An Ethnopharmacological, Phytochemical and Pharmacological Review on Lignans from Mexican Bursera spp.

The genus Bursera belongs to the family Burseraceae and has been used in traditional Mexican medicine for treating various pathophysiological disorders. The most representative phytochemicals isolated from this genus are terpenoids and lignans. Lignans are phenolic metabolites known for their antioxidant, apoptotic, anti-cancer, anti-inflammatory, anti-bacterial, anti-viral, anti-fungal, and anti-protozoal properties. Though the genus includes more than 100 species, we have attempted to summarize the biological activities of the 34 lignans isolated from selected Mexican Bursera plants.


Introduction
The genus Bursera Jacq. ex L. (family Burseraceae, order Sapindales), named after the Danish botanist Joachim Burser (1583-1639), is a monophyletic genus [1] that includes about 105 species of small trees and shrubs distributed from Southern U.S. to Peru and the Caribbean, particularly in Mexico (ca. 92 species) [2]. These plants are characterized by the production of resins that are exuded from the trunk and leaves and provide a chemical defense against specialized herbivores [3]. Once dried, the resin obtained by Bursera spp. is called "copal", a term which is also used to describe a large group of resins characterized by hardness and a relative high melting point, which also is found in other plants [4]. The loss of the essential oils and the oxidation and polymerization processes transform copal into amber.
The phytochemistry of this genus is characterized by the presence of volatile metabolites such as simple hydrocarbons and terpenoids as well as phenolics [5][6][7][8]. Among the compounds present in the volatile fraction, heptane, αand β-pinene, β-phellandrene, and limonene are among the most frequent [5], whereas β-caryophyllene and germacrene D are the most common sesquiterpenes in the genus Bursera [8]. Cembrane and verticillane diterpenoids are often present [9][10][11]. Pentacyclic triterpenoids are largely present in the resin of several species, and the study of triterpenoidic composition of resins is important to define the botanical origin of archaeological samples of copal [12]. In Bursera microphylla resin, malabaricane triterpenoids were also found [11]. Leaves and branches of some Bursera also contain flavonoids [13][14][15] and luteolin 3 -O-rhamnoside is very common [13].
Lignans are naturally occurring plant phenolics, biosynthetically derived from phenylpropanoids, that are important components in foods and medicines; their chemical and biological properties have been reviewed [16]. The aim of this review is to summarize literature findings on the botanical characterization, distribution, ethnopharmacology, and biological activities of Mexican Bursera that produce lignans. Different Bursera species have been sorted according to, and synonyms are those traditionally attributed medicinal properties including providing relief from pain, inflammation, rheumatism, and can help treat illnesses such as colds, skin tumors, polyps, and venereal diseases [27][28][29][30]. The following are reported lignan-producing Bursera plants from Mexico listed according to the subgenus they belong to and sorted alphabetically. Traditional uses, when found, and biological properties of the isolated compounds are described for each species.

Bursera citronella McVaugh and Rzed.
B. citronella (synonyms: none reported) is also known as xochicopal (Náhuatl name) or lináloe, and as almárciga in Spanish [31]. It is a 10 m tree with grey trunk bark and unifoliate or trifoliolate leaves, distributed in Western Mexico (Michoacan, Colima, Jalisco, and Guerrero). It belongs to the subsection glabrifolia [5]. The resin is mostly used as incense. It has been reported that B. citronella is used as antitussive in several regions in Mexico [32].
B. cuneata (synonym: Elaphrium cuneatum Schltdl. L.) is a tree that grows up to 10 m in height with no-peeling grey-reddish bark. It has imparipinnate leaves of coriaceous texture with 3 to 13 leaflets, 6.5 cm long and 2.3 cm wide, and margin roughly serrated. Their flowers are clustered in inflorescences up to 8 cm long. Its flowers are white and its fruits are up to 1.2 cm long with a black pit, almost completely covered by a yellow or orange pseudoaril. It is native to Mexican oak-tropical deciduous forest transition zones from Jalisco to Oaxaca and is often known as copal or copalillo [72]. Although B. cuneata is characterized by seeds covered by pseudoaril, Becerra and Venable did not classify it into the copallifera group [22]. No medical uses have been reported for this species, but it is largely used as incense during sacred ceremonies and to prepare handcrafted objects.
Koulman isolated three lignans from this species: hinokinin (1), savinin (2), and cubebin (3) (Figure 1) [33]. Cubebin was first isolated by Chatterjee in 1968 from Piper cubeba [73] and then from several Aristolochia spp. Biological activities of cubebin have been recently reviewed by Cunha et al. [16]. In particular, trypanocidal activity of this compound against free amastigote forms of Trypanosoma cruzi has been studied by de Souza et al. [52], and Bastos et al. showed it is inactive against trypomastigote forms [74]. Notably, cubebin (3) is usually the starting material for the semi-synthetic preparation of hinokinin (1) and other lignans [52]. Recently, cubebin was proven to induce vasorelaxation via nitric oxide activation without prostacyclin involvement [75]. Because of its therapeutic potential, the effects of cubebin on mutagenicity and genotoxicity has been deeply studied by several research groups [76]. The authors found that cubebin (3) was cytotoxic at high doses (280 µM), but at lower concentrations, no cytotoxic, mutagenic, or proliferative effects were observed for this compound. The mutagenicity of cubebin (3), alone or in combination with doxorubicin (DXR), using standard (ST) and high bioactivation (HB) crosses of the wing Somatic Mutation And Recombination Test (SMART) in Drosophila melanogaster was also studied [77]. Even in this case, the effect of cubebin was dose-dependent. At lower doses (<1 mM), it reduces DXR toxicity, whereas at higher doses (>2.0 mM), it is cytotoxic. The biological activities of cubebin have been recently reviewed [78].
Lignans that contain a methylenedioxy group show high antifeedant or deterrent activity against insects. Polar substituents on the aromatic rings, such as hydroxyl or glycosyl groups, reduce this activity. Guayadequiol (6) was isolated for the first time from Bupleurum salicifolium [89]. No biological data for this compound have been reported. The hexane extract of B. excelsa was shown to possess in vivo anti-inflammatory activity [29].
B. graveolens (synonyms: Amyris caranifera, A. graveolens, B. andersonii, B. pilosa, B. tatamaco, Elaphrium graveolens, E. pilosum, Terebinthus graveolens, and T. pilosa) is called copal and mizquixochicopalli in Náhuatl language [90]. Its Spanish common name is palo santo and it is native to the tropical dry forests from the Yucatan Peninsula of Mexico, south to Peru, and the Galapagos Islands of Ecuador. These are trees and sometimes shrubs up to 15 m tall, highly fragrant, with grey bark. Their leaves are imparipinnate, sometimes bipinnate, up to 30 cm long and 18 cm wide, with 7 to 11 leaflets. The leaflets are 3 to 9 cm long and 1 to 4 cm wide, of acuminate apex, and margin roughly serrated. Their small flowers are yellowish, white, or green and their fruits glabrous and are up to 1.0 cm long. Their seeds are black and about two-thirds covered by an orange-red pseudoaril. Traditionally, the alcoholic extract of the bark is used for rheumatism, and the bark infusion, as a digestive and for respiratory problems. In recent years, the resin and oils have been extracted from the wood by the perfume industry. From the active methanol extract of stems, Nakanishi et al. isolated a new aryltetralin lignan, burseranin (7), and picropolygamain (8) (Figure 2) along with known triterpenes, lupeol and epi-lupeol [91]. The two isolated lignans 7 and 8 showed important cytotoxic activity against the human HT1080 fibrosarcoma cell line. Both compounds exhibited potent inhibitory effects in comparison with adriamycin as a positive control (5.5 and 1.9 µg/mL vs. 0.1 µg/mL). Picropolygamain (8) was isolated for the first time in 1985 from Commiphora incisa resin [92] and later from Bursera simaruba [93]. This compound was shown to be active against LNCaP (androgen-sensitive human prostate adenocarcinoma) cell line (ED 50 1.1 µg/mL) during tests aimed at developing an in vivo Hollow Fiber Assay [94]. and MDA-MB-468) with IC50 values of 1.18 and 1.62 μg/mL, respectively, but demonstrated lower cytotoxicity on normal breast cell lines (IC50 higher than 11 μg/mL). Cell cycle studies showed that this compound induced cell apoptosis and drove cells toward the G2/M phase. Moreover, it decreased topoisomerase II and Bcl-2. The authors observed an increasing in p53, p21, bax, cytochrome c, and caspase-8, -7, and -3 activities, except caspase-9, suggesting that kusunokinin has potent anticancer activity through the extrinsic pathway and G2/M phase arrest [88]. Lignans that contain a methylenedioxy group show high antifeedant or deterrent activity against insects. Polar substituents on the aromatic rings, such as hydroxyl or glycosyl groups, reduce this activity. Guayadequiol (6) was isolated for the first time from Bupleurum salicifolium [89]. No biological data for this compound have been reported. The hexane extract of B. excelsa was shown to possess in vivo anti-inflammatory activity [29].

Bursera graveolens (Kunth) Triana and Planch.
B. graveolens (synonyms: Amyris caranifera, A. graveolens, B. andersonii, B. pilosa, B. tatamaco, Elaphrium graveolens, E. pilosum, Terebinthus graveolens, and T. pilosa) is called copal and mizquixochicopalli in Náhuatl language [90]. Its Spanish common name is palo santo and it is native to the tropical dry forests from the Yucatan Peninsula of Mexico, south to Peru, and the Galapagos Islands of Ecuador. These are trees and sometimes shrubs up to 15 m tall, highly fragrant, with grey bark. Their leaves are imparipinnate, sometimes bipinnate, up to 30 cm long and 18 cm wide, with 7 to 11 leaflets. The leaflets are 3 to 9 cm long and 1 to 4 cm wide, of acuminate apex, and margin roughly serrated. Their small flowers are yellowish, white, or green and their fruits glabrous and are up to 1.0 cm long. Their seeds are black and about two-thirds covered by an orange-red pseudoaril. Traditionally, the alcoholic extract of the bark is used for rheumatism, and the bark infusion, as a digestive and for respiratory problems. In recent years, the resin and oils have been extracted from the wood by the perfume industry. From the active methanol extract of stems, Nakanishi et al. isolated a new aryltetralin lignan, burseranin (7), and picropolygamain (8) (Figure 2) along with known triterpenes, lupeol and epi-lupeol [91]. The two isolated lignans 7 and 8 showed important cytotoxic activity against the human HT1080 fibrosarcoma cell line. Both compounds exhibited potent inhibitory effects in comparison with adriamycin as a positive control (5.5 and 1.9 μg/mL vs. 0.1 μg/mL). Picropolygamain (8) was isolated for the first time in 1985 from Commiphora incisa resin [92] and later from Bursera simaruba [93]. This compound was shown to be active against LNCaP (androgen-sensitive human prostate adenocarcinoma) cell line (ED50 1.1 μg/mL) during tests aimed at developing an in vivo Hollow Fiber Assay [94]. B. penicillata (synonyms: Amyris penicillata, Bursera mexicana, Elaphrium delpechianum, E. mexicanum, E. penicillatum, Terebinthus delpechiana, and T. mexicana) belongs to the section glabrifolia. Its common names are coyoluche, torote incienso, and torote copal [95]. These are trees up to 12 m tall of grey or reddish grey bark, and are very fragrant, even sometimes from a distance. Their leaves are imparipinnate, 12 to 38 cm long, rachis-winged, and with 3 to 15 leaflets. The leaf blades are finely pubescent on both surfaces and the margins strongly toothed. Their flowers are small, white, and arranged in few to many inflorescences up to 14 cm long. Fruits are 1 to 1.3 cm long, 0.8 to 1.1 cm B. penicillata (synonyms: Amyris penicillata, Bursera mexicana, Elaphrium delpechianum, E. mexicanum, E. penicillatum, Terebinthus delpechiana, and T. mexicana) belongs to the section glabrifolia. Its common names are coyoluche, torote incienso, and torote copal [95]. These are trees up to 12 m tall of grey or reddish grey bark, and are very fragrant, even sometimes from a distance. Their leaves are imparipinnate, 12 to 38 cm long, rachis-winged, and with 3 to 15 leaflets. The leaf blades are finely pubescent on both surfaces and the margins strongly toothed. Their flowers are small, white, and arranged in few to many inflorescences up to 14 cm long. Fruits are 1 to 1.3 cm long, 0.8 to 1.1 cm wide with a black pit, and partially covered by a red, orange, or pale pseudoaril. Endemic to Northwest Mexico, this species prospers in tropical deciduous forests and sporadically thornscrub and transition areas to oak woodland, from Southeastern Sonora and Southwest Chihuahua to Michoacan. According to Gentry, the leaves are used to treat the common cold and the gum is used for toothaches. It is also used as incense [96]. Koulman reported the presence of savinin (2) in this species [33].
B. submoniliformis (synonyms: Bursera subsessiliformis Engl. and Elaphrium submoniliforme (Engl.) Marchand ex Engl.) is commonly known as copal chino. These trees are up to 12 m tall with grey to reddish gray bark. Their leaves are imparipinnate, up to 20 cm long and 7 cm wide, with 9 to 17 leaflets. The leaflets are velvety, 1.3 to 5 cm long, 0.5 to 2 cm wide, and have toothed margins. They have small white flowers that are arranged in inflorescences. Fruits are 7.5 to 12 mm long with a black pit almost or completely covered by a yellow or orange pseudoaril. Endemic to Mexico, this species inhabits tropical deciduous forests at altitudes of 500 to 1600 m of the Balsas and Papaloapan river basins in the states of Mexico, Michoacan, Guerrero, Puebla, Morelos, and Oaxaca. It belongs to the subsection copallifera. The gum resin is used to alleviate pain associated with flatulence and tooth-ache [97]. The only reference about the phytochemistry of B. submoniliformis is by Koulman, who reported the presence of savinin (2) in this species [33].

pseudoaril.
Nieto-Yañez et al. evaluated the anti-leishmanial activity of a B. aptera methanolic extract. The extract showed strong activity against Leishmania mexicana both in the in vitro and in vivo tests. The gas chromatography-mass spectrometry (GC-MS) phytochemical analysis of the extract showed the presence of 11 compounds. Most of these compounds were fatty acids and fatty acid esters, but they revealed the presence of podophyllotoxin (19) (Figure 3) [100].  . It is commonly known as zapotillo [99]. These are small trees, often shrubs, of reddish-brown exfoliating bark with leaves up to 2.5 cm long and 1 cm wide, comprising 3 to 11 leaflets. Their flowers are very small, reddish, and solitary. Their fruits are solitary or in pairs, over short and pilose peduncles 1 to 2 mm long, with a seed completely covered by a pale yellow pseudoaril [101]. It belongs to the microphylla subsection. Traditionally, the plant latex is topically used for healing wounds and skin eruptions [102] in the Tehuacán-Cuicatlán valley. Bursera arida has different medicinal uses such as a disinfectant, cough suppressant, and antidepressant [103].
The phytochemistry of B. arida was studied by Ionescu, who prepared a chloroform extract of the stems, leaves, twigs, and bark, and found naringenin, β-sitosterol, betulonic acid, and four lignans: (+)-3-hydroxymethyl-5-methoxy-6,7-methylenedioxy-1-(3′,4′-methylenedioxybenzene)-l,2,3,4-tetrahydro naphthalene-2-carboxylic acid lactone (9) (      B. ariensis (synonyms B. panosa Engl., B. sessiflora Engl., E. ariensis Kunth, and E. brachypodium Rose). These are trees and sometimes shrubs between 2 and 8 m tall with greenish-gray trunks and bark that exfoliates in papery sheets that are yellowish or beige, sometimes with orange tones, with whitish resin that darkens upon contact with air. Their leaves are hairy especially when young, 5 to 22 cm long, and 2 to 7 cm wide, with a winged rachis and 5 to 9 leaflet pairs. Their flowers can be solitary but often develop in conglomerates at the end of branches of reddish-yellow color. Their fruits are 6 to 8 mm long, growing in thick conglomerates, with a pit completely covered by a yellow or orange pseudoaril. It is distributed in Mexico (Chiapas, Guerrero, Jalisco, and Oaxaca regions) where it is commonly known as guande and cuajiote blanco (Náhuatl name) [101] and used to treat colds and inflammation. It belongs to the fagaroides group and is poorly studied. From the acetonic extract of the bark, Hernandez isolated a new lignan named ariensin (12) [105]. Ariensin was shown to be active against the RAW246.7 murine cell line (IC 50  B. fagaroides, or "fragrant bursera" (B. obovata Turcz., B. schaffneri S. Wats) [2] is a dioecious shrub or tree, occasionally hermaphrodite, 0.5 to 10 m high, and highly resinous. The trunk is green with a bark that exfoliates in yellowish-gray papery sheets. The leaves are most often compound, with 5 to 13 leaflets, although occasionally they are unifoliolate or trifoliolate. They have whitish-green or yellow flowers, with a few of them arranged in small inflorescences or solitary. Male flowers are most often 5-merous (sometimes 3-and 4-). Female flowers are 3-merous. Fruits are typically 0.5 to 0.8 cm long with short peduncles no more than 2 mm long that terminate in a sharp point. When the pits mature, they are covered by a yellow or red pseudoaril. It is commonly known as cuajiote amarillo (in Morelos) or pima bajo [106]. This species belongs to the fagaroides group. Three subspecific variants of this species were recognized by McVaugh and Rzedowski (1965). B. fagaroides var. fagaroides, commonly known as xixote and jiote [72], are most often shrubs with leaves with serrated margins and are distributed in Northern, Central, and Western Mexico. B. fagaroides var. purpusii (common name aceitillo) [107] are most often trees with leaves of entire margin (not toothed) distributed throughout Southeastern Mexico. B. fagaroides var. elongata, common Mayo name to'oro sahuali [95], is from Northwestern Mexico, and has been classified by recent molecular studies as a separate taxon not belonging within B. fagaoides [108].
Podophyllotoxin and deoxypodophyllotoxin are secondary metabolites of many plants [125]. The biological activities and the importance of podophyllotoxin (19), as the lead compound in the development of new anticancer agents, are well known [126][127][128]. The problem connected with its use is the scarce amount isolated from natural sources. For this reason, biotechnological production of this lignan has been studied [129]. Deoxypodophyllotoxin (15) is a promising anticancer agent [130,131].
Ornithine decarboxylases (ODC) are enzymes that catalyze the decarboxylation of ornithine to produce putrescine in the biosynthesis of polyamines. Polyamine metabolism is closely related with the progression of growth, proliferation, and cell regeneration. The in vitro effect of an ethanolic extract from the stem bark of Bursera fagaroides on ODC activity, and on the growth of Entamoeba histolytica, was studied by Rosas-Arreguín et al. using metronidazole and G418 as positive controls [135]. The authors found growth inhibition, with IC 50 values in the order of 0.05 mg/mL. The ODC activity was inhibited by 12% at 4.0 mg/mL.
2.3.5. Bursera microphylla A. Gray B. microphylla, or "elephant tree" (Elaphrium microphyllum (A. Gray) Rose, Terebinthus microphylla (A. Gray) Rose), is commonly known as xoop (Seri name) and torote blanco [95]. It is typically a small tree that grows up to 10 m tall, with a thickened trunk and thickened lower branches, with light gray to white peeling bark, with younger branches having a reddish color. The leaves are 3 to 8 cm long and have 7 to 35 small, linear, and glabrous leaflets. The leaflets are up to 1.5 cm long. The flowers are yellowish white or greenish and inconspicuous. The fruits are brownish red at maturity with a black pit completely covered by a yellow-orange pseudoaril [26]. It belongs to the microphylla group. The Seri Indians from Sonora, Mexico use the bark, leaves, flowers, and fruits to treat a variety of maladies such as inflammation, diarrhea, and venereal diseases. The first lignan isolated from Bursera microphylla was burseran (30) (Figure 1) [137]. Cole et al. showed that burseran has cytotoxic activity against human epidermoid carcinoma of the nasopharynx (9KB cell line) in a Cancer Chemotherapy National Service Center (CCNSC) test (ED 50 < 10 µg/mL) acting as a spindle poison. Tomioka et al. synthetized cis (H 8 α) and trans burseran and tested them in a cilia regeneration test in Tetrahymena, that is a useful model for studying the antitubulinic activity of spindle poisons [138]. Both trans and cis burseran have shown inhibitory activity, but the antitumor activity was higher for trans burseran [139]. An analysis of the chemical composition of the methanol extract of B. microphylla resin from the Sonora Desert (Mexico), revealed the presence of several known lignans: ariensin (12), burseranin (7), dihydroclusin diacetate (25), picropolygamain (8), desmethoxy-yatein (18), hemiariensin (31) (Figure 5), and dihydroclusin 9 -acetate (23); and two new ones: podophyllotoxin butanoate (32) and dihydroclusin 9-acetate (33) (Figures 3 and 5) [11,140]; in addition to burseran (30). Compound 32 was already known as a synthetic derivative of podophyllotoxin [141] but it was new as a natural product. Burseran (30) and dihydroclusin diacetate (25) were tested against human cancer cell lines: A549 (lung cancer), HeLa (cervix cancer), and PC-3 (prostate cancer), and on murine cell lines M12.C3.F6 (B cell lymphoma) and RAW264.7 (macrophages transformed by virus Abelson leukemia); which were found to be more active against murine cell lines in micromolar range (IC 50 13.8, 36.3, and 2.5 µM, respectively). The anti-proliferative activities of dihydroclusin 9-acetate (31), dihydroclusin 9 -acetate (23), burseranin (7), picropolygamain (8), and hemiariensin (31) were evaluated on the human cancer cell lines A549, LS 180, and HeLa, and on the human non-cancer cell line ARPE-19. None of the evaluated compounds had statistically significant anti-proliferative effects with respect to dimethyl sulfoxide (DMSO) control on LS 180, A549, and ARPE cell lines. However, burseranin (7) and picropolygamain (8) [101], where it is commonly known as coabinillo [99]. It is a tree up to 13 m tall with red bark that exfoliates in thin sheets. Its leaves are 5 to 11 cm long and 1.5 to 4.5 cm wide, with 15 to 51 linear leaflets. The flowers are yellow, pink, greenish, or white. The fruits are 0.5 to 1 cm long, with a pit completely covered by a pale yellow pseudoaril. It belongs to the microphylla group. The only two papers describing the phytochemistry of B. morelensis address the composition and the anti-inflammatory activity of the essential oil [142] and the isolation of deoxypodophyllotoxin (15) and morelensin (16) from the resin [110]. Morelensin (16), although highly active against the KB (epidermoid carcinoma) cancer cells, demonstrated only marginal activity against the porcine stable (PS) kidney cell line [110].

Bursera roseana Rzed., Calderón & Medina
B. roseana (synonyms: Bursera acuminata (Rose) Engl. and Terebinthus acuminata Rose) is a 12-20 m high tree with bark peeling in reddish-orange stripes. It is imparipinnate with 3 to 7 (sometimes 9) leaflets with a hairy underside but a bright and glabrous upper side. The leaflets are typically of oval shape, 4.5 to 15 cm long and 2 to 6 cm wide, ending in a long point. The flowers are white or greenish and the is fruit is glabrous, 0.9 to 1.2 cm long, with a pit completely covered by a pale pseudoaril [143].
This species grows in moist canyons in the transition zone between highland pine-oak forest and lowland tropical subdeciduous forest. It is common in Nayarit, Zacatecas, Aguascalientes, Jalisco, Colima, Michoacán, Estado de México, and Guerrero [143]. It belongs to the simaruba group. The only phytochemical study on this species was reported by Koulman, who found 5 -desmethoxy yatein [bursehernin or (−)-trans-methylpluviatolide [144] (+)-trans-methylpluviatolide, which has been called dextrobursehernin [145] (18)], morelensin (16), deoxypodophyllotoxin (15), and β-peltatin-A methylether (13). Bursehernin (18) was studied by Ito et al. for its inhibitory effects on Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells [146]. The data reported demonstrated that bursehernin (18) was slightly weaker than β-carotene, which is commonly used in cancer prevention studies [147] so it might be a valuable antitumor promoter. Bursehernin (18) is able to inhibit the growth of Neisseria gonorrhoeae [148]. The trypanocidal activity of racemic mixtures of cisand trans-bursehernin was evaluated in vitro against trypomastigote forms of two strains of Trypanosoma cruzi, and results showed that the racemic cis-stereoisomer was inactive, whereas the racemic trans-stereoisomer displayed trypanocidal activity, with an IC 50~8 9.3 µM. These results were different from those obtained for pure (−)-trans-methylpluviatolide by Bastos et al., but the difference could be ascribed to the use of the racemic mixture [74].
B. schlechtendalii (synonyms: Bursera jonesii Rose, Elaphrium jonesii (Rose) Rose, Terebinthus jonesii (Rose) Rose, and Terebinthus schlechtendalii (Engl.) Rose) is a small tree or shrub, 4-6 m high, with a strong turpentine smell, and known as sak chakaj. It has a glossy greyish pink bark that peels off in thin papery sheets; the branches are thick and stout. The leaves are simple (unifoliolate), often less than 6 cm long and 2.5 cm wide. The flowers are small, usually solitary, with yellow or reddish petals, and the fruits are 4 to 8 mm long with a pit completely covered by a yellow or red pseudoaril. It is used to treat the flu. It is found at altitudes of 200-400 m on dry rocky hillsides or in thickets in Southern Mexico and Guatemala. It belongs to the fagaroides group. In 1972, McDoniel et al. isolated from stems and leaves the chloroform extract of Mexican B. schlechtendalii Engl. yatein (17) and bursehernin (18).
B. simaruba or "gumbo-limbo" (Bursera simaruba var. yucatanensis Lundell) is commonly known as yala-guito [99]. It is a 6-15 m high tree with a peeling reddish bark that reveals a smooth grey underbark. The leaves are compound, bright, and mostly glabrous when mature. Leaves have 3 to 13 leaflets, 4 to 9 cm long and 1.8 to 3.5 cm wide. The small flowers have pink, pale yellow-green, or white petals and are arranged in inflorescences. The fruits are glabrous, red to brownish, 1 to 1.5 cm long, ending in a point, with a pit completely covered by a red pseudoaril. This is perhaps the most widespread species of Bursera, occurring from Southern Florida and the Caribbean, along both coasts of Mexico, to South America. Taken orally or as curative baths, the leaves and bark are attributed a variety of medicinal properties. It belongs to the simaruba group. In 1992, Peraza-Sánchez and Peña-Rodriguez isolated picropolygamain (8), which showed activity in the brine shrimp assay (LC 50 = 52.2 ppm). Further in vitro evaluation against three human tumor cell lines (A-549, lung), MCF-7 (breast), and HT-29 (colon) showed that 8 has cytotoxic activity comparable to that of Adriamycin [93]. Noguera et al. isolated the anti-inflammatory β-peltatin A-methyl ether (13) from the leaf hexane extract of B. simaruba. It inhibited the carrageenan-induced rat paw edema, in a dose-and time-dependent manner (three hours = 9.55%, five hours = 34.37%, and seven hours = 35.6%) [149]. Maldini

Conclusions
Lignans are phenolic secondary metabolites characterized by a large variety of biological activities. Among these, the cytotoxic and anti-proliferative ones are perhaps the most common and most studied. Literature analysis of Mexican plants producing lignans Burseara spp., revealed that the most common lignan types are dibenzyl butyrolactones (nine compounds), picro aryltetraline derivatives (three compounds), aryltetraline derivatives (nine compounds), 7 ,8 -dehydro-aryltetraline derivatives (five compounds), and dibenzylbutane diols (eight compounds). Notably, all the examined Elaphrium subgenus species produce only dibenzyl butyrolactones and picro aryltetraline derivatives, whereas Bursera subgenus produce all lignan types. The most common compound, up to now, appears to be bursehernin (18), which is present in five species belonging to the Bursera section. Hinokinin (1) and savinin (2) are also widespread (four species), both in the Elaphrium and Bursera sections. Compounds  3, 8, 12, 13, 15, 16, 17, and 33 were isolated from three species.

Conflicts of Interest:
The authors declare no conflict of interest.