Panax ginseng-derived Exosome-like Nanoparticles Prevent LPS-induced Septic Shock by Modulating TLR4 Glycosylation in Macrophages = 인삼 유래 엑소좀 유사 나노입자의 대식세포 TLR4 당화 조절을 통한 LPS 유도 패혈성 쇼크 예방

국문 초록 (Abstract)

대식세포는　패혈증의　병태생리에서　핵심적인　면역　반응을　수행하며，발병　초기부터　진행　과정　전반에　걸쳐서　중점적인　기능을　담당한다．패혈증의　다양한　치료제　중，Panax ginseng의　뿌리에서　추출된　화합물을　강력한　항염증　효과로　주목받아　왔다．　최근에는　안정성과　생체적합성이　매우　우수하며　다양한　생리활성　물질을　함유하고　있는　ginseng-derived exosome-like particles (GDEs)로　연구의　초점이　이동하였다．본　연구에서는　대식세포를　중심으로　GDEs가　지질다당류（LPS）로　인해　발생한　패혈성　쇼크에　미치는　보호　효과를　탐구하였다．한국산　Panax ginseng으로부터　분리된　GDEs는　구형　형태를　띄며，Rb1, Rg1, Rg3와　같은　생리활성　화합물을　안정적으로　봉입하는　특성을　나타내었다．GDEs는　대식세포　내에서　Toll-Like Receptor 4 (TLR4)의　당화를　감소시킴으로서　TLR4와　LPS의　결합을　억제하고，이를　통해　대식세포에서　LPS로　유래된　급성　염증을　유의하게　억제하였다．TLR4의　당화　감소는　일산화질소　 및　염증성　사이토카인　（인터류킨－1β，인터류킨－６，종양괴사인자－α）의　생성을　억제하고，세포　내의　활성산소종과　NF-κB 활성화를 차단하였다．또한，LPS로　유도된　마우스의　패혈성　쇼크　모델에서　GDEs의　처리는　마우스의　생존율을　유의하게　향상시키고，폐，간，비장과　같은　주요　장기의　손상을　감소시켰다．이러한　결과는　GDEs가　부작용　없이　대식세포의　활성을　표적조절하는　탁월한　나노의약품으로서　패혈증　예방에　유망함을　시사한다．

다국어 초록 (Multilingual Abstract)

Macrophages play a crucial role in the pathophysiology of sepsis, as they play a central part in both the onset and progression of the condition. Among the various therapeutic agents investigated, compounds extracted from the roots of Panax ginsengare distinguished for their potent anti-inflammatory properties. Recently, the focus has shifted toward ginseng-derived exosome-like particles (GDEs), due to their encapsulation of diverse bioactive compounds with excellent stability and biocompatibility. This study investigated the protective effects of GDEs against LPS-induced septic shock by focusing on their effect on macrophages. GDEs, isolated from Korean Panax ginseng, were characterized by their spherical shape, stability, and bioactive compound encapsulation, including Rb1, Rg1, and Rg3. GDEs significantly mitigate LPS-induced inflammation in macrophages by decreasing TLR-4 glycosylation, thereby inhibiting LPS binding. The reduced TLR4 glycosylation suppressed nitric oxide and proinflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α) production while preventing intracellular reactive oxygen species spike and NF-κB activation. Furthermore, GDE treatment in an LPS-induced sepsis mouse model significantly improved survival rates and reduced lung, liver, and spleen damage. These results indicate that GDEs hold promise as a nanomedicine for sepsis prevention, providing a targeted approach to modulate macrophage activity without adverse effects.

목차 (Table of Contents)

• 제 1 장 Introduction 1
• 제 2 장 Materials and Methods 4
• 제 1 절 4
• 제 2 절 3
• 제 3 절 5
• 제 4 절 6
• 제 5 절 6
• 제 6 절 7
• 제 7 절 8
• 제 8 절 9
• 제 9 절 9
• 제 10 절 10
• 제 11 절 12
• 제 12 절 12
• 제 13 절 13
• 제 14 절 14
• 제 15 절 14
• 제 3 장 Results 15
• 제 1 절 15
• 제 2 절 17
• 제 3 절 20
• 제 4 절 24
• 제 5 절 27
• 제 6 절 30
• 제 7 절 32
• 제 4 장 Discussion 36
• 제 5 장 Conclusion 39
• 제 6 장 Acknowledgement 40
• 참고문헌 41
• Abstract 47