The Immune-Enhancing Properties of Hwanglyeonhaedok-Tang-Mediated Biosynthesized Gold Nanoparticles in Macrophages and Splenocytes

Abstract

Background: Despite great advances in the field of immunotherapy, there is still a need for novel and effective immunostimulants to overcome challenges, such as instability and autoinflammatory toxicity, associated with conventional immunostimulants. Nanotechnology provides the possibility to overcome these challenges. The well-known classical Chinese formula, Hwanglyeonhaedok-tang (HHT) has been widely used to treat immune-related diseases in clinical practice. Methods: We developed novel gold nanoparticles (AuNPs) utilizing one-pot synthesis with the herbal formula-HHT. The optimal conditions for HHT-AuNP biosynthesis were established, and physicochemical properties of the optimized HHT-AuNPs were identified using various spectrometric and microscopic techniques. Bio-TEM analysis revealed that HHT-AuNPs were highly engulfed within RAW264.7 cells without inducing cytotoxicity. The effect of HHT-AuNPs on immunostimulatory activity was evaluated in innate and adaptive immune cells (RAW264.7 macrophages and ICR mice splenocytes) using qRT-PCR, immunoblotting, and ELISA. Results:The HHT-AuNPs remarkably increased the nitric oxide (NO) and immune-related cytokines production by activating the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways in RAW264.7 cells. Furthermore, HHT-AuNPs exerted immunostimulatory effects on mouse splenocytes by priming T/B-cells and macrophages. Discussion: The present study is the first to demonstrate that HHT-AuNPs could be utilized as immunostimulators to activate both innate and adaptive immune systems. These results provide a foundation for the application of traditional Chinese medicinal formulae in the field of nanomedicine.

hCeO2@ Cu5.4O nanoparticle alleviates inflammatory responses by regulating the CTSB–NLRP3 signaling pathway

“…Immune cells are the first barrier for nanoparticles to penetrate into cells ( 50 ). It is necessary to study the uptake of nanoparticles by macrophages, which is essential for nanoparticles to exert their effects and potentially induce a toxic response.…”

Integrative Korean Medicine Treatment for Idiopathic Glossopharyngeal Neuralgia: A Case Report

“…So-yeom pharmacopuncture contains the same active constituent as HHT, and was expected to exert a similar effect to HHT tablets [19]. The HHT tablets were expected to reduce the heat sensation and pain of unknown origin by increasing nitric oxide and immune-related cytokines to increase immunity [20]. However, because HHT tablets were started on Day 8, it is recognized that the treatment tools should have been implemented uniformly for similar cases in the future.…”

Immunostimulatory Effect of Postbiotics Prepared from Phellinus linteus Mycelial Submerged Culture via Activation of Spleen and Peyer’s Patch in C3H/HeN Mice

“…Splenocytes are composed of various types of immune cells. Activated splenocytes elicit subsequent immune system activation by releasing various cytokines [ 24 , 25 ]. IFN-γ is a major immunostimulatory cytokine involved in cellular immunity, including both innate and adaptive immune cells [ 26 ].…”

“…IL-6 is a pleiotropic cytokine that plays multiple roles in the regulation of hematopoiesis, immune responses, and acute phase reactions, and is broadly secreted not only by activated lymphocytes but also by various types of non-lymphoid cells [ 28 ]. Many studies have established these cytokines as biomarkers that support immunostimulation through splenocyte activation [ 25 , 29 ]. We confirmed that the production of IFN-γ, TNF-α, and IL-6 was significantly increased in splenocytes by oral administration of PLME ( Figure 3 b–d), suggesting activation of the spleen-mediated immune system following PLME consumption.…”