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.

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.

New Isoflavonoids from the extract of Rhynchosia precatoria (Humb. & Bonpl. ex Willd.) DC. and their antimycobacterial activity.

ETHNOPHARMACOLOGY RELEVANCE: The evaluation of the antimycobacterial activity of extracts of medicinal plants used by Mayos against tuberculosis and respiratory problems, allowed the identification of Rhynchosia precatoria (Humb. & Bonpl. ex Willd.) DC (Fabaceae) as the best candidate to find new antimycobacterial compounds. AIM OF THE STUDY: To isolate and characterize the compounds of R. precatoria responsible for the inhibitory and bactericidal activity against Mycobacterium tuberculosis H37Rv and Mycobacterium smegmatis ATCC 700084. To determine antimycobacterial synergistic effect of pure compounds and their selectivity index towards Vero cells. MATERIALS AND METHODS: A total of six flavonoids were purified by silica gel column chromatography. Structural elucidation of the isolated compounds was achieved by using 1D and 2D NMR spectroscopy techniques. The configuration at the C-3 chiral center was established by quantum mechanical calculation of the electronic circular dichroism (ECD) spectrum. In vitro inhibitory and bactericidal activity against M. tuberculosis and M. smegmatis were determined with the redox indicator Alamar Blue (resazurin). Synergy was determined by X/Y quotient. Cytotoxicity was measured by MTT assay. RESULTS: The isolated compounds were identified as precatorin A (1), precatorin B (2), precatorin C (3), lupinifolin (4), cajanone (5) and lupinifolinol (6). Compounds 1-3 are new. Compounds 1 to 5 inhibited the growth of M. tuberculosis (MIC ≥31.25µg/mL); compounds 1, 2, 4 and 5 killed the bacteria (MBC ≥31.25µg/mL) and also inhibited M. smegmatis (MIC ≥125µg/mL), while 1 and 4 also resulted bactericidal (MBC ≥125µg/mL). Compounds 4 and 5 presented synergistic effect (X/Y quotient value <0.5) at a concentration of 1/2 MIC of each compound in the combination. Cytotoxicity in murine macrophages (RAW 264.7 cells) gave IC50 values of 13.3-46.98µM, for compounds 1-5. CONCLUSIONS: In this work we isolated two new isoflavanones (1 and 2), and one new isoflavone (3) with a weak antimycobacterial activity. The (3R) absolute configuration was assigned to 1 by computational analysis of its ECD spectrum and to 2 and 5 by similarity of their ECD spectra with that of 1. We are also reporting by first time, activity against virulent strain of M. tuberculosis for compounds 4 and 5 and their antimycobacterial synergistic effect.

General, Mild, and Metal-Free Synthesis of Phenyl Selenoesters from Anhydrides and Their Use in Peptide Synthesis.

A mild, practical, and simple procedure for phenyl selenoesters synthesis from several anhydrides and diphenyl diselenide was developed. This transition-metal-free method provides a straightforward entry to storable Fmoc-amino acid selenoesters which are effective chemoselective acylating reagents. An application to oligopeptide synthesis was illustrated.

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.

Effect of substituted stilbenes on platelet function.

Stilbenes, including resveratrol, are polyphenols provided with protective actions on the cardiovascular system. Some natural derivatives of resveratrol, like pterostilbene, have a better bioavailability than the parent compound. The aim of the present study was to prepare different substituted stilbenes (dimethylallyloxy-stilbene, dimethylallyloxy-pterostilbene) and compare them with resveratrol, p-hydroxy-stilbene and pterostilbene for their biologic activities on platelet aggregation, platelet radical oxygen species (ROS) production, and platelet nitric oxide (NO) synthesis. The results show that the increase of stilbene derivative lipophilicity enhances their biologic activities.

Diterpenoids and Triterpenoids from the Resin of Bursera microphylla and Their Cytotoxic Activity.

A chemical study of the nonpolar fraction of a methanol-soluble extract of Bursera microphylla resin yielded a variety of di- and triterpenoids. In total, 15 compounds were isolated, of which three are new, namely, malabaricatrienone (1), malabaricatrienol (2), and microphyllanin (3). The antiproliferative activity of the major compounds was evaluated in different murine cancer cell lines (M12.C3.F6 and RAW264.7) and human cancer cells (A549, HeLa, and PC-3). The new compounds (1-3) did not show significant antiproliferative activity. The known compounds ariensin (4), burseran (5), and dihydroclusin diacetate (6) were effective against the RAW264.7 cell line, with IC50 values in the micromolar range.

Antioxidant and antifungal activity of different extracts obtained from aerial parts of Inula crithmoides L.

The total phenolic content, antioxidant and antifungal activities of three Inula crithmoides extracts (n-hexane, methylene chloride and MeOH) were investigated. The methanolic extract showed the highest total phenolic content. In the DPPH assay, the methanolic and hexane extracts exhibited the highest DPPH-radical scavenging activity; in the 5-lipoxygenase assay, the hexane extract showed greater inhibitory effect with an IC50 similar to that of Trolox and ascorbic acid. The antifungal activity of the methanolic extract revealed a higher activity against Phytophtora cryptogea and Alternaria solani.

Hinokinin, an emerging bioactive lignan.

Hinokinin is a lignan isolated from several plant species that has been recently investigated in order to establish its biological activities. So far, its cytotoxicity, its anti-inflammatory and antimicrobial activities have been studied. Particularly interesting is its notable anti-trypanosomal activity.

Antigenotoxic effect, composition and antioxidant activity of Dendrobium speciosum.

The chemical composition, the antiradical properties of Dendrobium speciosum (Orchidaceae) leaves and stem extracts have been studied. Furthermore, in view of the use of this orchid as "bush foods", the genotoxic/antigenotoxic effects of the extracts have been evaluated.

Furanodien-6-one from Commiphora erythraea inhibits the NF-κB signalling and attenuates LPS-induced neuroinflammation.

We investigated the in vitro anti-inflammatory activity of 1(10),4-furanodien-6-one, one the most active compounds of the hexane extract of Commiphora erythraea (Ehrenb.) Engl., by exposing microglial BV-2 cells to lipopolysaccharide. We showed that furanodien-6-one pre-treatment restored cell viability and ROS to control levels while halving NO generation. Production of pro-inflammatory IL-6, IL-23, IL-17, TGF-ß, and INF-γ, significantly induced by LPS, was also markedly reduced by furanodien-6-one treatment. We further showed that furanodien-6-one protects primary neuronal cultures against the inflammatory/toxic insults of LPS-treated BV-2 conditioned media, indicating that furanodien-6-one exerts anti-inflammatory/cytoprotective effects in neuronal cells. We then investigated whether furanodien-6-one exerts anti-inflammatory properties in an in vivo model of microglial activation. In adult mice ip-injected with LPS we found that furanodien-6-one had strong cerebral anti-inflammatory properties by inhibiting liver and brain TNFα as well as IL-1ß expression. Results were not unexpected since FTIR-metabolomic analyses showed that furanodien-6-one-treated mice had a reduced dissimilarity to control animals and that the response to LPS treatment was markedly modified by furanodien-6-one. In conclusion our data provide strong evidence of the anti-inflammatory properties of furanodien-6-one that could be exploited to counteract degenerative pathologies based on neuroinflammation.

Quantitative evaluation of auraptene and umbelliferone, chemopreventive coumarins in citrus fruits, by HPLC-UV-FL-MS.

An analytical strategy, based on the development of two HPLC methods with spectrophotometric (UV), spectrofluorometric (FL), and mass spectrometric (MS) detection, has been developed to investigate the presence of and to quantitate two important chemopreventive coumarins, auraptene and umbelliferone, in foodstuffs. The analytes were determined in fruits, and fruit parts, of plants belonging to the Citrus , Poncirus , and Fortunella genera, to test their nutraceutical potential. The method validation has been carried out according to international guidelines, with good results in terms of precision (RSD < 6.9%) and extraction yields (>91%). Application to the quantitative analysis of auraptene and umbelliferone in several kinds of citrus fruits was successful, providing reliable and consistent data. Exploiting three different kinds of detection, the analytical methodology proposed herein has been demonstrated to be sound but versatile, as well as reliable. Performances and results were compared and always found in good agreement among themselves. Thus, this approach is suitable for the identification and simultaneous quantitation of auraptene and umbelliferone in citrus fruits, with the aim of evaluating their nutraceutical potential.

Protective effects of Commiphora erythraea resin constituents against cellular oxidative damage.

By bioguided fractionation of the hexane extract of Commiphora erythraea resin we isolated four furanosesquiterpenoids that were tested for their protective activity against oxidative stress. Furanodienone and 1,10(15)-furanogermacra-dien-6-ones showed to be potent inhibitors of lipid peroxidation (IC(50) of -0.087 µM), being more active than the methoxylated analogues. Furthermore, using BV2 microglial cells, we found that furanodienone from C. erythraea is able to counteract LPS-induced cell death and decrease LPS-induced NO generation thus protecting microglial cells from LPS-induced cytotoxicity. Finally, docking studies were undertaken to gain insight into the possible binding mode of the isolated compounds at 5-LOX binding site.

Chromatographic methods for metabolite profiling of virus- and phytoplasma-infected plants of Echinacea purpurea.

This study was focused on the effects of virus and phytoplasma infections on the production of Echinacea purpurea (L.) Moench secondary metabolites, such as caffeic acid derivatives, alkamides, and essential oil. The identification of caffeic acid derivatives and alkamides was carried out by means of high-performance liquid chromatography-diode array detection (HPLC-DAD), HPLC-electrospray ionization-mass spectrometry (ESI-MS), and MS(2). Quantitative analysis of these compounds was carried out using HPLC-DAD. The results indicated that the presence of the two pathogens significantly decreases (P < 0.05) the content of cichoric acid, the main caffeic acid derivative. Regarding the main alkamide, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamide, a significant decrease (P < 0.05) in the content of this secondary metabolite was observed in virus-infected plants in comparison with healthy plants, while in the phytoplasma-infected sample the variation of this secondary metabolite was not appreciable. The % relative area of the E/Z isomers of this alkamide was also found to change in infected samples. The gas chromatography (GC) and GC-MS analysis of E. purpurea essential oil enabled the identification of 30 compounds. The main significant differences (P < 0.05) in the semiquantitative composition were observed for three components: limonene, cis-verbenol, and verbenone. The results indicate that the presence of virus and phytoplasma has an appreciable influence on the content of E. purpurea secondary metabolites, which is an important issue in defining the commercial quality, market value, and therapeutic efficacy of this herbal drug.

Searching for novel cancer chemopreventive plants and their products: the genus Zanthoxylum.

The genus Zanthoxylum (Rutaceae) comprises about 250 species, of which many are used as food, often as condiments, substituting pepper due to the pungent taste of fruits, seeds, leaves, and bark, and therapeutic remedies especially in Eastern Asian countries and in Central America. The whole plant is also consumed as an ingredient of soups and salads. The aim of this review is to examine in detail from a phytochemical and pharmacological point of view what is reported in the current literature about the anti-cancer and chemopreventive properties of phytopreparations or individual active compounds obtained from edible plants belonging to this genus.

Topical anti-inflammatory activity of boropinic acid and its natural and semi-synthetic derivatives.

Boropinic acid is a natural isopentenyloxycinnamic acid extracted from the aerial parts of Boronia pinnata Sm. (Rutaceae) with soybean 5-lipoxygenase inhibitory activity. In this paper the topical anti-inflammatory activity of boropinic acid and some of its natural and semi-synthetic derivatives was evaluated using the Croton oil ear test in mice as a model of acute inflammation. Some of the tested compounds (15, 17, 19, 20) revealed an effect comparable (ID(50)=0.18÷0.72µmol/cm(2)) to that of the reference drug indomethacin (ID(50)=0.23µmol/cm(2)), a non-steroidal anti-inflammatory drug.

Composition and antioxidant activity of Inula crithmoides essential oil grown in central Italy (Marche region).

The chemical composition of the essential oil obtained from the aerial parts of Inula crithmoides L. was analyzed by GC and GC/MS and 22 components were identified, the major ones being p-cymene (30.1%), 1-methylethyl-trimethylbenzene (18.7%), scopoletin (15.3%) and alpha-pinene (13.1%). The antioxidant activity of the oil was evaluated by the DPPH test and 5-lipoxygenase assay. The essential oil exerted a good antioxidant activity in the protection of lipid peroxidation when compared with known antioxidants.

Chemical composition of the essential oil of Commiphora erythraea.

The essential oil composition of Commiphora erythraea (Ehrenb) Engl. is reported for the first time. The oil is rich in sesquiterpenes, particularly furanosesquiterpenes (50.3%). GC-MS analysis of the oil permitted differentiation between C. erythraea and C. kataf, two often confused species.

Insights on novel biologically active natural products: 7-isopentenyloxycoumarin.

7-Isopentenyloxycoumarin is a prenyloxyphenylpropanoid derivative found in low concentration in a restricted number of plant families (Apiaceae, Asteraceae, and Rutaceae). Synthetic schemes were recently developed enabling sufficient quantities of the title coumarin to be obtained in order to evidence its valuable biological effects, mainly as an anti-cancer agent. The aim of this review is to examine the phytochemical and pharmacological properties of this compound.

Chemistry and pharmacology of collinin, active principle of Zanthoxylum spp.

Collinin is a geranyloxycoumarins isolated in small amounts from plants of the Rutaceae family. Synthetic schemes were recently developed allowing to handle collinin in sufficient quantities to put in evidence valuable biological effects. The aim of this review is to examine the phytochemical and pharmacological properties of this compound.