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Article ; Online: Can Hypericum perforatum (SJW) prevent cytokine storm in COVID-19 patients?

Masiello, Pellegrino / Novelli, Michela / Beffy, Pascale / Menegazzi, Marta

2020 Volume 34, Issue 7, Page(s) 1471–1473

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Cytokines ; Humans ; Hypericum ; Pandemics ; Phytotherapy ; Pneumonia, Viral ; SARS-CoV-2
Chemical Substances	Cytokines
Keywords	covid19
Language	English
Publishing date	2020-06-05
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.6764
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Article ; Online: 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.

Novelli, Michela / Masiello, Pellegrino / Beffy, Pascale / Menegazzi, Marta

International journal of molecular sciences

2020 Volume 21, Issue 21

Abstract: 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 ... ...

Abstract	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
MeSH term(s)	Animals ; Diabetes Mellitus, Type 2/etiology ; Diabetes Mellitus, Type 2/pathology ; Diabetes Mellitus, Type 2/prevention & control ; Humans ; Hypericum/chemistry ; Inflammation/drug therapy ; Phloroglucinol/analogs & derivatives ; Phloroglucinol/pharmacology ; Phytotherapy ; Plant Extracts/pharmacology ; Terpenes/pharmacology
Chemical Substances	Plant Extracts ; Terpenes ; Phloroglucinol (DHD7FFG6YS) ; hyperforin (RM741E34FP)
Keywords	covid19
Language	English
Publishing date	2020-10-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21218108
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Article: Can Hypericum perforatum (SJW) prevent cytokine storm in COVID-19 patients?

Masiello, Pellegrino / Novelli, Michela / Beffy, Pascale / Menegazzi, Marta

Phytother. res

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32501634
Database	COVID19

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Article ; Online: Can Hypericum perforatum (SJW) prevent cytokine storm in COVID-19 patients?

Masiello, Pellegrino / Novelli, Michela / Beffy, Pascale / Menegazzi, Marta

2020

Abstract: no abstract available] ...

Abstract	[no abstract available]
Keywords	hyperforin ; covid19
Language	English
Publishing country	it
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Can Hypericum perforatum ( SJW ) prevent cytokine storm in COVID ‐19 patients?

Masiello, Pellegrino / Novelli, Michela / Beffy, Pascale / Menegazzi, Marta

Phytotherapy Research

2020 Volume 34, Issue 7, Page(s) 1471–1473

Keywords	Pharmacology ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.6764
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Selective beta-cell toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin on isolated pancreatic islets.

Novelli, Michela / Beffy, Pascale / Masini, Matilde / Vantaggiato, Chiara / Martino, Luisa / Marselli, Lorella / Marchetti, Piero / De Tata, Vincenzo

Chemosphere

2020 Volume 265, Page(s) 129103

Abstract: An association between exposure to environmental pollutants and diabetes risk has been repeatedly shown by epidemiological studies. However, the biological basis of this association still need to be clarified. In this research we explored the effects of ... ...

Abstract	An association between exposure to environmental pollutants and diabetes risk has been repeatedly shown by epidemiological studies. However, the biological basis of this association still need to be clarified. In this research we explored the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on isolated pancreatic islets. After 1, 6 and 24 h exposure of isolated islets to different concentrations (1-50 nM) of TCDD we assayed: i) cell survival; ii) ultrastructure; iii) glucose-stimulated insulin secretion (GSIS); iv) expression of selected genes. A significant, dose-related increase of both necrosis and apoptosis was observed isolated rat islets after 24 h exposure to TCDD. The electron microscopic analysis revealed, at the same time point, the presence of several ultrastructural alterations (mitochondrial swelling, increased mitophagy, dilation of the endoplasmic reticulum) that, very interestingly, were exclusively observed in beta cells and not in other endocrine cells. Similar results were obtained in isolated human islets. GSIS was rapidly (1 h) and persistently (6 and 24 h) decreased by TCDD exposure even at the smallest concentration (1 nM). TCDD exposure significantly affected gene expression in isolated islets: Glut2, Gck, Bcl-xL, MafA, Pdx1 FoxO1 and IRE1 gene expression was significantly decreased, whereas Puma, DP5, iNOS and Chop gene expression was significantly increased after 6 h exposure to TCDD. In conclusion, our results clearly indicated that pancreatic beta cells represent not only a sensitive but also a specific target of the toxic action of dioxin.
MeSH term(s)	Animals ; Environmental Pollutants/metabolism ; Environmental Pollutants/toxicity ; Insulin Secretion ; Insulin-Secreting Cells ; Islets of Langerhans/metabolism ; Polychlorinated Dibenzodioxins/metabolism ; Polychlorinated Dibenzodioxins/toxicity ; Rats
Chemical Substances	Environmental Pollutants ; Polychlorinated Dibenzodioxins
Language	English
Publishing date	2020-11-30
Publishing country	England
Document type	Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2020.129103
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Article ; Online: Fermented wheat powder induces the antioxidant and detoxifying system in primary rat hepatocytes.

La Marca, Margherita / Beffy, Pascale / Pugliese, Annalisa / Longo, Vincenzo

PloS one

2013 Volume 8, Issue 12, Page(s) e83538

Abstract: 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 ...

Abstract	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.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Antioxidants/pharmacology ; Cells, Cultured ; Fermentation ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Hydrogen Peroxide/toxicity ; Metabolic Detoxication, Phase II ; NF-E2-Related Factor 2/metabolism ; NF-kappa B/metabolism ; Plant Extracts/pharmacology ; Plant Preparations ; Powders ; Protein Transport/drug effects ; Rats ; Triticum/chemistry
Chemical Substances	Antioxidants ; Lisosan G ; NF-E2-Related Factor 2 ; NF-kappa B ; Nfe2l2 protein, rat ; Plant Extracts ; Plant Preparations ; Powders ; Hydrogen Peroxide (BBX060AN9V)
Language	English
Publishing date	2013-12-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0083538
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Article ; Online: Persistence of STAT-1 inhibition and induction of cytokine resistance in pancreatic β cells treated with St John's wort and its component hyperforin.

Novelli, Michela / Beffy, Pascale / Gregorelli, Alex / Porozov, Svetlana / Mascia, Fabrizio / Vantaggiato, Chiara / Masiello, Pellegrino / Menegazzi, Marta

The Journal of pharmacy and pharmacology

2017 Volume 71, Issue 1, Page(s) 93–103

Abstract: Objectives: St John's wort extract (SJW) and its component hyperforin (HPF) were shown to potently inhibit cytokine-induced STAT-1 and NF-κB activation in pancreatic β cells and protect them against injury. This study aimed at exploring the time course ... ...

Abstract	Objectives: St John's wort extract (SJW) and its component hyperforin (HPF) were shown to potently inhibit cytokine-induced STAT-1 and NF-κB activation in pancreatic β cells and protect them against injury. This study aimed at exploring the time course of STAT-1 inhibition afforded by these natural compounds in the β-cell line INS-1E. Methods: INS-1E cells were pre-incubated with SJW extract (2-5 μg/ml) or HPF (0.5-2 μm) and then exposed to a cytokine mixture. In some experiments, these compounds were added after or removed before cytokine exposure. STAT-1 activation was assessed by electrophoretic mobility shift assay, apoptosis by caspase-3 activity assay, mRNA gene expression by RT-qPCR. Key findings: Pre-incubation with SJW/HPF for 1-2 h exerted a remarkable STAT-1 downregulation, which was maintained upon removal of the compounds before early or delayed cytokine addition. When the protective compounds were added after cell exposure to cytokines, between 15 and 90 min, STAT-1 inhibition also occurred at a progressively decreasing extent. Upon 24-h incubation, SJW and HPF counteracted cytokine-induced β-cell dysfunction, apoptosis and target gene expression. Conclusions: SJW and HPF confer to β cells a state of 'cytokine resistance', which can be elicited both before and after cytokine exposure and safeguards these cells from deleterious cytokine effects.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Cytokines/metabolism ; Dose-Response Relationship, Drug ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation/drug effects ; Hypericum/chemistry ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Phloroglucinol/administration & dosage ; Phloroglucinol/analogs & derivatives ; Phloroglucinol/isolation & purification ; Phloroglucinol/pharmacology ; Plant Extracts/administration & dosage ; Plant Extracts/pharmacology ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; STAT1 Transcription Factor/antagonists & inhibitors ; STAT1 Transcription Factor/metabolism ; Terpenes/administration & dosage ; Terpenes/isolation & purification ; Terpenes/pharmacology ; Time Factors
Chemical Substances	Cytokines ; Plant Extracts ; STAT1 Transcription Factor ; Stat1 protein, rat ; Terpenes ; Phloroglucinol (DHD7FFG6YS) ; hyperforin (RM741E34FP)
Language	English
Publishing date	2017-10-09
Publishing country	England
Document type	Journal Article
ZDB-ID	3107-0
ISSN	2042-7158 ; 0022-3573 ; 0373-1022
ISSN (online)	2042-7158
ISSN	0022-3573 ; 0373-1022
DOI	10.1111/jphp.12823
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Article ; Online: St. John's wort extract and hyperforin inhibit multiple phosphorylation steps of cytokine signaling and prevent inflammatory and apoptotic gene induction in pancreatic β cells.

Novelli, Michela / Menegazzi, Marta / Beffy, Pascale / Porozov, Svetlana / Gregorelli, Alex / Giacopelli, Daniela / De Tata, Vincenzo / Masiello, Pellegrino

The international journal of biochemistry & cell biology

2016 Volume 81, Issue Pt A, Page(s) 92–104

Abstract: The extract of the herbaceous plant St. John's wort (SJW) and its phloroglucinol component hyperforin (HPF) were previously shown to inhibit cytokine-induced STAT-1 and NF-κB activation and prevent damage in pancreatic β cells. To further clarify the ... ...

Abstract	The extract of the herbaceous plant St. John's wort (SJW) and its phloroglucinol component hyperforin (HPF) were previously shown to inhibit cytokine-induced STAT-1 and NF-κB activation and prevent damage in pancreatic β cells. To further clarify the mechanisms underlying their protective effects, we evaluated the phosphorylation state of various factors of cytokine signaling pathways and the expression of target genes involved in β-cell function, inflammatory response and apoptosis induction. In the INS-1E β-cell line, exposed to a cytokine mixture with/without SJW extract (2-5μg/ml) or HPF (1-5μM), protein phosphorylation was assessed by western blotting and expression of target genes by real-time quantitative PCR. SJW and HPF markedly inhibited, in a dose-dependent manner (from 60 to 100%), cytokine-induced activating phosphorylations of STAT-1, NF-κB p65 subunit and IKK (NF-κB inhibitory subunit IκBα kinase). MAPK and Akt pathways were also modulated by the vegetal compounds through hindrance of p38 MAPK, ERK1/2, JNK and Akt phosphorylations, each reduced by at least 65% up to 100% at the higher dose. Consistently, SJW and HPF a) abolished cytokine-induced mRNA expression of pro-inflammatory genes; b) avoided down-regulation of relevant β-cell functional/differentiation genes; c) corrected cytokine-driven imbalance between pro- and anti-apoptotic factors, by fully preventing up-regulation of pro-apoptotic genes and preserving expression or function of anti-apoptotic Bcl-2 family members; d) protected INS-1E cells against cytokine-induced apoptosis. In conclusion, SJW extract and HPF exert their protective effects through simultaneous inhibition of multiple phosphorylation steps along various cytokine signaling pathways and consequent restriction of inflammatory and apoptotic gene expression. Thus, they have a promising therapeutic potential for the prevention or limitation of immune-mediated β-cell dysfunction and damage leading to type 1 diabetes.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cytokines/metabolism ; DNA/metabolism ; Enzyme Activation/drug effects ; Hypericum/chemistry ; Insulin-Secreting Cells/cytology ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; NF-kappa B/metabolism ; Phloroglucinol/analogs & derivatives ; Phloroglucinol/pharmacology ; Phosphorylation/drug effects ; Plant Extracts/pharmacology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rats ; STAT1 Transcription Factor/metabolism ; Signal Transduction/drug effects ; Terpenes/pharmacology ; Transcriptional Activation/drug effects
Chemical Substances	Cytokines ; NF-kappa B ; Plant Extracts ; RNA, Messenger ; STAT1 Transcription Factor ; Terpenes ; DNA (9007-49-2) ; Phloroglucinol (DHD7FFG6YS) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; hyperforin (RM741E34FP)
Language	English
Publishing date	2016-10-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1228429-4
ISSN	1878-5875 ; 1357-2725
ISSN (online)	1878-5875
ISSN	1357-2725
DOI	10.1016/j.biocel.2016.10.017
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Article ; Online: ST. JOHN's wort extract and hyperforin inhibit multiple phosphorylation steps of cytokine signaling and prevent inflammatory and apoptotic gene induction in pancreatic β cells.

Novelli, Michela / Menegazzi, Marta / Beffy, Pascale / Porozov, Svetlana / Gregorelli, Alex / Giacopelli, Daniela / Tata, Vincenzo De / Masiello, Pellegrino

The international journal of biochemistry & cell biology

2016

Abstract	The extract of the herbaceous plant St. John's wort (SJW) and its phloroglucinol component hyperforin (HPF) were previously shown to inhibit cytokine-induced STAT-1 and NF-κB activation and prevent damage in pancreatic β cells. To further clarify the mechanisms underlying their protective effects, we evaluated the phosphorylation state of various factors of cytokine signaling pathways and the expression of target genes involved in β-cell function, inflammatory response and apoptosis induction. In the INS-1E β-cell line, exposed to a cytokine mixture with/without SJW extract (2-5μg/ml) or HPF (1-5μM), protein phosphorylation was assessed by Western blotting and expression of target genes by real-time quantitative PCR. SJW and HPF markedly inhibited, in a dose-dependent manner (from 60 to 100%), cytokine-induced activating phosphorylations of STAT-1, NF-κB p65 subunit and IKK (NF-κB inhibitory subunit IκBα kinase). MAPK and Akt pathways were also modulated by the vegetal compounds through hindrance of p38 MAPK, ERK1/2, JNK and Akt phosphorylations, each reduced by at least 65% up to 100% at the higher dose. Consistently, SJW and HPF a) abolished cytokine-induced mRNA expression of pro-inflammatory genes; b) avoided down-regulation of relevant β-cell functional/differentiation genes; c) corrected cytokine-driven imbalance between pro- and anti-apoptotic factors, by fully preventing up-regulation of pro-apoptotic genes and preserving expression or function of anti-apoptotic Bcl-2 family members; d) protected INS-1E cells against cytokine-induced apoptosis. In conclusion, SJW extract and HPF exert their protective effects through simultaneous inhibition of multiple phosphorylation steps along various cytokine signaling pathways and consequent restriction of inflammatory and apoptotic gene expression. Thus, they have a promising therapeutic potential for the prevention or limitation of immune-mediated β-cell dysfunction and damage leading to type 1 diabetes.
Language	English
Publishing date	2016-10-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1228429-4
ISSN	1878-5875 ; 1357-2725
ISSN (online)	1878-5875
ISSN	1357-2725
DOI	10.1016/j.biocel.2016.10.017
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