Research suggests that papain, a proteolytic enzyme derived from papaya, may possess anti-inflammatory properties, with the most directly relevant evidence coming from a 2024 animal and cell culture study showing that oral papain supplementation reduced eczema-like skin inflammation in mice by inhibiting MAPK and STAT signaling pathways and enhancing antioxidant enzyme activity. A 2025 review of enzyme-based therapies also supports the broader plausibility of papain-class enzymes as anti-inflammatory agents, noting that protease enzymes can work by neutralizing reactive oxygen species, breaking down inflammatory signaling molecules, and supporting tissue repair. Studies indicate that much of the available evidence is preclinical in nature, relying on animal models and laboratory cell experiments rather than human clinical trials, and several linked studies addressing related enzymes or compounds were not directly focused on papain itself. The overall body of evidence is preliminary and limited in scope, and while the mechanistic rationale is scientifically grounded, more rigorous human studies would be needed to draw firm conclusions about papain's anti-inflammatory effects in people.
Citations from PubMed and preprint sources. Match score (0-100) reflects automated search ranking, not clinical appraisal.
| Title | Type | Year | Direction | Match |
|---|---|---|---|---|
| Enzyme-Based Anti-Inflammatory Therapeutics for Inflammatory Diseases. | Review | 2025 | Supports | 100 |
| Antioxidant, Anti-inflammatory, and Immunomodulatory Roles of Nonvitamin Anti... | Review | 2022 | Neutral | 95 |
| Papain Suppresses Atopic Skin Inflammation through Anti-Inflammatory Activiti... | Other | 2024 | Supports | 90 |
| Single-cell and spatial transcriptomic analyses of gene therapy-associated re... | Other | 2025 | Neutral | 85 |
| Natural Products with Tandem Anti-inflammatory, Immunomodulatory and Anti-SAR... | Other | 2022 | Neutral | 85 |
| Molecular mechanism of naturally-encoded signaling-bias at the complement ana... | Other | 2025 | Neutral | 80 |
| Chondroprotective and anti-inflammatory effects of sesamin. | Other | 2012 | Neutral | 80 |
| Tissue Engineered Elastic Cartilage-Mimetic Auricular Grafts for Ear Reconstr... | Other | 2025 | Neutral | 75 |
| Investigating the cellular antioxidant and anti-inflammatory effects of the n... | Other | 2022 | Neutral | 75 |
| Human placental stem cells induce a novel multiple myeloid cell-driven immuno... | Other | 2025 | Neutral | 70 |
| Chemical structure, anti-inflammatory and antinociceptive activities of a sul... | Other | 2020 | Neutral | 70 |
| Liensinine inhibits IL-1β-stimulated inflammatory response in chondrocytes an... | Other | 2024 | — | 65 |
| Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoi... | Other | 2023 | Neutral | 65 |
| TNF-<i>α</i>disrupts the malate-aspartate shuttle, driving metabolic rewiring... | Other | 2025 | Neutral | 60 |
| Triamcinolone acetonide activates an anti-inflammatory and folate receptor-po... | Other | 2015 | Neutral | 60 |
| Purification and Characterization of Anti-Inflammatory Peptide Fractions from... | Other | 2025 | Neutral | 55 |
| Microbially Produced Bile Acids are Associated with High Levels of IgG Autoan... | Other | 2024 | Neutral | 55 |
| Co-delivery of anti-inflammatory and antioxidant agents via polymersomes for ... | Other | 2025 | Neutral | 50 |
| Diverse Strategies Utilized by Coronaviruses to Evade Antiviral Responses and... | Other | 2022 | Neutral | 50 |
| Immunoglobulin M regulates airway hyperresponsiveness independent of T helper... | Other | 2023 | Neutral | 45 |
| An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Alle... | Other | 2015 | Mixed | 45 |
| NMN-primed exosomes derived from infrapatellar fat pad mesenchymal stem cells... | Other | 2026 | Neutral | 40 |
| Activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain ... | Other | 2022 | Neutral | 40 |
| Transcriptional and cellular maturation of the chick spinal cord in the conte... | Other | 2025 | Neutral | 35 |
| Can osteoarthritis be treated with light? | Other | 2013 | Neutral | 35 |
| Peripheral gating of pain by glial endozepine | Other | 2023 | Neutral | 30 |
| Free radical scavenging and anti-inflammatory potential of a protein hydrolys... | Other | 2019 | Supports | 30 |
| Astrocyte-derived PEA116 increases adult hippocampal neurogenesis and confers... | Other | 2024 | Neutral | 25 |
| SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replicatio... | Other | 2023 | Neutral | 20 |
| An ultra-long heavy chain bovine antibody neutralizes SARS-CoV-2 and reacts b... | Other | 2025 | Neutral | 15 |