St. John’s Wort Promotes Adipocyte Differentiation and Modulates NF-κB Activation in 3T3-L1 Cells

Abstract

St. John's wort (SJW), or Hypericum perforatum, is a perennial herb that has been used in the treatment of depression in several countries. Though its therapeutic effect on depression has been extensively studied, its influence on metabolic syndrome is yet to be fully characterized. Therefore, we investigated the effect of SJW extract on adipocyte differentiation and its anti-inflammatory effects by using 3T3-L1 preadipocytes. Oil Red O staining indicated that SJW promotes adipocyte differentiation, while immunoblots indicated that SJW increases the expression of peroxisome proliferator activated receptor γ (PPARγ), a nuclear receptor regulating adipocyte differentiation, and adiponectin, an anti-inflammatory adipokine. Furthermore, the anti-inflammatory activity of SJW was demonstrated by its inhibition of the activation of nuclear factor-κB (NF-κB), an inflammatory transcription factor. Stimulation of mature 3T3-L1 adipocytes by tumor necrosis factor-α (TNF-α) decreased the expression of the NF-κB inhibitor IκBα, and increased its phosphorylation. Treatment with SJW further decreased the TNF-α-induced perturbation in IκBα expression and phosphorylation, which indicated that SJW mediated the inhibition of NF-κB activation. In addition, SJW decreased the TNF-α-induced increase in the mRNA levels of pro-inflammatory adipokines, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Collectively, our results indicate that SJW treatment could promote adipocyte differentiation probably through its anti-inflammatory activity, which in turn suggests that SJW has the potential to minimize the risk factors of metabolic syndrome.

Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms

“…3 Indeed, NF-κB has a pivotal role in the regulation of many genes responsible for the generation of mediators in Our results showed marked decline of renal NF-кB expression in HP treated groups. Similar findings were obtained by Hatano et al 37 who showed the ability of HP in reducing NF-кB expression in rat with metabolic syndrome. Furthermore, our results showed that HP caused dose-dependent reductions of the elevated levels of TNFα and IL-1β in the kidney of HP treated groups.…”

“…Our results showed marked decline of renal NF‐кB expression in HP treated groups. Similar findings were obtained by Hatano et al . who showed the ability of HP in reducing NF‐кB expression in rat with metabolic syndrome.…”

Examining the Potential of Developing and Implementing Use of Adiponectin-Targeted Therapeutics for Metabolic and Cardiovascular Diseases

“…Both fish oil (123) and omega-3 (124,125) supplementation increased adiponectin levels in human studies. St. John's Wort (Hypericum perforatum) (126) and Groundsel Bush (Baccharis halimifolia) extract (127) induce 3T3-L1 adipocyte differentiation leading to enhanced adiponectin expression. Additional supplements that have been shown to increase circulating adiponectin in humans and animals include grape-seed extract (128-130) green tea extract (131,132), walnuts (133,134), α-linolenic acid (135), resveratrol (136)(137)(138), and Radix Astragali isolated compounds (astragaloside II and isoastragaloside I) (139).…”

Potentially Beneficial Effects of St. John’s Wort (Hypericum perforatum) in Patients with Metabolic Syndrome

“…There were discrepancies between these findings and those of similar in vitro studies. Notably, 50 µg/mL of SJW extract was used in our study [38] which was a slightly higher concentration than that used in previous in vitro reports [36,37], suggesting that the content and/or concentration of the bioactive ingredients in our SJW extract possibly differed from those used in other studies. The differences in the ingredients might be responsible for the varying study results.…”

“…Concentrations of extract in the range of 25-50 µg/mL were used for the experiments. Commercially available extracts from the flower tops of SJW have also been investigated [38]. In our study, treatment of 3T3-L1 cells with SJW extract facilitated differentiation of adipocytes without cell hypertrophy and increased the expression and secretion of adiponectin.…”