Boswellia serrata Extract and Its Bioactive Compound 3-O-Acetyl-11-Keto-β-Boswellic Acid Induce ROS-Mediated Intracellular Clearance of Porphyromonas gingivalis in Human Gingival Epithelial Cells
- David Ojcius
- 2 minutes ago
- 3 min read
Abstract
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.
Keywords:
Boswellia serrata; AKBA; Porphyromonas gingivalis; reactive oxygen species; ROS; natural products; periodontitis
1. Introduction
Porphyromonas gingivalis is a key intracellular pathogen in periodontitis, capable of invading human gingival epithelial cells and persisting within tissues, thus contributing to the chronic inflammatory characteristic of the disease. Intracellular persistence of P. gingivalis is facilitated by its ability to evade host defenses and modulate local host immune responses, which contribute to P. gingivalis’ association with oral and several systemic diseases. The increasing rate of antibiotic resistance and the fact that conventional antibiotics may not always be successful against intracellular pathogens highlight the need for alternative strategies to eliminate pathogens. Natural products are considered safer for human consumption than synthetic drugs and, therefore, represent ideal candidates for therapeutic treatments.
Frankincense oil can be extracted from Boswellia serrata, a medicinal plant widely recognized for its anti-inflammatory properties. The B. serrata extract contains bioactive boswellic acids with diverse biological activities, including antimicrobial effects against oral pathogens. We have previously reported that the B. serrata extract eliminates P. gingivalis planktonic cell growth and reduces P. gingivalis biofilm formation. Other groups have shown that different compounds from B. serrata inhibit other oral pathogens, such as Streptococcus mutans and Enterococcus faecalis. Boswellic acids and several of their acetylated components exhibit antibacterial activity against Gram-positive bacteria and can synergize with antibiotics, making them potential therapeutic agents.
Reactive oxygen species (ROS)-mediated killing is a canonical host defense mechanism employed by immune cells and epithelial cells. ROS production plays a central role in epithelial antimicrobial activity, directly damaging intracellular pathogens and promoting their clearance. Boswellic acid compounds have been shown to induce ROS production in host cells. Mechanistic studies demonstrate that 11-keto-boswellic acids stimulate ROS synthesis in polymorphonuclear leukocytes via NADPH oxidase and MAPK signaling in a Ca2+-dependent manner. However, B. serrata and related boswellic acids can also exhibit antioxidant effects in non-immune cells, indicating that responses may vary depending on the cell type.
Our recent studies demonstrate that B. serrata extracts inhibit the growth of P. gingivalis and biofilm formation, and can reduce intracellular infection in human gingival epithelial cells, without exhibiting cytotoxic effects. These findings suggest that bioactive B. serrata compounds may act by modulating host responses to limit intracellular survival of P. gingivalis, although the precise mechanisms underlying this effect remain to be elucidated.
We hypothesize that bioactive compounds from B. serrata restrict P. gingivalis infection in human gingival epithelial cells by enhancing host antimicrobial responses. Here, we demonstrate that treatment with B. serrata compounds reduced intracellular bacterial load and increased ROS production, while ROS scavenging reversed the antimicrobial effect. Understanding the cellular mechanism and identifying the bioactive compounds from B. serrata involved in this effect may support the development of strategies for managing periodontal infections.
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