Phylogenetic Relationship of Plastid Large Single Copy Genome and Potential of Ginsenoside Compounds from Panax notoginseng in Alzheimer Disease
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Jun 30, 2025
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Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most prevalent cause of dementia, marked by cognitive decline and memory loss. Current treatments are largely symptomatic and do not halt disease progression, underscoring the urgent need for novel therapeutics. Natural products, such as Panax notoginseng, offer promising alternatives due to their structural diversity and multi-target potential. This study investigates the therapeutic potential of 125 terpenoid compounds identified from P. notoginseng, focusing on their relevance to AD. Eight ginsenosides demonstrated notable neuroprotective effects, including improvements in memory and cognitive function. Among them, Ginsenoside Rb1 and Notoginsenoside R1 exhibited low predicted toxicity via oral and intraperitoneal routes, indicating favorable safety profiles. Target prediction and molecular docking suggest these compounds interact with G protein-coupled receptors implicated in cognition and neuroprotection, such as dopaminergic, serotonergic, muscarinic, and adrenergic receptors. However, their deviation from Lipinski’s Rule of Five may limit oral bioavailability. To address this, nanotechnology-based delivery systems are proposed to enhance solubility, permeability, and drug-likeness. These findings support the continued exploration of P. notoginseng ginsenosides as potential anti-dementia agents and highlight nanotechnology's role in overcoming pharmacokinetic limitations
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References
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[36]. Dobrovolskaia, M. A. (2015). Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy. Journal of Controlled Release, 220, 571-583.
[37]. Rodríguez-Gómez, F. D., Penon, O., Monferrer, D., & Rivera-Gil, P. (2023). Classification system for nanotechnology-enabled health products with both scientific and regulatory application. Frontiers in Medicine, 10, 1212949.
[2]. Zhu, T., & Wan, Q. (2023). Pharmacological properties and mechanisms of Notoginsenoside R1 in ischemia-reperfusion injury. Chinese Journal of Traumatology, 26(1), 20-26.
[3]. Alzheimer's Association. (2016). 2016 Alzheimer's disease facts and figures. Alzheimer's & Dementia, 12(4), 459-509.
[4]. Wu, J. J., Yang, Y., Wan, Y., Xia, J., Xu, J. F., Zhang, L., ... & Peng, C. (2022). New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer’s disease. Biomedicine & pharmacotherapy, 152, 113207.
[5]. Ye, X., Zhang, H., Li, Q., Ren, H., Xu, X., & Li, X. (2023). Structural-activity relationship of rare ginsenosides from red ginseng in the treatment of Alzheimer’s disease. International Journal of Molecular Sciences, 24(10), 8625.
[6]. Razgonova, M. P., Veselov, V. V., Zakharenko, A. M., Golokhvast, K. S., Nosyrev, A. E., Cravotto, G., ... & Spandidos, D. A. (2019). Panax ginseng components and the pathogenesis of Alzheimer's disease. Molecular Medicine Reports, 19(4), 2975-2998.
[7]. He, S., Shi, J., Chai, H., Ma, L., Pei, H., Zhang, P., ... & Li, H. (2024). Mechanisms with network pharmacology approach of Ginsenosides in Alzheimer's disease. Heliyon, 10(5).
[8]. Burnim, A. A., Spence, M. A., Xu, D., Jackson, C. J., & Ando, N. (2022). Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade. Elife, 11, e79790.
[9]. Kusch, S., Pesch, L., & Panstruga, R. (2016). Comprehensive phylogenetic analysis sheds light on the diversity and origin of the MLO family of integral membrane proteins. Genome Biology and Evolution, 8(3), 878-895.
[10]. Fang, X., Zhou, X., Wang, Y., Zhang, W., Wu, H., Xu, L., ... & Xiao, H. (2024). Determining the genetic basis of ginsenosides variation during ginseng domestication by evolutionary transcriptomics. Industrial Crops and Products, 212, 118369.
[11]. Akrami, A. M., Meratian Esfahani, S., & Soorni, A. (2025). Decoding the chloroplast genomes of five Iranian Salvia species: insights into genomic structure, phylogenetic relationships, and molecular marker development. BMC genomics, 26(1), 1-16.
[12]. Li, L., Jiang, Y., Liu, Y., Niu, Z., Xue, Q., Liu, W., & Ding, X. (2020). The large single-copy (LSC) region functions as a highly effective and efficient molecular marker for accurate authentication of medicinal Dendrobium species. Acta Pharmaceutica Sinica B, 10(10), 1989-2001.
[13]. Saddhe, A. A., & Kumar, K. (2018). DNA barcoding of plants: selection of core markers for taxonomic groups. Plant Science Today, 5(1), 9-13.
[14]. Ahmed, S., Ibrahim, M., Nantasenamat, C., Nisar, M. F., Malik, A. A., Waheed, R., ... & Alam, M. K. (2022). Pragmatic applications and universality of DNA barcoding for substantial organisms at species level: a review to explore a way forward. BioMed Research International, 2022(1), 1846485.
[15]. Leaks, K., El, A., Alsaidi, Z., Benton, K., Chase, J., Lewis, S., & Kassem, M. A. (2025). Comparative Phylogenetic Analysis of Six Angiosperm Families Using rbcL and matK Chloroplast Markers. Journal of Artificial Intelligence, Machine Learning, and Bioinformatics, 29-39.
[16]. El-Sherif, N., & Ibrahim, M. (2020). Implications of rbcL and rpoC1 DNA barcoding in phylogenetic relationships of some Egyptian I L. cultivars. Egyptian Journal of Botany, 60(2), 451-460.
[17]. Skuza, L., Szućko, I., Filip, E., & Adamczyk, A. (2019). DNA barcoding in selected species and subspecies of Rye (Secale) using three chloroplast loci (matK, rbcL, trnH-psbA). Notulae Botanicae Horti Agrobotanici Cluj-Napoca, 47(1), 54-62.
[18]. Xia, P., Huang, Y., & Zhu, J. (2025). The complete chloroplast genome sequences of 11 Panax species: Providing insights for evolution and species identification. Industrial Crops and Products, 223, 120160.
[19]. Osathanunkul, M., Suwannapoom, C., Osathanunkul, K., Madesis, P., & De Boer, H. (2016). Evaluation of DNA barcoding coupled high resolution melting for discrimination of closely related species in phytopharmaceuticals. Phytomedicine, 23(2), 156-165.
[20]. Yang, H., Ni, Y., Zhang, X., Li, J., Chen, H., & Liu, C. (2023). The mitochondrial genomes of Panax notoginseng reveal recombination mediated by repeats associated with DNA replication. International Journal of Biological Macromolecules, 252, 126359.
[21]. Nguyen, V. B., Park, H. S., Lee, S. C., Lee, J., Park, J. Y., & Yang, T. J. (2017). Authentication markers for five major Panax species developed via comparative analysis of complete chloroplast genome sequences. Journal of agricultural and food chemistry, 65(30), 6298-6306.
[22]. Chen, W., Balan, P., & Popovich, D. G. (2020). Comparison of ginsenoside components of various tissues of New Zealand forest-grown Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolium L.). Biomolecules, 10(3), 372.
[23]. Kim, K., Nguyen, V. B., Dong, J., Wang, Y., Park, J. Y., Lee, S. C., & Yang, T. J. (2017). Evolution of the Araliaceae family inferred from complete chloroplast genomes and 45S nrDNAs of 10 Panax-related species. Scientific reports, 7(1), 4917.
[24]. van der Koog, L., Gandek, T. B., & Nagelkerke, A. (2022). Liposomes and extracellular vesicles as drug delivery systems: a comparison of composition, pharmacokinetics, and functionalization. Advanced healthcare materials, 11(5), 2100639.
[25]. Alvarez, B. D., Cavazos, C., Morales, C. A., M. Lopez, S., & Amodeo, D. A. (2022). Impact of specific serotonin receptor modulation on restricted repetitive behaviors. Frontiers in behavioral neuroscience, 16, 1078983.
[26]. Zhang, G., & Stackman Jr, R. W. (2015). The role of serotonin 5-HT2A receptors in memory and cognition. Frontiers in pharmacology, 6, 225.
[27]. Dwomoh, L., Tejeda, G. S., & Tobin, A. B. (2022). Targeting the M1 muscarinic acetylcholine receptor in Alzheimer’s disease. Neuronal Signaling, 6(1), NS20210004.
[28]. Miliotou, A. N., Kotsoni, A., & Zacharia, L. C. (2025). Deciphering the Role of Adrenergic Receptors in Alzheimer’s Disease: Paving the Way for Innovative Therapies. Biomolecules, 15(1), 128.
[29]. Tan, Y., Chen-Chen, S., Zi-Hui, X., He, F., Ya-Li, Z., Ya-Lei, W., ... & Tong-Hua, L. (2020). The neuroprotective role of Panax notoginseng saponins in APP/PS1 transgenic mice through the modulation of cerebrovascular. Traditional Medicine Research, 5(5), 355.
[30]. Spencer, A. P., Torrado, M., Custódio, B., Silva-Reis, S. C., Santos, S. D., Leiro, V., & Pêgo, A. P. (2020). Breaking barriers: bioinspired strategies for targeted neuronal delivery to the central nervous system. Pharmaceutics, 12(2), 192.
[31]. Umar, M., Rehman, Y., Ambreen, S., Mumtaz, S. M., Shaququzzaman, M., Alam, M. M., & Ali, R. (2024). Innovative Approaches to Alzheimer's Therapy: Harnessing the Power of Heterocycles, Oxidative Stress Management, and Nanomaterial Drug Delivery System. Ageing Research Reviews, 102298.
[32]. Pinto, M., Silva, V., Barreiro, S., Silva, R., Remião, F., Borges, F., & Fernandes, C. (2022). Brain drug delivery and neurodegenerative diseases: Polymeric PLGA-based nanoparticles as a forefront platform. Ageing Research Reviews, 79, 101658.
[33]. Gajbhiye, K. R., Pawar, A., Mahadik, K. R., & Gajbhiye, V. (2020). PEGylated nanocarriers: A promising tool for targeted delivery to the brain. Colloids and Surfaces B: Biointerfaces, 187, 110770.
[34]. Balusamy, S. R., Perumalsamy, H., Huq, M. A., Yoon, T. H., Mijakovic, I., Thangavelu, L., ... & Rahimi, S. (2023). A comprehensive and systemic review of ginseng‐based nanomaterials: Synthesis, targeted delivery, and biomedical applications. Medicinal Research Reviews, 43(5), 1374-1410.
[35]. Sindhwani, S., & Chan, W. C. (2021). Nanotechnology for modern medicine: next step towards clinical translation. Journal of Internal Medicine, 290(3), 486-498.
[36]. Dobrovolskaia, M. A. (2015). Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy. Journal of Controlled Release, 220, 571-583.
[37]. Rodríguez-Gómez, F. D., Penon, O., Monferrer, D., & Rivera-Gil, P. (2023). Classification system for nanotechnology-enabled health products with both scientific and regulatory application. Frontiers in Medicine, 10, 1212949.