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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

1
Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, 56126 Pisa, Italy
2
Institute of Clinical Physiology, CNR, 56124 Pisa, Italy
3
Department of Neuroscience, Biomedicine and Movement Sciences, Biochemistry Section, School of Medicine, University of Verona, 37134 Verona, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(21), 8108; https://doi.org/10.3390/ijms21218108
Received: 30 September 2020 / Revised: 26 October 2020 / Accepted: 27 October 2020 / Published: 30 October 2020
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. View Full-Text
Keywords: St. John’s wort; hyperforin; hypericin; cytokines; inflammatory signaling; pancreatic beta cells; diabetes; obesity; metabolic syndrome; insulin resistance St. John’s wort; hyperforin; hypericin; cytokines; inflammatory signaling; pancreatic beta cells; diabetes; obesity; metabolic syndrome; insulin resistance
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MDPI and ACS Style

Novelli, M.; Masiello, P.; Beffy, P.; Menegazzi, M. 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. Int. J. Mol. Sci. 2020, 21, 8108. https://doi.org/10.3390/ijms21218108

AMA Style

Novelli M, Masiello P, Beffy P, Menegazzi M. 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. International Journal of Molecular Sciences. 2020; 21(21):8108. https://doi.org/10.3390/ijms21218108

Chicago/Turabian Style

Novelli, Michela; Masiello, Pellegrino; Beffy, Pascale; Menegazzi, Marta. 2020. "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" Int. J. Mol. Sci. 21, no. 21: 8108. https://doi.org/10.3390/ijms21218108

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