Anti-Inflammatory and bone-protective effects of Pimpinella brachycarpa extract in a rat periodontitis model

Journal of Molecular Histology (2026) 57:36 https://doi.org/10.1007/s10735-025-10690-2 ORIGINAL PAPER Anti-Inflammatory and bone-protective effects of Pimpinella brachycarpa extract in a rat periodontitis model Su-Bin Park1 · Yun Mi Lee2 · Hwa Young Yu1 · Jae-Eun Jung1 · Eunjung Son2 · Junghyun Kim1,3 Received: 1 September 2025 / Accepted: 12 December 2025 © The Author(s) 2026, modified publication 2026 Abstract Pimpinella brachycarpa has been used in food and traditional herbal medicine for its anti-inflammatory and antimicrobial properties. This study evaluated the therapeutic potential of P. brachycarpa extract (PBE) in a rat model of ligature-induced periodontitis and identified its active compounds, such as green tea catechin (GTC), chlorogenic acid (CGA), and their combination (MIX). Seven-week-old rats received PBE (150–300 mg/kg/day) for 14 days post-ligation to induce periodontitis. Outcomes were assessed using gross morphology, histology, TRAP staining, and immunohistochemistry. UPLC revealed CGA as a major constituent in PBE. PBE significantly reduced alveolar bone loss and inflammatory responses compared to the vehicle-treated ligature-induced periodontitis group (LIG), with effects comparable to or exceeding those of ISD (Zea mays L. extract and Magnolia cortex extract-containing herbal formulaas a reference drug), GTC, CGA, and MIX. TRAP and IHC analyses indicated suppression of osteoclast activity and decreased expression of CD45, IL-1β, and TNF-α. These findings suggest that PBE mitigates periodontitis via modulation of osteoclastogenesis and immune responses. Given its efficacy and bioactive profile, PBE may serve as a promising candidate for the development of natural therapeutics against periodontal disease. Keywords Pimpinella brachycarpa · Periodontitis · Alveolar bone loss · Green tea catechin · Chlorogenic acid Background Periodontitis is a chronic multifactorial inflammatory disease characterized by the progressive destruction of toothsupporting tissues, including the periodontal ligament and alveolar bone (Van Dyke et al. 2020). It is one of the most prevalent oral diseases worldwide and a leading cause of tooth loss in adults. According to the 2017 Classification of Periodontal and Peri-Implant Diseases and Conditions (AAP/ EFP), periodontitis is now defined by a multidimensional Su-Bin Park and Yun Mi Lee have contributed equally to this work. Junghyun Kim 1 Department of Oral Pathology, School of Dentistry, Jeonbuk National University, Jeonju 54896, South Korea 2 KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea 3 College Department of Oral Pathology, School of Dentistry, Jeonbuk National University, Jeonju 54896, Korea staging and grading framework that replaces the outdated “chronic” and “aggressive” categories. This system allows classification by severity, complexity, and risk of progression, thereby improving diagnostic accuracy and prognostic value (Papapanou et al. 2018; Tonetti et al. 2018) The pathogenesis of periodontitis involves a complex interplay between pathogenic microorganisms in dental plaque and the host immune response, which results in the release of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) (de Oliveira et al. 2023; Lee et al. 2020). These mediators stimulate osteoclast differentiation and promote alveolar bone resorption, contributing to the progression of periodontal tissue destruction (Kim et al. 2018). Current treatment strategies for periodontitis include mechanical debridement and adjunctive use of antimicrobial agents or host modulation therapy. However, long-term use of antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) can result in serious adverse effects, including gastrointestinal ulceration, alteration of gut microbiota with opportunistic infections, and the emergence of antibioticresistant strains. Moreover, the efficacy of these drugs often 36 Page 2 of 11 diminishes upon discontinuation, contributing to frequent recurrence of periodontal disease(Oh and Yu 2021; Van Dyke 2008). These limitations underscore the importance of developing safer, more sustainable therapies. In this context, natural agents such as Pimpinella brachycarpa extract (PBE), which possess anti-inflammatory and boneprotective properties, may provide promising alternatives to conventional treatment strategies. In recent years, plantderived polyphenolic compounds have attracted significant attention due to their anti-inflammatory, antioxidant, and bone-protective properties (German et al. 2024). Natural substances such as green tea catechins (GTC) and chlorogenic acid (CGA) have demonstrated promising results in experimental periodontitis models, including the inhibition of osteoclastogenesis, reduction of oxidative stress, and suppression of pro-inflammatory cytokine production (German et al. 2024; Lee et al. 2020; Nishida et al. 2023). Several studies have shown that GTC attenuates alveolar bone loss and inflammatory infiltration in ligature-induced models, while CGA has been reported to modulate NF-κB and MAPK pathways, thereby inhibiting osteoclast differentiation and inflammatory signaling (Park and Yoon 2022; Shen et al. 2024; Yoshinaga et al. 2014). Pimpinella brachycarpa (Kom.) Nakai, commonly known as “Chamnamul” in Korea, has been used as an edible vegetable as well as a traditional medicinal herb in East Asia for its anti-inflammatory, anti-bacterial, antioxidant, and hepatoprotective effects (Sathasivam et al. 2025; Wu et al. 2023). Pimpinella species, commonly used in folk medicine, are applied to the oral cavity due to their antiseptic and anti-inflammatory properties. They are used as mouthwashes and gargles to soothe inflamed gums and freshen breath (Bakhshi et al. 2022; Lavaee et al. 2022). The antiinflammatory and antibacterial properties of P. brachycarpa have made it a valuable remedy for infections and inflammatory conditions in the oral cavity. Despite its ethnomedicinal relevance, the potential of P. brachycarpa extract (PBE) in preventing or ameliorating periodontitis has not been thoroughly investigated. Preliminary phytochemical analyses have revealed that PBE contains several bioactive flavonoids and phenolic acids, including chlorogenic acid, luteolin-7-O-glucuronide, and apigenin-7-O-glucuronide, which are known to modulate inflammatory responses and bone metabolism (Sathasivam et al. 2025; Shen et al. 2024). While the individual components of PBE have demonstrated biological activity in other inflammatory conditions, their combined effects in the context of periodontal disease remain unexplored. To our knowledge, no previous in vivo study has systematically compared the anti-periodontitis efficacy of PBE with established polyphenolic agents such as GTC and CGA. Moreover, few studies have addressed the synergistic 13 Journal of Molecular Histology (2026) 57:36 potential of combining th (...truncated)