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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/21/8108 |
| _version_ | 1797549337260064768 |
|---|---|
| author | Michela Novelli Pellegrino Masiello Pascale Beffy Marta Menegazzi |
| author_facet | Michela Novelli Pellegrino Masiello Pascale Beffy Marta Menegazzi |
| author_sort | Michela Novelli |
| collection | DOAJ |
| description | 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 <i>Hypericum perforatum</i> 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. |
| first_indexed | 2024-03-10T15:13:15Z |
| format | Article |
| id | doaj.art-b5d03824dab344479a3995589cb21a4f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:13:15Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b5d03824dab344479a3995589cb21a4f2023-11-20T19:10:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121810810.3390/ijms21218108Protective 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 StudiesMichela Novelli0Pellegrino Masiello1Pascale Beffy2Marta Menegazzi3Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, 56126 Pisa, ItalyDepartment of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, 56126 Pisa, ItalyInstitute of Clinical Physiology, CNR, 56124 Pisa, ItalyDepartment of Neuroscience, Biomedicine and Movement Sciences, Biochemistry Section, School of Medicine, University of Verona, 37134 Verona, ItalyDiabetes 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 <i>Hypericum perforatum</i> 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.https://www.mdpi.com/1422-0067/21/21/8108St. John’s worthyperforinhypericincytokinesinflammatory signalingpancreatic beta cells |
| spellingShingle | Michela Novelli Pellegrino Masiello Pascale Beffy Marta Menegazzi 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 St. John’s wort hyperforin hypericin cytokines inflammatory signaling pancreatic beta cells |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | St. John’s wort hyperforin hypericin cytokines inflammatory signaling pancreatic beta cells |
| url | https://www.mdpi.com/1422-0067/21/21/8108 |
| work_keys_str_mv | AT michelanovelli protectiveroleofstjohnswortanditscomponentshyperforinandhypericinagainstdiabetesthroughinhibitionofinflammatorysignalingevidencefrominvitroandinvivostudies AT pellegrinomasiello protectiveroleofstjohnswortanditscomponentshyperforinandhypericinagainstdiabetesthroughinhibitionofinflammatorysignalingevidencefrominvitroandinvivostudies AT pascalebeffy protectiveroleofstjohnswortanditscomponentshyperforinandhypericinagainstdiabetesthroughinhibitionofinflammatorysignalingevidencefrominvitroandinvivostudies AT martamenegazzi protectiveroleofstjohnswortanditscomponentshyperforinandhypericinagainstdiabetesthroughinhibitionofinflammatorysignalingevidencefrominvitroandinvivostudies |