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To investigate the differential therapeutic effects of XuanFei HuaZhuo pill (XFHZP) on rat pneumonia models with damp-heat pneumonia (DH) syndrome, and to elucidate the underlying mechanisms using proteomics, to provide experimental evidence for the use of traditional Chinese medicine (TCM) in the treatment of pneumonia.
A DH group model was established. Therapeutic effects were evaluated via clinical signs and scores (general information, tongue, ear, claw nail, urine, feces), lung index, histopathology (hematoxylin-eosin), enzyme-linked immunosorbent assay for pulmonary interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels, hematology (white blood cell count (WBC), granulocytes (Gran), monocytes (Mon), mean platelet volume (MPV)), and pulmonary function (respiratory frequency (F), minute ventilation (MV)). Astral data-independent acquisition quantitative proteomics was performed on the right inferior lung lobes from control (CON) group, DH group, and XFHZP + DH group to identify differentially expressed proteins (DEPs) between CON vs. DH and DH vs. XFHZP + DH groups. Key DEPs were verified by immunohistochemistry and Western Blot, including their downstream targets (phospho-MLC2, phospho-eIF4E).
Compared with CON group, DH group exhibited hyperactive behavior, red tongues, ear-vessel dilation, yellow urine, and sticky feces, and displayed elevated lung indices, alveolar wall thickening, inflammatory infiltration, and capillary congestion, plus increased IL-6 and TNF-α (P < 0.05), WBC, Gran, Mon, MPV, F (P < 0.05), and reduced MV (P < 0.05). XFHZP treatment significanly ameliorated lung pathology, reduiced IL-6、TNF-α (P < 0.05), and nomalized WBC、Gran、Mon、MPV、F (P < 0.05), MV (P < 0.05) in DH rats (XFHZP + DH). Proteomics identified 1348 DEPs in the CON vs. DH and 448 in the DH vs. XFHZP + DH group, including AAK1、CACNα2δ1、eIF4E、HSD11β1、ROCK1、TDP1. KEGG analysis highlighted cGMP-dependent protein kinase G and insulin-signaling pathways as potential mechanisms for XFHZP in DH pneumonia. ROCK1/MKNK1 was upregulated in DH lungs, accompanied by increased MLC2/eIF4E phosphorylation, which were suppressed by XFHZP.
XFHZP exerts significant therapeutic effects on DH syndrome pneumonia, likely by downregulating ROCK1/MKNK1 expression, inhibiting MLC2/eIF4E phosphorylation, relaxing airway smooth muscle, and attenuating inflammation. This study provides molecular-level evidence for XFHZP's efficacy and offers novel insights into TCM-based pneumonia treatment.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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