Articles

Plumbago zeylanica

Synonyms

No documentation

Vernacular Names:

Malaysia

Celaka, Celaka bukit, Celaka Putih, Ceraka

English White flower lead wort; Ceylon leadwort
Indonesia

Ceraka (Sumatera); Daun encok, Ki encok (Sunda); Gadong encok, Poksor (Jawa); Kareka (Madura); Bama (Bali); Oporie (Timor);

Philippine

Sagdikit (Tagalog); Bagbag, Talankaw (Iloc)

India

Agnimata, Chitraka (Sanskrit); Chita (Hindi), Jvala, Agni, Chitrak, Chitra, Chitrakmula, Chica, Chitri, Chiti (Hindi), Chittiramulam, Vellai (Tamil)

Nepal

Chitu

Tibet

Tsi tra ka (Wylie) [1] [2] [3] [5] [7] [8] [9] [13] [14] [15]

General Information

Description

Plumbago zeylanica has a straggling shrub up to 3m tall; stems erect, trailing or climbing, wiry, diffusely branched, glabrous, with prominent longitudinal ridges and often with white waxy dots. The leaves alternate, simple and entire. The stipules absent. The petiole measures 0.5 mm long with small auricles present in young leaves; blade ovate, ovate-lanceolate, elliptical or oblong in shape, meauring 2.5-13 cm x 1-6 cm, base cuneate, apex acute, acuminate or obtuse, with white waxy dots underneath. The inflorescence a terminal raceme, measures 6-30cm long, sometimes paniculate, many-flowered. The bracts ovate to lanceolate in shape, measure 3-7 mm long. The peduncle measures 1-1.5 cm long, with prominent sessile glands. The flowers bisexual, regular, 5-merous, sweet-scented. The pedicel measres 1 – 2 mm long while the calyx tubular measures 7-11 mm long, 5-ribbed, with stalked glands along ribs. The lobes measure up to 1.5 mm long while the corolla tube measures 15-30 mm long, lobes oblong to ovate in shape, measuring 5-12 mm long, spreading, mucronate, white; stamens free, included; ovary superior, 1-celled, style filiform, with 5 elongated stigma lobes. The fruit an oblong capsule measuring 7.5-8 mm long, apex acute with 5 furrows, 1-seeded.  The seed oblong in shape, measures 5-6 mm long, reddish brown to dark brown in colour. [4]

Plant Part Used

Whole plant, roots, leaves and fruits [3] [9] [14] [45] [59]

Chemical Constituents

2, 5-dimethyl-7-hydroxychromone; 2-methyl-5-hydroxy-1, 4-naphthoquinone; 3-3’-biplumbagin; 3-chloroplumbagin; 3’-O-β-glucopyranosyl plumbagic acid; 3’- O-β-glucopyranosyl plumbagic acid methylester; 4-hydroxybenzaldehyde; 5-methoxyseselin; beta-sitosterol; beta-sitosteryl-3beta-glucopyranoside; beta-sitosteryl-3beta-glucopyranoside-6'-O-palmitate; chitranone; chitranone (3-6’ biplumbagin); dihydroserone; droserone; droserone (2- hidroxy plumbagin); elliptinone; indole-3-carboxaldehyde; isoshinanolone 2-methylnaphthazarin; lupenone; lupenyl; lupeol; lupeol acetate; maritinone; napthoquinonemethylene3’ 3-diplumbagin; nisoshinanolone; plumbagic acid; plumbagin; plumbagol; plumbazeylanone isozeylinone; plumbazeylone; sesellin; suberosin; trans-cinnamic acid; trilinolein; vanillic acid; xanthyletin; xanthoxyletin; zeylinon; zeylone;[2] [8] [9] [15]

Traditional Used:

P. zeylanica is considered a stimulant, diaphoretic, stomachic, abortifacient and narcotic. Based on these believes it is being used in treating a number of diseases.

Gastrointestinal Diseases

The Chinese believes that P. zeylanica has the ability to increase digestive heat with fire-like power. In Nepals it is being used to treat dyspepsia, diarrhea and haemorrhoids. In Ayurveda, the plant is recommended for removing worms, stimulating appetite, absorbing excess fluids from the intestines, destroying toxins and as a digestive. In Mauritius and Rodrigues Islands, the inhabitants recognized the roots as a remedy for diarhhoea and dyspepsia. Amongst the worms that succumbs to it is the hookworm. In Ghana the roots are applied as an enema for the treatment of haemorrhoids.[1] [2] [4] [7] [9] [10] [12] [14] [15]

Respiratory Diseases

The Ayurvedic practioners sometimes use the plant to treat cough and breathing difficulties. In Zimbabwe, an infusion of the roots is used for shortness of breath.[2] [4]

Gynaecological and Obstetrical Diseases

The Malays provide decoction of the plant on the third day post-partum. The leaves are eaten as a vegetable as a measure of delaying menstruation. Illicit induction of abortion is done by giving a decoction of the roots; a practice which should be frowned upon by the society. In Africa the pulped roots or aerial parts are inserted into the vagina to induce abortion; a dangerous practice which could result in death.[3] [4] [5] [6] [9] [13]

Genito-Urinary Diseases

In Indonesia the leaves is applied over the pubic region to help ease dysuria. The barks, roots or leaves are used to treat gonorrhea and syphilis.[4] [7]

Inflammatory Diseases

In Ethopia the powdered bark, root or leaves is used to treat gonorrhea, syphilis, and tuberculosis. The Zambians make use of the roots boiled in milk as a remedy for inflammation of the mouth, throat and chest. In Himachal Pradesh the native use a paste of the roots to induce drainage of abscesses. In Indonesia it is used as an antirheumatic remedy by local application over the affected site. However, it has to be used with great caution because of its vesicant effects on the skin.[4] [7] [8] [10]

 

Skin Diseases

Decoction of the roots is used for scabies. It is widely used to treat various skin affections including leprosy, ringworms, dermatitis, acne, sores and ulcers. Most of the time the roots are the part that is being used for skin problems. However, care must be taken as it can also cause skin irritation and vesicular eruptions. Dried and pulverized roots is a remedy for parasitic skin infestation. Paste of the root in vinegar, milk and water is used to treat influenza and balckwater fever in Africa.[4] [6] [7] [10] [15] [16]

 

Other Uses

Extracts of the roots is used to treat hypertension in a Malay community. A paste of the roots is applied behind the ear to help relieve headache. Another way of relieving headache is by applying the root paste in the palate. Tincture of the root bark is an antiperiodic and a sudorific. The root cooked with meat in a soup is considered an aphrodisiac amongst the Zimbabwe people.[3] [4] [5] [7] [10] [11]

Pre-Clinical Data

Pharmacology

Effects on blood coagulation profile activity

The structure of the active compound in P. zeylanica was found to be similar to that of vitamin K. Based on this Vijayakumar et al[17] studied the effects of extract of P. zeylanica on blood coagulation profile. They found that it did not change the platelet count but significantly decreased the platelet adhesion. Chronic admintration of the extract prolonged the bleeding time by altering platelet adhesiveness and the coagulation. Since these finding were similar to the group treated with naphthoquinone it is believed that the changes observed in the P. zeylanica extracts may be due to this component.

Antiallergic activity

70% ethanol extract of P. zeylanica stems show ability to inhibit mnast cell-dependent immediate allergic reaction. This is evidenced by the fact that the extract could inhibit systemic anaphylactic shock induced by compound 48/80 in mice, reduce homologouc passive cutaneous anaphylaxis and skin reactions induced by histamine or serotonin in rats. In vitro, the extract could reduce histamine release from rat peritoneal mast cells caused by compound 48/80 and antigen. It also markedly increased intracellular cAMP content of rat mast cells.[18]

CNS stimulation activity

Bopaiah CP et al[19] studied the central nervous system (CNS) stimulatory action of 50% ethanol extract of the root of P. zeylanica. The study revealed that the extract could increase spontaneous motility in rats with higher ambuloatory and rotaory behaviour which is dose dependent. The extract specifically enhanced the spontaneous ambulatory activity without inducing stereotypic behaviour. Neurochemical estimations revealed elevated leves of Dopamine and Homovanilic acid in striatum the levels being highest at dose of 200mg/kb but begins to decline as the dose is increased. These behavioural and biochemical results is indicative of stimulatory properties of the extract being mediated by dopaminergic mechanisms in the rat brain.

Hyperglycemic activity

Olagunju JA et al[20] noted that their ethanol extract of the roots of P. zeylanica reduced key glycolysis enzymes (hexokinase, phospofructokinase, pyruvate kinase and lactate dehydrogenase) activities in the thigh muscles of rats. Serum pyruvate and lactate were significantly lowered. This results suggest that there is a reduction in flux across the glycolytic pathway, a result of impaired delivery to, and utilization of, glucose by the peripheral tissues. This substantiate the reported hyperglycemia in the extract-treated rats. Parimala et al[21] identified Plumbagin as the compound responsible for this action when they studied it’s activity in 3MeDAB induced hepatoma in Wistar male mice.

Genotoxicity activity

Plumbagin, the most active compound in extracts of the roots of P. zeylanica was found to induce micronuclei at all doses studied (4mg/kg, 8mg/kg and 16mg/kg) and proved to be toxic to bone marrow cells of Swiss albino mice. Glutathione S-transferase (GST) activity was significantly inhibited by higher doses of plumbagin (8 mg and 16 mg/kg b.w.). While plumbagin by itself has genotoxic activity, the same investigator (Sivakumar et al) found that the alcoholic extract of the root of P. zeylanica in total proved to protect their Swiss albino mice from the genotoxic effects of cyclophosphamide. The extract instead significantly reduced the frequency of micronucleated polychromatic erythrocytes, increased the PCE/NCE ratio in the bone marrow, and decreased the levels of lipid peroxidation products with concomitant changes in the status of antioxidant. While plumbagin per se could cause genotoxicity, Demma et al proved that when in low dose (non-DNA damaging dose) in combination with NQNO or catechol, it could significantly reduce the catechol-induce DNA damage. This proves tha the non-DNA damaging concentration of plumbagin diminished the DNA damage induced by catechol by an antioxidative action.[22] [23] [24] [25]

Antioxidant activity

Tilak JC et al[26] found that the boiled ethanol extract of the roots of P. zeylanica has the most effective antioxidant activity. This extract was found to have high levels of polyphenols and flavonoids. They also found that plumbagin was another component of the extract that has strong antioxidant activity.

Anti-inflammatory activity

Various extracts of the leaves of P. zeylanica were tested for their anti-inflammatory and analgesic properties. Sheeja et al[27] found that the acetone extract has a significant anti-inflammatory activity while the acetone and petroleum ether extracts significantly decrease pain stimulus only in the late phase of formalin tgest indicating that it is a peripheral action. The bio-assay-guided fractionation of the acetone extracts lead to the isolation and identification of plumbagin.

Immunomodulatory activity

It has been reported that plubagin from the roots of P. zeylanica could suppress the activation of NF-kappa B in tumour cells. Consequently Checker R et al[28] found that it affect the biological functions of leukocytes participating in various immune responses. This is evidenced by the following: 1. inhibit T-cell proliferation in response to polyclonal mitogen Concanavalin A (ConA) by blocking cell cycle progression; 2. suppressed expression of early and late activation markers CD69 and CD25 repectively in activated T-cells; 3. decrease in levels of Con A induced IL-2, IL-4, IL-6 and IFN-gamma cytokines; 4. completely inhibit ConA induced IkappaB-alpha degradation and NF-kappaB activation. Tsai WJ et al[29] isolated another compound (seselin) from Plumbago zeylanica which seem to have almost similar effects on human peripheral blood mononuclear cells.

Antifertility activity

The acetone and ethanol extracts of leaves of P. zeylanica showed effective interruption in oestrous cycle of rats. There was prolonged dioestrous stage of the oestrous cycle corresponding to a temporary inhibition of ovulation. This antiovulatory activity is reversible upon discontinuation of the treatment.[30]

Abortifacient activity

Treatment with powdered root of P. zeylanica during the first 7 days of pregnancy resulted in perimplantationary loss together with loss of uterine proteins of 13,000; 19,000 and 26,000 and 75,000 Da molecular weights. For those given the root from day 6 to day 17 of pregnancy proteins of molecular weights 55,000 and 65,000 Da were absent. This shows that proteins of 13,000; 19,000; 26,000 and 75,000 Da influence implantations while those of 55,000 and 65,000 Da are required for maintenance of pregnancy.[31]

Lipid metabolism activity

Plumbagin was reported to have the following effects on lipid metabolism of rabbits: 1. reduce serum cholesterol and LDL-cholesterol by 53% - 86% and 61% - 91 % respectively; 2. lower cholesterol/phospholipid ration by 45.8%; 3. elevates decreased HDL-cholesterol significantly. It was also observed that it could prevent accumulation of cholesterol and triglycerides in liver and aorta and regressed atheroma plaques of thoracic and abdominal aorta. The treated rabbits excreted more faecal cholesterol and phospholipids.[32]

Antimicrobial activity

Various researcher have found that P. zeylanica extracts showed potentials of antimicrobial activities. They found that P. zeylanica extracts are active against multidrug resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA).[33] [34] [35]

Plumbagin isolated from the roots of P. zeylanica could enhance the effects of antibiotics (streptomycin and rifampicin) against antibiotic resistant strains of bacteria (Escherichia coli and Staphylococcus aureus).[36] Plumbagin was also found to have antimycobacterial activity.[37] Jetty A et al[38] isolated two more antibacterial compounds from the roots i.e. neoisoshinanolone and 1-epineo-isoshinanolone.

Antiplasmodial

Simonsen et al[42] found that P. zeylanica was amongst the five species out of 47 species of plants they studied, to have antiplasmodial activity.

Antiviral

Chen W et al[43] found that water soluble extract of P. zeylanica (a component of Ganduqing) has the ability to inhibit HBeAg and HBsAg expressed by 2.2.15 cells. Gebre-Mariam T et al[44] found 80% methanol extract of Plumbago zeylanica could inhibit Influenza A virus and Coxsakie virus B3.

Anti-Helicobacter pylori activity

In a preliminary study of 50 Taiwanese folk medicinal plants for their anti-Helicobacter pylori activity, Wang YC et al found that the 95% ethanol extract of P. zeylanica possess the highest anti-Helicobacter pylori activity. They went on the study the activity further to find that the organic solvent (ethyl acetate, acetone, and ethanol) extracts were more effective than the aqueous extract. Ethyl acetate extract showed the lowest MIC against 5 strains of H. pylori ranging from 0.32 to 1.28 mg/ml. This is followed, in ascending order, by acetone, ethanol and water analogs. Bactericidal activity again was seen highest in ethyl acetate (MIC of 5.12 – 20.48 mg/ml) followed by acetone, and ethanol. The ethyl acetate extract showed high stability within pH range of 1 – 7. They finally identified plumbagin to be one of the compounds responsible for this activity.[39] [40] [41]

Cytotoxic activity

P. zeylanica showed significant cytotoxic activity. Various workers had isolated a number of compounds and determined their range of effects on cancer cells.

  1. Plumbagin[45] [46] [47] [48] [49] [50] [51] [53] – Raji, Calu-1, HeLa, Wish tumour, MCF7, Bowes, APL (human acute promyelocytic leukemia), NB4, Human Prostatic cancer and human pancreatic cancer cell lines.
  2. beta-sitosteryl-3beta-glucopyranoside-6'-O-palmitate[46] – MCF7 and Bowes cancer cell lines
  3. beta-sitosterol[46] – Bowes cell lines
  4. 3beta-hydroxylup-20(29)-ene-27,28-dioic acid[52] – MDA-MB-231 cell line

Plumbagin was found to have cell growth modulatory, anticarcinogenic and radiosensitizing effects due to its ability to inhibit NF-kappaB activation and NF-kappaB-regulated gene products via modulation of p65 and IkappaB-alpha kinase activation.[47] Nazeem S et al[57] and Powolny AA et al[54] suggested the possibility of an important role played by ROS in plumbagin-induced apoptosis in human prostate cancer cells. The ROS factor was also suggested by Xu KH et al[55] in their study on human promeyelocytic leukemia cells. Aziz et al[56] found that plumbagin could inhibit the growth and invasiveness of prostatic cancer, inhibits multiple molecular targets including PKC-epsilon, a predictive biomarker of prostatic cancer aggressiveness.

Toxicities

Toxicity studies done by Teshome K et al[58] showed that the primary irritant index to be 2.00 in rabbits; sensitization test in mice showed it to be non-sensitizer in the dose range of 4 – 10 mg/ml; acute dermal toxicity test on rats did not produce any overt signs of toxicity except for a weight gain difference between the test and control groups of female rats. Repeated dose toxicity test was associated with increased relative testes weight as well as higher values for Blood Urea Nitrogen and K+, an observation not supported by histopathological analyses.

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

Can cause vesication of the skin.

Used in Certain Conditions

Pregnancy / Breastfeeding

It is absolutely contraindicated in cases of pregnancy both due to its wide used in traditional medicine to induce abortion and also the scientific evidence to this effect.

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

No documentation

References

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    3. Kamarudin Mat-Salleh, A. Latiff, Tumbuhan Ubatan Malaysia, Pusat Pengurusan Penyelidikan Universiti Kebangsaan Malaysia, Selangor, 2002. Pg204-205
    4. Gabriëlla Harriët Schmelzer, Ameenah Gurib-Fakim, Plant Resources of Tropical Africa (Program), Medicinal plants, PROTA, Netherlands, 2008. pg 475-477
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    48. Aziz MH, Dreckschmidt NE, Verma AK. Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer. Cancer Res. 2008 Nov 1;68(21):9024-32.
    49. Nazeem S, Azmi AS, Hanif S, Ahmad A, Mohammad RM, Hadi SM, Kumar KS. Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells. Mutagenesis. 2009 Sep;24(5):413-8.
    50. Xu KH, Lu DP. Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in vivo. Leuk Res. 2010 May;34(5):658-65.
    51. Chen CA, Chang HH, Kao CY, Tsai TH, Chen YJ. Plumbagin, isolated from Plumbago zeylanica, induces cell death through apoptosis in human pancreatic cancer cells. Pancreatology. 2009;9(6):797-809.
    52. Sathya S, Sudhagar S, Vidhya Priya M, Bharathi Raja R, Muthusamy VS, Niranjali Devaraj S, Lakshmi BS. 3beta-Hydroxylup-20(29)-ene-27,28-dioic acid dimethyl ester, a novel natural product from Plumbago zeylanica inhibits the proliferation and migration of MDA-MB-231 cells. Chem Biol Interact. 2010 Jul 27.
    53. Chen CA, Chang HH, Kao CY, Tsai TH, Chen YJ. Plumbagin, isolated from Plumbago zeylanica, induces cell death through apoptosis in human pancreatic cancer cells. Pancreatology. 2009;9(6):797-809.
    54. Powolny AA, Singh SV. Plumbagin-induced apoptosis in human prostate cancer cells is associated with modulation of cellular redox status and generation of reactive oxygen species. Pharm Res. 2008 Sep;25(9):2171-80.
    55. Xu KH, Lu DP. Plumbagin induces ROS-mediated apoptosis in human promyelocytic leukemia cells in vivo. Leuk Res. 2010 May;34(5):658-65.
    56. Aziz MH, Dreckschmidt NE, Verma AK. Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer. Cancer Res. 2008 Nov 1;68(21):9024-32.
    57. Nazeem S, Azmi AS, Hanif S, Ahmad A, Mohammad RM, Hadi SM, Kumar KS. Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells. Mutagenesis. 2009 Sep;24(5):413-8.
    58. Teshome K, Gebre-Mariam T, Asres K, Perry F, Engidawork E. Toxicity studies on dermal application of plant extract of Plumbago zeylanica used in Ethiopian traditional medicine. J Ethnopharmacol. 2008 May 8;117(2):236-48
    59. Zhang QR, Mei ZN, Yang GZ, Xiao YX. [Chemical constituents from aerial parts of Plumbago zeylanica Linn] Zhong Yao Cai. 2007 May;30(5):558-60.