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Title Herbal Mouth Rinses May Be Less Cytotoxic to Fibroblasts and SCAPs Than Chlorhexidine
Clinical Question Do human gingival fibroblasts and SCAPs exposed to chlorhexidine gluconate mouth rinse demonstrate increased cytotoxicity as compared to those exposed to an herbal mouth rinse?
Clinical Bottom Line Human gingival fibroblasts and oral stem cells of the apical papilla (SCAPs) demonstrate statistically significant increased cytotoxicity to chlorhexidine gluconate as compared to an herbal mouth rinse. This is supported by three independent in vitro studies comparing these mouth rinses and their impacts via assays assessing viability, proliferation, cell migration, and gene expression. These studies demonstrate that, in vitro, herbal mouth rinses have the potential to be more biocompatible and less cytotoxic than 0.12% or 0.2% chlorhexidine gluconate and may even have an improved healing potential through increased transcription of type 1 collagen.
Best Evidence (you may view more info by clicking on the PubMed ID link)
PubMed ID Author / Year Patient Group Study type
(level of evidence)
#1) 33868021Zhou/2021Fibroblasts and primary oral SCAPsLaboratory study
Key resultsThe results in this study are compared against a phosphate buffered saline (PBS) control. StellaLife rinse is a mixture of four herbal compounds. 1. In a 30s challenge to mouth rinse, as compared to PBS, StellaLife (herbal rinse) showed no cytotoxicity of SCAPs (p>0.05), while 0.12% chlorhexidine gluconate demonstrated significant toxicity (p<0.0001). 2. On a scratch wound assay, StellaLife and PBS were statistically similar in regard to promoting wound closure (p<0.01), while 0.12% chlorhexidine gluconate demonstrated cell death at 24 hours and an increase in wound margin by 48 hours (indicating decreased wound healing and increase cytotoxicity [p<0.01]). 3. In an intermittent assay of “rinsing” every 3 days, StellaLife demonstrated increased deposition of type 1 collagen as compared to 0.12% chlorhexidine gluconate (post hoc p<0.001). 4. In all studies, fibroblasts and SCAPs showed no cytotoxicity to StellaLife at clinically relevant exposure times. As compared to 0.12% chlorhexidine gluconate, which demonstrated significant cytotoxicity in multiple assessments.
#2) 32708895Fujioka-Kobayashi/2020Gingival fibroblasts and SCAPsLaboratory study
Key resultsComparing StellaLife rinse (herbal rinse) to 0.2% Chlorhexidine gluconate 1. At clinically relevant concentrations and rinsing times, 0.2% chlorhexidine gluconate demonstrated increase cytotoxicity to SCAPs compared to StellaLife. 2. At identical dilutions and regarding human gingival fibroblasts, StellaLife exposed cells showed similar cell migration and proliferation as those exposed to a control, whereas 0.2% chlorhexidine gluconate exposed cells demonstrated inhibited migration and proliferation (p<0.05). 3. As compared to a control, StellaLife exposed cells expressed similar cytokines and collagen production. 0.2% Chlorhexidine gluconate exposed cells demonstrated statistically significant increases in expression of TNF-alpha and IL-6 (indicating inflammation) and a decrease in type 1 collagen production (p<0.05). 4. This study supports the findings that StellaLife, an herbal mouth rinse, had similar effects as a control on gingival fibroblasts and SCAPs, while 0.2% chlorhexidine gluconate demonstrated increased cytotoxicity and decreased cytocompatibility in multiple assays.
#3) 34854484Batra/2022Human gingival fibroblastsLaboratory study
Key resultsComparing dilutions of StellaLife gel and 0.12% Chlorhexidine Gluconate 1. StellaLife did not impact human gingival fibroblast proliferation as compared to a control (p>0.05), whereas 1/10 and 1/100 dilutions of 0.12% chlorhexidine gluconate significantly impacted human gingival fibroblast proliferation (P<0.05) 2. In a Lactate Dehydrogenase Assay of Human Gingival Fibroblasts (Indicator of cytotoxicity via cell damage), StellaLife failed to demonstrate cytotoxicity at any dilution as compared to a control (P>0.05), whereas 0.12% chlorhexidine demonstrated significant cytotoxicity at all test dilutions (p<0.05). 3. These findings support 0.12% chlorhexidine gluconate as being more cytotoxic to human gingival fibroblasts, as compared to StellaLife, in an in vitro experimental setting.
Evidence Search 1.chlorhexidine AND Herbal AND Cytotoxicity 2.chlorhexidine AND gingival fibroblasts AND oral antiseptic
Comments on
The Evidence
All three studies evaluated cell cytotoxicity, migration, proliferation, and gene expression in response to the mouth rinses and found that an herbal rinse was less cytotoxic than 0.2% chlorhexidine gluconate rinse. One drawback of the Fujioka-Kobayashi study is that they used 0.2% chlorhexidine gluconate, which has previously been demonstrated to be more cytotoxic than the version more commonly used in the U.S., which is 0.12%. These articles are all in vitro studies on 2D cell cultures and therefore they are a low level of evidence for decision making as directly applicable to human subjects. However, this is the highest level of evidence currently available on this topic and all the articles used controlled experiments with good basic science protocols. The assays used in these studies are routine lab experiments and the statistics indicate the validity of the results. Three independent studies demonstrated the same results, which makes these findings reliable.
Applicability This study is not directly applicable to a clinical scenario because it was a lab study on 2D cell cultures. It informs on what happens to cells in culture exposed to these mouth rinses, but not necessarily what happens to cells of the oral cavity in their 3D organization. More research is needed on this topic in a 3D cell model or human randomized controlled trial. Currently, oral antiseptic mouth rinses are the standard of care for managing oral post-operative complications. Until there is more evidence, 0.12% chlorhexidine gluconate cannot necessarily be removed as the gold standard rinse. However, if a patient or provider is opposed to the use of chlorhexidine because it isn’t homeopathic, these studies provide evidence that an herbal mouth rinse could be a useful alternative.
Specialty/Discipline (General Dentistry) (Oral Surgery) (Periodontics) (Basic Science)
Keywords Chlorhexidine, Herbal, Cytotoxicity, Gingival Fibroblasts, Oral Antiseptic, Cytocompatibility
ID# 3500
Date of submission: 12/01/2022spacer
E-mail padalino@livemail.uthscsa.edu
Author Alexander Padalino, DDS
Co-author(s) Dr. Zaara Baig
Co-author(s) e-mail baigz@livemail.uthscsa.edu
Faculty mentor/Co-author Angela A. Palaiologou-Gallis, DDS, MS
Faculty mentor/Co-author e-mail PalaiologouA@uthscsa.edu
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