Daisaikoto restores mitochondrial function and suppresses inflammation induced by periodontal bacteria-derived lipopolysaccharides

Authors

• Suzuka Tozawa, Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
• Kazuo Tomita, Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanFollow
• Kento Igarashi, Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
• Yoshikazu Kuwahara, Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Miyagi, Japan
• Junichi Kitanaka, Laboratory of Drug Addiction and Experimental Therapeutics, Department of Pharmacy, School of Pharmacy, Hyogo Medical University, Hyogo, Japan
• Nobue Kitanaka, Department of Pharmacology, School of Medicine, Hyogo Medical University, Hyogo, Japan
• Mehryar Habibi Roudkenar, Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Burn and Regenerative Medicine Research Center, Velayat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
• Amaneh Mohammadi Roushandeh, Department of Anatomy, School of Biomedical Sciences, Medicine & Health, The University of New South Wales, Sydney, NSW, Australia
• Akihiro Kurimasa, Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Miyagi, Japan
• Tomoaki Sato, Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, JapanFollow

DOI

https://doi.org/10.1016/j.jds.2026.01.010

Abstract

Background/purpose

Periodontal disease affects approximately half of the world's population and is the leading cause of tooth loss. This study aimed to identify effective drug candidates for mitigating oral inflammation induced by Porphyromonas gingivalis lipopolysaccharide (P. g LPS), a major virulence factor of periodontal pathogens. We investigated daisaikoto (DST), known for its anti-inflammatory properties in various tissues, and compared its efficacy with shosaikoto (SSK) and hainosankyuto (HNST), both reported to have beneficial effects against periodontitis.

Materials and methods

Human periodontal ligament fibroblasts were treated with DST, SSK, HNST, and their active components before and after P. g LPS stimulation. Anti-inflammatory effects were evaluated by quantifying IL-6, COX2, and PGES2 gene expression using qPCR. Mitochondrial function was assessed via measurements of mitochondrial membrane potential (Ψm), Fe²⁺ content (mtFe²⁺), and reactive oxygen species (mtROS). In addition, ATP production and glycolytic gene expression were analyzed.

Results

DST markedly suppressed IL-6 and PGES2 expression more effectively than SSK and inhibited IL-6 more strongly than HNST. P. g LPS elevated mtROS and mtFe²⁺ levels while reducing Ψm; these mitochondrial impairments were reversed exclusively by DST. Moreover, DST restored ATP production diminished by P. g LPS exposure.

Conclusion

DST exhibits superior anti-inflammatory activity compared with SSK and HNST and uniquely reverses mitochondrial dysfunction caused by P. g LPS. Given the association between mitochondrial dysfunction, diabetes, and periodontal disease progression, DST emerges as a promising therapeutic candidate for periodontitis.

Recommended Citation

Tozawa, Suzuka; Tomita, Kazuo; Igarashi, Kento; Kuwahara, Yoshikazu; Kitanaka, Junichi; Kitanaka, Nobue; Roudkenar, Mehryar Habibi; Roushandeh, Amaneh Mohammadi; Kurimasa, Akihiro; and Sato, Tomoaki, "Daisaikoto restores mitochondrial function and suppresses inflammation induced by periodontal bacteria-derived lipopolysaccharides" (2026). Articles in Press. 21.
https://jds.ads.org.tw/articles_in_press/21