| Description: |
Kakkalide is a potent lactate dehydrogenase (LDH) inhibitor, it has anti-inflammatory effects. Kakkalide can inhibit ROS-associated inflammation and ameliorated insulin-resistant endothelial dysfunction by beneficial effects on IRS-1 function.Kakkalide attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils, it also shows protective effects on ethanol-induced lethality and hepatic injury are dependent on its biotransformation by human intestinal microflora.
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| Targets: |
IL Receptor | NF-kB | ROS | Akt | PI3K | IkB | NO | PGE | COX | TNF-α | IKK | LDH |
| In vitro: |
| J Diabetes. 2013 Mar;5(1):13-24. | | Kakkalide ameliorates endothelial insulin resistance by suppressing reactive oxygen species-associated inflammation.[Pubmed: 23190749 ] | Kakkalide is the predominant isoflavone derived from the flowers of Pueraria lobata (Willd.) Ohwi. The aim of the present study was to investigate the effects of kakkalide on insulin resistance in the endothelium.
METHODS AND RESULTS:
Human umbilical vein endothelial cells (HUVEC) were stimulated with 100 μmol/L palmitate (PA) for 30 min and the effects of 30 min pretreatment with 0.1-10 μmol/L kakkalide on reactive oxygen species (ROS)-associated inflammation in cells were evaluated by western blot analysis and reverse transcription-polymerase chain reaction. Furthermore, we investigated the biomodulation of insulin signaling by kakkalide along the insulin receptor substrate (IRS)-1/Akt/endothelial nitric oxide synthase (eNOS) pathway. We also determined the effects of 30 min pretreatment with 0.1-10 μmol/L kakkalide on insulin-mediated endothelium-dependent vasodilation of rat aorta in vitro following stimulation with 100 μmol/L PA.
Kakkalide inhibited ROS overproduction and effectively restored mitochondrial membrane potential, demonstrating its chemoprotection of mitochondrial function. In addition, kakkalide inhibited ROS-associated inflammation in the endothelium by inhibiting tumor necrosis factor-α and interleukin-6 production and gene expression, as well as suppressing the phosphorylation of c-Jun N-terminal kinase and IκB kinase β/nuclear factor-κB. Inflammation impaired insulin phosphatidylinositol 3-kinase (PI3K) signaling and reduced insulin-mediated NO production in endothelial cells. Kakkalide facilitated PI3K signaling by positively regulating serine/tyrosine phosphorylation of IRS-1.
CONCLUSIONS:
Kakkalide inhibited ROS-associated inflammation and ameliorated insulin-resistant endothelial dysfunction by beneficial effects on IRS-1 function. |
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| In vivo: |
| Mol Nutr Food Res. 2017 Feb;61(2). | | Irisolidone attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils.[Pubmed: 27546737] | This study was designed to determine whether irisolidone and its glycoside kakkalide, which are the major constituents of the flower of Pueraria lobata (Kudzu) can attenuate ethanol-induced gastritic injury in mice.
METHODS AND RESULTS:
Irisolidone and kakkalide inhibited IL-8 secretion and NF-κB activation in lipopolysaccharide-stimulated KATO III cells. Therefore, we investigated their protective effects against ethanol-induced gastric injury in mice. Pretreatment with kakkalide or irisolidone decreased the area of hemorrhagic ulcerative lesions caused by ethanol and suppressed stomach myeloperoxidase activity, CXCL4 secretion, and NF-κB activation. The ameliorating effect of irisolidone was more potent than that of kakkalide.
CONCLUSIONS:
Irisolidone may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, particularly neutrophils, through the regulation of CXCL-4 or IL-8 secretion. | | J Pharmacol Sci. 2003 Nov;93(3):331-6. | | Protective effects of kakkalide from Flos puerariae on ethanol-induced lethality and hepatic injury are dependent on its biotransformation by human intestinal microflora.[Pubmed: 14646251] |
METHODS AND RESULTS:
When kakkalide, which was isolated from Flos Puerariae, was incubated with human fecal bacteria, kakkalide was metabolized to irisolidone via kakkalidone. When kakkalide (250 mg/kg) was orally administered to rats, irisolidone, but not kakkalide, was detected in the blood. The mortality associated with ethanol treatment was slightly reduced when the mice were intraperitoneally treated with kakkalide. Intraperitoneally administered kakkalide and kakkalidone did not reduce alcohol toxicity. However, orally administered kakkalide and intraperitoneally administered irisolidone significantly reduced the mortality. Orally administered kakkalide and intraperitoneally injected irisolidone greatly reduced serum alanine aminotransferase and aspartate aminotransferase activities in ethanol-intoxified mice.
CONCLUSIONS:
Orally administered kakkalide and intraperitoneally administered irisolidone significantly lowered the level of blood ethanol. The results indicate that kakkalide is a prodrug of irisolidone in protecting against ethanol-induced lethality and hepatic injury. |
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