Herbal Medicine for Treating Herpes Labialis: A Systematic Review.

Abstract

Introduction: Herpes labialis, commonly caused by herpes simplex virus type 1, affects millions globally and is traditionally managed with nucleoside antiviral drugs. However, increasing interest in complementary and integrative therapies has led to the exploration of topical herbal treatments as potential alternatives or adjuncts in managing this condition. Methods: A systematic review was conducted in accordance with Cochrane guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, with prior registration. A comprehensive search of Medline/PubMed, Scopus, and the Cochrane Central Register of Controlled Trials was performed from inception to June 17, 2024. After screening 7,386 nonduplicate records and assessing 346 full-text articles, 7 randomized controlled trials (RCTs) encompassing 1,250 patients were included. Data were extracted regarding intervention types, outcomes, and adverse events, and the risk of bias was evaluated using the Cochrane Risk of Bias Tool. Results: The included studies evaluated topical formulations of lemon balm (Melissa officinalis L.), olive leaf extract (Olea europaea L.), propolis, and a combined sage-rhubarb cream (Salvia officinalis L., Rheum palmatum L., and Rheum officinale Baill.). Lemon balm preparations consistently reduced pain intensity and swelling, with some studies also reporting a significant decrease in lesion size compared with placebo or acyclovir. Olive leaf extract demonstrated a statistically significant faster improvement in symptoms and a shorter healing time compared with acyclovir. Compared with acyclovir, propolis formulations significantly shortened the median time to lesion encrustation and complete healing compared with acyclovir, and the combined sage-rhubarb cream showed a comparable efficacy to acyclovir in mean healing time. Overall, the risk of bias was judged to be low in two trials, while five trials raised some concerns. The total sample size across studies was small, potentially limiting the generalizability of the results. Across all studies, adverse events were minimal or absent. Discussion: The findings indicate that topical herbal therapies may provide effective and well-tolerated alternatives or adjuncts to conventional antiviral treatments for herpes labialis. However, considerable heterogeneity in intervention protocols and outcome measures, as well as the underrepresentation of pediatric populations, limit the generalizability of these findings. Conclusion: Topical herbal interventions, including lemon balm, olive leaf extract, propolis, and sage-rhubarb formulations, demonstrate potential benefits in managing herpes labialis with favorable safety profiles. Future well-designed, large-scale RCTs employing standardized methodologies are necessary to confirm these findings and to establish optimal treatment protocols for diverse patient populations (Inplasy protocol number: 202350038).