Ceylon leadwort

Other Names

AgiyachitAgnachitAgniAgnimathaBai Hua DanBilichitramoolaBilichitramulaCheetaCheetahChitaChitamulaChitarakaChitavurChithramoolamChitoparuChitraChitrakChitrakaChitramoolamChitramulChitramulaChitramulamuChitroChittiraChittiriChittramoolamChituCitrakaDoctorbushFindlaya albaHierba de AlacránHiguilloHilieeInabiriJvalanaKähautaKodivaeliKodiveliLauhihiLeadwortMeladillo silvestreMolubda scandensOnaya akoPenchitarPervenche à fleurs blanchesPitaroPitilloPlombago de CeylanPlumbagidium scandensPlumbagoPlumbago americanaPlumbago auriculata BlumePlumbago flaccida MoenchPlumbago floridana Nutt.Plumbago floridana Raf.Plumbago junceaPlumbago lacteaPlumbago littoralisPlumbago maximowicziiPlumbago mexicanaPlumbago occidentalisPlumbago roseaPlumbago sarmentosaPlumbago sauvagePlumbago scandensPlumbago scandens L.Plumbago scandens var. densifloraPlumbago scandens var. erectaPlumbago scandens var. normalisPlumbago toxicariaPlumbago viscosaPlumbago zeylanicaPlumbago zeylanica L.SheetarSheetarajSheetraj HindiSheetranj HindiTellachitraThela albaThumpokkoduveliVaellakoduveliVahniVellakeduveliVit BlyblommaWhite leadwortWhite PlumbagoWhite-flowered leadwortWild leadwortWild PlumbagoʻIlieoʻIlieʻeʻIliheʻe

Synopsis

Ceylon Leadwort (Plumbago zeylanica L.): A Comprehensive Reference

1. Identity and Botanical Description

Nomenclature and Taxonomy

Plumbago zeylanica, commonly known as Ceylon leadwort, doctorbush, or wild leadwort, is a species of plumbago with a pantropical distribution. Plumbago zeylanica Linn. is a perennial shrub belonging to the Angiosperm category, commonly known as Ceylon leadwort, and belongs to the family Plumbaginaceae. In Ayurvedic medicine it is most widely recognized by the Sanskrit name Chitraka (also spelled Chitraka or Citraka), while Unani medicine refers to it as Sheetraj Hindi and Siddha medicine as Chittramoolam. It is known by many names: Chitrak (Ayurveda), Sheetraj Hindi (Unani), and Chittramoolam (Siddha).

Carl Linnaeus described the paleotropical P. zeylanica and Neotropical P. scandens as separate species, but they are currently considered synonymous. The genus Plumbago includes three species — Plumbago indica L. (P. rosea L.), P. capensis L., and P. zeylanica L. — which are distributed in several parts of India. Among these species, Plumbago zeylanica L. is more popular due to its therapeutic properties.

Morphology and Distribution

Plumbago zeylanica is a herbaceous plant with glabrous stems that are climbing, prostrate, or erect. The leaves are petiolate or sessile and have ovate, lance-elliptic, or spatulate to oblanceolate blades that measure 5–9 × 2.5–4 cm in length. The plant grows in three varieties producing white, red, and blue coloring flowers. The white variety is used as Chitrak.

The natural place of Plumbago occurrence is South Asia, especially India. Moreover, it can be found in subtropical and tropical regions above 2,000 m above sea level, where soils are rich in trace elements. It is distributed throughout tropical Africa with collection of the plant reported in Senegal, Guinea, Sierra Leone, Liberia, Ghana, Togo, Nigeria, Zambia, and Equatorial Guinea. Plumbago zeylanica L. is a semiclimbing subshrub widely used in ethnomedicine around the world including India, Bangladesh, Sri Lanka, and Australia.

Etymology

The Plumbago genus name, originating from the Latin word plumbum ("lead"), is believed to refer to the lead-blue flower colour, the ability of the sap to create lead-colored stains on skin, or the belief that the plant was a cure for lead poisoning.

Common Preparations and Dosage Forms

The root and root bark of this herb are utilized in the preparation of varied Ayurvedic medicines. In the traditional system of medicine, it has been indicated for its significant protective role in enlarged liver and spleen. The study explores the extraction methods of bioactive compounds from the bark and leaves of Plumbago zeylanica. Different solvents, including petroleum ether, ethyl acetate, and 70% methanol, were used for extracting compounds from the plant material through Soxhlet extraction. The extracts were then purified and dried, and their yield was determined. In Ayurvedic practice, the plant is incorporated in compound formulations. The incorporation of Chitrak in various Ayurvedic formulations like Chitrakadivati and Chitrakadi Ghee signifies its integrative role in holistic health. The plant is also used in the form of root powder (churna), decoctions (kwatha), and as a paste applied topically.

2. Traditional and Historical Use

Ayurvedic Tradition (India, from antiquity)

Plumbago zeylanica has been a plant used within the scope of Ayurvedic medicine, found in the primary texts of Ayurveda such as the Charaka Samhita, dating back thousands of years. It is one of the oldest herbs reported to be used in Ayurveda for several disorders over thousands of years and is most commonly used in the traditional medicinal system of India. In Ayurveda, it is considered as a rasayana (rejuvenator).

In the Sushrutha Samhita, it has been described as antiseptic, febrifuge, detoxicant, antihelminthic, and considered valuable for curing migraine, jaundice, urinary calculi, internal abscesses, seminal weakness, vaginal discharges, and insanity.

The principal Ayurvedic uses of the root centered on the digestive system: Chitrak is traditionally used in Ayurveda to improve digestion, stimulate appetite, and treat digestive disorders such as bloating, constipation, and indigestion. The roots of Plumbago zeylanica are used in Ayurveda for the treatment of various diseases related to the digestive system, including impaired or weak digestion, grahni, piles, abdominal pain, and skin diseases. It is a bitter tonic and suggested as a rejuvenator, well known for its use in chronic colds and cough. It also finds its use in correcting chronic menstrual disorders, viral warts, and chronic diseases of the nervous system.

As per Ayurvedic classical literature, Chitrak is one of the herbs present in Panchkola and Shadushana Churna, which are among the most popular formulations. In texts such as the Garuḍapurāṇa, Plumbago zeylanica (citraka) is used in the Viśodhana ("washing off the wound's impurities") of wounds; it is ground with castor root, turmeric, ginger, garlic, and rock salt in buttermilk or sour gruel.

The herb's ability to enhance digestive fire (Agni), detoxify the body, and balance doshas demonstrates its multifaceted role in promoting gastrointestinal health, treating skin disorders, and alleviating chronic pain, particularly those associated with Vata disorders.

Unani Tradition

Commonly called Ceylon leadwort or Chitrak, the plant has good medicinal potential and enjoys an important place among medicinal plants around the world for treatment of various diseases. It is held in high esteem in both Ayurveda and Unani. The use of the roots of P. zeylanica for treating skin problems has been recorded by early Muslim physicians. In Unani medicine, the plant (known as Sheetraj Hindi) is used for conditions including rheumatism, arthritis, and digestive complaints.

African Traditional Medicine

The plant is distributed throughout tropical Africa and its roots are used traditionally to treat tuberculosis, gonorrhea, diarrhea, syphilis, wounds, and rheumatic pains and swellings. Studies from Ethiopia note its traditional use for the treatment of intestinal worms and skin diseases.

Other Regional Traditions

Traditionally, the roots and leaves of P. zeylanica are widely used in India and China for the treatment of diabetes mellitus. Traditionally it is used as a stimulant, digestant, expectorant, laxative, abortifacient, and in the treatment of muscular pain and rheumatic disease. Traditionally it is used to treat a variety of diseases such as dysmenorrhea, leprosy, anemia, rheumatic pain, cold, cough, arthritis, and many more.

3. Key Chemical Constituents and Active Compounds

Overview of Phytochemistry

The plant consists of various bioactive compounds such as alkaloids, flavonoids, naphthoquinones, glycosides, saponins, steroids, triterpenoids, coumarins, phenolic compounds, tannins, carbohydrates, fixed oils, fats, and proteins.

Plumbagin — The Principal Active Compound

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a naturally occurring naphthoquinone isolated from the roots of the medicinal plant Plumbago zeylanica L. As a vitamin K3 analog and a prooxidant, it has been reported to possess diverse biological activities, such as anti-inflammatory, anticancer, antidiabetic, antioxidant, antibacterial, antifungal, anti-atherosclerosis, and analgesic activities.

Plumbagin is a naphthoquinone-derived yellow crystalline phytochemical. It has a wide range of biological effects including cytotoxicity against cancer cells both in vitro and in vivo. Among the plant's chemical constituents, the most important is plumbagin, which is chiefly present in the roots and bestows the plant with its curative qualities.

Additional Naphthoquinones from the Root

The root yields several pigments, including 3-chloroplumbagin, 3,3-biplumbagin, a binaphthoquinone identified as 3′,6′-biplumbagin, and four other pigments identified as isozeylanone, zeylanone, elliptinone, and droserone. The isolation of plumbagin, droserone, isoshinanolone, and a new napthalenone (1,2(3)-tetrahydro-3,3′-plumbagin) is reported from the phenolic fraction of the light petrol extract of the roots. Two plumbagic acid glucosides — 3′-O-beta-glucopyranosyl plumbagic acid and 3′-O-beta-glucopyranosyl plumbagic acid methyl ester — along with five naphthoquinones have also been identified.

Two plumbagic acid glucosides and five naphthoquinones (plumbagin, chitranone, maritinone, elliptinone, and isoshinanolone), and five coumarins (seselin, 5-methoxyseselin, suberosin, xanthyletin, and xanthoxyletin) were isolated from the roots of Plumbago zeylanica.

Constituent Distribution Across Plant Parts

The stem contains plumbagin, campesterol, sitosterol, stigmasterol, isozeylanone, and zeylanone. The leaves are reported to contain chitanone, plumbagic acid, and plumbagin. The presence of alkaloids, glycosides, reducing sugars, simple phenolics, tannins, lignin, saponins, and flavonoids are reported from qualitative phytochemical analysis of the leaves. Seeds mainly contain plumbagin. The stem also reveals plumbagin, zeylanone, isozeylanone, sitosterol, stigmasterol, campesterol, and dihydroflavonol. Plumbagin, zeylanone, and sitosterol are identified in the flowers. The fruit confirmed the presence of plumbagin, glucopyranoside, and sitosterol.

The leaves and stem contain little or no plumbagin. The aerial parts contain naphthoquinones, sitosterol, lupeol, lupenylacetate, hentriacontane, and amino acids.

4. Mechanisms of Action

Anticancer Mechanisms

Due to the pleiotropic nature of plumbagin, it shows anticancer effects by targeting several molecular mechanisms including apoptosis and autophagic pathways, cell cycle arrest, anti-angiogenic pathways, and anti-invasion and anti-metastasis pathways. Among many signaling pathways, the key regulatory genes regulated by plumbagin are NF-κβ, STAT3, and AKT. Plumbagin is also a potent inducer of reactive oxygen species (ROS), a suppressor of cellular glutathione, and causes DNA strand breaks by oxidative DNA base damage.

Plumbagin-induced cell death involves loss of mitochondrial membrane potential and morphological changes characteristic of apoptosis; it also involves release of mitochondrial cytochrome c and apoptosis-inducing factor (AIF), thus activating both caspase-dependent and caspase-independent pathways, as shown by plumbagin-mediated activation of caspases-3 and -9.

Anti-inflammatory Mechanisms

Plumbagin inhibits NF-κβ-regulated gene transcription of pro-inflammatory cytokines and other related molecules like IFN-γ, IL-6, and inducible nitric oxide synthase. A study also suggests that the activity of plumbagin may also involve the inhibition of Jak/STAT signaling.

Antidiabetic Mechanisms

In the diabetic state, due to the deficiency of insulin, GLUT4 translocation does not take place efficiently and GLUT4 transporters remain inside the cell where they are not functional. This results in decreased uptake of glucose by muscle cells, which contributes significantly to elevated glucose levels. Therefore, compounds facilitating GLUT4 translocation can be potentially beneficial for the treatment of diabetes. Plumbagin enhanced GLUT4 translocation and contributed to glucose homeostasis in preclinical models.

5. Scientific Evidence by Area of Use

5.1 Anticancer Activity

Plumbagin, a natural naphthoquinone constituent isolated from the roots of Plumbago zeylanica L., exhibited anticancer activity against a variety of cancer cell lines including breast cancer, hepatoma, leukemia, melanoma, prostate cancer, brain tumor, tongue squamous cell carcinoma, esophageal cancer, oral squamous cell carcinoma, lung cancer, kidney adenocarcinoma, cholangiocarcinoma, gastric cancer, lymphocyte carcinoma, osteosarcoma, and canine cancer.

In studies on non-small cell lung cancer, plumbagin significantly inhibited the growth of H460 cells and downregulated the expression of EGFR/Neu and its downstream signaling (Akt, NF-κB, Bcl-2, and survivin). In addition, plumbagin upregulated the expression of p53 and p21(CIP1/WAF1), causing cell cycle arrest in the G2/M-phase by downregulating G2/M regulatory proteins. It activated JNK/p38 signaling, leading to caspase-3 activation and induction of apoptosis. Plumbagin exerted anticancer activity on NSCLC cells by modulating pro-survival and pro-apoptotic signaling.

In breast cancer research, PLB not only exerted antibreast cancer effects independently but also had synergistic effects with other drugs such as reversing drug resistance of antibreast cancer drugs. A combination of PLB with zoledronic acid synergistically suppressed human breast cancer MDA-MB-231SArfp cells in vitro. PLB also demonstrated a synergistic inhibitory effect with tamoxifen on the growth of endocrine-resistant breast cancer cells.

For lung cancer cell lines at the preclinical level, the anticancer potential of plumbagin was demonstrated by MTT assay and the results suggested that it showed cytotoxicity in both gefitinib-sensitive (A549) and gefitinib-resistant (A549GR) lung cancer cells, with IC50 values of 3.2 μM and 4.5 μM, respectively.

Cytotoxicity of isolated compounds to various tumor cell lines was evaluated, and plumbagin significantly suppressed growth of Raji, Calu-1, HeLa, and Wish tumor cell lines.

Evidence strength: Preclinical only. All anticancer evidence is derived from in vitro cell-line experiments and animal model studies. More research and clinical trials are required to verify its safety and therapeutic potential. No completed controlled human clinical trials on cancer treatment have been reported in the reviewed literature.

5.2 Antidiabetic Activity

Traditionally, the roots and leaves of P. zeylanica are widely used in India and China for the treatment of diabetes mellitus.

In a key preclinical study, plumbagin isolated from P. zeylanica root and its effect on GLUT4 translocation were evaluated in STZ-induced diabetic rats. Plumbagin (15 and 30 mg/kg body weight) was orally administered to STZ-induced diabetic rats for 28 days. An oral glucose tolerance test was performed on day 21. The effect of plumbagin on body weight, blood glucose, plasma insulin, total protein, urea, creatinine, liver glycogen, plasma enzymes (SGOT, SGPT, and ALP), and carbohydrate metabolism enzymes was investigated. GLUT4 mRNA and protein expression in skeletal muscles were also studied. Plumbagin significantly reduced blood glucose and significantly altered all other biochemical parameters to near normal.

Another study by Zarmouh et al. reported antidiabetic activity of ethanolic extract of Plumbago zeylanica roots, conducted in streptozotocin-induced diabetic rats at doses of 100–200 mg/kg for six weeks. Results showed a marked increase in hepatic hexokinase activity and reduction in hepatic glucose-6-phosphatase, serum acid phosphatase, alkaline phosphatase, and lactate dehydrogenase levels.

Evidence strength: All evidence is from animal (rodent) models. No human clinical trials on glycemic control have been identified in the reviewed literature.

5.3 Anti-inflammatory and Analgesic Activity

A bioassay-guided study published on PubMed examined anti-inflammatory and antinociceptive activities: various leaf extracts were studied using in vivo experimental models at two dose levels (200 and 400 mg/kg, p.o.). Anti-inflammatory activity was tested using the carrageenan-induced rat hind paw edema method while analgesic activity was studied using the hot plate and formalin-induced models. The acetone extract significantly (p < 0.01) reduced inflammation in the rats when compared to the control group.

Evidence strength: Preclinical animal studies. No human trials documented in reviewed sources.

5.4 Antimicrobial Activity

The methanolic extracts of the stem and leaves of Plumbago zeylanica were tested against six bacterial species and nine fungal species, and both extracts showed antimicrobial activity in a dose-dependent manner. The leaf extract of Plumbago zeylanica showed maximum antimicrobial activity against both Staphylococcus aureus subsp. aureus and Fusarium oxysporum. The stem extract was found to be more antimicrobial against Pseudomonas aeruginosa and Penicillium expansum species.

Plumbago zeylanica roots contain astringent tannins, which could account for the antimicrobial effect and support an antiulcer effect.

Evidence strength: Predominantly in vitro microbiology experiments. No human clinical antimicrobial trials found in reviewed literature.

5.5 Hepatoprotective Activity

A study was conducted to evaluate the hepatoprotective activity of methanolic extract of aerial parts of Plumbago zeylanica in CCl₄-induced hepatotoxicity in Wistar rats. The extract of aerial parts showed very significant hepatoprotection against CCl₄-induced hepatotoxicity by reducing serum total bilirubin, SGPT, SGOT, and ALP levels. Histopathological studies also confirmed the hepatoprotective nature of the extract.

Evidence strength: Animal model only. No human hepatoprotection trials found.

5.6 Nephroprotective Activity

The protective effect of hydroalcoholic extract of P. zeylanica (HAPZ) in cisplatin-induced nephrotoxicity was analyzed in Swiss albino mice. Treatment with the higher dose (400 mg/kg) of HAPZ significantly reversed the adverse effect of cisplatin on kidney weight, serum urea, and creatinine, indicating a renoprotective effect. The antioxidant effect of the drug was evident from its significant effect on catalase, glutathione peroxidase, and lipid peroxidation activities.

Evidence strength: Animal model only. No human nephroprotection trials found.

5.7 Antiplasmodial (Antimalarial) Activity

The major component of the roots of the plant is plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a yellowish pigment. It has been reported to possess several biological activities including anticancer, antioxidant, antibacterial, antifungal, anti-inflammatory, antimalarial, and antiparasitic activities.

Evidence strength: Largely preclinical and in vitro. Ethnobotanical use for malaria is documented in Africa, but no registered controlled clinical trials in humans were identified in reviewed sources.

6. Body Systems and Health Areas

Gastrointestinal system: In the Indian system of medicine (Ayurveda), Plumbago (Chitrakmool) is used as an ingredient in various formulations as an effective appetizer, anti-inflammatory, and aids in digestion by stimulating gastric secretions.
Metabolic / endocrine system: Experimental trials confirmed the antidiabetic effect of Plumbago zeylanica L. in various studies.
Immune and inflammatory systems: The plant shows many pharmacological activities including anti-inflammatory, anti-cancer, anti-bacterial, anti-plasmodial, anti-tumor, and anti-fungal activities due to the presence of various secondary metabolites.
Hepatobiliary system: In the traditional system of medicine, it has been indicated for its significant protective role in enlarged liver and spleen.
Renal system: Preclinical studies support a renoprotective role, particularly in models of cisplatin-induced nephrotoxicity.
Oncology (preclinical): Plumbagin exhibited anticancer activity against a wide variety of cancer cell lines.
Reproductive system: Plumbagin has pharmacological properties including anti-implantation, abortifacient, and anti-fertility effects documented in animal studies (see Safety section).
Skin: Chitrak is applied externally for skin conditions, wound healing, and to reduce inflammation.
Respiratory system: Plumbago zeylanica L. is greatly valued in Ayurveda for treatment of cough, asthma, and gastrointestinal disorders.

7. Dosage Forms and Dosages Reported in Studies

No standard human clinical dosage for Plumbago zeylanica or its isolated constituents has been established through controlled trials. The following dosages are reported in preclinical (animal) studies only, and are provided solely for reference of what appears in the scientific literature:

Plumbagin (antidiabetic, rat model): Plumbagin was orally administered to STZ-induced diabetic rats at 15 and 30 mg/kg body weight for 28 days.
Ethanolic root extract (antidiabetic, rat model): The study was conducted in streptozotocin-induced diabetic rats at doses of 100–200 mg/kg for six weeks.
Leaf extract (anti-inflammatory, rat model): Various leaf extracts were studied using in vivo experimental models at two dose levels (200 and 400 mg/kg, p.o.).
Hydroalcoholic root extract (nephroprotective, mouse model): Treatment with a higher dose (400 mg/kg) of the hydroalcoholic extract significantly reversed the adverse effect of cisplatin on kidney weight, serum urea, and creatinine.
Plumbagin (anti-implantation, rat model): Antifertility activity of plumbagin was studied; when given orally at 1 mg/100 g body weight, plumbagin showed significant anti-implantation and abortifacient activity in albino rats.
Plumbagin LD50 (acute toxicity, rodents): Acute toxicity studies in mice and rats showed plumbagin to be toxic, its LD50 value being 4 mg and 6.5 mg/100 g body weight, respectively.

8. Safety Considerations and Interactions

Established Toxicity Data

The plant P. zeylanica contains plumbagin, which is considered to be toxic with an oral LD50 of 65 mg/kg. In comparative toxicity testing, the petroleum ether extract was more toxic than acetone and hydroalcoholic extracts, based on LD50 values of 93.45, 928.4, and 928.4 mg/kg, respectively. This potency difference directly correlates with the plumbagin content of the extracts.

Hepatotoxicity and Nephrotoxicity

The findings of one study demonstrate that liver and kidney are the primary organs being adversely affected following sub-acute administration of P. zeylanica root extract in rats. With regard to sub-acute toxicity, a significant increase in organ weights (liver, adrenal glands, and/or heart) was observed in petroleum ether and acetone extract-treated groups.

Reproductive Toxicity and Antifertility Effects

Root extract exhibited significant anti-implantation and abortifacient activity at tested dose levels (300 and 500 mg/kg, p.o.) in female Wistar rats. The same dose of plumbagin had a significant anti-ovulatory effect in rabbits. Plumbagin has shown anti-implantation and abortifacient activities, as well as testicular lesions and testis-weight reduction in animal models. These findings strongly indicate that the use of Plumbago zeylanica preparations during pregnancy or by those attempting to conceive carries documented preclinical risk.

Skin Irritant Properties

Plumbagin has a range of pharmacological properties, including anti-implantation, abortifacient, anti-microbial, anti-cancer, cardiotonic, and anti-fertility effects. Moreover, it is a potent irritant.

Bioavailability and Research Limitations

Plumbagin's therapeutic application is limited because of low bioavailability and toxicity risk factors. Chemical modifications and combination medicines are being studied to improve delivery, reduce toxicity, and increase efficacy.

General Evidence Gap

Ongoing research aims to better understand the mechanisms underlying the actions of plumbagin, optimize its distribution and formulation, and assess its efficacy and safety in clinical trials. Plumbagin is a bioactive compound that has several possible therapeutic uses; however, further studies are required to completely understand its advantages and disadvantages in clinical settings.

References

Health Conditions

Health conditions that Ceylon leadwort may help support.

No conditions available.

Body Systems

Body systems that Ceylon leadwort may help support.

No body systems available.