Author(s): Sushil Giri, Phool Chandra

Email(s): susilgiri4@gmail.com

DOI: 10.52711/0974-360X.2026.00292   

Address: Sushil Giri*, Phool Chandra
Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad - 244001, Uttar Pradesh, India.
*Corresponding Author

Published In:   Volume - 19,      Issue - 5,     Year - 2026


ABSTRACT:
Background: Parkinson’s disease (PD) is a gradually worsening neurological disorder that primarily emerges in older adults. It is marked by the progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc), resulting in reduced striatal dopamine (DA) content. Flavonoids are becoming increasingly recognized as novel therapeutics in treating neurological illnesses due to their antioxidant and neuroprotective properties. Tricin, a bioactive flavonoid combined with alpha-tocopherol, is proposed to offer a promising therapeutic approach for PD. Objectives: This study focused on assessing the therapeutic potential of tricin and alpha-tocopherol in a rotenone (ROT) induced animal model of PD. Material and methods: ROT mediated PD model was used to test the neuroprotective activity of tricin and alpha-tocopherol. Behavioral activity, such as open field test, narrow beam walk, rota-rod, actophotometer, catalepsy bar test, grip strength test, footprint analysis, antioxidant activity, mitochondrial function and mounts of DA and its metabolic byproducts in rat SNpc, was used to ascertain the neuroprotective impact of these compounds. Results: Tricin, in combination with alpha-tocopherol, enhances efficacy compared to their single dosage forms and alleviates behavioral anomalies induced by ROT in experimental rats. Furthermore, it mitigated the dopaminergic toxicity caused by ROT in the animal's striatum and SNpc. Subcellularly protected the functionality and stability of mitochondria in the rats' SNpc from the deterioration caused by ROT. Further, investigations on the individual ingredients concerning their antioxidant activity, alpha-tocopherol showed the most antioxidant activity. The results suggest that tricin may exhibit neuroprotective effects against ROT-induced damage in rats, maybe through the Nrf2-mediated pathway. Consequently, tricin and alpha-tocopherol may be regarded as a feasible option for the treatment of PD. Conclusion: The in-vivo findings suggest that the combination of tricin and alpha-tocopherol may exert synergistic neuroprotective effects, presenting a potential new therapeutic approach for managing PD.


Cite this article:
Sushil Giri, Phool Chandra. Protective Effects of Tricin and Alpha-tocopherol on Behavioral Alterations and Dopaminergic Neuron Loss in Rotenone-Induced Neurotoxicity in Rats. Research Journal Pharmacy and Technology. 2026;19(5):2039-6. doi: 10.52711/0974-360X.2026.00292

Cite(Electronic):
Sushil Giri, Phool Chandra. Protective Effects of Tricin and Alpha-tocopherol on Behavioral Alterations and Dopaminergic Neuron Loss in Rotenone-Induced Neurotoxicity in Rats. Research Journal Pharmacy and Technology. 2026;19(5):2039-6. doi: 10.52711/0974-360X.2026.00292   Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2026-19-5-13


REFERENCES:
1.    Hayes MT. Parkinson’s Disease and Parkinsonism. Am J Med. 2019 Jul; 132(7): 802–7. 
2.    Giri S, Varshney KK, Srivastava R. Therapeutic Potential and Prospects of L-arginine in Various Diseases and its Clinical Intervention. Curr Drug ther. 2024 Aug; 19(5): 529–45. 
3.    Stoker TB, Barker RA. Recent developments in the treatment of Parkinson’s Disease. F1000Res. 2020 Jul 31; 9: 862. 
4.    Li XX, Chen SG, Yue GGL, Kwok HF, Lee JKM, Zheng T, et al. Natural flavone tricin exerted anti-inflammatory activity in macrophage via NF-κB pathway and ameliorated acute colitis in mice. Phytomedicine. 2021 Sep; 90: 153625. 
5.    Giri S, Chandra P. Therapeutic Potential of Natural Flavonoids: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective on Parkinson’s Disease. Curr Drug ther. 2024 Dec 17; 20(3): 315–31. 
6.    Qin S, Wan X, Kong S, Xu K, Jin J, He S, et al. Isorhamnetin ameliorates dopaminergic neuronal damage via targeting FOSL1 to activate AKT/mTOR in 6-OHDA-induced SH-SY5Y cells. J Neurophysiol. 2025 Jan 1; 133(1): 22–33. 
7.    Chen M, Peng L, Gong P, Zheng X, Sun T, Zhang X, et al. Baicalein Induces Mitochondrial Autophagy to Prevent Parkinson’s Disease in Rats via miR-30b and the SIRT1/AMPK/mTOR Pathway. Front Neurol. 2022 Feb 14; 12. 
8.    Bhusal CK, Uti DE, Mukherjee D, Alqahtani T, Alqahtani S, Bhattacharya A, et al. Unveiling Nature’s potential: Promising natural compounds in Parkinson’s disease management. Parkinsonism Relat Disord. 2023 Oct; 115: 105799. 
9.    Wang Y, Bai M, Wang X, Peng Z, Cai C, Xi J, et al. Gastrodin: a comprehensive pharmacological review. Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun 2; 397(6): 3781–802. 
10.    Sousa A, DiFrancisco-Donoghue J. Cannabidiol and Tetrahydrocannabinol Use in Parkinson’s Disease: An Observational Pilot Study. Cureus. 2023 Jul 24; 
11.    Feng J, Zheng Y, Guo M, Ares I, Martínez M, Lopez-Torres B, et al. Oxidative stress, the blood–brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants. Acta Pharm Sin B. 2023 Oct; 13(10): 3988–4024. 
12.    Chen M, Ghelfi M, Poon JF, Jeon N, Boccalon N, Rubsamen M, et al. Antioxidant-independent activities of alpha-tocopherol. Journal of Biological Chemistry [Internet]. 2025 Apr 1 [cited 2025 Jul 13]; 301(4): 108327. Available from: https://www.sciencedirect.com/ science/article/pii/S0021925825001760
13.    Heurtaux T, Bouvier DS, Benani A, Helgueta Romero S, Frauenknecht KBM, Mittelbronn M, et al. Normal and Pathological NRF2 Signalling in the Central Nervous System. Antioxidants. 2022 Jul 22; 11(8): 1426. 
14.    Ngo V, Duennwald ML. Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants. 2022 Nov 27; 11(12): 2345. 
15.    Swanson LW. Brain maps 4.0—Structure of the rat brain : An open access atlas with global nervous system nomenclature ontology and flatmaps. Journal of Comparative Neurology. 2018 Apr 15; 526(6): 935–43. 
16.    Wang X, Hu W, Qu L, Wang J, Wu A, Lo HH, et al. Tricin promoted ATG-7 dependent autophagic degradation of α-synuclein and dopamine release for improving cognitive and motor deficits in Parkinson’s disease. Pharmacol Res. 2023 Oct; 196: 106874. 
17.    Ikeda S, Tohyama T, Yoshimura H, Hamamura K, Abe K, Yamashita K. Dietary α-Tocopherol Decreases α-Tocotrienol but Not γ-Tocotrienol Concentration in Rats. J Nutr [Internet]. 2003 Feb 1 [cited 2025 Jul 14]; 133(2): 428–34. Available from: https:// www.sciencedirect.com/science/article/pii/S0022316622156191?utm_source=chatgpt.com
18.    Xu M, Bohlen JK, Moore C, Nipper MA, Finn DA, Jones CE, et al. Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism. J Neurosci Res. 2019 Dec 18; 97(12): 1706–19. 
19.    Pinosanu LR, Boboc IKS, Balseanu TA, Gresita A, Hermann DM, Popa‐Wagner A, et al. Beam narrowing test: a motor index of post-stroke motor evaluation in an aged rat model of cerebral ischemia. J Neural Transm. 2024 Jul 10; 131(7): 763–71. 
20.    Akshayraj Vanrajbhai C, Thorat VM, Patel VS, Patil KP, Chawla LL. Evaluation of Anxiolytic Activity of Angiotensin Receptor Blockers Using Actophotometer Test in Wistar Rats. Cureus. 2024 Sep 20; 
21.    Chang HT, Chang ML, Chen YT, Chang ST, Hsu FL, Wu CC, et al. Evaluation of Motor Coordination and Antidepressant Activities of Cinnamomum osmophloeum ct. Linalool Leaf Oil in Rodent Model. Molecules. 2021 May 19; 26(10): 3037. 
22.    Fujiwara M, Iwata M, Inoue T, Aizawa Y, Yoshito N, Hayashi K, et al. Decreased grip strength, muscle pain, and atrophy occur in rats following long‐term exposure to excessive repetitive motion. FEBS Open Bio. 2017 Nov 16; 7(11): 1737–49. 
23.    Samal J, Rebelo AL, Pandit A. A window into the brain: Tools to assess pre-clinical efficacy of biomaterials-based therapies on central nervous system disorders. Adv Drug Deliv Rev. 2019; 148: 68-145. 
24.    Horka P, Langova V, Hubeny J, Vales K, Chrtkova I, Horacek J. Open field test for the assessment of anxiety-like behavior in Gnathonemus petersii fish. Front Behav Neurosci. 2024 Jan 10; 17. 
25.    Slézia A, Hegedüs P, Rusina E, Lengyel K, Solari N, Kaszas A, et al. Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson’s disease. Sci Rep. 2023 Nov 9; 13(1): 19478. 
26.    Isvoranu G, Manole E, Neagu M. Gait Analysis Using Animal Models of Peripheral Nerve and Spinal Cord Injuries. Biomedicines. 2021 Aug 19; 9(8): 1050. 
27.    Samarghandian S, Azimi-Nezhad M, Borji A, Samini M, Farkhondeh T. Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats. BMC Complement Altern Med. 2017 Dec 4; 17(1): 249. 
28.    Peters AL, Veldthuis M, van Leeuwen K, Bossuyt PMM, Vlaar APJ, van Bruggen R, et al. Comparison of Spectrophotometry, Chromate Inhibition, and Cytofluorometry Versus Gene Sequencing for Detection of Heterozygously Glucose-6-Phosphate Dehydrogenase-Deficient Females. Journal of Histochemistry & Cytochemistry. 2017 Nov 13; 65(11): 627–36. 
29.    Deshpande K, Kulkarni M, Rajput D. Evaluation of glutathione peroxidase in the blood and tumor tissue of oral squamous cell carcinoma patients. Journal of Oral and Maxillofacial Pathology. 2018; 22(3): 447. 
30.    Jayanthi S, Ladenheim B, Sullivan P, McCoy MT, Krasnova IN, Goldstein DS, et al. Biochemical Neuroadaptations in the Rat Striatal Dopaminergic System after Prolonged Exposure to Methamphetamine Self-Administration. Int J Mol Sci. 2022 Sep 3; 23(17): 10092. 
31.    Mishra J, Bevers K, Li K, Zare A, Heisner JS, Tong A, et al. Differential Ca2+ handling by isolated synaptic and non-synaptic mitochondria: roles of Ca2+ buffering and efflux. Front Synaptic Neurosci. 2025 May 27;17. 
32.    Ansari F, Yoval-Sánchez B, Niatsetskaya Z, Sosunov S, Stepanova A, Garcia C, et al. Quantification of NADH:ubiquinone oxidoreductase (complex I) content in biological samples. Journal of Biological Chemistry. 2021 Oct; 297(4): 101204. 
33.    Tan YY, Jenner P, Chen SD. Monoamine Oxidase-B Inhibitors for the Treatment of Parkinson’s Disease: Past, Present, and Future. J Parkinsons Dis. 2022 Feb 15; 12(2): 477–93. 
34.    Masini D, Plewnia C, Bertho M, Scalbert N, Caggiano V, Fisone G. A Guide to the Generation of a 6-Hydroxydopamine Mouse Model of Parkinson’s Disease for the Study of Non-Motor Symptoms. Biomedicines. 2021 May 25; 9(6): 598. 
35.    Mat Taib CN, Mustapha M. MPTP-induced mouse model of Parkinson’s disease: A promising direction of therapeutic strategies. Bosn J Basic Med Sci. 2020 Dec 14; 
36.    Pariyar R, Bastola T, Lee DH, Seo J. Neuroprotective Effects of the DPP4 Inhibitor Vildagliptin in In Vivo and In Vitro Models of Parkinson’s Disease. Int J Mol Sci. 2022 Feb 21; 23(4): 2388.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.52711/0974-360X 

1.3
2021CiteScore
 
56th percentile
Powered by  Scopus


SCImago Journal & Country Rank

Journal Policies & Information


Recent Articles




Tags


Not Available