Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease
Alzheimer's disease (AD) is a progressive condition marked by multiple underlying mechanisms. Therefore, the investigation of natural products that can target multiple pathways presents a potential gate for the understanding and management of AD. This study aimed to assess the neuroprotective e...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025007923 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832557520665706496 |
|---|---|
| author | Marjan Talebi Seyed Abdulmajid Ayatollahi Mohammad Ali As’Habi Farzad Kobarfard Mona Khoramjouy Farzaneh Niki Boroujeni Mehrdad Faizi Alireza Ghassempour |
| author_facet | Marjan Talebi Seyed Abdulmajid Ayatollahi Mohammad Ali As’Habi Farzad Kobarfard Mona Khoramjouy Farzaneh Niki Boroujeni Mehrdad Faizi Alireza Ghassempour |
| author_sort | Marjan Talebi |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is a progressive condition marked by multiple underlying mechanisms. Therefore, the investigation of natural products that can target multiple pathways presents a potential gate for the understanding and management of AD. This study aimed to assess the neuroprotective effects of the hydroalcoholic extract of Dracocephalum moldavica (DM) on cognitive impairment, biomarker changes, and putative metabolic pathways in a rat model of AD induced by intracerebroventricular streptozotocin (ICV-STZ). The DM extract was standardized and quantified based on examining total phenolic, total flavonoid, rosmarinic acid, and quercetin contents using colorimetry and high-performance liquid chromatography (HPLC) methods. The antioxidant potential of the extract was evaluated by 2,2-Diphenyl-1-picrylhydrazyl and nitric oxide radical scavenging assays. Male Wistar rats were injected with STZ (3 mg/kg, single dose, bilateral ICV) to induce a sporadic AD (sAD) model. Following model induction, rats were orally administered with DM extract (100, 200, and 400 mg/kg/day) or donepezil (5 mg/kg/day) for 21 days. Cognitive function was assessed using the radial arm water maze behavioral test. The histopathological evaluations were conducted in the cortex and hippocampus regions. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to assess metabolite changes in various brain regions. DM extract significantly attenuated cognitive dysfunction induced by ICV-STZ according to behavioral and histopathological investigations. Thirty-two discriminating metabolites related to the amino acid metabolism; the glutamate/gamma-aminobutyric acid/glutamine cycle; nucleotide metabolism; lipid metabolism (glycerophospholipids, sphingomyelins, ceramides, phosphatidylserines, and prostaglandins), and glucose metabolic pathways were identified in the brains of rats with sAD simultaneously for the first time in this model. Polyphenols in DM extract may contribute to the regulation of these pathways. After treatment with DM extract, 10 metabolites from the 32 identified ones were altered in the brain tissue of a rat model of sAD, most commonly at doses of 200 and 400 mg/kg. In conclusion, this study demonstrates the neuroprotective potential of DM by upregulation/downregulation of various pathophysiological biomarkers such as adenine, glycerophosphoglycerol, inosine, prostaglandins, and sphingomyelin induced by ICV-STZ in sAD. These findings are consistent with cognitive behavioral results and histopathological outcomes. |
| format | Article |
| id | doaj-art-7295ec24e20145918de024861387a201 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-7295ec24e20145918de024861387a2012025-02-03T04:16:49ZengElsevierHeliyon2405-84402025-02-01113e42412Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's diseaseMarjan Talebi0Seyed Abdulmajid Ayatollahi1Mohammad Ali As’Habi2Farzad Kobarfard3Mona Khoramjouy4Farzaneh Niki Boroujeni5Mehrdad Faizi6Alireza Ghassempour7Student Research Committee, Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranPhytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranMedicinal Plants and Drugs Research Institute, Shahid Beheshti University, G.C., Evin, Tehran, IranPhytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, IranPhytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Pathology, Sina Hospital, Tehran University of Medical Sciences, Tehran, IranDepartment of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Corresponding author. Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G.C., Evin, Tehran, Iran; Corresponding author. Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, 1983963113, Iran.Alzheimer's disease (AD) is a progressive condition marked by multiple underlying mechanisms. Therefore, the investigation of natural products that can target multiple pathways presents a potential gate for the understanding and management of AD. This study aimed to assess the neuroprotective effects of the hydroalcoholic extract of Dracocephalum moldavica (DM) on cognitive impairment, biomarker changes, and putative metabolic pathways in a rat model of AD induced by intracerebroventricular streptozotocin (ICV-STZ). The DM extract was standardized and quantified based on examining total phenolic, total flavonoid, rosmarinic acid, and quercetin contents using colorimetry and high-performance liquid chromatography (HPLC) methods. The antioxidant potential of the extract was evaluated by 2,2-Diphenyl-1-picrylhydrazyl and nitric oxide radical scavenging assays. Male Wistar rats were injected with STZ (3 mg/kg, single dose, bilateral ICV) to induce a sporadic AD (sAD) model. Following model induction, rats were orally administered with DM extract (100, 200, and 400 mg/kg/day) or donepezil (5 mg/kg/day) for 21 days. Cognitive function was assessed using the radial arm water maze behavioral test. The histopathological evaluations were conducted in the cortex and hippocampus regions. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to assess metabolite changes in various brain regions. DM extract significantly attenuated cognitive dysfunction induced by ICV-STZ according to behavioral and histopathological investigations. Thirty-two discriminating metabolites related to the amino acid metabolism; the glutamate/gamma-aminobutyric acid/glutamine cycle; nucleotide metabolism; lipid metabolism (glycerophospholipids, sphingomyelins, ceramides, phosphatidylserines, and prostaglandins), and glucose metabolic pathways were identified in the brains of rats with sAD simultaneously for the first time in this model. Polyphenols in DM extract may contribute to the regulation of these pathways. After treatment with DM extract, 10 metabolites from the 32 identified ones were altered in the brain tissue of a rat model of sAD, most commonly at doses of 200 and 400 mg/kg. In conclusion, this study demonstrates the neuroprotective potential of DM by upregulation/downregulation of various pathophysiological biomarkers such as adenine, glycerophosphoglycerol, inosine, prostaglandins, and sphingomyelin induced by ICV-STZ in sAD. These findings are consistent with cognitive behavioral results and histopathological outcomes.http://www.sciencedirect.com/science/article/pii/S2405844025007923Sporadic Alzheimer's diseaseChemoconnectomicsDracocephalum moldavicaMALDI-TOF MSMetabolomicsStreptozotocin |
| spellingShingle | Marjan Talebi Seyed Abdulmajid Ayatollahi Mohammad Ali As’Habi Farzad Kobarfard Mona Khoramjouy Farzaneh Niki Boroujeni Mehrdad Faizi Alireza Ghassempour Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease Heliyon Sporadic Alzheimer's disease Chemoconnectomics Dracocephalum moldavica MALDI-TOF MS Metabolomics Streptozotocin |
| title | Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease |
| title_full | Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease |
| title_fullStr | Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease |
| title_full_unstemmed | Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease |
| title_short | Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease |
| title_sort | investigating the neuroprotective effects of dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic alzheimer s disease |
| topic | Sporadic Alzheimer's disease Chemoconnectomics Dracocephalum moldavica MALDI-TOF MS Metabolomics Streptozotocin |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025007923 |
| work_keys_str_mv | AT marjantalebi investigatingtheneuroprotectiveeffectsofdracocephalummoldavicaextractanditseffectonmetabolomicprofileofratmodelofsporadicalzheimersdisease AT seyedabdulmajidayatollahi investigatingtheneuroprotectiveeffectsofdracocephalummoldavicaextractanditseffectonmetabolomicprofileofratmodelofsporadicalzheimersdisease AT mohammadaliashabi investigatingtheneuroprotectiveeffectsofdracocephalummoldavicaextractanditseffectonmetabolomicprofileofratmodelofsporadicalzheimersdisease AT farzadkobarfard investigatingtheneuroprotectiveeffectsofdracocephalummoldavicaextractanditseffectonmetabolomicprofileofratmodelofsporadicalzheimersdisease AT monakhoramjouy investigatingtheneuroprotectiveeffectsofdracocephalummoldavicaextractanditseffectonmetabolomicprofileofratmodelofsporadicalzheimersdisease AT farzanehnikiboroujeni investigatingtheneuroprotectiveeffectsofdracocephalummoldavicaextractanditseffectonmetabolomicprofileofratmodelofsporadicalzheimersdisease AT mehrdadfaizi investigatingtheneuroprotectiveeffectsofdracocephalummoldavicaextractanditseffectonmetabolomicprofileofratmodelofsporadicalzheimersdisease AT alirezaghassempour investigatingtheneuroprotectiveeffectsofdracocephalummoldavicaextractanditseffectonmetabolomicprofileofratmodelofsporadicalzheimersdisease |