Metabolites Profile of Extracts and Fractions of Erythroxylum mexicanum Kunth by UHPLC-QTOF-MS/MS and its Antibacterial, Cytotoxic and Nitric Oxide Inhibitory Activities.

The present study shows the untargeted metabolite profiling and in vitro antibacterial, cytotoxic, and nitric oxide (NO) inhibitory activities of the methanolic leaves extract (MLE) and methanolic stem extract (MSE) of Erythroxylum mexicanum, as well as the fractions from MSE. Using ultra-high performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS), a total of 70 metabolites were identified; mainly alkaloids in the MLE, while the MSE showed a high abundance of diterpenoids. The MSE fractions exhibited differential activity against Gram-positive bacteria. Notably, the hexane fraction (HSF) against Streptococcus pyogenes ATCC 19615 (MIC=62.5 µg/mL) exhibited a bactericidal effect. The MSE fractions exhibited cytotoxicity against all cancer cell lines tested, with selectivity towards them compared to a noncancerous cell line. Particularly, the HSF and chloroform fraction (CSF) showed the highest cytotoxicity against prostate cancer (PC-3) cells, with IC50 values of 19.9 and 18.1 µg/mL and selectivity indexes of 3.8 and 4.2, respectively. Both the HSF and ethyl acetate (EASF) fractions of the MSE inhibited NO production in RAW 264.7 macrophages, with NO production percentages of 50.0 % and 51.7 %, respectively, at a concentration of 30 µg/mL. These results indicated that E. mexicanum can be a source of antibacterial, cytotoxic, and anti-inflammatory metabolites.

Metabolomic Profile and Cytotoxic Activity of Cissus incisa Leaves Extracts.

Cissus incisa leaves have been traditionally used in Mexican traditional medicine to treat certain cancerous illness. This study explored the metabolomic profile of this species using untargeted technique. Likewise, it determined the cytotoxic activity and interpreted all data by computational tools. The metabolomic profile was developed through UHPLC-QTOF-MS/MS for dereplication purposes. MetaboAnalyst database was used in metabolic pathway analysis and the network topological analysis. Hexane, chloroform/methanol, and aqueous extracts were evaluated on HepG2, Hep3B, HeLa, PC3, A549, and MCF7 cancer cell lines and IHH immortalized hepatic cells, using Cell Titer proliferation assay kit. Hexane extract was the most active against Hep3B (IC50 = 27 ± 3 µg/mL), while CHCl3/MeOH extract was the most selective (SI = 2.77) on the same cell line. A Principal Component Analysis (PCA) showed similar profiles between the extracts, while a Venn diagram revealed 80 coincident metabolites between the bioactive extracts. The sesquiterpenoid and triterpenoid biosynthesis pathway was the most significant identified. The Network Pharmacology (NP) approach revealed several targets for presqualene diphosphate, phytol, stearic acid, δ-tocopherol, ursolic acid and γ-linolenic acid, involved in cellular processes such as apoptosis. This work highlights the integration of untargeted metabolomic profile and cytotoxic activity to explore plant extracts, and the NP approach to interpreting the experimental results.

Metabolic Profile and Evaluation of Biological Activities of Extracts from the Stems of Cissus trifoliata.

Cissus trifoliata (L.) L belongs to the Vitaceae family and is an important medicinal plant used in Mexico for the management of infectious diseases and tumors. The present study aimed to evaluate the metabolic profile of the stems of C. trifoliata and to correlate the results with their antibacterial and cytotoxic activities. The hexane extract was analyzed using gas chromatography coupled with mass spectrometry (GC-MS) and the CHCl3-MeOH and aqueous extracts by ultraperformance liquid chromatography quadrupole time of fly mass spectrometry (UPLC-QTOF-MS). The antibacterial activity was determined by broth microdilution and the cytotoxicity was evaluated using MTS cell proliferation assay. Forty-six metabolites were putatively identified from the three extracts. Overall, terpenes, flavonoids and stilbenes characterize the metabolic profile. No antibacterial activity was found in any extract against the fifteen bacteria strains tested (MIC >500 µg/mL). However, high cytotoxic activity (IC50 ≤ 30 µg/mL) was found in the hexane and aqueous extracts against hepatocarcinoma and breast cancer cells (Hep3B, HepG2 and MCF7). This is the first report of the bioactive compounds of C. trifoliata stems and their antibacterial and cytotoxic properties. The metabolic profile rich in anticancer compounds correlate with the cytotoxic activity of the extracts from the stems of C. trifoliata. This study shows the antitumor effects of this plant used in the traditional medicine and justifies further research of its anticancer activity.

Chemical composition of Helietta parvifolia and its in vitro anticholinesterase activity.

The chemical composition of the essential oil and the n-hexane (Hex), Ethyl Acetate (EtOAc) and butanol (BuOH) extracts from the leaves of Helietta parvifolia were determined by detailed GC-MS analysis, spectroscopic and spectrometric data. Eighty-four compounds were identified, revealing a furoquinoline alkaloid-rich composition. The phytochemical analysis of the extracts allowed the isolation of eigth furoquinoline alkaloids. Retention indices in GC-MS for six of this alkaloids are reported for the first time. Furoquinoline alkaloids are acethylcholinesterase inhibitors. Thus, the essential oil and extracts were submitted to this in vitro assay. The EtOAc and BuOH extracts showed potent activity, with IC50 of 9.7 and 12.9 µg mL-1, respectively. Additionaly, a correlation of their chemical constituents, established by principal component analysis (PCA) demostrated a similar profile and a high content of alkaloids. It is for these reasons that we can assume that the alkaloid content in these extracts could be responsible for their anticholinesterase activity.

In vitro COX-1 and COX-2 enzyme inhibitory activities of iridoids from Penstemon barbatus, Castilleja tenuiflora, Cresentia alata and Vitex mollis.

A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (36.0 ± 0.6%) and COX-2 (80.8 ± 4.0%) inhibition at 10 µM. Compound 10 shows a better inhibition against the COX-2 enzyme. Other iridoids tested in the present study showed weak or no inhibition against these enzymes. Furthermore, herein are presented key interactions of iridoid 10 with COX-1 and COX-2 enzymes through molecular docking studies. These studies suggest that 10 exhibits anti-inflammatory activity due to COX inhibition.

Cycloartanes from Krameria pauciflora and their in vitro PLA2, COX-1, and COX-2 enzyme inhibitory activities.

Krameria pauciflora is a species belonging to the Krameriaceae family. It has been used to treat inflammatory disorders in folkloric Mexican medicine; however, chemistry and pharmacological studies have not been carried out on this species. In this work, from the dichloromethane root extract of K. pauciflora, five cycloartane-type triterpenoids were isolated: cyclomargenyl-3-O-ß-caffeoyl ester (1), cyclomargenyl-3-O-ß-feruloyl ester (2), cyclomargenyl-3-O-ß-coumaroyl ester (3), cyclomargenol (4, polysthicol), and cyclomargenone (5). Additionally, the lignane 6'-methoxyrataniaphenol was isolated. To the best of our knowledge, compounds 1-3 are new natural products, whereas compounds 4 and 5 are isolated for the first time in the Krameria genus and the Krameriaceae family. The structures of all of these compounds were established by 1D and 2D NMR spectroscopy including ¹H, ¹³C, DEPT, COSY, HSQC, and HMBC experiments, as well as by EI mass spectrometry. There is an incomplete previous report about the spectroscopic data of compounds 4 and 5. However, in this work, a complete and unambiguous assignation has been realized. Due to the traditional use of this plant and other species from this genus, such as K. lappacea, cycloartanes isolated herein were evaluated by their inhibition of phospholipase A2, cyclooxygenase-1, and cyclooxygenase-2 enzymes. Cyclomargenyl-3-O-ß-caffeoyl ester (1) showed inhibition of phospholipase A2, cyclooxygenase-1, and cyclooxygenase-2 target enzymes for nonsteroidal anti-inflammatory drugs. Both cyclooxygenases were inhibited by cyclomargenol (4); however, cyclomargenyl-3-O-ß-feruloyl ester (2) showed inhibition only on cyclooxygenase-1.

Complete NMR assignment of 3, 4-seco-lup-20(29)-en-3-oic acid from Decatropis bicolor.

Complete (1) H and (13) C NMR chemical shift assignments for 3,4-seco-lup-20(29)-en-3-oic acid (1) have been established by means of two-dimensional COSY, HSQC, HMBC and NOESY spectroscopic experiments as well as by analysis of MS data. Compound 1 was isolated from Decatropis bicolor (Zucc.) Radlk. (Rutaceae) in addition to six coumarins and one alkaloid of known structure.

Phytochemical study and anti-inflammatory, antidiabetic and free radical scavenger evaluations of Krameria pauciflora methanol extract.

The plant Krameria pauciflora MOC et. Sessé ex DC. is used as an anti-inflammatory and antidiabetic in traditional medicine. The aim of this study was to evaluate the in vivo anti-inflammatory and antidiabetic effects of a methanol extract from the roots of K. pauciflora. Dichloromethane and ethyl acetate extracts obtained by partitioning the methanol extract were also evaluated. Complete methanol and dichloromethane extracts showed anti-inflammatory effects at 3 mg/kg. An anti-inflammatory effect similar to indomethacin (10 mg/kg) was observed when the methanol and dichloromethane extracts, which contain a cycloartane-type triterpene and an sterol, were administered orally at several doses (3, 10, 30 and 100 mg/kg), whereas no anti-inflammatory effect was observed at any dose for the ethyl acetate extract, which contains catechin-type flavonoids. The antidiabetic effect of each extract was also determined. An antihyperglycaemic effect was observed in diabetic rats, but no effect in normoglycaemic animals was observed when the methanol extract was administrated at 30 mg/kg. All of the extracts exhibited radical scavenger activity. Additionally, constituents from all of the extracts were identified by NMR. This article supports the use of K. pauciflora as an anti-inflammatory because it exhibits a similar effect to indomethacin. However, its antidiabetic effect is not completely clear, although it could be useful for preventing diabetic complications.