Introduction

The prevalence of cancer is speedily growing worldwide and rank second after cardiovascular diseases targeting both developed and developing countries. Limited supply of anticancer drugs, unaffordable cost of treatments, and lethal adverse effect of several available drugs have shown the way to adopt complementary and alternative medicine for the treatment and/or prevention of cancer Cragg et al., 1997McClellan et al., 2011. Almost twenty five percent of the modern medicine used today originates from plants and the examples include taxol from Taxus baccata (Yew), vincristine and vinblastine from Catharanthus roseus (Sadabahar), podophyllotoxin from Podophyllum peltatum (Mayapple), aspirin from Sahennax species (Willow bark), digitalis fromDigitalis purpurea (Foxglove), pilocarpine from Pilocarpus jaborandi (Jaborandi or Indian hemp). Since the dawn of civilization, plants are essential element of human society and used extensively in folk medicine for the treatment of innumerous ailments. Since then several species of plants have become a part of various indigenous system of treatment such as Ayurveda, Unani, Siddha and Homeopathy collectively known as AYUSH. Plants, rich in secondary metabolites and essential oils have been studied during the last few decades for potential source of drug. Today, it is ballparked that a propos of 70-95 % people dwelling in developing nation relies on traditional medicines for their primary health care Dahanukar et al., 2000. Drugs from plant origin posturing to become source for medicine have led to an unexpected augmentation in the number of herbal industries Kirtikar and Basu, 2005. The isolation of anti-cancer compounds such as vinblastine, vincristine from Catharanthus roseus and podophyllotoxins fromPodophyllum peltatum in 1950s promoted the researchers to explore anticancer agents from plant sources Cassady and Douros, 1980Cragg and Newman, 2005Shoeb,2005. Out of the available anticancer drugs in the market, two-third is either of natural origin or simple modification of the natural product Cragg et al., 1997.

Lawsonia inermis L. (Lythraceae), a monotypic genus, popularly known as ‘Mehndi’ or‘Henna’ is renowned as a cosmetic as well as medicinal agent in the Oriental parts of the world since time immemorial. The plant extracts and purified constituent of henna in folklore accounts for a variety of activities including antibacterial Malekzadeh, 1968, antifungal Tripathi et al., 1978, antioxidant and immunomodulatory (Hsouna et al., 2010)Mikhaeil et al., 2004, hepatoprotective Anand et al., 1992, analgesic, anti-inflammatory and antipyretic Ali et al., 1995, and cytotoxic Ali and Grever, 1998. The bactericidal and fungicidal action of this plant has been attributed through its tanning effect Wessjohann et al., 2003 and it has been confirmed that henna is neither an allergen nor a carcinogen Nayak et al., 2007. The key coloring agent present in henna leaves is a red-orange pigment lawsone (2- hydroxy-1, 4-naphthoquinone) Al-Tufail et al., 1999Lekouch et al., 2001, which makes this plant useful for dying of hair, as well as to color palms, fingers, fingernails and soles Cartwright, 2006Hanna et al., 1998. Lawsone is also a suitable reagent for the detection of latent fingermarks on paper, as contact evidence in criminology Khan and S., 2010. Lawsone (2-hydroxy-1, 4-naphthoquinone) is a starting material in the synthesis of many clinically useful anticancer compounds such as atovaquone, lapachol and dichloroallyl lawsone Pradhan et al., 2012.

In Ayurveda and Unani medicine, Henna has been considered as a source of non-toxic therapeutic agent for blood tonic, cancer, infectious disease, inflammation, tuberculosis, tumors and wounds when; given as single preparation of henna decoction or extract or as blended with other molecules. Translation of Henna compounds and its derivatives to modern drug discovery strategy results to potential new molecule for specific therapeutic agents. The description of lawsone derivatives in our review offers agreeable substantiation for the usefulness of some of these molecules against certain type cancers. It is worthy to notice that lawsone itself has significant antioxidant and anti-inflammatory activity that could be major characteristic of numerous anticancer phytochemicals.

Although Mehndi/Henna extracts and constituents are reported for its pharmacological properties but little attention has been paid to explore its anticancer potential. Therefore, in this review we prepared a palingenesis of information regarding anticancer reports on mehndi/henna by providing maximum available information from its In vitro and in vivo studies.

Information retrieval

Imperative information for the compilation of review was acquired from published literature in form of abstracts, articles, books, notes, peer reviewed papers, summary, texts etc. by using key words ‘Lawsonia inermis’, ‘Mehndi and/or ‘Henna as anticancer agent’, ‘anticancer activity of mehndi/henna’, ‘cytotoxicity of mehndi/henna’, ‘Extracts/ compounds in Mehndi/henna as anticancer agent’ ‘Anticancer/cytotoxicity activities of mehndi/henna extract and essential oil’, ‘Mehndi/henna and cancer cell lines’, ‘Mehndi/henna and cancer/tumor’, ‘chemopreventive properties of mehndi/henna’. Also a comprehensive bibliographic search on Mehndi/henna was carried out during March 2013-March 2014 exploring the worldwide accepted scientific databases of NISCAIR, SCIELO, PUBMED, SCOPUS, INFLIBNET, Sci-Finder, Science Direct and Google Scholar. Compilation of the information retrieved was done arbitrarily for the preparation of palingenesis of the review under the appropriate headings.

Phytochemistry

Noticed by researchers, Mehndi/Henna got its popularity due to presence of a unique chemical named lawsone. Other group of molecules reported from this plant include quinones, phenylpropanoids, flavonoids, terpenoids, phenolics, fatty acids, carbohydrates, proteins, tannins, alkaloids, xanthones, coumarin, glucosides, naphthoquinone, saponins, triterpenoids, sterols and dioxin derivatives. Some potent bioactive like isoplumpagin (a naphthaquinone from bark), lupeol, 30-norlupan-3-ol-20-one, betuhennan, betuhennanic acid and n-tridecanoate (bark), phenolic glycosides, lawsoniaside, β -sitosterol and stigmasterol (leaves) have been reported from Mehndi/Henna plant Bhardwaj et al., 1980Bhardwaj et al., 1978Chakrabortty et al.,1980Gupta et al., 1992Gupta et al., 1993Takeda and Fatope, 1988, 24-beta ethyl cholest-4-en-3-beta-ol have also been reported from the roots of henna Gupta et al.,1992. The seeds of Mehndi/Henna contain ~7.5 % viscous oil possessing palmitic, behenic, arachidic, stearic, oleic and linolenic acids Aggarwal et al., 1959Handa et al., 1997. Bioactivity guided fractionation of methanolic seed extract lead to isolation of two new triterpenoids lawnermis acid and its methyl ester Siddiqui et al., 2005. The leaves of Mehndi/Henna also contains apigenin-7-glucoside, apigenin-4-glycoside, luteohennan- 7-glucoside luteolin-3-glucoside Chakrabartty et al., 1982. The essential oil of Lawsonia inermis seeds contains about 23 components revealed in GC-MS analysis. The principal components were Tridecane (7.7%), phytol (10.30%), Hexadecane (14.88%), Tetradecane (16.77%), Heptadecane (23.48%) Rahmat et al.,2006. Structures of the reported anticancer molecules from Lawsonia inermis and some of the derivatives of lawsone is given in Figure 1 .

Anticancer/cytotoxicity activities of lawsonia inermis extract and essential oil

An assortment of anticancer activities of Lawsonia inermis extracts, essential oil, lawsone and its derivatives have been summarised in Table 1 . In addition, description of anticancer studies is provided under the following headings:

A Case Study

Hand Foot Syndrome (HFS), the most frequent cutaneous adverse effect of capecitabine (a prodrug of 5-Florouracil) is manifested as acral erythema with swelling and dysesthesia of the palms and soles. It interferes significantly with normal daily activities of patients undergoing treatment with capecitabine. A breast cancer patient undergoing capecitabine treatment at the Department of Medical Oncology, Ondokuz Mayis University Medical School, Turkey complained about the presence of skin rashes on her feet but not in hands. Later she was diagnosed with HFS and it was observed that she had applied mehndi/henna on her hands which was an exciting case for the researchers. Following it as an example case, six patients with severe case of HFS were recommended to apply mehndi/henna on their hands. Astoundingly, after using mehndi/henna, whinges were reduced in 48 h and disappeared in one week Yucel and Guzin, 2008.

Conclusions

Despite being used as a cosmetic agent in the Oriental regions of the world to dye hair and in body art, Mehndi/Henna holds several cytotoxic and chemopreventive agents in its possession. The present review recapitulates some important findings on the anticancer potential of Mehndi/Henna and to a great extent more work needs to be embark on to explore its novel target(s). Phytochemistry of Mehndi/Henna needs a broader study for the isolation of novel compounds and pharmacological studies on suitable models and clinically established cancer biomarkers will help to identify pioneering chemotherapeutic and/or chemopreventive agent. Future investigation on these aspects of Mehndi/Henna may offer great hope for the discovery of new anticancer agents from this miraculous plant.

Abbreviations

AYUSH: Ayurveda, Yoga & Naturopathy, Unani, Sidha and Homeopathy Medicine; IC- 50 percent inhibitory concentration; GSH: Glutathione; SOD: Superoxide dismutase; DLA: Dalton lymphoma ascitis; WBC: White blood cells; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatise; LDH: Lactate dehydrogenase; Hb: Haemoglobin; RBC: Red blood cells; PCV: Packed cell volume; PON: Peroxynitrile.