Therapeutic Potential of Santa Herba Extract in Obesity: Impact on Lipid Metabolism and Hormonal Balance

Abstract

Many studies have reported that flavonoids can effectively suppress metabolic diseases related to obesity. Santa Herba extract (SHE), which is rich in flavonoids, has shown potential anti-obesity effects through clinical evaluations, but its anti-obesity mechanisms remain unclear. Therefore, an obese mouse model was established to further investigate its underlying mechanisms and biological effects. C57BL/6 mice were fed a high-fat diet (HFD) for 4 weeks to induce obesity and subsequently treated for 12 weeks with Orlistat (30 mg/kg) or SHE (50, 100, or 200 mg/kg). Body weight, food intake, fat mass (DEXA), serum biochemistry, histological changes, and gene/protein expression in liver and adipose tissue were analyzed. SHE200 reduced body weight by approximately 10%, fat mass by 15%, liver weight by nearly 40%, and epididymal adipocyte size by about 24% compared to the HFD group. Serum HDL was increased by approximately 1.2-fold, while LDL, ALT, and AST levels were reduced to 0.8-, 0.5-, and 0.6-fold of HFD levels, respectively. Leptin levels were also reduced to 0.6-fold of HFD levels, reflecting improvements in hormonal balance. In adipose tissue, FAS and ACC were reduced to approximately 0.6-fold of HFD levels, while key adipogenic transcription factors SREBP1c, CEBPα, and PPARγ were decreased to 0.5-, 0.6-, and 0.3-fold, respectively. PGC1α and CPT1α expression were modulated by SHE treatment, showing a 1.9-fold increase and 0.4-fold reduction, respectively. In liver tissue, similar reductions were observed, with FAS and ACC downregulated to 0.6- and 0.7-fold, and SREBP1c, CEBPα, and PPARγ suppressed to 0.4-, 0.5-, and 0.3-fold, respectively. Notably, PGC1α expression increased by approximately 2.2-fold, while CPT1α was reduced to about 0.5-fold. The findings underscore the potential of SHE as a natural, multi-targeted therapeutic agent for managing obesity and associated metabolic disorders.

Keywords: body weight; caloric intake; flavonoids; homoeriodictyol; lipid accumulation; metabolic regulation.

FIGURE 1

UPLC analysis of SHE components. (a) UPLC chromatogram of SHE (detection at 288 nm). The red line represents SHE, and the blue lines represent standards for homoeriodictyol, eriodictyol, and sterubin. (b) Chemical structure of homoeriodictyol, eriodictyol, and sterubin.

FIGURE 2

Experimental design and effects of SHE on body weight and food intake in HFD‐induced obesity model. (a) Experimental timeline schematic. Mice were acclimated for 1 week, then fed an HFD for 16 weeks. Oral administration of Orlistat or SHE began in week 5 and continued for 12 weeks. (b) Baseline body weight at the start of treatment (week 0; after 4 weeks of ND or HFD feeding). (c) Weekly body weight measurements throughout the study. Statistical significance: ^## p < 0.01, ^### p < 0.001 versus ND; *p < 0.05, **p < 0.01, ***p < 0.001 versus HFD using two‐way ANOVA (post hoc Dunnett's test). (d) Final body weight at study completion. (e) Total body weight gain. (f) Average daily food intake per mouse in each group. HFD, high‐fat diet; SHE, Santa Herba extract. Data are presented as mean ± SD (n = 8 per group). Statistical significance: ^## p < 0.01, ^### p < 0.001 versus ND; *p < 0.05, **p < 0.01, ***p < 0.001 versus HFD using one‐way ANOVA (post hoc Dunnett's test).

FIGURE 3

Effects of SHE on fat mass, liver weight, and epididymal fat weight in HFD‐induced obese mice. (a) Representative body composition images obtained through DEXA. (b) Total fat mass measured via DEXA. (c) Liver weight. (d) Epididymal fat weight. HFD, high‐fat diet; SHE, Santa Herba extract. Data are presented as mean ± SD (n = 8 per group). Statistical significance: ^# p < 0.05, ^### p < 0.001 versus ND; *p < 0.05, **p < 0.01, ***p < 0.001 versus HFD using one‐way ANOVA (post hoc Dunnett's test).

FIGURE 4

Effects of SHE on serum biochemical markers in HFD‐induced obese mice. (a) Serum glucose levels. (b) TC levels. (c) TG levels. (d) HDL levels. (e) LDL levels. (f) HDL/LDL ratio. (g) ALT levels. (h) AST levels. (i) Leptin levels. (j) Adiponectin levels. (k) A/L ratio. A/L, adiponectin/leptin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HDL, high‐density lipoprotein; HFD, high‐fat diet; LDL, low‐density lipoprotein; SHE, Santa Herba extract; TC, total cholesterol; TG, triglyceride. Data are presented as mean ± SD (n = 8 per group). Statistical significance: ^# p < 0.05, ^## p < 0.01, ^### p < 0.001 versus ND; *p < 0.05, **p < 0.01, ***p < 0.001 versus HFD using one‐way ANOVA (post hoc Dunnett's test).

FIGURE 5

Effects of SHE on adipocyte size and gene expression related to lipogenesis, adipogenesis, and energy metabolism in epididymal adipose tissue of HFD‐induced obese mice. (a) Representative histological images of epididymal adipose tissue stained with H&E. Scale bar = 100 μm. (b) Average adipocyte size. (c) mRNA expression of lipogenic genes: FAS and ACC. (d) mRNA expression of adipogenic transcription factors: SREBP1c, CEBPα, and PPARγ. (e) mRNA expression of energy metabolism regulators: PGC1α and PPARα. (f) mRNA expression of the fatty acid oxidation regulator: CPT1α. (g) Protein expression of FAS and ACC as determined using Western blot analysis. HFD, high‐fat diet; SHE, Santa Herba extract. Data are presented as mean ± SD (n = 8 per group). Statistical significance: ^# p < 0.05, ^## p < 0.01, ^### p < 0.001 versus ND; *p < 0.05, **p < 0.01, ***p < 0.001 versus HFD using one‐way ANOVA (post hoc Dunnett's test).

FIGURE 6

Effects of SHE on lipid accumulation and gene expression related to lipogenesis, adipogenesis, and energy metabolism in liver tissue of HFD‐induced obese mice. Representative histological images of liver tissue stained with H&E. Scale bar = 100 μm. (b) mRNA expression of lipogenic genes: FAS and ACC. (c) mRNA expression of adipogenic transcription factors: SREBP1c, CEBPα, and PPARγ. (d) mRNA expression of energy metabolism regulators: PGC1α and PPARα. (e) mRNA expression of the fatty acid oxidation regulator: CPT1α. (f) Protein expression of FAS and ACC as determined through Western blot analysis. HFD, high‐fat diet; SHE, Santa Herba extract. Data are presented as mean ± SD (n = 8 per group). Statistical significance: ^# p < 0.05, ^## p < 0.01, ^### p < 0.001 versus ND; *p < 0.05, **p < 0.01, ***p < 0.001 versus HFD using one‐way ANOVA (post hoc Dunnett's test).