Reivew Article Anup Kumar Chakraborty et al. / Journal of Pharmacy Research 2011,4(3),573-576 ISSN: 0974-6943 Available online through http://jprsolutions.info odorata (L.) : An Overview Anup Kumar Chakraborty*, Sujit Rambhade, Umesh k Patil 1Department of Pharmaceutical chemistry, Faculty of Pharmacy, People’s Institute of Pharmacy & Research centre, People’s Group, Bhopal-462037, M.P., () Received on: 04-10-2010; Revised on: 17-12-2010; Accepted on:22-02-2011

ABSTRACT is a of flowering in the sunflower family, . It is native to North America, from Florida and Texasto and the , and has been introduced to tropical Asia, west , and parts of . It is used as a traditional medicine in Indonesia. The young leaves are crushed, and the resulting liquid can be used to treat skin wounds. According to traditional healing in yucatan, the boiled roots of Chromolaena odorata are used for urinary retention and leaves are used to cure malaria, gonorrhea, ulcers and blood in urine. The kani tribals of Kouthalai in Tirunelvelli hills used the leaves extract to cure skin diseases, poison bites, wounds and rheumatism. Following various folk claims for the ailment of various diseases, efforts have been made by the researchers to verify the efficacy of this weed through scientific biological screenings. A scrutiny of the literature revealed some notable pharmacological activities of the shrub like anthelmintic, Antimalerial, analgesic, anti-inflammatory, antipyretic, antispasmodic, antioxidant, antigonorrheal, antimycobacterial, insecticidal, fungicidal, wound healing, diuretic, blood coagulation, antibacterial. The present review is an attempt to highlight the various ethnobotanical and traditional uses as well as the phytochemical and pharmacological reports on Chromolaena odorata L.

Key words: Chromolaena odorata, ethnobotanical, phytochemical, pharmacological.

INTRODUCTION Chromolaena odorata is a species of flowering shrub in the sunflower family, Asteraceae. surface of the bush.[6] C. odorata is a big bushy herb with long rambling (but not twining) It is native to North America, from Florida and Texasto Mexico and the Caribbean, [1] and branches; stems terete, pubescent; leaves opposite, flaccid-membranous, velvety-pubes- has been introduced to tropical Asia, west Africa, and parts of Australia. Common names cent, deltoid-ovate, acute, 3-nerved, very coarsely toothed, each margin with 1-5 teeth, or include Siam Weed, Christmas Bush, and Common Floss Flower. It is sometimes grown entire in youngest leaves; base obtuse or subtruncate but shortly decurrent; petiole slen- as a medicinal and ornamental . It is used as a traditional medicine in Indonesia. der, 1-1.5cm long; blade mostly 5-12cm long, 3-6cm wide, capitula in sub-corymbose The young leaves are crushed, and the resulting liquid can be used to treat skin wounds. axillary and terminal clusters; peduncles 1-3cm long, bracteate; bracts slender, 10-12mm It was earlier taxonomically classified under the , but is now considered long; involucre of about 4-5 series of bracts, pale with green nerves, acute, the lowest ones more closely related to other genera in the tribe .[2] about 2mm long, upper ones 8-9mm long, all acute, distally ciliate, flat, appressed except the extreme divergent tip; florets all alike (disc-florets), pale purple to dull off-white, the Chromolaena odorata is considered invasive weed of field crops in its introduced range, styles extending about 4mm beyond the apex of the involucre, spreading radiately; and has been reported to be the most problematic invasive species within protected receptacle very narrow; florets about 20-30 or a few more, 10-12mm long; ovarian portion rainforests in Africa.[3] Chromolaena odorata is a fast-growing perennial shrub, native to 4mm long; corolla slender trumpet form; pappus of dull white hairs 5mm long; achenes and Central America. It has been introduced into the tropical regions of glabrous. The seeds of Siam weed are small (3-5mm long, ~1mm wide, and weigh about Asia, Africa and the Pacific, where it is an invasive weed. It is also known as Siam weed,[4] 2.5mg seed-1.[7] it forms dense stands that prevent the establishment of other plant species. It is an aggressive competitor and may have allelopathic effects. It is also a nuisance weed in Range agricultural land and commercial plantations.Chromolaena odorata contains carcino- Christmas bush is native from Florida through the West Indies and from through genic pyrrolizidine alkaloids.[5] Central and South America to Argentina.[8,9] It has been accidentally or deliberately intro- duced and has naturalized throughout much of the tropics, including Guam and Hawaii.[10] Synonyms: Eupatorium affine Hook & Arn., Eupatorium brachiatum Wikstrom, Eupatorium Ecology clematitis DC., Eupatorium conyzoides M. Vahl, Eupatorium divergens Less., Eupatorium Chromolaena odorata grows on a wide range of soils and grows in a range of vegetation floribundum Kunth, Eupatorium graciliflorum DC., Eupatorium odoratum L., Eupa- types, e.g. forests (annual rainfall 1500mm), grassland and arid bushveld (annual rainfall torium sabeanum Buckley, Eupatorium stigmatosum Meyen & Walp.,Osmia conyzoides less than 500mm).[11,7]In arid areas, it is restricted to riverbanks and it will only become (Vahl) Sch.-Bip.,Osmia divergens (Less.) Schultz-Bip., Osmia floribunda (Kunth) invasive in the frost-free areas of medium to arid woodland which are not water-stressed in Schultz-Bip., Osmia graciliflora (DC.)Sch. Bip., Osmiaodorata (L.) Schultz-Bip. the growing season.[12. 7] For good growth of Siam weed seedlings, the relative humidity Kingdom Plantae – should be in the range of 60 – 70%; at values higher than 80% the growth performance was Subkingdom Tracheobionta – Vascular plants poor.[13,7] Experiments show that Siam weed seedlings grew well at 30°C and even better Superdivision Spermatophyta – Seed plants on mulched soils at 25°C. In heavy shade, Siam weed will not seed. It has a negative Division Magnoliophyta – Flowering plants Class Magnoliopsida – Dicotyledons relationship with tree canopy cover and appears to be most abundant on the edge of Subclass Asteridae forested areas.[14,7] Witkowski (2002) reports that in north-eastern India, Siam weed is Order regarded as a nutrient-demanding early successional species.[15,7] It takes advantage of the Family Asteraceae – family Genus Chromolaena DC. – thoroughwort flush of soil that becomes available after a disturbance, such as fire or land clearing for [16,7] Species Chromolaena odorata (L.) King & H. Rob. – Jack in the bush agriculture, and exhibits relatively high foliar N, P and K contents.

General Description Reproduction Chromolaena odorata is an herbaceous perennial that forms dense tangled bushes 1.5- Christmas bush blooms annually and is an abundant producer of seeds. Flowering and 2.0m in height. It occasionally reaches its maximum height of 6m (as a climber on other fruiting begins after plants are 1 year old.[17] The flowers are pollinated by insects. The plants). Its stems branch freely, with lateral branches developing in pairs from the axillary small fruits mature in about a month. One collection of seeds in Puerto Rico averaged buds. The older stems are brown and woody near the base; tips and young shoots are green 2,670,000 seeds/kg but did not germinate. A second collection averaged 1,560,000 seeds/ and succulent. The root system is fibrous and does not penetrate beyond 20-30cm in most kg and gave 11 percent germination between 3 and 120 days after sowing. Germination is soils. The flowerheads are borne in terminal corymbs of 20 to 60 heads on all stems and epigeal. The seeds are wind dispersed, and transport by animals is possible because of branches. The flowers are white or pale bluish-lilac, and form masses covering the whole small hooks on the seeds. In India, it was observed that only about 1.4 percent of the first- year seedlings survived into the second year.[18] Stems root whenever they come in contact with the ground. *Corresponding author. Mr. Anup Kumar Chakraborty Growth and Management Asst. professor Individual stems last about 2 years and die back to or near the base and are replaced by new People’s Institute of Pharmacy and Research Center sprouts. Plants easily survive cutting and fire. The best current control method is me- chanical or hand cutting followed by herbicide treatment. Partial control can be obtained People’s Campus, Bhanpur, Bhopal-462037

Journal of Pharmacy Research Vol.4.Issue 3. March 2011 573-576 Anup Kumar Chakraborty et al. / Journal of Pharmacy Research 2011,4(3),573-576 through the use of aggressive cover crops. Relatively good biological control has been luteolin exhibited weak activity with the MIC values of 606.0, 704.2 and 699.3 µM obtained with Pareuchaetes pseudooinsulata Rego Barros () in Guam and respectively. Acacetin showed moderate cytotoxicity against human small cell lung cancer several other Pacific islands.[19] (NCI-H187) cells with the MIC value of 24.6 µM, whereas luteolin exhibited moderate toxicity against NCI-H187 cells and week toxicity against human breast cancer (BC) cells Ethnobotanical uses with the MIC values of 19.2 and 38.4 µM respectively. Chromolaena odorata is an ornamental plant that is sometimes encouraged for use in shifting slash-and-burn agriculture to compete with cylindrica (alang alang or Inhibition of Hydrated Collagen lattice Contraction by Normal Human Dermal cogon grass), which is harder to control. It is mainly used by the tribal people for the fibroblasts [27] treatment of cuts and wounds. Thang T. Phan et al. reported the significant inhibition of collagen gel contraction by eupolin extract at 50-200 µg/ml in various concentrations of collagen. When the extract at It is also used for the treatment of Amenorrhea, Amygdalitis, Bite(Leech) Hunan; 50-250 µg/ml was washed out of the lattices and replaced by fresh medium without eupolin, the contraction of collagen by cells was resumed. The visualization of cells in the Cataplasm; Catarrh; Cold,Decongestant Diabetes Diarrhea ; Fever, Gargle Hemostat ; lattices by incubation in a tetrazolium salt for 2 h showed live cells at 50-150 µg/ml of Hoarseness Inflammation Laryngitis Brutus, r; Leptospirosis ; Pertussis ; Rheumatism extract. In contrast all cells were killed in higher extract doses of 300 or 400 µg/ml. These Vermifuge. preliminary results showing the inhibitory effect of eupolin extract on collagen contrac- tion. General impacts Chromolaena odorata forms dense stands preventing establishment of other species, both Insecticidal Activity due to competition and allelopathic effects. When dry, C. odorata becomes a fuel which Chen Zetan[28] reported the significant antifeeding action and poisoning of the crude extract may promote wild bushfires (PIER 2003). C. odorata may also cause skin complaints from Eupatorium odoratum L against the Helicoverpa armigera. The results showed the and asthma in allergy-prone people. It is a major weed in plantations and croplands, antifeeding rate with 20g/L crude extracts against 3rd instar larvae of the insect pest was including plantations of rubber, oil palm, forestry and coffee plants. 73.81% in no-choice tests After treatment with 20g/L and 16g/L crude extracts in 48h, 69.3% and 63.6% of mortality were obtained, respectively. Biogas production by anaerobic digestion of Eupatorium odoratum L.[20] [29] Eupatorium odoratum L. is a prolific producer of biomass among the weeds introduced Essential oil extracts from their leaves were tested for efficacy on the morality of the into India and it can be used for energy production. Since freshly harvested biomass maize grain weevil, Sitophilus zeamais (Coleoptera, Curculionidae). Concentrations of contains inhibitors of microorganisms involved in methanogenesis, the effects of leaching the essential oils relative to the maize grains of 0.063, 0.125, 0.25 and 0.50% (v/w) for C. and partial aerobic decomposition of the weed before anaerobic digestion were studied (1·0 odorata . Significant insect mortality was obtained with essential oil extract of C. 3 odorata (LD50=6.78%). These result show that the essential oils of the leaves of C. m pilot-scale batch fermenters) in relation to biogas production. About 70% more biogas Odorata may be exploited for insect control in stored products. was produced by the pretreated waste, and it also gave a higher count of cellulolytic and methanogenic bacteria than the untreated material. Anti-oxidant effects on human dermal fibroblasts and epidermal keratinocytes [30] Pharmacological Activities of Figure 1: Leaves of Chromolaena odorata Phan Toan Thang et al. reported that the total ethanolic extract (TEE) at 400 and 800 Chromolaena odorata µg/ml showed maximum and consistent protective cellular effect on oxidant toxicity at low or high doses of oxidants. The 50 µg/ml concentration of TEE also had significant Anthelmintic Activity and slightly protective effects on fibroblasts against hydrogen peroxide and hypoxan- thine–xanthine oxidase induced damage, respectively. For keratinocytes, a dose-depen- Debidani Mishra et al.[21] found that all dent relationship of oxidant toxicity was only seen with hydrogen peroxide but the the doses of petroleum ether, ethanol protective action of the extract correlated with oxidant dosage. TEE at 400 and 800 µg/ml and chloroform extracts of the leaves of showed dose-dependent effects with both low and high concentration of oxidants. TEE at Eupatorium odoratum showed better 50 µg/ml had no effect on keratinocytes. Pre-treatment with the extracts did not show a anthelmintic activity than the standard protective effect on cells. Polyphenolic extract exhibited a slight anti-oxidant effect. drug albendazole except petroleum Protection of cells against destruction by inflammatory mediators may be one of the ways ether extract at 2.5 mg/ml of concen- in which the extracts from the plant, C. odorata, contribute to wound healing. tration. The extracts of three solvents Antigonorrhoeal activity at concentration of 2.5 and 5.0 mg/ml showed lesser anthelmintic activity than the [31] standard drug piperazine citrate. When the dose of the extract is increased, a gradual Armando Cáceres et al. reported the antigonorrhoeal activity of the alcoholic extract of increase in anthelmintic activity was observed. The ethanolic extract showed better C. odorata. Plants popularly used in Guatemala for the treatment of gonorrhoea were anthelmintic activity in comparison with petroleum ether and chloroform extracts. macerated in 50% alcohol and the tincture tested for in vitro activity against Neisseria gonorrhoeae using strains isolated from symptomatic patients and confirmed by standard Jitendra Patel et al.[22] studied the anthelmintic activity of the whole plant of Eupatorium bacteriological procedures. Odoratum against Pheretima posthuma and three concentrations (10, 50 and 100 mg/ml) Wound healing effect of each extracts were studied in activity, which involved the determination of time of [32] paralysis and time of death of the worm. Ethanolic extract exhibited significant anthelm- Biswal PR et al. investigated the wound healing effect of aqueous leaf extracts of intic activity at highest concentration of 100 mg/ml. Piperazine citrate in 10 mg/ml Eupatorium Odoratum Linn. in rabbits and antibacterial effect in different isolates of concentration as that of extract was included as standard reference and 1% Gum acacia in bacteria. Complete filling and healing of wounds was observed by 11th-13th day after normal saline as control. The anthelmintic activity of ethanolic extract was significant daily application of the aqueous leaf extract in experimentally created wounds. Similar followed by hydroalcoholic extract of Eupatorium Odoratum. findings were also observed with Himax ointment as well. The decrease in bacterial load varied depending on the type and nature of bacteria when bacterial isolates were subjected Antimalerial Activity to wet culture inhibition method Rungnapa Ongkana[23] found that chloroform extract of the leaves of Eupatorium odoratum Fungicidal Activity was effective against K1 strain of plasmodium falciparum in invitro cultures with an EC50 [33] value of 9.5 µg/ml. Ling Bing et al. were found that the volatile oil from C. odorata had significant biological activities on fungi and insects. The result showed that inhibitory effect of the Analgesic Activity oil at middle concentration (800 mg·l -1) for Pyricularia grisea was the strongest, the next Chakraborty et al.[24] found that only ethanolic extract shows maximum analgesic activity was to Phytophthora nicotianae , the weakest was to Fusarium oxysporum. The inhibi- at a dose of 300 mg/kg whereas petroleum ether extract and chloroform extract shows tory percentage was 61.40%,29.27% and 14.44% respectively.The volatile oil from C. moderate activity at the same dose when compared with the standard drug aspirin. odorata had significant oviposition deterrent effect on the striped flea beetle( Phyllotreta striolata) and the diamondback moth ( Plutella xylostella ) at dose 10•‘20 µl·plant. Anti-Inflammatory, Antipyretic and Antispasmodic Properties [25] Anti-inflammatory activity Oludare B. Taiwo et al. evaluated the anti-inflammatory as well as antipyretic activity [34] of methanolic extract of the leaves of Chromolaena odorata. The effects of the extract on Victor B. Owoyele et al investigated the anti-inflammatory activity of the aqueous intestinal transit of charcoal meal and castor oil-induced diarrhoea were also investigated. extract of Chromolaena odorata in rats using the carrageenan-induced oedema, cotton The extract (50-200 mg/kg) inhibited paw edema in rats and produced significant reduc- pellet granuloma and formalin-induced oedema methods. The extract was administered tion in rectal temperature of mice rendered hyperthermic by yeast suspension. Antimotility orally at doses of 25, 50, 100 and 200 mg/kg. In the carrageenan method the paw oedema and antidiarrhoeal effects were produced by the extract in intact mice. was significantly reduced by all the doses of the extract administered, with the 200 mg/ kg dose producing the highest oedema inhibition (80.5%). In the cotton pellet method, Antimycobacterial activity granuloma weight was significantly reduced from 14 ± 0.1 to 9.0 ± 0.1 mg, while in the Apichart Suksamrarn et al.[26] reported the antimycobacterial activity of four flavones formaldehyde induced arthritis the extract inhibited the oedema during the 10-day period. isolated from the flowers of Chromolaena odorata (Eupatorium odoratum). Isosakuranetin Diuretic activity exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with [35] the MIC value of 174.8 µM whereas 4?-hydroxy-5,6,7-trimethoxyflavanone, acacetin and Rejitha Gopinath investigated the diuretic activity for the infusions of Eupatorium odoratum Linn at 10, 20 and 30 % in albino rats. Urinary excretion of water, pH, density, Journal of Pharmacy Research Vol.4.Issue 3. March 2011 573-576 Anup Kumar Chakraborty et al. / Journal of Pharmacy Research 2011,4(3),573-576 conductivity and Na+, K + and Cl - content were investigated in saline-loaded rats. The extract showed a dose-dependent decrease diuretic effect, but augmented significantly with respect to the control group for the urinary excretion of water and sodium. Furthermore, CH a potassium-sparing effect at 10 and 20 % was showed. The diuretic effect does not seem 3 to be related to the potassium content of the starting material. The results justify the use of E. odoratum as diuretic agent by the Malaysian traditional medicine.

Blood Coagulating Activity Triratana T et al. [36] found that the compound 4', 5, 6, 7-tetramethoxyflavone from Eupatorium odoratum enhanced blood coagulation, the observed APTT being shorter than that observed in the control. The result suggested that the compound accelerated clotting time through the intrinsic pathway of the coagulation which may involve the Alpha-copaene. Luteolin reaction of factor XII, factor XI, factor IX or factor VIII.

Antimicrobial Activity Mullika Traidej Chomnawang et al. [37] investigated the antimicrobial activity of Eupato- rium odoratum against propionibacterium acnes.Propionibacterium acnes and S taphy- lococcus epidermidis have been recognized as pus-forming bacteria triggering an inflam- mation in acne. The disc diffusion method showed that Eupatorium odoratum had strong inhibitory effects against propionibacterium acnes. The MIC values were the (0.039 mg/ ml) for both bacterial species and the MBC values were 0.039 and 0.156 mg/ml Acacetin against Propionibacterium acnes and Staphylococcus epidermidis, respectively. Figure 2: Structures of some phytoconstituents isolated from Chromolaena odorata

CONCLUSION Chemical constituents of Chromolaena odorata 1. Thirty-three components were identified from the volatile oil of C. odorata. Terpe- Chromolaena odorata has been ethnomedicinally used as a therapeutic agent for a variety noid compounds are major components of the volatile oil. The main terpenic com- of diseases, as we have illustrated in this article. In this systematic review, the pharmaco- ponents are trans-caryophyllene(16.22%), d –cadinene (15.53%), a - copaene(11.32%), caryophyllene oxide(9.42%), germacrene-D(4.86%) and a – logic studies conducted on Chromolaena odorata indicate the immense potential of this humulene(4.23%).[33] plant in the treatment of conditions, such as wound healing, anti-inflammatory, analgesic, 2. The constituents of the Choloroform soluble and petroleum ether-soluble por- antipyretic, diuretic, antimicrobial, antimycobacterial and many more. Flavonoids, tions in the 95% ethanol extract were isolated and purified by means of chromatog- triterpenes, chalcones, steroids which were isolated from this plant may be responsible for raphy. Ten compounds were isolated and identified as odoratin, dillenetin, its pharmacological activities. From the literature survey it was found that the leaves pectolinarigenin, quercetin-7, 4'-dimethyl ether, kaempferol 4'-methyl ether, extract are more beneficial. Also the isolation of phytoconstituents has been done on [38] isosakuranetin, acacetin, dotriacontanic acid, â-sitosterol, daucossterol. leaves, roots, flowers but no work has been done on the stem part. So this part has to be 3. The purified compound, 4', 5, 6, 7-tetramethoxyflavone, is an active ingredient isolated from Eupatorium odoratum.[36] explored by the researchers. 4. Isosakuranetin and a new chalcone, odoratin, have been isolated from the leaves of Eupatorium odoratum. 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Journal of Pharmacy Research Vol.4.Issue 3. March 2011 573-576