Kaempferol 3-neohesperidoside

J Nat Prod. 2008 Apr;71(4):532-5.

Insulinomimetic effect of kaempferol 3-neohesperidoside on the rat soleus muscle.[Pubmed: 18303854]

METHODS AND RESULTS:
A stimulatory effect of Kaempferol 3-neohesperidoside ( 1) on glucose uptake (35% and 21%) was observed when the rat soleus muscle was incubated with 1 and 100 nM of this flavonoid glycoside, respectively. The concentration-response curve of insulin showed a stimulatory effect at 3.5 and 7.0 nM (42% and 50%) on glucose uptake when compared with the control group. The effect of Kaempferol 3-neohesperidoside on glucose uptake was completely nullified by pretreatment with LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), and RO318220, an inhibitor of protein kinase C (PKC). However, no significant change occurred on glucose uptake stimulated by Kaempferol 3-neohesperidoside when muscles were pretreated with PD98059, an inhibitor of mitogen-activated protein kinase (MEK), and cycloheximide, an inhibitor of protein synthesis. Kaempferol 3-neohesperidoside and insulin (7 nM) did not show a synergistic effect on glucose uptake. Additionally, 100 mg/kg of Kaempferol 3-neohesperidoside by oral gavage was able to increase glycogen content in the muscle.
CONCLUSIONS:
These results suggest that Kaempferol 3-neohesperidoside stimulates glucose uptake in the rat soleus muscle via the PI3K and PKC pathways and, at least in part, independently of MEK pathways and the synthesis of new glucose transporters.

Med.Chem. Res. 2013, 22(9):4269-77.

Phytochemical, cytotoxic, hepatoprotective and antioxidant properties of Delonix regia leaves extract[Reference: WebLink]

Hepatocellular carcinoma is considered the third most common cause of cancer-related death worldwide. Thus, the present study was designed to test for the first time the putative cytotoxic effect of Delonix regia extract, besides its hepatoprotective activity.
METHODS AND RESULTS:
In this context, this study targets four specific aims; first, the phytochemical investigation of D. regia extract which led to the isolation of seven flavonoid glycosides; Kaempferol 3-rhamnoside 1, Quercetin 3-rhamnoside 2, Kaempferol 3-glucoide 3, Kaempferol 3-rutinoside 4, Kaempferol 3-neohesperidoside 5, Quercetin 3-rutinoside 6 and Quercetin 3-glucoside 7. Second, the evaluation of in vitro cytotoxic activity of the extract, where the extract exhibited a potent cytotoxic effect against HepG2 cell line. Third, the hepatoprotective activity was investigated using carbon tetrachloride (CCl4)-induced liver injury. The plant extract at dose of 50, 100 and 200 mg/kg body weight reduced serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase as well as total and direct bilirubin in a dose dependent manner. The fourth aim was the investigation of the antioxidant activity of the extract as the treatment of rats with the extract at different doses significantly increased the liver tissue level of superoxide dismutase, catalase, reduced glutathione and total antioxidant capacity and decreased the level of malondialdehyde as compared to CCl4 treated group.
CONCLUSIONS:
The current findings concluded that the extract of D. regia possessed not only a significant anticancer effect against HepG2 cells, but also an effective and a dose dependent hepatoprotective and antioxidant activities due to the presence of flavonoids content.

Drug Metab Dispos . 2015 Aug;43(8):1181-9.

Ginsenosides Regulate PXR/NF-κB Signaling and Attenuate Dextran Sulfate Sodium-Induced Colitis[Pubmed: 25986850]

Abstract Pregnane X receptor (PXR) activation exhibits anti-inflammatory effects via repressing nuclear factor-κB (NF-κB); however, its overactivation may disrupt homeostasis of various enzymes and transporters. Here we found that ginsenosides restore PXR/NF-κB signaling in inflamed conditions without disrupting PXR function in normal conditions. The effects and mechanisms of ginsenosides in regulating PXR/NF-κB signals were determined both in vitro and in vivo. Ginsenosides significantly inhibited NF-κB activation and restored the expression of PXR target genes in tumor necrosis factor-α-stimulated LS174T cells. Despite not being PXR agonists, ginsenosides repressed NF-κB activation in a PXR-dependent manner. Ginsenosides significantly increased the physical association between PXR and the NF-κB p65 subunit and thereby decreased the nuclear translocation of p65. Ginsenoside Rb1 and compound K (CK) were major bioactive compounds in the regulating PXR/NF-κB signaling. Consistently, ginsenosides significantly attenuated dextran sulfate sodium-induced experimental colitis, which was associated with restored PXR/NF-κB signaling. This study indicates that ginsenosides may elicit anti-inflammatory effects via targeting PXR/NF-κB interaction without disrupting PXR function in healthy conditions. Ginsenoside Rb1 and CK may serve as leading compounds in the discovery of new drugs that target PXR/NF-κB interaction in therapy for inflammatory bowel disease. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Biochimie. 2009 Jul;91(7):843-9.

Signaling pathways of kaempferol 3-neohesperidoside in glycogen synthesis in rat soleus muscle.[Pubmed: 19376191]

Kaempferol 3-neohesperidoside is one of the several compounds that have been reported to have insulin-like properties in terms of glucose lowering.
METHODS AND RESULTS:
We studied the effect of Kaempferol 3-neohesperidoside in glycogen synthesis in rat soleus muscle through the incorporation of (14)C-d-glucose in glycogen. Kaempferol 3-neohesperidoside stimulates glycogen synthesis in rat soleus muscle by approximately 2.38-fold. Insulin at 100 nM showed a stimulatory effect on glycogen synthesis when compared with the control group. The stimulatory effect of kaempferol 3-neophesperidoside on glycogen synthesis was inhibited by wortmannin, the phosphatidylinositol 3-kinase (PI3K) inhibitor, and enhanced by lithium chloride, a glycogen synthase kinase 3 (GSK-3) inhibitor. Moreover, the stimulatory effect of Kaempferol 3-neohesperidoside was also nullified by PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK) and by calyculin A, an inhibitor of protein phosphatase 1 (PP1) activity.
CONCLUSIONS:
It was concluded that the PI3K - GSK-3 pathway and MAPK - PP1 pathway are involved in the stimulatory Kaempferol 3-neohesperidoside effect on glycogen synthesis in rat soleus muscle.