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Cymbopogon citratus (DC.) Stapf mitigates ER-stress induced by streptozotocin in rats via down-regulation of GRP78 and up-regulation of Nrf2 signaling
Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes mellitus, contributing to pancreatic dysfunction and insulin resistance. Ameliorating ER stress may be a viable therapeutic approach in the proper management of diabetes mellitus. Cymbopogon citratus (C.citratus) has been...
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| Published in: | Journal of ethnopharmacology 2020-11, Vol.262, p.113130, Article 113130 |
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| creator | Elekofehinti, Olusola Olalekan Onunkun, Afolashade Toritseju Olaleye, Tolulope Mary |
| description | Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes mellitus, contributing to pancreatic dysfunction and insulin resistance. Ameliorating ER stress may be a viable therapeutic approach in the proper management of diabetes mellitus. Cymbopogon citratus (C.citratus) has been used in traditional medicine in the management of diabetes mellitus. Although well known for its anti-diabetic effect, the mechanism underlying this effect remains unclear.
This study was designed to investigate the effect of C. citratus methanolic leaves extract on ER stress induced by streptozotocin (STZ) in wistar rats.
STZ (60 mg/kg) was used to induce ER stress in the pancreas of rats. The rats were administered C. citratus methanolic leaves extract via gastric gavage at doses 100, 200 and 400 mg/kg for two weeks while metformin (100 mg/kg) was used as positive control. Fasting blood glucose (FBG), expression of ER-stress related genes (GRP78, CHOP, ATF4, TRB3, PERK, IRE1), antioxidant (Nrf2 and AhR) and pro-inflammatory (TNF-α) genes were determined. Possible compounds responsible for this effect were also predicted through molecular docking.
Induction of ER stress using STZ significantly increased FBG while administration of C. citratus methanolic extract restored it to normal control level (p |
| doi_str_mv | 10.1016/j.jep.2020.113130 |
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This study was designed to investigate the effect of C. citratus methanolic leaves extract on ER stress induced by streptozotocin (STZ) in wistar rats.
STZ (60 mg/kg) was used to induce ER stress in the pancreas of rats. The rats were administered C. citratus methanolic leaves extract via gastric gavage at doses 100, 200 and 400 mg/kg for two weeks while metformin (100 mg/kg) was used as positive control. Fasting blood glucose (FBG), expression of ER-stress related genes (GRP78, CHOP, ATF4, TRB3, PERK, IRE1), antioxidant (Nrf2 and AhR) and pro-inflammatory (TNF-α) genes were determined. Possible compounds responsible for this effect were also predicted through molecular docking.
Induction of ER stress using STZ significantly increased FBG while administration of C. citratus methanolic extract restored it to normal control level (p < 0.05). Significant down-regulation of ER stress genes was observed upon treatment of ER stress induced rats with C. citratus methanolic extract when compared to ER-stress untreated rats. Significant up-regulation (p < 0.05) of genes coding for Nrf2 and AhR was also noticed upon treatment of ER stress induced rats with C. citratus methanolic extract. Molecular docking suggests that apigenin targets GRP78 with binding affinity of −9.3 kcal/mol while kaempferol and quercetin target Keap1 with binding affinity of −9.5 kcal/mol and may be responsible for this ameliorative effect on ER stress.
These observations suggest that C. citratus mitigate ER stress induced by STZ via its down-regulative effect on GRP78 and up-regulative effect on NRF2 signaling.
[Display omitted]
•Streptozotocin was used to induce endoplasmic reticulum stress(ER) in rats.•C. citratus methanolic leaves extract down-regulate the expression of ER stress marker genes.•C. citratus methanolic leaves extract up-regulate Nrf2 signaling.•Apigenin from C. citratus targets GRP78 while kaempferol and quercetin target Keap1.</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2020.113130</identifier><identifier>PMID: 32736056</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Animals ; Anti-diabetic herb ; Apoptosis ; C. citratus methanolic Extract ; Cymbopogon ; Diabetes mellitus ; Down-Regulation - drug effects ; Down-Regulation - physiology ; Endoplasmic reticulum stress ; Endoplasmic Reticulum Stress - drug effects ; Endoplasmic Reticulum Stress - physiology ; Heat-Shock Proteins - antagonists & inhibitors ; Heat-Shock Proteins - metabolism ; NF-E2-Related Factor 2 - agonists ; NF-E2-Related Factor 2 - metabolism ; Pancreas ; Plant Extracts - isolation & purification ; Plant Extracts - pharmacology ; Plant Leaves ; Rats ; Rats, Wistar ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Streptozocin - toxicity ; Up-Regulation - drug effects ; Up-Regulation - physiology</subject><ispartof>Journal of ethnopharmacology, 2020-11, Vol.262, p.113130, Article 113130</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-65ce377f261545a8f82b1b0595536d9ba1f9f86ec332f1f5156f3a386deb5bab3</citedby><cites>FETCH-LOGICAL-c353t-65ce377f261545a8f82b1b0595536d9ba1f9f86ec332f1f5156f3a386deb5bab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32736056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elekofehinti, Olusola Olalekan</creatorcontrib><creatorcontrib>Onunkun, Afolashade Toritseju</creatorcontrib><creatorcontrib>Olaleye, Tolulope Mary</creatorcontrib><title>Cymbopogon citratus (DC.) Stapf mitigates ER-stress induced by streptozotocin in rats via down-regulation of GRP78 and up-regulation of Nrf2 signaling</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes mellitus, contributing to pancreatic dysfunction and insulin resistance. Ameliorating ER stress may be a viable therapeutic approach in the proper management of diabetes mellitus. Cymbopogon citratus (C.citratus) has been used in traditional medicine in the management of diabetes mellitus. Although well known for its anti-diabetic effect, the mechanism underlying this effect remains unclear.
This study was designed to investigate the effect of C. citratus methanolic leaves extract on ER stress induced by streptozotocin (STZ) in wistar rats.
STZ (60 mg/kg) was used to induce ER stress in the pancreas of rats. The rats were administered C. citratus methanolic leaves extract via gastric gavage at doses 100, 200 and 400 mg/kg for two weeks while metformin (100 mg/kg) was used as positive control. Fasting blood glucose (FBG), expression of ER-stress related genes (GRP78, CHOP, ATF4, TRB3, PERK, IRE1), antioxidant (Nrf2 and AhR) and pro-inflammatory (TNF-α) genes were determined. Possible compounds responsible for this effect were also predicted through molecular docking.
Induction of ER stress using STZ significantly increased FBG while administration of C. citratus methanolic extract restored it to normal control level (p < 0.05). Significant down-regulation of ER stress genes was observed upon treatment of ER stress induced rats with C. citratus methanolic extract when compared to ER-stress untreated rats. Significant up-regulation (p < 0.05) of genes coding for Nrf2 and AhR was also noticed upon treatment of ER stress induced rats with C. citratus methanolic extract. Molecular docking suggests that apigenin targets GRP78 with binding affinity of −9.3 kcal/mol while kaempferol and quercetin target Keap1 with binding affinity of −9.5 kcal/mol and may be responsible for this ameliorative effect on ER stress.
These observations suggest that C. citratus mitigate ER stress induced by STZ via its down-regulative effect on GRP78 and up-regulative effect on NRF2 signaling.
[Display omitted]
•Streptozotocin was used to induce endoplasmic reticulum stress(ER) in rats.•C. citratus methanolic leaves extract down-regulate the expression of ER stress marker genes.•C. citratus methanolic leaves extract up-regulate Nrf2 signaling.•Apigenin from C. citratus targets GRP78 while kaempferol and quercetin target Keap1.</description><subject>Animals</subject><subject>Anti-diabetic herb</subject><subject>Apoptosis</subject><subject>C. citratus methanolic Extract</subject><subject>Cymbopogon</subject><subject>Diabetes mellitus</subject><subject>Down-Regulation - drug effects</subject><subject>Down-Regulation - physiology</subject><subject>Endoplasmic reticulum stress</subject><subject>Endoplasmic Reticulum Stress - drug effects</subject><subject>Endoplasmic Reticulum Stress - physiology</subject><subject>Heat-Shock Proteins - antagonists & inhibitors</subject><subject>Heat-Shock Proteins - metabolism</subject><subject>NF-E2-Related Factor 2 - agonists</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Pancreas</subject><subject>Plant Extracts - isolation & purification</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Leaves</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Streptozocin - toxicity</subject><subject>Up-Regulation - drug effects</subject><subject>Up-Regulation - physiology</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOAyEUhonR2Fp9ADeGpS6mwlBgGlemXhOjxsuaAAMTmnaYAKOpD-LzSlN14cLVyTn_JScfAIcYjTHC7HQ-nptuXKIy75hggrbAEFe8LDjlZBsMEeFVUfEJHoC9GOcIIY4naBcMSMkJQ5QNwedstVS-841voXYpyNRHeHwxG5_A5yQ7C5cuuUYmE-HlUxFTMDFC19a9NjVUK7i-dMl_-OS1a7MCc0WEb07C2r-3RTBNv5DJ5Xpv4fXTI6-gbGvYd3-k-2BLGF3TyoVrm32wY-UimoPvOQKvV5cvs5vi7uH6dnZ-V2hCSSoY1YZwbkuG6YTKylalwgrRKaWE1VMlsZ3aihlNSGmxpZgySySpWG0UVVKREcCbXh18jMFY0QW3lGElMBJrxmIuMmOxZiw2jHPmaJPperU09W_iB2o2nG0MJn_-5kwQUTvTZmIuGJ1E7d0_9V8WfY4M</recordid><startdate>20201115</startdate><enddate>20201115</enddate><creator>Elekofehinti, Olusola Olalekan</creator><creator>Onunkun, Afolashade Toritseju</creator><creator>Olaleye, Tolulope Mary</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20201115</creationdate><title>Cymbopogon citratus (DC.) Stapf mitigates ER-stress induced by streptozotocin in rats via down-regulation of GRP78 and up-regulation of Nrf2 signaling</title><author>Elekofehinti, Olusola Olalekan ; Onunkun, Afolashade Toritseju ; Olaleye, Tolulope Mary</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-65ce377f261545a8f82b1b0595536d9ba1f9f86ec332f1f5156f3a386deb5bab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Anti-diabetic herb</topic><topic>Apoptosis</topic><topic>C. citratus methanolic Extract</topic><topic>Cymbopogon</topic><topic>Diabetes mellitus</topic><topic>Down-Regulation - drug effects</topic><topic>Down-Regulation - physiology</topic><topic>Endoplasmic reticulum stress</topic><topic>Endoplasmic Reticulum Stress - drug effects</topic><topic>Endoplasmic Reticulum Stress - physiology</topic><topic>Heat-Shock Proteins - antagonists & inhibitors</topic><topic>Heat-Shock Proteins - metabolism</topic><topic>NF-E2-Related Factor 2 - agonists</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Pancreas</topic><topic>Plant Extracts - isolation & purification</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Leaves</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Streptozocin - toxicity</topic><topic>Up-Regulation - drug effects</topic><topic>Up-Regulation - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elekofehinti, Olusola Olalekan</creatorcontrib><creatorcontrib>Onunkun, Afolashade Toritseju</creatorcontrib><creatorcontrib>Olaleye, Tolulope Mary</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elekofehinti, Olusola Olalekan</au><au>Onunkun, Afolashade Toritseju</au><au>Olaleye, Tolulope Mary</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cymbopogon citratus (DC.) Stapf mitigates ER-stress induced by streptozotocin in rats via down-regulation of GRP78 and up-regulation of Nrf2 signaling</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2020-11-15</date><risdate>2020</risdate><volume>262</volume><spage>113130</spage><pages>113130-</pages><artnum>113130</artnum><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>Endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes mellitus, contributing to pancreatic dysfunction and insulin resistance. Ameliorating ER stress may be a viable therapeutic approach in the proper management of diabetes mellitus. Cymbopogon citratus (C.citratus) has been used in traditional medicine in the management of diabetes mellitus. Although well known for its anti-diabetic effect, the mechanism underlying this effect remains unclear.
This study was designed to investigate the effect of C. citratus methanolic leaves extract on ER stress induced by streptozotocin (STZ) in wistar rats.
STZ (60 mg/kg) was used to induce ER stress in the pancreas of rats. The rats were administered C. citratus methanolic leaves extract via gastric gavage at doses 100, 200 and 400 mg/kg for two weeks while metformin (100 mg/kg) was used as positive control. Fasting blood glucose (FBG), expression of ER-stress related genes (GRP78, CHOP, ATF4, TRB3, PERK, IRE1), antioxidant (Nrf2 and AhR) and pro-inflammatory (TNF-α) genes were determined. Possible compounds responsible for this effect were also predicted through molecular docking.
Induction of ER stress using STZ significantly increased FBG while administration of C. citratus methanolic extract restored it to normal control level (p < 0.05). Significant down-regulation of ER stress genes was observed upon treatment of ER stress induced rats with C. citratus methanolic extract when compared to ER-stress untreated rats. Significant up-regulation (p < 0.05) of genes coding for Nrf2 and AhR was also noticed upon treatment of ER stress induced rats with C. citratus methanolic extract. Molecular docking suggests that apigenin targets GRP78 with binding affinity of −9.3 kcal/mol while kaempferol and quercetin target Keap1 with binding affinity of −9.5 kcal/mol and may be responsible for this ameliorative effect on ER stress.
These observations suggest that C. citratus mitigate ER stress induced by STZ via its down-regulative effect on GRP78 and up-regulative effect on NRF2 signaling.
[Display omitted]
•Streptozotocin was used to induce endoplasmic reticulum stress(ER) in rats.•C. citratus methanolic leaves extract down-regulate the expression of ER stress marker genes.•C. citratus methanolic leaves extract up-regulate Nrf2 signaling.•Apigenin from C. citratus targets GRP78 while kaempferol and quercetin target Keap1.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>32736056</pmid><doi>10.1016/j.jep.2020.113130</doi></addata></record> |
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| source | ScienceDirect Freedom Collection |
| subjects | Animals Anti-diabetic herb Apoptosis C. citratus methanolic Extract Cymbopogon Diabetes mellitus Down-Regulation - drug effects Down-Regulation - physiology Endoplasmic reticulum stress Endoplasmic Reticulum Stress - drug effects Endoplasmic Reticulum Stress - physiology Heat-Shock Proteins - antagonists & inhibitors Heat-Shock Proteins - metabolism NF-E2-Related Factor 2 - agonists NF-E2-Related Factor 2 - metabolism Pancreas Plant Extracts - isolation & purification Plant Extracts - pharmacology Plant Leaves Rats Rats, Wistar Signal Transduction - drug effects Signal Transduction - physiology Streptozocin - toxicity Up-Regulation - drug effects Up-Regulation - physiology |
| title | Cymbopogon citratus (DC.) Stapf mitigates ER-stress induced by streptozotocin in rats via down-regulation of GRP78 and up-regulation of Nrf2 signaling |
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