{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:10:54Z","timestamp":1791544254689,"version":"4.3.4"},"reference-count":76,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional Animal Ethics Committee (IAEC)","award":["888\/PO\/Re\/S\/05\/CPCSEA"],"award-info":[{"award-number":["888\/PO\/Re\/S\/05\/CPCSEA"]}]},{"name":"Institutional Animal Ethics Committee (IAEC)","award":["RITS\/IAEC\/2014\/03\/06"],"award-info":[{"award-number":["RITS\/IAEC\/2014\/03\/06"]}]},{"name":"Institutional Animal Ethics Committee (IAEC)","award":["RSP2022R462"],"award-info":[{"award-number":["RSP2022R462"]}]},{"name":"RITS, Sirsa, Haryana, India","award":["888\/PO\/Re\/S\/05\/CPCSEA"],"award-info":[{"award-number":["888\/PO\/Re\/S\/05\/CPCSEA"]}]},{"name":"RITS, Sirsa, Haryana, India","award":["RITS\/IAEC\/2014\/03\/06"],"award-info":[{"award-number":["RITS\/IAEC\/2014\/03\/06"]}]},{"name":"RITS, Sirsa, Haryana, India","award":["RSP2022R462"],"award-info":[{"award-number":["RSP2022R462"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["888\/PO\/Re\/S\/05\/CPCSEA"],"award-info":[{"award-number":["888\/PO\/Re\/S\/05\/CPCSEA"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RITS\/IAEC\/2014\/03\/06"],"award-info":[{"award-number":["RITS\/IAEC\/2014\/03\/06"]}]},{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSP2022R462"],"award-info":[{"award-number":["RSP2022R462"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is characterised by dopaminergic neuronal loss in the brain area. PD is a complex disease that deteriorates patients\u2019 motor and non-motor functions. In experimental animals, the neurotoxin 6-OHDA induces neuropathological, behavioural, neurochemical and mitochondrial abnormalities and the formation of free radicals, which is related to Parkinson-like symptoms after inter-striatal 6-OHDA injection. Pathological manifestations of PD disrupt the cAMP\/ATP-mediated activity of the transcription factor CREB, resulting in Parkinson\u2019s-like symptoms. Forskolin (FSK) is a direct AC\/cAMP\/CREB activator isolated from Coleus forskohlii with various neuroprotective properties. FSK has already been proven in our laboratory to directly activate the enzyme adenylcyclase (AC) and reverse the neurodegeneration associated with the progression of Autism, Multiple Sclerosis, ALS, and Huntington\u2019s disease. Several behavioural paradigms were used to confirm the post-lesion effects, including the rotarod, open field, grip strength, narrow beam walk (NBW) and Morris water maze (MWM) tasks. Our results were supported by examining brain cellular, molecular, mitochondrial and histopathological alterations. The FSK treatment (15, 30 and 45 mg\/kg, orally) was found to be effective in restoring behavioural and neurochemical defects in a 6-OHDA-induced experimental rat model of PD. As a result, the current study successfully contributes to the investigation of FSK\u2019s neuroprotective role in PD prevention via the activation of the AC\/cAMP\/PKA-driven CREB pathway and the restoration of mitochondrial ETC-complex enzymes.<\/jats:p>","DOI":"10.3390\/molecules27227951","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T06:19:01Z","timestamp":1668665941000},"page":"7951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Effect of Natural Adenylcyclase\/cAMP\/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson\u2019s Rats: Preventing Mitochondrial, Motor and Histopathological Defects"],"prefix":"10.3390","volume":"27","author":[{"given":"Metab","family":"Alharbi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9888-9826","authenticated-orcid":false,"given":"Abdulrahman","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurpreet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Rajendra Institute of Technology and Sciences, Hisar Road, 4th Mile Stone, Sirsa, Haryana 125055, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Kalra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Rajendra Institute of Technology and Sciences, Hisar Road, 4th Mile Stone, Sirsa, Haryana 125055, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0034-835X","authenticated-orcid":false,"given":"Sidharth","family":"Mehan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Rajendra Institute of Technology and Sciences, Hisar Road, 4th Mile Stone, Sirsa, Haryana 125055, India"},{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Suri","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swesha","family":"Chhabra","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2761-004X","authenticated-orcid":false,"given":"Wael A.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7757-6732","authenticated-orcid":false,"given":"Aliah R.","family":"Alshanwani","sequence":"additional","affiliation":[{"name":"Physiology Department, College of Medicine & King Khalid University Hospital, King Saud University, Riyadh 12372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-8734","authenticated-orcid":false,"given":"Abdullah Hamed","family":"AL-Ghamdi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Care Department, Namerah General Hospital, Ministry of Health, Namerah 65439, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Acharan S.","family":"Narula","sequence":"additional","affiliation":[{"name":"Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7764-3640","authenticated-orcid":false,"given":"Reni","family":"Kalfin","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, 1113 Sofia, Bulgaria"},{"name":"Department of Healthcare, South-West University \u201cNeofitRilski\u201d, Ivan Mihailov St. 66, 2700 Blagoevgrad, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","first-page":"109","article-title":"The differential diagnosis of Parkinson\u2019s disease","volume":"21","author":"Greenland","year":"2018","journal-title":"Exon Publ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/978-94-007-5416-4_16","article-title":"Maguire-Zeiss","volume":"65","author":"Mhyre","year":"2012","journal-title":"Protein Aggreg. Fibrillogenesis Cereb. Syst. 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