Chronic toxicity and modulatory effects of Deprungsith formulation in Wistar Albino rats
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Yosita Kasemnitichok
Abstract
Objectives
Psoriasis is a systematic skin disease. Treatment choice is limited due to unsatisfactory clinical efficacy. The study evaluated the safety of Deprungsith formulation following long-term administration (chronic toxicity test) and its potential modulatory effect on hepatic cytochrome P450 (CYP) enzymes in rats.
Methods
Wistar rats were randomly grouped to receive Deprungsith (125, 500, and 1,000 mg/kg/day) and the satellite (1,000 mg/kg bw) to observe reversibility, as well as distilled water (untreated control) for 9 months. The sentinel-1 group was for environmental risk assessment after 6 months, and the sentinel-2 group was for environmental risk assessment after 9 months). Clinical and behavioral signs, mortality, and histopathology were monitored.
Results
The chronic toxicity study of Deprungsith revealed no evidence of mortality or serious clinical signs at any dosage level. However, changes in WBC count, serum albumin, and sodium, were observed. Histopathological examination identified mild to moderate liver necrosis and renal interstitial inflammation. Low-dose (125 mg/kg bw) significantly induced CYP1A2 and CYP3A1, while high-dose (1,000 mg/kg bw) inhibited CYP1A2 and CYP3A1 activities.
Conclusions
Deprungsith formulation was well-tolerated with an MTD (maximum tolerated dose) and NOAEL (no-observed-adverse-effect level) of 1,000 mg/kg bw. Long-term use of Deprungsith formulation in psoriasis patients should be carefully monitored for therapeutic outcomes (side effects from accumulated levels or unsatisfactory efficacy from inadequate CYP1A2 and CYP3A1-mediated metabolism) and potential herb-drug interactions.
Funding source: National Research Council of Thailand
Award Identifier / Grant number: 2567-1
Funding source: Thailand Research Fund under the Royal Golden Jubilee Ph.D. Program
Award Identifier / Grant number: PHD/0094/2561
Funding source: Thailand Science Research and Innovation (TSRI)
Acknowledgments
We thank the staff of the Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma for their technical support.
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Research ethics: Thammasat University Ethics Committee for Animal Research of Thammasat University approved the study (No. 014/2020).
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Informed consent: Not applicable.
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Author contributions: Conceptualization: KNB; formal analysis: AT; methodology: WS; supervision: KNB and WS; writing original draft: AT; writing, review and editing: KNB. All authors have read and agreed to the submitted version of the manuscript.
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Use of Large Language Models, AI and Machine Learning Tools: ChatGPT was used to check grammar and improve language clarity. These tools were not used for content generation, data analysis, or interpretation of results.
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Conflict of interest: The authors have no competing interests to declare that are relevant to the content of this article.
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Research funding: This research was financially supported by the following organizations: Kesara Na-Bangchang is funded by National Research Council of Thailand (NRCT), grant number 2567-1. Yosita Kasemnitichok is supported by Thailand Research Fund under The Royal Golden Jubilee Ph.D. Program (grant number PHD/0094/2561. All funders have no roles in publication. Tullayakorn plengsuriyakarn is supported by Thailand Science Research and Innovation (TSRI), fiscal year 2025.
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Data availability: Not applicable.
References
1. Chaiyamahapurk, WP. Prevalence and characteristics of psoriasis patients in a primary care area in Thailand. J Med Assoc 2021;104:610–4.10.35755/jmedassocthai.2021.04.11913Search in Google Scholar
2. Woo, YR, Park, CJ, Kang, H, Kim, JE. The risk of systemic diseases in those with psoriasis and psoriatic arthritis: from mechanisms to clinic. Int J Mol Sci 2020;21:7041. https://doi.org/10.3390/ijms21197041.Search in Google Scholar PubMed PubMed Central
3. Swindell, WR, Johnston, A, Xing, X, Voorhees, JJ, Elder, JT, Gudjonsson, JE. Modulation of epidermal transcription circuits in psoriasis: new links between inflammation and hyperproliferation. PLoS One 2013;8:e79253. https://doi.org/10.1371/journal.pone.0079253.Search in Google Scholar PubMed PubMed Central
4. Salgado-Boquete, L, Carrascosa, JM, Llamas-Velasco, M, Ruiz-Villaverde, R, de la Cueva, P, Belinchón, I. A new classification of the severity of psoriasis: what’s moderate psoriasis? Life (Basel) 2021;11:627. https://doi.org/10.3390/life11070627.Search in Google Scholar PubMed PubMed Central
5. Kim, WB, Jerome, D, Yeung, J. Diagnosis and management of psoriasis. Can Fam Physician 2017;63:278–85.Search in Google Scholar
6. Lee, HJ, Kim, M. Challenges and future trends in the treatment of psoriasis. Int J Mol Sci 2023;24:210–22. https://doi.org/10.3390/ijms241713313.Search in Google Scholar PubMed PubMed Central
7. Rendon, A, Schäkel, K. Psoriasis pathogenesis and treatment. Int J Mol Sci 2019;20:145–50.10.3390/ijms20061475Search in Google Scholar PubMed PubMed Central
8. Thawornwet, PPK. Foundation for restoration and promotion of traditional Thai medicine and school ayurvedic treatment situation of Faculty of Applied Thai Traditional Medicine Siriraj Hospital Medicine Mahidol University textbook traditional Thai medicine (Phaetsat Songkhro). Bangkok: Suphawanichkan Pim; 2012.Search in Google Scholar
9. Na-Bangchang, K, Teerachaisakul, M, Muhamad, P, Kasemnitichok, Y, Sangnarong, N, Boonprasert, K, et al.. Antiproliferative and anti-inflammatory activities of deprungsith formulation and its bioactive compounds against mild psoriasis and potential of metabolic herb-drug interactions. J Evid Based Integr Med. 2023;28:2515690x231191101. https://doi.org/10.1177/2515690x231191101.Search in Google Scholar
10. Seewaboon sireeratawong. Final report: the second phase of the research project of efficacy and safety of Dephrangsith for psoriasis treatment.; 2019.Search in Google Scholar
11. World Health Organization. WHO guideline on good manufacturing practices (GMP) for herbal medicine. 20 Avenue Appia, 1211 Geneva 27, Switzerland; 2007.Search in Google Scholar
12. World Health Organization. WHO guidelines for assessing quality of herbal medicines with reference to contaminants and residues. 20 Avenue Appia, 1211 Geneva 27, Switzerland; 2007.Search in Google Scholar
13. World Health Organization (WHO). Guidelines for the regulation of herbal medicines in the South-East Asia Region. New Delhi: WHO Regional Office for South-East Asia; 2004.Search in Google Scholar
14. Muhamad, N, Plengsuriyakarn, T, Na-Bangchang, K. Atractylodes lancea for cholangiocarcinoma: modulatory effects on CYP1A2 and CYP3A1 and pharmacokinetics in rats and biodistribution in mice. PLoS One 2022;17:e0277614. https://doi.org/10.1371/journal.pone.0277614.Search in Google Scholar PubMed PubMed Central
15. Patel, S, Patel, S, Kotadiya, A, Patel, S, Shrimali, B, Joshi, N, et al.. Age-related changes in hematological and biochemical profiles of Wistar rats. Lab Anim Res 2024;40:7–14. https://doi.org/10.1186/s42826-024-00194-7.Search in Google Scholar PubMed PubMed Central
16. Mary, LA, Giknis, PD, Charles, B, Clifford, D. Clinical laboratory parameters for the Crl:CD(SD) rats. USA, Canada: Charles River Laboratories; 2006 Technical report.Search in Google Scholar
17. OECD guidelines for the testing of chemicals: repeated dose 90-day oral toxicity study in rodents (test no. 408). USA, UK, France, Germany: OECD Publishing; 2018. https://doi.org/10.1787/9789264070707-enSearch in Google Scholar
18. Lee, J, Beers, JL, Geffert, RM, Jackson, KD. A review of CYP-mediated drug interactions: mechanisms and in vitro drug-drug interaction assessment. Biomolecules 2024;14:99. https://doi.org/10.3390/biom14010099.Search in Google Scholar PubMed PubMed Central
19. Martignoni, M, Groothuis, GMM, de Kanter, R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Exp Opin Drug Metab Toxicol 2006;2:875–94. https://doi.org/10.1517/17425255.2.6.875.Search in Google Scholar PubMed
20. Amundsen, R, Åsberg, A, Ohm, IK, Christensen, H. Cyclosporine A- and tacrolimus-mediated inhibition of CYP3A4 and CYP3A5 in vitro. Drug Metab Dispos 2012;40:655–61. https://doi.org/10.1124/dmd.111.043018.Search in Google Scholar PubMed
21. Spear, SJ, McLachlan, JM. Cytochrome P450 1A2 and its role in carcinogenesis. Toxicol Appl Pharmacol 2001;171:74–80.Search in Google Scholar
22. Sirisangtrakul, W, Jarukamjorn, K, Nemoto, N, Yenjai, C, Sripanidkulchai, B. Effect of ethyl-p-methoxy cinnamate from Kaempferia galanga on cytochrome P450 enzymes expression in mouse hepatocytes. Chiang Mai J Sci 2011;38:253–60.Search in Google Scholar
23. Sørensen, HT, Christensen, S, Kragh Andersen, P, Johnsen, SP, Thomsen, RW, Sørensen, M, et al.. Impact of gender on drug metabolism and response. Eur J Clin Pharmacol 2006;62:501–7.Search in Google Scholar
24. Qiang, Ma, Lu, Anthony YH. CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies. Drug Metab Dispos 2007;35:1009–16. https://doi.org/10.1124/dmd.107.015826.Search in Google Scholar PubMed
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