Lawsone

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Known as hennotannic acid, is a red-orange dye present in the leaves of the henna plant (Lawsonia inermis) as well as jewelweed (Impatiens balsamina).^[5] Humans have used henna extracts containing lawsone as hair and skin dyess for more than 5000 years. Lawsone reacts chemically with the protein known as keratin in skin and hair, in a process known as Michael addition, resulting in a strong permanent stain that lasts until the skin or hair is shed. Lawsone strongly absorbs UV light, and aqueous extracts can be effective sunless tanning and sunscreens.

ETHNOBOTANICAL USES

Henna has been used cosmetically and medicinally for over 9,000 years. Traditionally in India, mehndi is applied to hands and feet. Henna symbolizes fertility. Its use became popular in India because of its cooling effect in the hot Indian summers. Henna leaves, flowers, seeds, stem bark and roots are used in traditional medicine to treat a variety of ailments as rheumatoid arthritis, headache, ulcers, diarrhoea , leprosy, fever, leucorrhoea, diabetes, cardiac disease, hepatoprotective and colouring agent. Henna leaf has an orange-red dye and leaf paste or powder is widely used for decorating hands, nails and feet with patterns. It is also used as a hair dye. It is used for alleviating jaundice, skin diseases, venereal diseases, smallpox and spermatorrhoea. Flowers are very fragrant and used to extract a perfume, which is used as base for local scents. An infusion of the flowers is a valuable application to bruises. Decoction of the flowers is describes as an emmenagogue. Seeds are deodorant. Powered seeds with real ghee (clarified butter) are effective against dysentery. Seeds in powered form are good medicine for liver disorders and associated problems. The bark is applied in the form of a decoction to burns and scalds. It is given internally in a variety of

affections, such as jaundice, enlargement of the spleen, calculus, as an alternative in leprosy and obstinate skin affections. Root is considered as a potent medicine for gonorrhoea and herpes infection. Root is astringent may be pulped and used for sore eyes. Pulped root may also be applied to the heads of children for boils. Cambodians drink a decoction as a diuretic. Decoction of the root generally in combination with prepared indigo as a powerful abortifacient. The root is supposed to be useful in treatment of hysteria and nervous disorders.^[20]

BIOLOGICAL REVIEW

Although this plant has been widely used in various symptoms and diseases, however few pharmacological

studies have been reported. Antidiabetic activity Ethanol (70 %) extract of L. inermis showed significant

hypoglycaemic and hypolipidaemic activities in alloxaninduced diabetic mice after oral administration. The feeding of 0.8 g/kg of L. inermis extract decreased the concentration of glucose, cholesterol and triglycerides to normal. ^[4] Methanol (95 %) extract of leaves of L. inermis showed significant in-vitro antihyperglycemic effect.Immunomodulatory effect Methanol extract of henna leaves at 1 mg/ml concentration had displayed immunostimulant action as indicated by promotion of T-lymphocyte proliferative responses. Seven compounds were isolated adopting the lymphocyte transformation assay (LTA)-guided fractionation of the total methanolic extract of henna leaves.Naphthoquinone fraction obtained from leaves L. inermis showed significant immunomodulatory effect.  Hepatoprotective activity Alcoholic extract of the bark of L. inermis showedhepatoprotective effect and antioxidant activity.Antioxidant effect Modulator effect of 80 % ethanol extract of leaves of henna on drug metabolising phase I and phase II enzymes, antioxidant enzymes, lipid peroxidation in the liver of Swiss Albino mice. Antibacterial activity Ethanol extracts of 20 plants species used by Yemeni traditional healers to treat infectious diseases were screenedfor their antibacterial activity against both gram positive and gram negative bacteria. The ethyl acetate extract of L.inermis L. was found to be the most active against all the bacteria in the test system. ^[5] Quinonic compounds from henna were studied in-vitro for antimicrobial properties. Genotoxic studies on lawsone suggested that it was a weak bacterial mutagen for Salmonella typhimurium strain TA98 and was more clearly mutagenic for strain TA2637. Overall, the weight of evidence suggested that henna and hydroxyl napthaquinone possess no genotoxic risk to the consumer. ^[6] Antifungal activity Ethanol extract of  Lawsone  could be used as alternative source of antifungal agents for protection of plants or crops against fungal infection. Antiviral activity The ethanol soluble fraction of L. inermis fruits displayedhighly potent activity against Sembiki forest virus (SFV) antitrypanosomal activity,antidermatophytic activity ,tuberculostatic activity .The tuberculostatic activity of henna was tested in-vitro and in-vivo. Antifertility activity Ethanol extract prepared from the powdered seeds of L.inermis L. failed to show any antifertility activity. However in subsequent studies it was observed that the powdered leaves of when administered as suspension or incorporated into the diet inhibited the fertility of rats. The fertility induced appeared to be permanent. ^[7] Analgesic activity the ethanol extract of 25 plants commonly used in traditionalArab system of medicine for treatment of pain, fever and rheumatism were investigated for their analgesic andantipyretic activities. The extract of leaves of henna showed significant analgesic as well as antipyretic activity. Cytotoxic activity , Isoplumbagin exhibited up to a 1000 fold range of differential sensitivity, which represents distinct fingerprint of cellular responsiveness. At concentration of 10.5–10.8 M, the compound typically produced LC50 – level responses against a majority of the melanoma and colon cancer cell lines as well as against several of the non- small cell lungs, colon, CNS, and renal cell lines. Isoplumbagin showed an interesting profile of cytotoxic activity.  Chloroform extract of leaves of L. inermis displayed the cytotoxic effectsagainst liver (HepG2) and Human breast (MCF-7) with IC50 values of 0.3 and 24.85μg/ml by microculture tetrazolium salt assay (MTT). ^[7] CAT assay, a zone of inhibition test of bacterial growth and colony-forming efficiency test of transformant Escherichia coli strains that express mammalian catalase gene derived from normal catalase mice (Csa) and catalase-deficient mutant mice (Csb), Ames mutagenicityassay and H2O2 generation assay are carried out.^[20]

Diosgenin:

a steroidsapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of Dioscoreawild yam, such as the Kokoro. The sugar-free (aglycone), diosgenin is used for the commercial synthesis of cortisone, pregnenolone, progesterone, and other steroid products.^[9]

Sources:

It is present in Costus speciosus, Smilax menispermoidea, species of Paris, Trigonella, and Trillium, and many species of Dioscorea - D. althaeoides, colletti, futschauensis, gracillima, hispida, hypoglauca, floribunda, mexicana and composita^[10] nipponica, panthaica, parviflora, septemloba, and zingiberensis.^[11]

Clinical uses:

Diosgenin is the precursor for the semisynthesis of progesterone^[13] which in turn was used in early combined oral contraceptive pills.^[14] The unmodified steroid has estrogenic activity^[15] and can reduce the level of serumcholesterol.^[18]

ACTIVITIES REPORTED ON PLANT:

Diosgenin has been used in traditional medicine as an antihypercholesterolemia, antihypertriacylglycerolemia, antidiabetes and antihyperglycemia agent . Several reports have showed that diosgenin inhibits proliferation and induces apoptosis in a wide variety of tumor cells of human colon, osteosarcoma, leukemia ], erythroleukemia, breast, and liver . The anti-cancer effect of diosgenin has been demonstrated through cell cycle arrest , activation of p53 and caspase.^[14] In addition, diosgenin inhibits NF-κB activity and NF-κB-regulated gene expression and subsequently reducing proliferation, invasion and osteoclastogenesis . Diosgenin also abolishes cyclooxygenase-2  and lipoxygenase , which are implicated in carcinogenesis and as important targets for cancer chemoprevention and therapy.^[15] Therefore, diosgenin may possess the cancer chemotherapeutic potential and its activity involves multiple cellular and molecular targets.Prostate cancer is one of the most commonly diagnosed tumors in men and the second leading cause of cancer mortality in the United States .^[16] Although prostate cancer at the early stage can be treated with surgery and androgen-deprivation therapy, it eventually progress to more malignant, metastasis, and hormone refractory prostate cancer (HRPC), Cancer metastasis is a highly coordinated step-wise process that includes detachment of cells from the primary tumor, local proteolysis of the extracellular matrix (ECM), penetration through the basement membrane of capillary and lymphatic vessels, intravasation, and then invasion into new tissue and growth .^[17] The process of metastasis is promoted by expressing and secreting various proteolytic enzymes that can degrade most ECM components. Matrix metalloproteinases (MMPs), a family of Zn-dependent endopeptidases, are the major proteases participating in tumor cell migration, spreading, tissue invasion and metastasis . Among the MMPs, MMP-2 and MMP-9 are key enzymes for degrading type IV collagen and contribute to the process of metastasis . MMP-2 and MMP-9 are also capable of cleaving type I collagen , the major component forming a lattice structure in stroma . The activation of these enzymes have been associated with increasing tumor metastasis, suggesting an central functional role for these proteases in the metastatic process . Proteolytic degradation of stromal microenvironment plays a critical role in promoting invasion.^[19]