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      <journal-id journal-id-type="publisher-id">advances-in-behavioral-neuroscience</journal-id>
      <journal-title-group>
        <journal-title>Advances in Behavioral Neuroscience</journal-title>
      </journal-title-group>
      <publisher>
        <publisher-name>Directive Publications</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.52338/aibn.2025.1002</article-id>
      <article-categories><subj-group subj-group-type="heading"><subject>Research</subject></subj-group></article-categories>
      <title-group>
        <article-title>Assessment of Sutherlandia frutescens Neuroprotective Potential in a Rotenone Induced Parkinsons Disease Rat Model</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Center</surname>
            <given-names>Kansas Cancer</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>City</surname>
            <given-names>Kansas</given-names>
          </name>
        </contrib>
      </contrib-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>19</day>
        <month>06</month>
        <year>2026</year>
      </pub-date>
      <permissions>
        <copyright-statement>© 2026 The Author(s). Published by Directive Publications.</copyright-statement>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0).</license-p>
        </license>
      </permissions>
      <abstract>
        <p>In South Africa, the herb Sutherlandia frutescens (SF) has long been used to treat a variety of illnesses, including neurological diseases. The loss of dopaminergic neurons in the substantia nigra is the hallmark of Parkinson’s disease (PD), a progressive neurodegenerative illness that causes motor symptoms. Both in vitro and in vivo investigations have connected the pesticide rotenone to symptoms similar to Parkinson’s disease. However, there hasn’t been much research done on how SF specifically affects PD symptoms. This study used an open-field test to evaluate motor behavior and in vivo electrical recordings from the hippocampus to examine the possible neuroprotective effects of SF against rotenone-induced Parkinson’s disease.Rats were split up into three groups: one that received sunflower oil as a control, one that received rotenone treatment, and one that received SF extract that was hydroponically cultivated. Motor behavior was assessed using an open-field test. Rats given SF showed noticeably more motor activity than rats given either sunflower oil or rotenone, indicating that SF has an activating effect on motor behavior. The rotenone group, on the other hand, showed decreased levels of activity and exploratory behavior, underscoring the drug’s inhibitory effect on motor function. According to these results, SF may provide neuroprotective benefits against rotenone-induced PD- like symptoms by modulating hippocampus neuronal activity. In an arotenone-induced Parkinson’s disease model, SF, a plant with traditional medicinal uses, exhibits promise in modifying motor behavior and hippocampus neuronal activity.</p>
      </abstract>
      <kwd-group kwd-group-type="author">
        <kwd>Sutherlandia Frutescen</kwd>
        <kwd>Open-Field Testing</kwd>
        <kwd>Parkinson’s Disease</kwd>
        <kwd>In Vivo Electrophysiology.</kwd>
      </kwd-group>
    </article-meta>
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      <p>Advances in Behavioral Neuroscience Assessment Of Sutherlandia Frutescens Neuro - protective Potential In A Rotenone-Induced Par- kinsons Disease Rat Model. *Corresponding Author: Lilit Darbinyan, University of Kansas Cancer Center, Kansas City, KS. Received: 05-Jan-2025, ; Editor Assigned: 06-Jan-2025 ; Reviewed: 20-Jan-2025, ; Published: 25-Jan-2025. Citation: Lilit Darbinyan. Assessment of Sutherlandia frutescens’ Neuroprotective Potential in a Rotenone-Induced Parkinson’s Disease Rat Model. Advances in Behavioral Neuroscience. 2025 January; 1(1). Copyright © 2025 Lilit Darbinyan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Research Article Lilit Darbinyan, Uaren Simonyan, Karisa Manukyan, Vaghinak Sarkisian, Lusya Hovhannisyan, Lilia Hambardzumyan. University of Kansas Cancer Center, Kansas City, KS. www.directivepublications.org Abstract In South Africa, the herb Sutherlandia frutescens (SF) has long been used to treat a variety of illnesses, including neurological diseases. The loss of dopaminergic neurons in the substantia nigra is the hallmark of Parkinson’s disease (PD), a progressive neurodegenerative illness that causes motor symptoms. Both in vitro and in vivo investigations have connected the pesticide rotenone to symptoms similar to Parkinson’s disease. However, there hasn’t been much research done on how SF specifically affects PD symptoms. This study used an open-field test to evaluate motor behavior and in vivo electrical recordings from the hippocampus to examine the possible neuroprotective effects of SF against rotenone-induced Parkinson’s disease.Rats were split up into three groups: one that received sunflower oil as a control, one that received rotenone treatment, and one that received SF extract that was hydroponically cultivated. Motor behavior was assessed using an open-field test. Rats given SF showed noticeably more motor activity than rats given either sunflower oil or rotenone, indicating that SF has an activating effect on motor behavior. The rotenone group, on the other hand, showed decreased levels of activity and exploratory behavior, underscoring the drug’s inhibitory effect on motor function. According to these results, SF may provide neuroprotective benefits against rotenone-induced PD- like symptoms by modulating hippocampus neuronal activity. In an arotenone-induced Parkinson’s disease model, SF, a plant with traditional medicinal uses, exhibits promise in modifying motor behavior and hippocampus neuronal activity. Keywords : Sutherlandia Frutescen, Open-Field Testing, Parkinson’s Disease, In Vivo Electrophysiology. INTRODUCTION Overview Sutherlandia frutescens (L.) (SF), also known as Lessertia frutescens in taxonomy, is a member of the Faba- ceae family of legumes. For ages, different ethnic groups in southern Africa have utilized it in traditional medicine to treat a variety of illnesses, such as urogenital, gastrointestial, and gynecological conditions. The review notes that no negative treatment results have been documented from its traditional use, which is noteworthy [1]. The anticancer capabilities of SF have been the subject of numerous studies. The antiproliferative effects of SF extracts on diabetic and cancer cells have been demonstrated in vitro [2, 3]. Although SF’s effectiveness as a cancer treatment has not been definitively demonstrated in human research, a few case reports indicate that it may help cancer patients feel less fatigued [4]. SF is one of the herbal medications used to treat NDDs, which include amyotrophic lateral sclerosis, Parkinson’s disease (PD), and Alzheimer’s diseammatory responses [8, 9]. Consuming SF was shown to reduce microglial activity in the striatum and hippocampal regions of animals with ischemic brains [10]. More clinical study is required to completely comprehend the safety and effectiveness of SF in treating a variety of illnesses, despite its lengthy history of traditional use and encouraging scientific findings. However, the evidence that is now available indicates that SF is a plant with significant therapeutic promise that merits more research. FINDINGS Findings In this work, the neuroprotective effects of SF were examined in a rat model of Parkinson’s disease caused by arotenone. The following are the measurement parameters: 1. Electrophysiological recordings In order to evaluate</p>
      <p>Directive Publications Lilit Darbinyan synaptic plasticity, extracellular hippocampal spike activity was measured following high-frequency stimulation (HFS) of the entorhinal cortex (EC). 2. OFT, or open-field test: Total distance traveled and line crossings were two behavioral tests used to gauge locomotor activity and inquisitive behavior. CONVERSATION Conversation Although no model accurately simulates the human state, animal models are crucial for Parkinson’s disease research. In animals, certain neurotoxins can cause symptoms similar to Parkinson’s disease, such as motor deficits and loss of dopaminergic neurons in the substantia nigra pars compacta [29]. Protease dysfunction, oxidative stress, and mitochondrial impairment are only a few of the intricate interactions between environmental and genetic factors that contribute to the pathophysiology of Parkinson’s disease. The neurodegenerative process of Parkinson’s disease (PD) has been linked to excessive ROS generation, which results in the death of dopaminergic neurons [30].A 33% incidence of TD neurons was seen in the CSF group in our study (Figure 2), indicating a reduction of synaptic transmission. Complex modulation of synaptic plasticity, possibly involving both depression and potentiation pathways, is indicated by the presence of TD-PTD at 22.95% and TD-PTP at 44.3%. A strong inhibition of synaptic activity was indicated by the significantly larger percentage of TD neurons (93%) in the sunflower oil- treated group (SO, Figure 3). Seven percent of the neurons are nonreactive, which indicates that they are not responding to the applied stimuli. The percentage of TD neurons decreased to 17.74% after rotenone (R) treatment (Figure 1), suggesting a partial reversal of the synaptic suppression seen in the SO group (Figure 3). In rats, rotenone, a common pesticide, selectively degenerates nigral dopamine neurons and produces symptoms similar to Parkinson’s disease [36]. Dopaminergic and nondo-paminergic neurons, as well as other brain cell types including astrocytes, are known to experience progressive neurodegeneration as a result. According to studies, rotenone can cause Parkinson’s disease pathology at brain concentrations of up to 30 nM [37]. Hippocampal atrophy may be a biomarker for cognitive deterioration in Parkinson’s disease, according to new research. Research has demonstrated that people with Parkinson’s disease (PD) have changed hippocampal functional connectivity, including reduced connectivity with areas like the paracingulate gyrus [38]. CONCLUSIONS Although the effectiveness of existing treatments in neurotoxin-induced animal models of Parkinson’s disease (PD) is limited, there is hope that behavioral phenotyping in these animals will open the door to future treatments that are more effective. Our findings point to hydroponic SF’s potential as a therapeutic agent for neurological conditions by indicating that it may modulate hippocampus activity through GABAergic systems. To fully investigate the therapeutic potential of hydroponic SF in the context of Parkinson’s disease and other neurological diseases, as well as to clarify the precise pathways involved, more research is necessary. RESOURCES AND PROCEDURES Declarations of Ethics. The Ethics Committee of Yerevan State Medical University in Yerevan, Armenia, approved all animal studies, which were carried out in accordance with the guidelines set forth in the National Institutes of Health’s (NIH) Guide for the Care and Use of Laboratory Animals (ethicalapproval number: N4 IRB). During the trial phase, every attempt was made to minimize the suffering of the animals.1. Group CSF (control + Sutherlandia): For three weeks, commencing on day 1, the rats in this group were given hydroponically administered Sutherlandia (82.6 mg/ kg/day, oral administration) on alternate days. 2. Group R (rotenone): For five weeks, rats were given rotenone dissolved in sunflower oil at a dose of 2.0 mg/kg/day, subcutaneously. Group SO (sunflower oil): For five weeks, rats were given the vehicle (sunflower oil, 1 mL/kg/day, intramuscularly) every day. 4. Rotenone + Sutherlandia Group RSF: For five weeks, rats in this group were given rotenone (2 mg/kg/day, subcutaneously), and then they were given hydroponically administered Sutherlandia (82.6 mg/kg/day, oral administration) for three weeks. REFERENCES 1. C. von Wrangel, K. Schwabe, N. John, J. K. Krauss, andM. Alam, “The rotenone-induced rat model of Parkinson’s dis-ease: behavioral and electrophysiological ﬁndings,” Behav-ioural Brain Research, vol. 279, pp. 52–61, 2015. 2. C. Sia, “Spotlight on ethnomedicine: usability of Sutherlandiafrutescens in the treatment of diabetes,” The Review of DiabeticStudies, vol. 1, no. 3, pp. 145–149, 2004. 3. W. A. Chadwick, S. Roux, M. van de Venter, J. Louw, andW. Oelofsen, “Anti-diabetic eﬀects of Sutherlandia frutescensin Wistar rats fed a diabetogenic diet,” Journal of Ethnophar-macology, vol. 109, no. 1, pp. 121–127, 2007.Figure 6: Hydroponic Sutherlandia: a practical method for growing Sutherlandia hydroponically.8 Behavioural Neurology Page - 2Open Access, Volume 1 , 2025</p>
      <p>Lilit Darbinyan Directive Publications 4. N. B. Skerman, A. M. Joubert, and M. J. Cronjé, “The apoptosisinducing eﬀects of Sutherlandia spp. extracts on an oesopha-geal cancer cell line,” Journal of Ethnopharmacology, vol. 137,no. 3, pp. 1250–1260, 2011. 5. S. Shaik, N. Singh, and A. Nicholas, “Comparison of theselected secondary metabolite content present in the cancer-bush Lessertia (Sutherlandia) frutescens L. extracts,” AfricanJournal of Traditional, Complementary, and Alternative Medi-cines, vol. 8, no. 4, pp. 429–434, 2011. 6. J. Jiang, D. Y. Chuang, Y. Zong et al., “Sutherlandia frutescensethanol extracts inhibit oxidative stress and inﬂammatoryresponses in neurons and microglial cells,” PLoS One, vol. 9,no. 2, Article ID e89748, 2014. 7. M. Shariﬁ-Rad, C. Lankatillake, D. A. Dias et al., “Impact ofnatural compounds on neurodegenerative disorders: from pre-clinical to pharmacotherapeutics,” Journal of Clinical Medi-cine, vol. 9, no. 4, p. 1061, 2020. 8. W. Lei, J. D. Browning Jr., P. A. Eichen et al., “Unveiling theanti-inﬂammatory activity of Sutherlandia frutescens usingmurine macrophages,” International Immunopharmacology,vol. 29, no. 2, pp. 254–262, 2015. 9. D. Y. Chuang, J. Cui, A. Simonyi et al., “Dietary Sutherlandiaand elderberry mitigate cerebral ischemia- induced neuronaldamage and attenuate p47phox and phospho-ERK1/2 expres-sion in microglial cells,” ASN Neuro, vol. 6, no. 6, Article ID1759091414554946, 2014. 10. W. R. Folk, A. Smith, H. Song et al., “Does concurrent useof some botanicals interfere with treatment of tuberculo-sis?,” Neuromolecular Medicine, vol. 18, no. 3, pp. 483–486, 2016.[11] C. Coleman and I. Martin, “Unraveling Parkinson’s diseaseneurodegeneration: does aging hold the clues?,” Journal of Par-kinson’s Disease, vol. 12, no. 8, pp. 2321–2338, 2022. 11. R. Chen, A. Berardelli, A. Bhattacharya et al., “Clinical neuro-physiology of Parkinson’s disease and parkinsonism,” ClinicalNeurophysiology Practice, vol. 7, pp. 201–227, 2022. 12. A. D. Van Laar, K. R. Webb, M. T. Keeney et al., “Transientexposure to rotenone causes degeneration and progressiveparkinsonian motor deﬁcits, neuroinﬂammation, and synu-cleinopathy,” NPJ Parkinson’s Disease, vol. 9, no. 1, p. 121,2023. 13. K. A. Jellinger, “Pathobiology of cognitive impairment in par-kinson disease: challenges and outlooks,” International Journalof Molecular Sciences, vol. 25, no. 1, p. 498, 2024. 14. R. Camicioli, M. M. Moore, A. Kinney, E. Corbridge,K. Glassberg, and J. A. Kaye, “Parkinson’s disease is associatedwith hippocampal atrophy,” Movement Disorders, vol. 18,no. 7, pp. 784–790, 2003. 15. S. Villar-Conde, V. Astillero-Lopez, M. Gonzalez- Rodriguezet al., “The human hippocampus in Parkinson’s disease: anintegrative stereological and proteomic study,” Journal of Par-kinson’s Disease, vol. 11, no. 3, pp. 1345–1365, 2021. 16. L. E. Llewelyn, M. Kornisch, H. Park, and T. Ikuta, “Hippo- campal functional connectivity in Parkinson’s disease,” Neuro-degenerative Diseases, vol. 22, no. 1, pp. 29–33, 2022.[18] M. Kumaresan and S. Khan, “Spectrum of non- motor symp-toms in Parkinson’s disease,” Cureus, vol. 13, no. 2, ArticleID e13275, 2021. 17. N. Titova and K. R. Chaudhuri, “Non-motor Parkinson dis-ease: new concepts and personalised management,” The Med-ical Journal of Australia, vol. 208, no. 9, pp. 404–409, 2018. 18. L. V. Kalia and A. E. Lang, “Parkinson’s disease,” Lancet,vol. 386, no. 9996, pp. 896–912, 2015. 19. K. Radad, R. Moldzio, C. Krewenka, B. Kranner, and W. D.Rausch, “Pathophysiology of non-motor signs in Parkin-son’s disease: some recent updating with brief presentation,”Exploration of Neuroprotective Therapy, vol. 3, pp. 24–46,2023. Page - 3Open Access, Volume 1, 2025</p>
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