Page 62 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology TCM regulates gut microbiota in pediatric MP pneumonia

cell differentiation and inhibiting Th2 cell function. This activities of cytokines, chemokines, and inflammatory
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immune imbalance significantly contributes to various enzymes, thereby exerting antibacterial, antioxidant, and
inflammatory diseases; thus, modulating the levels of anti-inflammatory effects. For example, quercetin strongly
TNF-α and IL-6 and restoring the Th1/Th2 balance are inhibits pro-inflammatory cytokines by inhibiting the
crucial strategies for treating these conditions (Figure S1). phosphorylation of NF-κB p and Akt, thereby reducing
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The active ingredients of Ma Xing Shi Gan Tang target the release of IL-1β, IL-6, and TNF-α and exerting anti-
cytokines such as TNF, IL-6, and IL-1β through various inflammatory effects. 60,61 High mobility group protein B1
signaling pathways, regulating the immune system and (HMGB1) is closely related to both innate and adaptive
inhibiting the inflammatory response.49 For example, using immunity and acts as an upstream regulator of the NF-κB
the Network Pharmacology–TCM Target method, Wang pathway. Naringenin reduces HMGB1 levels and inhibits
et al. identified 1604 effector targets (e.g., TNF) through the activation of the HMGB1/NF-κB signaling pathway
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which Ma Xing Shi Gan Tang exerts its therapeutic effects by downregulating HMGB1, NF-κB mRNA, and protein
on pneumonia. These targets were significantly enriched expression. Similarly, Sangbaekpi extract inhibits the
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in 19 pathways (e.g., the NF-κB pathway). These findings HMGB1/TLR4 signaling pathway. Both compounds
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further support the notion that Ma Xing Shi Gan Tang downregulate pro-inflammatory factors and upregulate
treats pneumonia through its antiviral, anti-inflammatory, anti-inflammatory factors, thereby modulating excessive
and immunomodulatory effects. In addition, a study by immune responses and alleviating lung tissue injury.
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Wang and Tao confirmed that Ma Xing Shi Gan Tang,
with modifications, can regulate Th1/Th2 and Th17/Treg 4.2.2. Regulation of microbiota balance by TCM
cytokine levels in children with MPP, significantly reducing Modern medicine has proposed the concept of the
serum IFN-γ and IL-17 levels. “lung-gut axis,” which highlights the strong correlation
The pathogenesis of MPP is complex and remains between the lungs and intestines in terms of tissue origin,
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incompletely understood. By comparing the baseline mucosal immunity, and ecological changes. Budden
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characteristics of healthy children and those with MPP, et al. suggests that the lung-gut axis is closely related to
it was found that serum NF-κB, CXC motif chemokine the microbiota and that bidirectional regulation of the
ligand 8 (CXCL8), and soluble B7-H3 (sB7-H3) are closely microbiota can modulate immune responses and influence
associated with disease severity and prognosis in children distal immune responses. Specifically, the lung microbiota
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with MPP, with all three significantly elevated in the may influence or be influenced by the intestinal microbial
MPP group. NF-κB, a key regulator of the inflammatory immune response. Therefore, regulating the balance of
signaling pathway, modulates the expression of various the intestinal microbiota and maintaining the intestinal
chemokines and inflammatory factors, such as IL-8 mucosal immune system may improve the prognosis and
(CXCL8). Its activation is closely associated with the therapeutic outcomes in children with MPP. Research
persistent increase in inflammatory response. CXCL8, findings indicate that herbal interventions can treat
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a key mediator of the host immune response, is activated pulmonary diseases by modulating inflammatory factors,
at sites of infection and injury, mediating neutrophil mucosal immunity, protein expression, and maintaining
migration and attracting various inflammatory cells to the homeostatic balance of pulmonary and intestinal
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lung tissues, thereby inducing tissue immune injury. microbiota. Short-chain fatty acids (SCFAs), produced by
sB7-H3, an immune regulatory molecule of the B7 family, the fermentation of undigested carbohydrates by anaerobic
activates downstream signaling pathways (e.g., the NF-κB bacteria in the colon, regulate epithelial barrier function as
pathway) at high levels, leading to chemokine activation, well as mucosal and systemic immunity. 67,68 TCM has been
enhanced pro-inflammatory cytokine production, and shown to effectively increase the abundance of beneficial
subsequent immune system damage. 55-57 Therefore, intestinal bacteria and promote the production of SCFAs
inhibiting the NF-κB signaling pathway is crucial for through active ingredients such as polysaccharides and
reducing pro-inflammatory factors. It is noteworthy that flavonoids, along with the synergistic effects of compound
the main active ingredients of Ma Xing Shi Gan Tang formulations. S. baicalensis polysaccharide has been shown
include formononetin, kaempferol, luteolin, naringenin, to alter the composition of the intestinal microbiota,
and quercetin. Among these, kaempferol, luteolin, and reduce the expression levels of TLR4 and NF-κB p65,
quercetin – common to several herbs – are flavonoid inhibit the activation of the TLR4/NF-κB signaling
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compounds. Flavonoids have been shown to interact with pathway, and decrease the production of inflammatory
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various molecules involved in the inflammatory pathway by factors. Dong’s experiment demonstrated that, in cases
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targeting the NF-κB, MAPK, extracellular signal-regulated of antibiotic-induced intestinal dysbiosis, the abundance
kinase, and Akt pathways. These interactions reduce the of Bifidobacteria and Lactobacilli increased significantly,
Volume 9 Issue 2 (2025) 54 doi: 10.36922/ejmo.8602