Immunostimulatory activity of Hovenia dulcis branches extracts through TLR4/JNK-dependent macrophage activation and TLR4-dependent macrophage autophagy in RAW264.7 cells

다국어 초록 (Multilingual Abstract)

Hovenia dulcis, one of the traditional medicinal plants, is currently being used as a functional ingredient for the development of health functional foods that protects the liver from alcohol damage in Korea. A variety of pharmacological effects of Hovenia dulcis have been reported so far, but studies on immune-enhancing activity are insufficient. Thus, in this study, we report that Hovenia dulcis branches (HDB) induce the activation of macrophages. HDB increased the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. TLR4 inhibition blocked HDB-mediated production of immunostimulatory factors. In addition, the JNK inhibition reduced the HDB-mediated production of immunostimulatory factors, and the HDB-mediated JNK activation was blocked by the TLR4 inhibition. HDB increased the level of LC3-II and p62/SQSTM1. TLR4 inhibition blocked HDB-mediated increase in the level of LC3-II and p62/SQSTM1. These findings indicate that HDB may induce TLR4/JNK-dependent macrophage activation and TLR4-dependent macrophage autophagy.

참고문헌 (Reference)

1 나천수 ; 동미숙 ; 홍철이 ; 나대승 ; 김진범 ; 윤순영 ; 이상범, "헛개나무 열매 열수추출물 투여에 의한 생쥐의 지구력 운동 수행 능력 향상 및 피로개선 효과" 한국생약학회 44 (44): 83-90, 2013

2 Chou YJ, "Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy" 10 : 8422-, 2020

3 Barbara JA, "Tumour necrosis factor-alpha (TNF-α): the good, the bad and potentially very effective" 74 : 434-443, 1996

4 Apetoh L, "Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy" 13 : 1050-1059, 2017

5 Li H, "Thymosin beta 4 attenuates oxidative stress-induced injury of spinal cord-derived neural stem/ progenitor cells through the TLR4/MyD88 pathway" 707 : 136-142, 2019

6 Hirayama D, "The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis" 19 : 92-, 2018

7 Hong SH, "The immune-enhancing activity of Cervus nippon mantchuricus extract(NGE)in RAW264. 7 macrophage cells and immunosuppressed mice" 99 : 623-629, 2017

8 Medzhitov R, "TLR-mediated innate immune recognition" 19 (19): 1-2, 2007

9 Wang, M, "Preparation, preliminary characterization and immunostimulatory activity of polysaccharide fractions from the peduncles of Hovenia dulcis" 138 : 41-47, 2013

10 Merkley SD, "Modulating T cell responses via autophagy : The intrinsic influence controlling the function of both antigen-presenting cells and T cells" 9 : 2914-, 2018

11 Tayor PR, "Macrophage receptors and immune recognition" 23 : 901-944, 2005

12 Medzhitov R, "Innate immune recognition : mechanisms and pathways" 173 : 89-97, 2000

13 Xu Z, "Immunomodulatory mechanism of a purified polysaccharide isolated from Isaria cicadae Miquel on RAW264. 7 cells via activating TLR4-MAPK-NF-κB signaling pathway" 164 : 432-4338, 2020

14 Li Y, "Immune regulation mechanism of Astragaloside IV on RAW264. 7 cells through activating the NF-κB/MAPK signaling pathway" 49 : 38-49, 2017

15 Sferrazza G, "Hovenia dulcis Thumberg : Phytochemistry, pharmacology, toxicology and regulatory framework for its use in the European union" 26 : 903-, 2021

16 Seillet C, "Complexity of cytokine network regulation of innate lymphoid cells in protective immunity" 70 : 1-10, 2014

17 Wu MY, "Autophagy and macrophage functions : Inflammatory response and phagocytosis" 9 : 70-, 2020

18 Pedroza LA, "Autoimmune regulator(AIRE)contributes to Dectin-1-induced TNF-α production and complexes with caspase recruitment domaincontaining protein 9(CARD9), spleen tyrosine kinase(Syk), and Dectin-1" 129 : 464-472, 2012

19 Lee MS, "Anti-inflammatory activities of an ethanol extract of Ecklonia stolonifera in lipopolysaccharide-stimulated RAW 264. 7 murine macrophage cells" 60 : 9120-9129, 2012

20 Marshall JS, "An introduction to immunology and immunopathology" 14 (14): 49-, 2018

21 Chen Y, "An immunostimulatory polysaccharide(SCP-IIa)from the fruit of Schisandra chinensis(Turcz. )Baill" 50 : 844-848, 2012