Wendan Decoction ameliorates metabolic phenotypes in rats with metabolic syndrome and phlegm syndrome by modulating the gut microbiota-bile acid axis

doi:10.12122/j.issn.1673-4254.2025.06.07

Abstract

Abstract:

Objective To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome (MS). Methods Forty Wistar rats were randomly divided into normal control group (n=8) and 3 phlegm syndrome model groups (induced by high-fat, high-sugar, and high-salt feeding and a single-dose intraperitoneal STZ injection; n=24) treated with daily gavage of saline, Wendan Decoction (3.6 g/kg), or metformin (0.1 g/kg) for 4 weeks. General conditions and glucose and lipid metabolism parameters of the rats were monitored, and serum LPS, liver histopathology, hepatic expressions of FXR, CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined. Gut microbiota structure was analyzed using 16S rDNA sequencing, and serum bile acids were quantified with UHPLC-MS/MS. Results The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis, increased body weight, abdominal circumference, Lee's index, FBG, FINS, HOMA-IR, TG, TC, LDL and LPS, and decreased HDL level. The abundance of Bacteroidetes, Megamonas, and Bacteroides in gut microbiota increased while Firmicutes, Lachnospiraceae_NK4A136_group, isohyodeoxycholic acid, and glycohyodeoxycholic acid decreased significantly; hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models. Treatment with Wendan Decoction effectively alleviated hepatic pathology, reduced body weight and abdominal circumference, improved glucose and lipid metabolic profiles and gut microbiota structure, and reversed the changes in hepatic and ileal protein expressions. Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes, Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid. Conclusion Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.

Key words: metabolic syndrome, intestinal flora, bile acid, phlegm syndrome, Wendan Decoction, metabolic phenotype

Kaiyue HUANG, Jingxin QI, Wenqian LUO, Yixuan LIN, Meimei CHEN, Huijuan GAN. Wendan Decoction ameliorates metabolic phenotypes in rats with metabolic syndrome and phlegm syndrome by modulating the gut microbiota-bile acid axis[J]. Journal of Southern Medical University, 2025, 45(6): 1174-1184.

Figures/Tables 19

References 32

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Indicator	NC group (n=8)	MG group (n=24)
Weight (g)	363.74±14.85	387.68±26.37*
Body length (cm)	22.66±0.40	22.57±0.41
Abdominal girth (cm)	18.94±0.32	20.60±0.67**
Lee's index	314.96±2.72	322.88±2.08**
TG [mmol/L, M (P25, P75)]	1.13(1.01, 1.20)	1.48(1.15,1.78)**
TC (mmol/L)	2.49±0.07	3.56±0.57**
HDL (mmol/L)	1.32±0.10	0.63±0.14**
LDL (mmol/L)	0.30±0.11	1.78±0.59**
FBG (mmol/L)	4.35±0.26	12.27±2.59**
FINS (μU/mL)	40.21±5.37	75.83±17.89**
HOMA-IR	7.82±1.45	41.68±14.63**

Indicator	NC group (n=8)	MG group (n=24)
Weight (g)	363.74±14.85	387.68±26.37*
Body length (cm)	22.66±0.40	22.57±0.41
Abdominal girth (cm)	18.94±0.32	20.60±0.67**
Lee's index	314.96±2.72	322.88±2.08**
TG [mmol/L, M (P25, P75)]	1.13(1.01, 1.20)	1.48(1.15,1.78)**
TC (mmol/L)	2.49±0.07	3.56±0.57**
HDL (mmol/L)	1.32±0.10	0.63±0.14**
LDL (mmol/L)	0.30±0.11	1.78±0.59**
FBG (mmol/L)	4.35±0.26	12.27±2.59**
FINS (μU/mL)	40.21±5.37	75.83±17.89**
HOMA-IR	7.82±1.45	41.68±14.63**

Indicators	NC group	MOD group	WDT group	MET group
Weight (g)	373.76±13.28	392.61±25.51	353.84±27.74^△△	359.29±29.29^△
Body length (cm)	23.68±0.25	23.44±0.27	23.63±0.23	23.54±0.29
Abdominal girth (cm)	20.28±0.30	21.93±0.30**	19.71±0.48^△△	19.99±0.59^△△
Lee's index	304.22±1.45	312.27±3.52**	299.17±5.08^△△	301.81±5.57^△△
TG (mmol/L)	0.70±0.10	1.07±0.11**	0.78±0.15^△△	0.93±0.14^△
TC (mmol/L)	2.43±0.09	3.63±0.39**	2.73±0.40^△△	2.83±0.33^△△
HDL (mmol/L)	0.97±0.20	0.59±0.14**	1.06±0.13^△△	0.99±0.17^△△
LDL (mmol/L)	0.26±0.02	1.08±0.18**	0.40±0.09^△△	0.49±0.13^△△
FBG (mmol/L)	4.84±0.17	14.23±1.66**	8.45±3.07^△△	9.66±2.66^△△
FINS [μU/mL, M(P25, P75)]	67.12(61.33, 69.65)	81.30(80.17, 84.82)**	67.75(64.43, 71.07)^△△	72.92(70.53, 79.02)
HOMA-IR	14.15±0.84	52.72±6.74**	25.24±9.67^△△	32.00±10.06^△△
LPS (ng/mL)	0.99±0.24	3.68±0.41**	1.94±0.18^△△	2.48±0.27^△△

Indicators	NC group	MOD group	WDT group	MET group
Weight (g)	373.76±13.28	392.61±25.51	353.84±27.74^△△	359.29±29.29^△
Body length (cm)	23.68±0.25	23.44±0.27	23.63±0.23	23.54±0.29
Abdominal girth (cm)	20.28±0.30	21.93±0.30**	19.71±0.48^△△	19.99±0.59^△△
Lee's index	304.22±1.45	312.27±3.52**	299.17±5.08^△△	301.81±5.57^△△
TG (mmol/L)	0.70±0.10	1.07±0.11**	0.78±0.15^△△	0.93±0.14^△
TC (mmol/L)	2.43±0.09	3.63±0.39**	2.73±0.40^△△	2.83±0.33^△△
HDL (mmol/L)	0.97±0.20	0.59±0.14**	1.06±0.13^△△	0.99±0.17^△△
LDL (mmol/L)	0.26±0.02	1.08±0.18**	0.40±0.09^△△	0.49±0.13^△△
FBG (mmol/L)	4.84±0.17	14.23±1.66**	8.45±3.07^△△	9.66±2.66^△△
FINS [μU/mL, M(P25, P75)]	67.12(61.33, 69.65)	81.30(80.17, 84.82)**	67.75(64.43, 71.07)^△△	72.92(70.53, 79.02)
HOMA-IR	14.15±0.84	52.72±6.74**	25.24±9.67^△△	32.00±10.06^△△
LPS (ng/mL)	0.99±0.24	3.68±0.41**	1.94±0.18^△△	2.48±0.27^△△

Group	FXR/GAPDH	CYP7A1/GAPDH	FGFR4/GAPDH
NC	0.59±0.08	0.65±0.18	0.61±0.06
MOD	0.27±0.06**	3.00±0.15**	0.19±0.10**
WDT	0.45±0.04^△△	1.58±0.25^△△	0.33±0.02^△
MET	0.41±0.06^△	2.60±0.64	0.32±0.03^△