Sparstolonin B nano-formulation attenuates LPS-induced lung injury
IntroductionNanomedicines can improve drug delivery and efficacy while reducing side effects. Our study examines the impact of a nano-formulation of Sparstolonin B (nSsnB), a TLR-4 antagonist, on LPS-induced inflammation in RAW264.7 cells and lung injury in mice.MethodsRAW264.7 cells were treated wi...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1532391/full |
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| author | Qinghe Meng Qinghe Meng Xiaojing Wang Dandan Guo Gary Zhang Changying Shi Adam Novak Xiguang Yang Juntao Luo Juntao Luo Juntao Luo Robert N. Cooney Robert N. Cooney |
| author_facet | Qinghe Meng Qinghe Meng Xiaojing Wang Dandan Guo Gary Zhang Changying Shi Adam Novak Xiguang Yang Juntao Luo Juntao Luo Juntao Luo Robert N. Cooney Robert N. Cooney |
| author_sort | Qinghe Meng |
| collection | DOAJ |
| description | IntroductionNanomedicines can improve drug delivery and efficacy while reducing side effects. Our study examines the impact of a nano-formulation of Sparstolonin B (nSsnB), a TLR-4 antagonist, on LPS-induced inflammation in RAW264.7 cells and lung injury in mice.MethodsRAW264.7 cells were treated with LPS (1 μg/mL) ± nSsnB (2–64 μg/mL) for 24 h. Cell viability was assessed, cytokine levels in media were measured, and cell lysates were used to quantify NF-κB activation. C57BL/6 mice were treated with prophylactic intratracheal (IT) nSsnB (0.625 mg/kg) ± IT LPS (2.5 mg/kg). Blood and BALF were collected for cytokine, protein and cytological analysis. Lung histology was scored to evaluate lung injury. The relative abundance of MyD88 and phosphorylated NF-κB were measured in lung and HLL mice were used to measure NF-κB activation in vivo.ResultsnSsnB demonstrated reduced toxicity vs. free SsnB. nSsnB ameliorated the LPS-induced increase in TNF-α, IL-6 and NF-κB P65 phosphorylation in RAW264.7 cells. LPS-treated mice revealed histologic ALI, elevated BALF neutrophils/macrophages/total protein, and increased levels of TNF-α/IL-6 in both BALF and plasma. Prophylactic nSsnB attenuated all these parameters in the LPS/nSsnB group. The increased levels of MyD88 and P-NF-κB P65 in lung from LPS-treated mice were reduced in the LPS/nSsnB group and nSsnB attenuated the increase in NF-κB activation induced by IT LPS in HLL mice.ConclusionnSsnB demonstrates less toxicity than free SsnB and attenuates the effects of LPS on inflammation in RAW264.7 cells. Prophylactic nSsnB attenuates LPS-induced ALI by reducing inflammation via MyD88/NF-κB signaling pathways. Collectively these findings support the therapeutic potential of nano-formulated nSsnB for ALI treatment. |
| format | Article |
| id | doaj-art-a3d9bfe5f61c4b6eb891bd24b45f7968 |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-a3d9bfe5f61c4b6eb891bd24b45f79682025-08-20T02:08:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15323911532391Sparstolonin B nano-formulation attenuates LPS-induced lung injuryQinghe Meng0Qinghe Meng1Xiaojing Wang2Dandan Guo3Gary Zhang4Changying Shi5Adam Novak6Xiguang Yang7Juntao Luo8Juntao Luo9Juntao Luo10Robert N. Cooney11Robert N. Cooney12Department of Surgery, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesSepsis Interdisciplinary Research Center (SIRC), State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Pharmacology, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Pharmacology, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Surgery, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Pharmacology, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Surgery, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Pharmacology, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Surgery, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesSepsis Interdisciplinary Research Center (SIRC), State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Pharmacology, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesDepartment of Surgery, State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesSepsis Interdisciplinary Research Center (SIRC), State University of New York (SUNY), Upstate Medical University, Syracuse, NY, United StatesIntroductionNanomedicines can improve drug delivery and efficacy while reducing side effects. Our study examines the impact of a nano-formulation of Sparstolonin B (nSsnB), a TLR-4 antagonist, on LPS-induced inflammation in RAW264.7 cells and lung injury in mice.MethodsRAW264.7 cells were treated with LPS (1 μg/mL) ± nSsnB (2–64 μg/mL) for 24 h. Cell viability was assessed, cytokine levels in media were measured, and cell lysates were used to quantify NF-κB activation. C57BL/6 mice were treated with prophylactic intratracheal (IT) nSsnB (0.625 mg/kg) ± IT LPS (2.5 mg/kg). Blood and BALF were collected for cytokine, protein and cytological analysis. Lung histology was scored to evaluate lung injury. The relative abundance of MyD88 and phosphorylated NF-κB were measured in lung and HLL mice were used to measure NF-κB activation in vivo.ResultsnSsnB demonstrated reduced toxicity vs. free SsnB. nSsnB ameliorated the LPS-induced increase in TNF-α, IL-6 and NF-κB P65 phosphorylation in RAW264.7 cells. LPS-treated mice revealed histologic ALI, elevated BALF neutrophils/macrophages/total protein, and increased levels of TNF-α/IL-6 in both BALF and plasma. Prophylactic nSsnB attenuated all these parameters in the LPS/nSsnB group. The increased levels of MyD88 and P-NF-κB P65 in lung from LPS-treated mice were reduced in the LPS/nSsnB group and nSsnB attenuated the increase in NF-κB activation induced by IT LPS in HLL mice.ConclusionnSsnB demonstrates less toxicity than free SsnB and attenuates the effects of LPS on inflammation in RAW264.7 cells. Prophylactic nSsnB attenuates LPS-induced ALI by reducing inflammation via MyD88/NF-κB signaling pathways. Collectively these findings support the therapeutic potential of nano-formulated nSsnB for ALI treatment.https://www.frontiersin.org/articles/10.3389/fphar.2025.1532391/fullsparstolonin B (nSsnB)LPSALI/ARDSTLR-4NF-κBinflammation |
| spellingShingle | Qinghe Meng Qinghe Meng Xiaojing Wang Dandan Guo Gary Zhang Changying Shi Adam Novak Xiguang Yang Juntao Luo Juntao Luo Juntao Luo Robert N. Cooney Robert N. Cooney Sparstolonin B nano-formulation attenuates LPS-induced lung injury Frontiers in Pharmacology sparstolonin B (nSsnB) LPS ALI/ARDS TLR-4 NF-κB inflammation |
| title | Sparstolonin B nano-formulation attenuates LPS-induced lung injury |
| title_full | Sparstolonin B nano-formulation attenuates LPS-induced lung injury |
| title_fullStr | Sparstolonin B nano-formulation attenuates LPS-induced lung injury |
| title_full_unstemmed | Sparstolonin B nano-formulation attenuates LPS-induced lung injury |
| title_short | Sparstolonin B nano-formulation attenuates LPS-induced lung injury |
| title_sort | sparstolonin b nano formulation attenuates lps induced lung injury |
| topic | sparstolonin B (nSsnB) LPS ALI/ARDS TLR-4 NF-κB inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1532391/full |
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