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Emerging therapeutic potential of curcumin in the management of dermatological diseases: an extensive review of drug and pharmacological activities
Future Journal of Pharmaceutical Sciences volume 9, Article number: 42 (2023)
Abstract
Background
Curcumin is a bright colored polyphenolic moiety which is derived from the rhizomes of Curcuma longa of family Zingiberaceae. Its simple molecular structure, high efficacy, variable therapeutic effects and multidimensional use make it ideal for various treatment regimens.
Main body
It has been used for centuries for its antioxidant, anti-inflammatory and antibacterial characteristics which makes it ideal in the determent and treatment of skin inflammation, psoriasis, acne, premature skin aging and skin cancers. It also exhibits antiviral, antiulcer, anticarcinogenic, antimutagenic, antibacterial, hypocholesteremia and antifungal, benefits making it a perfect multifunctional moiety for treating numerous disorders. Curcumin offers protection against skin damage induced by persistent UVB exposure. Curcumin has substantial therapeutic potentials against various skin conditions like anti-inflammatory, antioxidant effects, wound healing efficiency any many more. It illustrates a multiplicity of important medicinal properties which has a great potential in treating various dermatological diseases.
Conclusion
The study seeks to provide a comprehensive update on curcumin and its exceptional medicinal profile, which can be efficaciously and appropriately utilized in treating skin conditions like psoriasis, acne, dermatitis, scleroderma, skin cancers, skin aging, fungal infections and wounds.
Background
Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant which belongs to the family Zingiberaceae and is known for its medicinal properties since ancient times. In India, it is extensively used as a home cure for a variety of ailments in Siddha, Ayurveda and Unani. In South East Asian nations, it is used as a coloring agent, spice, preservative and culinary ingredient.
Turmeric is being actively used for multiple conditions like liver disorders, jaundice, dyspepsia, flatulence, biliary disorders, urinary tract infections, burns and several other skin problems [1]. It is composed of around 300 different chemical components which includes terpenoids and phenolic constituents [2]. Diferuloylmethane or curcumin (75%), demethoxycurcumin (20%) and bisdemethoxycurcumin (5%) [3] are the naturally occurring curcuminoids present in turmeric. Curcumin is responsible for turmeric’s vivid yellow color, and it is made up of curcumin I (94%), curcumin II (6%) and curcumin III (0.3%) [4].
Curcumin (1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a natural polyphenol which is lipophilic in nature (Fig. 1). Its simple molecular structure, high efficacy, variable therapeutic effects and multidimensional use make it ideal for various treatment regimens [5]. Curcumin interacts to several proteins and suppresses the action of kinases. It modulates the expression of several cytokines, enzymes and cell survival proteins by influencing the activation of different transcription factors [6].
It is well known for its wide range of therapeutic effects like antioxidant, anti-inflammatory, anticarcinogenic, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antiulcer and anticoagulant activities to name a few [7, 8]. The literature suggests that oral and topical use of turmeric helps in preventing and treating various skin diseases like premature aging, dermatitis, wounds, inflammation and psoriasis [9].
The human skin spreads over an area of about 20 square feet and is composed of tissue layer which safeguards the muscles and organs beneath. It protects, separates and shields the body from its surroundings, regulates body temperature and performs sensory tasks. Researches show that curcumin has substantial therapeutic potentials against various skin conditions like anti-inflammatory, antioxidant effects, wound healing efficiency any many more as shown in Figs. 2 and 3.
Table 1 shows some of the products of curcumin available in the market for the treatment of skin disorders. The study seeks to provide a comprehensive update on curcumin and its exceptional therapeutic activities which can be efficaciously and appropriately utilized in treating skin conditions.
Main text
Curcumin as an active antioxidant
The phenol and diketone moieties are potent free radical quenchers which are highly responsible for the antioxidant properties of curcumin [10]. The free radicals are generated when human skin is exposed to solar radiations, mechanical stress or chemical pollutants. These free radicals lead to skin damage, inflammation and in severe cases skin cancer. Researches shows that curcumin can improvise the systemic markers of oxidative stress markers [11] and can enhance the serum activities of various antioxidants like superoxide dismutase [12,13,14]. Curcumin acts on the harmful free radicals through various mechanisms It can regulate the activity of antioxidant enzymes like glutathione peroxidase, superoxide dismutase and catalase which actively neutralizes the free radicals [15, 16]. It can actively prohibit ROS generating enzymes like as lipoxygenase/cyclooxygenase and xanthine hydrogenase/oxidase [15]. Additionally, being lipophilic in nature, it is a chain breaking antioxidant as it can scavenge peroxyl radicals [17]. The literature-based evidences reveal that curcumin has a strong protective action against hydrogen peroxide-induced skin damage to the keratinocytes and fibroblasts [18].
Treatment for psoriasis
Psoriasis is a severe, persistent and multifactorial autoimmune disease which affects about 3% population of the world. It is caused by hereditary and immunological causes, and it has a significant impact on the skin and joints [19]. The T cell-mediated immunity leads to excessive hyperproliferation of the keratinocytes which results in inflammation, causing excessive cell buildup on the skin surface which rapidly forms inflamed and painful red patches and scales. The normal growth cycle of the skin cell takes approximately 28 to 30 days, but in a psoriasis the skin cells get matured and replaced in every 3–5 days, which results in scaling on the surface of the skin.
The beneficial effect of curcumin in psoriasis is due to its anti-inflammatory, immunomodulating and antioxidant activities. A study was conducted by taking different skin samples of untreated psoriatic patients, patients undergoing topical therapy and non-psoriatic subjects.
Reduced phosphorylase kinase level was found in the patients who were being given topical 1% curcumin alcoholic gel. It revealed that curcumin can suppress the activity of phosphorylase kinase which is responsible for the activation of NF-kB (NF-kB-nuclear factor kappa light chain enhancer of activated B cells) and thus constrain human psoriasis [20, 21]. Curcumin can suppress the exorbitant production of TNF-α (tumor necrotic factor alpha) through activated macrophages [22] and can block the TNF dependent activation of NF-κB by binding to the receptor-binding sites of TNF-α through covalent and non-covalent interactions [22, 23].
Jun Sun et al. demonstrated that daily dose of 1% curcumin gel can diminish imiquimod-induced skin psoriasis-like inflammation by blocking potassium channels expressed in T cells and lowering IL17A, IL17F, IL22 (interleukins) and other pro-inflammatory cytokines in mouse ear samples [24]. Kang et al. in research showed that oral administration of curcumin for 20 days in mice like psoriasis model can reduce generation of T cell inflammatory factors like IL‐17, IL‐22, IFN‐γ, IL‐2, IL‐8 and TNF‐α by 30–60% [25].
Bahraini et al. did a study with forty patients who had scalp psoriasis, and it was inferred that in comparison with the placebo, daily administration of turmeric tonic reduced cutaneous symptoms like scaling, erythema, lesions and also enhanced the patients’ quality of life [26].
Antiga et al. in a clinical trial reported that (oral curcumin) Meriva which was a novel lecithin-based delivery system of curcumin was effective as an adjuvant therapy in treating psoriasis vulgaris and was also found to reduce the serum levels of IL-22 [27].
Sun et al. (2017) investigated the effects of curcumin (dose: 0.25 mg/day) and tacrolimus formulations (dose: 0.1 mg/day) on the psoriasis-like mouse model. Their findings revealed that tacrolimus and 50 nm Curcumin nanoparticles gel reduced the thickness of white scales and the pink coloration in inflamed skin [28].
A clinical study confirmed that administration of oral curcumin is efficacious in plaque psoriasis and has an exceptional safety profile [29].
Bilia et al. in a randomized, placebo controlled, double-blind clinical trial affirmed that curcumin-loaded nanoparticles along with oral acitretin are effective in treating moderate-to-severe psoriasis and improve the lipid serum profile of the psoriatic patients [30].
A study suggested that administration of nanostructured lipid carriers of curcumin and caffeine topically can significantly treat psoriasis and the combination has a great potential in treating psoriasis locally [31]. In a recent study, Jin et al. used smart pearls technology in combination with glycyrrhizic acid to enhance the permeation and anti-psoriatic activity of curcumin in an imiquimod-induced psoriasiform mice. Smart Pearls are a dermal delivery system for poorly soluble active agents, containing nanoporous silica particles loaded with amorphous active agents to increase bioavailability [32].
Curcumin in acne
The cutaneous and long-term disease of skin is acne which occurs when oil and dead cells of the skin clog the follicles of hair which results in abnormal production of sebum. There are several factors that play a prominent role in the generation and pathophysiology of acne, but the major factors are genetics, inflammation, hyperproliferation of follicles, infection by Propionibacterium acnes and sebaceous glands producing sebum in excess amount [31, 33]. Genes such as CYP1A1, interleukins (IL-1α) and tumor necrosis factor (TNF-α) when varied contribute to the development of acne. Lesions formed due to acne can be classified as inflammatory or non-inflammatory, and these lesions affect parts of chest and back but the major area of infection is face. For the treatment of acne, mostly antibiotics are prescribed but they are associated with adverse effects and sometimes also develops resistance. The resistance of Propionibacterium acnes to therapies of antibiotics has steadily increased in recent years, with increasing resistance to clindamycin and erythromycin [34, 35]. Thus, there is a need of developing novel herbal therapies to treat this infection that are devoid of these drawbacks. Due to its wide safety profile and uses, curcumin’s antimicrobial activity has been extensively being studied even at high doses in the clinical trials [36].
The antimicrobial and anti-inflammatory properties of curcumin make it a good candidate for treating acne. In a study, microemulsion of curcumin containing myristic acid was formulated which delivered curcumin in less duration and was able to inhibit bacteria (S. epidermidis) responsible for acne [37]. In another study, lauric acid-based emulsion incorporating curcumin was developed which was able to inhibit Propionibacterium acnes. Also, the smaller size of the emulsion increased its contact and penetration into the membrane of cells [38].
Rajanikant and Jagetia developed a formulation containing curcumin (100 mg/kg) and used mouse skin as a model for in vivo studies for 20 days. Curcumin antioxidant properties reduced the peroxidation of lipids, increased the concentration of glutathione and enhanced the activity of the enzyme superoxide dismutase and glutathione peroxidase in the skin. Thus, improving the condition of acne [39].
A dose-dependent, in vitro microbicide activity against both Propionibacterium acnes and Staphylococcus aureus was obtained with curcumin activated by blue light. This may be due to the action of vanillin (product obtained by photolytic degradation of curcumin) which disrupted the membrane of the bacterial cell [40].
Potential against scleroderma
The disease of connective tissue which results in fibrosis and vasculopathy of organs and skin is called scleroderma [41]. Scleroderma may be due to increased production of extracellular matrix (ECM) vascular abnormalities and fibrosis [42]. It has been discovered that the oxidative stress has significant role in disease development [43]. Many studies have confirmed that scleroderma patients have increased free radical content, such as peroxynitrite and hydroxyl radicals, and the 8-isoprostane levels in serum increases [44]. In addition, mice treated with free radical release agents demonstrate cutaneous fibrosis [45]. Thus, many diseases of skin can be related to oxidative stress, leading to inflammatory diseases. Scleroderma features include immune system activation and inflammatory cells perivascular infiltration, and thus, for treatment, immune-suppression can be taken into consideration [46]. Scleroderma hallmark is ECM accumulation in excessive amount which induces inflammation [47, 48]. When ECM of the tissues is disrupted, it can initiate and propagate the inflammation which liberate ECM molecules like sulfated proteoglycans, tenascins and hyaluronan fragments. These molecules result in triggering and amplification of inflammation and acts as ‘alarmins’ [45].
Curcumin has the anti-fibrosis effect, characterized by formation of keloid, production of ECM in fibrosis and reduced deposition of collagen [49]. In scleroderma, significant role is played by isoforms of protein kinase C (PKC), i.e., ε and δ. A study with the administration of curcumin, done in vitro and in vivo, found that fibrosis and accumulation of ECM reduced due to decline in the PKC δ levels [50]. Nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF-κB) and cytokines responsible for fibrosis and angiogenesis are abnormally regulated [21]. In scleroderma lung fibroblasts (SLF), curcumin induces HO-1 and GST P1 which inhibits protein kinase C epsilon (PKCε), thus inducing apoptosis. Curcumin was also able to modulate cascade of TGF-β by inhibiting decline of TGIF (TGF-β induced factor) [51]. Another research indicated that curcumin may have a beneficial impact in scleroderma care as it may provide protection to rats from lung fibrosis caused due to numerous agents [52]. This shows that curcumin has a potential role in the scleroderma treatment, but ample work is also required.
Anti-inflammatory and wound healing effect of curcumin
Stimuli like irritants and pathogens make the defense mechanism of the body to act and involve molecular mediators, blood vessels and immune cells, resulting in inflammation (acute and chronic). Inflammation signs include heat, swelling, immobility, redness and pain. The immunoregulatory responses and inflammation of skin are due to several factors like mitogen‐activated protein kinase (MAPK), c‐Jun NH2‐terminal kinase, NF-κB activation, IL-1, IL-6, IL-8, IL-10 and IL-21 induced by TNF-α and cytokines. Cytokine receptors alteration, cytokines dysregulation and cytokines overproduction are associated with disorders of skin inflammation.
The anti-inflammatory properties of curcumin have been unambiguously identified in various organs, such as the skin and liver, by modulating autoimmune disease and preventing damage to the tissues of the organs [53, 54]. Curcumin reduces the expression of the two principal cytokines—TNF-α and IL-1 produced by macrophages and monocytes, and thus helps in modulating inflammation [3, 25]. NF-κB (transcriptional pro-inflammatory factor) is also inhibited by curcumin. This regulates genes responsible for response of inflammation. The anti-inflammatory activities of curcumin may be used to regulate skin inflammation caused by various skin diseases. In a study conducted ex vivo and in vitro, to avoid bovine serum albumin denaturation, the anti-inflammatory activities of curcumin nanospheres and curcumin were investigated and compared with diclofenac sodium. Curcumin nanospheres showed highest anti-inflammatory activity in the in vitro test [55].
Skin is an important, environmental-protective organ for the body. Chronic skin injuries allow the body to begin a complex and multistep healing process to restore the integrity of the tissue. These processes include remodeling, proliferation, inflammation and homeostasis [56, 57]. After injury, clot is formed due to platelet aggregation. Inflammation starts at the site of injury due to migration of macrophages and neutrophils at wound location. They promote the migration of fibroblast at the wound site which starts blood vessels generation and re-epithelialization. This phase is called proliferation, and collagen plays a major role in that [58, 59]. Wound healing final step is scar tissue formation and remodeling of collagen. Neutrophils is attracted to the site of injury which releases IL-1 and TNF-α [55]. The phase of inflammation is prolonged due to increased level of reactive oxygen species and destructive proteases associated with neutrophils in the area of wound, and this delays the healing of wound [60, 61].
The anti-infective, anti-inflammatory and antioxidant properties of curcumin play a significant role in healing of wound [3, 58]. In order to improve the rate of healing of wound, curcumin topical application showed facilitation of re-epithelialization in areas of burn wound [59, 62]. Various clinical trials showed that curcumin improved the healing of wound, increased cuticular layer thickness and epidermal growth rate in comparison with the subjects untreated [63,64,65,66].
Another study on rat skin showed that curcumin when applied topically improved the healing of burn wound, enhanced epithelialization, formation of granulation tissue, angiogenesis in comparison with control group [59]. In research, nanovesicles of curcumin were prepared and studied in both in vitro and in vivo which helped in the prevention of skin lesions formation and damage of epithelia by inhibiting the biochemical process [63]. The nanovesicles also increased the penetration of curcumin into the skin.
Active antifungal agent
In general, fungal infections occurring in humans in mostly tropical and subtropical areas are more conducive to the growth and spread of fungi [67]. They posed a persistent and real danger to the lives of humans at this period. Healthy people are helpless against numerous systemic infections, subcutaneous, cutaneous and superficial infections that can change from specific conditions to serious dangerous diseases threatening to life [64, 65]. Dermatophytes are majorly responsible for fungal infections of nails, hair and skin. Candida species are also responsible for infections that further persuade to deep tissues and may be threatening to life [68]. Continuous improvement is made in treating skin-related fungal infections with treatment, but they remain difficult to manage. In general, traditional formulations (shampoo, spray, cream) do not cause any adverse effects, although sometimes causes little redness, burning or itching, while oral medications may lead to several side effects. Researchers have been investigating the use of many herbs that can be used effectively as potent antifungal agents.
It is stated from studies that curcumin has significant antimicrobial activity against parasites, viruses, fungi and bacteria. The fungal inhibitory activity of curcumin (0.8 g/L) was shown in a study of plant tissue culture [69]. Curcumin antifungal activity is shown by its action against C-5 sterol desaturase and ergosterol inhibiting activity by producing reactive oxygen species and thus shows prominent activity toward Paracoccidioides brasiliensis [70, 71]. Curcumin also modifies the ATPase movement properties and decreases proteinase emission, contributing its antifungal activity [72]. It was found responsible for the inhibition of the candida species, as it inhibits H + extrusion and provides acidic environment [73]. Curcumin’s anti-inflammatory effects have rendered it the most effective agent for candidiasis treatment. It was able to inhibit fungi growth in mice more than that of dexamethasone administered orally [74]. Curcumin with photodynamic treatment was confirmed as a viable technique for antifungal activity against the yeasts’ planktonic form [75]. The problem of development of resistance is occurring with already available antifungals, and thus, combined treatment is the medical endeavor to remedy the current condition and eradicate the fungal infection altogether. It provides synergistic action, fewer resistance, low toxicity and broad spectrum [76]. Curcumin when used along with miconazole, fluconazole, ketoconazole, voriconazole and itraconazole showed higher potency against fungi. Similar affect was observed with nystatin and amphotericin. The minimum inhibitory concentration against candida was reduced when curcumin was used with ascorbic acid [77]. Table 2 shows the efficacy of Curcumin as an active antifungal agent.
Protection against skin cancer
Skin cancer is a condition in which the skin outer layers show cells malignant in nature. Skin cancer is classified into two types, i.e., melanoma and non-melanoma. In melanoma cancer, melanocytes are involved, whereas in case of non-melanoma, squamous or basal cells are involved. Majority of skin cancers are categorized as non-melanoma [78]. The interaction between the environment and genes is responsible for skin cancer. The main cause of the cancer in skin is sun exposure but genetic factor also plays a crucial role in the occurrence of the cancer. Some other factors which contribute to the skin cancer are arsenic exposure, trauma and X-rays [79].
Studies have shown that expression of cytokine can promote melanoma cell metastasis and growth. It is reported in a study that more than 80 percent of cell lines of human melanoma contain osteopontin, growth factor AA derived from platelet, vascular endothelial growth factor, interleukins—1α,6,8, transforming growth factor β and cytokines in excessive amount that stimulates angiogenesis, invasion and tumor development [80].
A study conducted in vitro with curcumin (dose ranging from 5-50 µm) on the cell lines of fibroblast of lungs (MRC-5) and cell lines of melanoma (M14, MV3, A375) showed that as the curcumin concentration increased, melanoma cells viability decreased. Curcumin was found responsible for triggering of melanocytes apoptosis as it suppressed NF-κB activation and proliferation. It also suppressed expression of myeloid cell leukemia-1 and protein of B cell lymphoma (Bcl-2). The induction of apoptosis by curcumin was confirmed by the increase in ratio of t-bax to Bcl-2. Thus, curcumin was able to provide relief in the antitumor activity by inducing apoptosis [81]
Jose et al. [82] formulated liposomes of 1,2-dioleoyl-3-trimethylammonium-propane in which curcumin was encapsulated along with small interfering RNA transcription 3 activators and signal transducers. This combination was able to inhibit the weight of tumor and progress in its volume in melanoma-based animal model in comparison with alone small interfering RNA transcription 3 activators and curcumin liposome.
Tsai et al. [83] demonstrated in his study that curcumin can provide protection against UVB radiation-induced skin cancer growth in a mouse model. Li et al. [84] illustrated that curcumin has a chemoprotective potential against skin carcinogenesis in vivo and in vitro.
In carcinogenesis of skin, crucial role is played by oxidative stress. Oxidative cell stress is generated by free radicals produced by activation of oxygen. These free radicals are produced mainly by chemicals and UV light. Thus, curcumin which has an antioxidant property may be used as an important chemo-preventive agent for carcinogenesis of the skin of the mouse [85]. The ability of curcumin to inhibit cancer of skin can be justified by this data and thus can be used as an adjuvant therapy in its treatment.
Anti-aging property
Continuous exposure of the skin to ultraviolet radiations, i.e., UV either from sunlight or any other artificial source, can lead to premature aging of the skin which is called as ‘photoaging’ and can alter the normal skin structure.
The antioxidant and anti-inflammatory action of curcumin helps it in averting the premature aging of the skin. It can protect the skin partially against UV deterioration which reduces the chance of skin tumors development thereby preventing premature aging. [86].
A clinical study evaluated the usefulness and efficiency of an herbal gel (Tricutan®) which was a combination of gotu kola, rosemary and turmeric on 28 women who were in there 30’s. The study revealed that using the herbal gel for four weeks can significantly ameliorate the signs of photoaging and skin firmness [9].
A molecular-based biology study illustrated inhibitory effects of curcumin on UVB-induced generation of reactive oxygen species (ROS) and in vitro expression of matrix metalloproteinase (MMP) by inhibiting the activation UVB-induce of nuclear factor-κB (NF-κB), mitogen-activated protein kinase and AP-1 transcription factor signal pathways [87]. Thus, curcumin can be helpful in treating photoaging.
Curcumin in atopic dermatitis
Atopic dermatitis is a chronic disease of skin with a still unclear etiology and stems from a complex combination of factors like immunity, environment and genetics [88]. Infants are likely to be affected along which it is highly prevalent in adults as well [89]. Pathogenesis of atopic dermatitis critically includes an imbalance in the subsets of T cell. Cytokines such as IL-31,13,5,3 are abnormally reduced by Th2 in the initial stage, whereas this response switches over to Th1 type-immune response in the later stages, along with an intense increase in IL-18,12,6,1 and TNF α by monocytes [90]. Curcumin has historically been used in the countries of Asia to treat symptoms of atopic dermatitis [91].
Curcuma longa is used to isolate p-hydroxycinnamic acid (a phytocomponent) which inhibits the activation of T cell by modulating the pathway of PKCθ (protein kinase C theta) [20]. When p-hydroxycinnamic acid was administered in a model study of animals, it was observed that the keratinocytes produced reduced number of cytokines both in vitro and tissues of ear. This led to improvement in inflammation and thickening of epidermal layer [93].
In patients 150 patients of eczema, Herbavate® (an herbal cream) along with C. longa when used daily shows significant alleviation of itching, thickening, scaling and erythema assessed by a 4-point score weekly (p < 0.001). Safety profile was also good, as only 5 patients reported side effects, there was no local intolerance and no patient showed adverse events [94].
Some reports showed contact urticaria and dermatitis after the application of cream containing curcumin topically [95,96,97]. Thus, there is a need to establish more trial study to investigate the curcumin role in the management of atopic dermatitis.
Potential activity in iatrogenic dermatitis
Iatrogenic dermatitis includes a number of conditions of skin inflammation which can be directly linked to medical procedures and the administration of drugs. For instance, radiation-induced dermatitis and allergic contact dermatitis fall under this category. Various studies demonstrate the efficacy of curcumin for the prophylaxis of iatrogenic dermatitis. In a model, curcumin when applied topically shows significant improvement in recovery of epithelial cell and irradiated skin, due to its anti-inflammatory activity [98].
A randomized study that assessed curcumin (administered orally 6 g/day) in patients of breast cancer (n = 30) while undergoing sessions of radiotherapy shows a significant reduction in the severity of dermatitis induced by radiations [49, 99]. When 4 g/day of curcumin was administered in the patients of cancer (n = 40) undergoing under capecitabine treatment, curcumin was found to prevent the syndrome of hand–foot induced by capecitabine. However, the mechanism for this action of curcumin was not elucidated fully [82, 91, 92].
In another study, 1 g of curcumin when administered orally daily along with piperine for the period of four weeks in 46 patients, symptoms of chronic pruritus induced by sulfur mustard was improved. Due to the curcumin antioxidant properties, the levels and activities of catalase, glutathione, superoxide dismutase in serum along with levels of markers of inflammation were reduced [9].
Conclusion
Curcumin illustrates a multiplicity of important medicinal properties which has a great potential in treating various dermatological diseases. The clinical studies cited in the article reveal that curcumin has an exceptional anti-inflammatory, antioxidant and antibacterial activities, which can be efficaciously and appropriately utilized in treating skin conditions like psoriasis, acne, dermatitis, scleroderma, skin cancers, skin aging, fungal infections and wounds.
Availability of data and materials
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
Hewlings SJ, Kalman DS (2017) Curcumin: a review of its’ effects on human health. Foods 6(10):92
Aggarwal BB, Yuan W, Li S, Gupta SC (2013) Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric. Mol Nutr Food Res 57(9):1529–1542
Akbik D, Ghadiri M, Chrzanowski W, Rohanizadeh R (2014) Curcumin as a wound healing agent. Life Sci 116(1):1–7
Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R (1995) Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 94(1):79–83
Cheppudira B, Fowler M, McGhee L, Greer A, Mares A, Petz L et al (2013) Curcumin: a novel therapeutic for burn pain and wound healing. Expert Opin Investig Drugs 22(10):1295–1303
Harsh M (2006) Textbook of pathology, 5th edn. New Delhi, Medical Publisher Ltd
Chattopadhya I, Biswas K, Bandoyopadhyay U, Bannerjee RK (2004) Turmeric and curcumin: biological action and medical applications. Curr Sci 87(1):44–53
Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B et al (2008) Biological activities of curcumin and its analogues (congeners) made by man and mother nature. Biochem Pharmacol 76(11):15090–21611
Vaughn AR, Branum A, Sivamani RK (2016) Effects of turmeric (curcuma longa) on skin health: a systematic review of the clinical evidence. Phytother Res 30(8):1243–1264
Lee WH, Loo CY, Bebawy M, Luk F, Mason RS, Rohanizadeh R (2013) Curcumin and its derivatives: their application in neuropharmacology and neuroscience in the 21st century. Curr Neuropharmacol 11(4):338–378
Sahebkar A, Serbanc MC, Ursoniuc S, Banach M (2015) Effect of curcuminoids on oxidative stress: a systematic review and meta-analysis of randomized controlled trials. J Funct Foods 18:898–909
Banach M, Serban C, Aronow WS, Rysz J, Dragan S, Lerma EV (2014) Lipid, blood pressure and kidney update 2013. Int Urol Nephrol 46:947–961
Menon VP, Sudheer AR (2008) Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol 595:105–125
Panahi Y, Alishiri GH, Parvin S, Sahebkar A (2016) Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized controlled trial. J Diet Suppl 13:209–220
Lin YG, Kunnumakkara AB, Nair A, Merritt WM, Han LY, Armaiz-Pena GN et al (2007) Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-κB pathway. Clin Cancer Res 13:3423–3430
Marchiani A, Rozzo C, Fadda A, Delogu G, Ruzza P (2014) Curcumin and curcumin-like molecules: from spice to drugs. Curr Med Chem 21:204–222
Priyadarsini KI, Maity DK, Naik GH, Kumar MS, Unnikrishnan MK, Satav JG (2003) Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. Free Radic Biol Med 35:475–484
Phan TT, See P, Lee ST, Chan SY (2001) Protective effects of curcumin against oxidative damage on skin cells in vitro: its implication for wound healing. J Trauma 51(5):927–931
Lowes MA, Suárez-Fariñas M, Krueger JG (2014) Immunology of psoriasis. Annu Rev Immunol 32:227–255
Heng MC, Song MK, Harker J, Heng MK (2000) Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters. Br J Dermatol 143(5):937–949
Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41(1):40–59
Abe Y, Hashimoto S, Horie T (1999) Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 39:41–47
Gupta SC, Prasad S, Kim JH, Patchva S, Webb LJ, Priyadarsini IK (2011) Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep 28:1937–1955
Sun J, Zhao Y, Hu J (2013) Curcumin inhibits imiquimod-induced psoriasis-like inflammation by inhibiting IL-1beta and IL-6 production in mice. PLoS ONE 8(6):e67078
Kang D, Li B, Luo L, Jiang W, Lu Q, Rong M, Lai R (2016) Curcumin shows excellent therapeutic effect on psoriasis in mouse model. Biochimie 123:73–80
Bahraini P, Rajabi M, Mansouri P, Sarafian G, Chalangari R, Azizian Z (2018) Turmeric tonic as a treatment in scalp psoriasis: a randomized placebo-control clinical trial. J Cosmet Dermatol 17(3):461–466
Antiga E, Bonciolini V, Volpi W, Del Bianco E, Caproni M (2015) Oral curcumin (meriva) is effective as an adjuvant treatment and is able to reduce IL-22 serum levels in patients with psoriasis vulgaris. Biomed Res Int 283634
Sun L, Liu Z, Wang L, Cun D, Tong HHY, Yan R, Zheng Y (2017) Enhanced topical penetration, system exposure and anti-psoriasisactivity of two particle-sized, curcumin-loaded PLGA nanoparticles inhydrogel. J Control Release 254:44–54
Iriventi P, Gupta NV (2020) Topical delivery of curcumin and caffeine mixture-loaded nanostructured lipid carriers for effective treatment of psoriasis. Phcog Mag 16:206–217
Bilia AR, Bergonzi MC, Isacchi B, Antiga E, Caproni M (2018) Curcumin nanoparticles potentiate therapeutic effectiveness of acitrein in moderate-to-severe psoriasis patients and control serum cholesterol levels. J Pharm Pharmacol 70(7):919–928
Beylot C, Auffret N, Poli F, Claudel JP, Leccia MT, Del Giudice P (2014) Propionibacterium acnes: an update on its role in the pathogenesis of acne. J Eur Acad Dermatol Venereol 28(3):271–278
Jin N, Lin J, Yang C, Wu C, He J, Chen Z et al (2020) Enhanced penetration and anti-psoriatic efficacy of curcumin by improved smartPearls technology with the addition of glycyrrhizic acid. Int J Pharm 578:119101
Williams HC, Dellavalle RP, Garner S (2012) Acne vulgaris. Lancet 379(9813):361–372
Del Rosso JQ (2016) Topical and oral antibiotics for acne vulgaris. Semin Cutan Med Surg 35(2):57–61
Dessinioti C, Katsambas A (2017) Propionibacterium acnes and antimicrobial resistance in acne. Clin Dermatol 35(2):163–167
Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K (2014) A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int 2014:186864
Liu CH, Huang HY (2012) Antimicrobial activity of curcumin-loaded myristic acid microemulsions against Staphylococcus epidermidis. Chem Pharm Bull (Tokyo) 60(9):1118–1124
Liu CH, Huang HY (2013) In vitro anti-propionibacterium activity by curcumin containing vesicle system. Chem Pharm Bull (Tokyo) 61(4):419–425
Jagetia GC, Rajanikant GK (2015) Curcumin stimulates the antioxidant mechanisms in mouse skin exposed to fractionated γ-irradiation. Antioxidants (Basel) 4(1):25–41
Yang MY, Chang KC, Chen LY, Hu A (2018) Low-dose blue light irradiation enhances the antimicrobial activities of curcumin against propionibacterium acnes. J Photochem Photobiol B 189:21–28
Lambova S (2014) Cardiac manifestations in systemic sclerosis. World J Cardiol 6(9):993–1005
Nguyen TA, Friedman AJ (2013) Curcumin: a novel treatment for skin-related disorders. J Drugs Dermatol 12(10):1131–1137
Zhou CF, Yu JF, Zhang JX, Jiang T, Xu SH, Yu QY (2013) N-acetylcysteine attenuates subcutaneous administration of bleomycin-induced skin fibrosis and oxidative stress in a mouse model of scleroderma. Clin Exp Dermatol 38(4):403–409
Avouac J, Borderie D, Ekindjian OG, Kahan A, Allanore Y (2010) High DNA oxidative damage in systemic sclerosis. J Rheumatol 37(12):2540–2547
Servettaz A, Goulvestre C, Kavian N, Nicco C, Guilpain P, Chéreau C et al (2009) Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse. J Immunol 182(9):5855–5864
Cappelli S, Bellando-Randone S, Guiducci S, Matucci-Cerinic M (2014) Is immunosuppressive therapy the anchor treatment to achieve remission in systemic sclerosis? Rheumatology (Oxford) 53(6):975–987
Gaudet AD, Popovich PG (2014) Extracellular matrix regulation of inflammation in the healthy and injured spinal cord. Exp Neurol 258:24–34
Mukherjee PK, Maity N, Nema NK, Sarkar BK (2011) Bioactive compounds from natural resources against skin aging. Phytomedicine 19(1):64–73
Hsu YC, Chen MJ, Yu YM, Ko SY, Chang CC (2010) Suppression of TGF-β1/SMAD pathway and extracellular matrix production in primary keloid fibroblasts by curcuminoids: its potential therapeutic use in the chemoprevention of keloid. Arch Dermatol Res 302(10):717–724
Conboy L, Foley AG, O’Boyle NM, Lawlor M, Gallagher HC, Murphy KJ (2009) Curcumin-induced degradation of PKC delta is associated with enhanced dentate NCAM PSA expression and spatial learning in adult and aged Wistar rats. Biochem Pharmacol 77(7):1254–1265
Song K, Peng S, Sun Z, Li H, Yang R (2011) Curcumin suppresses TGF-β signaling by inhibition of TGIF degradation in scleroderma fibroblasts. Biochem Biophys Res Commun 411(4):821–825
Thresiamma KC, George J, Kuttan R (1996) Protective effect of curcumin, ellagic acid and bixin on radiation induced toxicity. Indian J Exp Biol 34(9):845–847
Agrawal R, Sandhu SK, Sharma I, Kaur IP (2015) Development and evaluation of curcumin-loaded elastic vesicles as an effective topical anti-inflammatory formulation. AAPS PharmSciTech 16(2):364–374
Koop HS, de Freitas RA, de Souza MM, Savi R Jr, Silveira JL (2015) Topical curcumin-loaded hydrogels obtained using galactomannan from Schizolobium parahybae and xanthan. Carbohydr Polym 116:229–236
Arunraj TR, Sanoj Rejinold N, Mangalathillam S, Saroj S, Biswas R, Jayakumar R (2014) Synthesis, characterization and biological activities of curcumin nanospheres. J Biomed Nanotechnol 10(2):238–250
Hussain Z, Thu HE, Ng SF, Khan S, Katas H (2017) Nanoencapsulation, an efficient and promising approach to maximize wound healing efficacy of curcumin: A review of new trends and state-of-the-art. Colloids Surf B Biointerfaces 150:223–241
Margolis DJ, Hoffstad O, Nafash J, Leonard CE, Freeman CP, Hennessy S, Wiebe DJ (2011) Location, location, location: geographic clustering of lower-extremity amputation among Medicare beneficiaries with diabetes. Diabetes Care 34(11):2363–2367
Mohanty C, Sahoo SK (2017) Curcumin and its topical formulations for wound healing applications. Drug Discov Today 22(10):1582–1592
Kulac M, Aktas C, Tulubas F, Uygur R, Kanter M, Erboga M, Ceber M, Topcu B, Ozen OA (2013) The effects of topical treatment with curcumin on burn wound healing in rats. J Mol Histol 44(1):83–90
Guo S, Dipietro LA (2010) Factors affecting wound healing. Version 2. J Dent Res 89(3):219–29
Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U (2017) Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res 58(1–2):81–94
López-Jornet P, Camacho-Alonso F, Jiménez-Torres MJ, Orduña-Domingo A, Gómez-García F (2011) Topical curcumin for the healing of carbon dioxide laser skin wounds in mice. Photomed Laser Surg 29(12):809–814
Castangia I, Nácher A, Caddeo C (2014) Fabrication of quercetin and curcumin bionanovesicles for the prevention and rapid regeneration of full-thickness skin defects on mice. Acta Biomater 10(3):1292–1300
Gupta M, Goyal AK, Paliwal SR, Paliwal R, Mishra N, Vaidya B, Dube D, Jain SK, Vyas SP (2010) Development and characterization of effective topical liposomal system for localized treatment of cutaneous candidiasis. J Liposome Res 20(4):341–350
Kumar L, Verma S, Bhardwaj A, Vaidya S, Vaidya B (2014) Eradication of superficial fungal infections by conventional and novel approaches: a comprehensive review. Artif Cells Nanomed Biotechnol 42(1):32–46
Wen H, Wu G, Chen W, Yang H, Fu J (2012) Topical application of leptin promotes burn wound healing in rats. Nan Fang Yi Ke Da Xue Xue Bao 32(5):703–706
Hsu LY, Wijaya L, Shu-Ting Ng E, Gotuzzo E (2012) Tropical fungal infections. Infect Dis Clin N Am 26(2):497–512
Martiska J, Snejdrova E, Drastik M, Matysova L, Dittrich M, Loskot J, Jilek P (2019) Terbinafine-loaded branched PLGA-based cationic nanoparticles with modifiable properties. Pharm Dev Technol 24(10):1308–1316
Upendra RS, Khandelwal P, Reddy AHM (2011) Turmeric powder (Curcuma longa Linn.) as an antifungal agent in plant tissue culture studies. Int J Eng Sci 3:7899–7904
Martins CV, da Silva DL, Neres AT et al (2009) Curcumin as a promising antifungal of clinical interest. J Antimicrob Chemother 63(2):337–339
Sharma M, Manoharlal R, Puri N, Prasad R (2010) Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans. Biosci Rep 30(6):391–404
Neelofar K, Shreaz S, Rimple B, Muralidhar S, Nikhat M, Khan LA (2011) Curcumin as a promising anticandidal of clinical interest. Can J Microbiol 57(3):204–210
Khan N, Shreaz S, Bhatia R, Ahmad SI, Muralidhar S, Manzoor N, Khan LA (2012) Anticandidal activity of curcumin and methyl cinnamaldehyde. Fitoterapia 83(3):434–440
Karaman M, Arıkan Ayyıldız Z, Fırıncı F, Kiray M, Bağrıyanık A, Yilmaz O, Uzuner N, Karaman O (2011) Effects of curcumin on lung histopathology and fungal burden in a mouse model of chronic asthma and oropharyngeal candidiasis. Arch Med Res 42(2):79–87
Dovigo LN, Pavarina AC, Carmello JC, Machado AL, Brunetti IL, Bagnato VS (2011) Susceptibility of clinical isolates of Candida to photodynamic effects of curcumin. Lasers Surg Med 43(9):927–934
Carrillo-Muñoz AJ, Finquelievich J, Tur-Tur C, Eraso E, Jauregizar N, Quindós G, Giusiano G (2014) Combination antifungal therapy: a strategy for the management of invasive fungal infections. Rev Esp Quimioter 27(3):141–158
Sharma M, Manoharlal R, Negi AS, Prasad R (2010) Synergistic anticandidal activity of pure polyphenol curcumin I in combination with azoles and polyenes generates reactive oxygen species leading to apoptosis. FEMS Yeast Res 10(5):570–578
Kondapalli L, Soltani K, Lacouture ME (2005) The promise of molecular targeted therapies: protein kinase inhibitors in the treatment of cutaneous malignancies. J Am Acad Dermatol 53(2):291–302
Ramirez CC, Federman DG, Kirsner RS (2005) Skin cancer as an occupational disease: the effect of ultraviolet and other forms of radiation. Int J Dermatol 44(2):95–100
Elias EG, Hasskamp JH, Sharma BK (2010) Cytokines and growth factors expressed by human cutaneous melanoma. Cancers (Basel) 2(2):794–808
Jiang AJ, Jiang G, Li LT, Zheng JN (2015) Curcumin induces apoptosis through mitochondrial pathway and caspases activation in human melanoma cells. Mol Biol Rep 42(1):267–275
Jose A, Labala S, Ninave KM, Gade SK, Venuganti VVK (2018) Effective skin cancer treatment by topical co-delivery of curcumin and STAT3 siRNA using cationic liposomes. AAPS PharmSciTech 19(1):166–175
Tsai KD, Lin JC, Yang SM, Tseng MJ, Hsu JD, Lee YJ, Cherng JM (2012) Curcumin protects against UVB-induced skin cancers in SKH-1 hairless mouse: analysis of early Molecular markers in carcinogenesis. Evid Based Complement Altern Med 593952
Lin JK, Lin-Shiau SY (2001) Mechanisms of cancer chemoprevention by curcumin. Proc Natl Sci Counc Repub China B 25(2):59–66
Ahmad N, Katiyar SK, Mukhtar H (2001) Antioxidants in chemoprevention of skin cancer. Curr Probl Dermatol 29:128–139
Bala K, Tripathy BC, Sharma D (2006) Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions. Biogerontology 7(2):81–89
Hwang BM, Noh EM, Kim JS, Kim JM, You YO, Hwang JK, Kwon KB, Lee YR (2013) Curcumin inhibits UVB-induced matrix metalloproteinase-1/3 expression by suppressing the MAPK-p38/JNK pathways in human dermal fibroblasts. Exp Dermatol 22(5):371–374
Grammatikos AP (2008) The genetic and environmental basis of atopic diseases. Ann Med 40(7):482–495
Lee HS, Choi EJ, Lee KS, Kim HR, Na BR, Kwon MS, Jeong GS, Choi HG, Choi EY, Jun CD (2016) Oral administration of p-hydroxycinnamic acid attenuates atopic dermatitis by downregulating Th1 and Th2 cytokine production and keratinocyte activation. PLoS ONE 11(3):e0150952
Gupta SC, Kismali G, Aggarwal BB (2013) Curcumin, a component of turmeric: from farm to pharmacy. BioFactors 39(1):2–13
Lee HS, Kim YD, Na BR, Kim HR, Choi EJ, Han WC, Choi HK, Lee SH, Jun CD (2012) Phytocomponent p-Hydroxycinnamic acid inhibits T-cell activation by modulation of protein kinase C-θ-dependent pathway. Int Immunopharmacol 12(1):131–138
Panahi Y, Sahebkar A, Amiri M, Davoudi SM, Beiraghdar F, Hoseininejad SL, Kolivand M (2012) Improvement of sulphur mustard-induced chronic pruritus, quality of life and antioxidant status by curcumin: results of a randomised, double-blind, placebo-controlled trial. Br J Nutr 108(7):1272–1279
Rawal RC, Shah BJ, Jayaraaman AM, Jaiswal V (2009) Clinical evaluation of an Indian polyherbal topical formulation in the management of eczema. J Altern Complement Med 15(6):669–672
Calapai G, Miroddi M, Minciullo PL, Caputi AP, Gangemi S, Schmidt RJ (2014) Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 1: Achillea millefolium-Curcuma longa. Contact Dermatitis 71(1):1–12
Lopez-Villafuerte L, Clores KH (2016) Contact dermatitis caused by turmeric in a massage oil. Contact Dermatitis 75(1):52–53
Liddle M, Hull C, Liu C, Powell D (2006) Contact urticaria from curcumin. Dermatitis 17(4):196–197
Kim J, Park S, Jeon BS, Jang WS, Lee SJ, Son Y, Rhim KJ, Lee SI, Lee SS (2016) Therapeutic effect of topical application of curcumin during treatment of radiation burns in a mini-pig model. J Vet Sci 17(4):435–444
Ryan JL, Heckler CE, Ling M, Katz A, Williams JP, Pentland AP, Morrow GR (2013) Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res 180(1):34–43
Scontre VA, Martins JC, de Melo Sette CV, Mutti H, Cubero D, Fonseca F, Del Giglio A (2018) Curcuma longa (turmeric) for prevention of capecitabine-induced hand-foot syndrome: a pilot study. J Diet Suppl 15(5):606–612
Garcia-Gomes AS, Curvelo JA, Soares RM, Ferreira-Pereira A (2012) Curcumin acts synergistically with fluconazole to sensitize a clinical isolate of Candida albicans showing a MDR phenotype. Med Mycol 50(1):26–32
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BK contributed to conceptualization, methodology, writing—original draft, writing—review and editing, and visualization; RA was involved in writing—original draft, and writing—review and editing. UP contributed to writing—original draft, and writing—review and editing. PKS was involved in supervision and review. All authors gave their individual critical revision and final approval of the version to be submitted.
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Kumar, B., Aggarwal, R., Prakash, U. et al. Emerging therapeutic potential of curcumin in the management of dermatological diseases: an extensive review of drug and pharmacological activities. Futur J Pharm Sci 9, 42 (2023). https://doi.org/10.1186/s43094-023-00493-1
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DOI: https://doi.org/10.1186/s43094-023-00493-1