Protective role of St. John's Wort and its components hyperforin and hypericin against diabetes through Inhibition of inflammatory signaling: evidence from in vitro and in vivo studies

Diabetes mellitus is a very common chronic disease with progressively increasing prevalence. Besides the well-known autoimmune and inflammatory pathogenesis of type 1 diabetes, in many people, metabolic changes and inappropriate lifestyle favor a subtle chronic inflammatory state that contributes to development of insulin resistance and progressive loss of β-cell function and mass, eventually resulting in metabolic syndrome or overt type 2 diabetes. In this paper, we review the anti-inflammatory effects of the extract of Hypericum perforatum L. (St. John's wort, SJW) and its main active ingredients firstly in representative pathological situations on inflammatory basis and then in pancreatic β cells and in obese or diabetic animal models. The simultaneous and long-lasting inhibition of signal transducer and activator of transcription (STAT)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPKs)/c-jun N-terminal kinase (JNK) signaling pathways involved in pro-inflammatory cytokine-induced β-cell dysfunction/death and insulin resistance make SJW particularly suitable for both preventive and therapeutic use in metabolic diseases. Hindrance of inflammatory cytokine signaling is likely dependent on the hyperforin content of SJW extract, but recent data reveal that hypericin can also exert relevant protective effects, mediated by activation of the cyclic adenosine monophosphate (cAMP)/protein kinase cAMP-dependent (PKA)/adenosine monophosphate activated protein kinase (AMPK) pathway, against high-fat-diet-induced metabolic abnormalities. Actually, the mechanisms of action of the two main components of SJW appear complementary, strengthening the efficacy of the plant extract. Careful quantitative analysis of SJW components and suitable dosage, with monitoring of possible drug-drug interaction in a context of remarkable tolerability, are easily achievable pre-requisites for forthcoming clinical applications

Human myotonic dystrophy protein kinase effect in S. cerevisiae

n/

Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.

We describe a new class of NO-donor hypoglycemic products obtained by joining tolbutamide, a typical hypoglycemic sulfonylurea, with a NO-donor moiety through a hard link. As NO-donors we chose either furoxan (1,2,5-oxadiazole 2-oxide) derivatives or the classical nitrooxy function. A preliminary biological characterization of these compounds, including stimulation of insulin release from cultured rat pancreatic b-cells and in vitro vasodilator and anti-aggregatory activities, is reporte

Can Hypericum perforatum (SJW) prevent cytokine storm in COVID-19 patients?

[no abstract available

Fermented wheat powder induces the antioxidant and detoxifying system in primary rat hepatocytes.

UNLABELLED:Many plants exhibit antioxidant properties which may be useful in the prevention of oxidative stress reactions, such as those mediated by the formation of free radical species in different pathological situations. In recent years a number of studies have shown that whole grain products in particular have strong antioxidant activity. Primary cultures of rat hepatocytes were used to investigate whether and how a fermented powder of wheat (Lisosan G) is able to modulate antioxidant and detoxifying enzymes, and whether or not it can activate Nrf2 transcription factor or inhibit NF-kB activation. All of the antioxidant and detoxifying enzymes studied were significantly up-regulated by 0.7 mg/ml Lisosan G treatment. In particular, NAD(P)H:quinone oxidoreductase and heme oxygenase-1 were induced, although to different degrees, at the transcriptional, protein and/or activity levels by the treatment. As for the Nrf2 transcription factor, a partial translocation of its protein from the cytosol to the nucleus after 1 h of Lisosan G treatment was revealed by immunoblotting. Lisosan G was also observed to decrease H2O2-induced toxicity Taken together, these results show that this powder of wheat is an effective inducer of ARE/Nrf2-regulated antioxidant and detoxifying genes and has the potential to inhibit the translocation of NF-kB into the nucleus

Effect of Lisosan G on activity of antioxidant and phase II drug-metabolizing enzymes.

<p>NAD(P)H:quinone oxidoreductase (control value: 53.23±2.5 nmol/min/mg prot) (A); Heme oxygenase-1 (control value: 9.57±3.86 pmol/min/mg prot) (B); Glutathione-S-transferase (control value: 239.5±12.12 nmol/min/mg prot) (C); Catalase (control value: 147.41±11.1 nmol/min/mg prot) (D). Activities were measured in microsomes or cytosol of control cells (CTR) and 24 h treated cells. Results are expressed as percentages of control values. Mean ± SE of cells from five rats. • Significantly different from controls, p<0,05. ••p<0.01. ••• p<0.001. ○○○ Significantly different from H₂O₂, p<0.001.</p

Effect of Lisosan G on GSH levels.

<p>The activity was measured in homogenates of 24 h treated hepatocytes. Results are expressed as percentages of control activity (125.67±28.04 nmol/mg prot.). Mean ± SE of cells from five rats. ••Significantly different from control, p<0.01. ••• p<0.001. ○○○ Significantly different from H₂O₂, p<0.001.</p

A representative RT-PCR analysis.

<p>NQO1 (A), HO-1 (B) genes performed with 25, 27 and 29 cycles in primary rat hepatocytes of control (CTR) and treated with Lisosan G or Lisosan G+H₂O₂. PCR products were separated by electrophoresis on agarose gels and stained with ethidium bromide. Quantitative representation of the RT-PCR analysis is reported in the histograms and the results have been normalized to β-actin levels and are expressed as percentages of control. Mean ± SE of cells from five independent experiments using five rats. •• Significantly different from controls, p<0.01. ••• p<0.001. ○ Significantly different from H₂O₂, p<0.05. ○○○ p<0.001.</p

Western Blotting analysis of NF-kB.

<p>In nuclear extracts of control cells (CTR) and cells treated with Lisosan G or Lisosan G+H₂O₂. Protein samples (30 µg) were subjected to SDS-PAGE, electrophoretically transferred to a nitrocellulose membrane, and probed with polyclonal antibodies raised against rat NF-kB. Densitometric analysis of the western blot data are shown in the histogram. The results have been normalized to β-actin levels and are expressed as percentages of control. Mean ± SE of cells from five independent experiments using five rats. ••• Significantly different from controls, p<0.001. ○○○ Significantly different from H₂O₂, p<0.001.</p