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Antimicrobial properties of Lawsonia inermis (henna): a review.

Naphthoquinones are compounds present in various families of plants; their molecular structures endow them with redox properties which confer activity in various biological oxidative processes. In ethnomedicine, plants containing naphthoquinones have been employed for treatment of a number of diseases including cancer. Lawsonia inermis (henna) is widely cultivated and used in many oriental, Middle Eastern and northern African countries. It is best known for its colouring matter contained in the leaves. Henna extract contains lawsone (C10H6O3), the active ingredient and a naturally occurring naphthoquinone. The development of new antimicrobial agents is a research area of utmost importance. Antimicrobial resistance among key microbial pathogens continues to grow at an alarming rate worldwide. The challenge of synthesising derivatives of natural antimicrobial naphthoquinones to improve their pharmaceutical properties has been accepted by several laboratories. In this review we describe the antimicrobial activity of Lawsonia inermis Linn as a natural resource of naphthoquinones. Work in our laboratory in this area will also be elucidated.

Keywords: henna, Lawsonia inermis, naphthoquinones, antibacterial, antiviral, antiparasitic

Introduction

The small shrub of henna (Lawsonia inermis Linn.) is widely cultivated and used in many oriental, Middle Eastern and northern African countries. This dwarf shrub grows outdoors unsheltered at temperatures higher than 11[degrees]C (60[degrees]F). It needs around 5 years to mature and produce leaves with useful levels of tannins. It grows better in arid regions than moist or wet regions and achieves a height of 8 to 10 feet. It grows heavy sweet-smelling white and yellow flowers. The plant belongs to the family Lythraceae and is best known for its colouring matter contained in the leaves. Various cultures used the plant leaves as powdered, dissolved and then turned into paste mainly as a cosmetic. It has been used for dyeing wool, and in ancient times it was used in pigments and for dyeing hair and nails with the reddish-yellow tint.

Henna extract contains lawsone ([C.sub.10][H.sub.6][O.sub.3]), the active ingredient and a naturally occurring naphthoquinone (2-hydroxy-1,4-naphthoquinone 2) (Fig 1). When applied to wool and nylon it behaves as an acid levelling non metallised acid dye. Dye uptake increases with increased pH (Badri 1993) and it stains tissue preparations in histological paraffin sections of different organs (Veereshkumar 2005). The dye was used for colouring leather and skins. It was widely used in Europe from 1890 for tinting hair with many shades prepared by mixing the leaves with other plants such as indigo, catechu or lucerne. Henna brown colouring constituents are of a resinoid fracture having chemical properties similar to tannins, hence the name hennotannic acid.

Quinones (Fig 1) are aromatic rings (dienes = unsaturated hydrocarbon alkene containing two carbon-to-carbon double bonds) with two ketone substitutions. The word quinone refers to the entire class of cyclohexadienediones. They are ubiquitous in nature and are characteristically highly reactive. These compounds, being coloured, are responsible for the browning reaction in cut or injured fruits and vegetables and are an intermediate in the melanin synthesis pathway in human skin (Schmidt 1988).

[FIGURE 1 OMITTED]

Naphthoquinones are widely distributed in plants, fungi and some animals. Their biological activities have long been reported to include antibacterial effects on several species of both aerobic and anaerobic organisms (Didry 1968) and parasites (Wendel 1946).

Early discovery of henna's medicinal properties

Seeking healing by using plants is an ancient practice. Various cultures applied poultices and imbibed infusions of hundreds, if not thousands of indigenous plants dating back to prehistory.

Reports of Neanderthals living 60,000 years ago in present day Iraq used plants such as hollyhock (Alcea spp) (Stockwell 1988, Thompson 1978). Such plants are still used in ethnomedicine worldwide.

Ancient Egyptians are said to have prepared both oil and an ointment from the henna flowers for making the limbs supple. In early Islamic culture henna usage is very evident in the book of "Prophetic Medicine" where the medicinal practices of the Prophet Mohammed (PBUH), as mentioned by his followers and others that were close to him in his household, were recorded (Al-Arnaoutt 1987).

Henna was then used for the treatment of headaches, migraine, albinism, skin abrasions and ulcers, burns, smallpox, leprosy boils, wounds, some mycotic infections and cancers. It was also used for the treatment of scalp and hair infections and ailments.

Recent developments

The development of new antimicrobial agents is a research area of the utmost importance. Resistance to such antimicrobial agents by pathogens (Chopra 1992, Bhavani 2000) continues to be alarming worldwide. The increased prevalence of antibiotic resistant bacteria emerging from the extensive use of antibiotics may render the current antimicrobial agents insufficient to control at least some bacterial infections.

The challenge of synthesising derivatives of natural antimicrobial naphthoquinones to improve their pharmaceutical properties has been accepted and practiced by many laboratories. Indeed the synthesis and evaluation of antimicrobial activity of bioactive analogues of certain substances has been reported (Nagata 1998, Oliveira 2001). American Indian have used plants containing naphthoquinones in treating a number of diseases including cancer (Pinto 1977, Kapadia 1997). Such activity was confirmed by several research reports (Sieber 1976, Dinnen 1997, Pink 2000).

Furthermore several other biological activities for naphthoquinones have been described such as being anti-inflammatory (De Almeida 1990), bactericidal (Binutu 1996) fungicidal, (Gafner 1996), virucidal (Heinrich 2004), trypanocidal (De Moura 2001), anti-Plasmodium falciparum (De Moura 2001), the causative agent of malaria, and anti-Schistosoma mansoni (Pinto 1977), an agent of Schistosomiasis. Although naphthoquinones do appear to exhibit a wide spectrum of biological activities, the mechanism/s of action remains somewhat unclear.

However studies on Plasmodium spp. showed that their susceptibility to the toxicity of naphthoquinones is due to interaction with the mitochondrial respiratory chain (Ball 1947). Furthermore it was demonstrated that a variant of lawsone, dichloroallyl lawsone, an analogue of ubiquinone, is a potent inhibitor of nucleotide biosynthesis with consequent anti-cancer activity against certain experimental tumours (Kempt 1986).

The biosynthesis of pyrimidine nucleotides is essential to sustain the rapid growth of cancer cells. The addition of dichloroallyl lawsone (DCL) to leukemic cells results in a rapid depletion of uridine and cytidine nucleotides; carbamyl aspartate and dihydroorotate accumulate to high levels in an equilibrium ratio of 20.5:1 and orotate, orotidine and uridine-monophosphate (UMP) increase transiently before decreasing to levels approaching their original steady states (Kempt 1986). This is consistent with inhibition of the conversion of UMP to uridine-diphosphate (UDP) initially followed by potent inhibition of conversion of dihydroorotate to orotate (Kempt 1986).

Antimicrobial activity of lawsone

The antimicrobial activity of Lawsonia inermis is no longer in doubt. Many workers reportedly demonstrated such activity on a wide spectrum of microbes. We will review such activity under various microbial categories, namely bacteria, fungi, viruses and parasites.

Antibacterial activity

The antimycobacterial activity of quinonoid compounds, particularly those isolated from natural sources, has remained unexplained. There are reports of tuberculostatic activity of Lawsonia inermis that implicate lawsone (2-hydroxynaphthoquinone) which is known to be the major constituent of this herb (Sharma 1995, Tripathi 1978). However in its dimeric form lawsone was found to be inactive (Lall 2003). This observation is consistent with the enormous influence of structural modification on the biological activity of the bisnaphthonquinonoid namely diospyrin (Hazra 1995), the positive contribution of an aminoacetate substituent being introduced into the allylic double bond of diospyrin. Hence newer analogues of the aminoacetate derivatives (of diospyrin dimethyl ether) have to be designed to resolve the structure activity relationship in this series leading to the development of more effective antimycobacterial agents. However lawsone was shown to elicit in vivo lower toxic effects in mussel tissues than tissues in higher organisms. This may be due to the lower detectable levels of xanthine oxidase in the invertebrate mussels (Osman 2004).

The antibacterial activity of the natural naphthoquinone products alkannin and shikonin and their derivatives has been investigated (Riffel 2002). In general they are active against gram positive bacteria such as Staphylococcus aureus, Enterococcus faecium and Bacillus subtilis, but are inactive against gram negative bacteria (Papageorgiou 1999). In nosocomial infection, Staphylococcus aureus is one of the most prevalent microorganisms worldwide. Methicillin resistant strains represent 15-45% of all Staphylococcus aureus isolates (Emori 1993). This may explain the arduous search for new antimicrobial agents as an important line of research.

For the naphthoquinones to have such antimicrobial activity, active compounds must possess at least a substitution at position 2 (as is the case in lawsone Fig 1) or 3, which is either an electron releasing or weaker electron withdrawing group (Greshon 1975). This structure activity relationship is reinforced further with studies that indicated the antimicrobial activity of a family of isoxazolylnaphthoquinones requires a free keto group at position 1, and the substituent at position 2 must be a hydroxyl group (Bogdanov 1993). Such compounds were found to protect mice infected with Staphylococcus aureus, inhibiting septicaemia in vivo (Albesa 1995).

Inhibitory action of henna was shown against both gram negative and gram positive microbes. In one report the inhibitory action was greatest against B. anthracis as it stood out from other tested bacteria (Malekzadeh 1968). Lawsone, the antimicrobial agent in henna (Malekzadeh 1968, Sharma 1995) is highly soluble in water, partially soluble in 70% ethyl alcohol and heat stable. Chromatography studies demonstrated the presence of phenolic compounds in the substance (Malekzadeh 1968). Such compounds exerted inhibitory effects upon common nosocomial urinary tract pathogens such as Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeroginosa and Staphylococcus aureus at certain concentrations (Bhuvaneswari 2002).

Decoction of henna leaves has been used as a gargle in sore throats (Chopra 1958). Crude and ethonolic extract of Lawsonia inermis leaves showed dose dependent analgesic, antipyretic and anti-inflammatory effect in rats (Ali 1995). The effects of water and chloroform extracts of the leaves of henna plant against the primary invaders of burnt wounds was also investigated (Muhammad 2005). Inhibition of the growth of such microorganisms suggests that henna may be valuable in the management of burnt wound infections (Muhammad 2005).

In our own laboratory we have undergone investigations on crude extracts of fresh and dry local (Omani) henna leaves and seeds against 3 standard bacterial strains, Staphylococcus aureus, Escherichia coli and Pseudomonas aerugenosa, and eleven different bacterial strains obtained from patients attending hospital clinics. We found, as shown above, that all fresh and dry henna leaves and seeds possessed antibacterial activity against all microorganisms tested in vitro (Habbal 2005).

[FIGURE 2 OMITTED]

Our results demonstrated that the most striking antimicrobial effect of henna was the inhibitory effect of all dilutions on both Shigella sonnei and Staphylococcus aureus (Fig 2 and Table 1). This is reassuring since certain henna ingredients such as flavonoids, quinones and simple phenols have been reported to have antimicrobial activity on Shigella sonnei (Vijaya 1995) which supports our own findings.

The dry leaves seemed to have stronger activity on the Shigella sonnei than the fresh leaves, which were shown to be more effective at higher concentrations. This may be due to the presence of certain natural constituents in the fresh leaves such as chlorophyll and water.

We noticed that the antimicrobial activity of the henna sample was generally more evident in the leaves of the plant rather than the seeds, the latter having only demonstrated a limited antibacterial activity and at higher concentrations. The anti Candida albicans activity is self evident as it demonstrated sensitivity to the leaves but not the seeds. It is the presence of quinones in henna which gives that material its dyeing properties (Fessenden 1998).

The switch between diphenol (or hydroquinone) and diketone (or quinone) occurs easily through oxidation and reduction reactions. The individual redox potential of the particular quinone hydroquinone pair is very important in many biological systems. Hydroxilated amino acids may be made into quinones in the presence of suitable enzymes such as a polyphenoloxidase (Thastrup 1985). In addition to providing a source of stable free radicals, quinones are known to complex irreversibly with nucleophilic amino acids in proteins (Stern 1985) often leading to inactivation of the protein and loss of function.

For that reason the potential range of quinone antimicrobial effects is great. Portable targets in the microbial cell are surface exposed adhesions, cell wall polypeptides, and membrane bound enzymes. Quinones may also render substrates unavailable to the microorganism. In addition they were shown to inhibit cell growth in culture (Kamei 1998).

Leaves of the henna are strikingly most effective against the spectrum of bacteria we tested compared to seeds. This is probably due to the inherent characteristics of the fully grown plant and the maturity of its chemically active constituents such as quinones. Such constituents would not have been established in seeds. Although fresh leaves did demonstrate bacteriostatic activity in general, this was less evident when compared with the effect of dry leaves. It is possible that the drying effect on the plant causes the active ingredients to be more concentrated than those in the green leaves, where water and other constituents are still present.

Table 1 elucidates our findings of antimicrobial activities of henna both against a wide spectrum of bacterial strains and against Candida albicans. Work is underway in our laboratory to test henna against a wider spectrum of bacterial strains and other microbes.

Antimycotic activity

Lawsone has been shown to be effective against oral Candida albicans isolated from patients with HIV/AIDS (Prasirst 2004). We have reported activity against Candida albicans using Omani henna (Habbal 2005). During antifungal screening of higher plants, the leaves of Lawsonoia inermis were found to exhibit strong fungitoxicity where naphthoquinones were found to be the active factor (Tripathi 1978).

Fungotoxic studies against ringworm fungi were demonstrated. Barks of 30 plant species were screened against Microsporum gypseum and Trichophyton mentagrophytess; only Lawsonia inermis exhibited absolute toxicity (Singh 1989). The Lawsonia bark extract was found to possess a fungistatic nature at its maximum inhibitory dilution of 1:30 (W/V) against both test pathogens, but became fungicidal at 1:10 (W/V) (Bogdanov 1993).

The extract showed broad fungitoxic spectrum when tested against 13 ringworm fungi (Singh 1989). This role of a cosmetic and antimycotic has been reported by others (Itani 1973).

Molluscicidal activity of leaf, bark and seed of Lawsonia inermis against Lymnaea acuminata and Indoplanorbis exustus was studied with the highest toxicity observed in the seed of the plant (Singh 2001).

Virucidal activity

Bhandarkar and Khan (2003) suggest hepatoprotective and antioxidant activity of extract of Lawsonia alba Lam. against hepatic damage in albino rats. This may indirectly indicate an important role of henna as an antiviral agent. Hepatitis related viruses such as hepatitis C virus (HCV) and hepatitis E virus (HEV), and the new infectious diseases such as the Ebola virus, Legionella pneumophila and human immunodeficiency virus (HIV), have been discovered in the past 20 years. The emergence of drug resistant strains is a big challenge that faces antibacterial medicine.

The ethanol extract of Lawsonia inermis was studied (Mouhajir 2001) along side 75 other Morocaon plants that are used traditionally to treat diseases that could be caused by viruses and microbes. These plants were tested against three mammalian viruses: herpes simplex virus, Sindbis virus and poliovirus, at non toxic concentrations. Lawsonia inermis extract inhibited Sindbis virus at a minimum concentration of 1.5 4g/mL. Such findings indicate that the plant is a potentially potent drug against infectious diseases caused by viruses.

However in the same study the discriminatory effect of various plants against specific microorganisms suggests the presence of different chemical compounds. Light is a determining factor in the activity of photosensitisers and should be taken into account in this kind of work.

Quinones include various quinine derivatives including naphthoquinones. The multi quinine compounds can include identical quinine monomers or two or more different quinine monomers. Trimeric naphthoquinones were found to inhibit the growth and replication of viruses, particularly retroviruses such as HIV (Koyama 2006). The inhibitory activity of some naphthoquinones on RNase H activity associated with HIV-1 reverse transcriptase has been described (Min 2002).

A model of 5,8-dihydroxy-1,4-naphthoquinone interaction with the zinc finger region of the retroviral integrase protein was proposed (Singh 2001) and was found to inhibit HIV type 1 integrase (Fesen 1993).

The virucidal activity of Lawsonia inermis needs more work. Limited literature is available. In this laboratory we are in the process of exploring such activity and will report in due course.

Antiparasitic activity

The discovery of quinine (Badri 1993) from Cinchona succiruba (Rubiaceae) and its subsequent development as an antimalarial drug (Wendel 1946) represented a milestone in the history of antiparasitic drugs from nature for the treatment of all parasitic diseases caused by Plasmodium, Leishmania (Kayser 2000) and Trypanosomia (Kayser 2003) species.

Discovering untapped natural sources of novel antiprotozoal compounds from nature remains a major challenge and a source of novelty in the era of combinatorial chemistry and genomics. The plant derived product hydrolapachol (2-hydroxy-1,4-naphthoquinone) was shown to have activity against Plasmodium lophurae in ducks in the 1940s (Wolfson 1941).

Plasmodium falciparum is the causative agent of the most serious and fatal malarial infections and has developed resistance to commonly employed chemotherapeutics. The de novo pyrimidine biosynthesis enzymes offer potential as targets for drug design because unlike the host, the parasite does not have pyrimidine salvage pathways (Bladwin 2005). Dihydroorotate dehydrogenase (DHODH) is a flavin dependent mitochondrial enzyme that catalyses the fourth reaction in this essential pathway; coenzyme Q (CoQ) is utilised as the oxidant. Potent and species selective inhibitors of malarial DHODH were identified by high throughput screening of a chemical library which contained 220,000 drug-like molecules (Baldwin 2005).

These novel inhibitors represent a diverse range of chemical scaffolds including a series of halogenated phenyl benzamide/naphthamides and urea based compounds containing napthyl or quinolinyl substituents. Inhibitors in these classes with IC50 values below 600 nM were purified by HPLC, characterised by mass spectroscopy and subjected to kinetic analysis against the parasite and human enzymes (Krishnarju 2006). The most active compound is a competitive inhibitor of CoQ with an IC50 against malarial DHODH of 16 nM, being 12,500-fold less active against the human enzyme (Krishnarju 2006). The structural basis for the species selective enzyme inhibition is explained by the variable amino acid sequence in this binding site, making DHODH a particularly strong candidate for the development of new antimalarial compounds.

Quinine has been used for the treatment of malaria for more than 350 years and has its origin in Peru in the early 17th century (Meinhardt 1965). Quinine was the lead structure in the discovery of new synthetic derivatives such as mefloquine that have higher antimalarial activity (Kayser 2002). Earlier reports showed that certain 2-hydroxy-3-alkyly-naphthoquinones had the capacity to inhibit the growth of Plasmodium (Wendel 1946).

The re-emergence of malaria as a public health problem is due mainly to the development of resistance of Plasmodium falciparum to cheap highly effective drugs such as chloroquine and pyrimethamine. The hydroxynaphthoquinone atovaquone identified as an antimalarial (Hudson 1985) in the early 1980s has proved to be highly effective in clinical trials but has to be used in combination with proguanil (as Malarone) to prevent the development of resistance (Srivastava 1999).

A new 8-aminoquinoline tafenoquine is on clinical trial as a potential replacement for primaquine to treat Plasmodium vivax malaria (Shanks 2001) and holds promise as a prophylactic against Plasmodium falciparum (Shanks 2001). The site of action of the antimalarial compound 2-[trans-4-(4'-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80) would appear to be the mitochondrial respiratory chain (Fry 1992).

Studies reported herein have demonstrated 566C80 to be a potent and selective mitochondrial inhibitor with mitochondria isolated from Plasmodium falciparum and Plasmodium yoelii (Hudson 1991). Atovaquone, an analog of ubiquinone, acts by interfering with the electron transport chain of mitochondria at site bc1 (complex III) in Plasmodium species (Riffel 2002) consequently inhibiting nucleic acid and ATP synthesis (Fry 1992).

In pneumonia caused by Pneumocystis carinii, prophylaxis by atovaquone (2-[trans-4-(4-chlorophenyl)-cyclohexyl]-3-hydroxy-1,4-naphthoquinone) is approved as the drug of choice (Madden 2007).

Although the mechanism of action of naphthoquinones has not been completely elucidated, [beta]-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2] pyran-5,6-dione) is an antimicrobial naphthoquinone that caused increased generation of superoxide anion and hydrogen peroxide in Trypanosoma cruzi (Docampo 1978). Antiparasitic effects of naphthoquinones against Toxoplasma gondii, Leishmania spp and Plasmodium spp have been reported (Sarciron 2002), the most active compounds against a virulent RH strain of Trypanosoma gondii reported to be the bisheterocyclic quinones (Sarciron 2002).

There has been a dramatic increase in the number of cases of visceral Leishmanisis (VL) in north eastern India that do not respond to antimonials (Sundar 2003). These drugs have been in use for over 50 years, require long courses of parenteral administration and have toxic side effects. Alternative treatments for visceral Leishmanisis include the polyene antibiotic amphotericin B that has highly effective less toxic lipid formulations (Sundar 2003). A parenteral formulation of the aminoglycoside paromomycin (aminosidine) and the orally available alkylphospholipid miltefosine are also potential treatments for VL (Sundar 2003).

Experimental studies and treatment of AIDS patients have revealed that successful treatment with some drugs requires the active participation of the immune system (Villanueva 2000, Mofredj 2002). As the result of an ethnopharmacological search for new antileishmanial drugs, aryl- and alkyl-quinolines were isolated from Galipea longiflora (Rutaceae) (Kouznetsov 2005). These simple natural quinoline derivatives 2-n-propylquinoline, chimanine B, chimanine D, 2-n-pentylquinoline, 4-methoxy-2-phenylquinoline, and 2-(3,4-methylenedioxyphenyl)-quinoline were tested against strains of parasites causing cutaneous leishmaniasis and exhibited therapeutic activity (Fournet 1996). Only chimanine B was active in vivo (Fournet 1996). No mechanism has been found to explain these effects.

Many naphthoquinones have been isolated but frequently their potential use has been limited by low bioavailability and high toxicity (Wright 1990). Activity and mutagenicity of bisbenzylisoquinolines and quinones against Trypanosomacruzi trypomastigotes were reported to have no structure activity relationship (De Arias 1994). The only active naphthoquinone, plumbagin is an antiprotozoal compound with activity against Leishmania anzazorzensis and Leishmania doizovani in vitro and in vivo (Croft 1985; Fournet 1992) and antibacterial and antifungal activities (Gujar 1990). A dimeric naphthoquinone diospyrin from Diospyros montana (Ebenaceae) was found to be active against Leishmania donovani (Ardley 1996). The inhibition of Type I DNATopoisomerase in this parasite has been suggested as a mechanism of action (Tazi 2005).

Anthraquinones and xanthones are naturally occurring product groups which are related to naphthoquinones in structure and biological activity (Thomson 1991). The main chemical difference between the groups is the tricyclic aromatic system with a paraquinoid substitution (Schnur 1983). Some derivatives have activity in vitro against Leishmania spp (Fournet 1992) but few naturally occurring anthraquinones have been tested.

Anti-carcinogenic activity of henna

Henna's anticarcinogenic property was reported (Endrini 2002) using a chloroform extract of Lawsonia inermis by the culture tetrazollium salt (MTT) assay on the human breast, colon and liver carcinogenic cell lines and normal human liver cell lines (Endrini 2002).

The preliminary results showed that henna extract displayed cytotoxic effects against HepG2 (liver cells) and MCF-7 (hormone dependent breast cells), but no significant activity was recorded against colonic, hormone nondependent breast cell lines and normal liver cells at the concentrations tested. These results indicate the selectivity of such cytotoxic activity.

The antioxidative activity of this henna extract was found to be highest compared to vitamin E or [alpha]-tochopherol, attributing to the strong cytotoxic activity of the extract (Endrini 2002). Additionally inhibition of malignant cell growth in culture by quinones using HCT-15 cells derived from human colon carcinoma was shown to be due to lawsone as a member group of the quinone group (Kamei 1998).

This appears to be achieved by blocking the S-phase of cell cycle. The protective role of henna was also reported using an ethanol-water extract (1:1) against CCl4-induced liver toxicity in mice (Anand 1992).

Dichloroallyl lawsone (DCL, NSC-126771) (McKelvey 1979), a synthetic analogue of the antimalarial lapachol, is potentially useful in cancer chemotherapy (McKelvey 1979). Unlike most anticancer agents DCL is not significantly myelosuppressive in animals but it induces acute cardiac toxicity in the rhesus monkey (McKelvey 1979). This cardiac toxicity seems to be correlated with the maximal plasma DCL concentration, about 130 mg/L in the monkey. McKelevy et al (1979) have tested the DCL pharmacokinetics in patients in an attempt to define safe dose limits for the Phase I clinical trial. After the rapid intravenous infusion of 10 mg/m2 of radioactive [1- or 4-14C]DCL, 250 muCi per patient, the mean peak plasma concentration of unchanged DCL in four patients was 2.9 +/- 0.3 mg/L.

The drug had a mean initial plasma half life of 48.9 +/- 19 min and a terminal half life of 20.3 +/- 1.8 hr, with a CXt of 50.1 +/- 12 mg/L/hr and a clearance rate of 0.08 ml/kg/min. This data suggests that in clinical trials the DCL dose given by rapid intravenous infusion should not exceed 450 mg/m2 so that the maximal plasma drug concentration remains below 130 mg/L.

Dichloroallyl lawsone was found to be a potent inhibitor of nucleotide biosynthesis with consequent anticancer activity against certain experimental tumours (Kempt 1986). Biosynthesis of pyrimidine nucleotides is essential to sustain the rapid growth of cancer cells. DCL inhibition of pyrimidine biosynthesis in leukemia cells was reported as 25 [micro]g of dichloroallyl lawsone caused the arrested growth of L1210 cells (Kempt 1986).

A number of synthetic derivatives of lapachol, such as monoarylimines quinones derived from [beta]lapachone showed cytotoxicity against human cancer cells (Balassiano 2005). Naphthoquinones related to lapachol 2 have been shown to exhibit notable cancer preventive potential (Girard 1987, Balassiano 2005). Furthermore various amine derivatives have been shown to interact with DNA (Cunha 2006).

With the wide usage of henna painting for body adornment and hair dyeing, there are reports of allergic reactions to some contaminants of the commercially available natural henna powder (Nawaf 2003) including acute allergic contact dermatitis and acute hemolytic effects that were reported in a G6PD-deficient patient (Soker 2000) and newborns (Kandil 1996).

In addition our laboratory has demonstrated that henna extract could be used in histological preparations as a naturally occurring stain (Al-Abri unpublished).

Conclusion

Henna has a wide spectrum of antimicrobial activity including antibacterial, antiviral, antimycotic and antiparasitic activities. With the ever increasing resistant strains of microorganisms to the already available and synthesised antibiotics, the naturally available Laswonia inermis (henna) could be a potential alternative.

References

Al-Abri A, Al-Abri H, Al-Hashmi N, Al-Mukhaini N, El-Hag A, Habbal O. Omani henna (Lawsonia inermis) as a natural histological stain. Unpublished.

Al-Arnaoutt S, Al-Arnaoutt AK. 1987. In Al-Jozieh IK Prophetic Medicine. Beirut: Al-Risala Publishing.

Albesa I, Bogdanov PM, Eraso A, Sperandeo NR, Bertorello MM. 1995. Antibiotic activity of isoxazolilnaphthoquinones imines on mice infected with Staphylococcus aureus. J App Bacteriol 78:373-7.

Ali BH, Bashir AK, Tanira MO. 1995. Anti-inflammatory, antipyretic and analgesic effects of Lawsonia inermis L (henna) in rats. Pharmacol 51:356-63.

Anand KK, Singh B, Chand D, Chandan BK. 1992. An evaluation of Lawsonia inermis alba extract as hepatoprotective agent. Planta Med 58(1):22-5.

Ardley V, Snowdon D, Croft S, Hazra B. 1996. In vitro activity of Diospyrin and derivatives against Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Phytother Res 10(7):559-62.

Badri BM, Burkinshaw SM. 1993. Dyeing of wool and nylon 6.6 with henna and lawsone. Dyes & Pigments 22(1):15-25.

Balassiano IT, De Paulo SA, Henriques Silva N, Cabral MC, de Gloria da Costa Carvalho M. 2005. Demonstration of the lapachol as a potential drug for reducing cancer metastasis. Oncol Rep 13(2):329-33.

Baldwin J, Michnoff CH, Malmquist NA, White J, Roth MG, Rathod PK, Phillips MA. 2005. High throughput screening for potent and selective inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. J Biol Chem 280(23):21847-53.

Ball EG, Anfinsen CB, Cooper O. 1947. The inhibitory action of napthoquinones on respiratory processes. J Biol Chem 168:257-70.

Bhandarkar M, Khan A. 2003. Protective effect of Lawsonia alba Lam. against CCl4 induced hepatic damage in albino rats. Indian J Exp Biol 41(1):85-7.

Bhavani SM, Ballow CH. 2000. New agents for gram-positive bacteria. Current opinion in Microbiol 3:528-34.

Bhuvaneswari K, Gnana Poongathai S, kuruvilla A, Appala Raju A. 2002. Inhibitory concentrations of Lawsonai innermis dry powder for urinary pathogens. Indian J Pharmacol 34:260-3.

Binutu OA, Adesogan KE, Okogun JI. 1996. Antibacterial and antifungal compounds from Kigelia pinnata. Planta Med 62:352-3.

Bogdanov PM, Albesa I, Sperandeo NR, De Bertorello MM. 1993. Actividad antibacteriana in vitro de isoxazolil-naftoquinonas. Revista Argentina Microbiol 25:119-28.

Brueckner R. 2001. A new primaquine analogue, afenoquine (WR238605), for prophylaxis against Plasmodium Falciparum. Malaria 33:1968-74.

Chopra I, Hawkey PM, Hinton M. 1992. Tetracyclines, molecular and clinical aspects. J Antimicrob Chemother 29:245-77.

Chopra RN (ed). 1958. In: Chopra's Indigenous Drugs of India 2nd edn. Calcutta India: Dhur UN & Sons.

Croft SL, Evans AT, Neal RA. 1985. The activity of plumbagin and other electron carriers against Leishmania donovani and Leishmania mexicana amazonensis. Ann Trop Med Parasitol 79;651-3.

Cunha SA, Lima ELS, Pinto AC, Esteves-Souza A, Echevarria A, Camara CA, Vargas MD, Torrese JC. 2006. Synthesis of novel naphthoquinone-spermidine conjugates and their effects on DNA-topoisomerases I and II-a. J Braz Chem Soc 17(3):439-42.

De Almeida ER, da Silva Filho AA, dos Santos ER, Lopes CA. 1990. Antiinflammatory action of lapachol. Ethnopharmacol 29;239-41.

De Arias AR, Inchausti A, Ascurrat M, Fleitas N, Rodriguez E, Fournet A. 1994. In vitro activity and mutagenicity of bisbenzylisoquinolines and quinones against Trypanosoma cruzi trypomastigotes. Phytother Res 8:141-4.

De Moura KCG, Emery FS, Neves-Pinto C, Pinto MCFR, Dantas AP, Sulomao K, De Castro SL, Pinto AV. 2001. Trypanocidal activity of isolated naphthoquinones from Tabebuia and some heterocyclic derivatives: a review from an interdisciplinary study. J Braz Chem Soc 12(3):325-38.

Didry N, Pinkas M, Dubreil L. 1968. Activitie antibacterienne de naphthoquinones d'origine vegetale. Ann Pharmaceut Franc 44:73-8.

Dinnen RD, Ebisuzaki K. 1997. The search for novel anticancer agents: a differentiation-based assay and analysis of a folklore product. Anticancer Res 17:1027-33.

Docampo R, Cruz FS, Boveris A, Muniz RPA, Esquivel DMS. 1978. Lipid peroxidation and the generation of free radicals, superoxide anion, and hydrogen peroxide in [beta]-lapachone-treated Trypanosoma cruzi epimastigotes. Arch Biochem & Biophys 186:292-7.

Emori TG, Gaynes RP. 1993. An overview of nosocomial infections including the role of microbiology laboratory. Clin Microbiol Rev 6:428-42.

Endrini S, Rahmat A, Patimah I, Yap Yun Hin T. 2002. Carcinogenic properties and antioxidant activity of henna (Lawsonia inermis). J Med Sci 2(4):194-7.

Fesen MR, Kohn KW, Leteurtre F, Pommier Y. 1993. Inhibitors of human immuno-deficiency virus integrase. Proc Nat Acad Sci 90(6):2399-2403.

Fessenden RJ, Fessenden JS (eds). 1998. Organic Chemistry 6th edn. Pacific Grove California: Brooks Cole Publishing Co.

Fournet A, Angelo Barrios A, Munoz V, Roblot F, Hocquemiller R, Cave A. 1992. Biological and chemical studies of Pera benensis, a Bolivian plant used in folk medicine as a treatment of cutaneous leishmaniasis. J Ethnopharmacol 37:159-64.

Fournet A, Ferreira ME, De Arias AR, De Ortz ST, Fuetes S, Nakayama H, Schinini A, Hocquemiller R. 1996. In vivo efficacy of oral and intra-lesional administration of 2-substituted quinolines in experimental treatment of new world cutaneous Leishmaniasis caused by Leishmania amazonensis. Antimicrob Agents Chemother 40(11):2447-51.

Fry M, Pudney M. 1992. Site of action of the antimalarial hydroxynaphthoquinone,2-[trans-4-(4'chlorophenyl)cyclohexyl]- 3-hydroxy-1,4-naphthoquinone (566C80). Biochem Pharmacol 43(7):1545-53.

Gafner S, Wolfender JL, Nianga M, Stoeckli-Evans H, Hostettmann K. 1996. Antifungal and antibacterial naphthoquinones from Newbouldia laevis roots. Phytochem 42(5):1315-20.

Girard M, Ethier J-C, Kindack D, Dawson BAA, Wang DVC. 1987. Mass spectral characterization of naphthoquinones related lapachol. J Nat Prod 50(6):1149-51.

Greshon H, Shanks L. 1975. Fungitoxicity of 1,4-naphthoquinones to Candida albicans and trichophyton menthagrophytes. Canad J Microbiol 21:57-9.

Gujar GT. 1990. Plumbagin, a naturally occurring naphthoquinone. Its pharmacological and pesticidal activity. Fitoterapia 59;387-93.

Habbal OA, Al-Jabri AA, El-Hag AH, AL-Mahrooqi ZH, AL-Hashmi NA. 2005. In vitro antimicrobial activity of Lawsonia inermis Linn (henna). A pilot study on the Omani henna. Saudi Med J 26(1):447-50.

Hazra B, Ghosh R, Banerjee A, Kirby GC, Warhurst DC, Phillipson JD. 1995. In vitro antiplasmoidial effects of diospyrin, a plant-derived naphthoquinonoid, and a novel series of derivatives. Phytother Res 9:72-4.

Heinrich M, Barnes J, Gibbons S, Williamson EM (eds). 2004. In: Fundamentals of Pharmacognosy and Phytotherapy: Important Natural Products and Phytomedicines in Pharmacy and Medicine. London: Elsevier Health Sci.

Hudson AT, Dickins M, Ginger CD, Gutteridge WE, Holdich T, Hutchinson DB, Pudney M, Randall AW, Latter VS. 1991. 566C80: a potent spectrum anti-infective agent with a ctivity against malaria and oppurtinistic infections in AIDS patients. Drugs Exp Clin Res 17(9):427-35.

Hudson AT, Randall AW, Ginger CD, Hill B, Latter VS, McHardy N, Williams RB. 1985. Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoan activity. Parasitol 90:45-5.

Itani ZS. 1973. Henna: the cosmetic antimycotic drug. Hautrzt 24(2):83-5.

Kamei H, Koide T, Kojima T, Hashimoto Y, Hasegawa M. 1998. Inhibition of cell growth in culture by quinines. Cancer Biother Radiopharm 13:185-8.

Kamei H, Koide T, Kojima T, Hashimoto Y, Hasegawa M. 1998. Inhibition of cell growth in culture by quinones. Cancer Biother Radiopharm 13(3):185-8.

Kandil HH, Al-Ghanem MM, Sarwat MA, Al-Thallab FS. 1996. Henna (Lawsonia innermis Linn) inducing hemolysis among G6PD deficient newborns. A clinical observation. Ann Trop Paediatr 6:284-91.

Kapadia GJ, Balasubramanian V, Tokuda H, Konoshima T, Takasaki M, Koyama J, Tagahaya K, Nishino H. 1997. Anti-tumor promoting effects of naphthoquinone derivatives on short term Epstein-Barr early antigen activation assay and in mouse skin carcinogenesis. Cancer Lett 113(1-2):47-53.

Kayser O, Kiderlen AF, Brun R. 2001. In vitro activity of aurones against Plasmodium falciparum strains K1 and NF54. Planta Med 67:718-21.

Kayser O, Kiderlen AF, Laatsch H, Croft SL. 2000. In vitro leishmanicidal activity of monomeric and dimeric naphthoquinones. Acta Tropica 77(3):307-14.

Kayser O, Masihi KN, Kiderlen AF. 2003. Natural products and synthetic compounds as immunomodulators. Exp Rev Anti-infective Ther 1(2):319-35.

Kempt AJ, Lyons SD, Chrisopherson RI. 1986. Effects of Acivicin and dichloroallyl lawsone upon pyrimidine biosynthesis in mouse L1210 leukemia cells. J Biol Chem 261(32):14891-5.

Kouznetsov VV, Mendez LYV, Gomez CM. 2005. Recent progress in the synthesis of quinolines. Curr Org Chem 9(2):141-61.

Koyama J. 2006. Anti-infective quinone derivatives of recent patents. Drug Discovery 1:113-25.

Krishnarju AV, Rao TVN, Saundaraju D, Vanisree M, Tsay HS, Subbaraju. 2006. Biological screening of medicinal plants collected from Eastern Ghats of India using Artemia salina (brine shrimp test). Int J Appl Sci Eng 4(2):115-25.

Lall N, Das Sarma M, Hazra B, Meyer JJM. 2003. Antimycobacterial activity of diospyrin derivatives and structural analogue of diospyrin against Mycobacterium tuberculosis in vitro. J Antimicrobial Chemother 51:435-8.

Madden RM, Pui CH, Hughes WT, Flynn PM, Leung W. 2007. Prophylaxis of Pneumocystis carinii pneumonia with atovaquone in children with leukemia. Cancer in print.

Malekzadeh F. 1968. Antimicrobial activity of Lawsonia inermis L. App Microbiol 16:4;663-4.

McKelvey EM, Lomedico M, Lu K, Chadwick M, Loo TL. 1979. Dichloroallyl lawsone. Clin Pharmacol Ther 5:1;586-90.

Meinhardt J. 1965. On Therapy of Malaria in the 17th Century. Sudhoffs Arch Gesch Med Naturwiss 49:4;431-5.

Min BS, Miyashiro H, Hattori M. 2002. Inhibitory effects of quinones on RNase H activity asscociated with HIV-1 reverse transcriptase. Phytother Res 16:S1;57-62.

Mofredj A Guerin JM, Leibinger F, Masmoudi R. 2002. Visceral Leishmaniasis with pericarditis in an HIV-infected Patient. Scand. J Infect Dis 34:2;151-3.

Mouhajir F, Hudson JB, Rejdali GHN, Towers GHN. 2001. Multiple Antiviral Activities of Endemic Medicinal Plants Used by Berber Peoples of Morocco. Pharmaceut Biol 39:5; 364-74.

Muhammad HS and Muhammad S. 2005. The use of Lawsonia inermis Linn. (henna) in the management of burn wound infections. Africa J Biotech 4:9;934-7.

Nagata K, Hirai KI, Koyama J, Wada Y and Tamura T. 1998. Antimicrobial activity of novel furanonaphthoquinone analogs. Antimicrob Agents & Chemother 42;700-2.

Nawaf AM, Joshi A, Nour-Eldin O. 2003. Acute allergic contact dermatitis due to para-phynylenediamine after temporary henna painting. J Dermatol 30:11;797-800.

Oliveira CGT, Miranda FF, Ferreira VF, Freitas CC, Rabello RF, Carballido JM and Correa LCD. 2001. Synthesis and antimicrobial evaluation of 3-hydrazino-naphthoquinone as analogs of lapachol. J Brazillian Chem Soc 12;339-45.

Osman AM, Rotteveel S, den Besten PJ, van Noort PC. 2004. In vivo exposure of Dreissena polymorpha mussles to the quinones mendione and lawsone: menadione is more toxic to mussles than lawsone. J Appl Toxicol 24:2;135-41.

Papageorgiou VP, Assimopoulou AN, Couladouros EA, Hepworth D, Nicolaou KC. 1999. The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products. Angewandte Chemie Int 38;270-300.

Pink JJ, Planchon SM, Tagliarino C, Varnes ME, Siegel D, Boothman DA. 2000. NAD(P)H:Quinone oxidoreductase activity is the principal determinant of beta-lapachone cytotoxicity. J Biol Chem 275;5416-24.

Pinto AV, Pinto MCFR, Gilbert B, Peligrino J, Mello RT. 1977. Trypanocidal Activity Due to the Synergistic effect of [beta]-Lapachone with Taxol in a Great Variety of Crude Natural Extracts. Trans Roy Soc Trop Med Hyg 71;133-5.

Prasirst J, Leewatthanakorn T, Piamsawad U, Dejrudee A, Panichayupakaranant P, Teanpaisan R, Nittayananta W. 2004. Antifungal activity of potassium Lawsone methyl ether mouthwash in comparison with Chlorhexidine mouthwash on oral Candida isolated from HIV/AIDS subjects. Abstract from 5th World Workshop on Oral Health and Disease in AIDS, Phuket Thailand July 6-9.

Riffel A, Medina LF, Stefani V, Santos RC, Bizani D, Brandelli A. 2002. In vitro antimicrobial activity of a new series of 1,4-naphthoquinones. Braz J Med Biol Res 35;811-18.

Sarciron ME, Nebois P, Pautie F, Petavy AF, Fillion H, Walchshofer N. 2002. Quinonic derivatives active against Toxoplasma gondii. Parasitol Res 88:11;969-71.

Schmidt B. 1988. Phenol oxidase (E.1.14.18.1), a marker enzyme for defence cells. Progress in histochemistry and cytochemistry vol 17. New York: Gustav Fischer.

Schnur L, Bachrach U, Bar-Ad G, Haran M, Tashma Z, Talmi M, Katzhendler J. 1983. The effect of diaminoalkyl-anthraquinone derivatives on the growth of the promastigotes of Leishmania tropica minor, L. t. major, L. donovani and L. aethiopica. Biochem Pharmacol 2:11;1729-32.

Shanks GD, Oloo AJ, Aleman GM, Ohrt C, Klotz FW, Braitman D, Horton J, Sharma VK. 1995. Tuberculostatic Activity of Henna (Lawsonia inermis Linn). Tubercle 71;293-5.

Sieber SM, Mead JA, Adamson RH. 1976. Pharmacology of antitumor agents from higher plants. Cancer Treat Rep 60;1127-39.

Singh A, Singh DK. 2001. Molluscicidal activity of Lawsonia inermis and its binary and tertiary combinations with other plant derived molluscicides. Indian J Exp Biol 39:3;263-8.

Singh VK, Pandey DK. 1989. Fungitoxic studies on bark extract of Lawsonia inermis against ringworm fungi. Hindustani Antibiot Bull 31:1;32-5.

SOker M, DeveciogluC, Haspolat K, Dikicl B, Dugru O. 2000. Henna induced acute hemolysis is a G6PD-deficient patient: A case report. Int Paediatrics 15:2;114-16.

Srivastava IK, Vaidya AB. 1999. A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antmicrob Agents Chemother 43:6;1334-9.

Stern JL, Hagerman AE, Steinberg PD, Mason PK. 1996. Phlorotannin-protein interactions. J Chem Ecol 22;1887-99.

Stockwell C. 1988. Nature's Pharmacy. London: Century Huchinson Ltd.

Sundar S. 2003. Indian kala-azar--better tools needed for diagnosis and treatment. J PostGrad Med 49:1;29-30.

Tazi J, Bakkour N, Soret J, ZekriL, Hazra B, Laine W, Baldeyrou B, Lansiaux A, Bailly C. 2005. Selective Inhibition of Topoisomerase I and Various Steps of Spliceosome Assembly by Diospyrin Derivatives. Mol Pharmacol 67;1186-94.

Thastrup O, Knudsen JB, Lemmich JL and Winther K. 1985. Inhibition of human platelet aggregation by dihydropyrano- and dihydrofurano-coumarins, a new class of cAMP phosphodiesterase inhibitors. Biochem Pharmacol 34;2137-40.

Thompson WAR (ed). 1978. In: Medicines from the Earth. Maidenhead UK: McGraw-Hill Book Company.

Thomson RH. 1991. Distribution of naturally occurring quinones. Pharm World & Sci 13:2; 70-3.

Tripathi RD, Srivastava HS, Dixit SN. 1978. A fungitoxic principle from the leaves of Lawsonia inermis Linn. Experientia 15:34;51-2.

Veereshkumar SS. 2005. Staining properties of Extract Lawsonia alba. J Anatomical Soc India 54;1 abstract.

Vijaya KS, Ananthan S, Nalini R. 1995. Antibacterial effect of theaflavin, polyphenon 60 (Camellia sinensis) and Euphorbia hirta on Shigella spp--a cell cultures study. J Ethnopharmacol 49;115-18.

Villanueva JL, Alarcon A, Bernabeu-Wittel, Cordero E, Prados D, Regordan C, Avlar. 2000. Prospective Evaluation and Follow-up of European Patients with Visceral Leishmaniasis and HIV-1 Coinfection in the Era of Highly Active Antiretroviral Therapy. Eur J Clin Microbiol Inf Dis 19:10;798-801.

Wendel WB. 1946. The influence of naphthoquinones upon the respiratory and carbohydrate metabolism of malaria parasites. Fed Proc 5;406-7.

Wolfson F. 1941. Avian Hosts for Malaria Research. Quarterly rev Biol 16:4;462-73.

Wright CW, Phillipson JD. 1990. Natural products and development of selective antiprotozoal drugs. Phytother Res 4;127-39.

Habbal OA (1), Al-Jabri AA (2), El-Hag AG (1)

(1) Department of Human & Clinical Anatomy

(2) Department of Microbiology & Immunology College of Medicine & Health Sciences, Sultan Qaboos University, Sultanate of Oman

Correspondence: Dr O Habbal, Head of Department, Department of Human & Clinical Anatomy, College of Medicine & Health Sciences, PO Box 35, Sultan Qaboos University, Muscat PC 123, Sultanate of Oman Email habbal@squ.edu.om
Table 1
Anti microbial activity of henna leaves and seeds at 50% concentrations
(Habbal 2005)

 Henna Extract

Micro-organisms Fresh Fresh
 Leaves Seeds

Bacteria

Escherichia coli (NCTC 10418) ++ +
Pseudomonas aeruginosa (NCTC 10662) ++ ++
Staphylococcus aureus (NCTC 6571) +++ ++
Enteropathogenic Escherichia col + +
Shigella sonnei +++ ++
Bacillus species ++ ++
Klebsiella pneumoniae ++ ++
Salmonella species ++ +
Bacteriodes fragilis + +
Corynebacterium ++ ++
Streptococcus pyogenes + +
Citrobacter frewndii + +
Vibrio cholerae ++ ++
Streptococcus Pneumoniae + +

Yeast

Candida albicans + -

 Henna Extract

Micro-organisms Dry Dry
 Seeds Leaves

Bacteria

Escherichia coli (NCTC 10418) + ++
Pseudomonas aeruginosa (NCTC 10662) + ++
Staphylococcus aureus (NCTC 6571) +++ +++
Enteropathogenic Escherichia col ++ ++
Shigella sonnei ++ ++++
Bacillus species + +++
Klebsiella pneumoniae ++ +++
Salmonella species + ++
Bacteriodes fragilis + +
Corynebacterium ++ ++
Streptococcus pyogenes + ++
Citrobacter frewndii + ++
Vibrio cholerae ++ ++
Streptococcus Pneumoniae + ++

Yeast

Candida albicans - +

++++ = >40 mm zone of inhibition
+++ = 31-40 mm
++ = 21-30 mm
+ = 10-20 mm
- = 0 mm (No inhibitory activity detected)
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Title Annotation:Global dispensary
Author:Habbal, O.A.; Al-Jabri, A.A.; El-Hag, A.G.
Publication:Australian Journal of Medical Herbalism
Geographic Code:8AUST
Date:Sep 22, 2007
Words:6971
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