Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation

Wang, Su Bin; Jang, Ji Yong; Chae, Yun Hee; Min, Ji Hyun; Baek, Jin Young; Kim, Myung‐Hee; Park, Yunjeong; Hwang, Gwi Seo; Ryu, Jae Sang; Chang, Tong Shin

doi:10.1016/j.freeradbiomed.2015.01.018

Cited by 51 publications

(32 citation statements)

References 85 publications

(159 reference statements)

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“…However, it is notable that masked in the resting state. Phosphorylation of p47-phox exposes these two SH3 domains for p22-phox binding and activates NOX [19,20]. We propose that SN shows its protective effect by interacting with p47-phox and its domains, although this requires further studies for confirmation.…”

Section: Discussionmentioning

confidence: 84%

“…NOX is a multi-component enzyme for ROS generation, consisting of a catalytic subunit NOX2/gp91-phox and p22 phox, and several cytosolic regulatory subunits, including p47-phox and p67-phox [19,20]. The p47-phox protein, a major regulatory subunit, is located at the plasma membrane and assembles with other subunits that are required for the full activation of NOX [21].…”

Section: Introductionmentioning

confidence: 99%

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Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes

Wang

Cai

Tang

et al. 2016

Kidney Blood Press Res

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Background/Aims: Sinomenine, a pure alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, and sinomenine hydrochloride (SN) has been successfully used for the therapy of rheumatoid arthritis (RA) and kidney diseases. Autophagy is a cytoprotective mechanism used by podocytes and other cells to alleviate the effects of oxidative stress, and angiotensin II (Ang II) significantly promotes podocyte autophagy. However, excessive autophagy may lead to cell death and podocyte depletion. The present study evaluated the effect of SN in podocytes induced by Ang II. Methods: Podocytes were pretreated with graded concentrations (10^-8 M ∼ 10^-4 M) of SN and then stimulated with Ang II. The LC3B protein and the p47-phox membrane fraction were measured by Western blot. Autolysosomes were assessed by transmission electron microscopy. FACS was used to quantify the ROS produced by podocytes. The translocation of p47-phox to the membrane was investigated by immunofluorescence. Results: The 10^-8 M ∼ 10^-4 M of SN alone did not effect ROS generation or podocyte autophagy. The 10^-8 M and 10^-6 M SN attenuated Ang II-induced autophagy in podocytes. Furthermore, SN decreased the level of ROS generation in Ang II-induced podocytes via inhibition of NOX subunit p47-phox translocation to the membrane. Conclusion: The appropriate concentration of SN attenuated Ang II-induced podocyte autophagy through ROS generation, at least in part, by regulating NOX subunit p47-phox translocation to the membrane.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes

Wang

Cai

Tang

et al. 2016

Kidney Blood Press Res

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“…Washed platelets were prepared by differential centrifugation as described previously334143. Briefly, venous blood samples were collected in citrate by standard venous puncture from rats, and the first 2 mL of blood was discarded to avoid artificial activation.…”

Section: Methodsmentioning

confidence: 99%

“…Adherent platelets were fixed with cold 4% paraformaldehyde for 15 min and then washed with PBS. The perfusion was live-monitored with a fluorescence microscope (Nikon TE-2000S; Nikon, Melville, NY, USA) equipped with a Nikon DS-2MBWc-U1 CCD camera (Nikon)344344.…”

Section: Methodsmentioning

confidence: 99%

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release

Xin

Wei

et al. 2016

Sci Rep

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Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.

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“…In addition, quercetin, the aglycone of quercitrin, inhibited collagen-induced platelet aggregation by blocking hydrogen peroxidase production, calcium mobilization, and 1,3,4-inositol triphosphate formation in human platelets (Pignatelli et al ., 2000). Furthermore, kaempferol, the aglycon of afzelin, inhibited collagen-induced platelet aggregation and adhesion in vitro by suppressing the tyrosine phosphorylation of key components involved in the collagen receptor signaling cascade, such as spleen tyrosine kinase (Syk), Bruton’s tyrosine kinase (Btk) and PLCγ2 (Wang et al ., 2015). Although we confirmed that quercitrin and afzelin are the major constituents of LLE, the pharmacological effects of these compounds were not investigated.…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet and Antithrombotic Effects of the Extract of Lindera obtusiloba Leaves

Kim

Lee²,

Kang

et al. 2016

Biomolecules & Therapeutics

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Lindera obtusiloba has been used in traditional herbal medicine for the treatment of blood stasis and inflammation. The leaves of Lindera obtusiloba have been reported to exhibit various physiological activities. However, there is little information available on their antiplatelet and antithrombotic activities. Thus, the present study aimed to evaluate the effect of Lindera obtusiloba leaf extract (LLE) on platelet activities, coagulation and thromboembolism. In a platelet aggregation study, LLE significantly inhibited various agonist-induced platelet aggregations in vitro and ex vivo. Furthermore, LLE significantly inhibited collagen-induced thromboxane A2 (TXA2) production in rat platelets. In addition, oral administration of LLE was protective in a mouse model of pulmonary thromboembolism induced by intravenous injection of a mixture of collagen and epinephrine. Interestingly, LLE did not significantly alter prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study indicates that the antithrombotic effects of LLE might be due to its antiplatelet activities rather than anticoagulation. Taken together, these results suggest that LLE may be a candidate preventive and therapeutic agent in cardiovascular diseases associated with platelet hyperactivity.

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Kaempferol suppresses collagen-induced platelet activation by inhibiting NADPH oxidase and protecting SHP-2 from oxidative inactivation

Cited by 51 publications

References 85 publications

Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes

Sinomenine Attenuates Angiotensin II-Induced Autophagy via Inhibition of P47-Phox Translocation to the Membrane and Influences Reactive Oxygen Species Generation in Podocytes

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release

Antiplatelet and Antithrombotic Effects of the Extract of Lindera obtusiloba Leaves

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