Alpha Pinene Affects Intestinal Permeability and Protects the Gastrointestinal System Against Rotenone Toxicity via the Keap1/Nrf2 Pathway in Rats

Allenspach M, Steuer C (2021) α-Pinene: A never-ending story. Phytochemistry 190:112857

CAS  PubMed  Google Scholar 

Betarbet R, Sherer T, MacKenzie G, Garcia-Osuna M, Panov AV, Timothy GJ (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306

CAS  PubMed  Google Scholar 

Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Gastric alpha-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 396(1):67–72

CAS  PubMed  Google Scholar 

Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT (2009) A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis 34(2):279–290

CAS  PubMed  PubMed Central  Google Scholar 

Cirrik S, Hacioglu G, Kabartan E, Tezcan Yavuz B, Sirin TC (2024) Can Alpha-pinene prevent methotrexate-induced cardiac and hepatic damage? Physiol Res 73(4):621–631

CAS  PubMed  PubMed Central  Google Scholar 

Dumitrescu L, Marta D, Dănău A, Lefter A, Tulbă D, Cozma L, Manole E, Gherghiceanu M, Ceafalan LC, Popescu BO (2021) Serum and fecal markers of intestinal inflammation and intestinal barrier permeability are elevated in Parkinson’s disease. Front Neurosci 15:689723

PubMed  PubMed Central  Google Scholar 

Erdoğan MA, Taşkıran D (2019) Effect of glucagon like peptide-1 analogue exenatide on neuron survival in rotenone-induced in vitro Parkinson’s disease model. Sdu Journal of Health Sciences 10:4

Google Scholar 

Fernando RA, Fennell TR, Watson SL, Silinski MAR, Blake JC, Robinson VG, Waidyanatha S (2022) Development and validation of an analytical method for quantitation of Alpha-pinene oxide in rodent blood and mammary glands by GC-MS. J Anal Toxicol 46(3):270–276

CAS  PubMed  Google Scholar 

Fu Y, Wu HQ, Cui HL, Li YY, Li CZ (2018) Gastroprotective and anti-ulcer effects of oxymatrine against several gastric ulcer models in rats: Possible roles of antioxidant, antiinflammatory, and prosurvival mechanisms. Phytother Res 32(10):2047–2058

CAS  PubMed  Google Scholar 

Gaballah HH, Zakaria SS, Elbatsh MM, Tahoon NM (2016) Modulatory effects of resveratrol on endoplasmic reticulum stress-associated apoptosis and oxido-inflammatory markers in a rat model of rotenone-induced Parkinson’s disease. Chem Biol Interact 251:10–16

CAS  PubMed  Google Scholar 

Goudarzi S, Rafieirad M (2017) Evaluating the effect of α-pinene on motor activity, avoidance memory and lipid peroxidation in animal model of Parkinson disease in adult male rats. Res J Pharmacogn 4(2):53–63

CAS  Google Scholar 

Hashemi P, Ahmadi S (2023) Alpha-pinene exerts antiseizure effects by preventing oxidative stress and apoptosis in the hippocampus in a rat model of temporal lobe epilepsy induced by kainate. Mol Neurobiol 60(6):3227–3238

CAS  PubMed  Google Scholar 

Heinz S, Freyberger A, Lawrenz B, Schladt L, Schmuck G, Ellinger-Ziegelbauer H (2017) Mechanistic Investigations of the Mitochondrial Complex I Inhibitor Rotenone in the Context of Pharmacological and Safety Evaluation. Sci Rep 7:45465

CAS  PubMed  PubMed Central  Google Scholar 

Johnson ME, Stringer A, Bobrovskaya L (2018) Rotenone induces gastrointestinal pathology and microbiota alterations in a rat model of Parkinson’s disease. Neurotoxicology 65:174–185

CAS  PubMed  Google Scholar 

Khan-Mohammadi-Khorrami MK, Asle-Rousta M, Rahnema M, Amini R (2022) Neuroprotective effect of alpha-pinene is mediated by suppression of the TNF-α/NF-κB pathway in Alzheimer’s disease rat model. J Biochem Mol Toxicol 36(5):e23006

CAS  PubMed  Google Scholar 

Khoshnazar M, Bigdeli MR, Parvardeh S, Pouriran R (2019) Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat. J Pharm Pharmacol 71(11):1725–1733

CAS  PubMed  Google Scholar 

Khoshnazar M, Parvardeh S, Bigdeli MR (2020) Alpha-pinene exerts neuroprotective effects via anti-inflammatory and anti-apoptotic mechanisms in a rat model of focal cerebral ischemia-reperfusion. J Stroke Cerebrovasc Dis 29(8):104977

PubMed  Google Scholar 

Levin JO, Eriksson K, Falk A, Löf A (1992) Renal elimination of verbenols in man following experimental alpha-pinene inhalation exposure. Int Arch Occup Environ Health 63(8):571–573

CAS  PubMed  Google Scholar 

Liu J, Li Y, Wu S, Zhang Z, Li D (2025) Hyperbaric oxygen upregulates Mst1 to activate Keap1/Nrf2/HO-1 pathway resisting oxidative stress in a rat model of acute myocardial infarction. Mol Biotechnol 67(1):284–293

CAS  PubMed  Google Scholar 

Michel HE, Tadros MM, Hendy MS, Mowaka S, Ayoub BM (2022) Omarigliptin attenuates rotenone-induced Parkinson’s disease in rats: possible role of oxidative stress, endoplasmic reticulum stress and immune modulation. Food Chem Toxicol 164:113015

CAS  PubMed  Google Scholar 

Nemutlu Samur D, Akçay G, Yıldırım S, Özkan A, Çeker T, Derin N, Tanrıöver G, Aslan M, Ağar A, Özbey G (2022) Vortioxetine ameliorates motor and cognitive impairments in the rotenone-induced Parkinson’s disease via targeting TLR-2 mediated neuroinflammation. Neuropharmacology 208:108977

CAS  PubMed  Google Scholar 

Pan-Montojo F, Schwarz M, Winkler C, Arnhold M, O’Sullivan GA, Pal A, Said J, Marsico G, Verbavatz JM, Rodrigo-Angulo M, Gille G, Funk RHW, Reichmann H (2012) Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep 2:898

PubMed  PubMed Central  Google Scholar 

Parkhe A, Parekh P, Nalla LV, Sharma N, Sharma M, Gadepalli A, Kate A, Khairnar A (2020) Protective effect of alpha mangostin on rotenone induced toxicity in rat model of Parkinson’s disease. Neurosci Lett 716:134652

CAS  PubMed  Google Scholar 

Porres-Martínez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP (2016) In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells. Z Naturforsch C J Biosci 71(7–8):191–199

PubMed  Google Scholar 

Qi Y, Liu G, Jin S, Jian R, Zou Z, Wang C, Zhang Y, Zhao M, Zhu H, Yan P (2024) Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway. BMC Complement Med Ther 24(1):175

CAS  PubMed  PubMed Central  Google Scholar 

Rahimi K, Shirvani N, Sanaie P, Javadi A, Khademi M (2023) The effects of alpha-pinene on the Nrf2-HO1 signaling pathway in gastric damage in rats. Mol Biol Rep 50(10):8615–8622

CAS  PubMed  Google Scholar 

Rahmani H, Moloudi MR, Hashemi P, Hassanzadeh K, Izadpanah E (2023) Alpha-pinene alleviates motor activity in animal model of Huntington’s disease via enhancing antioxidant capacity. Neurochem Res 48(6):1775–1782

CAS  PubMed  Google Scholar 

Sai Y, Chen J, Ye F, Zhao Y, Zou Z, Cao J, Dong Z (2013) Dopamine release suppression dependent on an increase of intracellular Ca(2+) contributed to rotenone-induced neurotoxicity in PC12 cells. J Toxicol Pathol 26(2):149–157

PubMed  PubMed Central  Google Scholar 

Salehi B, Upadhyay S, Erdogan Orhan I, Kumar Jugran A, L D Jayaweera S, A Dias D, Sharopov F, Taheri Y, Martins N, Baghalpour N, Cho WC, Sharifi-Rad J. 2019. ''Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature'', Biomolecules, 9(11):738.

Shabani M, Erfani S, Abdolmaleki A, Ephtekhar Afzali F, Khoshnazar SM (2023) Alpha-pinene modulates inflammatory response and protects against brain ischemia via inducible nitric oxide synthase-nuclear factor–kappa B-cyclooxygenase-2 pathway. Mol Biol Rep 50:6505–6516

CAS  PubMed  Google Scholar 

Srivastava R, Choudhury PK, Dev SK, Rathore V (2021) Neuroprotective effect of α-pinene self-emulsifying nanoformulation against 6-OHDA induced neurotoxicity on human SH-SY5Y cells and its in vivo validation for anti-Parkinson’s effect. J Biochem Mol Toxicol 35(11):e22902

CAS  PubMed  Google Scholar 

Srivastava R, Choudhury PK, Dev SK, Rathore V (2024) Alpha-pine self-emulsifying nano formulation attenuates rotenone and trichloroethylene-induced dopaminergic loss. Int J Neurosci 24:1–18

Google Scholar 

Stevens BR, Goel R, Seungbum K, Richards EM, Holbert RC, Pepine CJ, Raizada MK (2018) Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut 67(8):1555–1557

CAS  PubMed  Google Scholar 

Tasselli M, Chaumette T, Paillusson S, Monnet Y, Lafoux A, Huchet-Cadiou C, Aubert P, Hunot S, Derkinderen P, Neunlist M (2013) Effects of oral administration of rotenone on gastrointestinal functions in mice. Neurogastroenterol Motil 25(3):e183–e193

CAS  PubMed  Google Scholar 

Ulasov AV, Rosenkranz AA, Georgiev GP, Sobolev AS (2022) Nrf2/Keap1/ARE signaling: towards specific regulation. Life Sci 291:120111

CAS  PubMed  Google Scholar 

Waidyanatha S, Hackett M, Black SR, Stout MD, Fennell TR, Silinski MR, Watson SL, Licause J, Robinson VG, Sparrow B, Fernando RA, Cooper S, Rider CV (2021) Toxicokinetic evaluation of the common indoor air pollutant, α-pinene, and its potential reactive metabolite, α-pinene oxide, following inhalation exposure in rodents. Toxicol Appl Pharmacol 418:115496

CAS  PubMed  PubMed Central  Google Scholar 

Waidyanatha S, Black SR, Witt KL, Fennell TR, Swartz C, Recio L, Watson SL, Patel P, Fernando RA, Rider CV (2022) The common indoor air pollutant α-pinene is metabolised to a genotoxic metabolite α-pinene oxide. Xenobiotica 52(3):301–311

CAS  PubMed 

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