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Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments.

Identifieur interne : 000086 ( Main/Exploration ); précédent : 000085; suivant : 000087

Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments.

Auteurs : Mabozou Kpemissi [Inde] ; Adrian-Valentin Potârniche [Roumanie] ; Povi Lawson-Evi [Togo] ; Kossi Metowogo [Togo] ; Mamatchi Melila [Togo] ; Pare Dramane [Burkina Faso] ; Marian Taulescu [Roumanie] ; Vivek Chandramohan [Inde] ; Doddamavattur Shivalingaiah Suhas [Inde] ; Tumbadi Adinarayanashetty Puneeth [Inde] ; Vijaya Kumar S [Inde] ; Laurian Vlase [Roumanie] ; Sanda Andrei [Roumanie] ; Kwashie Eklu-Gadegbeku [Togo] ; Bogdan Sevastre [Roumanie] ; Veeresh Prabhakar Veerapur [Inde]

Source :

RBID : pubmed:32673708

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders.

AIM OF THE STUDY

To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ.

MATERIAL AND METHODS

Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-β-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg

RESULTS

At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 μg/mg of extract) and quercitrin (19.07 μg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein.

CONCLUSIONS

Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum.


DOI: 10.1016/j.jep.2020.113133
PubMed: 32673708


Affiliations:


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<name sortKey="Taulescu, Marian" sort="Taulescu, Marian" uniqKey="Taulescu M" first="Marian" last="Taulescu">Marian Taulescu</name>
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<name sortKey="Chandramohan, Vivek" sort="Chandramohan, Vivek" uniqKey="Chandramohan V" first="Vivek" last="Chandramohan">Vivek Chandramohan</name>
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<name sortKey="S, Vijaya Kumar" sort="S, Vijaya Kumar" uniqKey="S V" first="Vijaya Kumar" last="S">Vijaya Kumar S</name>
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<name sortKey="Vlase, Laurian" sort="Vlase, Laurian" uniqKey="Vlase L" first="Laurian" last="Vlase">Laurian Vlase</name>
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<name sortKey="Veerapur, Veeresh Prabhakar" sort="Veerapur, Veeresh Prabhakar" uniqKey="Veerapur V" first="Veeresh Prabhakar" last="Veerapur">Veeresh Prabhakar Veerapur</name>
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<title level="j">Journal of ethnopharmacology</title>
<idno type="eISSN">1872-7573</idno>
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<date when="2020" type="published">2020</date>
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<p>
<b>ETHNOPHARMACOLOGICAL RELEVANCE</b>
</p>
<p>Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>AIM OF THE STUDY</b>
</p>
<p>To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>MATERIAL AND METHODS</b>
</p>
<p>Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-β-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>RESULTS</b>
</p>
<p>At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 μg/mg of extract) and quercitrin (19.07 μg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>CONCLUSIONS</b>
</p>
<p>Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum.</p>
</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="In-Process" Owner="NLM">
<PMID Version="1">32673708</PMID>
<DateRevised>
<Year>2020</Year>
<Month>08</Month>
<Day>31</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1872-7573</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>261</Volume>
<PubDate>
<Year>2020</Year>
<Month>Oct</Month>
<Day>28</Day>
</PubDate>
</JournalIssue>
<Title>Journal of ethnopharmacology</Title>
<ISOAbbreviation>J Ethnopharmacol</ISOAbbreviation>
</Journal>
<ArticleTitle>Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments.</ArticleTitle>
<Pagination>
<MedlinePgn>113133</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0378-8741(20)33014-2</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jep.2020.113133</ELocationID>
<Abstract>
<AbstractText Label="ETHNOPHARMACOLOGICAL RELEVANCE" NlmCategory="BACKGROUND">Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders.</AbstractText>
<AbstractText Label="AIM OF THE STUDY" NlmCategory="OBJECTIVE">To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ.</AbstractText>
<AbstractText Label="MATERIAL AND METHODS" NlmCategory="METHODS">Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-β-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg
<sup>2+</sup>
), calcium (Ca
<sup>2+</sup>
), phosphorus (P), were estimated. Blood glycosylated hemoglobin (HbA1
<sub>C</sub>
) were also estimated. kidney and liver were used for biochemical estimation of oxidative stress markers such as lipid peroxidation, superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity. The kidney and pancreas were used for histopathological study. Further, HPLC chemoprofiling of CM extract and in-silico molecular simulation experiments were performed.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 μg/mg of extract) and quercitrin (19.07 μg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum.</AbstractText>
<CopyrightInformation>Copyright © 2020 Elsevier B.V. All rights reserved.</CopyrightInformation>
</Abstract>
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<Author ValidYN="Y">
<LastName>Kpemissi</LastName>
<ForeName>Mabozou</ForeName>
<Initials>M</Initials>
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<Affiliation>University of Lomé, Togo; University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania; Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. Electronic address: mabozou@gmail.com.</Affiliation>
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<LastName>Potârniche</LastName>
<ForeName>Adrian-Valentin</ForeName>
<Initials>AV</Initials>
<AffiliationInfo>
<Affiliation>University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Lawson-Evi</LastName>
<ForeName>Povi</ForeName>
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<ForeName>Kossi</ForeName>
<Initials>K</Initials>
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<Initials>M</Initials>
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<ForeName>Pare</ForeName>
<Initials>P</Initials>
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<Affiliation>University of Ouagadougou UFR/SVT, 09 BP 848, Ouagadougou 09, Burkina Faso.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Taulescu</LastName>
<ForeName>Marian</ForeName>
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<LastName>Chandramohan</LastName>
<ForeName>Vivek</ForeName>
<Initials>V</Initials>
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<ForeName>Doddamavattur Shivalingaiah</ForeName>
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<Affiliation>Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India.</Affiliation>
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<LastName>Puneeth</LastName>
<ForeName>Tumbadi Adinarayanashetty</ForeName>
<Initials>TA</Initials>
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<Affiliation>Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India.</Affiliation>
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<ForeName>Vijaya Kumar</ForeName>
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</AffiliationInfo>
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<Affiliation>University of Medicine and Pharmacy "Iuliu Hateganu", Emil Isaac Street 13, 400023, Cluj-Napoca, Romania.</Affiliation>
</AffiliationInfo>
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<LastName>Andrei</LastName>
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<Initials>S</Initials>
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<LastName>Eklu-Gadegbeku</LastName>
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<LastName>Veerapur</LastName>
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<AffiliationInfo>
<Affiliation>Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. Electronic address: veeresh36@gmail.com.</Affiliation>
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<Language>eng</Language>
<PublicationTypeList>
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<Year>2020</Year>
<Month>07</Month>
<Day>14</Day>
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</Article>
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<Country>Ireland</Country>
<MedlineTA>J Ethnopharmacol</MedlineTA>
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<ISSNLinking>0378-8741</ISSNLinking>
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<CitationSubset>IM</CitationSubset>
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<Keyword MajorTopicYN="N">Combretum micranthum</Keyword>
<Keyword MajorTopicYN="N">Diabetic nephropathy</Keyword>
<Keyword MajorTopicYN="N">Molecular docking</Keyword>
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<li>Burkina Faso</li>
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