Author: Yang, Chih‐Hao ; Shu, Lan‐Hsin ; Hsia, Chih‐Hsuan ; Jayakumar, Thanasekaran ; Huang, Wei‐Chieh ; Lee, Ai‐Wei ; Yen, Ting‐Lin ; Chiou, Kuan‐Rau ; Tran, Oanh‐Thi ; Hsia, Chih‐Wei ; Sheu, Joen‐Rong

AbstractPlatelets assume a pivotal role in the cardiovascular diseases (CVDs). Thus, targeting platelet activation is imperative for mitigating CVDs. Ginkgetin (GK), from Ginkgo biloba L, renowned for its anticancer and neuroprotective properties, remains unexplored concerning its impact on platelet activation, particularly in humans. In this investigation, we delved into the intricate mechanisms through which GK influences human platelets. At low concentrations (0.5–1 μM), GK exhibited robust inhibition of collagen and arachidonic acid (AA)‐induced platelet aggregation. Intriguingly, thrombin and U46619 remained impervious to GK's influence. GK's modulatory effect extended to ATP release, P‐selectin expression, intracellular calcium ([Ca2+]i) levels and thromboxane A2 formation. It significantly curtailed the activation of various signaling cascades, encompassing phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3‐kinase/Akt/glycogen synthase kinase‐3β and mitogen‐activated protein kinases. GK's antiplatelet effect was not reversed by SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor), and GK had no effect on the phosphorylation of vasodilator‐stimulated phosphoproteinSer157 or Ser239. Moreover, neither cyclic AMP nor cyclic GMP levels were significantly increased after GK treatment. In mouse studies, GK notably extended occlusion time in mesenteric vessels, while sparing bleeding time. In conclusion, GK's profound impact on platelet activation, achieved through inhibiting PLCγ2–PKC cascade, culminates in the suppression of downstream signaling and, ultimately, the inhibition of platelet aggregation. These findings underscore the promising therapeutic potential of GK in the CVDs.

01 Nov 2023·Phytotherapy Research

Ginkgolide K delays the progression of osteoarthritis by regulating YAP to promote the formation of cartilage extracellular matrix

Article

Author: Liu, Ruizhou ; He, Shiping ; Liu, Zhendong ; Chen, Hui ; Wang, Shihan ; Li, Xiaolei ; Dai, Jihang

AbstractOsteoarthritis (OA) is a degenerative disease characterized by cartilage wear and degradation. Ginkgolide K (GK) is a natural compound extracted from Ginkgo biloba leaves and possesses anti‐inflammatory and anti‐apoptotic effects. We found that the biological characteristics of GK were highly consistent with those of OA medications. This study aimed to determine and verify the therapeutic effect of GK on OA and mechanism of its therapeutic effect. For the in vivo experiment, OA rats were regularly injected in the articular cavity with GK, and the curative effects were observed after 4 and 8 weeks. For the in vitro experiment, we treated OA chondrocytes with different concentrations of GK and then detected the related indices of OA. Through the in vivo and in vitro experiments, we found that GK could promote the production of major components of the cartilage extracellular matrix. Transcriptome sequencing revealed that GK may activate hypoxia‐inducible factor 1 alpha via the hypoxia signaling pathway, which, in turn, activates yes‐associated protein and inhibits apoptosis of OA chondrocytes. GK has a therapeutic effect on OA and, therefore, has the potential to be developed into a new drug for OA treatment.

01 Nov 2023·Immunological investigations

Ginkgetin Alleviates Intervertebral Disc Degeneration by Inhibiting Apoptosis, Inflammation, and Disturbance of Extracellular Matrix Synthesis and Catabolism via Inactivation of NLRP3 Inflammasome.

Article

Author: Rui, Gang ; Lin, Shengrong ; Lin, Shan ; Hu, Baoshan

Apoptosis, inflammation, and the extracellular matrix (ECM) synthesis and catabolism are compromised with intervertebral disk degeneration (IDD).Ginkgetin (GK) has been demonstrated to alleviate several diseases; however, its effect on IDD remains unknown.The nucleus pulposus cells (NPCs) were stimulated with interleukin (IL)-1β to construct the IDD models in vitro.Rats were used for the construction of the IDD models in vivo via the fibrous ring puncture method.The effect and mechanism of GK on IDD were determined by cell counting kit-8 (CCK-8), flow cytometry, western blot, real-time quant. polymerase chain reaction (RT-qPCR), ELISA (ELISA), hematoxylin and eosin (HE) and safranine O staining, and immunohistochem. (IHC) assays, resp.GK increased the cell viability and upregulated the expressions of anti-apoptosis and ECM synthesis markers in NPCs treated with IL-1β.GK also decreased apoptosis rate, and downregulated the expressions of proteins related to pro-apoptosis, ECM catabolism, and inflammation in vitro.Mech., GK reduced the expression of nucleotide binding oligomeric domain like receptor protein 3 (NLRP3) inflammasome-related proteins.Overexpression of NLRP3 reversed the effect of GK on the proliferation, apoptosis, inflammation, and ECM degradation in IL-1β-induced NPCs.Moreover, GK attenuated the pathol. manifestations, inflammation, ECM degradation, and NLRP3 inflammasome expression in IDD rats.GK suppressed apoptosis, inflammation, and ECM degradation to alleviate IDD via the inactivation of NLRP3 inflammasome.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus	Preclinical	CN	Fujian Haixi New Drug Creation Co., Ltd	30 Nov 2021

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