Metabolic syndrome （MS） is a clinical syndrome characterized by obesity， insulin resistance， and dyslipidemia， and chronic inflammation is closely associated with its pathogenesis. The imbalance between pro-inflammatory and anti-inflammatory macrophage polarization， as one of the core pathological mechanisms of chronic inflammation， is a crucial driver of MS progression. According to Essential Questions in Yellow Emperor's Inner Canon： Distinctive Theory on Meridians and Diseased Pulses， "the spleen Qi dispersing essence... along all the meridians and collaterals". When the spleen fails in transportation and transformation， the distribution of refined essence becomes disordered， leading to internal accumulation of phlegm-dampness， forming a dynamic pathological state of "root deficiency with branch excess". Accordingly， the core traditional Chinese medicine （TCM） pathogenesis of MS is closely related to "spleen failing in transportation and transformation coupled with the internal accumulation of phlegm-dampness"； however， its modern biological basis remains elusive. Therefore， based on the theory of "spleen Qi dispersing essence" and recent advances in immunometabolism， this paper explored the modern scientific connotation of the TCM pathogenesis of MS from the perspective of macrophage polarization driven by glucose metabolic reprogramming. Through theoretical analysis and literature integration， it was proposed that mitochondrial oxidative phosphorylation participates in the energy metabolism process of "spleen Qi dispersing essence". The dysfunction of the spleen's transportation and transformation prompts macrophage metabolism to shift toward glycolysis， resulting in the accumulation of lactate and succinate， which represents the microscopic manifestation of "refined essence deviating from proper transformation" and can be defined as "microscopic phlegm-dampness". These metabolites subsequently drive M1 macrophage polarization via the hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway， triggering the release of pro-inflammatory cytokines and inducing systemic chronic low-grade inflammation， ultimately manifesting as insulin resistance， lipid metabolic disorders， and other core components of MS， thus achieving immune amplification from local "microscopic phlegm-dampness" to systemic "internal accumulation of phlegm-dampness". Therefore， macrophage polarization driven by glucose metabolic reprogramming constitutes an important biological link connecting the TCM concept of "spleen failing to disperse essence" with the pathology of MS. Furthermore， this paper reviewed the potential mechanisms by which TCM herbal formulas and their monomeric components that "restore spleen transportation and resolve phlegm-dampness" ameliorate MS by modulating macrophage metabolic remodeling， thereby providing novel biological connotations for the modern interpretation of the theory of "spleen Qi dispersing essence". Future research should integrate multi-omics technologies with disease-syndrome animal models to elucidate the regulatory network of formulas that "restore spleen transportation and resolve phlegm-dampness". Additionally， the feasibility of utilizing macrophage metabolic phenotypes as objective diagnostic biomarkers for the phlegm-dampness syndrome in MS warrants further investigation.

Metabolic syndrome （MS） is a clinical syndrome characterized by obesity， insulin resistance， and dyslipidemia， and chronic inflammation is closely associated with its pathogenesis. The imbalance between pro-inflammatory and anti-inflammatory macrophage polarization， as one of the core pathological mechanisms of chronic inflammation， is a crucial driver of MS progression. According to Essential Questions in Yellow Emperor's Inner Canon： Distinctive Theory on Meridians and Diseased Pulses， "the spleen Qi dispersing essence... along all the meridians and collaterals". When the spleen fails in transportation and transformation， the distribution of refined essence becomes disordered， leading to internal accumulation of phlegm-dampness， forming a dynamic pathological state of "root deficiency with branch excess". Accordingly， the core traditional Chinese medicine （TCM） pathogenesis of MS is closely related to "spleen failing in transportation and transformation coupled with the internal accumulation of phlegm-dampness"； however， its modern biological basis remains elusive. Therefore， based on the theory of "spleen Qi dispersing essence" and recent advances in immunometabolism， this paper explored the modern scientific connotation of the TCM pathogenesis of MS from the perspective of macrophage polarization driven by glucose metabolic reprogramming. Through theoretical analysis and literature integration， it was proposed that mitochondrial oxidative phosphorylation participates in the energy metabolism process of "spleen Qi dispersing essence". The dysfunction of the spleen's transportation and transformation prompts macrophage metabolism to shift toward glycolysis， resulting in the accumulation of lactate and succinate， which represents the microscopic manifestation of "refined essence deviating from proper transformation" and can be defined as "microscopic phlegm-dampness". These metabolites subsequently drive M1 macrophage polarization via the hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway， triggering the release of pro-inflammatory cytokines and inducing systemic chronic low-grade inflammation， ultimately manifesting as insulin resistance， lipid metabolic disorders， and other core components of MS， thus achieving immune amplification from local "microscopic phlegm-dampness" to systemic "internal accumulation of phlegm-dampness". Therefore， macrophage polarization driven by glucose metabolic reprogramming constitutes an important biological link connecting the TCM concept of "spleen failing to disperse essence" with the pathology of MS. Furthermore， this paper reviewed the potential mechanisms by which TCM herbal formulas and their monomeric components that "restore spleen transportation and resolve phlegm-dampness" ameliorate MS by modulating macrophage metabolic remodeling， thereby providing novel biological connotations for the modern interpretation of the theory of "spleen Qi dispersing essence". Future research should integrate multi-omics technologies with disease-syndrome animal models to elucidate the regulatory network of formulas that "restore spleen transportation and resolve phlegm-dampness". Additionally， the feasibility of utilizing macrophage metabolic phenotypes as objective diagnostic biomarkers for the phlegm-dampness syndrome in MS warrants further investigation.

Objective To investigate the inhibitory effect of Withaferin A ( WFA) on the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice and the mechanism of its antitumoral effect. Methods For in vivo model, anti-tumor efficacy of Withaferin A was evaluated in nude mice mod-els of human liver cancer orthotopic xenograft. The nude mice were randomly divided into model group, Sunitinib group,and Withaferin A groups [6, 3 mg/(kg·d)]. All mice were given intraperitoneal injec-tion for 14 days. Tumor volume and tumor weight were observed. Antiangiogenic effects were assessed in vi-vo by the tumor inhibition rate and microvessel density. Quantitative polymerase chain reaction ( QPCR) as-say was used to detect the mRNA expression of vascular endothelial growth factor ( VEGF) , basic fibroblast growth factor (bFGF), angiopoietin-2 (Ang-2), vascular endothelial growth factor receptor 2 (VEGFR2) from tumor tissues. For in vitro experiments, the cell count kit 8 ( CCK8 ) assay was used to detect the effect of Withaferin A on HepG2 cells proliferation. QPCR assay and enzyme-linked immunosorbent assay ( ELISA) were used to detect the mRNA expression of VEGF. Results Compared to the model group, the high-dose Withaferin A group and the Sunitinib group had a significantly lower tumor weight (P<0. 05). The tumor inhibition rate was 42. 69％ in the high-dose Withaferin A group, 20. 22％ in the low-dose With-aferin A group, and 49. 43％ in the Sunitinib group. The growth of HepG2 cells was significantly inhibited by different concentrations of Withaferin A,and the 50％ concentration of inhibition ( IC50 ) of Withaferin A were (2. 64 ± 0. 18)μmol/L at 24 h. Withaferin A (6,3 μmol/L) could inhibit the protein and mRNA ex-pression of VEGF ( P<0. 05 ) . Conclusions Withaferin A significantly reduces the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice via antiangiogenic effect. Downregulation of the protein and mRNA expression of VEGF by WFA may be one mechanism of its anti-liver cancer effect.