Chemoprevention of Skin Cancer: Effect of Lawsonia Inermis L. (Henna) Leaf Powder and its Pigment Artifact, Lawsone in the Epstein- Barr Virus Early Antigen Activation Assay and in Two-Stage Mouse Skin Carcinogenesis Models.

Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20059, USA.
Anti-cancer agents in medicinal chemistry (Impact Factor: 2.47). 06/2013; 13(10). DOI: 10.2174/18715206113139990096
Source: PubMed


In continuation of our studies with chemoprevention potential of plant-derived naphthoquinone derivatives, leaf powder of the medicinal plant Lawsonia inermis L, commonly known as 'henna', was evaluated by its inhibition of the Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Lawsone (2-hydroxy-1,4-naphthoquinone), the reddish orange pigment artifact formed during the extraction or preparation of the dye from henna leaves and believed to be the active component, was also assessed in this in vitro assay. Both showed a profound inhibition (>88%) of EBV-EA activation. In the in vivo two-stage mouse skin carcinogenesis study using UV-B radiation for initiation and TPA for tumor promotion, oral feeding of henna (0.0025%) in drinking water ad libitum decreased tumor incidence by 66% and multiplicity by 40% when compared to the positive control at 10 weeks of treatment. Similarly, in the above mouse model, orally fed lawsone (0.0025%) decreased tumor incidence by 72% and multiplicity by 50%. The tumor inhibitory trend continued throughout the 20-week test period. Similar antitumor activities were observed when henna (0.5 mg/ml) was applied topically on the back skin in the UV-B initiated, TPA promoted and peroxynitrite initiated, TPA promoted mouse skin carcinogenesis models. Topically applied lawsone (0.015 mg/ml) also exhibited similar protection against tumor formation in the 7,12-dimtehylbenz(a)anthracene induced and TPA promoted skin cancer in mice. Also, there was a delay of 1 to 2 weeks in tumor appearance in both henna and lawsone treated groups compared to control in all three test models. This study ascertains the skin cancer chemopreventive activity of henna leaf powder and lawsone when administered by either oral (through drinking water) or topical (by application on the back skin) routes. Further, it emphasizes the need for the evaluation of these henna-derived green chemopreventive candidates in combination with currently used sunscreen agents for complementary anticancer potential against UV-induced skin carcinogenesis.

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    ABSTRACT: Background: Naphthoquinones are natural pigments that are widely distributed in nature and have important biological activities. Lawsone (2-hydroxy-1,4-naphthoquinone) and its synthetic derivatives, and especially those containing nitrogen, have promising potential for the treatment of different diseases due to their antibacterial, antifungal, antiviral, antitumor and antiparasitic effects, and for pest control via their molluscicidal and insecticidal activities. Their pharmacological activities and mechanisms of action are related to their oxide/reduction and acid/base properties, and can be modulated by directly adding a substituted to the 1,4-naphthoquinone ring. Due to this, naphthoquinones and their derivatives are at the center of multiple areas of research. In this manuscript, we present a structured review of lawsone, a hydroxyl derivative of naphthoquinone, and discuss relevant reports about the chemistry and synthesis of derivatives. Finally, we present the pharmacological activities and mechanism of action reported. Objective: The purpose of this review is to present recent reports from the literature about the chemistry, synthesis and pharmacological properties of lawsone and its amine derivatives. Methods: This structured review presents a discussion about lawsone literature over the last ten years. The most representative studies including those about the chemistry of lawsone, the synthesis of its derivatives, and pharmacological properties were identified and selected. The information has been compiled, organized and presented into logical topics in order to provide a current review for the field of lawsone chemistry. Results: A general overview of the principal aspects of lawsone chemistry, the synthesis of its derivatives and their pharmacological activities and mechanism of action has been obtained. This provides researchers in the area with a framework from which to investigate further. Conclusions: Lawsone and its derivatives have promising potential for treating several diseases due to their antibacterial, antifungal, antiviral, antitumor and antiparasitic effects and have the potential to control pests via their molluscicidal and insecticidal properties. For this reason, it would be of interest to evaluate the synthetic derivatives of this compound for their pharmacologic actions; in the future, synthetic derivatives of lawsone could potentially be used to treat disease and be used as pesticides.
    Full-text · Article · Jan 2014 · Vitae
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    ABSTRACT: Ethnopharmacological relevance: The use of Lawsonia inermis L. (henna) for medicinal and cosmetic purposes is inextricably linked to ancient and modern cultures of North Africa and Asia. Literature and artwork indicates that Lawsonia inermis played an important holistic role in the daily lives of some ancient cultures, providing psychological and medicinal benefits, as well as being used for personal adornment. Although henna was historically applied to the hands and feet to protect against fungal pathogens and to hair to combat lice and dandruff, other traditional uses include the treatment of liver and digestive disorders, reduction of tissue loss in leprosy, diabetic foot disorders and ulcers. Phytochemistry: Almost 70 phenolic compounds have been isolated from various parts of the plant. Naphthaquinones, which include the dyeing principle lawsone, have been linked to many of the pharmacological activities. The terpene, β-ionone is largely responsible for the pungent odour of the essential oil isolated from the flowers. In addition to other volatile terpenes, some non-volatile terpenoids, a single sterol, two alkaloids and two dioxin derivatives have also been isolated from the plant. Bioactivity: Henna is a pharmacologically important plant with significant in vitro and in vivo biological activities. Although a myriad of pharmacological activities have been documented, the antioxidant and antimicrobial activities are the most thoroughly investigated. Some incidents of adverse reactions following application to the skin have been reported, but these are mainly confined to cases involving individuals with glucose-6-phosphate dehydrogenase deficiency and reactions to adulterants added to henna products. Conclusions: Adulteration of henna is very common and may have resulted in unwarranted scientific findings. Phytochemical profiling studies of the plant, which are crucial for the establishment of proper quality control protocols, are lacking and hamper the development of medicinal products. Although many in vitro studies have been conducted to evaluate the pharmacological activities and many in vivo studies have focussed on the toxicity of extracts, more in vivo studies to validate pharmacological activities are needed. The roles of specific compounds and their synergies have not been comprehensively investigated.
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