Madalene CY Heng*
1Professor of Medicine/Dermatology, UCLA School of Medicine, USA
Received: 19 April, 2017; Accepted: 05 July, 2017; Published: 06 July, 2017
Madalene C.Y. Heng, Professor of Medicine/Dermatology, UCLA School of Medicine, USA, E-Mail:
Heng MCY (2017) Topical Curcumin: A Review of Mechanisms and uses in Dermatology. Int J Dermatol Clin Res 3(1):010-017. DOI: 10.17352/2455-8605.000020
© 2017 Heng MCY, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Curcumin, the active ingredient in the spice turmeric, has been used in many Eastern countries for its known anti-inflammatory activity. Recently, analysis of multiple studies have cast doubt with regard to the efficacy of oral curcumin in several diseases. While the effectiveness of oral curcumin is hindered by its low bioavailability and poor absorption by the oral route, this is not the case for topical curcumin. In this review, we discuss the mechanisms for its anti-inflammatory and anti-apoptotic activity based on its inhibitory activity on the enzyme, phosphorylase kinase, and present evidence for its salutary effects on burns, wounds, surgical scars, photo-damaged skin and psoriasis.
Curcumin (diferuloylmethane) is one of the ingredients found in the spice, turmeric. Turmeric has been used for centuries in many Eastern countries both as a spice and as a medicine. In recent years, extensive studies have been done on the potential medicinal value of curcumin, particularly when taken orally. The effectiveness of oral curcumin, however, is hindered by poor bioavailability because the unconjugated curcumin molecule, which is hydrophobic, is poorly absorbed by the gastrointestinal tract. Very low curcumin levels are detected in blood and tissues following curcumin ingestion [1-3]. The molecule is mainly absorbed as water-soluble curcumin glucoronate or sulfate metabolites, which are largely inactive products. In contrast, topical curcumin can be formulated to be better absorbed through the skin, particularly when the skin barrier becomes defective in the presence of skin injury and disease. Largely because of the unfavorable pharmacokinetics of oral curcumin, the extensive literature on therapeutic potential of oral curcumin in clinical trials has been disappointingly negative . There have been much fewer studies with topical curcumin despite the fact that the use of topical curcumin is not hindered by issues of gastrointestinal absorption.
In this review, we will present our clinical experience with topical curcumin in several dermatologic disorders, and discuss the mechanisms that may underlie the biologic basis of how topical curcumin may potentially be useful in these conditions. We found topical curcumin to be effective in a number of conditions associated particularly with skin injury and inflammation. We believe that the most likely mechanism responsible for these results is related to the unique ability of curcumin to inhibit the enzyme, phosphorylase kinase. In addition, topical preparations can be more easily formulated to increase penetration of the hydrophobic curcumin through the skin, unlike the problems encountered with curcumin bioavailability in the gut. Skin penetration of topical curcumin may also be enhanced in dermatologic disorders because of inflammation and loss of the normal skin barrier function. These factors make the potential therapeutic value of topical curcumin much more promising than that found so far with oral curcumin.
Curcumin is widely known to have anti-inflammatory properties . In cell cultures, it has been shown to suppress the proliferation of a wide variety of tumor cells, downregulate transcription factors (NF-kB, AP-1), downregulate the expression of cytokines (TNF-α), cell surface adhesion molecules and cyclin D, and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinase, and protein serine/threonine kinases .
How curcumin may have therapeutic benefits became better understood after discovery that curcumin is a selective inhibitor of phosphorylase kinase , Phosphorylase kinase is an enzyme responsible for breaking down glycogen, eventually to form ATP, and plays an important role in phosphorylation reactions . Phosphorylase kinase is released within 5 mins after injury and plays a key role in the injury pathway with significant effect on activation of inflammatory cells [7-9], wound healing and scar tissue formation . Inhibition of phosphorylase kinase activity by curcumin results in modulation of the inflammatory response because of downregulation of transcription factors, cytokines, adhesion molecules, cyclin kinases, and a variety of protein kinases.
Curcumin has been reported to induce apoptosis in damaged cells [11-13]. The process may allow more rapid replacement of the injured cells by normal healthy cells . This may be the mechanism for our clinical observations of improved healing of burns and sun-burns. Curcumin-induced apoptosis may also function in the improvement observed with the application of curcumin gel on sun-damaged skin. The removal of damaged premalignant cells by apoptosis allows the space for replacement by new, healthy cells without the potential of malignant transformation . By blocking phosphorylation, curcumin may block the DNA Damage Repair (DDR) pathway through histone-mediated DNA repair, and as a consequence, accelerate apoptosis . Curcumin-mediated apoptosis has been shown to occur through the mediation of the mitochondrial pathway .
The mechanism of curcumin-induced apoptosis may also be achieved by inhibition of phosphorylase kinase. Georgoussi et al., has reported that phosphorylase kinase also exhibits phosphatidylinositol kinase activity . This is significant since the early participants in the DDR pathway include a family of phosphatidylinositol kinases responsible for Cell Cycle Arrest, Nucleotide Excision and Repair and DNA replication . It is probable that curcumin induces apoptosis by blocking phosphorylation of the phosphatidylinositol kinases through phosphorylase kinase inhibition.
Injury Pathway and NF-KB Activation in the Inflammatory Response: The key molecule in the tissue injury pathway (Figure 1) is a transcription activator, nuclear factor-kB, which is expressed as early as 30 mins after injury [15,16]. In the non-activated state, NF-kB exists as a pair of dimers (p50/p65) within the cytoplasm. When activated by injury, phosphorylation occurs at several serine specific sites (Ser276; Ser529, Ser536), and the dimers translocate to the nucleus, where they bind to the kB site on the DNA, resulting in turning on over 200 genes related to inflammation, cell migration, cell cycling, and cell proliferation [7-10]. Before the dimers are able to translocate to the nucleus, the inhibitory molecule, IkBα is removed, and the removal requires the activation of its kinase, IkBα kinase. Activation of the IkBα kinase requires phosphorylation of both serine (Ser171, Ser181) and tyrosine (Tyr188, Tyr199) moieties [7-10]. Phosphorylation of both Serine and Tyrosine moieties is achieved by the dual specificity kinase, phosphorylase kinase.