Search Results (35)

Bursera bipinnata (DC.) Engl. (B. bipinnata), commonly known as “copal chino,” is a widely distributed Mexican tree found in transitional zones between pine-oak and deciduous forests. It is valued for its high-quality copal resin, traditionally used in ceremonies and offerings. Additionally, B. bipinnata is recognized for its significant value in traditional medicine, particularly in treating ailments associated with inflammation. In this work, the inhibition of nitric oxide (NO) production of the volatile fraction and resin of B. bipinnata in LPS-stimulated RAW 264.7 macrophage cells were demonstrated. In contrast, the volatile fraction exhibited 37.43 ± 7.13% inhibition at a concentration of 40 µg/mL. Chromatographic analyses of the total resin enabled the chemical characterization of eleven pentacyclic triterpenes belonging to the ursane, oleanane, and lupane series, as well as eight monoterpenes. Notably, the structures of compounds 15, 17, and 29–35 are reported for the first time from the resin of Bursera bipinnata. The anti-inflammatory activity observed for B. bipinnata resin in this study may be attributed to its high content of the triterpenes α-amyrin (15, 29.7%) and 3-epilupeol (17, 38.1%), both known for their anti-inflammatory properties. These findings support the traditional use of this copal resin. Full article

A total of 31 compounds were isolated from the ethyl acetate and n-butanol fractions of Anchusa italica Retz., which contained one ursane triterpenoid, 2α,3β,19α-trihydroxy-23-formyl-urs-12-en-28,21β-olide (1), and five norisoprenoids: (2R,6R,9S)-9-hydroxy-4-megastigmen-3-one-2-O-β-D-glucopyranoside (3); (2R,6S,9S)-9-hydroxy-megastigman-4,7-dien-3-one-2-O-β-D-glucopyranoside (4); (+)-isololiolide β-D-glucopyranoside (5); (2S,8R)-loliolide β-D-glucopyranoside (6a); and (2R,8S)-loliolide β-D-glucopyranoside (6b). It also contained 25 known compounds (2 and 7–30). The chemical structures of the compounds, inclusive of their absolute configurations, were ascertained using spectroscopic methods such as NMR, HR-MS, and quantum chemical calculations (computational NMR and ECD), in combination with relevant literature data. Moreover, the chemotaxonomic significance of the isolated substances was discussed, with compounds 1, 2, and 7–13 potentially broadening the application of triterpenes as taxonomic markers for the classification of the genus Anchusa. Full article

Alzheimer’s disease (AD) poses a significant public health issue. Despite the fact that today there are several methods of maintenance therapy, one of the most widely used methods is designed to correct the deficiency of acetylcholine. In the search for new potential inhibitors of cholinesterase enzymes, eight new derivatives of 3-oxo- or 2,3-indolo-triterpenic acid conjugated with amino-quinuclidine bicyclic cores were designed and synthesized. Then, the obtained compounds were screened in Ellman’s assays for their ability to inhibit acetylcholinesterase enzyme, and for each of the active compounds, the type of inhibition was determined. The obtained results demonstrate the dependence of the activity on the triterpenoid structure and the type of substituents. The best activity for ursolic acid derivatives was observed for the 3-oxoamide 8, with an IC₅₀ value of 0.43 µM, acting as a mixed-type inhibitor. In turn, for the oleanane type, the amide with an indole unit in the A ring 11 exhibited the best activity with an IC₅₀ value of 0.47 µM (while the ursane-type analog was weakly active) and led to an uncompetitive type of inhibition. Thus, 3-amidoquinuclidine-triterpenoids conjugates could be considered novel inhibitors of acetylcholinesterase with a different mechanism of action. Full article

Recently, there has been great interest in plant-derived compounds known as phytochemicals. The pentacyclic oleanane-, ursane-, and lupane-type triterpenes are phytochemicals that exert significant activity against diseases like cancer. Lung cancer is the leading cause of cancer-related death worldwide. Although chemotherapy is the treatment of choice for lung cancer, its effectiveness is hampered by the dose-limiting toxic effects and chemoresistance. Herein, we investigated six pentacyclic triterpenes, oleanolic acid, ursolic acid, asiatic acid, betulinic acid, betulin, and lupeol, on NSCLC A549 cells. These triterpenes have several structural variations that can influence the activation/inactivation of key cellular pathways. From our results, we determined that most of these triterpenes induced apoptosis, S-phase and G2/M-phase cycle arrest, the downregulation of ribonucleotide reductase (RR), reactive oxygen species, and caspase 3 activation. For chemoresistance markers, we found that most triterpenes downregulated the expression of MAPK/PI3K, STAT3, and PDL1. In contrast, UrA and AsA also induced DNA damage and autophagy. Then, we theoretically determined other possible molecular targets of these triterpenes using the online database ChEMBL. The results showed that even slight structural changes in these triterpenes can influence the cellular response. This study opens up promising perspectives for further research on the pharmaceutical role of phytochemical triterpenoids. Full article

We chemically linked corosolic and asiatic acids and a synthetic polyoxygenated analogue of ursolic acid via an alkyl linker to the cationic mitochondrial targeting compound F16 (4-(1H-indole-3-ylvinyl)-N-methylpyridinium iodide). The conjugates were tested for cytotoxic activity against two human lung adenocarcinoma cell lines, H1299 and A549, and non-cancerous mouse embryonic fibroblast cells. The results showed that conjugation of polyoxygenated triterpene acids with the terminal cationic fragment F16 in the C-28 side chain enhanced cytotoxicity (30–35 fold) compared to the original natural ursolic acid. However, the presence of hydroxyl or acetyl functions in the A-ring of F16 conjugates of corosolic or asiatic acids resulted in a significant decrease in cytotoxicity compared to their structural analogue, the F16 derivative of ursolic acid. Full article

In a framework aimed at the recovery and enhancement of medicinal plants endemic to the territory of the Cilento and Vallo di Diano National Park, Lavandula austroapennina N.G. Passal., Tundis and Upson has aroused interest. An insight into the chemical composition of the corolla, calyx, leaf, stem, and root organs was carried out following ultrasound-assisted maceration in n-hexane. The obtained lipophilic extracts were explored using ultra-high-performance chromatography coupled to high-resolution mass spectrometry (UHPLC-ESI-QqTOF-MS/MS). The extracts from the different organs varied in their relative content of fatty acids, ursanes, and oleanane-type triterpenes. In particular, the oleanolic acid content appeared to increase in the order of corolla < leaf < stem. An MTT assay was performed to verify the possible cytotoxicity of the organ extracts of L. austroapennina at a concentration ranging from 12.5 to 400 µg/mL on the Vero CCL-81 cell line. Antiviral activity against herpes simplex virus type 1 (HSV-1), alpha human coronavirus 229E (HCoV-229E), and poliovirus type 1 (PV-1) was evaluated via a plaque reduction assay in the same cellular model. All the extracts did not show cytotoxic effects after 2 and 24 h exposure times, and the antiviral efficacy was particularly important for the stem extract, capable of completely inhibiting the tested viruses at low doses. The antiviral activity in a non-enveloped virus PV-1 allowed the assertion that the extracts from the organs of L. austroapennina, and especially the stem extract, interfered directly with the viral envelope. This study underlines how much knowledge of a territory’s medicinal plant heritage is a harbinger of promising discoveries in the health field. Full article

The present work shows the cytotoxic effects of novel conjugates of ursolic, oleanolic, maslinic, and corosolic acids with the penetrating cation F16 on cancer cells (lung adenocarcinoma A549 and H1299, breast cancer cell lines MCF-7 and BT474) and non-tumor human fibroblasts. It has been established that the conjugates have a significantly enhanced toxicity against tumor-derived cells compared to native acids and also demonstrate selectivity to some cancer cells. The toxic effect of the conjugates is shown to be due to ROS hyperproduction in cells, induced by the effect on mitochondria. The conjugates caused dysfunction of isolated rat liver mitochondria and, in particular, a decrease in the efficiency of oxidative phosphorylation, a decrease in the membrane potential, and also an overproduction of ROS by organelles. The paper discusses how the membranotropic- and mitochondria-targeted effects of the conjugates may be related to their toxic effects. Full article

Chinese jujube (Ziziphus jujuba Mill.) and its wild ancestor, sour jujube (Z. acidojujuba C.Y. Cheng & M.J. Liu), is a Ziziphus genus in the Rhamnaceae family. ZJ and ZA are rich in a variety of active ingredients, with triterpenoids being a unique active ingredient, which are present in the fruit, leaves, branches, and roots. More than 120 triterpenoids have been identified in ZJ and ZA, and have various biological activities. For example, betulinic and ursolic acids have anticancer, antioxidant, antibacterial and antiviral activities. ceanothic, alphitolic, and zizyberanalic acids possess anti-inflammatory activities. The MVA pathway is a synthetic pathway for triterpenoids in ZJ and ZA, and 23 genes of the MVA pathway are known to regulate triterpene synthesis in ZJ and ZA. In order to better understand the basic situation of triterpenoids in ZJ and ZA, this paper reviews the types, content dynamic changes, activities, pharmacokinetics, triterpenoid synthesis pathways, and the effects of domestication on triterpenoids in ZJ and ZA, and provides some ideas for the future research of triterpenoids in ZJ and ZA. In addition, there are many types of ZJ and ZA triterpenoids, and most of the studies on their activities are on lupane- and ursane-type triterpenes, while the activities of the ceanothane-type and saponin are less studied and need additional research. Full article

Native Mexican plants are a wide source of bioactive compounds such as pentacyclic triterpenes. Pentacyclic triterpenes biosynthesized through the mevalonate (MVA) and the 2-C-methyl-D-erythritol-phosphate (MEP) metabolic pathways are highlighted by their diverse biological activity. Compounds belonging to the oleanane, ursane, and lupane groups have been identified in about 33 Mexican plants, located geographically in the southwest of Mexico. The works addressing these findings have reported 45 compounds that mainly show antimicrobial activity, followed by anti-inflammatory, cytotoxic, anxiolytic, hypoglycemic, and growth-stimulating or allelopathic activities. Extraction by maceration and Soxhlet with organic solvents and consecutive chromatography of silica gel have been used for their whole or partial purification. Nanoparticles and nanoemulsions are the vehicles used in Mexican formulations for drug delivery of the pentacyclic triterpenes until now. Sustainable extraction, formulation, regulation, isolation, characterization, and bioassay facilities are areas of opportunity in pentacyclic triterpenes research in Mexico while the presence of plant and human resources and traditional knowledge are strengths. The present review discusses the generalities of the pentacyclic triterpene (definition, biogenic classification, and biosynthesis), a summary of the last two decades of research on the compounds identified and their evaluated bioactivity, the generalities about the extraction and purification methods used, drug delivery aspects, and a critical analysis of the advantages and limitations of research carried out in this way. Full article

The Celastraceae family comprises about 96 genera and more than 1.350 species, occurring mainly in tropical and subtropical regions of the world. The species of this family stand out as important plant sources of triterpenes, both in terms of abundance and structural diversity. Triterpenoids found in Celastraceae species display mainly lupane, ursane, oleanane, and friedelane skeletons, exhibiting a wide range of biological activities such as antiviral, antimicrobial, analgesic, anti-inflammatory, and cytotoxic against various tumor cell lines. This review aimed to document all triterpenes isolated from different botanical parts of species of the Celastraceae family covering 2001 to 2021. Furthermore, a compilation of their ¹³C-NMR data was carried out to help characterize compounds in future investigations. A total of 504 pentacyclic triterpenes were compiled and distinguished as 29 aromatic, 50 dimers, 103 friedelanes, 89 lupanes, 102 oleananes, 22 quinonemethides, 88 ursanes and 21 classified as others. Full article

The phytochemical constituents from the roots of Millettia speciosa were investigated by chromatographic isolation, and their chemical structures were characterized using the MS and NMR spectroscopic methods. A total of 10 compounds, including six triterpenoids, two flavonoids, and two phenolic compounds, were identified from the roots of M. speciosa. Out of the isolated compounds, eight showed inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, with IC₅₀ values ranging from 43.9 to 449.5 µg/mL. Ursane-type triterpenes significantly suppressed NO production compared to the remaining compounds. In addition, these compounds also exhibited remarkable inhibitory effects on α-glucosidase. Among the tested compounds, 4, 5, and 10 exhibited excellent α-glucosidase inhibition, with IC₅₀ values ranging from 1.1 to 2.2 µg/mL. Almost all of the test compounds showed little or no acetylcholinesterase inhibition, except for 5, which showed moderate anti-acetylcholinesterase activity in vitro. The molecular docking study of α-glucosidase inhibition by 3–5 and 10 was conducted to observe the interactions of these molecules with the enzyme. Compounds 4, 5, and 10 exhibited a better binding affinity toward the targeted receptor and the H-bond interactions located at the entrance of the enzyme active site pocket in comparison to those of 3 and the positive control acarbose. Our findings evidence the pharmacological potential of this species and suggest that the phytochemicals derived from the roots of M. speciosa may be promising lead molecules for further studies on the development of anti-inflammatory and anti-diabetes drugs. Full article

The triterpenes in bitter gourd (Momordica charantia) show a variety of medicinal activities. Oxidosqualene cyclase (OSC) plays an indispensable role in the formation of triterpene skeletons during triterpene biosynthesis. In this study, we identified nine genes encoding OSCs from bitter gourd (McOSC1–9). Analyses of their expression patterns in different tissues suggested that characteristic triterpenoids may be biosynthesized in different tissues and then transported. We constructed a hairy root system in which McOSC7 overexpression led to an increased accumulation of camaldulenic acid, enoxolone, and quinovic acid. Thus, the overexpression of McOSC7 increased the active components content in bitter gourd. Our data provide an important foundation for understanding the roles of McOSCs in triterpenoid synthesis. Full article

Maesa membranacea A. DC. (Primulaceae) is a plant species that has been frequently used by practitioners of the traditional ethnobotany knowledge from northern and central Vietnam. However, the chemical constituents of the plant remained unknown until recently. Chromatographic separation of a chloroform-soluble fraction of extract from leaves of M. membranacea led to the isolation of two new polyesterified ursane triterpenes (1–2) and two known apocarotenoids: (+)-dehydrovomifoliol (3) and (+)-vomifoliol (4). The chemical structures of the undescribed triterpenoids were elucidated using 1D and 2D MNR and HRESIMS spectral data as 2α,6β,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20β-diol (1) and 2α,6β,22α-triacetoxy-urs-12-ene-3α,11α,20β-triol (2). The newly isolated triterpenoids were tested for their cytotoxic activity in vitro against two melanoma cell lines (HTB140 and A375), normal skin keratinocytes (HaCaT), two colon cancer cell lines (HT29 and Caco-2), two prostate cancer cell lines (DU145 and PC3) and normal prostate epithelial cells (PNT-2). Doxorubicin was used as a reference cytostatic drug. The 2α,6β,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20β-diol demonstrated cytotoxic activity against prostate cancer cell lines (Du145—IC₅₀ = 35.8 µg/mL, PC3—IC₅₀ = 41.6 µg/mL), and at a concentration of 100 µg/mL reduced viability of normal prostate epithelium (PNT-2) cells by 41%. Full article

Globimetula braunii is a hemi-parasitic plant used in African ethnomedicine for the management of microbial infections, rheumatic pain and tumors amongst others. We report the isolation and characterization of eight compounds with their antioxidant and antimicrobial activities. The air-dried powdered leaf was macerated in EtOH/H₂0 (4:1). The extract was solvent-partitioned into n-hexane, EtOAc, n-BuOH and aqueous fractions. The fractions were screened for their antioxidant properties, using DPPH, FRAP, TAC and FIC assays. Antimicrobial analysis was performed using the micro-broth dilution method. The active EtOAc fraction was purified for its putative compounds on a repeated silica gel column chromatography monitored with TLC-bioautography. The isolated compounds were characterized using spectroscopic methods of UV, FT-IR, NMR and MS. Eight compounds (1–8) were isolated and characterized as 13,27-cycloursane (1), phyllanthone (2), globraunone (3), three phenolics: methyl 3,5-dihydroxy-4-methoxybenzoate (4), methyl 3-methyl-4-hydroxybenzoate (5) and guaiacol (6), as well as two phenol derivatives: 4-formaldehyde phenone (7) and 6-methoxy-2H-inden-5-ol (8). The study identified 4 and 6 as natural antioxidant compounds with potential as antimicrobial agents. Full article

Cancer persists as a global challenge due to the extent to which conventional anticancer therapies pose high risks counterbalanced with their therapeutic benefit. Naturally occurring substances stand as an important safer alternative source for anticancer drug development. In the current study, a series of modified lupane and ursane derivatives was subjected to in vitro screening on the NCI-60 cancer cell line panel. Compounds 6 and 7 have been identified as highly active with GI₅₀ values ranging from 0.03 µM to 5.9 µM (compound 6) and 0.18–1.53 µM (compound 7). Thus, these two compounds were further assessed in detail in order to identify a possible antiproliferative mechanism of action. DAPI (4′,6-diamidino-2-phenylindole) staining revealed that both compounds induced nuclei condensation and overall cell morphological changes consistent with apoptotic cell death. rtPCR analysis showed that both compounds induced upregulation of proapoptotic Bak and Bad genes while downregulating Bcl-XL and Bcl-2 antiapoptotic genes. Molecular docking analysis revealed that both compounds exhibited high scores for Bcl-XL inhibition, while compound 7 showed higher in silico Bcl-XL inhibition potential as compared to the native inhibitor ATB-737, suggesting that compounds may induce apoptotic cell death through targeted antiapoptotic protein inhibition, as well. Full article