Alantolactone induces platelet apoptosis by activating the Akt pathway
Creators: name: Sun, Yueyue
name: Yang, Mengnan
name: Li, Shujun
name: Hu, Ying
name: Yang, Biao
name: Li, Xu
name: Yan, Rong
name: Dai, Kesheng
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Biochemistry
subject: Medicine
subject: Pharmacology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Science Policy
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Mental Health
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences

description: Alantolactone (ALT), a sesquiterpene lactone compound isolated from <i>Inula helenium L</i>., has recently attracted much attention for its anti-tumor properties. ALT reportedly functions by regulating the Akt pathway, which has been shown to be involved in programmed platelet death (apoptosis) and platelet activation. However, the precise effect of ALT on platelets remains unclear. In this study, washed platelets were treated with ALT <i>in vitro</i>, and apoptotic events and platelet activation were detected. <i>In vivo</i>, platelet transfusion experiments were employed to detect the effect of ALT on platelet clearance. Platelet counts were examined after intravenous injection of ALT. We found that ALT treatment induced Akt activation and Akt-mediated apoptosis in platelets. ALT-activated Akt elicited platelet apoptosis by activating phosphodiesterase (PDE3A) and PDE3A-mediated protein kinase A (PKA) inhibition. Pharmacological inhibition of the PI3K/Akt/PDE3A signaling pathway or PKA activation was found to protect platelets from apoptosis induced by ALT. Moreover, ALT-induced apoptotic platelets were removed faster <i>in vivo</i>, and ALT injection resulted in the platelet count decline. Either PI3K/Akt/PDE3A inhibitors or a PKA activator could protect platelets from clearance, ultimately ameliorating the ALT-induced decline in platelet count in the animal model. These results reveal the effects of ALT on platelets and their related mechanisms, suggesting potential therapeutic targets for the prevention and alleviation of possible side effects resulting from ALT treatments. <i>What is the context?</i>In the past several decades, natural products, including traditional Chinese medicine (TCM), have been developed for the treatment of a variety of diseases.Alantolactone (ALT), a natural herb compound mainly extracted from the root of <i>Inula helenium L</i>., is the essential active component in many TCM formulas. ALT has attracted extensive attention because of its anti-cancer capacity recently.However, adverse events (AEs) induced by drugs are common in chemotherapy, and the side effects of ALT treatment remain unclear. In the past several decades, natural products, including traditional Chinese medicine (TCM), have been developed for the treatment of a variety of diseases. Alantolactone (ALT), a natural herb compound mainly extracted from the root of <i>Inula helenium L</i>., is the essential active component in many TCM formulas. ALT has attracted extensive attention because of its anti-cancer capacity recently. However, adverse events (AEs) induced by drugs are common in chemotherapy, and the side effects of ALT treatment remain unclear. <i>What is new?</i>In this study, experiments were conducted to clarify the precise effect of ALT on platelets. We demonstrated for the first time that ALT induces platelet apoptosis and platelet count decline, suggesting possible side effects of ALT treatment.ALT-activated Akt elicited platelet apoptosis by activating phosphodiesterase (PDE3A) and PDE3A-mediated protein kinase A (PKA) inhibition.Our work provides experimental evidence supporting the hypothesis that the effects of ALT on Akt may vary depending on cell types. Therefore. More research is needed to explore the side effects of ALT on other cells before clinical application. In this study, experiments were conducted to clarify the precise effect of ALT on platelets. We demonstrated for the first time that ALT induces platelet apoptosis and platelet count decline, suggesting possible side effects of ALT treatment. ALT-activated Akt elicited platelet apoptosis by activating phosphodiesterase (PDE3A) and PDE3A-mediated protein kinase A (PKA) inhibition. Our work provides experimental evidence supporting the hypothesis that the effects of ALT on Akt may vary depending on cell types. Therefore. More research is needed to explore the side effects of ALT on other cells before clinical application. <i>What is the impact?</i>This study reveals possible side effects of ALT treatment, providing the reference for clinic drug administrate and estimation of medicine safety. Significantly, our findings demonstrated relevant molecular mechanisms, providing strategies for controlling or alleviating these side effects in the future. This study reveals possible side effects of ALT treatment, providing the reference for clinic drug administrate and estimation of medicine safety. Significantly, our findings demonstrated relevant molecular mechanisms, providing strategies for controlling or alleviating these side effects in the future.