ArticlePloS one2014
From a traditional medicinal plant to a rational drug: understanding the clinically proven wound healing efficacy of birch bark extract.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 103 citations in OpenAlex.
- Complement factor D regulates collagen type I expression and fibroblast migration to enhance human tendon repair and healing outcomes.Frontiers in immunology · 2023Trial
- Triterpenes for Well-Balanced Scar Formation in Superficial Wounds.Molecules (Basel, Switzerland) · 2016Trial
- Wound-Healing Effects of Birch Bark and Propolis Extracts on Epidermolysis Bullosa Keratinocytes.International journal of molecular sciences · 2026Article
- Phytochemical Profile and Antioxidant Potential ofAntioxidants (Basel, Switzerland) · 2026Article
- Innovations in topical epidermolysis bullosa treatment: integrating advanced dressings, bioactive therapies and tissue-engineered skin.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- Butenolides and triterpenoids from the fungusFrontiers in fungal biology · 2026Article
- Towards Extracellular Vesicles in the Treatment of Epidermolysis Bullosa.Bioengineering (Basel, Switzerland) · 2025Review
- Betulin gel alleviates esophageal stricture following endoscopic submucosal dissection: an animal study.Esophagus : official journal of the Japan Esophageal Society · 2025Article
- Emerging Trends in the Treatment of Skin Disorders by Herbal Drugs: Traditional and Nanotechnological Approach.Pharmaceutics · 2024Review
- Obtaining New Biocompatible Composite Materials with Antibacterial Properties Based on Diatomite and Biologically Active Compounds.Molecules (Basel, Switzerland) · 2024Article
- Targeted inhibition of colorectal cancer proliferation: The dual-modulatory role of 2,4-DTBP on anti-apoptotic Bcl-2 and Survivin proteins.Journal of cellular and molecular medicine · 2024Article
- Natural Compounds in Non-Melanoma Skin Cancer: Prevention and Treatment.Molecules (Basel, Switzerland) · 2024Review
- Kick-Starting Wound Healing: A Review of Pro-Healing Drugs.International journal of molecular sciences · 2024Review
- Macrofungal Mediated Biosynthesis of Silver Nanoparticles and Evaluation of Its Antibacterial and Wound-Healing Efficacy.International journal of molecular sciences · 2024Article
- Hydrolat of Helichrysum italicum promotes tissue regeneration during wound healing.Physiological research · 2023Article
- Evaluation of Oleogels Stabilized by Particles of Birch Outer Bark Extract through a Novel Approach.Gels (Basel, Switzerland) · 2023Article
- Review
- Effect of Betulin Colloidal Particles on Proliferation and Cytokine Secretion of Human Skin Fibroblasts.Plants (Basel, Switzerland) · 2023Article
- Pharmacological Potential of Betulin as a Multitarget Compound.Biomolecules · 2023Review
- New Data on Anti-Inflammatory and Wound Healing Potential of TransgenicInternational journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBirch bark has a long lasting history as a traditional medicinal remedy to accelerate wound healing. Recently, the efficacy of birch bark preparations has also been proven clinically. As active principle pentacyclic triterpenes are generally accepted. Here, we report a comprehensive study on the underlying molecular mechanisms of the wound healing properties of a well-defined birch bark preparation named as TE (triterpene extract) as well as the isolated single triterpenes in human primary keratinocytes and porcine ex-vivo wound healing models. METHODOLOGY/PRINCIPAL
findingsWe show positive wound healing effects of TE and betulin in scratch assay experiments with primary human keratinocytes and in a porcine ex-vivo wound healing model (WHM). Mechanistical studies elucidate that TE and betulin transiently upregulate pro-inflammatory cytokines, chemokines and cyclooxygenase-2 on gene and protein level. For COX-2 and IL-6 this increase of mRNA is due to an mRNA stabilizing effect of TE and betulin, a process in which p38 MAPK and HuR are involved. TE promotes keratinocyte migration, putatively by increasing the formation of actin filopodia, lamellipodia and stress fibers. Detailed analyses show that the TE components betulin, lupeol and erythrodiol exert this effect even in nanomolar concentrations. Targeting the actin cytoskeleton is dependent on the activation of Rho GTPases. CONCLUSION/SIGNIFICANCE: Our results provide insights to understand the molecular mechanism of the clinically proven wound healing effect of birch bark. TE and betulin address the inflammatory phase of wound healing by transient up-regulation of several pro-inflammatory mediators. Further, they enhance migration of keratinocytes, which is essential in the second phase of wound healing. Our results, together with the clinically proven efficacy, identify birch bark as the first medical plant with a high potential to improve wound healing, a field which urgently needs effective remedies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.