Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity
One of the primary therapeutic approaches for managing Alzheimer’s disease (AD) involves the modulation of Acetylcholine esterase (AChE) activity to elevate acetylcholine (ACh) levels inside the brain. The current study employed computational chemistry approaches to evaluate the inhibitory effects o...
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MDPI AG
2023-11-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/11/1133 |
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| author | Pavani K D S. N. B. K. Prasanth Murthy K. R. Shadakshara Sheikh F. Ahmad Ramanjaneyulu Seemaladinne Mithun Rudrapal Praveen Kumar Pasala |
| author_facet | Pavani K D S. N. B. K. Prasanth Murthy K. R. Shadakshara Sheikh F. Ahmad Ramanjaneyulu Seemaladinne Mithun Rudrapal Praveen Kumar Pasala |
| author_sort | Pavani K |
| collection | DOAJ |
| description | One of the primary therapeutic approaches for managing Alzheimer’s disease (AD) involves the modulation of Acetylcholine esterase (AChE) activity to elevate acetylcholine (ACh) levels inside the brain. The current study employed computational chemistry approaches to evaluate the inhibitory effects of CTN on AChE. The docking results showed that Citronellal (CTN) and standard Donepezil (DON) have a binding affinity of −6.5 and −9.2 Kcal/mol, respectively, towards AChE. Further studies using molecular dynamics (MD) simulations were carried out on these two compounds. Binding free energy calculations and ligand-protein binding patterns suggested that CTN has a binding affinity of −12.2078. In contrast, DON has a much stronger binding relationship of −47.9969, indicating that the standard DON has a much higher binding affinity than CTN for AChE. In an in vivo study, Alzheimer-type dementia was induced in mice by scopolamine (1.5 mg/kg/day i.p) for 14 days. CTN was administered (25 and 50 mg/kg. i.p) along with scopolamine (SCO) administration. DON (0.5 mg/kg orally) was used as a reference drug. CTN administration significantly improved the mice’s behavior as evaluated by the Morris water maze test, evident from decreased escape latency to 65.4%, and in the CPS test, apparent from reduced escape latency to 69.8% compared to the positive control mice. Moreover, CTN significantly increased the activities of antioxidant enzymes such as catalase and superoxide dismutase (SOD) compared to SCO. Furthermore, CTN administration significantly decreased SCO-induced elevated AChE levels in mice. These results were supported by histopathological and in silico molecular docking studies. CTN may be a potential antioxidant and neuroprotective supplement. |
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| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T16:37:15Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-79a14ea482134ea9aea83f6fdfc416822023-11-24T14:55:26ZengMDPI AGMetabolites2218-19892023-11-011311113310.3390/metabo13111133Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase ActivityPavani K0D S. N. B. K. Prasanth1Murthy K. R. Shadakshara2Sheikh F. Ahmad3Ramanjaneyulu Seemaladinne4Mithun Rudrapal5Praveen Kumar Pasala6Department of Pharmacology, Santhiram College of Pharmacy, Jawaharlal Nehru Technological University Anantapur, Nandyal 518112, Andhra Pradesh, IndiaDepartment of Pharmacognosy, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada 520010, Andhra Pradesh, IndiaDepartment of Chemical Engineering, Siddaganga Institute of Technology, Tumkur 572103, Karnataka, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Chemistry and Biochemistry, Lamar University Beaumont, Beaumont, TX 77705, USADepartment of Pharmaceutical Sciences, School of Biotechnology and Pharmaceutical Sciences, Vignan’s Foundation for Science, Technology & Research (Deemed to be University), Guntur 522213, Andhra Pradesh, IndiaDepartment of Pharmacology, Raghavendra Institute of Pharmaceutical Education and Research, JNTUA, Anantapuramu 515721, Andhra Pradesh, IndiaOne of the primary therapeutic approaches for managing Alzheimer’s disease (AD) involves the modulation of Acetylcholine esterase (AChE) activity to elevate acetylcholine (ACh) levels inside the brain. The current study employed computational chemistry approaches to evaluate the inhibitory effects of CTN on AChE. The docking results showed that Citronellal (CTN) and standard Donepezil (DON) have a binding affinity of −6.5 and −9.2 Kcal/mol, respectively, towards AChE. Further studies using molecular dynamics (MD) simulations were carried out on these two compounds. Binding free energy calculations and ligand-protein binding patterns suggested that CTN has a binding affinity of −12.2078. In contrast, DON has a much stronger binding relationship of −47.9969, indicating that the standard DON has a much higher binding affinity than CTN for AChE. In an in vivo study, Alzheimer-type dementia was induced in mice by scopolamine (1.5 mg/kg/day i.p) for 14 days. CTN was administered (25 and 50 mg/kg. i.p) along with scopolamine (SCO) administration. DON (0.5 mg/kg orally) was used as a reference drug. CTN administration significantly improved the mice’s behavior as evaluated by the Morris water maze test, evident from decreased escape latency to 65.4%, and in the CPS test, apparent from reduced escape latency to 69.8% compared to the positive control mice. Moreover, CTN significantly increased the activities of antioxidant enzymes such as catalase and superoxide dismutase (SOD) compared to SCO. Furthermore, CTN administration significantly decreased SCO-induced elevated AChE levels in mice. These results were supported by histopathological and in silico molecular docking studies. CTN may be a potential antioxidant and neuroprotective supplement.https://www.mdpi.com/2218-1989/13/11/1133Citronellal (CTN)acetylcholine esteraseAlzheimer’s disease (AD)molecular dynamicantioxidant activity |
| spellingShingle | Pavani K D S. N. B. K. Prasanth Murthy K. R. Shadakshara Sheikh F. Ahmad Ramanjaneyulu Seemaladinne Mithun Rudrapal Praveen Kumar Pasala Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity Metabolites Citronellal (CTN) acetylcholine esterase Alzheimer’s disease (AD) molecular dynamic antioxidant activity |
| title | Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity |
| title_full | Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity |
| title_fullStr | Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity |
| title_full_unstemmed | Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity |
| title_short | Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity |
| title_sort | citronellal as a promising candidate for alzheimer s disease treatment a comprehensive study on in silico and in vivo anti acetylcholine esterase activity |
| topic | Citronellal (CTN) acetylcholine esterase Alzheimer’s disease (AD) molecular dynamic antioxidant activity |
| url | https://www.mdpi.com/2218-1989/13/11/1133 |
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