## 1 Introduction
For these reasons, instead of prescribing antibiotics for the onset of inflammatory diseases like periodontitis, it is recommended to use mouthwashes with antimicrobial properties, such as chlorhexiidine or benzidamine hydrochloride, which can directly eliminate _P. gingivalis_, the Gram-negative oral anaerobic bacteria involved in periodontitis [15]. However, chlorhexiidine, while being effective in improving oral health and reducing hospital-acquired infections, can cause discomfort, staining of teeth, and a burning sensation. benzidamine hydrochloride offers analgesic, anti-inflammatory, and microbial reduction effects but can irritate the oral mucosa, leading to mucosal tissue damage, muted taste sensation, and tongue discoloration [15]. Due to these issues, interest is growing in mouth rinses containing natural substances with fewer harmful components to the human body. An ideal antimicrobial agent within the oral environment should selectively target bacteria causing dental caries, periodontitis, or halitosis over other normal oral microbiota while maintaining low toxicity to humans and the environment [16]. Research is actively being conducted to develop antimicrobials derived from natural substances that meet these criteria [17]. Recently, a study demonstrated the efficacy of propolis as a natural antimicrobial product against _Pseudomonas aeruginosa (P. aeruginosa)_, a Gram-negative opportunistic pathogen that is highly resistant to disinfectants, antibiotics, and host defense mechanisms due to various toxic factors [18], and another study demonstrated the efficacy of _MicroRepair (MicroR)_ and _Punica grantatum L. (PomeGr)_ as an inhibitor of biofilm formation against _P. aeruginosa, Staphylococcus aureus (S. aureus)_, and _Candida albicans (C. albicans)_[19]. The continuous use of chemical antibiotics for oral diseases can cause side effects such as hypersensitivity, skin and allergic diseases, and can change the bacterial microbiome, leading to resistance, so alternative treatments using natural substances are needed [20]. Given the complex interplay between microbial pathogens like _P. gingivalis_ and periodontal disease, and the limitations of the current antimicrobial treatments, exploring natural substances such as _Lespedeza cuneta_, which may offer targeted antimicrobial activity with fewer side effects, becomes particularly relevant. _Lespedeza cuneta G. Don_, known by various names such as bi-suri and samyeobcho, is a perennial herb in the legume family, distributed in countries including Korea, Japan, China, and Taiwan. It is utilized as a medicinal resource to protect liver and kidney functions, enhance lung function, and improve blood circulation [21]. The main components of _Lespedeza cuneta_ include pinitol, tannin, \(\beta\)-sistosterol, avicularin, juglanin, trifolin, quercetin, kaempfer, vitexin, and orientin [22; 23], and it is reported to have antioxidant, hypoglycemic, cell-protective, insulin-secretion-promoting, and antimicrobial effects [24]. Natural substances can exhibit a broad-spectrum, non-selective antimicrobial effect, potentially disrupting the balance of normal oral microbiota and leading to the emergence of resistant strains, thereby creating an oral ecosystem imbalance [25]. Therefore, an ideal antimicrobial agent for use in the oral environment requires a substance with selective antimicrobial efficacy against periodontal pathogens like _P. gingivalis_ rather than that against other normal oral microbiota, and low human and environmental toxicity. The stability of _Lespedeza cuneta_ must be verified to determine if it meets these requirements. Periodontal connective tissue primarily consists of human gingival fibroblasts (HGFs), which produce the fibers and connective tissue matrix, as well as DNA and proteins. Through interactions with various infiltrating inflammatory cells, HGFs play a crucial role in the development of periodontal disease and in maintaining and repairing periodontal tissue during wound healing due to their regenerative capacity [26; 27].