Review Article - International Research Journal of Plant Science ( 2020) Volume 11, Issue 1
Received: 19-May-2020 Published: 24-Jun-2020, DOI: 10.14303/irjps.2020.006
Lawsonia inermis L., commonly known as Henna plant, have been reported to be useful both medicinally and commercially. The phytochemical extract of this plant leaves have been reported to be a rich source of phenols, glycosides, anthraquinones and many other active constituents. Therapeutically, this plant has been used to treat diabetes, arthritis, obesity, ulcers, wounds, microbial infections, inflammation and liver damage. The extracts have also been instrumental in lowering blood sugar and cholesterol levels in mice. But one of the most crucial aspects of this plant is, limiting the growth of malignant cells. Extracts have shown apoptosis promoting activity in human cancer cell lines like breast cancer cells. The pigment lawsone, is commercially used on a large scale, as a dying agent for fabrics and skin. This component has shown potential role in reducing oxidative burst in cell, hence, establishing its role as an antioxidant, which should help researchers to manipulate the property, for establishing new potential drugs against cancer. Apart from “Lawsone” the small molecule reservoir of Lawsonia inermis L.have not been commercially utilized effectively and in the future these bioactive compound set should be explored for formulating new chemical entities.
Red henna or Lawsonia inermis L. (Lythraceae), is a perennial shrub, widely cultivated in tropical regions of Egypt, America, India and Middle East (Singh, et al., 2012), commonly known as Mehndi. Commonly known as Cypress shrub, Samphire, Mendika, Timir, Rakigarbha, Goranta, Kormi, Maruthani and Mayilanchi, this plant develops white and rose-red flowers. The plant grows to a height of about six meters. Leaves are opposite, sub-sessile, acuminate, lanceolate, glabrous and contain lawsone, (naphthoquinone) which is used to dye fingers, fabrics and hair. Henna fruits usually ripen at the end of summer, each fruit bearing about 40-45 seeds. When young, the plant has low dye content and lacks spine. As the plant matures, the dye content increases and spine formation occurs. In India, commercial Henna production is found in states of Rajasthan (Jodhpur and Pilani), Thane, Kalyan and Badlapur (Phirke, et al., 2013). In the Rajasthan region, due to an arid atmosphere, low rainfall and poor soil fertility conditions, cultivation of Henna plant by the farmers, provide a good source of income. Also, uninterrupted growth of Henna plant in elevated temperatures and poor soil conditions indicate the potential role of this plant in fixing atmospheric carbon at a time of climate crisis due to rise in global warming.
Henna plant leaves have a wide plethora of medicinal uses. Extracts of mainly leaves can be used as an diabetic (Widyawati, et al., 2019), anti-arthritis (Ramya, et al., 2015; Kadhem, 2016), in treatment of bacterial infections (Hussain, et al., 2011; Habbal, et al., 2011; Raja, et al., 2013; Rahiman, et al, 2013; Akintunde, et al., 2017), fungal infections (Rizvi, et al., 2013), diarrhea, obesity, liver damage (Bhaskaran and Shruthi, 2016; Mohamed, et al., 2016), ulcers (Goswami, et al., 2011; Sravanthi, et al., 2011; Basipogu and Syed, 2015), gingivitis and stimulation of immune system (Uthayakumar, et al., 2014), when taken orally. There have also been reports that extract of seeds of this plant has potential antioxidant capacity (Chaibi, et al., 2017) and plant extract has helped in reducing proliferative growth of human cancer cell lines (Eldrini, et al., 2007). The extracts have also successfully tackled oxidative burst in cells. This antioxidant property was mainly due to the high polyphenolic content of the extracts (Uma, et al., 2010; Zohourian, et al., 2011). Commercial exploitation of phytochemicals from Henna plant in treating ailments has put this plant on high demand. Hence, there arises a need for mass scale Henna plant cultivation. Apart from “Lawsone” the small molecule reservoir of Lawsonia inermis L. have not been commercially utilized effectively. The bioactive compound set should be explored for formulating new chemical entities for future use.
Medicinal Importance
Anti-carcinogenic properties
The effects of leaf extracts of Lawsonia inermis when tested on various cancer cell lines to assess the anti-carcinogenic effects, showed significant cytotoxic effects. The extracts slowed down the tumour growth of the breast cancer and colon cancer cell lines, but no effects were seen against liver cancer cell lines (Eldrini, et al., 2007). Lawsonia leaf extracts were reported to be a free radical scavenger, which could reduce the oxidative stress in serum, kidney and liver of Wister albino rats. The activity of hydrogen peroxidase, lipid peroxide in serum and tissue homogenates was found to be high with rats treated with high dose of henna extract. There was a significant decline in catalase activity (Al- Damegh, 2014). It was seen that Lawsonia extracts showed effective DPPH radical scavenging activities. It also showed lipid peroxidation activities. Mice which were treated with Lawsonia extracts showed low levels of glucose, cholesterol, triacylglycerol and lipoprotein cholesterol in their blood (Ojewunmi, et al., 2013). This potential antioxidant activity was mainly attributed to the phytochemical constituent of the leaves, specially the high phenolic content.
Treating infections
The methanolic extracts of different plants were tested for their antibacterial activities, by disc diffusion method (Hussain, et al., 2011; Raja, et al., 2013). Lawsonia inermis showed antibacterial activity against Escherichia coli, Bacillus cereus, Staphylococcus aureus and many other strains. These effective activities against the bacterial strains are mainly due to flavonoids and glycosides, the main constituents of the leaves. Recent research has also suggested that lawsone, from the leaves of Lawsonia inermis, can be used externally due to its low toxicity. The extract of Henna leaves was also found to be effective on the strains of Enterococcus, Micrococcus, Trueperella, Klebsiella, Proteus, and Shigella (Akintunde, et al., 2017). Antibacterial and antifungal activities for Henna plants, growing in vivo (growing on soil) and in vitro (growing in tissue culture laboratory) showed no drastic difference in their activities against C. albicans, S. aureus, P. aeruginosa, B. cereus, E. coli, A. niger, Trichoderma sp. and Fusarium sp. (Rahiman, et al., 2013). Methanolic extracts of the leaves when evaluated showed potential activity against disease causing bacteria. Extracts also showed inhibition to the growth of fungus like, Fusarium, Alternaria and Mucor (Rizvi, et al., 2013). Potential antifungal action was found in the leaf extracts of the plant against clinical isolates of Candida sp. (Yigit, 2017). Apart from alcoholic extracts, petroleum ether extracts of the leaves were reported to possess antifungal activities against Candida albicans, Saccharomyces cerevisiae, Trichophyton mentagrophytes, Trichophyton violaceum and Aspergillus flavus (Suleiman and Mohamad, 2014). Lawsone (commercial) was treated with a base in the presence of water to yield naphthoquinone derivatives, which were effective on fungal and bacterial strains but showed less effects on strains of Candida sp (Rahmoun, et al., 2012). Convenient and low-cost metal nanoparticles were obtained, using leaf extracts of Lawsonia inermis, showed effective antibacterial properties (Naseem and Farukh, 2015). A comparison was drawn where the in vitro antifungal property of the chloroform, methanol and aqueous extracts of Lawsonia leaves showed potential action against Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum gypsum and Microsporum fulvum, which are commonly involved in causing skin diseases (Sharma, et al., 2011). Certain plant products like alkaloids, steroids, flavonoids, terpenoids, and saponins, found in ethanol extract were accounted responsible for inhibiting bacterial growth. Hexane and ethyl-acetate extracts, rich in glycosides, showed potent antibacterial activity as well (Yusuf, 2016). Silver nanoparticles, coated with henna leaf extracts, evaluated for their antibacterial activity, successfully inhibited growth of bacteria, as seen by disc diffusion method (Kumar and Kathireswari, 2016). In a study, 63 patients (divided into 5 groups) suffering from gingivitis, a disease caused by formation of bacterial plaque eventually infect the underlying tissue, causing periodontitis, were asked to rinse with 3 different concentrations of Lawsonia inermis leaf extracts (50000 μg/ ml, 10000 μg/ml and 5000 μg/ml). Leaf infusions having a concentration of 10000 μg/ml was found to be most effective in curing the infection (Zubardiah, et al., 2012).
Anti-ulcer effects
The antiulcer effects of water, chloroform and ethanolic extracts of leaves of Lawsonia inermis on rats with ulcers were tested (Goswami, et al., 2011). In case of aspirin induced ulcers, chloroform extracts showed a significant reduction of ulcers with an increase in dose. Volume of gastric juice, total acidity, ulcer index and free acidity were the parameters used to assess the ulcer conditions. Methanolic extracts of the leaves, showed effective results on ulcer induced rats, up to above 50% (Goswami, et al., 2011). Cold stress induced ulcers were also cured by ethanolic leaf extracts in Wistar rats. After phytochemical screening, a large number of chemical compounds like alkaloids, glycosides, naphthoquinones, terpenoids, tannins, phenolic compounds and carbohydrates were identified which directly or indirectly helped to cure the ulcers (Sravanthi, et al., 2011).
Analgesic activity
Methanolic leaf extracts were seen to exhibit analgesic, anti-inflammatory and CNS depressant activities on mice. Analgesic activity was measured by using acetic acidinduced writhing model and formalin-induced licking and biting in mice. The CNS depressant activity was investigated and seen that a dose of 500 mg/kg body weight induced higher analgesic activity in mice affected with acetic acid induced pain. Also, the methanolic leaf extracts showed significant CNS depressant and anti-inflammatory activity in a dose dependant manner (Nesa, et al., 2014).
Antiarthritic effect
Rheumatic arthritis is an inflammatory, autoimmune illness. Aqueous extracts of Lawsonia inermis leaves at different concentrations (50, 100, 250, 500, 1000, 2000 μg/ml) were used to assess the inhibition of protein denaturation and membrane lysis. The effects of leaf extracts were compared with diclofenac sodium drug. It was seen that the leaf extracts were successful in protective activity against arthritis due to the active constituents of the leaves (Ramya, et al., 2015).
Anti-diabetic property
The hypoglycaemic and antihyperlipidemic effects of leaf extracts were evaluated. For this purpose, mice, which were subjected to hyperglycaemic conditions were treated with 70% ethanolic extract of leaves of Lawsonia. The results showed that mice which were treated with leaf extracts showed normal glucose levels in their blood. It was also observed that triacylglycerols and cholesterols were low for mice which were treated with leaf extracts (Abdillah, et al., 2008). The extracts also showed inhibitory effects on the glucose utilization. It was seen that triacylglycerol accumulation was inhibited to a certain extent (Arayne, et al., 2007).
Hepatoprotective activity
Wistar albino rats were administered with paracetamol (750 mg/kg) to induce liver damage. When subjected to Lawsonia inermis leaf extracts (ethanolic), it was seen that a dose of 400 mg/kg lowered the bilirubin level and heightened the SGPT and total protein levels, exhibiting hepatoprotective activities (Bhaskaran and Shruthi, 2016). Liver damage in mice, induced by carbon tetrachloride treatments were also treated by Lawsonia inermis leaf extracts, when administered orally at a dose of 100 mg/kg and 200 mg/kg body weight. It was seen that, mice, which were administered with Lawsonia extracts, showed quick recovery from liver damage at a dose dependant manner (Mohamed, et al., 2016).
Immuno-stimulatory effects
Methanolic extracts of Lawsonia inermis leaves were administered in fishes, affected with ulcers. There was an increase in levels of red blood cells, white blood cells, haematocrit and haemoglobin. Mean corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration decreased. Thus, henna plant extracts were reported to have immunostimulatory functions (Uthayakumar, et al., 2014).
Chemical analysis of leaf extract of Henna
High performance liquid chromatography (HPLC) has been a very reliable method in reporting the phytochemical constituents of plant extract. Chemical composition of the extract of leaves of Henna depends on the conditions of extraction and the solvent used. Microwave assisted extraction reported a higher level of phenol and antioxidant potential, compared to those extracted at normal room temperature (Zohourian, et al., 2011). Factors like temperature, time, acetone concentrations are necessary parameters that regulate proper phenol extraction from leaves (Uma, et al., 2010). It was reported that a temperature of 39.57â°C, time of 73.78 minutes and acetone concentration of 48.07% resulted in optimum phenol extraction (7203.74 mg GAE/100g of dry weight). Phytochemical screening of the extracts, not only showed high phenols, but also proved to have flavonoids, alkaloids, tannins and anthraquinones. All these chemicals impart antibacterial, antioxidant and cytotoxic property to the extracts (Mansoor, et al., 2016). ß-sitosterol, reported from the leaves also contained potential antioxidant capacity (Badhai, et al., 2016). A study reported that the extracts helped to stop the growth of human breast cancer cells (Omran, et al., 2017). Silica gel column chromatography identified a new compound with powerful antioxidant potential. This compound was further purified and characterized by spectroscopic methods as 1,2,4-trihydroxynapthalene-2-O-ß-D-glucopyranoside (Dhouafli, et al., 2017). Three other compounds, lalioside (2, 3, 4,6-tetrahydroxyacetophenone-2-O-ß-D-glucopyranoside), luteolin-7-O-ß-D-glucopyranoside and lawsoniaside (1,2,4-trihydroxynaphthalene-1,4-di-O-ß-D-glucopyranoside) were also reported in L. inermis. The antioxidant activity of these compounds was evaluated by DPPH and ß-carotene assays (Hsouna, et al., 2010). The various polyphenols, antioxidant, anti-proliferative and antigenotoxic effects of polar and non-polar extracts were analyzed (Kumar, et al., 2014). The extracts were seen to reduce the mutagenic effects of mutagens like 4-nitroquinoline1- oxide and nitrofurantoin and protected DNA damage against strong oxidants. The extracts were effective against the growth of cancer cell lines, like PC3 and Colo 205. Partial purification of the phenolics and flavonoids was done by adsorption chromatography, using a silica gel column. The phenolics and flavonoids were estimated using gallic acid and quercetin as standards. The antioxidant potential was measured by ABTS assay.
Lawsonia inermis L. plant extract was reported to have potent antioxidant properties (Saeed, et al., 2013). Extracts made with various solvents were also evaluated for their phenolic contents and radical scavenging properties. It was seen that, ethanolic preparations showed high antioxidant capacities.
The chemical space of Bioactive compounds in Lawsonia inermis L. and their potential use in Computer Aided Drug Discovery
Half of the world’s repertoire of approved drugs over the last 30 years have come either directly from natural products or are derivatives of the original bioactive small molecule of plant origin. From the 1940s to date, of the 175 small molecules approved as drugs, 85 actually have natural origin. The history of plants towards treatment of myriad diseases is long and illustrious. However, internationally the rate of approval of new drugs has slowed down considerably. Despite technological advances in drug discovery, between 1996 and 2007, the number of new molecular entities approved by the US FDA has fallen from 53 to 17 per year—the same rate as over 50 years ago (FitzGerald, 2008; Munos, 2009). This trend has been attributed to the following factors:
1. The most acceptable hypothesis involves the overutilization of the “lowest hanging fruits” in terms of small molecule drug candidates that have been extensively investigated, and computational challenges hinder extension of traditional methods to more complex structures. Researchers refer to “rediscovering the sweet spot” as the discovery process (Brown and Superti-Furga, 2003), which have the potential to produce targeted screening libraries that ideate the anticipated characteristics of lead compounds (Welsch et al., 2010; Cheng, et al., 2012).
2. The second problem lies with the complexity of the diseases and the failure to identify suitable drug targets. Thus, making the process of prediction lead compounds difficult (Ramsay, et al., 2018).
3. Clinical trials involving model organisms often do not provide suitable results due to inter-species variations that are crucial to therapeutic action, thus making the process of drug discovery difficult (Hunter, 2008; Ehret, et al., 2017).
The Small Molecule Reservoir
It has reported that, 80% the plant derived drugs have established ethnopharmacological literature sources. Workers have indicated that co interactions can actually increase the potency of plant crude extracts and has attributed the reduction in efficiency of isolated and purified plant products as a result of this lack of co interactions (Lila and Raskin, 2005). As we are all aware that additive and synergistic effects results in potentiation, in which a group of compounds in a mixture interact to provide a combined effect that is equal to the sum of the effects of the individual components (additive) or where combinations of bioactive substances exert effects that are greater than the sum of individual components (synergistic) (Veeresham, 2012). Since Lawsonia posses a large repertoire of active principles, such as quinones, phenylpropanoids, flavonoids, terpenoids, phenolics, tannins, alkaloids, xanthones, coumarin, glucosides, naphthoquinone, saponins, triterpenoids, sterols and dioxin derivatives; it is a rich source for such potentiation and natural product-based drug discovery studies (Table Ι). Some identified small molecules such as isoplumpagin (a naphthoquinone 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 along with 24-beta ethyl cholest-4-en-3-betaol from roots. (Singh and Luqman, 2014).
Phytochemical | Formula | Molecular weight (g/mol) |
Amount present (%) |
---|---|---|---|
1. Lawsone (Mohamed, et al., 2016) | C10H6O3 | 174.15 | 0.5-1.0 |
2. Gallic acid (Bhaskaran and Suruthi, 2016) | C7H6O5 | 170.12 | 0.24-0.72 |
3. Catechin (Bhaskaran and Shruthi, 2016) | C15H14O6 | 290.26 | 0.76-1.50 |
4. Chlorogenic acid (Bhaskaran and Shruthi, 2016) | C16H18O9 | 354.31 | 1.21-2.20 |
5. Epicatechin (Bhaskaran and Shruthi, 2016) | C15H14O6 | 290.26 | 0.03-0.22 |
6. Caffeic acid (Bhaskaran and Shruthi, 2016) | C9H8O4 | 180.16 | 0.07-0.14 |
7. Umbelliferone (Bhaskaran and Shruthi, 2016) | C9H6O3 | 162.14 | 0.04-0.28 |
8. Rutin (Bhaskaran and Shruthi, 2016) | C27H30O16 | 610.52 | 0.21-0.79 |
9. Ellagic acid (Bhaskaran and Shruthi, 2016) | C14H6O8 | 302.197 | 0.23-5.92 |
10. Quercetin (Bhaskaran and Shruthi, 2016) | C15H10O7 | 302.236 | 0.13-0.41 |
11. Kaempferol (Bhaskaran and Shruthi, 2016) | C15H10O6 | 286.23 | 0.63-3.98 |
12. Coumaric acid (Bhaskaran and Shruthi, 2016) | C9H8O3 | 164.0473 | 0-0.015 |
13. 1,2,4-trihydroxynapthalene-2-O-ß-D-glucopyranoside (Akintunde, et al., 2017) | C16H1808 | 338.31 | Not reported |
14. 2,3,4,6 tetrahydroxyacetophenone-2-O-ß-D-glucopyranoside (Goswami, et al., 2011) | C14H18O10 | 346.29 | Not reported |
15. 1,2,4-trihydroxynaphthalene-1,4-di-O-ß-D-glucopyranoside (Goswami, et al., 2011) | C22H28O13 | 500.45 | Not reported |
16. Luteolin-7-O-ß-D-glucopyranoside (Goswami, et al., 2011) | C21H20O11 | 448.38 | Not reported |
All the above active constituents should be incorporated in natural product libraries and passed through standard virtual screening pipelines (Figure. 1) and evaluated for their efficacies as potential lead compounds for therapeutic interventions.
Reports show that Lawsonia inermis L. is a plant, rich in phytochemicals which can be used to treat a vast range of human diseases like arthritis, diabetes, ulcers, inflammation, wound, blood sugar, microbial infection and many more. The potential action of the extract in inhibiting proliferation of cancer cells makes this plant seek all the more attention. Apart from the commercial and economic aspect, if the antioxidant and radical scavenging potential of the plant is exploited in a proper manner, then Henna plant can be potentially used to treat grave human diseases, like cancer. Also, in silico data analysis could be very helpful in the current times, for the development of potential drugs from the phytochemicals isolated. For this, focus should be on the correct manipulation of the parameters of extraction and the physiological conditions in which the plants grow. As the threat of microbial resistance and emerging infectious diseases gradually increase and mankind’s therapeutic arsenal starts to dry up, more and more ethnopharmacologically important herbal explorations have to be undertaken to ascertain the continuous supply of lead molecules which can be formulated as drugs.
This work was financially supported by DST.
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