Annona muricata L.-Derived Polysaccharides as a Potential Adjuvant to a Dendritic Cell-Based Vaccine in a Thymoma-Bearing Model

Abstract

Dendritic cells (DCs) are powerful antigen-presenting cells that are often used to evaluate adjuvants, particularly for adjuvant selection for various vaccines. Here, polysaccharides (named ALP) isolated from leaves of Annona muricata L., which are used in traditional medicine such as for bacterial infections and inflammatory diseases, were evaluated as an adjuvant candidate that can induce anti-tumor activity. We first confirmed the phenotypic (surface molecules, cytokines, antigen uptake, and antigen-presenting ability) and functional alterations (T cell proliferation/activation) of DCs in vitro. We also confirmed the adjuvant effect by evaluating anti-tumor activity and immunity using an ALP-treated DC-immunized mouse model. ALP functionally induced DC maturation by up-regulating the secretion of Th1-polarizing pro-inflammatory cytokines, the expression of surface molecules, and antigen-presenting ability. ALP triggered DC maturation, which is dependent on the activation of the MAPK and NF-κB signaling pathways. ALP-activated DCs showed an ample capacity to differentiate naive T cells to Th1 and activated CD8+ T cells effectively. The systemic administration of DCs that pulse ALP and ovalbumin peptides strongly increased cytotoxic T lymphocyte (CTL) activity (by 9.5% compared to that in the control vaccine groups), the generation of CD107a-producing multifunctional T cells, and Th1-mediated humoral immunity, and caused a significant reduction (increased protection by 29% over that in control vaccine groups) in tumor growth. ALP, which triggers the Th1 and CTL response, provides a basis for a new adjuvant for various vaccines.

Polysaccharides from Annona muricata leaves protect against cisplatin‑induced cytotoxicity in macrophages by alleviating mitochondrial dysfunction

“…Leaves of A. muricata were purchased from Todam (Cheonan, Korea). ALPS were prepared following a previously described method ( 22 ). Briefly, 50 g of A. muricata leaf powder were extracted with 500 ml of deionized water at 100°C for 2 h. The extract was filtered through Whatman no.…”

Bombyx batryticatus Protein-Rich Extract Induces Maturation of Dendritic Cells and Th1 Polarization: A Potential Immunological Adjuvant for Cancer Vaccine

“…The cells were analyzed using flow cytometry and FlowJo software (BD Bioscience). The intracellular levels of TNF-α, IL-12p70, and IL-10 in CD11c-positive cells were detected by flow cytometry [ 53 ].…”

“…The reaction was developed using 3,3’, 5,5’’-tetramethylbenzidine (TMB) substrate (Sigma-Aldrich), and the enzyme reaction was terminated by adding 2 N H 2 SO 4 . The optical density was detected at 495 nm within 20 min using a microplate ELISA reader [ 53 ].…”

Regulation of innate and adaptive immunity using herbal medicine: benefits for the COVID-19 vaccination

“…They significantly elongated dendrites, reduced their phagocytic abilities, and altered the phenotypic CD40/MHCII/CD80/CD86 expression in BMDCs [ 80 ] . Polysaccharides isolated from Annona muricata L also functionally induced DC maturation by upregulating Th1 - polarizing cytokine secretion and surface molecule expression, which in turn enhanced the antigen-presenting ability [ 81 ] . Similar to macrophages, DCs have important toll-like receptors on their membranes.…”