{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:08:44Z","timestamp":1780304924038,"version":"3.54.0"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Essential tremor (ET) is a widespread neurological disorder with mild cerebellar degeneration that affects motor coordination, causing involuntary, rhythmic tremors during action. Excessive brain renin-angiotensin system activation favors pro-inflammatory milieu that is associated with neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The present study aimed to investigate the neuroprotective effects of Telmisartan (TELMI), an angiotensin receptor blocker, in a harmaline-induced model of essential tremor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male rats were assigned to three groups: control, harmaline (30\u00a0mg\/kg; i. p.) and a treatment group receiving TELMI (3\u00a0mg\/kg\/day; p. o.) administered 5\u00a0days before harmaline induction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TELMI reduced tremor severity and enhanced performance in the rotarod, wire grip strength, footprint test, open field test, and gait kinematics. Cerebellar molecular analysis revealed that TELMI significantly increased MAS receptor expression and angiotensin 1-7 levels, while concurrently downregulating angiotensin II type 1 and 2 receptors. The levels of ACE1\/ACE2 confirmed the favoring of the beneficial RAS arm. This modulation notably inhibited the activation of p38 MAPK and reduced pro-inflammatory cytokines, including TNF-alpha, IL-1-beta, IL-6, and chemokine receptor type 4. Neurotransmitter analysis showed restoration of the excitatory\/inhibitory balance between GABA and glutamate levels. Immunohistochemical analysis of Bergmann cells in the cerebellum demonstrated marked reductions in the proliferative marker; Ki67, and markers of glial and progenitor cell activity; S100\u03b2 and SOX2 expression, respectively, concurrently with, the suppression of the neural stem cell marker; nestin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that TELMI protects against cerebellar neurodegeneration in essential tremor by exerting anti-inflammatory, anti-excitotoxic, and receptor-modulatory effects through the Ang 1\u20137\/MAS receptor and p38 MAPK signaling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1810499","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:53:09Z","timestamp":1779785589000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective effects of telmisartan in a harmaline-induced model of essential tremor: modulation of the renin-angiotensin system and inflammatory pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Sama M.","family":"Farrag","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology (MUST)","place":["6th of October City, Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr M.","family":"Emam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology (MUST)","place":["6th of October City, Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed S.","family":"Kamel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy and Drug Technology, Egyptian Chinese University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed A.","family":"Saad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University","place":["Ajman, United Arab Emirates"]},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona A.","family":"Kortam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha H.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevine","family":"Fathy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1111\/BPH.13581","article-title":"Cannabinoid type 1 receptor antagonism ameliorates harmaline-induced essential tremor in rat","volume":"173","author":"Abbassian","year":"2016","journal-title":"Br. 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