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Revista Brasileira de Farmacognosia

Print version ISSN 0102-695X

Rev. bras. farmacogn. vol.22 no.5 Curitiba Sept./Oct. 2012  Epub Apr 24, 2012 

Genus Lantana: chemical aspects and biological activities



Erlânio O. SousaI,II; José G.M. CostaI,II,*

IRede Nordeste de Biotecnologia, Universidade Estadual do Ceará, Brazil
IILaboratorio de Pesquisa de Produtos Naturais, Departamento de Química Biológica, Universidade Regional do Cariri, Brazil




Species of the genus Lantana, belonging to the family Verbenaceae, is among the various species studied scientifically. These species are mainly native to the tropical and subtropical regions of the Americas. Currently, they are present in various countries, where they are often grown as ornamental plants. For decades, species of Lantana have been of great interest for phytochemical, biological and pharmacological studies, which have been recently intensified. The components isolated from different species of Lantana cited in the literature constitute the focus of this review. Information ethnopharmacology of Lantana, as well as the activities of their different phytochemicals are discussed. In this review, it was observed that the genus Lantana has been widely studied in relation to its phytochemical components and terpenoids, flavonoids and phenylpropanoids are the more common secondary metabolites in Lantana. All these aspects, considered in this review, allow an evaluation of the ethnopharmacological potential of Lantana for the utilization of the large biomass of these plants.

Keywords: flavonoids, furanonaphthoquinones, iridoid glycosides, Lantana, phenylethanoid glycosides, steroids, terpenes.




Although the curative potential of plants has been known for a long time, only in the last decades has there been an intensified interest from the pharmaceutical industry, institutes and research groups in chemical and pharmacological studies of plants in search of knowledge with respect to their therapeutic properties and to new active principles (Novais et al., 2003).

Among the innumerous species studied scientifically are the species of the genus Lantana, which belong to the family Verbenaceae. The family Verbenaceae comprises one hundred genus and about 2600 species distributed in tropical and subtropical regions around the world (Joly, 1993). Many genera belonging to this family appear to possess various biological and pharmacological properties, among which the genus Lantana has been widely studied.

The genus Lantana was described by Linnaeus in 1753 and contained seven species, six from South America and one from Ethiopia (Munir, 1996). The term Lantana probably comes from the old Latin name of the genus Viburnum, which resemble a little in leaves and inflorescence. Taxonomically, this genus shows difficult classification, because normally, the species are not stable, hybridization is very widespread, the shape of the inflorescence changes with age, and color of the flowers varies with age and maturity (Ghisalbert, 2000). Due to this characteristic, species of this Lantana have been much studied with respect to cytogenetics within the family Verbenaceae.

Lantana is mainly native to the tropical and subtropical Americas, but a few taxa are originally from tropical Asia and Africa; currently, they occur in approximately fifty countries with a very large number of species and subspecies. This genus includes herbaceous and shrubby plants, which can reach a height of over 2 m, where they are very often planted for decorative purposes due to the beauty of their flowers (Joly, 1993).

Some species of Lantana, mainly varieties of L. camara, are responsible for clinical pictures of secondary photosensitization, a disease of seasonal nature, related to clinical episodes in ruminants, with the majority of cases of intoxication occurring in the winter (Ranjhan & Pathak, 1992). The principal factor for intoxication to occur is related to feeding on pastures with the presence of some toxic variety of L. camara. The toxic effects of the leaves have usually been attributed to a series of pentacyclic triterpenes, in which lantadenes A and B are typical members (Sharma et al., 1988). The nontoxic species do not contain these lantadenes or possess them in low quantities.

Species of genus Lantana are plants practically immune to attack by herbivores, due to the presence of a great diversity of secondary metabolites (Kohli et al., 2006). They also have anti-rheumatic, stimulant and sudorific properties, and are used to treat broncho-pulmonary disorders, and some species are utilized in biological control as a pesticide (Ghisalbert, 2000; Dua et al., 2003; 2010). Organic extracts and essential oils of Lantana have shown a wide variety of biological and pharmacological activities.

Phytochemical studies conducted by various research groups have resulted in the isolation of various constituents from different parts of species of the genus Lantana. Therefore, the aim of the present review is to provide a complete compilation of the phytochemical components of Lantana recorded in the literature. The botanical classification and ethnopharmacology of Lantana have been included.

The aim of this review was to summarize the main chemical, biological and pharmacological aspects of species of the genus Lantana, indicating when possible the compounds identified in each species, as well as the biological and/or pharmacological actions described in the literature. We believe that this review can be used in innovative applications and investigative incentives in the search for more details of the plants of this important botanical genus.


Material and Methods

The study was conducted using data obtained from a bibliographic search, using mainly the science search engines "Web of Science", "Science@direct", "Pubmed", "Scielo" and "Scirus", with findings updated up to April 2011. The following key words were utilized, alone or in combinations: Lantana, chemical constituents, biological or pharmacological activities, and natural products.


Occurrence and distribution

This and the next section will cover only species of Lantana that were more studied with respect to phytochemical properties and biological and pharmacological activities. Lantana hispida Kunth is a widely distributed Mexican ornamental plant (Jiménez-Arellanes et al., 2007). Lantana cujabensis Schauer is a shrub that grows at an elevation of up to 1000 m and is found in both the Amazon and Andean forests of South America (Brako & Zarucchi, 1993). Lantana viburnoides var. kisi is indigenous to Tanzania (Innocent et al., 2008). Lantana lilacina Desf., a 50-to 120 cm tall native Brazilian shrub, which produces pink or purple flowers, is regarded as a weed and an ornamental plant (Lorenzi, 2002; Pereira et al., 2008). Lantana salvifolia Jacq is found growing wild from Ethiopia to the Congo (Ouamba et al., 2006). Lantana indica Roxb., a wild perennial shrub, native to India, is regarded both as notorious weed and a popular ornamental garden plant (Kumar et al., 2010). Lantana montevidensis Briq., a shrub native to Brazil and Uruguay, is popularly known as "cambara", and it was introduced to many countries as an ornamental plant (Nagão et al., 2002; Barreto et al., 2010). Lantana achyranthifolia Desf. is a shrub found in the Americas (Hernández et al., 2005). Lantana tiliifolia Cham. is the most common Lantana in Brazil, but it is not considered a weed because it is controlled by a complex of natural predators including insects and fungi (Rwangabo et al., 1988). Lantana canescens Kunth is listed as a rare species in Florida, U.S.A. and is used mainly for xeriscaping, as it is drought-tolerant. Efforts are being made to propagate this species in residential areas by local gardening groups (Sena Filho et al., 2010). Lantana trifolia L. is a small shrub that occurs in all regions of Brazil (Julião et al., 2010). Lantana fucata Lindl. and Lantana radula Sw. are small shrubs distributed in Southeast Brazil and grow in higher elevation fields (Julião et al., 2009). Lantana camara L., commonly known as wild sage, is the most widespread species of this genus, growing luxuriantly at elevations up to 2000 m in tropical, sub-tropical and temperate regions (Ghisalberti, 2000).


Traditional application

L. hispida Kunth traditionally is used in Mexico to treat tuberculosis, bronchitis, cough, cold, asthma, stomach ailments, kidney pain and diarrhea (Jiménez-Arellanes et al., 2007). In Bolivia, leaves of L. cujabensis Schauer are crushed between fingers and sniffed to treat head colds (Okunade & Lewis, 2004). L. viburnoides var kisi has ethnobotanical importance in Tanzania, where it is used to repel mosquitoes and in traditional medicine for stomach ache relief (Innocent et al., 2008). L. lilacina Desf. it has been used in traditional medicine to treat colds and bronchitis (Lorenzi, 2002). L. salvifolia Jacq is a plant widely used in the Congo as an herbal tea. The decoction of the leaves is used against typhoid fever (Ouamba et al., 2006). L. indica Roxb. is used as a sudorific, intestinal antiseptic and diaphoretic, and in treatment of tetanus, rheumatism and malaria in Indian medicine (Ghisalberti, 2000). A previous ethnobotanical study showed that L. achyranthifolia Desf. was recognized as one of the most important among the 44 species used for the treatment of gastrointestinal illnesses in Zapotitlan de las Salinas, Puebla (Mexico). Infusions of the aerial part of these plants have been used by native people to treat this type of disorder (Hernández et al., 2003). L. canescens Kunth is used mainly for xeriscaping, as it is drought-tolerant. In Northeast Brazil, the local community in Timbauba city (Pernambuco State) uses this species as an analgesic (Sena Filho et al., 2010). The concoction from the leaves of L. radula Sw. is used in Brazil as a tea to treat coughs, influenza and bronchitis (Sena Filho et al., 2010). Lantana trifolia L. is popularly used to treat colds, flu and sore throat (Silva et al., 2005). L. fucata Lindl. is a Brazilian species used in folk medicine for the treatment of respiratory disorders (Julião et al., 2009). L. camara has been used for the treatment of various human ailments, such as ulcers, malaria, influenza, tumors, swellings, bilious fever, eczema eruptions, stomach ache, toothache and as antiseptic for wounds (Ghisalberti, 2000). L. montevidensis Briq. have been used in folk medicine for the same purposes as L. camara (Nagão et al., 2002).


Chemical constituents

The search for new chemotherapeutic compounds in species of the genus Lantana has led to the isolation of various constituents with varying structural patterns and belonging mainly to the terpenoids, flavonoids, phenylethanoid glycosides, furanonaphthoquinones, iridoid glycosides and steroids. Phytochemical investigations have reported many constituents and are classified as described in the following subsections.

Monoterpenes and sesquiterpenes

Various studies have reported the chemical composition of essential oils of species of the genus Lantana collected in different places and origins. By means of surveys, it was observed that the essential oil of aerial parts obtained by hydrodistillation shows a yield of 0.01-0.7%. Various constituents, namely mono- and sesquiterpenes, were identified in the essential oils of Lantana, but with a greater predominance of the latter (Oliveira et al., 2008; Dambolena et al., 2010). Cited among the common major constituents identified in the oils are the sesquiterpenes, caryophillene, ß-caryophillene, E and Z-caryophillene, isocaryophillene, caryophyllene oxide, caryophyllene epoxide, germacrene D and bicyclogermacrene (Sena Filho et al., 2010). The caryophyllene isomers (Z, E and ß-caryophyllene) were present among the main constituents of the essential oil of L. camara from Northeast Brazil at different times of day (Sousa et al., 2010a). In the seasonal evaluation of the essential oil of L. camara from Madagascar, the concentration of ß-caryophyllene was found to be consistently high throughout the year, independent of sampling seasons (Randrianalijaona et al., 2005).


Studies of different Lantana species have shown that a total of seventy-four triterpenoids were isolated from this genus (Table 1). The structure of the different types of triterpenoids are shown in structures 1-74 and given below. The compounds 1-69 possess a pentacyclic triterpene structure, while the compounds 70-74 possess a tetracyclic triterpene structure. Most of the compounds, namely 1-39, are based on the oleanane nucleus. Among the triterpenes with an oleanane nucleus, nineteen (1-19) have a common skeleton (Skeleton-I), ten (25-34) have Skeleton-II, two compounds (36, 37) have a common skeleton (Skeleton-III), and the other two (38, 39) have Skeleton-IV, while others have individual structures. Several other compounds (40-64) incorporate an ursane nucleus. Three compounds (40-42) have Skeleton-V, five compounds (43-47) have a common skeleton (Skeleton-VI), and ten compounds (54-63) have Skeleton-VII, while others have individual structures. Compounds (66-69) possess a lupane nucleus. Among them, three compounds (65-67) have Skeleton-VIII and others have individual structures. Five compounds (70-74) incorporate a euphane nucleus. Four of them (70-73) possess Skeleton-IX.


Thirty-three flavonoids (compounds 75-107), all based on a flavone or flavonol nucleus, have been isolated from Lantana species (Table 2). Two flavonoids (75, 76) have Skeleton-X and the flavonoids (77-107) have a common skeleton (Skeleton-XI).

Phenylethanoid glycosides

Sixteen phenylethanoid (108-123) have been reported from different Lantana species and are listed in Table 3. Among them, two compounds (108, 109) have Skeleton XII, five compounds (112-116) have a common skeleton (Skeleton-XIII), two (117, 118) have Skeleton-XIV, and four compounds (120-123) have a common skeleton (Skeleton-XV), whereas three others have individual structures.


The structures of ten (124-133) furanonaphthoquinones isolated from Lantana are shown in Table 4. Among the furanonaphthoquinones, two compounds (124, 125) have Skeleton XVI, but two compounds (126, 127) have a common skeleton (Skeleton-XVII) and six others have individual structures.

Iridoid glycosides

Eight iridoid glycosides isolated from Lantana species are characterized by the structures 134-141 (Table 5). Three compounds (134-136) have Skeleton XVIII, three other compounds (137-139) have a common skeleton (Skeleton-XIX) and two (140, 141) have individual structures.


Click to enlarge



Ten steroidal compounds (142-152) have been reported from different Lantana species (Table 6) and all have the tetracyclic hydrocarbon derivative of the steroid nucleus. Among the steroids, five steroids (142-146) have a common skeleton (Skeleton-XX), and two (147, 148) have Skeleton-XXI, while three others have individual structures.

Miscellaneous compounds

Hydroxycinnamic acid-sugar derivatives, oligosaccharides, different types of organic acids and other compounds with varying structural patterns have been summarized under this category. They are characterized by the structures 153-175 (Table 7). Among the miscellaneous compounds, two compounds (153, 154) have Skeleton XXII, two other compounds (155, 156) have a common skeleton (Skeleton-XXIII), three (157-159) have Skeleton-XXIV, seven (161-167) have a common skeleton (Skeleton-XXV), and two (169, 170) have Skeleton-XXVI, whereas others have individual structures.


Activities attributed to the genus Lantana

Species of the genus Lantana are of great interest for phytochemical, biological and pharmacological studies. Phytochemical investigations have established the presence of terpenoids, phenylpropanoids and flavonoids, as the main class components with relevant biological activities (Ghisalbert, 2000). Studies on the biological and pharmacological activities of phytoconstituents isolated from the genus Lantana, as well as works related to the activities of extracts and/or essential oils are reported below.

Anthelminthic activity (anti-filarial activity and nematicidal activity)

Begum et al. (2008b) isolated seven compounds from the aerial parts of L. camara L., and tested them for nematicidal activity against the root-knot nematode Meloidogyne incognita. The lantanolic acid (28), pomolic acid (46), and lantoic acid (54) showed 100% mortality at 1.0% concentration after 24 h, while camarin (23), camarinin (37), lantacin (45) and ursolic acid (47) exhibited 100% mortality at 1.0% concentration after 48 h. Lantanoside (75), linaroside (76) and camaric acid (29) isolated from the aerial parts of L. camara L. showed 90, 85 and 100% mortality, respectively, at 1.0% concentration (Begum et al., 2000). All results were comparable with the conventional nematicide furadan (100% mortality at 1.0% concentration after 24 h).

In another study, extracts of stems and isolated compounds from seedlings of L. camara L. were assessed for anti-filarial activity in vitro and in vivo (Misra et al., 2007). The crude extract at 1 g/kg for five days, administered orally, killed 43.05% of the adult Brugia malayi parasites and sterilized 76% of surviving female worms in the rodent model Mastomys coucha. A 34.5% adulticidal activity along with sterilization of 66% of female worms could be demonstrated using the chloroform fraction. In the same study, the extract was also found to be effective against a subcutaneous rodent filariid Acanthocheilonema viteae maintained in M. coucha, where it exerted strong microfilaricidal (95.04%) and sterilization (60.66%) efficacy with mild macrofilaricidal action. Two compounds, oleanonic acid (8) and oleanolic acid (9), isolated from the hexane and chloroform fractions showed LC100 of 31.25 and 62.5 µg/mL, respectively, against B. malayi in vitro. McGaw & Eloff (2005) assessed the anthelminthic activity of acetone extracts of L. rugosa

Thunb. leaves against the free-living test nematode Caenorhabditis elegans. L. rugosa showed notable antinematode effects at a concentration of 1 mg/mL. Extracts of L. camara L. with organic solvents were found to cause significant mortality in vitro of Meloidogyne javanica in mungbean, while aqueous and methanolic extracts demonstrated greater inhibition compared to ethyl acetate or hexane extracts, indicating that active principles were polar in nature (Ali et al., 2001).

Anti-protozoal activity (anti-plasmodial, anti-malarial and leishmanicidal activity)

Valadeu et al. (2009) showed that the ethanolic extract from Lantana sp. has low activity against Plasmodium falciparum (FCR3), a chloroquine-resistant strain, (IC50 17.5±6.0 µg/mL). In the same study, the extract displayed interesting leishmanicidal activities (IC50 10±2.1 µg/mL). The experiments were conducted on axenic amastigotes of Leismania amazonensis (strain MHOM/BR/76/LTB-012).

The dichloromethane extract leaf from L. camara L. (pink flower) was analyzed in one study and showed very promising activity when tested in vitro against cultures of chloroquine-sensitive (3D7) and chloroquine resistant (W2) strains of P. falciparum (IC50 8.7±1.0 µg/ mL and 5.7±1.6 µg/mL, respectively) (Jonville et al., 2008). The dichloromethane extract from L. camara L. (orange flower) also showed promising activity (IC50 14.1±8.4 µg/mL and 12.2±2.9 µg/mL, respectively). In the same study, the dichloromethane extract (50 mg/kg) was investigated in vivo against Plasmodium berghei infected mice, and exhibited only 5% inhibition. Another in vivo study reported 8% inhibition of the parasite (Hakizamungu & Weri, 1988). On the other hand, the aqueous extract of at doses of 250 and 500 mg/kg/day were tested in vivo in rats infected with P. berghei; the extract showed partial antimalarial activity at the doses tested, reducing parasite load by 25 and 49%, respectively (Carrillo-Rosario & Diaz de Ramirez, 2006).

Katuura et al. (2007) screened extracts of the aerial part of L. trifolia L. for in vitro antiplasmodial activity against wild-type strains of P. falciparum using the nitro-tetrazolium blue-based lactate dehydrogenase assay. The petroleum ether extract of L. trifolia showed moderate antiplasmodial activity (13.2 µg/mL). Clarkson et al. (2004) reported that an extract of L. camara L. leaves demonstrated in vitro anti-plasmodial activity against a chloroquine-sensitive strain (D10) with an IC50 value of 11 µg/mL. The non-polar extract of root-bark also displayed high anti-malarial activity against the multidrug resistant K1 strain (Weenen et al., 1990). An ethanol extract of L. cujabensis Schauer showed lower activity when tested against chloroquine-resistant and chloroquine-sensitive strains of P. falciparum (IC50 14.7 µg/mL and 23.3 µg/ mL, respectively) (Desjardins, 1979).

Toxicity activity in vitro

One study reported that essential oils from the leaves of L. camara L. and Lantana sp. were evaluated to toxicity activity using Artemia salina larvae. The oils exhibited significant activities with LC50 of 14 µg/mL for L. camara and 24 µg/mL for Lantana sp. (Costa et al., 2009). In other study, the essential oil of L. camara L. leaves showed an LC50 value of 10 µg/mL (Sonibare & Effiong, 2008). The potential toxicity of the acetone extract of L. rugosa Thunb. leaves was also investigated and the results showed that L. rugosa exhibited toxicity with an LC50 of 0.69 mg/mL (McGaw & Eloff, 2005).

Fatore et al. (2002) studied the extracts of leaves, twigs, stems and roots of L. camara L., which were partitioned and analyzed for activity in the brine-shrimp lethality test. The active fractions yielded lantadene A (1), oleanonic acid (8), and oleanolic acid, which were very toxic to brine shrimp larvae. The three compounds were not lethal to Spodoptera littoralis Biosduval (Lepidoptera: Noctuidae), Clavigralla tomentosicollis Stal. (Hemiptera: Coreidae) and Aphis craccivora Koch (Homoptera: Aphididae) when tested at 5000 µg/mL. Lantadene A, however, suppressed the fecundity of C. tomentosicollis at this concentration.

Insecticidal activity

A wide variety of extracts/essential oils of Lantana and their constituents possess varying degrees of pest-controlling properties. A recent study investigated the insecticidal activity of essential oil from the leaves of L. camara L. against mosquito vectors (Dua et al., 2010). LD50 values of the oil were 0.06, 0.05, 0.05, 0.05 and 0.06 mg/cm2 while LD90 values were 0.10, 0.10, 0.09, 0.09 and 0.10 mg/cm2 against Aedes aegypti, Culex quinquefasciatus, Anopheles culicifacies, An. fluvialitis and An. Stephensi, respectively. KDT50 of the oil were 20, 18, 15, 12, and 14 min, and KDT90 values were 35, 28 25, 18, 23 min against Ae. aegypti, quinquefasciatus, An. culicifacies, An. fluviatilis and An. stephensi, respectively, on 0.208 mg/cm2 impregnated paper. Dharmagadda et al. (2005) showed that 200 ppm oil of L. camara L. produced 100% mortality in C. quinquefasciarus larvae in 15 min.

The essential oils from leaves of L. camara L. and L. montevidensis Briq. were tested for larvicidal activity against A. aegypti larvae at the third developmental stage (Costa et al., 2010). The results showed that both species have larvicidal potential: L. camara with LC50 of 42.3±0.85 µg/mL, and L. montevidensis with LC50 of 117±0.5 µg/mL. The essential oil also showed insecticidal activity against adults of Sitophilus oryzae L. (LC50 0.22 mg/cm2) and Tribolium castaneum (LC50 0.22 mg/cm2), and revealed low fumigant toxicity against S. oryzae (LC50 29.47 µL/L) and against T. castaneum (LC50 47.68 µL/L) (Mohamed & Abdelgaleil, 2008).

Kumar & Maneemegalai (2008) investigated the methanol and ethanol extracts of leaves and flowers of L. camara L. and showed mosquito larvicidal activity against 3rd and 4th instar larvae of the mosquito species A. aegypti and C. quinquefasciatus. Extracts at 1.0 mg/mL caused maximal mortality in A. aegypti exposed for 24 h. In the case of C. quinquefasciatus, maximal mortality was seen when the concentration was increased to 3.0 mg/mL. Repellent properties of different fractions obtained from L. camara L. flowers have been evaluated against Aedes mosquitoes (Ae. albopictus, Ae. vittatus and Ae. aegypti) (Dua et al., 2003). The results showed that one application of the chloroform fraction gave 100% protection for 2 h and up to 75.8% protection at 7 h against Ae. mosquito bites.

A methanolic extract of L. camara L. was tested on larval weight, pupation and adult emergence of cabbage butterfly (Sharma & Mehta, 2009a). L. camara resulted in significantly lower effect on reduction in weight (1.25%). Pupal formation increased significantly (0.0-43.1%) with a decrease in concentration from 5.0 to 1.25%. A similar trend was observed with respect to adult emergence of Plasmodiophora brassicae (Sharma & Mehta, 2009b). On the other hand, the methanolic extract of L. camara caused a significant reduction in aphid establishment (less than 50%) at 5.0%.

L. viburnoides var kisi was tested for insecticidal activity against late 3rd or early 4th instar larvae of Anopheles gambiae s.s., which were exposed to various concentrations of extracts, fractions, blends and pure compounds (Innocent et al., 2008). The crude extract (LC50 7.70 ppm at 72 h) and fractions exhibited different levels of mosquito larvicidal activity with subtraction of some fractions resulting in activity enhancement. The active fractions contained furanonaphthaquinones regioisomers (LC50 5.48-5.70 ppm at 72 h) and camaric acid (29) (LC50 6.19 ppm at 72 h) as active principles, while betulinic acid (65) (LC50 <10 ppm in 72 h) was obtained from the least active fraction.

Extracts of L. camara var. aculeata leaves were studied for their termiticidal effects against adult termite workers (Verma & Verma, 2006). Only 5% chloroform extract exhibited excellent termite mortality. With respect to LC50, the effect of 5% chloroform extract against Microcerotermes beesoni termites was the most interesting, compared to 0.5% chlorpyrifos.

Iannacone & Lamas (2003) studied the effects of extracts of L. camara L. on eggs, first instar larvae and adults of Phthorimaea operculella in bioassays of insecticidal effectiveness. The results showed that hatched eggs were affected by the hexane extract, and that first instar larva mortality was affected by hexane, acetone and water extracts at 10% concentrations.

The petroleum ether and methanol extracts of the aerial part of L. camara L. have been reported to be toxic to Callosobruchus chinensis (Dixit et al., 1992). The extracts showed 10-43% mortality at 5% concentrations, with fecundity loss at higher doses, and the antioviposition values were 30 mg/100 g for the petroleum ether extract and 40 mg/100 g of seed for the methanol extract.

In other studies, the essential oils of leaves and flowers of L. camara L. revealed insecticidal activity against 3rd instar larvae of Musca domestica, demonstrating mortality rates of 80 and 100%, respectively (Abdel-Hady et al., 2005), and the oil of leaves was effective against adults of Sitophilus zeamais (LC50 0.16% at 24 h) (Bouda et al., 2001). Essential oil of L. camara L. leaves also showed insecticidal properties against 3rd instar larvae of Helicoverpa armigera, causing 56% inhibition (Kathuria & Kaushik, 2006), and activity against fresh 5th instar nymphs of Dysdercus similies (Singh & Upadhyay, 1993).

Anti-viral activity

Garcia et al. (2010) screened the essential oil of L. grisebachii var. grisebachii L. for cytotoxicity and in vitro inhibitory activity against different virus types. The results showed that a better relationship between cytotoxicity and inhibitory activity was observed for the essential oil against dengue virus type 2 (DENV-2) and herpes simplex virus type 1 (HSV-1) with IC50 values of 21.1 and 26.1 ppm, respectively. Furthermore, this oil was also an effective inhibitor of HSV-2 and acyclovir-resistant variants of herpes virus.

Antioxidant activity

Bhakta & Ganjewala (2009) showed that premature leaves of L. camara L. on twigs are very active in the biosynthesis and accumulation of secondary metabolites and, hence, exhibit greater potential antioxidant activity (DPPH scavenging activity, 62%). It was also found that older leaves had less antioxidant activity (55%), indicating loss of secondary metabolites as result of leaf senescence. In another study, L. camara L. essential oil showed high antioxidant activity evaluated by the Trolox equivalent antioxidant capacity assay (TEAC) with a level of 29.0 mmol Trolox/kg (Benites et al., 2009).

Antifeedant activity

The chloroform, petroleum ether and methanol extracts of L. camara L. showed antifeedant activity against the tea mosquito bug (Helopeltis theivora Waterhouse), and among all the extracts, the chloroform extract showed the highest antifeedant effect (Deka et al., 1998). An aqueous extract of leaves was tested for its antifeedant effects on Plutella xylostella (Fracknath, 2006). The results showed that cabbage plants sprayed weekly with the extract protected the cabbage from P. xylostella to varying degrees. An antifeedant effect of crude lantadene from L. camara L. on P. xylostella and Spodoptera litura larvae has also been reported (Dong et al., 2005).

Phytotoxic activity

Previous evaluations of L. camara L. growing in Spain showed that an aqueous extract was not as effective against germination or seedling growth of Amaranthus hybridus and Portulaca oleracea as its essential oil (Verdeguer et al., 2009). The results suggest that its essential oil could be used as a potential allelopathic substance.

Zhang et al. (2009) reported the allelopathic effect of aqueous extracts of leaf and reproductive organs (flower and fruit) of L. camara L. on seed germination, seedling growth and dry matter production of radish and lettuce. The results showed that fruit extracts were more stimulatory, while flower and leaf extracts had similar stimulatory/inhibitory effects. L. camara reproductive organs exerted stronger allelopathic effects compared to vegetative organs. Thus, the allelopathic effect of its reproductive organs makes it more competitive and invasive.

Sousa et al. (2009) investigated for the first time the cytotoxic and genotoxic effects of aqueous extracts of L. camara L. leaves on Lactuca sativa (lettuce) root tip meristem cells using a cytogenetic approach. The results showed that the highest concentration (30 g/L) of aqueous extracts decreased the mitotic index, seed germination and root development of lettuce. The extracts also induced chromosome aberrations and cell death in root cells of L. sativa.

The extracts of L. camara L. leaves and their fractions were shown to reduce the biomass of Eichhornia crassipes and Microcystis aeruginosa within 7 days under laboratory conditions (Kong et al., 2005). Two fractions with highly inhibitory activity were isolated from the extract and subsequently identified as lantadene A (1) and lantadene B (2). Both compounds significantly inhibited E. crassipes and M. aeruginosa growth, even at a low concentration.

Antibacterial, antifungal activity

Species of Lantana have been widely evaluated in various works with respect to antimicrobial activity. One study showed inhibitory activity of an ethanolic extract of L. montevidensis Briq. leaves determined by the microdilution test against multiresistant strains of Escherichia coli (MIC 16 µg/mL) and Staphylococcus aureus (MIC 128 µg/mL) (Sousa et al., 2011a). An investigation of acetone extracts of leaves of L. camara L. and L. rugosa Thunb. showed growthinhibitory effects against two Gram-negative (E. coli and Pseudomonas aeruginosa) and two Gram-positive (Enterococcus faecalis and S. aureus) bacteria, with MIC values varying from 0.39 mg/mL to 6.3 mg/mL (McGaw & Eloff, 2005).

The antifungal activity of L. indica Roxb was found to be greater in the leaf essential oil than leaf extracts (Kumar et al., 2010). The oil inhibited the growth of Aspergillus flavus Link completely at 1.5 mg/mL, while ethanolic and chloroform extracts of leaves showed a MIC of 7.5 and 10.0 mg/mL, respectively. The essential oil of aerial parts of L. achyranthifolia also displayed antifungal activity against the five fungal strains A. niger, Fusarium nomiliforme, F. sporotrithum, Trichophyton mentagrophytes, Rhyzoctonia solani (IC50 100-180 µg/ mL) (Hernández et al., 2008).

The essential oil of the leaves of L. camara L. has been examined for antibacterial activity by the microdilution test (Sousa et al., 2010b). The results showed an inhibitory activity against the multiresistant strains E. coli (MIC 512 µg/mL) and S. aureus (MIC 256 µg/mL). The essential oils of L. trifolia L. and L. fucata Sw. leaves were investigated for their activity against M. tuberculosis. Both oils exhibited in vitro antibacterial activity by the Microplate Alamar Blue assay (MABA) with a MIC of 80 µg/mL for L. trifolia and 100 µg/mL for L. fucata (Julião et al., 2009).

A hexane extract from L. hispida Kunth aerial parts demonstrated growth inhibition in M. tuberculosis H37Rv (MIC 200 µg/mL), as well as in MDR-TB clinical isolates, including isoniazid- and rifampinresistant variant strains of M. tuberculosis H37Rv (Jiménez-Arellanes et al., 2003). The compounds 22βangeloyloxy-3β-hydroxyolean-12-en-28-oic acid (5), 22β-dimethylacryloyloxy-3β-hydroxyolean-12-en-28oic acid (6), and oleanenoic acid (11), isolated from L. hispida Kunth, have been shown to be active against M. tuberculosis H37Rv with a MIC of 50, 50, and 2 µg/ mL, respectively. Oleanenoic acid (11) showed a MIC of 25 µg/mL against the streptomycin- and isoniazid resistant strains of M. tuberculosis H37Rv and 50 µg/mL against rifampin-and ethambutol-resistant variants. The compounds 5 and 6 were also active at 50 µg/mL against all the drug-resistant variants of M. tuberculosis H37Rv tested (Jiménez-Arellanes et al., 2007). The compounds lantanoside (75), linaroside (76) and isolated from L. camara L. were also effective against strains of M. tuberculosis, both with a MIC of 6.25 µg/mL (Begum et al., 2000).

Verbascoside (113) isolated from L. lilacina Desf. showed antibacterial activity with MIC and MBC values against Aspergillus hydrophila, Bacillus subtilis, P. aeruginosa and S. aureus of 0.12, 1.00, 1.00 and 0.25 mg/ mL, respectively (Pereira et al., 2008). In an agar dilution assay, Proteus mirabilis and S. aureus were growth inhibited by verbascoside at 0.128 mg/mL (Didry et al., 1999).

The antibacterial activity of lantic acid (57) isolated from L. camara leaves was studied in Grampositive and Gram-negative bacteria using bioautography assays (Saleh et al., 1999). Lantic acid was found to possess strong antibacterial activity against E. coli and Bacillus cereus, in which 0.08 and 0.1 µg were the minimum inhibitory doses, respectively, compared to 0.05 and 0.005 µg for chloramphenicol, respectively.

Camarinic acid (55) isolated from L. camara L. leaves was found to be active (30 mg/disk) against S. aureus and Salmonella typhi with an average antibacterial index of 0.95 and 0.55, respectively. By comparison, chloramphenicol against S. aureus and tetracycline against S. typhi had an index of respectively 1.6 and 0.8 at the same concentration (Barre et al., 1997). Rwangabo et al. (1988) reported that umuhengerin (90) isolated from L. trifolia L. leaves exhibited antimicrobial activity against Salmonella typhimurium, S. aureus, Candida tropicalis, Aspergillus niger, A. fumigatus, Trichophyton mentagrophytes and Microsporum canis.

Modulatory activity

Modulatory activity has been studied and demonstrated in species of Lantana. In one study, a synergistic effect of gentamicin and amikacin against S. aureus was observed in the presence of the essential oil constituents of L. montevidensis Briq., by the gaseous contact method. Enhancement of the antibacterial activity of amikacin and gentamicin was found against P. aeruginosa, where the essential oil increased amikacin activity by 102% (Sousa et al., 2011b).

The synergistic effects of the ethanolic extracts of leaves and roots of L. montevidensis Briq. on aminoglycoside activity were demonstrated by the microdilution test. The maximum effects were obtained with the root extract on gentamicin activity against multiresistant strains of E. coli with a reduction in MIC from 312 to 2 µg/mL (Sousa et al., 2011a). On the other hand, the ethanolic extract of L. montevidensis Briq. root combined with amikacin against P. vulgaris, also reduced the MIC (625 to 20 µg/mL) (Sousa et al., 2011c). Synergism between the essential oil of the leaves of L. camara L. and aminoglycosides was demonstrated with a significant reduction in MIC (1250 to 5 µg/mL) against E. coli.

The modulatory evaluation of a mixture of the compounds 22β-dimethylacryloyloxy-3βhydroxyolean-12-en-28-oic acid (6) and oleanenoic acid (11) of L. hispida Kunth against M. tuberculosis H37Rv and drug-resistant variants of H37Rv strains showed MIC values ranging from 50 to 100 µg/mL, suggesting that a synergistic effect did not occur (Jiménez-Arellanes et al., 2007).

Antiinflammatory, analgesic, sedative and antipyretic activity

The sedative properties of L. trifolia L. extracts were demonstrated using the open field method, and one hour after their administration, the ethanolic and ethyl acetate extracts produced an intense sedative effect in all animals, expressed as a reduction in walked squares, with similar pattern and intensity at 1 and 10 mg/kg (Julião et al., 2010).

Ghosh et al. (2010) investigated the antiinflammatory activity of oleanonic acid (8) isolated from L. camara L. using the carrageenan-induced rat paw edema model. Oleanonic acid caused a reduction in edema, which validated its in vivo antiinflammatory effect. Another study reported that L. camara essential oil showed a relatively low antiinflammatory activity due to its weak ability to inhibit lipooxygenase (IC50 81.5 mg/mL) (Benites et al., 2009). On the other hand, in vitro assays showed that the alcoholic extract and fucatoside C (121) isolated from L. fucata Lindl. had significant antiinflammatory effects, inhibiting NO release in the LPS-induced J774. A1 murine macrophage cell line (Julião et al., 2009).

Silva et al. (2005) studied the antiinflammatory and analgesic activities of L. trifolia L. leaves. ethanol, dichloromethane, ethyl acetate, butanol and aqueous extracts (at 30 mg/kg) inhibited carrageenan-and histamine-induced rat paw edema. The most powerful reduction in paw edema was obtained with the ethanol (80%) and butanol (70%) extracts. Although the extracts did not show any effect on acetic acid-induced writhings, they all produced a significant increase in the tail flick antinociceptive index (doses varying between 1 and 30 mg/kg), indicating a spinal antinociceptive effect.

The methanolic extract of aerial parts of L. trifolia L. was evaluated for antiinflammatory, analgesic and antipyretic properties (Uzcátegui et al., 2004). The extract produced an inhibition of edema induced by carrageenan in the rat paw at doses of 10-300 mg/ kg. The extract also produced a small but significant increase in the response latency of rats submitted to the hot plate test, a test for thermal pain, which detects analgesia by high efficacy agents. The extract did not show antipyretic activity.

Whole plant and ethanolic extracts of fresh leaves of L. camara L. were investigated for their antiinflammatory properties using the cotton pellet antiinflammatory bioassay technique (Oyedapo et al., 1999). The treatments of the inflamed rats with the extracts resulted in the inactivation of phosphatase and transaminase activities and the stimulation of adenosine triphosphatase activity in plasma and exudates.

Antiproliferative (antitumor and anticancer) and cytotoxic activity

In a study by Shikha et al. (2010), oleanolic acid (9), isolated from the roots of L. camara L., was converted into six semi-synthetic ester and seven amide derivatives. The ester derivatives showed 3-6 times more selective activity than did oleanolic acid against the human ovarian cancer cell line IGR-OV-1, while amide derivatives showed 16-53 times more selective activity against the human lung cancer cell line HOP-62.

A crude extract of L. camara L. leaves had a cytotoxic effect on HeLa cells at 36 h (at 100 µg/ mL) to 72 h (at 25 µg/mL), by employing the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay (Srivastava et al., 2010). The results showed that an increase in the concentration or duration of the extract treatment was effective in killing cancer cells.

The compounds raduloside (119) and radulignan (174), isolated from L. radula Sw. roots, were tested for cytotoxicity against several cell lines (HL-60, K562, U937, CEM, KG-1, Jurkat, U266, and NCI-H929) and were found to have no effect on cell viability at 10 µM (Sena Filho et al., 2009). Lantadenes A (1), B (2), C (3) and 22β-dimethylacryloyloxy-24-hydroxy-3-oxo-olean12-en-28-oic acid (17), isolated from leaves of L. camara L., displayed weak to moderate cytotoxic activities against four cancer cell lines: human oral epidermoid carcinoma (KB), human colon cancer (HCT-116), human breast cancer (MCF-7), and mouse lymphocytic leukemia (L1210) (IC50 values of 4.7-44.7 µM) (Litaudon et al., 2009).

Litaudon et al. (2009) evaluated the compounds icterogenin (16) and 22β-dimethylacryloyloxy-24hydroxy-3-oxo-olean-12-en-28-oic acid (17), isolated from leaves of L. camara L., for their interaction with the antiapoptotic protein Bcl-xL/Bak association. The two compounds exhibited binding activity with Ki values between 7.6 and 5.3 µM, indicating that they both act as antagonists of the Bcl-xL/Bak association.

Sharma et al. (2008) studied methyl ester derivatives of lantadene obtained from the lantadene fraction of leaves of L. camara L. and showed cytotoxicity against four human cancer cell lines (HL-60, HeLa, colon 502713, and lung A-549). Cytotoxicity increased as the length of the side chain increased from acetoxy to propoxy. There was a significant decrease in cytotoxicity with branching of the side chain. The C-17 methyl esters were all more cytotoxic, with 22 showing the best activity (IC50 19.3-22.4 µg/mL). In the same study, lantadene A

(1) and four methyl ester derivatives of lantadene exhibited tumor inhibitory activity on two-stage squamous cell carcinogenesis in Swiss albino mice, induced by DMBA and promoted by TPA. Lantadene A showed an 18.1% incidence of tumors and a delay of three weeks, while animals in the group treated with a derivate compound showed a significant decrease in the incidence of cancer (17.2% vs 100%) at the end of twenty weeks.

Dichloromethane extracts of leaves from L. camara L. (colors of flowers: pink and orange) were tested for in vitro cytotoxicity against human WI-38 fibroblasts. The dichloromethane extracts showed IC50 values of 69.5±12.1 and 97.2±2.4 µg/mL for L. camara with pink and orange flowers, respectively (Jonville et al., 2008).

The flavonoid fraction from the leaves of L. montevidensis Briq. showed antiproliferative activity against human gastric adenocarcinoma (MK-1, GI50 12 µg/mL), human uterine carcinoma (HeLa, 5 µg/ mL), and murine melanoma (B16F10, 5 µg/mL) cells in vitro (Nagão et al., 2002). In the same study, flavones isolated from the flavonoid fraction of this plant, 5,3',4'trihydroxy-6,7,5'-trimethoxyflavone (95), apigenin (90), cirsiliol (98) and eupafolin (99), showed higher activity against the three tumor cell lines followed by eupatorin (92), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (80), 5,6,4'-trihydroxy-7,3',5'-trimethoxiflavone (96) and 5,6,3'trihydroxy-7,4'-dimethoxyflavone (81). cirsilineol (91) and 5,4'-dihydroxy-6,7,3',5'-tetramethoxyflavone (94) were the least active, although cirsilineol showed high selective activity against MK-1 cells. In addition, the methanolic extracts of L. camara L. and L. montevidensis Briq. leaves were very effective in inhibiting tumor cell growth, where 50% growth inhibition (GI50) was seen at concentrations of 8 µg/mL in MK-1, 3 µg/mL, in HeLa and 4 µg/mL in B16F10 for L. montevidensis extract, which was more potent than the L. camara extract (12.5 µg/mL in MK-1 and 25 µg/mL in HeLa and B16F10). The inhibitory activity was found to be localized in the nonglycoside fraction that contains several flavonoids.

Another study found that the leaf extract of L. camara L., administered at dose of 400 mg/kg, showed a chemopreventive effect against DMBA-induced squamous cell carcinogenesis in Swiss albino mice (Sharma et al., 2007a). It was also found that lantadene A (1) induces apoptosis in human leukemia HL-60 cells by activating the caspase-3 pathway and through down- and upregulation of Bcl-2 and Bax expression, respectively (IC50 value of 19.8±0.10 µg/mL following 48 h incubation) (Sharma et al., 2007b).

Verbascoside (113) isolated from L. camara was shown to be an inhibitor of protein kinase C (PKC) from rat brain (Herbert et al., 1991). The study reported that half-maximal inhibition of the kinase occurs at 25 µM. Verbascoside interacts with the catalytic domain of PKC and is a competitive inhibitor with respect to ATP (Ki 22 µM) and a non-competitive inhibitor with respect to the phosphate acceptor (histone IIIS). The antitumor activity of verbascoside measured in vitro may be due at least in part to the inhibition of PKC.

Antiulcerogenic activity

Sathisha et al. (2011) studied the antiulcerogenic effect of a methanolic extract of L. camara L. in aspirininduced gastric ulcerogenesis in pylorus-ligated rats and ethanol-induced gastric ulcer, and cysteamine-induced duodenal ulcer models. The extract was administered orally at two different doses, 250 and 500 mg/kg. The results showed that the extract significantly reduced the ulcer index and total acidity and significantly increased gastric pH of aspirin- and pylorus ligation-induced ulcerogenesis and ethanol-induced intestinal ulcer model. The extract also significantly reduced the ulcer index of cysteamineinduced duodenal ulcer.

Anti-motility activity

L. camara L. var. acuelata leaf powder, methanolic extract, lantadene A (1), neostigmine and neostigmine but with methanolic extract were evaluated for antimotility activity in the intestine of treated mice (Sagar et al., 2005). Neostigmine was used as a promotility agent and the intestinal motility was assessed by the charcoal meal test. In this evaluation, the percent intestinal transit significantly increased with neostigmine, but significantly decreased by all concentrations of methanolic extract and lantadene A. In the same study, an anti-diarrheal effect of the methanolic extract was studied in the castor oil-induced diarrhea model in mice. When the plant extract at 125 and 250 mg/kg doses was administered intraperitoneally, there was a significant reduction in fecal output compared with castor oil-treated mice. At higher doses (500 and 1000 mg/ kg), fecal output was almost completely stopped.

Anti-fertility activity

Mello et al. (2005) investigated the effects of the hydroalcoholic extract of the leaves of L. camara var. aculeate on reproduction. Three doses were tested in pregnant rats, 1, 3 and 7 g equivalent of plant material/kg body weight. The extract decreased the frequency of fetal skeleton anomalies in females and induced embryotoxicity as indicated by post-implantation loss, without any signs of maternal toxicity. In another study, the hydroalcoholic extract of L. camara L. leaves on fertility did not interfere with overall weight or internal organ weights of male rats, but interfered with sperm count, daily sperm production and sperm morphology in a dose-dependent manner (Melo et al., 2003).

Anticoagulant activity

Methanolic extracts prepared from the leaves of L. camara L. were found to inhibit human R-thrombin (O'Neill et al., 1998). The activity was shown to be associated with the euphane lactone triterpenes (70-74). The mechanism of the inhibition of the blood-clotting cascade was shown to involve acylation of the active-site Ser 195 residue of thrombin. This acylating activity is generic towards other serine proteases. Weir et al. (1998) showed that the inhibitors bind to the active site of human R-thrombin and R-chymotrypsin Tight-binding reversible competitive inhibition was shown by euphane lactone B (70-71). Protease inhibition involves the opening of the lactone ring and acylation of the active-site serine 195. The IC50 with α-thrombin, α-chymotrypsin and trypsin was respectively 0.004, 0.07 and 0.07 for euphane lactone B (70) and 0.004, 0.01, 0.12 mM for euphane lactone C (72).

Toxicity activity in vivo

Tokarnia et al. (1999) diagnosed an outbreak of poisoning by L. camara var. aculeata in cattle in Quatis County, state of Rio of Janeiro. The results showed that the plant caused lethal poisoning when given as a single dose of 40 g/kg; 20 g/kg caused severe poisoning, 10 g/kg slight or no poisoning and 5 g/kg failed to provoke symptoms. Another study showed that ingestion of 340-453 g of leaves of the L. camara L. causes liver and kidney damage, photosensitization, intestinal hemorrhage, paralysis of the gall bladder, and death in 1-4 days in horses, cattle and sheep (not goats) (Motion, 1994).

Lantadene C (3) isolated from L. camara var. aculeata leaves was shown to elicit a strong hepatotoxic response in guinea pigs associated with decrease in fecal output, feed intake, hepatomegaly, hepatic injury at the cellular and subcellular level, and increase in plasma bilirubin and acid phosphatase activity (Sharma et al., 1992).

Sharma et al. (1989) had also reported that the oral administration (125 mg/kg) of a toxin fraction obtained from L. camara L. leaves, whose main constituents were lantadene A (1) and lantadene B (2), in male and female guinea pigs, caused icterus and photosensitization within 48 h. A single dose of the lantadene A at 1-3 mg/kg injected intravenously in sheep was found to cause mild hepatocellular injury characterized by transient rises in serum enzymes, with or without hyperbilirubinemia, where higher doses resulted in hepatic necrosis (Pass et al., 1979).

In other studies, a partially purified fraction obtained from L. camara L. leaves containing seven chemicals was investigated. Lantadene A and lantadene B were the major compounds and nontoxic to guinea pigs (Sharma et al., 1987). 22ß-hydroxyoleanonic acid (7) was isolated from the lantadene fraction of L. camara and was studied for hepatotoxicity using lantadene A(1) as standard and found to be nontoxic (Sharma & Sharma, 2006).

Antimutagenic activity

A study of the compounds lantanilic acid (27) and camarinic acid (55), which were isolated from L. camara L., showed high antimutagenic activity in the mouse; at 6.75 mg/kg, they reduced the number of micronucleated polychromatic erythrocytes induced by mitomycin C by 76.7% and 60%, respectively (Barre et al., 1997).


Concluding remarks

In the present review, we compiled ethnopharmacological, phytochemical, pharmacological and toxicological information on the genus Lantana. The studies reported in the literature revealed the presence of terpenoids, flavonoids, phenylethanoid glycosides, furanonaphthoquinones, iridoid glycosides and steroids, demonstrating thus that the genus Lantana includes species that are a rich source of a variety of organic compounds with varying structural patterns.



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Received 3 Feb 2012
Accepted 26 Mar 2012



* Correspondence: José Galberto Martins Costa, Department of Chemistry Biological, Laboratory of Research in Natural Products, Regional University of Cariri Av. Cel Antonio Luiz, 1161. 63000-000 Crato-CE, Brazil Tel.: +55 88 3102 1212 Fax: +55 88 3102 1212

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