Biological Activity of Bursera schlechtendalii Essential oil and the Roles of Its Chemical Components in the Wound Healing Process.

Essential oils are composed of terpenes, some of which have properties related to healing. Bursera schlechtendalii essential oil (BSEO) is used to heal superficial wounds. However, there have been no studies verifying this property. The objectives of this study were to evaluate the healing activity of BSEO in a murine model and to propose the roles of its chemical components in this process. Healing activity was evaluated by an incision model, histological analysis was performed, and tensile strength and antibacterial activity were measured. The chemical composition of BSEO was determined by gas chromatography coupled with mass spectrometry (GC-MS), and the mechanisms of action of each chemical component during the phases of the healing process were proposed. In addition, acute dermal toxicity was evaluated. BSEO showed better wound closure at the macroscopic, histological, and tensile strength levels compared to controls and had an antibacterial effect. The major compound in BSEO was α-phellandrene. However, most of the monoterpenes identified in BSEO were in agreement with information found in the literature, so the possibility of synergy between the chemical components and their different targets in the healing process was schematically proposed. BSEO was shown to be safe in the dermal toxicity evaluation.

Composición química y actividad AChE-BuChE del aceite esencial de palo santo Bursera graveolens (Kunth) Triana & Planch de Jipijapa, Ecuador / Chemical composition and AChE-BuChE activities of the essential oil of palo santo Bursera graveolens (Kunth) Tr iana & Planch from Jipijapa, Ecuador

Abstract: This article describes the chemical composition, physical properties and acetylcholinesterase (A ChE) and butyrylcholinesterase (BuChE) activity of stem - distilled essential oil (E O ) from Bursera graveolens wood chips, Burseraceae. The plant material was acquired in Quimis (Bosque de Sancán), city of Jipijapa in the province of Manabí, coastal region o f Ecuador. Thirty - six components were identified by CG - MS, which represented 98.54% of the volatile oil. The main components were limonene (68.52%) and mentofuran (20.37%). The hydrocarbon monoterpenes constituted the most abundant fractions. The average y ield of the E O was 1.26%. Regarding the physical properties of E O , the following values were obtained: relative density (1,029 g/mL), refractive index (1,477) and specific rotation (+4,567). The E O presented IC 50 inhibition values of 47.2 and 51.9 µg/mL fo r the enzymes AChE and BuChE, respectively.

Resumen: Este artículo describe la composición química, propiedades físicas y actividad acetilcolinesterasa (AChE) y butirilcolinesterasa (BuChE) del aceite esencial (AE) destilado a vapor de astillas de madera de Bursera graveolens , Burseraceae. La materia vegetal fue adquirida en Quimis (Bosque de Sancán), ciudad de Jipijapa en la provincia de Manabí, región costera d e Ecuador. Treinta y seis componentes fueron identificados por CG - MS, que representaron al 98.54 % del aceite volátil. Los componentes principales fueron limoneno (68.52%) y mentofurano (20.37%). Los monoterpenos hidrocarburos constituyeron las fracciones m ás abundantes. El rendimiento medio del AE fue de 1.26%. Con respecto a las propiedades físicas del AE se obtuvo los siguientes valores, densidad relativa (1.029 g/mL), índice de refracción (1.477) y rotación específica (+4.567). El AE presentó valores de inhibición IC 50 de 47.2 y 51.9 µg/mL para las enzimas AChE y BuChE, respectivamente.

Essential oils of Bursera morelensis and Lippia graveolens for the development of a new biopesticides in postharvest control.

Fruit and vegetable crops that are not consumed immediately, unlike other agricultural products, require economic and time investments until they reach the final consumers. Synthetic agrochemicals are used to maintain and prolong the storage life of crops and avoid losses caused by phytopathogenic microorganisms. However, the excessive use of synthetic agrochemicals creates health problems and contributes to environmental pollution. To avoid these problems, less toxic and environment-friendly alternatives are sought. One of these alternatives is the application of biopesticides. However, few biopesticides are currently used. In this study, the biopesticide activity of Bursera morelensis and Lippia graveolens essential oils was evaluated. Their antifungal activity has been verified in an in vitro model, and chemical composition has been determined using gas chromatography-mass spectrometry. Their antifungal activity was corroborated in vitro, and their activity as biopesticides was subsequently evaluated in a plant model. In addition, the persistence of these essential oils on the surface of the plant model was determined. Results suggest that both essential oils are promising candidates for producing biopesticides. This is the first study showing that B. morelensis and L. graveolens essential oils work by inhibiting mycelial growth and spore germination and are environment-friendly biopesticides.

Wound Healing Activity of α-Pinene and α-Phellandrene.

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. Recently, it was shown that the essential oil (EO) of B. morelensis has wound healing activity, accelerating cutaneous wound closure and generating scars with good tensile strength. α-pinene (PIN) and α-phellandrene (FEL) are terpenes that have been found in this EO, and it has been shown in different studies that both have anti-inflammatory activity. The aim of this study was to determine the wound healing activity of these two terpenes. The results of in vitro tests demonstrate that PIN and FEL are not cytotoxic at low concentrations and that they do not stimulate fibroblast cell proliferation. In vivo tests showed that the terpenes produce stress-resistant scars and accelerate wound contraction, due to collagen deposition from the early stages, in wounds treated with both terpenes. Therefore, we conclude that both α-pinene and α-phellandrene promote the healing process; this confirms the healing activity of the EO of B. morelensis, since having these terpenes as part of its chemical composition explains part of its demonstrated activity.

Wound Healing Activity of the Essential Oil of Bursera morelensis, in Mice.

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. It is an endemic tree known as "aceitillo", and the antibacterial and antifungal activity of its essential oil has been verified; it also acts as an anti-inflammatory. All of these reported biological activities make the essential oil of B. morelensis a candidate to accelerate the wound-healing process. The objective was to determine the wound-healing properties of B. morelensis' essential oil on a murine model. The essential oil was obtained by hydro-distillation, and the chemical analysis was performed by gas chromatography-mass spectrometry (GC-MS). In the murine model, wound-healing efficacy (WHE) and wound contraction (WC) were evaluated. Cytotoxic activity was evaluated in vitro using peritoneal macrophages from BALB/c mice. The results showed that 18 terpenoid-type compounds were identified in the essential oil. The essential oil had remarkable WHE regardless of the dose and accelerated WC and was not cytotoxic. In vitro tests with fibroblasts showed that cell viability was dose-dependent; by adding 1 mg/mL of essential oil (EO) to the culture medium, cell viability decreased below 80%, while, at doses of 0.1 and 0.01 mg/mL, it remained around 90%; thus, EO did not intervene in fibroblast proliferation, but it did influence fibroblast migration when wound-like was done in monolayer cultures. The results of this study demonstrated that the essential oil was a pro-wound-healing agent because it had good healing effectiveness with scars with good tensile strength and accelerated repair. The probable mechanism of action of the EO of B. morelensis, during the healing process, is the promotion of the migration of fibroblasts to the site of the wound, making them active in the production of collagen and promoting the remodeling of this collagen.

Anesthetic Efficiency of Three Medicinal Plant Oils for Aquatic Species: Coriander Coriandrum sativum, Linaloe Tree Bursera delpechiana, and Lavender Lavandula hybrida.

This study evaluated the potential of three essential oils (EOs) that were obtained from coriander Coriandrum sativum (CEO), linaloe tree Bursera delpechiana (BEO), and lavender Lavandula hybrida (LEO) as anesthetic agents. Convict Cichlids Amatitlania nigrofasciata (Günther 1867) were exposed to eight concentrations of anesthetic (50, 75, 100, 125, 150, 200, 250, and 300 µL/L). After exposure to the anesthetic, the fish were transferred to clean water to recover. All of the EOs produced an anesthetic effect after exposure to the compounds for 30 min at the minimal effective concentration (MEC), which was identified according to deep anesthesia (A5  < 3 min) and full recovery (R3  < 5 min) times. At 50 and 75 µL/L, the total loss of equilibrium was not observed for all tested EOs. The total loss of reflex was induced at a faster rate with higher concentrations of anesthetic in all groups. The recovery time generally increased as the concentration of the anesthetic increased. These findings suggest that CEO, BEO, and LEO are all novel potential anesthetics for aquaculture, and the optimal concentrations were identified as 150 µL/L (A5 ; 156 ± 1.7 s and R3 ; 165 ± 2.9 s), 125 µL/L (A5 ; 176 ± 3.5 s; R3 ; 125 ± 2.0 s), and 200 µL/L (A5 ; 20.1 ± 2.4 s and R3 ; 162 ± 3.4 s), respectively. When considering the active ingredients of EOs, this study also demonstrated that future studies should be focused on the major components such as linalyl acetate, 1.8-cineole, α-pinene, geraniol, and linalool. Their synergistic effects should be examined in herbal anesthetic treatments, since new commercial anesthetics will likely contain them.

Volatile chemical composition of essential oil from Bursera graveolens (Kunth) Triana & Planch and their fumigant and repellent activities

The objectives of this work were the study of the volatile chemical composition of essential oils (EO’s) from Bursera graveolens obtained in the locality of Malagana, municipality of Mahates, Bolívar, Colombia, as well as to evaluate their repellent and fumigant properties. EO’s were extracted by hydro-distillation and characterized by gas chromatography-mass spectrometry (GC-MS). The major compounds found in B. graveolens were limonene (42.2%), pulegone (20.9%), carvone (7.5%), caryophyllene (4.1%), and trans-carveol (3.8%). The repellent activity of EO’s was determined by the area preference method, where the EO of B. graveolens presented repellent activity against the Tribolium castaneum weevil at a concentration of 1 at 2% and 4 hours of exposure (88.1 and 88.6% respectively). B. graveolens essential oil was more effective in its fumigant activity with LC50 of 108.2 μg oil mL-1. Also, the fumigant and repellent activities of two individual compounds present in the oil were evaluated, that is, limonene (majority) and caryophyllene. The results indicated that B. graveolens essential oil could be a promising alternative to new natural repellents and biocides.

Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos.

By using a zebrafish embryo model to guide the chromatographic fractionation of antimitotic secondary metabolites, seven podophyllotoxin-type lignans were isolated from a hydroalcoholic extract obtained from the steam bark of Bursera fagaroides. The compounds were identified as podophyllotoxin (1), ß-peltatin-A-methylether (2), 5'-desmethoxy-ß-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7). The biological effects on mitosis, cell migration, and microtubule cytoskeleton remodeling of lignans 1⁻7 were further evaluated in zebrafish embryos by whole-mount immunolocalization of the mitotic marker phospho-histone H3 and by a tubulin antibody. We found that lignans 1, 2, 4, and 7 induced mitotic arrest, delayed cell migration, and disrupted the microtubule cytoskeleton in zebrafish embryos. Furthermore, microtubule cytoskeleton destabilization was observed also in PC3 cells, except for 7. Therefore, these results demonstrate that the cytotoxic activity of 1, 2, and 4 is mediated by their microtubule-destabilizing activity. In general, the in vivo and in vitro models here used displayed equivalent mitotic effects, which allows us to conclude that the zebrafish model can be a fast and cheap in vivo model that can be used to identify antimitotic natural products through bioassay-guided fractionation.

Volatile Profiling, Insecticidal, Antibacterial and Antiproliferative Properties of the Essential Oils of Bursera glabrifolia Leaves.

The present article describes the chemical composition and biological activities of the essential oils of B. glabrifolia leaves obtained in four consecutive years (2015-2018). The essential oils contained α-terpineol (17.9-29.7 %), α-terpinene (12.6-17.4 %), limonene (14.9-26.8 %) and ß-pinene (2.1-16.7 %) as the most abundant volatiles. The essential oils and these volatiles showed a significant adulticide activity (p<0.01; LC50 <100 µg mL-1 ) on the maize weevil (Sitophilus zeamais) with a 100 % mortality rate within a period of 5 h. Also, the essential oils showed a strong antibacterial activity on Enterococcus faecalis ATCC 29212 (MIC, 132.7-173.6 µg mL-1 ) and Helicobacter pylori ATCC 43504 (MIC, 74.8-199.2 µg mL-1 ). The assessment of the main volatiles revealed α-terpineol as the principal antibacterial agent (MIC, 78.6-149.7 µg mL-1 ). Similarly, the essential oils exhibited a substantial in vitro antiproliferative activity on the human prostate cancer cell lines PC-3 (LC50 , 15.2-19.4 µg mL-1 ), the human ovarian carcinoma cell lines OVCAR-3 (LC50 , 27.3-53.7 µg mL-1 ) and the myelogenous leukemia cell lines K-562 (LC50 , 32.4-75.9 µg mL-1 ). α-Terpineol (LC50 , 32.4-75.9 µg mL-1 ) exhibited the strongest antiproliferative effect on these cancer cell lines (LC50 , 22.4-48.1 µg mL-1 ).

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.

Chemical profile and pharmacological effects of the resin and essential oil from Bursera slechtendalii: A medicinal "copal tree" of southern Mexico.

This study reports on the volatile profile and pharmacological activities of the essential oil and resin from Bursera slechtendalii, an aromatic medicinal tree commercialized in southern Mexico. The essential oil contained 25 volatiles including p-cymen-8-ol (25.4-35.7%), n-hexyl hexanoate (6.8-17.6%) and n-octyl hexanoate (7.6-14.8%), whereas the crystallized resin contained 14 volatiles, including n-octyl acetate (29.6-34.2%), limonene (15.8-18.7%) and n-octyl butyrate (12.6-17-6%). The inhalation of vapors from the resin and essential oil caused a significant anxiolytic-like effect (p < .01) in ICR mice after 20 min of exposure at a dose of 50-150 mg L-1. The prolonged inhalation of the essential oil (for 40 days, for 15 min, twice a day) produced a significant decrease (p < .01) in total cholesterol and LDL-c content as well as an increase of HDL-c levels in the same murine model. Interestingly, levels of hepatic lipid hydroperoxide decreased, whereas the hepatic activity of superoxide dismutase and glutathione peroxidase was significantly enhanced (P < .05). The detection of p-cymen-8-ol and n-octyl acetate in the plasma of mice strongly suggests their bioavailability and possible role in the biological activities described herein. Also, both the resin and essential oil from B. slechtendalii, as well as their main volatiles, showed a potent repellence activity against Aedes aegypti (p < .01).

Bursera copallifera Extracts Have Cytotoxic and Migration-Inhibitory Effects in Breast Cancer Cell Lines.

Plants from the Bursera genus are widely distributed in the tropical dry forests of Mexico. In traditional medicine, extracts from different species of Bursera have been used for a wide range of biological activities, including the treatment of cancer-related symptoms. Compounds present in the Bursera genus include lignans, flavonoids, steroids, short-chain aliphatic alkanes, acetates, alcohols, ketones, and terpenoids. In some instances, secondary metabolites of these classes of compounds may induce cytotoxicity, and therefore we sought to investigate the effects of B. copallifera leaf extracts in breast cancer cell lines to evaluate their potential therapeutic value for the treatment of breast cancer, one of the most prevalent types of cancer in women worldwide. Two B. copallifera leaf extracts exerted cytotoxic effects on both the MCF7 and MDA-MB-231 breast cancer cell line models. The cytotoxic effect was more evident in the MDA-MB-231 triple negative cell line inhibiting also the migration of these cells. We identified hydroxycinnamic acid and flavonol derivatives as major phenolic components of the extracts. Our results strongly suggest a potential use of the Bursera leaf extracts rich in phenolic compounds, their individual phenolic compounds, or their combinations for the treatment of breast cancer.

Two new lignans from the resin of Bursera microphylla A. gray and their cytotoxic activity.

Two new lignans, namely 7-O-podophyllotoxinyl butyrate (1) and dihydroclusin 9-acetate (2), were isolated from the dichloromethane fraction of a methanol extract of Bursera microphylla (Burseraceae), along with eight known lignans (3-10). Their structures were determined by means of comprehensive spectroscopic analysis. Lignans 2-6 were tested for their anti-proliferative activity on the cancer cell lines LS180, A549 and HeLa, and on a non-cancer cell line, ARPE-19. Only compounds 4 and 5 showed an interesting activity on HeLa cells.

The Hexane Fraction of Bursera microphylla A. Gray Induces p21-Mediated Anti-Proliferative and Pro-Apoptotic Effects in Human Cancer-Derived Cell Lines.

Bursera microphylla (BM), one of the common elephant trees, is widely distributed in the Sonoran Desert in Mexico. The Seri ethnic group in the Sonoran Desert uses BM as an anti-inflammatory and painkiller drug for the treatment of sore throat, herpes labialis, abscessed tooth, and wound healing. Dried stems and leaves of BM are used in a tea to relieve painful urination and to stimulate bronchial secretion. Furthermore, BM is used for fighting venereal diseases. To investigate the effects of the hexane fraction of resin methanol extract (BM-H) on cell growth, the acute myeloid cell line (OCI-AML3) was treated with 250, 25, or 2.5 µg/mL of BM-H. The first 2 concentrations were able to significantly decrease OCI-AML3 cell number. This reduced cell number was associated with decreased S-phase, blockade of the G2/M phase of the cell cycle, and increased cell death. Similar results were obtained on all tested tumor cell lines of different origins. We found that blockade of the cell cycle was due to upregulation of p21 protein in a p53-independent way. Increase of p21 was possibly due to upstream upregulation of p-ERK (which stabilizes p21 protein) and downregulation of p-38 (which promotes its degradation). Regarding cell death, activation of caspase-3, but not of caspase-8 or -9, was detectable after BM-H treatment. In conclusion, these data suggest that the BM's hexane fraction inhibited proliferation of cell lines mainly by a p21-dependent, p53-independent mechanism and promoted apoptosis through activation of caspase-3, but not caspase-8 or -9.

Anti-Candida Activity of Bursera morelensis Ramirez Essential Oil and Two Compounds, α-Pinene and γ-Terpinene-An In Vitro Study.

The candidiasis caused by C. albicans is a public health problem. The abuse of antifungals has contributed to the development of resistance. B. morelensis has demonstrated antibacterial and antifungal activities. In this work the activity of the essential oil of B. morelensis was evaluated and for its two pure compounds with analysis of the different mechanisms of pathogenesis important for C. albicans. The essential oil was obtained by the hydro-distillation method and analyzed using GC-MS. The anti-Candida activity was compared between to essential oil, α-Pinene and γ-Terpinene. GC-MS of the essential oil demonstrated the presence of 13 compounds. The essential oil showed antifungal activity against four C. albicans strains. The most sensitive strain was C. albicans 14065 (MFC 2.0 mg/mL and MIC50 0.125 mg/mL) with α-Pinene and γ-Terpinene having MFCs of 4.0 and 16.0 mg/mL respectively. The essential oil inhibited the growth of the germ tube in 87.94% (8.0 mg/mL). Furthermore, it was observed that the essential oil diminishes the transcription of the gene INT1. This work provides evidence that confirms the anti-Candida activity of the B. morelensis essential oil and its effect on the growth of the germ tube and transcription of the gene INT1.

IN VIVO AND IN VITRO ANTILEISHMANIAL EFFECTS OF METHANOLIC EXTRACT FROM BARK OF BURSERA APTERA.

BACKGROUND: Cutaneous leishmaniasis lacks effective and well-tolerated treatments. The current therapies mainly rely on antimonial drugs that are inadequate because of their poor efficacy. Traditional medicine offers a complementary alternative for the treatment of various diseases. Additionally, several plants have shown success as anti-leishmanial agents. Therefore, we sought to evaluate the in vitro and in vivo activity of MEBA against Leishmania mexicana. MATERIALS AND METHODS: Methanolic extract of B. aptera was obtained by macetration, after we determined in vitro anti-leishmanial activity of MEBA by MTT assay and the induced apoptosis in promastigotes by flow cytometry. To analyze the in vivo anti-leishmanial activity, we used infected mice that were treated and not treated with MEBA and we determined the levels of cytokines using ELISA. The phytochemical properties were determined by CG-MS and DPPH assay. RESULTS: We determined of LC50 of 0.408 mg/mL of MEBA for in vitro anti-leishmanial activity. MEBA induced apoptosis in promastigotes (15.3% ± 0.86). Treated mice exhibited smaller lesions and contained significantly fewer parasites than did untreated mice; in addition, we found that IFN-γ and TNF-α increased in the sera of MEBA-treated mice. GC-MS analysis showed that podophyllotoxin was the most abundant compound. Evaluation of the activity by DPPH assay demonstrated an SC50 of 11.72 µg/mL. CONCLUSION: Based on the above data, it was concluded that MEBA is a good candidate in the search for new anti-leishmanial agents.

Antigiardial Activity of Podophyllotoxin-Type Lignans from Bursera fagaroides var. fagaroides.

Giardiasis, a diarrheal disease, is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; unfortunately, all of them have variable efficacies and adverse effects. Bursera fagaroides has been known for its anti-inflammatory and antidiarrheal properties in Mexican traditional medicine. We investigated the in vitro anti-giardial activities of four podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides, namely, 5'-desmethoxy-ß-peltatin-A-methylether (5-DES), acetylpodophyllotoxin (APOD), burseranin (BUR), and podophyllotoxin (POD). All lignans affected the Giardia adhesion and electron microscopy images revealed morphological alterations in the caudal region, ventral disk, membrane, and flagella, to different extents. Only 5-DES, APOD, and POD caused growth inhibition. Using the Caco-2 human cell line as a model of the intestinal epithelium, we demonstrated that APOD displayed direct antigiardial killing activity and low toxicity on Caco-2 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.

ANTIMICROBIAL ACTIVITY OF BURSERA MORELENSIS RAMÍREZ ESSENTIAL OIL.

BACKGROUND: Bursera morelensis, known as "Aceitillo", is an endemic tree of Mexico. Infusions made from the bark of this species have been used for the treatment of skin infections and for their wound healing properties. In this work, we present the results of a phytochemical and antimicrobial investigation of the essential oil of B. morelensis. MATERIALS AND METHODS: The essential oil was obtained by a steam distillation method and analyzed using GC-MS. The antibacterial and antifungal activities were evaluated. RESULTS: GC-MS of the essential oil demonstrated the presence of 28 compounds. The principal compound of the essential oil was a-Phellandrene (32.69%). The essential oil had antibacterial activity against Gram positive and negative strains. The most sensitive strains were S. pneumoniae, V. cholerae (cc) and E. coli (MIC 0.125 mg/mL, MBC 0.25 mg/mL). The essential oil was bactericidal for V. cholera (cc). The essential oil inhibited all the filamentous fungi. F. monilifome (IC50 = 2.27 mg/mL) was the most sensitive fungal strain. CONCLUSIONS: This work provides evidence that confirms the antimicrobial activity of the B. morelensis essential oil and this is a scientific support about of traditional uses of this species.

The Hexane Fraction of Bursera microphylla A Gray Induces p21-Mediated Antiproliferative and Proapoptotic Effects in Human Cancer-Derived Cell Lines.

Bursera microphylla (BM), one of the common elephant trees, is widely distributed in the Sonoran desert in Mexico. The Seri ethnic group in the Sonoran desert uses BM as an anti-inflammatory and painkiller drug for the treatment of sore throat, herpes labialis, abscessed tooth, and wound healing. Dried stems and leaves of BM are used in a tea to relieve painful urination and to stimulate bronchial secretion. Furthermore, BM is used for fighting venereal diseases. To investigate the effects of the hexane fraction of resin methanol extract (BM-H) on cell growth, the acute myeloid cell line (OCI-AML3) was treated with 250, 25, or 2.5 µg/mL of BM-H. The first 2 concentrations were able to significantly decrease OCI-AML3 cell number. This reduced cell number was associated with decreased S-phase, blockade of G2/M phase of the cell cycle, and increased cell death. Similar results were obtained on all tested tumor cell lines of different origins. We found that blockade of the cell cycle was a result of upregulation of p21 protein in a p53-independent way. Increase of p21 was possibly a result of upstream upregulation of p-ERK (which stabilizes p21 protein) and downregulation of p-38 (which promotes its degradation). Regarding cell death, activation of caspase-3, but not of caspase-8 or -9, was detectable after BM-H treatment. In conclusion, these data suggest that BM-H inhibited proliferation of cell lines mainly by a p21-dependent, p53-independent mechanism and promoted apoptosis through activation of caspase-3 but not caspase-8 or -9.

Anti-inflammatory and antioxidative effects of six pentacyclic triterpenes isolated from the Mexican copal resin of Bursera copallifera.

BACKGROUND: Bursera copallifera (Burseraceae) releases a resin known as "copal ancho" which has been used, since pre-Colombian times, as ceremonially burned incense and to treat tooth ache, tumors, arthritis, cold, cough, and various inflammatory conditions; however, its anti-inflammatory potential is poorly studied. The aim of the present study was to isolate, quantify, and to investigate the anti-inflammatory activity of triterpene compounds isolated from the copal resin of B. copallifera. METHODS: The constituents present in the total resin of B. copallifera were obtained by successive chromatographic procedures, and quantitative analysis was performed by High Performance Liquid Chromatography (HPLC). Anti-inflammatory effects of the isolated triterpenes were investigated to determine their inhibitory effects on phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema in mice, viability and nitric oxide (NO) production inhibition on lipopolysaccharide (LPS)-activated RAW 264.7 macrophages, and inhibition of cyclooxygenase (COX)-1, COX-2 and secretory Phospholipase A2 (sPLA2) activities in vitro. RESULTS: Quantitative phytochemical analysis of the copal resin showed the presence of six pentacyclic triterpenes of which, 3-epilupeol (59.75 % yield) and α-amyrin (21.1 % yield) are the most abundant. Among the isolated triterpenes, 3-epilupeol formiate (Inhibitory Concentration 50 % (IC50) = 0.96 µmol), α.amyrin acetate (IC50 = 1.17 µmol), lupenone (IC50 = 1.05 µmol), and 3-epilupeol (IC50 = 0.83 µmol) showed marked inhibition of the edema induced by TPA in mice. α-amyrin acetate and 3-epilupeol acetate, at 70 µM, also inhibited the activity of COX-2 by 62.85 and 73.28 % respectively, while α-amyrin and 3-epilupeol were the best inhibitors of the production of NO in LPS-activated RAW 264.7 cells with IC50 values of 15.5 and 8.98 µM respectively, and did not affected its viability. All compounds moderately inhibited the activity of PLA2. CONCLUSIONS: This work supports the folk use of B. copallifera and provides the basis for future investigations about the therapeutic use of this resin in treating inflammation.