Hyoscyamus albus nortropane alkaloids reduce hyperglycemia and hyperinsulinemia induced in HepG2 cells through the regulation of SIRT1/NF-kB/JNK pathway.
Apoptosis
/ drug effects
Caspases
/ metabolism
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Cytokines
/ metabolism
Gluconeogenesis
/ drug effects
Glucose
/ metabolism
Hep G2 Cells
Humans
Hyoscyamus
/ chemistry
Hyperglycemia
/ drug therapy
Hyperinsulinism
/ drug therapy
Inflammation
/ metabolism
Inflammation Mediators
/ metabolism
Insulin
/ metabolism
Insulin Resistance
MAP Kinase Signaling System
/ drug effects
Mitochondria
/ drug effects
NF-kappa B
/ metabolism
Nortropanes
/ pharmacology
Oxidative Stress
Plant Extracts
/ pharmacology
Seeds
/ chemistry
Signal Transduction
/ drug effects
Sirtuin 1
/ metabolism
TOR Serine-Threonine Kinases
/ metabolism
Calystegines
HepG2
Hyoscyamus albus
Hyperglycemia
Insulin Resistance
NF-κB
Sirt1
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
25 05 2021
25 05 2021
Historique:
received:
02
01
2021
accepted:
24
03
2021
entrez:
26
5
2021
pubmed:
27
5
2021
medline:
27
1
2022
Statut:
epublish
Résumé
Chronic superphysiological glucose and insulin concentrations are known to trigger several tissue and organ failures, including insulin resistance, oxidative stress and chronic low-grade inflammation. Hence, the screening for molecules that may counteract such conditions is essential in current existing therapeutic strategies, thereby the use of medicinal plant derivatives represents a promising axis in this regard. In this study, the effect of a selected traditional medicinal plant, Hyoscyamus albus from which, calystegines have been isolated, was investigated in an experimental model of hyperinsulinemia and hyperglycemia induced on HepG2 cells. The mRNA and protein expression levels of different insulin signaling, gluconeogenic and inflammatory pathway- related molecules were examined. Additionally, cell viability and apoptosis, oxidative stress extent and mitochondrial dysfunctions were assayed using flow cytometric and qRT-PCR techniques. Treatment of IR HepG2 cells with calystegines strongly protected the injured cells from apoptosis, oxidative stress and mitochondrial integrity loss. Interestingly, nortropane alkaloids efficiently regulated the impaired glucose metabolism in IR HepG2 cells, through the stimulation of glucose uptake and the modulation of SIRT1/Foxo1/G6PC/mTOR pathway, which is governing the hepatic gluconeogenesis. Furthermore, the alkaloidal extract restored the defective insulin signaling pathway, mainly by promoting the expression of Insr at the mRNA and protein levels. What is more, treated cells exhibited significant mitigated inflammatory response, as evidenced by the modulation and the regulation of the NF- κB/JNK/TLR4 axis and the downstream proinflammatory cytokines recruitment. Overall, the present investigation demonstrates that calystegines from Hyoscyamus albus provide cytoprotection to the HepG2 cells against insulin/glucose induced insulin resistance and apoptosis due to the regulation of SIRT1/Foxo1/G6PC/mTOR and NF-κB/JNK/TLR4 signaling pathways. Video Abstract.
Sections du résumé
BACKGROUND
Chronic superphysiological glucose and insulin concentrations are known to trigger several tissue and organ failures, including insulin resistance, oxidative stress and chronic low-grade inflammation. Hence, the screening for molecules that may counteract such conditions is essential in current existing therapeutic strategies, thereby the use of medicinal plant derivatives represents a promising axis in this regard.
METHODS
In this study, the effect of a selected traditional medicinal plant, Hyoscyamus albus from which, calystegines have been isolated, was investigated in an experimental model of hyperinsulinemia and hyperglycemia induced on HepG2 cells. The mRNA and protein expression levels of different insulin signaling, gluconeogenic and inflammatory pathway- related molecules were examined. Additionally, cell viability and apoptosis, oxidative stress extent and mitochondrial dysfunctions were assayed using flow cytometric and qRT-PCR techniques.
RESULTS
Treatment of IR HepG2 cells with calystegines strongly protected the injured cells from apoptosis, oxidative stress and mitochondrial integrity loss. Interestingly, nortropane alkaloids efficiently regulated the impaired glucose metabolism in IR HepG2 cells, through the stimulation of glucose uptake and the modulation of SIRT1/Foxo1/G6PC/mTOR pathway, which is governing the hepatic gluconeogenesis. Furthermore, the alkaloidal extract restored the defective insulin signaling pathway, mainly by promoting the expression of Insr at the mRNA and protein levels. What is more, treated cells exhibited significant mitigated inflammatory response, as evidenced by the modulation and the regulation of the NF- κB/JNK/TLR4 axis and the downstream proinflammatory cytokines recruitment.
CONCLUSION
Overall, the present investigation demonstrates that calystegines from Hyoscyamus albus provide cytoprotection to the HepG2 cells against insulin/glucose induced insulin resistance and apoptosis due to the regulation of SIRT1/Foxo1/G6PC/mTOR and NF-κB/JNK/TLR4 signaling pathways. Video Abstract.
Identifiants
pubmed: 34034759
doi: 10.1186/s12964-021-00735-w
pii: 10.1186/s12964-021-00735-w
pmc: PMC8152357
doi:
Substances chimiques
Cytokines
0
Inflammation Mediators
0
Insulin
0
NF-kappa B
0
Nortropanes
0
Plant Extracts
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Caspases
EC 3.4.22.-
Sirtuin 1
EC 3.5.1.-
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
61Subventions
Organisme : Narodowe Centrum Nauki
ID : 2018/29/B/NZ7/02662
Commentaires et corrections
Type : ErratumIn
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