Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (2): 285-293.DOI: 10.19852/j.cnki.jtcm.2026.02.002
• Original Articles • Previous Articles Next Articles
Gut microbiota-mediated short-chain fatty acids contribute to the protective effects of Xiaoxuming decoction (小续命汤) against lipopolysaccharide-induced acute lung injury
XIANG Yijin1(
), YANG Zhigang2, GONG Shaomin3, LI Xiangting1, CAI Min1
- 1
Department of Integrative Medicine ,Zhongshan Hospital, Fudan University Shanghai 200032, China
2Department of Neurosurgery ,Zhongshan Hospital, Fudan University Shanghai 200032, China
3Department of Nephrology ,Zhongshan Hospital, Fudan University Shanghai 200032, China
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Received:2024-09-26Accepted:2025-06-24Online:2026-04-15Published:2026-04-04 -
Contact:XIANG Yijin, Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China. qqdemi728@126.com; Telephone: +86-21-64041990
Cite this article
XIANG Yijin, YANG Zhigang, GONG Shaomin, LI Xiangting, CAI Min. Gut microbiota-mediated short-chain fatty acids contribute to the protective effects of Xiaoxuming decoction (小续命汤) against lipopolysaccharide-induced acute lung injury[J]. Journal of Traditional Chinese Medicine, 2026, 46(2): 285-293.
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Figure 1 The gut microbiota contributes to the protective effects of XXMD against LPS-induced acute lung injury A: lung tissue HE staining was used to analyze the pathological changes of lung injury; B: histological injury score of the lungs; C: lung wet-to-dry weight ratio; D: ELISA was used to detect the content of TNF-α, IL-1β, and IL-6 in the BALF of the mouse; E: qRT-PCR was used to detect the levels of acetate-producing bacteria — Blautia hydropropica, Bacteroides thetaiotaomicron, Akkermansia muciniphila, Bacteroides vulgatus in feces; F: biochemical detection of the fecal acetate content; G: Western blot detection of lung tissue ZO-1 and occludin expression; H: Western blot detection of lung tissue p-NF-κBp65 and NF-κBp65 expression; I: seven-day survival rates; A1: control group; A2: LPS group; A3: LPS + XXMD group; A4: LPS + XXMD + Antibiotics group. Control group: give purified water 0.3 mL/d; LPS group: give 5 mg/kg LPS; LPS + XXMD group: give 5 mg/kg LPS and 100 mg/kg XXMD (twice a day). LPS + XXMD + Antibiotics group: give 5 mg/kg LPS, 100 mg/kg XXMD (twice a day) and antibiotics (120 units/mL polymyxin B and 0.6 mg/mL neomycin). XXMD: Xiaoxuming decoction; LPS: lipopolysaccharide; HE: hematoxylin and eosin; ELISA: enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1beta; BALF: bronchoalveolar lavage fluid; qRT-PCR: quantitative real time-PCR; ZO-1: zonula occludens-1; p-NF-κB: phosphorylated nuclear factor-kappa B. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. Data are presented as the mean ± standard deviation (n = 8). Compared with control group, aP < 0.01; compared with LPS group, bP < 0.01.
Figure 1 The gut microbiota contributes to the protective effects of XXMD against LPS-induced acute lung injury A: lung tissue HE staining was used to analyze the pathological changes of lung injury; B: histological injury score of the lungs; C: lung wet-to-dry weight ratio; D: ELISA was used to detect the content of TNF-α, IL-1β, and IL-6 in the BALF of the mouse; E: qRT-PCR was used to detect the levels of acetate-producing bacteria — Blautia hydropropica, Bacteroides thetaiotaomicron, Akkermansia muciniphila, Bacteroides vulgatus in feces; F: biochemical detection of the fecal acetate content; G: Western blot detection of lung tissue ZO-1 and occludin expression; H: Western blot detection of lung tissue p-NF-κBp65 and NF-κBp65 expression; I: seven-day survival rates; A1: control group; A2: LPS group; A3: LPS + XXMD group; A4: LPS + XXMD + Antibiotics group. Control group: give purified water 0.3 mL/d; LPS group: give 5 mg/kg LPS; LPS + XXMD group: give 5 mg/kg LPS and 100 mg/kg XXMD (twice a day). LPS + XXMD + Antibiotics group: give 5 mg/kg LPS, 100 mg/kg XXMD (twice a day) and antibiotics (120 units/mL polymyxin B and 0.6 mg/mL neomycin). XXMD: Xiaoxuming decoction; LPS: lipopolysaccharide; HE: hematoxylin and eosin; ELISA: enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1beta; BALF: bronchoalveolar lavage fluid; qRT-PCR: quantitative real time-PCR; ZO-1: zonula occludens-1; p-NF-κB: phosphorylated nuclear factor-kappa B. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. Data are presented as the mean ± standard deviation (n = 8). Compared with control group, aP < 0.01; compared with LPS group, bP < 0.01.
Figure 2 Acetate inhibits LPS-induced ALI via SCFA receptor GPR43 A: lung tissue HE staining was used to analyze the pathological changes of lung injury; B: histological injury score of the lungs; C: Lung wet-to-dry weight ratio; D: ELISA was used to detect the content of TNF-α, IL-1β, and IL-6 in the BALF of the mouse; E: Western blot detection of lung tissue ZO-1 and occludin expression; F: Western blot detection of lung tissue p-NF-κBp65 and NF-κBp65 expression; G: seven-day survival rates. A1: control group; A2: LPS group; A3: LPS + Acetate group; A4: LPS + Acetate + GLPG0974 group. Control group: give purified water 0.3 mL/d; LPS group: give 5 mg/kg LPS; LPS + Acetate group: give 5 mg/kg LPS and 500 mg/kg acetate (twice a day); LPS + Acetate + GLPG0974 group: give 5 mg/kg LPS, 500 mg/kg acetate (twice a day) and GLPG0974 (1 mg·kg-1·d-1). LPS: lipopolysaccharide; ALI: acute lung injury; SCFA: short-chain fatty acid; GPR43: G-protein coupled receptor 43; HE: hematoxylin and eosin; ELISA: enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1 beta; BALF: bronchoalveolar lavage fluid; ZO-1: zonula occludens-1; p-NF-κB: phosphorylated nuclear factor-kappa B. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. Data are presented as the mean ± standard deviation (n = 8). Compared with control group, aP < 0.01; compared with LPS group, bP < 0.01.
Figure 2 Acetate inhibits LPS-induced ALI via SCFA receptor GPR43 A: lung tissue HE staining was used to analyze the pathological changes of lung injury; B: histological injury score of the lungs; C: Lung wet-to-dry weight ratio; D: ELISA was used to detect the content of TNF-α, IL-1β, and IL-6 in the BALF of the mouse; E: Western blot detection of lung tissue ZO-1 and occludin expression; F: Western blot detection of lung tissue p-NF-κBp65 and NF-κBp65 expression; G: seven-day survival rates. A1: control group; A2: LPS group; A3: LPS + Acetate group; A4: LPS + Acetate + GLPG0974 group. Control group: give purified water 0.3 mL/d; LPS group: give 5 mg/kg LPS; LPS + Acetate group: give 5 mg/kg LPS and 500 mg/kg acetate (twice a day); LPS + Acetate + GLPG0974 group: give 5 mg/kg LPS, 500 mg/kg acetate (twice a day) and GLPG0974 (1 mg·kg-1·d-1). LPS: lipopolysaccharide; ALI: acute lung injury; SCFA: short-chain fatty acid; GPR43: G-protein coupled receptor 43; HE: hematoxylin and eosin; ELISA: enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1 beta; BALF: bronchoalveolar lavage fluid; ZO-1: zonula occludens-1; p-NF-κB: phosphorylated nuclear factor-kappa B. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. Data are presented as the mean ± standard deviation (n = 8). Compared with control group, aP < 0.01; compared with LPS group, bP < 0.01.
Figure 3 Acetate inhibits LPS-mediated cell viability and permeability in HPAEpiCs A: HPAEpiCs were pretreated with acetate at concentrations of 0, 12.5, 25, 50, 100, 200, and 400 μM for 24 h, followed by LPS treatment at a concentration of 10 mg/L, and CCK-8 was used to detect cell viability at 0, 6, 12, and 24 h; B: ELISA was used to detect TNF-α, IL-1β, and IL-6 expression; C: the TEER analysis; D: FITC leakage experiments were used to analyze cell permeability; E: the Western blot analysis was used to detect ZO-1 and occludin expression; F: the Western blot analysis was used to detect p-NF-κBp65 and NF-κBp65 expression. Control group: untreated HPAEpiCs; LPS group: HPAEpiCs treated with 10 mg/L LPS; LPS + 12.5 μM group: HPAEpiCs treated with 10 mg/L LPS and 12.5 μM acetate; LPS + 25 μM group: HPAEpiCs treated with 10 mg/L LPS and 25 μM acetate; LPS + 50 μM group: HPAEpiCs treated with 10 mg/L LPS and 50 μM acetate; LPS + 100 μM group: HPAEpiCs treated with 10 mg/L LPS and 100 μM acetate; LPS + 200 μM group: HPAEpiCs treated with 10 mg/L LPS and 200 μM acetate; LPS + 400 μM group: HPAEpiCs treated with 10 mg/L LPS and 400 μM acetate. LPS: lipopolysaccharide; CCK-8: cell counting kit-8; ELISA: enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1 beta; TEER: transepithelial electrical resistance; FITC: fluorescein isothiocyanate; ZO-1: zonula occludens-1; p-NF-κB: phosphorylated nuclear factor-kappa B. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. Data are presented as the mean ± standard deviation (n = 3). Compared with LPS group, aP < 0.01 and bP < 0.05; compared with control group, cP < 0.01.
Figure 3 Acetate inhibits LPS-mediated cell viability and permeability in HPAEpiCs A: HPAEpiCs were pretreated with acetate at concentrations of 0, 12.5, 25, 50, 100, 200, and 400 μM for 24 h, followed by LPS treatment at a concentration of 10 mg/L, and CCK-8 was used to detect cell viability at 0, 6, 12, and 24 h; B: ELISA was used to detect TNF-α, IL-1β, and IL-6 expression; C: the TEER analysis; D: FITC leakage experiments were used to analyze cell permeability; E: the Western blot analysis was used to detect ZO-1 and occludin expression; F: the Western blot analysis was used to detect p-NF-κBp65 and NF-κBp65 expression. Control group: untreated HPAEpiCs; LPS group: HPAEpiCs treated with 10 mg/L LPS; LPS + 12.5 μM group: HPAEpiCs treated with 10 mg/L LPS and 12.5 μM acetate; LPS + 25 μM group: HPAEpiCs treated with 10 mg/L LPS and 25 μM acetate; LPS + 50 μM group: HPAEpiCs treated with 10 mg/L LPS and 50 μM acetate; LPS + 100 μM group: HPAEpiCs treated with 10 mg/L LPS and 100 μM acetate; LPS + 200 μM group: HPAEpiCs treated with 10 mg/L LPS and 200 μM acetate; LPS + 400 μM group: HPAEpiCs treated with 10 mg/L LPS and 400 μM acetate. LPS: lipopolysaccharide; CCK-8: cell counting kit-8; ELISA: enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1 beta; TEER: transepithelial electrical resistance; FITC: fluorescein isothiocyanate; ZO-1: zonula occludens-1; p-NF-κB: phosphorylated nuclear factor-kappa B. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. Data are presented as the mean ± standard deviation (n = 3). Compared with LPS group, aP < 0.01 and bP < 0.05; compared with control group, cP < 0.01.
Figure 4 Acetate inhibits LPS-mediated cell viability and permeability in HPAEpiCs via GPR43 A: ELISA was used to detect TNF-α, IL-1 β, and IL-6 expression; B: The TEER analysis; C: the FITC leakage assay was used to analyze cell permeability; D: the Western blot analysis was used to detect ZO-1 and occludin expression; E: the Western blot analysis was used to detect p-NF-κBp65 and NF-κBp65 expression. Control group: untreated HPAEpiCs; LPS group: HPAEpiCs treated with 10 mg/L LPS; LPS + Acetate group: HPAEpiCs treated with 10 mg/L LPS and 200 μM acetate; LPS + Acetate + GLPG0974 group: HPAEpiCs treated with 10 mg/L LPS, 200 μM acetate and 100 nM GLPG0974. LPS: lipopolysaccharide; GPR43: G-protein coupled receptor 43; ELISA: enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1beta; TEER: transepithelial electrical resistance; FITC: fluorescein isothiocyanate; ZO-1: zonula occludens-1; p-NF-κB: phosphorylated nuclear factor-kappa B. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. Data are presented as the mean ± standard deviation (n = 3). Compared with control group, aP < 0.01; compared with LPS group, bP < 0.01.
Figure 4 Acetate inhibits LPS-mediated cell viability and permeability in HPAEpiCs via GPR43 A: ELISA was used to detect TNF-α, IL-1 β, and IL-6 expression; B: The TEER analysis; C: the FITC leakage assay was used to analyze cell permeability; D: the Western blot analysis was used to detect ZO-1 and occludin expression; E: the Western blot analysis was used to detect p-NF-κBp65 and NF-κBp65 expression. Control group: untreated HPAEpiCs; LPS group: HPAEpiCs treated with 10 mg/L LPS; LPS + Acetate group: HPAEpiCs treated with 10 mg/L LPS and 200 μM acetate; LPS + Acetate + GLPG0974 group: HPAEpiCs treated with 10 mg/L LPS, 200 μM acetate and 100 nM GLPG0974. LPS: lipopolysaccharide; GPR43: G-protein coupled receptor 43; ELISA: enzyme-linked immunosorbent assay; TNF-α: tumor necrosis factor-alpha; IL-1β: interleukin-1beta; TEER: transepithelial electrical resistance; FITC: fluorescein isothiocyanate; ZO-1: zonula occludens-1; p-NF-κB: phosphorylated nuclear factor-kappa B. Statistical analyses were measured by using one-way analysis of variance to analyze the differences between the groups. Data are presented as the mean ± standard deviation (n = 3). Compared with control group, aP < 0.01; compared with LPS group, bP < 0.01.
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