The ameliorative effect of Piper trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats
In traditional system of medicine, Piper species, or its components are widely used to treat many diseases including memory improvement. One of the wild species Piper trioicum Roxb. (Piperaceae) is found in South Asian countries. The whole plant is used as folk medicine to improve memory. Aim of the...
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| creator | Dash, Umesh Chandra Swain, Sandeep Kumar Jena, Atala Bihari Dandapat, Jagneshwar Sahoo, Atish Kumar |
| description | In traditional system of medicine, Piper species, or its components are widely used to treat many diseases including memory improvement. One of the wild species Piper trioicum Roxb. (Piperaceae) is found in South Asian countries. The whole plant is used as folk medicine to improve memory.
Aim of the study: To our knowledge, no previous research has investigated the neuroprotective activities of P. trioicum. So, we studied the ameliorative effect of P. trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats.
Wistar rats were exposed to scopolamine (3 mg/kg, i. p.) for 14 consecutive days, and the effect of P. trioicum (HAPT; oral, 300, 400 mg/kg) on scopolamine-invoked neurotoxicity in brain were studied. During the experimental period, behaviour analyses of rats were observed 30 min post-drug administration. The role of antioxidants of HAPT in scavenging cellular oxygen/peroxyl radicals were studied. Acetylcholinesterase and butyrylcholinesterase inhibitions, and mode of inhibition kinetics of HAPT were studied. Pathogenic cellular oxidative (MDA, GSH, SOD, and CAT), DNA damage (8-oxodG), neurochemical (acetyl- and, butyryl-cholinesterase), β-secretase (BACE-1 and 2), MAPτ, and neuroinflammation (IL-6, TNF-α) biomarkers in extension to the histopathological observation of brain cortex were studied. GC-MS/MS analysis was carried out to investigate the presence of bioactive constituents in HAPT.
HAPT, a rich source of phenol and flavonoid type antioxidants were responsible in quenching oxygen/peroxyl radicals and protected the cellular membrane, and lipoproteins against ROS in DPPH, ORAC, and CAPe tests. HAPT inhibited acetylcholinesterase and butyrylcholinesterase activities, and showed competitive-inhibition (reversible) towards cholinesterase activities. HAPT-400 significantly improved the learning and memory-impairment by restoring oxidative MDA, GSH, SOD, CAT, and DNA damage (8-oxodG) markers of serum, and cortex. It also improved acetyl- and, butyryl-cholinesterase, β-secretase, and MAPτ level in brain by restoring proinflammatory cytokines IL-6, and TNF-α indicators in neurotoxic rats. GC-MS/MS reported therapeutic significance active compounds were molecular-docked towards target proteins, found that proscillaridin showed the highest affinity towards AChE, BuChE, BACE1, and BACE2 with binding energy of ΔGb −9.1, ΔGb −10.2, ΔGb −11.4 and ΔGb −11.5 Kcal/mol, respectively. Cymarin and morphine-3-glucuronide sh |
| doi_str_mv | 10.1016/j.jep.2023.116911 |
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Aim of the study: To our knowledge, no previous research has investigated the neuroprotective activities of P. trioicum. So, we studied the ameliorative effect of P. trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats.
Wistar rats were exposed to scopolamine (3 mg/kg, i. p.) for 14 consecutive days, and the effect of P. trioicum (HAPT; oral, 300, 400 mg/kg) on scopolamine-invoked neurotoxicity in brain were studied. During the experimental period, behaviour analyses of rats were observed 30 min post-drug administration. The role of antioxidants of HAPT in scavenging cellular oxygen/peroxyl radicals were studied. Acetylcholinesterase and butyrylcholinesterase inhibitions, and mode of inhibition kinetics of HAPT were studied. Pathogenic cellular oxidative (MDA, GSH, SOD, and CAT), DNA damage (8-oxodG), neurochemical (acetyl- and, butyryl-cholinesterase), β-secretase (BACE-1 and 2), MAPτ, and neuroinflammation (IL-6, TNF-α) biomarkers in extension to the histopathological observation of brain cortex were studied. GC-MS/MS analysis was carried out to investigate the presence of bioactive constituents in HAPT.
HAPT, a rich source of phenol and flavonoid type antioxidants were responsible in quenching oxygen/peroxyl radicals and protected the cellular membrane, and lipoproteins against ROS in DPPH, ORAC, and CAPe tests. HAPT inhibited acetylcholinesterase and butyrylcholinesterase activities, and showed competitive-inhibition (reversible) towards cholinesterase activities. HAPT-400 significantly improved the learning and memory-impairment by restoring oxidative MDA, GSH, SOD, CAT, and DNA damage (8-oxodG) markers of serum, and cortex. It also improved acetyl- and, butyryl-cholinesterase, β-secretase, and MAPτ level in brain by restoring proinflammatory cytokines IL-6, and TNF-α indicators in neurotoxic rats. GC-MS/MS reported therapeutic significance active compounds were molecular-docked towards target proteins, found that proscillaridin showed the highest affinity towards AChE, BuChE, BACE1, and BACE2 with binding energy of ΔGb −9.1, ΔGb −10.2, ΔGb −11.4 and ΔGb −11.5 Kcal/mol, respectively. Cymarin and morphine-3-glucuronide showed the second highest binding affinity towards AChE (ΔGb −8.8) and BuChE (ΔGb −10.0), respectively. In BACE-1, betulin showed the second highest binding affinity ΔGb −10.7 Kcal/mol and in BACE-2, morphine-3-glucuronide showed the second highest binding affinity ΔGb −9.8 Kcal/mol.
Synergistic impact of proscillaridin, Cymarin, morphine-3-glucuronide, betulin like compounds in HAPT improved memory impairment, healing of tissue architecture of cortex with the restoration of neurochemical, neuroinflammation, and oxidative indicators in neurotoxic rats.
[Display omitted]
•Piper triocum (HAPT) attenuates cholinergic, β-secretase, and MAPt markers in neurotoxic rats.•HAPT restores redox-neuroinflammation (TNF-α, IL-6) status in neurotoxic rats.•Molecular-docking of proscillaridin in HAPT demonstrated the highest affinity towards AChE.•Molecular-docking of morphine-3-glucuronide demonstrated the highest affinity towards BuChE.•Betulin and proscillaridin had the highest affinity towards BACE1 and BACE2.</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2023.116911</identifier><identifier>PMID: 37451488</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Betulin ; CAPe ; Cholinesterase ; Molecular docking ; Morphine-3-glucuronide ; Neuroinflammation ; ORAC ; Piper trioicum ; Proscillaridin ; β-secretase</subject><ispartof>Journal of ethnopharmacology, 2024-01, Vol.318, p.116911-116911, Article 116911</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-6e2f9f870176e0e14720508d953e24121c5540a7f473d2c0b40b24c05f3216e63</citedby><cites>FETCH-LOGICAL-c353t-6e2f9f870176e0e14720508d953e24121c5540a7f473d2c0b40b24c05f3216e63</cites><orcidid>0000-0002-6524-4642</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378874123007791$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37451488$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dash, Umesh Chandra</creatorcontrib><creatorcontrib>Swain, Sandeep Kumar</creatorcontrib><creatorcontrib>Jena, Atala Bihari</creatorcontrib><creatorcontrib>Dandapat, Jagneshwar</creatorcontrib><creatorcontrib>Sahoo, Atish Kumar</creatorcontrib><title>The ameliorative effect of Piper trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>In traditional system of medicine, Piper species, or its components are widely used to treat many diseases including memory improvement. One of the wild species Piper trioicum Roxb. (Piperaceae) is found in South Asian countries. The whole plant is used as folk medicine to improve memory.
Aim of the study: To our knowledge, no previous research has investigated the neuroprotective activities of P. trioicum. So, we studied the ameliorative effect of P. trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats.
Wistar rats were exposed to scopolamine (3 mg/kg, i. p.) for 14 consecutive days, and the effect of P. trioicum (HAPT; oral, 300, 400 mg/kg) on scopolamine-invoked neurotoxicity in brain were studied. During the experimental period, behaviour analyses of rats were observed 30 min post-drug administration. The role of antioxidants of HAPT in scavenging cellular oxygen/peroxyl radicals were studied. Acetylcholinesterase and butyrylcholinesterase inhibitions, and mode of inhibition kinetics of HAPT were studied. Pathogenic cellular oxidative (MDA, GSH, SOD, and CAT), DNA damage (8-oxodG), neurochemical (acetyl- and, butyryl-cholinesterase), β-secretase (BACE-1 and 2), MAPτ, and neuroinflammation (IL-6, TNF-α) biomarkers in extension to the histopathological observation of brain cortex were studied. GC-MS/MS analysis was carried out to investigate the presence of bioactive constituents in HAPT.
HAPT, a rich source of phenol and flavonoid type antioxidants were responsible in quenching oxygen/peroxyl radicals and protected the cellular membrane, and lipoproteins against ROS in DPPH, ORAC, and CAPe tests. HAPT inhibited acetylcholinesterase and butyrylcholinesterase activities, and showed competitive-inhibition (reversible) towards cholinesterase activities. HAPT-400 significantly improved the learning and memory-impairment by restoring oxidative MDA, GSH, SOD, CAT, and DNA damage (8-oxodG) markers of serum, and cortex. It also improved acetyl- and, butyryl-cholinesterase, β-secretase, and MAPτ level in brain by restoring proinflammatory cytokines IL-6, and TNF-α indicators in neurotoxic rats. GC-MS/MS reported therapeutic significance active compounds were molecular-docked towards target proteins, found that proscillaridin showed the highest affinity towards AChE, BuChE, BACE1, and BACE2 with binding energy of ΔGb −9.1, ΔGb −10.2, ΔGb −11.4 and ΔGb −11.5 Kcal/mol, respectively. Cymarin and morphine-3-glucuronide showed the second highest binding affinity towards AChE (ΔGb −8.8) and BuChE (ΔGb −10.0), respectively. In BACE-1, betulin showed the second highest binding affinity ΔGb −10.7 Kcal/mol and in BACE-2, morphine-3-glucuronide showed the second highest binding affinity ΔGb −9.8 Kcal/mol.
Synergistic impact of proscillaridin, Cymarin, morphine-3-glucuronide, betulin like compounds in HAPT improved memory impairment, healing of tissue architecture of cortex with the restoration of neurochemical, neuroinflammation, and oxidative indicators in neurotoxic rats.
[Display omitted]
•Piper triocum (HAPT) attenuates cholinergic, β-secretase, and MAPt markers in neurotoxic rats.•HAPT restores redox-neuroinflammation (TNF-α, IL-6) status in neurotoxic rats.•Molecular-docking of proscillaridin in HAPT demonstrated the highest affinity towards AChE.•Molecular-docking of morphine-3-glucuronide demonstrated the highest affinity towards BuChE.•Betulin and proscillaridin had the highest affinity towards BACE1 and BACE2.</description><subject>Betulin</subject><subject>CAPe</subject><subject>Cholinesterase</subject><subject>Molecular docking</subject><subject>Morphine-3-glucuronide</subject><subject>Neuroinflammation</subject><subject>ORAC</subject><subject>Piper trioicum</subject><subject>Proscillaridin</subject><subject>β-secretase</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kE1v1DAQhi0EotuPH8AF-cgli8d2Yq84oapQpErtoZwtrzMuXiVxsJ2qvfPDcdjCkZM10vO-43kIeQdsCwy6j4ftAectZ1xsAbodwCuyAa14o1olXpMNE0o3Wkk4Iac5HxhjCiR7S06Eki1IrTfk1_0PpHbEIcRkS3hEit6jKzR6ehdmTLSkEINbRhomakvBaanc9EBdfJjCn0SPPrhQViC7OMfBjmHCOvaLw55OuKRY4tPKPK8QPtXeMOJU7EDr1nxO3ng7ZLx4ec_I9y9X95fXzc3t12-Xn28aJ1pRmg6533mtGKgOGYJUnLVM97tWIJfAwbWtZFZ5qUTPHdtLtufSsdYLDh124ox8OPbOKf5cMBczhuxwGOyEccmGa6F5KwBEReGIuhRzTujNXL9s07MBZlb55mCqfLPKN0f5NfP-pX7Zj9j_S_y1XYFPRwDrkY8Bk8ku4FQlhVSdmz6G_9T_BpYPloI</recordid><startdate>20240110</startdate><enddate>20240110</enddate><creator>Dash, Umesh Chandra</creator><creator>Swain, Sandeep Kumar</creator><creator>Jena, Atala Bihari</creator><creator>Dandapat, Jagneshwar</creator><creator>Sahoo, Atish Kumar</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6524-4642</orcidid></search><sort><creationdate>20240110</creationdate><title>The ameliorative effect of Piper trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats</title><author>Dash, Umesh Chandra ; Swain, Sandeep Kumar ; Jena, Atala Bihari ; Dandapat, Jagneshwar ; Sahoo, Atish Kumar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-6e2f9f870176e0e14720508d953e24121c5540a7f473d2c0b40b24c05f3216e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Betulin</topic><topic>CAPe</topic><topic>Cholinesterase</topic><topic>Molecular docking</topic><topic>Morphine-3-glucuronide</topic><topic>Neuroinflammation</topic><topic>ORAC</topic><topic>Piper trioicum</topic><topic>Proscillaridin</topic><topic>β-secretase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dash, Umesh Chandra</creatorcontrib><creatorcontrib>Swain, Sandeep Kumar</creatorcontrib><creatorcontrib>Jena, Atala Bihari</creatorcontrib><creatorcontrib>Dandapat, Jagneshwar</creatorcontrib><creatorcontrib>Sahoo, Atish Kumar</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dash, Umesh Chandra</au><au>Swain, Sandeep Kumar</au><au>Jena, Atala Bihari</au><au>Dandapat, Jagneshwar</au><au>Sahoo, Atish Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The ameliorative effect of Piper trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2024-01-10</date><risdate>2024</risdate><volume>318</volume><spage>116911</spage><epage>116911</epage><pages>116911-116911</pages><artnum>116911</artnum><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>In traditional system of medicine, Piper species, or its components are widely used to treat many diseases including memory improvement. One of the wild species Piper trioicum Roxb. (Piperaceae) is found in South Asian countries. The whole plant is used as folk medicine to improve memory.
Aim of the study: To our knowledge, no previous research has investigated the neuroprotective activities of P. trioicum. So, we studied the ameliorative effect of P. trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats.
Wistar rats were exposed to scopolamine (3 mg/kg, i. p.) for 14 consecutive days, and the effect of P. trioicum (HAPT; oral, 300, 400 mg/kg) on scopolamine-invoked neurotoxicity in brain were studied. During the experimental period, behaviour analyses of rats were observed 30 min post-drug administration. The role of antioxidants of HAPT in scavenging cellular oxygen/peroxyl radicals were studied. Acetylcholinesterase and butyrylcholinesterase inhibitions, and mode of inhibition kinetics of HAPT were studied. Pathogenic cellular oxidative (MDA, GSH, SOD, and CAT), DNA damage (8-oxodG), neurochemical (acetyl- and, butyryl-cholinesterase), β-secretase (BACE-1 and 2), MAPτ, and neuroinflammation (IL-6, TNF-α) biomarkers in extension to the histopathological observation of brain cortex were studied. GC-MS/MS analysis was carried out to investigate the presence of bioactive constituents in HAPT.
HAPT, a rich source of phenol and flavonoid type antioxidants were responsible in quenching oxygen/peroxyl radicals and protected the cellular membrane, and lipoproteins against ROS in DPPH, ORAC, and CAPe tests. HAPT inhibited acetylcholinesterase and butyrylcholinesterase activities, and showed competitive-inhibition (reversible) towards cholinesterase activities. HAPT-400 significantly improved the learning and memory-impairment by restoring oxidative MDA, GSH, SOD, CAT, and DNA damage (8-oxodG) markers of serum, and cortex. It also improved acetyl- and, butyryl-cholinesterase, β-secretase, and MAPτ level in brain by restoring proinflammatory cytokines IL-6, and TNF-α indicators in neurotoxic rats. GC-MS/MS reported therapeutic significance active compounds were molecular-docked towards target proteins, found that proscillaridin showed the highest affinity towards AChE, BuChE, BACE1, and BACE2 with binding energy of ΔGb −9.1, ΔGb −10.2, ΔGb −11.4 and ΔGb −11.5 Kcal/mol, respectively. Cymarin and morphine-3-glucuronide showed the second highest binding affinity towards AChE (ΔGb −8.8) and BuChE (ΔGb −10.0), respectively. In BACE-1, betulin showed the second highest binding affinity ΔGb −10.7 Kcal/mol and in BACE-2, morphine-3-glucuronide showed the second highest binding affinity ΔGb −9.8 Kcal/mol.
Synergistic impact of proscillaridin, Cymarin, morphine-3-glucuronide, betulin like compounds in HAPT improved memory impairment, healing of tissue architecture of cortex with the restoration of neurochemical, neuroinflammation, and oxidative indicators in neurotoxic rats.
[Display omitted]
•Piper triocum (HAPT) attenuates cholinergic, β-secretase, and MAPt markers in neurotoxic rats.•HAPT restores redox-neuroinflammation (TNF-α, IL-6) status in neurotoxic rats.•Molecular-docking of proscillaridin in HAPT demonstrated the highest affinity towards AChE.•Molecular-docking of morphine-3-glucuronide demonstrated the highest affinity towards BuChE.•Betulin and proscillaridin had the highest affinity towards BACE1 and BACE2.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>37451488</pmid><doi>10.1016/j.jep.2023.116911</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-6524-4642</orcidid></addata></record> |
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| subjects | Betulin CAPe Cholinesterase Molecular docking Morphine-3-glucuronide Neuroinflammation ORAC Piper trioicum Proscillaridin β-secretase |
| title | The ameliorative effect of Piper trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats |
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