Porphyromonas gingivalis is a keystone pathogen in periodontitis, known for its ability to invade gingival epithelial cells and persist intracellularly. Conventional antimicrobials are often ineffective against intracellular pathogens, and natural products remain poorly explored in this context. Here, we investigated the antimicrobial effects of Boswellia serrata extract and its bioactive compounds on the dynamics of P. gingivalis infection in human gingival epithelial cells. During early times of infection, B. serrata extracts stimulate endocytic mechanisms and increased bacterial internalization, suggesting a modulation of epithelial uptake mechanisms. At later times of infection, B. serrata increased production of reactive oxygen species (ROS) in host cells and markedly reduced intracellular bacterial load. The antimicrobial effect was abolished by the ROS scavenger N-acetylcysteine, confirming a role for oxidative mechanisms in the clearance of P. gingivalis. Similar results were obtained with 3-O-acetyl-11-keto-β-boswellic acid (AKBA), one of the major boswellic acid derivatives found in B. serrata extract. These findings reveal a dual role of B. serrata compounds in response to P. gingivalis infection, in which B. serrata initially facilitates bacterial entry and subsequently promotes ROS-dependent intracellular killing. These findings provide new mechanistic insights into the regulation of host-pathogen interactions by the natural products found in B. serrata. Our results support the therapeutic potential of B. serrata–derived compounds for managing periodontal infections.

Porphyromonas gingivalis is a keystone pathogen in periodontitis, known for its ability to invade gingival epithelial cells and persist intracellularly. Conventional antimicrobials are often ineffective against intracellular pathogens, and natural products remain poorly explored in this context. Here, we investigated the antimicrobial effects of Boswellia serrata extract and its bioactive compounds on the dynamics of P. gingivalis infection in human gingival epithelial cells. During early times of infection, B. serrata extracts stimulated phagocytosis and increased bacterial internalization, suggesting modulation of epithelial uptake mechanisms. At later times of infection, B. serrata increased production of reactive oxygen species (ROS) in host cells and markedly reduced intracellular bacterial load. The antimicrobial effect was abolished by the ROS scavenger N-acetylcysteine, confirming a role for oxidative mechanisms in the clearance of P. gingivalis. Similar results were obtained with 3-O-acetyl-11-keto-β-boswellic acid (AKBA), one of the major boswellic acid derivatives found in B. serrata extract. These findings reveal a dual role of B. serrata compounds in response to P. gingivalis infection, in which B. serrata initially facilitates bacterial entry and subsequently promotes ROS-dependent intracellula These findings provide new mechanistic insights into the regulation of host–pathogen interactions by the natural products found in B. serrata. Our results support the therapeutic potential of B. serrata-derived compounds for managing periodontal infections.