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Annona muricata is one of the most important traditional medicinal plants which contains numerous chemicals that exhibit various pharmacological properties. In this study, silver nanoparticles were prepared using A. muricata peel extract as a reducing agent and the effect was enhanced through A. muricata like pharmaceutical activity. AgNPs formation was confirmed by color changes, UV-visible spectroscopy, SEM, DLS, and XRD. The anti-proliferative activity of AgNPs against THP-1, AMJ-13, and HBL cell lines was studied. Apoptotic markers were tested using AO/EtBr staining assay, cell cycle phases using flowcytometry, and the expression of P53. Autophagy takes an essential part in controlling inflammasome activation by primary bone marrow-derived macrophages (BMDMs). We report novel functions for AgNPs-affected autophagy, represented by the control of the release of IL-1β, caspase-1, adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and NLRP3 in BMDMs following treatment with LPS+ATP. The current study revealed that the AgNPs inhibited THP-1 and AMJ-13 cell proliferation. Meanwhile, the AgNPs significantly increased autophagy and reduced IL-1b and NLRP3 levels in both in vivo and in vitro models. The secretion of IL-1β was reduced whereas the degradation of NLRP3 inflammasome was enhanced. These findings propose that AgNPs apply an anti-proliferative activity against THP-1 and AMJ-13 cells through the stimulation of apoptosis via mitochondrial damage and induction of p53 protein pathway. In addition, AgNP-induced autophagy reduced the levels of IL-1β and NLRP3 inflammasome activation. This indicated that the AgNPs augment autophagy controlled by the IL-1β pathway via two different novel mechanisms. The first one is regulating activation of the IL-1 β, caspase-1, and ASC, while the second is NLRP3 targeting for lysosomal degradation. Overall, this study suggests that AgNPs could be a potent therapy for various types of cancer and an alternative treatment for preventing inflammation via enhancing autophagy. [ABSTRACT FROM AUTHOR]