Citation: Bellere, A.D.; Yu, D.; Oh, S.; Kim, M.; Jung, J.; Fang, M.; Zheng, S.; Yi, T.-H. Antiperiodontitis Effects of Siegesbeckia glabrescens In Vitro. Antioxidants 2023, 12, 471. https:// doi.org/10.3390/antiox12020471 Academic Editor: Mario Allegra Received: 26 January 2023 Revised: 6 February 2023 Accepted: 10 February 2023 Published: 13 February 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). antioxidants Article Antiperiodontitis Effects of Siegesbeckia glabrescens In Vitro Arce Defeo Bellere 1,† , Duna Yu 1,† , Sarang Oh 2 , Myeongju Kim 1 , Jeyong Jung 1 , Minzhe Fang 1 , Shengdao Zheng 2 and Tae-Hoo Yi 1, * 1 Graduate School of Biotechnology, Kyung Hee University, Yongin-si 17104, Republic of Korea 2 Snowwhitefactory Co., Ltd., 807 Nonhyeon-ro, Gangnam-gu, Seoul 06032, Republic of Korea * Correspondence: drhoo@khu.ac.kr; Tel.: +82-31-201-3693 † These authors equally contributed to this work. Abstract: Siegesbeckia glabrescens is generally grown in fields or roadsides in Korea and used for the treatment of inflammatory diseases. The effects of S. glabrescens on periodontitis are unknown. In this study, we determined the effects of an S. glabrescens 30% EtOH extract (SGE) on periodontitis and analyzed the antioxidant activity (DPPH, ABTS, and SOD), antimicrobial (disc diffusion, MIC, and MBC), inhibition of GTFs, biofilm formation, and the anti-inflammation of lipopolysaccharide from P. gingivalis (LPS-PG)-induced primary equine periodontal ligament fibroblasts (PDLFs). We report that SGE increased DPPH, ABTS, and SOD antioxidant activities in a dose-dependent manner. SGE caused a clear zone with a diameter of 15 mm or more against periodontal pathogens. SGE (2.50 mg/mL) inhibited GTFs and biofilm by 89.07% and 85.40%, respectively. SGE treatment (100 μg/mL) also significantly decreased the secretion of inflammatory mediators in sensitized PDLF, including cytokines and matrix metalloproteinase (MMP)-3, -8, -9, and -13. Overall, we confirmed that SGE had excellent antioxidant, antimicrobial, and anti-inflammatory effects against periodontal pathogens. These results suggest that it has the potential to develop as a prophylactic agent for periodontitis. Keywords: Siegesbeckia glabrescens; periodontitis; Porphyromonas gingivalis; antioxidants; biofilms 1. Introduction Oral health enhances nutrient intake and digestion, and it is vital to maintain systemic health. Major diseases representing oral health conditions include dental caries, periodontal disease, and oral cancer [1]. If left untreated, these diseases not only result in tooth loss; they also cause serious effects throughout the body and, in some cases, lead to death. Periodontitis, a type of gum disease, is a chronic inflammatory disease with symptoms, such as red, bleeding, and swollen gums, caused by an organized bacterial community (biofilm) called a plaque [2]. Higher risk factors of periodontal disease are associated with diabetes, medication, age, hereditary, poor oral hygiene, smoking, and stress [3]. The excessive proliferation of pathogenic bacteria present in dental plaque and the gingival sulcus is considered a direct cause of periodontal disease. Among these bacteria, the ones that are recognized as the cause of periodontal disease are mainly Gram-negative anaerobic bacteria, such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola, Prevotella intermedia, and Fusobacterium nucleatum. Socransky et al. [4]. classified subgingival biofilm bacteria into five complexes, namely red, orange, yellow, green, and purple, based on the results of staining reaction, colony morphology, and pigment production [5]. Among the five complexes, the red complex colonizes during the late stage of periodontitis, has the strongest pathogenicity, and is highly correlated with clinical indicators of periodontal diseases, such as deep periodontal pockets and bleeding [6]. Streptococcus spp. is a resident bacterium in the oral cavity and is one of the causes of periodontitis. Endogenous enzymes in cells are activated by surface proteins of these Antioxidants 2023, 12, 471. https://doi.org/10.3390/antiox12020471 https://www.mdpi.com/journal/antioxidants