α-Mangostin Is a Xanthone Derivative from Mangosteen with Potent Immunomodulatory and Anti-Inflammatory Properties
Abstract
:1. Introduction
2. Search Methodology
3. Anti-Inflammatory Effects of α-Mangostin
3.1. Joint Disorders
3.2. Digestive and Metabolic Disorders
3.3. Hepatic Disorders
3.4. Neurological Disorders
3.5. Respiratory Disorders
4. Immunomodulatory Effects of α-Mangostin
4.1. Effects on T Cells and Adaptive Immunity
4.2. Effects on B Cells and Humoral Immunity
4.3. Effects on Macrophages and Innate Immunity
5. Signaling Pathways Underlying Immunomodulatory and Anti-Inflammatory Effects of α-Mangostin
5.1. NF-κB Signaling Pathway
5.2. MAPK Signaling Pathway
5.3. Nrf2 Signaling Pathway and Antioxidant Effects
5.4. Oncostatin M (OSM) Signaling Pathway
5.5. Crosstalk Between Signaling Pathways
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Joint Disorders | Digestive and Metabolic Disorders | Hepatic Disorders | Neurological Disorders |
---|---|---|---|
↓ paw swelling | ↓ ROS | ↓ macrophage infiltration | ↓ IL-6 |
↓ joint deformation | ↓ NO | ↓ MCP-1 | ↓ COX-2 |
↓ granulocytes | ↓ MPO | ↓ IL-6 | ↓ TSPO |
↓ lymphocytes | ↑ MCP-1 | ↓ AST | ↓ Iba-1 |
↓ intermediate cells | ↓ TLR-2 | ↓ ALT | ↓ TNFα |
↓ neutrophil cells | ↓ TNFα | ↓ TGF-β1 | ↓ iNOS |
↓ platelet cells | ↑ ICAM-1 | ↓ α-SMA | ↓ NO |
↓ IL-6 | ↓ VCAM-1 | ↓ TIMP-1 | ↓ microglial migration |
↓ TGF-β | ↑ colon length | ↓ MDA | ↓ phagocytic cells |
↓ HIF-1α | ↓ surface epithelial cell damage | ↓ TNFα | ↓ neuronal death |
↓ VEGF | ↓ inflammatory cell infiltration | ↓ IL-1β | ↓ dendritic damage |
↓ COX-2 | ↓ submucosal edema | ↓ cell necrosis | ↓ ROS |
↓ HUVEC migration | ↓ IL-6 | ↑ antioxidant enzymes | ↓ IL-1β |
↓ TNFα | ↓ IL-1β | ↑ SOD | ↑ neuron survival |
↓ IL-β | ↓ COX-2 | ↓ iNOS | |
↑ hemoglobin count | ↓ iNOS | ↓ ALP | Respiratory Disorders |
↑ NAMPT | ↓ triglyceride levels | ↓ LDH | ↓ IL-1β |
↑ SIRT1 | ↓ LDL-C | ↓ γ-GT | ↓ TNFα |
↑ PPARγ | ↓ cholesterol | ↓ lipid peroxidation | ↑ α7nAChR |
↑ glucose | ↓ AST | ↓ NF-κB | ↑ Ach |
↑ triglyceride levels | ↓ ALT | ↓ interalveolar septal thickening | |
↓ IL-1β | ↓ miR-155 | ↓ alveolar hemorrhage | |
↑ SOD | ↓ IL-8 | ↓ inflammatory cell infiltration | |
↓ MCP-1 | ↓ IFNg-IP-10 | ↓ leucocytes | |
↓ NAMPT | ↑ PPARγ | ↑ SOD | |
↓ NAD+ | ↓ peribronchial fibrosis | ||
↓ synovial hyperplasia | ↓ IL-4 | ||
↑ collagen II | ↓ IL-5 | ||
↑ Aggrecan | ↓ IL-13 | ||
↑ SOX-9 | ↓ IgE | ||
↓ MMP-13 | |||
↓ ADAMTS-5 | |||
↓ matrix degradation | |||
↓ cartilage damage | |||
↓ PGE2 expression | |||
↓ NO expression | |||
↓ p-p65 | |||
↓ p-IκB | |||
↓ iNOS | |||
↓ MMP-3 | |||
↓ MMP-9 | |||
↓ CXCL5 | |||
↓ CXCL10 | |||
↓ CCL5 | |||
↓ CXCL9 | |||
↓ IL-33 | |||
↓ IL-12 | |||
↓ IL-10 | |||
↑ α7nAChR | |||
↑ ACh |
Main Effects | Experimental Model | Dosage | Administration Mode | Administration Duration | References |
---|---|---|---|---|---|
| Male Wistar rats HUVEC cell line | 30 mg/kg 2, 4, and 6 μg/mL | Oral administration | 32 days, daily 24 h | [32] |
| Male Sprague Dawley rats Rat chondrocytes | 10 mg/kg 1.25, 2.5, and 5.0 μg/mL | Intraperitoneal administration | 8 weeks, on alternate days 24 h | [38] |
| Male Sprague Dawley rats Pre-adipocytes | 50 mg/kg 4 μg/mL | Oral administration | 30 days 24 h | [34] |
| Male DBA/1J mice mBMDCs | 40 mg/kg 1, 3, 5, 7, and 10 μg/mL | Oral administration | 33 days, daily 4 h | [39] |
| Male C57BL/6J mice RAW 264.7 cells | 10 mg/kg 25 and 50 mg/kg 5 μM | Intraperitoneal administration Oral administration | 5 days, daily 8 weeks, daily Pretreatment for 1 h | [46] |
| Male C57BL/6 mice | 50 mg/kg/day | Oral administration | 12 weeks | [51] |
| RAW 264.7 macrophages MDM cells THP-1 cells HepG2 cells Caco-2 HTB-37 cells HT-29 cells | 1, 3, and10 μM 4.5 μM 10 μM 7 μM 15 μM 10 μM | N/A N/A N/A N/A N/A N/A | Pretreatment for 2 h Pretreatment for 4 h Pretreatment for 4 h Pretreatment for 16 h Pretreatment for 4 h Pretreatment for 1 h | [20] |
| Male ICR mice | 30 mg/kg | Oral administration | Pretreatment for 7 days, daily | [42] |
| Female C57BL/6J mice | 40 mg/kg | Oral administration | Pretreatment for 14 days, daily | [56] |
| Male Sprague Dawley rats | 20 mg/kg | Oral administration | 16 days, daily | [59] |
| IEC-6 cells | 2.5, 5, and 10 μM | N/A | Pretreatment for 1 h | [22] |
| Male BALB/c mice Murine macrophages | 3 mg/kg 10, 20, 40, 80 μM | Intravenous administration | 7 days 24 h | [28] |
| Male Wistar rats | 50 mg/kg | Intraperitoneal administration | 8 weeks, twice weekly | [52] |
| Male Sprague Dawley rats RAW 264.7 macrophages | 15 and 45 mg/kg 1, 3, and 5 μg/mL | Oral administration | 3 days 4 h | [63] |
| Human primary adipocytes | 3 μM | N/A | 24 h | [49] |
| Human U937 monocytes | 3, 10, and 30 μM | N/A | 2 h | [50] |
| Male Sprague Dawley rats RAW 264.7 cells | 40 mg/kg 5 μg/mL | Oral administration N/A | 3 days 0.5, 1, 2, 4, and 6 h | [62] |
| Male Sprague Dawley rats Rat and human PBMCs | 40 mg/kg 2.5, 5, and 10 μg/mL | Oral administration | 45 days 2 h | [40] |
| Male Sprague Dawley Rats RAW 264.7 macrophages | 40 mg/kg 5 μg/mL | Oral administration | 45 days 24 h | [41] |
| Male Sprague Dawley rats Human FLSs | 40 mg/kg 8, 10, and 12 μg/mL | Oral administration | 45 days 6 h | [35] |
| Female BALB/c mice | 10 and 30 mg/kg | Oral administration | 3 days | [64] |
| Male Sprague Dawley rats IEC-6 cells | 50 mg/kg 10 μM | Intragastrical administration | Pretreatment for 5 days, every day Pretreatment for 1 h | [23] |
| Male HR-1 mice (UVB-induced inflammation) | 100 mg/kg | Oral administration | Pretreatment for 12 weeks | [24] |
| RAW 264.7 macrophage cells | 3–100 μg/mL 3, 10, and 30 μM | N/A | Incubated for 48 h Incubated for 20 h | [21] |
| Huh-7 cells | 10, 15, and 20 μM | N/A | 24, 48, and 72 h | [27] |
| HepG2 cells | 5, 10, 20, and 40 μM | N/A | 24 and 48 h | [26] |
| Human peripheral blood mononuclear cells | 5, 10, and 20 μM | N/A | 24 and 48 h | [25] |
| NF-κB-RE/GFP adipocytes Nrf2-P/YFP adipocytes | 10 μM 1–20 μM | N/A | 7 days 8 days | [67] |
| Male Sprague Dawley rats HFLS-RA cells | 40 mg/kg 6, 8, 10, 12, and 14 μg/mL | Intragastric administration N/A | 35 days, daily 24 h | [33] |
| Rat chondrocyte cells 6-week-old male Sprague Dawley rats | 3, 6, and 12 μM 10 mg/kg | N/A Intraperitoneal injection | 2 h Every other day for 8 weeks after OA-inducing surgery | [36] |
| BV-2 microglial cells Mouse hippocampal neurons Male C57BL/6 mice (20–25 g) | 50–1000 nM 500 nM 100–500 nM 50 mg/kg | N/A Daily oral gavage | 24 h Pretreatment for 1 h Pretreatment for 1 h Once per day for 14 days | [60] |
| Adult male ICR mice (20–22 g) | 12.5 and 25 mg/kg | Intragastric administration | Once daily for 7 days | [53] |
| 4–5-week-old male ICR mice (20–25 g) | 12.5 and 25 mg/kg | Intragastric administration | Once daily for 6 days | [54] |
| 6-week-old mice | 30 and 100 mg/kg | Orally | 3 days pretreatment followed by 10-day treatment (after DSS administration) | [44] |
| Primary rat microglial cells and mesencephalic neuron–glia cultures | 1, 10, and 100 nM | N/A | 24 h | [61] |
| Adult male Swiss albino mice (20–25 g) | 25 and 50 mg/kg | Oral administration | 7 days | [55] |
| U937 cells | 6.0, 7.6, 12.0, 12.5, 13.4, and 30.5 nM | N/A | 4 h | [66] |
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Majdalawieh, A.F.; Khatib, B.K.; Terro, T.M. α-Mangostin Is a Xanthone Derivative from Mangosteen with Potent Immunomodulatory and Anti-Inflammatory Properties. Biomolecules 2025, 15, 681. https://doi.org/10.3390/biom15050681
Majdalawieh AF, Khatib BK, Terro TM. α-Mangostin Is a Xanthone Derivative from Mangosteen with Potent Immunomodulatory and Anti-Inflammatory Properties. Biomolecules. 2025; 15(5):681. https://doi.org/10.3390/biom15050681
Chicago/Turabian StyleMajdalawieh, Amin F., Bayan K. Khatib, and Tala M. Terro. 2025. "α-Mangostin Is a Xanthone Derivative from Mangosteen with Potent Immunomodulatory and Anti-Inflammatory Properties" Biomolecules 15, no. 5: 681. https://doi.org/10.3390/biom15050681
APA StyleMajdalawieh, A. F., Khatib, B. K., & Terro, T. M. (2025). α-Mangostin Is a Xanthone Derivative from Mangosteen with Potent Immunomodulatory and Anti-Inflammatory Properties. Biomolecules, 15(5), 681. https://doi.org/10.3390/biom15050681