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A novel Plasma-Based Ionization Approach to Enhance Herbal Combinations: Application to Perilla frutescens and Taraxacum platycarpum Dahlst
  • Mijeong Choi 1, *,   
  • Haekyoung Lee 1,   
  • Yuri Kim 1,   
  • Byeongju Kang 1,   
  • Taehwa Jeong 1,   
  • Gyumin Choi 1,   
  • Gyumiji Kim 1,   
  • Kwangseop Han 2,   
  • Hyunjik Noh 2,   
  • Saerok Shim 3, 4, *

Received: 22 Apr 2025 | Revised: 10 Jun 2025 | Accepted: 13 Jun 2025 | Published: 20 Jun 2025

Abstract

Herbal medicinal products are gaining attention due to their accessibility and relative safety, yet challenges such as inconsistent efficacy and potential cytotoxicity remain. In this study, to overcome these limitations, we applied a plasma-based ionization method to a combination of Perilla frutescens and Taraxacum platycarpum Dahlst and evaluated its biological effects. THP-1 and Raw 264.7 cells were treated with either ionized or non-ionized extracts, followed by assessments of cell morphology, confluency, viability, and pro-inflammatory cytokine production. Ionization effectively reduced cytotoxic effects, as evidenced by preserved normal cell morphology and viability, and the absence of elevated proinflammatory cytokines. Notably, non-ionized extracts alone induced significant levels of pro-inflammatory cytokines in both cell types, suggesting a potential risk of undesirable immune activation. Although anti-inflammatory activity was not significantly enhanced, it was maintained in Raw 264.7 cells. In THP-1 cells, the ionized extract showed a trend toward enhanced anti-inflammatory activity, with reduced variability compared to the non-ionized extract. These findings suggest that plasma-based ionization may stabilize and improve the reliability of herbal extract efficacy without introducing adverse effects.

References 

  • 1.
    Petrovska, B.B. Historical review of medicinal plants’ usage. Pharmacogn. Rev. 2012, 6, 1–5. https://doi.org/10.4103/0973-7847.95849.
  • 2.
    Park, H.; Kim, H.S. Korean traditional natural herbs and plants as immune enhancing, antidiabetic, chemopreventive, and antioxidative agents: A narrative review and perspective. J. Med. Food 2014, 17, 21–27. https://doi.org/10.1089/jmf.2013.3059.
  • 3.
    Yuan, H.; Ma, Q.; Ye, L.; Piao, G. The Traditional Medicine and Modern Medicine from Natural Products. Molecules 2016, 21, 559. https://doi.org/10.3390/molecules21050559.
  • 4.
    Kumar, H.; Song, S.Y.; More, S.V.; Kang, S.M.; Kim, B.W.; Kim, I.S.; Choi, D.K. Traditional Korean East Asian medicines and herbal formulations for cognitive impairment. Molecules 2013, 18, 14670–14693. https://doi.org/10.3390/molecules181214670.
  • 5.
    Wanjari, A.S.; Wanjari, D.S. An Overview on Herbal Medicine. Res. J. Pharmacogn. Phytochem. 2019, 11, 14–17. https://doi.org/10.5958/0975-4385.2019.00003.7.
  • 6.
    Sanjoy Kumar Pal, Y.S. Herbal Medicine: Current Status and the Future. Asian Pac. J. Cancer Prev. 2003, 4, 281–288.
  • 7.
    Ekor, M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol. 2014, 4, 177. https://doi.org/10.3389/fphar.2013.00177.
  • 8.
    Ben-Shabat, S.; Yarmolinsky, L.; Porat, D.; Dahan, A. Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies. Drug Deliv. Transl. Res. 2020, 10, 354–367. https://doi.org/10.1007/s13346-019-00691-6.
  • 9.
    Che, C.T.; Wang, Z.J.; Chow, M.S.; Lam, C.W. Herb-herb combination for therapeutic enhancement and advancement: Theory, practice and future perspectives. Molecules 2013, 18, 5125–5141. https://doi.org/10.3390/molecules18055125.
  • 10.
    Choi, M.; Hwang, J.; Han, K.; Noh, H.; Kang, B.; Jeong, T.; Choi, G.; Lee, H.; Kim, Y.; Ryu, H.; et al. Natural Plant Extracts as Novel Antiviral Candidates: Citrus extracts. J. Inflamm. Infect. Med. 2025, 1, 3. https://doi.org/10.53941/jiim.2025.100003.
  • 11.
    Wang, Y.; Yang, H.; Chen, L.; Jafari, M.; Tang, J. Network-based modeling of herb combinations in traditional Chinese medicine. Brief. Bioinform. 2021, 22, bbab106. https://doi.org/10.1093/bib/bbab106.
  • 12.
    Ai, S.; Li, Y.; Zheng, H.; Zhang, M.; Tao, J.; Liu, W.; Peng, L.; Wang, Z.; Wang, Y. Collision of herbal medicine and nanotechnology: A bibliometric analysis of herbal nanoparticles from 2004 to 2023. J. Nanobiotechnol. 2024, 22, 140. https://doi.org/10.1186/s12951-024-02426-3.
  • 13.
    Bonifacio, B.V.; Silva, P.B.; Ramos, M.A.; Negri, K.M.; Bauab, T.M.; Chorilli, M. Nanotechnology-based drug delivery systems and herbal medicines: A review. Int. J. Nanomed. 2014, 9, 1–15. https://doi.org/10.2147/IJN.S52634.
  • 14.
    Moradi, S.Z.; Momtaz, S.; Bayrami, Z.; Farzaei, M.H.; Abdollahi, M. Nanoformulations of Herbal Extracts in Treatment of Neurodegenerative Disorders. Front. Bioeng. Biotechnol. 2020, 8, 238. https://doi.org/10.3389/fbioe.2020.00238.
  • 15.
    Teja, P.K.; Mithiya, J.; Kate, A.S.; Bairwa, K.; Chauthe, S.K. Herbal nanomedicines: Recent advancements, challenges, opportunities and regulatory overview. Phytomedicine 2022, 96, 153890. https://doi.org/10.1016/j.phymed.2021.153890.
  • 16.
    Sasidharan, S.; Chen, Y.; Saravanan, D.; Sundram, K.M.; Yoga Latha, L. Extraction, isolation and characterization of bioactive compounds from plants’ extracts. Afr. J.Tradit. Complement. Altern. Med. 2011, 8, 1–10.
  • 17.
    Atanasov, A.G.; Waltenberger, B.; Pferschy-Wenzig, E.M.; Linder, T.; Wawrosch, C.; Uhrin, P.; Temml, V.; Wang, L.; Schwaiger, S.; Heiss, E.H.; et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv. 2015, 33, 1582–1614. https://doi.org/10.1016/j.biotechadv.2015.08.001.
  • 18.
    Zhao, Q.; Luan, X.; Zheng, M.; Tian, X.H.; Zhao, J.; Zhang, W.D.; Ma, B.L. Synergistic Mechanisms of Constituents in Herbal Extracts during Intestinal Absorption: Focus on Natural Occurring Nanoparticles. Pharmaceutics 2020, 12, 128. https://doi.org/10.3390/pharmaceutics12020128.
  • 19.
    Wagner, H.; Ulrich-Merzenich, G. Synergy research: Approaching a new generation of phytopharmaceuticals. Phytomedicine 2009, 16, 97–110. https://doi.org/10.1016/j.phymed.2008.12.018.
  • 20.
    Hou, Z.; Shi, D.; Lin, J.; Zhao, X.; Zhang, H.; Ding, J. Effect of ion pair strategy on transdermal delivery of guanfacine: Which factor dominates drug permeation? Int. J. Pharm. 2024, 652, 123835. https://doi.org/10.1016/j.ijpharm.2024.123835.
  • 21.
    Ristroph, K.D.; Prud’homme, R.K. Hydrophobic ion pairing: Encapsulating small molecules, peptides, and proteins into nanocarriers. Nanoscale Adv. 2019, 1, 4207–4237. https://doi.org/10.1039/c9na00308h.
  • 22.
    Samiei, N.; Foroutan, S.M.; Razipour, F.; Zarghi, A.; Shafaati, A. An investigation into the ability of alendronate ion pairs to increase oral absorption. Int. J. Pharm. 2017, 527, 184–190. https://doi.org/10.1016/j.ijpharm.2017.05.042.
  • 23.
    Schütz, K.; Kammerer, D.R.; Carle, R.; Schieber, A. Characterization of phenolic acids and flavonoids in dandelion (Taraxacum officinale WEB. ex WIGG.) root and herb by high-performance liquid chromatography/electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 2005, 19, 179–186. https://doi.org/10.1002/rcm.1767.
  • 24.
    Qiu, Z.D.; Chen, J.L.; Zeng, W.; Ma, Y.; Chen, T.; Tang, J.F.; Lai, C.J.; Huang, L.Q. Real-time toxicity prediction of Aconitum stewing system using extractive electrospray ionization mass spectrometry. Acta Pharm. Sin. B 2020, 10, 903–912. https://doi.org/10.1016/j.apsb.2019.08.012.
  • 25.
    Su, H.; Liu, K.T.; Chen, B.H.; Lin, Y.P.; Jiang, Y.M.; Tsai, Y.H.; Chang, F.R.; Shiea, J.; Lee, C.W. Rapid identification of herbal toxins using electrospray laser desorption ionization mass spectrometry for emergency care. J. Food Drug Anal. 2019, 27, 415–427. https://doi.org/10.1016/j.jfda.2018.11.001.
  • 26.
    Chan, S.L.; Wong, M.Y.; Tang, H.W.; Che, C.M.; Ng, K.M. Tissue-spray ionization mass spectrometry for raw herb analysis. Rapid Commun. Mass Spectrom. 2011, 25, 2837–2843. https://doi.org/10.1002/rcm.5177.
  • 27.
    Bora, J.; Khan, T.; Mahnot, N. Cold Plasma Treatment Concerning Quality and Safety of Food: A Review. Curr. Res. Nutr. Food Sci. J. 2022, 10, 427–446. https://doi.org/10.12944/CRNFSJ.10.2.3.
  • 28.
    Pogorzelska-Nowicka, E.; Hanula, M.M.; Brodowska-Trębacz, M.; Górska-Horczyczak, E.; Jankiewicz, U.; Mazur, T.; Marcinkowska-Lesiak, M.; Półtorak, A.; Wierzbicka, A. The Effect of Cold Plasma Pretreatment on Water-Suspended Herbs Measured in the Content of Bioactive Compounds, Antioxidant Activity, Volatile Compounds and Microbial Count of Final Extracts. Antioxidants 2021, 10, 1740.
  • 29.
    Jin Su, Y.; Sang Yong, K.; Sang Hyun, K.; Tae Yong, S. Antiallergic and Anti-inflammatory Effects of Perilla frutescens var. acuta. Korean J. Pharmacogn. 2012, 43, 163–166.
  • 30.
    Son, H.-U.; Heo, J.-C.; Seo, M.-S.; Lee, S.-H. Effects of Perilla frutescens L. on anti-oxidant and anti-inflammation activity. Korean J. Food Preserv. 2010, 17, 757–761.
  • 31.
    Youn, I.; Han, S.; Jung, H.J.; Noh, S.G.; Chung, H.Y.; Koo, Y.K.; Shin, S.; Seo, E.K. Anti-Inflammatory Activity of the Constituents from the Leaves of Perilla frutescens var. acuta. Pharmaceuticals 2023, 16, 1655.
  • 32.
    Huang, B.P.; Lin, C.H.; Chen, Y.C.; Kao, S.H. Anti-inflammatory effects of Perilla frutescens leaf extract on lipopolysaccharide-stimulated RAW264.7 cells. Mol. Med. Rep. 2014, 10, 1077–1083. https://doi.org/10.3892/mmr.2014.2298.
  • 33.
    Kangwan, N.; Pintha, K.; Khanaree, C.; Kongkarnka, S.; Chewonarin, T.; Suttajit, M. Anti-inflammatory effect of Perilla frutescens seed oil rich in omega-3 fatty acid on dextran sodium sulfate-induced colitis in mice. Res. Pharm. Sci. 2021, 16, 464–473. https://doi.org/10.4103/1735-5362.323913.
  • 34.
    Yon-Suk, K.; Mi-Yeun, J.; Beom-Seok, R.; Pyo-Jam, P.; Jae-Hyun, J. Anti-Inflammatory Activities of Extracts from Fermented Taraxacum platycarpum D. Leaves Using Hericium erinaceum Mycelia. J. Korean Soc. Food Sci. Nutr. 2016, 45, 20–26.
  • 35.
    Talapphet, N.; Palanisamy, S.; Li, C.; Ma, N.; Prabhu, N.M.; You, S. Polysaccharide extracted from Taraxacum platycarpum root exerts immunomodulatory activity via MAPK and NF-κB pathways in RAW264.7 cells. J. Ethnopharmacol. 2021, 281, 114519. https://doi.org/10.1016/j.jep.2021.114519.
  • 36.
    Cheong, H.; Choi, E.J.; Yoo, G.S.; Kim, K.M.; Ryu, S.Y. Desacetylmatricarin, an anti-allergic component from Taraxacum platycarpum. Planta Med. 1998, 64, 577–578. https://doi.org/10.1055/s-2006-957520.
  • 37.
    Saxena, R.K.; Vallyathan, V.; Lewis, D.M. Evidence for lipopolysaccharideinduced differentiation of RAW264.7 murine macrophage cell line into dendritic like cells. J. Biosci. 2003, 28, 129–134. https://doi.org/10.1007/BF02970143.
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DOI
10.53941/jiim.2025.100011
Issue
Volume 1, Issue 2
How to Cite
Choi, M.; Lee, H.; Kim, Y.; Kang, B.; Jeong, T.; Choi, G.; Kim, G.; Han, K.; Noh, H.; Shim, S. A novel Plasma-Based Ionization Approach to Enhance Herbal Combinations: Application to Perilla frutescens and Taraxacum platycarpum Dahlst. Journal of Inflammatory and Infectious Medicine 2025, 1 (2), 5. https://doi.org/10.53941/jiim.2025.100011.
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