Poria in Fuling Zexie decoction for treating metabolic dysfunction-associated steatotic liver disease: Underlying mechanisms and key bioactive substances

Figure 1 Efficacy of Fuling Zexie decoction/Fuling Zexie decoction without Poria/Fuling Zexie decoction supplemented with Poria dregs against metabolic dysfunction-associated steatotic liver disease. A: Body weigh; B: Average food intake; C: Liver index; D: Liver weight; E: Serum total cholesterol; F: Serum triglyceride; G: Serum low-density lipoprotein cholesterol; H: Serum aspartate transaminase; I: Serum alanine transaminase; J: Serum interleukin-6; K: Serum high-density lipoprotein cholesterol; L: Serum tumor necrosis factor-α; M: Liver total cholesterol; N: Liver triglyceride; O: Liver alanine transaminase; P: Liver aspartate transaminase; Q: Liver interleukin-6; R: Liver interleukin-1β; S: Liver superoxide dismutase; T: Liver malondialdehyde; U: Hematoxylin-eosin staining sections (scale bar = 50 μm); V: Oil red O staining sections (scale bar = 50 μm); W: Masson trichrome staining sections (scale bar = 50 μm). n = 6, and the results are expressed as mean ± SD. ^aP < 0.05 vs the high-fat diet group, ^bP < 0.01 vs the high-fat diet group, ^cP < 0.001 vs the high-fat diet group, ^dP < 0.0001 vs the high-fat diet group. NC: Normal control; HFD: High-fat diet; FC: Fenofibrate capsules; LFZD: Low-dose Fuling Zexie decoction; HFZD: High-dose Fuling Zexie decoction; LZD: Low-dose Fuling Zexie decoction without Poria; HZD: High-dose Fuling Zexie decoction without Poria; LFFZD: Low-dose Fuling Zexie decoction supplemented with Poria dregs; HFFZD: High-dose Fuling Zexie decoction supplemented with Poria dregs; TC: Total cholesterol; TG: Triglyceride; LDL-C: Low-density lipoprotein cholesterol; AST: Aspartate transaminase; ALT: Alanine transaminase; IL: Interleukin; HDL-C: High-density lipoprotein cholesterol; TNF: Tumor necrosis factor.

Figure 2 Orthogonal partial least squares-discriminant analysis plot and permutation test plot. A: Serum; B: Liver; C: Urine; D: Feces. FC: Fenofibrate capsules; FFZD: Fuling Zexie decoction supplemented with Poria dregs; HZD: High-dose Fuling Zexie decoction without Poria; HFD: High-fat diet; NC: Normal control; ZD: Fuling Zexie decoction without Poria.

Figure 3 Integrated analysis of Fuling Zexie decoction/Fuling Zexie decoction without Poria components and metabolomics. A: Venn diagram of anti-metabolic dysfunction-associated steatotic liver disease targets of Fuling Zexie decoction (FZD)-derived components and FZD-regulated metabolic pathway targets; B: Venn diagram of anti-metabolic dysfunction-associated steatotic liver disease targets of Zexie decoction (ZD)-derived components and ZD-regulated metabolic pathway targets; C: Component-target-pathway-metabolite network of FZD; D: Component-target-pathway-metabolite network of ZD; E: Component-target-pathway-metabolite network of 17 targets specifically-regulated by FZD; F: Molecular docking between key components and core targets. MASLD: Metabolic dysfunction-associated steatotic liver disease; FZD: Fuling Zexie decoction without Poria; ZD: Fuling Zexie decoction without Poria; PIK3CB: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta; PIK3CA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.

Figure 4 Efficacy of key active components of Fuling Zexie decoction/Fuling Zexie decoction without Poria against hepatic steatosis. A: Cell oil red O staining (200 ×); B: Cell oil red O staining analysis; C: Cell total cholesterol; D: Cell triglyceride; E: Cell alanine transaminase; F: Cell aspartate transaminase; G: Cell phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; H: Cell aldo-keto reductase family 1 member B10; I: Liver phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; J: Liver phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta; K: Liver aldo-keto reductase family 1 member B1; L: Liver aldo-keto reductase family 1 member B10. ^aP < 0.05 vs the model group, ^bP < 0.01 vs the model group, ^cP < 0.001 vs the model group, ^dP < 0.0001 vs the model group. NC: Normal control; LFZDC: Low-dose key active compound ensemble of Fuling Zexie decoction; HFZD: High-dose Fuling Zexie decoction; LPRC: Low-dose key active compound ensemble of Poria in Fuling Zexie decoction; MOD: Model; LZD: Low-dose Fuling Zexie decoction without Poria; HZD: High-dose Fuling Zexie decoction without Poria; HPR: The key active compound ensemble of Poria in Fuling Zexie decoction; FC: Fenofibrate capsules; LWOC: Low-dose key active compound ensemble of Fuling Zexie decoction without Poria compounds; HWOC: High-dose key active compound ensemble of Fuling Zexie decoction without Poria compounds; LFZD: Low-dose Fuling Zexie decoction; HPRC: High-dose key active compound ensemble of Poria in Fuling Zexie decoction; LFFZD: Low-dose Fuling Zexie decoction supplemented with Poria dregs; HFFZD: High-dose Fuling Zexie decoction supplemented with Poria dregs.