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Ameliorative effect of AYUSH formulation against scopolamine induced learning and memory impairment in rat via attenuation of oxidative stress, neuroinflammation, acetylcholinesterase inhibition and Aβ plaques.

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Title: Ameliorative effect of AYUSH formulation against scopolamine induced learning and memory impairment in rat via attenuation of oxidative stress, neuroinflammation, acetylcholinesterase inhibition and Aβ plaques.
Authors: Samal M; Centre of Excellence in Unani Medicine, Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India., Zahiruddin S; Centre of Excellence in Unani Medicine, Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India., Srivastava V; Centre of Excellence in Unani Medicine, Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India., Penumallu NR; Centre of Excellence in Unani Medicine, Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India., Parveen B; Centre of Excellence in Unani Medicine, Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India., Parveen R; Centre of Excellence in Unani Medicine, Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India., Ansari SH; Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India., Ahmad S; Centre of Excellence in Unani Medicine, Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India; Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India. Electronic address: sahmad_jh@yahoo.co.in.
Source: Journal of ethnopharmacology [J Ethnopharmacol] 2026 Oct 28; Vol. 369, pp. 121853. Date of Electronic Publication: 2026 May 12.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE
Imprint Name(s): Publication: Limerick : Elsevier Sequoia
Original Publication: Lausanne, Elsevier Sequoia.
MeSH Terms: Cholinesterase Inhibitors*/pharmacology , Memory Disorders*/drug therapy , Memory Disorders*/chemically induced , Neuroprotective Agents*/pharmacology , Neuroprotective Agents*/administration & dosage , Neuroinflammatory Diseases*/drug therapy , Plaque, Amyloid*/drug therapy , Learning Disabilities*/chemically induced , Learning Disabilities*/drug therapy , Plant Extracts*/pharmacology, Scopolamine/toxicity ; Oxidative Stress/drug effects ; Acetylcholinesterase/metabolism ; Maze Learning/drug effects ; Amyloid beta-Peptides/metabolism ; Anti-Inflammatory Agents/pharmacology ; Animals ; Rats, Wistar ; Male ; Rats
Abstract: Ethnopharmacological Relevance: Itrifal Muqawwi Dimagh (IMD) is a traditional polyherbal Unani formulation known to support cognitive function. While it is traditionally believed to have neuroprotective and memory enhancing effects, systematic scientific studies validating it's therapeutic efficacy and the underlying mechanism of action are still limited.
Aim of the Study: The objective of the study was to determine the neuroprotective potential of IMD against scopolamine induced learning and memory impairment.
Materials and Methods: The quality control studies include the simultaneous quantification of gallica acid, and ellagic acid using developed HPTLC method. The dose-dependent neuroprotective potential of IMD were investigated in scopolamine induced model in albino Wistar rats at three doses levels to assess dose-dependent effects (86 mg/kg, 172 mg/kg, and 344 mg/kg). Neurobehavioral parameters were assessed using Morris water maze test and spontaneous alternation behaviour. The biochemical estimation using acetylcholinesterase inhibition, amyloid beta (Aβ) estimation, oxidative stress, and anti-inflammatory markers were also carried out followed by histological and immunohistological analysis. Furthermore, in-vivo pattern recognition analysis of IMD metabolites in serum, was done to gain further insights.
Results: The present investigation represents the first report on IMD in scopolamine induced learning and memory impairment model and tentative metabolomic profiling. Treatment with IMD significantly reduced escape latency and transfer latency, and increased percentage dwell time as compared to the scopolamine group, in a dose-dependent manner. Treatment with medium (IMDM) and high (IMDH) doses of IMD, significantly attenuated the elevated biochemical parameters, restored the antioxidant level (SOD), and regulated the expression of proinflammatory cytokines (TNF α, and IL-6) in brain tissue showing comparable results to that of standard. The neuroprotective effects of IMD were supported by its ability to inhibit acetylcholinesterase activity and mitigate amyloid beta accumulation, comparable to that of standard. The in-vivo pattern recognition analysis of IMD, revealed presence of 27 metabolites, out of which 20 metabolites were identified and seven metabolites were unidentified at different time intervals.
Conclusion: IMD supported overall brain function through multiple mechanisms including anti-oxidant, anti-inflammatory, AChE inhibition and anti-amyloidogenic pathways. While the current study suggests a possible neuroprotective effect of IMD, additional studies are needed to substantiate these findings and determine their broader applicability.
(Copyright © 2026 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: AYUSH formulation; Acetylcholinesterase inhibition; Amyloid beta; IMD; Neuroinflammation; Oxidative stress; Scopolamine
Substance Nomenclature: DL48G20X8X (Scopolamine)
0 (Cholinesterase Inhibitors)
0 (Neuroprotective Agents)
EC 3.1.1.7 (Acetylcholinesterase)
0 (Amyloid beta-Peptides)
0 (Anti-Inflammatory Agents)
0 (Plant Extracts)
Entry Date(s): Date Created: 20260512 Date Completed: 20260613 Latest Revision: 20260613
Update Code: 20260615
DOI: 10.1016/j.jep.2026.121853
PMID: 42119864
Database: MEDLINE
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  Data: Ameliorative effect of AYUSH formulation against scopolamine induced learning and memory impairment in rat via attenuation of oxidative stress, neuroinflammation, acetylcholinesterase inhibition and Aβ plaques.
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  Data: <searchLink fieldCode="MM" term="%22Cholinesterase+Inhibitors%22">Cholinesterase Inhibitors*</searchLink>/<searchLink fieldCode="MM" term="%22Cholinesterase+Inhibitors+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory+Disorders%22">Memory Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+Disorders+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory+Disorders%22">Memory Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+Disorders+chemically+induced%22">chemically induced</searchLink> <br /><searchLink fieldCode="MM" term="%22Neuroprotective+Agents%22">Neuroprotective Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Neuroprotective+Agents+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Neuroprotective+Agents%22">Neuroprotective Agents*</searchLink>/<searchLink fieldCode="MM" term="%22Neuroprotective+Agents+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Neuroinflammatory+Diseases%22">Neuroinflammatory Diseases*</searchLink>/<searchLink fieldCode="MM" term="%22Neuroinflammatory+Diseases+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Plaque%2C+Amyloid%22">Plaque, Amyloid*</searchLink>/<searchLink fieldCode="MM" term="%22Plaque%2C+Amyloid+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Learning+Disabilities%22">Learning Disabilities*</searchLink>/<searchLink fieldCode="MM" term="%22Learning+Disabilities+chemically+induced%22">chemically induced</searchLink> <br /><searchLink fieldCode="MM" term="%22Learning+Disabilities%22">Learning Disabilities*</searchLink>/<searchLink fieldCode="MM" term="%22Learning+Disabilities+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Plant+Extracts%22">Plant Extracts*</searchLink>/<searchLink fieldCode="MM" term="%22Plant+Extracts+pharmacology%22">pharmacology</searchLink><br /><searchLink fieldCode="MH" term="%22Scopolamine%22">Scopolamine</searchLink>/<searchLink fieldCode="MH" term="%22Scopolamine+toxicity%22">toxicity</searchLink> ; <searchLink fieldCode="MH" term="%22Oxidative+Stress%22">Oxidative Stress</searchLink>/<searchLink fieldCode="MH" term="%22Oxidative+Stress+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Acetylcholinesterase%22">Acetylcholinesterase</searchLink>/<searchLink fieldCode="MH" term="%22Acetylcholinesterase+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Maze+Learning%22">Maze Learning</searchLink>/<searchLink fieldCode="MH" term="%22Maze+Learning+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Amyloid+beta-Peptides%22">Amyloid beta-Peptides</searchLink>/<searchLink fieldCode="MH" term="%22Amyloid+beta-Peptides+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Anti-Inflammatory+Agents%22">Anti-Inflammatory Agents</searchLink>/<searchLink fieldCode="MH" term="%22Anti-Inflammatory+Agents+pharmacology%22">pharmacology</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%2C+Wistar%22">Rats, Wistar</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%22">Rats</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Ethnopharmacological Relevance: Itrifal Muqawwi Dimagh (IMD) is a traditional polyherbal Unani formulation known to support cognitive function. While it is traditionally believed to have neuroprotective and memory enhancing effects, systematic scientific studies validating it's therapeutic efficacy and the underlying mechanism of action are still limited.<br />Aim of the Study: The objective of the study was to determine the neuroprotective potential of IMD against scopolamine induced learning and memory impairment.<br />Materials and Methods: The quality control studies include the simultaneous quantification of gallica acid, and ellagic acid using developed HPTLC method. The dose-dependent neuroprotective potential of IMD were investigated in scopolamine induced model in albino Wistar rats at three doses levels to assess dose-dependent effects (86 mg/kg, 172 mg/kg, and 344 mg/kg). Neurobehavioral parameters were assessed using Morris water maze test and spontaneous alternation behaviour. The biochemical estimation using acetylcholinesterase inhibition, amyloid beta (Aβ) estimation, oxidative stress, and anti-inflammatory markers were also carried out followed by histological and immunohistological analysis. Furthermore, in-vivo pattern recognition analysis of IMD metabolites in serum, was done to gain further insights.<br />Results: The present investigation represents the first report on IMD in scopolamine induced learning and memory impairment model and tentative metabolomic profiling. Treatment with IMD significantly reduced escape latency and transfer latency, and increased percentage dwell time as compared to the scopolamine group, in a dose-dependent manner. Treatment with medium (IMDM) and high (IMDH) doses of IMD, significantly attenuated the elevated biochemical parameters, restored the antioxidant level (SOD), and regulated the expression of proinflammatory cytokines (TNF α, and IL-6) in brain tissue showing comparable results to that of standard. The neuroprotective effects of IMD were supported by its ability to inhibit acetylcholinesterase activity and mitigate amyloid beta accumulation, comparable to that of standard. The in-vivo pattern recognition analysis of IMD, revealed presence of 27 metabolites, out of which 20 metabolites were identified and seven metabolites were unidentified at different time intervals.<br />Conclusion: IMD supported overall brain function through multiple mechanisms including anti-oxidant, anti-inflammatory, AChE inhibition and anti-amyloidogenic pathways. While the current study suggests a possible neuroprotective effect of IMD, additional studies are needed to substantiate these findings and determine their broader applicability.<br /> (Copyright © 2026 Elsevier B.V. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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  Label: Contributed Indexing
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  Data: <i>Keywords: </i>AYUSH formulation; Acetylcholinesterase inhibition; Amyloid beta; IMD; Neuroinflammation; Oxidative stress; Scopolamine
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  Data: DL48G20X8X (Scopolamine)<br />0 (Cholinesterase Inhibitors)<br />0 (Neuroprotective Agents)<br />EC 3.1.1.7 (Acetylcholinesterase)<br />0 (Amyloid beta-Peptides)<br />0 (Anti-Inflammatory Agents)<br />0 (Plant Extracts)
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        Text: English
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        StartPage: 121853
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      – TitleFull: Ameliorative effect of AYUSH formulation against scopolamine induced learning and memory impairment in rat via attenuation of oxidative stress, neuroinflammation, acetylcholinesterase inhibition and Aβ plaques.
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