposure, and integrin-αIIbβ3 activation. Ultimately, Kaempferol inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice.
This study shows that Kaempferol impairs collagen-induced platelet activation through inhibition of NOX-derived ROS production and subsequent oxidative inactivation of SHP-2. This effect suggests that Kaempferol has therapeutic potential for the prevention and treatment of thrombovascular diseases.
|Int Immunopharmacol. 2015 Apr 11. |
|Kaempferol enhances the suppressive function of Treg cells by inhibiting FOXP3 phosphorylation.[Pubmed: 25870037]|
|Kaempferol is a natural flavonoid found in many vegetables and fruits. Epidemiologic studies have described that Kaempferol intake could reduce risk of cancer, especially lung, gastric, pancreatic and ovarian cancers. Recent studies have shown that Kaempferol could also be beneficial to the body to defend against inflammation, and infection by bacteria and viruses; however, the molecular mechanism of its immunoregulatory function remains largely unknown.
METHODS AND RESULTS:
Through screening a small molecule library of traditional Chinese medicine (TCM), we identified that Kaempferol could enhance the suppressive function of regulatory T cells (Tregs). Kaempferol was found to increase FOXP3 expression level in Treg cells and prevent pathological symptoms of collagen-induced arthritis in a rat animal model. Kaempferol could also reduce PIM1-mediated FOXP3 phosphorylation at S422.
Our study reveals a molecular mechanism that underlies the anti-inflammatory action of Kaempferol for the prevention and treatment of inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis.
|Br J Pharmacol. 2015 Jun;172(12):3003-14. |
|Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance Ca(2+) -activated K(+) channels.[Pubmed: 25652142]|
|BACKGROUND AND PURPOSE:
Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone.EXPERIMENTAL APPROACH:
The effect of Kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle.
METHODS AND RESULTS:
The effect of Kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of Kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs).
At a concentration without direct effect on vascular tone, Kaempferol (3 × 10(-6) M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by Kaempferol of the bradykinin-induced relaxation was not affected by N(ω)-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10(-4) M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10(-6) M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10(-3) M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa 1.1; 10(-7) M). Iberiotoxin also inhibited the potentiation by Kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin.
The present results suggest that, in smooth muscle cells of the porcine coronary artery, Kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of Kaempferol involved the activation of KCa 1.1 channels.