A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction
HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cel...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/18/6560 |
| _version_ | 1797578633938731008 |
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| author | Mesfin Yimam Teresa Horm Alexandria O’Neal Ping Jiao Mei Hong Lidia Brownell Qi Jia Mosi Lin Alex Gauthier Jiaqi Wu Kranti Venkat Mateti Xiaojian Yang Katelyn Dial Sidorela Zefi Lin L. Mantell |
| author_facet | Mesfin Yimam Teresa Horm Alexandria O’Neal Ping Jiao Mei Hong Lidia Brownell Qi Jia Mosi Lin Alex Gauthier Jiaqi Wu Kranti Venkat Mateti Xiaojian Yang Katelyn Dial Sidorela Zefi Lin L. Mantell |
| author_sort | Mesfin Yimam |
| collection | DOAJ |
| description | HMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution-induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense against air-pollution-induced oxidative stress and lung damage. Here, a standardized botanical antioxidant composition from <i>Scutellaria baicalensis</i> and <i>Acacia catechu</i> was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis. Murine models of disorders, including hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized. The effect of the botanical composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed cultured macrophages. Analyses, such as hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, Western blot analysis for proteins, including extracellular HMGB1, and bacterial counts in the lungs and airways, were performed. Statistically significant decreases in mortality (50%), proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage fluid (BALF), and increased bacterial clearance from airways and lungs; reduced airway total protein, and decreased extracellular HMGB1 were observed in in vivo studies. A statistically significant 75.9% reduction in the level of extracellular HMGB1 and an increase in phagocytosis were observed in cultured macrophages. The compilations of data in this report strongly suggest that the botanical composition could be indicated for oxidative-stress-induced lung damage protection, possibly through attenuation of increased extracellular HMGB1 accumulation. |
| first_indexed | 2024-03-10T22:25:34Z |
| format | Article |
| id | doaj.art-dd814b9fca4c4bbcb37f0f97fe0a2931 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T22:25:34Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-dd814b9fca4c4bbcb37f0f97fe0a29312023-11-19T12:09:09ZengMDPI AGMolecules1420-30492023-09-012818656010.3390/molecules28186560A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 ReductionMesfin Yimam0Teresa Horm1Alexandria O’Neal2Ping Jiao3Mei Hong4Lidia Brownell5Qi Jia6Mosi Lin7Alex Gauthier8Jiaqi Wu9Kranti Venkat Mateti10Xiaojian Yang11Katelyn Dial12Sidorela Zefi13Lin L. Mantell14Unigen Inc., 2121 South State Street, Suite #400, Tacoma, WA 98405, USAUnigen Inc., 2121 South State Street, Suite #400, Tacoma, WA 98405, USAUnigen Inc., 2121 South State Street, Suite #400, Tacoma, WA 98405, USAUnigen Inc., 2121 South State Street, Suite #400, Tacoma, WA 98405, USAUnigen Inc., 2121 South State Street, Suite #400, Tacoma, WA 98405, USAUnigen Inc., 2121 South State Street, Suite #400, Tacoma, WA 98405, USAUnigen Inc., 2121 South State Street, Suite #400, Tacoma, WA 98405, USACollege of Pharmacy and Health Sciences, St John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St John’s University, Queens, NY 11439, USACollege of Pharmacy and Health Sciences, St John’s University, Queens, NY 11439, USAHMGB1 is a key late inflammatory mediator upregulated during air-pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays a significant role in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 levels may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution-induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense against air-pollution-induced oxidative stress and lung damage. Here, a standardized botanical antioxidant composition from <i>Scutellaria baicalensis</i> and <i>Acacia catechu</i> was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis. Murine models of disorders, including hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized. The effect of the botanical composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed cultured macrophages. Analyses, such as hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, Western blot analysis for proteins, including extracellular HMGB1, and bacterial counts in the lungs and airways, were performed. Statistically significant decreases in mortality (50%), proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage fluid (BALF), and increased bacterial clearance from airways and lungs; reduced airway total protein, and decreased extracellular HMGB1 were observed in in vivo studies. A statistically significant 75.9% reduction in the level of extracellular HMGB1 and an increase in phagocytosis were observed in cultured macrophages. The compilations of data in this report strongly suggest that the botanical composition could be indicated for oxidative-stress-induced lung damage protection, possibly through attenuation of increased extracellular HMGB1 accumulation.https://www.mdpi.com/1420-3049/28/18/6560HMGB1inflammatory lung injuryoxidative stresssepsis |
| spellingShingle | Mesfin Yimam Teresa Horm Alexandria O’Neal Ping Jiao Mei Hong Lidia Brownell Qi Jia Mosi Lin Alex Gauthier Jiaqi Wu Kranti Venkat Mateti Xiaojian Yang Katelyn Dial Sidorela Zefi Lin L. Mantell A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction Molecules HMGB1 inflammatory lung injury oxidative stress sepsis |
| title | A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction |
| title_full | A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction |
| title_fullStr | A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction |
| title_full_unstemmed | A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction |
| title_short | A Standardized Botanical Composition Mitigated Acute Inflammatory Lung Injury and Reduced Mortality through Extracellular HMGB1 Reduction |
| title_sort | standardized botanical composition mitigated acute inflammatory lung injury and reduced mortality through extracellular hmgb1 reduction |
| topic | HMGB1 inflammatory lung injury oxidative stress sepsis |
| url | https://www.mdpi.com/1420-3049/28/18/6560 |
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