Dipotassium glycyrrhizate
Also known as: Dipotassium glycyrrhizinate, Dipotassium salt of glycyrrhizic acid, Dipotassium glycyrrhizate
Overview
Dipotassium glycyrrhizate (DPG) is a potassium salt derivative of glycyrrhizic acid, a triterpenoid saponin glycoside naturally found in licorice root (Glycyrrhiza glabra). It is primarily utilized in topical and oral formulations for its notable anti-inflammatory, antioxidant, and healing properties. DPG is recognized for its ability to promote wound healing, reduce inflammation in both skin and intestinal mucosa, and potentially modulate immune responses in inflammatory conditions such as inflammatory bowel disease (IBD). Beyond its anti-inflammatory actions, DPG also exhibits antiallergic, antibacterial, antiviral, gastroprotective, and antitumoral activities. While its primary applications are in dermatology and gastroenterology, research into its broader therapeutic potential is ongoing. The current body of evidence, though largely preclinical, suggests DPG is a promising agent for tissue repair and inflammation management.
Benefits
Dipotassium glycyrrhizate offers several evidence-based benefits, primarily centered around its anti-inflammatory and wound-healing capabilities. Strong preclinical evidence indicates its efficacy in accelerating intestinal mucosal healing, particularly in experimental colitis models. DPG achieves this by regulating pro-inflammatory gene expression (e.g., downregulating IL-1β, IL-6) and upregulating genes involved in extracellular matrix remodeling (e.g., VTN, PLAUR), thereby improving epithelial barrier function and reducing inflammation. Similarly, topical application of DPG has been shown to promote cutaneous wound healing in animal models, modulating inflammatory pathways and enhancing tissue regeneration, with histopathological improvements observed within 14 days. These effects are supported by well-controlled animal studies. Secondary benefits include its anti-inflammatory action against HMGB1 protein, a key mediator in various inflammatory and autoimmune disorders. While human data are limited, the strong preclinical findings suggest potential benefits for individuals with inflammatory bowel disease and those requiring enhanced skin wound healing. The effect sizes in animal studies are significant, showing accelerated healing and reduced inflammatory markers, indicating clinical relevance.
How it works
Dipotassium glycyrrhizate exerts its therapeutic effects primarily by modulating key inflammatory pathways and promoting tissue regeneration. Its main mechanism involves the inhibition of pro-inflammatory cytokines such as IL-1β and IL-6, as well as chemokines like CXCL1, CXCL3, and CXCL5. DPG also targets and inhibits the activity of HMGB1 protein, a crucial mediator in inflammation and tissue damage. Furthermore, it influences the expression of genes involved in extracellular matrix remodeling, such as vitronectin (VTN) and urokinase plasminogen activator receptor (PLAUR), which are essential for tissue repair and regeneration. By acting on immune and epithelial cells in the skin and gut mucosa, DPG effectively reduces inflammation and facilitates the body's natural healing processes.
Side effects
Dipotassium glycyrrhizate is generally considered safe, especially in topical and controlled oral applications, with no major adverse effects reported in animal studies. Common side effects are not well-documented, and topical formulations appear to be well tolerated, with only a potential for mild skin irritation in uncommon cases. Rare side effects have not been significantly reported. Regarding drug interactions, no well-established interactions exist. However, caution is advised when used concurrently with drugs metabolized by liver enzymes, as other glycyrrhizic acid derivatives are known to affect these pathways. Contraindications include individuals with a known hypersensitivity to licorice derivatives. Data on special populations, such as pregnant or lactating women, are limited, and caution is advised in these groups. While high doses of glycyrrhizic acid derivatives can lead to mineralocorticoid effects (e.g., pseudoaldosteronism), these effects are typically associated with systemic exposure to glycyrrhizic acid itself, and topical DPG use appears to be safe without such systemic concerns.
Dosage
The optimal dosage for Dipotassium glycyrrhizate in humans is not yet clearly established, as most efficacy data come from preclinical animal studies. In these studies, a topical cream at a 2% concentration has demonstrated efficacy in promoting wound healing in animal models. For skin wound healing, this 2% topical formulation was typically applied daily over a period of 14 days. The minimum effective dose for human use is not defined, and there is no clearly established maximum safe dose. While high doses of related glycyrrhizic acid derivatives can cause mineralocorticoid effects, topical use of dipotassium glycyrrhizate appears safe without these systemic concerns. Oral formulations are less studied, and specific dosage recommendations for oral use are not available. Topical absorption is considered adequate for local effects, but systemic bioavailability in humans remains largely unknown. No specific cofactors are identified as being required for its efficacy.
FAQs
Is dipotassium glycyrrhizate safe for long-term use?
Limited long-term human data exist, but topical use appears safe with minimal reported side effects. Further research is needed for definitive long-term safety conclusions.
Can it be used for all types of wounds?
Evidence primarily supports its use in cutaneous wounds and intestinal mucosal injury. Efficacy in other wound types requires further specific study and validation.
How quickly does it work?
Animal studies indicate that benefits, such as wound healing and reduced inflammation, can be observed within 1 to 2 weeks of consistent application.
Does it interact with other medications?
No significant drug interactions have been widely reported. However, caution is prudent with medications that are metabolized by liver enzymes, due to the known effects of related glycyrrhizic acid derivatives.
Is it suitable for oral use?
Dipotassium glycyrrhizate has been mostly studied for topical applications. While some oral uses exist, more comprehensive research is needed to establish its safety and efficacy for widespread oral consumption.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6498413/ – This preclinical animal study investigated Dipotassium glycyrrhizate's effect on DSS-induced colitis in mice. It found that DPG accelerated mucosal healing by modulating inflammatory and wound healing genes, improving epithelial barrier function. The study was well-controlled with gene expression and functional assays, but human translation is needed.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9965141/ – This in vivo animal study on Wistar rats demonstrated that a 2% DPG cream reduced inflammation and promoted skin wound closure over 14 days. The study used a randomized controlled design with histopathological and gene expression analyses, but its limitations include being an animal model and having a small sample size.
- https://pubmed.ncbi.nlm.nih.gov/36835248/ – This publication is a duplicate reference to the animal study on topical wound healing in rats. It confirms that 2% DPG cream reduced inflammation and promoted skin wound closure with histological improvements over 14 days, supporting the findings of the PMC article.
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1003697/pdf – This systematic review included RCTs on glycyrrhizic acid derivatives, noting their anti-inflammatory and organ-protective effects, with dipotassium glycyrrhizate mentioned as a related compound. While it highlights the potential, the review points out limitations such as heterogeneity and small sample sizes in the included studies, emphasizing the need for larger RCTs specifically for DPG.
