Agarwood Pill Enhances Immune Function in Cyclophosphamide-induced Immunosuppressed Mice

다국어 초록 (Multilingual Abstract)

Agarwood is a resinous wood from the tree in the family Thymelaeaceae. It has been used as traditional medicine in China and Southeast Asia countries. This study was conducted to evaluate the potential of agarwood pill (AP) as a supplement to enhance immune function. In this study, immunity-enhancing activity was demonstrated in BALB/c male mice administered with AP for 10 days after intraperitoneal injection of cyclophosphamide (CPA). Results demonstrated that AP supplementation ameliorated spleen index and body weight changes of CPA-injected mice by increasing the proliferation of T- and B-lymphocytes as well as the activity of natural killer cells. Analysis of spleen-derived lymphocytes showed that counts of CD4 + and CD8 + T-cells were slightly recovered in the spleen of mice treated with a high dosage of AP. Serum levels of Seon Yeong Ji, Hyun Hwangbo, Min Yeong Kim, Da Hye Kim, Beom Su Park, EunJin Bang, Yung Hyun Choi Anti-Aging Research Center, Dong-eui University, Busan 47340, Korea Seon Yeong Ji, Hyun Hwangbo, Min Yeong Kim, Da Hye Kim, Beom Su Park, EunJin Bang, Yung Hyun Choi * Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan 47227, Korea Tel: [phone]; Fax: [phone] E-mail: [e-mail] Hyesook Lee Department of Convergence Medicine, Pusan National University School of Medicine, Yangsan 50612, Korea Young Tae Koo, Jin Soo Kim, Ki Won Lee, Jong Cheul Ko Natural Products Convergence R&D Division, Kwangdong Pharmaceutical Co. Ltd., Seoul 06650, Korea Gi-Young Kim Department of Marine Life Science, Jeju National University, Jeju 63243, Korea immune-related cytokines of tumor necrosis factor-α were notably restored after AP administration. In addition, serum levels of immunoglobulin (Ig) M and IgG were recovered by AP administration at a medium dosage. Furthermore, in analysis of ex vivo bone marrow-derived macrophages and dendritic cells, counts of immune-related interleukin-12, major histocompatibility complex (MHC)-I, MHC-II, CD80, and CD86 were significantly increased by AP treatment in concentration-dependent manner. This study provides reference data for the development of AP as a supplementation to enhance human immune function.

참고문헌 (Reference)

• 1 Kumaraguru, U., "Toll-like receptor ligand links innate and adaptive immune responses by the production of heat-shock proteins" 73 : 574-583, 2003
• 2 Hu, S., "The role of helper innate lymphoid cells in cancer" 11 : 1067-1081, 2019
• 3 Heinzel, S., "The regulation of lymphocyte activation and proliferation" 51 : 32-38, 2018
• 4 Laidlaw, B. J., "The multifaceted role of CD4(+) T cells in CD8(+) T cell memory" 16 : 102-111, 2016
• 5 Cohen, I. R., "The immune system computes the state of the body: crowd wisdom, machine learning, and immune cell reference repertoires help manage inflammation" 10 : 10-, 2019
• 6 Nicholson, L. B., "The immune system" 60 : 275-301, 2016
• 7 Kashimura, M., "The human spleen as the center of the blood defense system" 112 : 147-158, 2020
• 8 Ulriksen, E. S., "The discovery of novel immunomodulatory medicinal plants by combination of historical text reviews and immunological screening assays" 296 : 115402-, 2022
• 9 den Haan, J. M., "The activation of the adaptive immune system: cross-talk between antigen-presenting cells, T cells and B cells" 162 : 103-112, 2014
• 10 Bayazid Al Borhan ; 장영아, "The Role of Andrographolide on Skin Inflammations and Modulation of Skin Barrier Functions in Human Keratinocyte" 한국생물공학회 26 (26): 804-813, 2021
• 11 Lewis, S. M., "Structure and function of the immune system in the spleen" 4 : eaau6085-, 2019
• 12 Gilboa-Geffen, A., "Stressing hematopoiesis and immunity: an acetylcholinesterase window into nervous and immune system interactions" 5 : 30-, 2012
• 13 Megha, K. B., "Role of immunoglobulin and antibodies in disease management" 169 : 28-38, 2021
• 14 Wang, S., "Research progress of herbal medicines on drug metabolizing enzymes: consideration based on toxicology" 21 : 913-927, 2020
• 15 Arora, G., "Possible herbal-drug interactions an evidenced base review" 28 : 70-77, 2022
• 16 Aamir Khurram ; Sugumar Vaisnevee ; Khan Hidayat Ullah ; Looi Chung Yeng ; Juneja Rajesh ; Waqas Muhammad ; Arya Aditya, "Non-toxic nature of chebulinic acid on biochemical, hematological and histopathological analysis in normal Sprague Dawley rats" 한국독성학회 38 (38): 159-174, 2022
• 17 Li, W., "Natural products in agarwood and Aquilaria plants: chemistry, biological activities and biosynthesis" 38 : 528-565, 2021
• 18 Díaz-Zaragoza, M., "Natural and adaptive IgM antibodies in the recognition of tumor-associated antigens of breast cancer (Review)" 34 : 1106-1114, 2015
• 19 A. S. M. Ali Reza, "Mechanistic insight into immunomodulatory effects of food-functioned plant secondary metabolites" Informa UK Limited 63 (63): 5546-5576, 2021
• 20 Bou Zerdan, M., "Mechanisms of immunotoxicity: stressors and evaluators" 22 : 8242-, 2021
• 21 Arango Duque, G., "Macrophage cytokines: involvement in immunity and infectious diseases" 5 : 491-, 2014
• 22 Ying, W., "Investigation of macrophage polarization using bone marrow derived macrophages" 76 : 50323-, 2013
• 23 박종권 ; 허윤정 ; 권순조, "Interaction Between Hepatocytes and Proximal Tubular Epithelial Cells in Hypoxia-induced Lipotoxicity" 한국생물공학회 27 (27): 30-39, 2022
• 24 Bottino, C., "Inhibitory axes impacting on the activity and fate of innate lymphoid cells" 80 : 100985-, 2021
• 25 Dahham, S. S., "In vivo toxicity and antitumor activity of essential oils extract from agarwood (Aquilaria crassna)" 16 : 236-, 2016
• 26 Shi, J., "Immunomodulatory drug discovery from herbal medicines: insights from organspecific activity and xenobiotic defenses" 10 : e73673-, 2021
• 27 Liu, H., "Immunomodulation of Chinese herbal medicines on NK cell populations for cancer therapy: a systematic review" 268 : 113561-, 2021
• 28 Ullrich, K. A., "Immunology of IL-12: an update on functional activities and implications for disease" 19 : 1563-1589, 2020
• 29 Scott-Taylor, T. H., "Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy" 6 : 13-33, 2018
• 30 McBride, J. A., "Imbalance in the game of T cells: what can the CD4/CD8 T-cell ratio tell us about HIV and health?" 13 : e1006624-, 2017
• 31 Singh, K., "IgA deficiency and autoimmunity" 13 : 163-177, 2014
• 32 Enioutina, E. Y., "How can we improve the safe use of herbal medicine and other natural products? A clinical pharmacologist mission" 13 : 935-944, 2020
• 33 Ratajczak, M. Z., "Hematopoiesis and innate immunity: an inseparable couple for good and bad times, bound together by an hormetic relationship" 36 : 23-32, 2022
• 34 Bharadwaj, N. S., "Harnessing invariant natural killer T cells to control pathological inflammation" 13 : 998378-, 2022
• 35 Zhu, Z., "HHX-5, a derivative of sesquiterpene from Chinese agarwood, suppresses innate and adaptive immunity via inhibiting STAT signaling pathways" 791 : 412-423, 2016
• 36 Jeong Mi Kyung ; Kim Bae-Hwan, "Grading criteria of histopathological evaluation in BCOP assay by various staining methods" 한국독성학회 38 (38): 9-17, 2022
• 37 Behl, T., "Exploring the multifocal role of phytochemicals as immunomodulators" 133 : 110959-, 2021
• 38 Hippen, K. L., "Emerging translational strategies and challenges for enhancing regulatory T cell therapy for graft-versus-host disease" 13 : 926550-, 2022
• 39 Jhonne Pedro Pedott Santana ; Priscyla Daniely Marcato ; Tais Nader Chrysostomo Massaro ; Naiane Lima Godoy ; Fernanda de Freitas Anibal ; Borra Ricardo Carneiro, "Efficacy of instillation of MB49 cells and thermoreversible polymeric gel in urothelial bladder carcinoma immunization" 한국실험동물학회 38 (38): 79-90, 2022
• 40 Gorovits, B., "Current considerations for immunoglobulin isotype characterization of antibody response against biotherapeutics" 22 : 144-, 2020
• 41 Chen, X., "Chemical composition and potential properties in mental illness (anxiety, depression and insomnia) of agarwood essential oil: a review" 27 : 4528-, 2022
• 42 Luckheeram, R. V., "CD4+ T cells: differentiation and functions" 2012 : 925135-, 2012
• 43 Peng, X., "Bidirectional effects and mechanisms of traditional Chinese medicine" 298 : 115578-, 2022
• 44 Hilligan, K. L., "Antigen presentation by dendritic cells and their instruction of CD4+ T helper cell responses" 17 : 587-599, 2020
• 45 Huo, H. X., "Anti-inflammatory 2-(2-phenylethyl)chromone derivatives from Chinese agarwood" 118 : 49-55, 2017
• 46 Shivanand, P., "Agarwood-the fragrant molecules of a wounded tree" 27 : 3386-, 2022
• 47 Tan, C. S., "Agarwood induction: current developments and future perspectives" 10 : 122-, 2019
• 48 Gray, K. J., "Adaptive immunity, chronic inflammation and the clock" 44 : 209-224, 2022