Proposed mechanisms and potential clinical benefits of marine-derived phytoconstituents in mpox management
| Marine-derived phytoconstituent | Experimental models | Potential mechanism | Potential clinical outcomes | References |
|---|---|---|---|---|
| MAAs | In vitro [cultured cyanobacteria, algae, fungi; HPLC/LC-MS; DPPH, ABTS assays; model protein (hen egg white lysozyme) glycation inhibition] | MAAs scavenge ROS, may activate the Nrf2 pathway, inhibit COX-2, iNOS, and NF-κB, modulate cytokine responses, and activate FAK/MAPK signaling—enhancing antioxidant defenses, reducing inflammation, balancing immunity, and promoting keratinocyte migration, proliferation, and wound healing | Reduces oxidative damage, protects tissues, and may limit viral spread. Decreases inflammation and pain, aiding recovery. Balances the immune response, lowering cytokine storm. Speeds healing, improves skin repair, and may prevent scarring and secondary infections | [82, 83] |
| Shinorine | In vitro (human THP-1 and THP-1-blue cell lines; LPS treatment of cell cultures; reporter assay in THP-1-blue cells; Kyn/Trp quantification) | Activates NF-κB in resting cells but suppresses it during inflammation. Reduces IDO-1 activity (↓ Kyn/Trp). Scavenges ROS | Balances immune response to reduce inflammation and tissue damage. May enhance T cell activity and viral clearance by lowering immune tolerance. Protects against oxidative stress, aiding tissue preservation and recovery in mpox | [84] |
| Porphyra-334 (P-334) | In vitro (human skin fibroblasts, DCF-DA fluorescence assay; HaCaT cells; ABTS, DPPH assay) | Suppresses T cell activation, NF-κB, and IFN signaling. Inhibits IFN-induced JAK-STAT signaling, potentially promoting viral persistence. Enhances cell-associated viremia through monocytes/macrophages, aiding viral spread and immune evasion | Antioxidant and immunomodulatory effects may restore immune activation, counteracting viral suppression. Reduces oxidative stress, supports JAK-STAT activation, enhances ISG expression, and promotes innate immune clearance while reducing inflammation and supporting adaptive immunity | [84, 85] |
| Omega-3 fatty acids (EPA & DHA) | In vitro (human THP-1 monocyte/macrophage cell line; HEK293T-ACE2; Vero E6-ACE2); in vivo (rodent model, ARDS models) | Alter membrane properties and enhance immune receptor signaling. Generate resolvins, protectins, and maresins to reduce inflammation. Suppress NLRP3 inflammasome, enhance IFN signaling, promote M2 macrophages, regulate T/B cell activation, and reduce oxidative stress and inflammation | Improve immune recognition and reduce viral immune evasion. Resolve excessive inflammation and balance antiviral defense with tissue protection. Strengthen antiviral responses, inhibit replication, enhance clearance, limit spread, and improve systemic control while preserving barriers and reducing dissemination | [86] |
| Carrageenan | In vitro (NCM460 cell line, human colonic mucosa, HCT-8 human colonic adenocarcinoma cells); in vivo (guinea pig, TLR5–/– mouse, IL-10–/– mouse, B16-F10 melanoma model, 4T1 mammary carcinoma model) | Macrophage toxicity suppresses T cell-dependent immunity, while TLR4-mediated NF-κB activation induces inflammation. λ-Carrageenan can promote immune cell infiltration (M1 macrophages, dendritic cells, T cells) and cytokine production, potentially enhancing antiviral immunity and limiting systemic spread, depending on its type and context | Carrageenan may impair antiviral macrophage function and dysregulate IFN responses, aiding immune evasion. Its adjuvant effects could enhance antiviral signaling, potentially improving vaccine efficacy and systemic immunity while balancing immune suppression and response | [87–89] |
| Squalene | In vivo (mouse C57BL/6, BALB/c, KO; ferret; NHP-macaques, human Covid-19 patient); ex vivo (lymph node) | Squalene promotes M2 anti-inflammatory responses (↑ IL-10, IL-4, IL-13), inhibits NF-κB-driven pro-inflammatory mediators, activates Keap1-Nrf2-ARE antioxidant pathways, enhances tissue-repair factors (TIMP-2, GM-CSF), and preserves mitochondrial and ER function, supporting immune balance and recovery in mpox | By balancing immune activation and preventing excessive inflammation, squalene may reduce immune evasion by the virus, support effective JAK-STAT antiviral signaling, and limit systemic viral dissemination | [90, 91] |
| Fucans | In vivo (rodents, zebrafish embryo); in vitro (RAW 264.7 murine macrophages, HaCaT human keratinocytes, Caco-2/RAW 264.7 co-culture) | TLR4 activation induces ROS, NO, and cytokines, inhibiting immune cell migration. It reduces IL-6, TNF-α, and IL-1β levels, modulates redox balance, enhances phagocytosis, increases antioxidant enzymes, and reduces oxidative stress and tissue damage | It reduces inflammation, enhances immune clearance, and protects against oxidative stress, helping resolve lesions, limit viral spread, and prevent severe complications | [92, 93] |
MAAs: mycosporine-like amino acids; ROS: reactive oxygen species; Nrf2: nuclear factor erythroid 2-related factor 2; COX-2: cyclooxygenase-2; iNOS: inducible nitric oxide synthase; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; FAK: focal adhesion kinase; MAPK: mitogen-activated protein kinase; IDO-1: indoleamine 2,3-dioxygenase 1; IFN: interferon; JAK: Janus kinase; STAT: signal transducers and activators of transcription; ISG: IFN-stimulated gene; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; NLRP3: NOD-like receptor family, pyrin domain containing 3; TLR5: Toll-like receptor 5; IL-10: interleukin-10; Keap1: Kelch-like ECH-associated protein 1; ARE: antioxidant response element; TIMP-2: tissue inhibitor of metalloproteinases-2; GM-CSF: granulocyte-macrophage colony-stimulating factor; ER: endoplasmic reticulum; TNF-α: tumor necrosis factor alpha; Kyn: kynurenine; Trp: tryptophan; HPLC: high performance liquid chromatography; LC-MS: liquid chromatography-mass spectrometry; DPPH: 2,2-diphenyl-1-picrylhydrazyl; ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid); THP-1: human acute monocytic leukemia cell line; LPS: lipopolysaccharide; DCF-DA: 2',7'-dichlorofluorescein diacetate; HaCaT: human adult keratinocyte cell line; ACE2: angiotensin-converting enzyme 2; ARDS: acute respiratory distress syndrome; HCT-8: human colorectal adenocarcinoma cell line; NHP: non-human primates