Pentacyclic Triterpenoids Isolated from Celastraceae: A Focus in the 13C-NMR Data.

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.

Chemodiversity of Essential Oils from Nine Species of Celastraceae.

Extracts and compounds obtained from several species of Celastraceae family are reported as potential sources of drugs due to their diverse pharmacological properties. Nevertheless, essential oil composition from these species is still little known. This work aimed at the analysis of essential oils obtained from different Brazilian Celastraceae species. A total of seventeen oils were obtained using hydrodistillation process and analyzed by gas chromatography/mass spectrometry (GC/MS). Principal component analysis (PCA) allowed the identification of a chemical composition pattern among the analyzed essential oils. Some compounds were more frequent among Celastraceae species, such as cis- and trans-linalool oxide (14/17 oil samples), nerylacetone (13/17), linalool (11/17), ß-ionone (10/17), α-ionone (9/17), nerolidol (10/17), decanal (10/17), and dodecanoic acid (10/17). These results contribute to the chemophenetics of Celastraceae species.

Cytotoxic Activity of Triterpenoids from Cheiloclinium cognatum Branches against Chronic and Acute Leukemia Cell Lines.

Cheiloclinium cognatum (Miers) A.C.Sm. is an endemic species of Brazilian Cerrado that belongs to Celastraceae family. The phytochemical study of C. cognatum branches led to the identification of ten triterpenoids (TPs), 3ß-acyloxyurs-12-ene (1), friedelin (2), ß-friedelinol (3), glut-5-en-3ß-ol (4), α-amyrin (5), ß-amyrin (6), ß-sitosterol (7), canophyllol (8), 29-hydroxyfriedelan-3-one (9) and friedelane-3ß,29-diol (10). TPs 4, 5 and 6 are described for the first Cheiloclinium genus and TPs 8 and 9 were isolated in expressive amounts. Their cytotoxic activities were evaluated against THP-1 and K562 leukemia cell lines. TPs 3 and 5 were the most active, exhibiting lower or similar IC50 against both cell lines when compared to the controls. Their mechanisms of action were investigated suggesting an intrinsic mitochondrial pathway of apoptosis evidenced by up-regulation of BAK mRNA expression. Chemometric studies indicated that their activities may be related to their molecular size and shape as well as electronic interactions of C-3 hydroxy group with molecular targets.

Using UHPLC-MS Profiling for the Discovery of New Dihydro-ß-Agarofurans from Australian Celastraceae Plant Extracts.

An analytical method using UHPLC-MS was developed and applied to 16 crude CH2Cl2 extracts from Australian Celastraceae plants; the endemic plant materials were accessed from Griffith University's NatureBank resource and included bark, fruit, leaf, root, twig and mixed samples, all of which were collected from Queensland, Australia. The generated UHPLC-MS data were analysed and dereplicated using the scientific databases Dictionary of Natural Products and SciFinder Scholar in order to potentially identify new dihydro-ß-agarofurans from local Celastraceae plants. These investigations led to the large-scale extraction and isolation work on a prioritised fruit sample that belonged to the rainforest plant Denhamia celastroides. Chemical investigations resulted in the purification of four new natural products, denhaminols O⁻R (1⁻4), along with the related and known compound, denhaminol G (5). The structures of all the new compounds were determined via detailed analysis of NMR and MS data.

Evaluation of the effects of extracts of Maytenus imbricata (Celastraceae) on the treatment of inflammatory and metabolic dysfunction induced by high-refined carbohydrate diet.

The Maytenus genus is a member of the Celastraceae family. Numerous medicinal uses were assigned to species of this genus, with the use of roots, bark, and leaves for the treatment of gastric ulcers, as anti-inflammatory, analgesic, antiallergic, antitumor, among others. Several studies have demonstrated that natural products derived from plants have an important role in the prevention and treatment of obesity. Accordingly, we evaluated the effect of Maytenus imbricata extracts in the treatment of obesity induced by diet rich in refined carbohydrate (HC). BALB/c mice were fed chow or HC diet for 8 weeks. At the beginning of the 9th week, the HC group was subdivided into three groups: (i) group of animals that continued to consume only HC diet; (ii) the group of animals fed HC diet supplemented with ethyl acetate extract of M. imbricata roots (HC + EAE); (iii) the group of animals fed HC diet supplemented with extract in hexane/ethyl ether (HC + HEE). The period of extracts supplementation was 4 weeks. It was observed that EAE and EHE when added to the HC diet modulated the metabolic and inflammatory changes, such as: reduced the adipocytes area, improved glucose intolerance, reduced the levels of triglycerides and resistin in serum, and the number of total leukocytes in blood. In the epididymal adipose tissue, the extracts reduced proinflammatory mediators' concentration. According to the results, it was concluded that the species Maytenus imbricata has the potential to be used for the treatment of obesity.

Repression of Acetaminophen-Induced Hepatotoxicity in HepG2 Cells by Polyphenolic Compounds from Lauridia tetragona (L.f.) R.H. Archer.

Lauridia tetragona (L.f) R.H. Archer is routinely used in traditional medicine; however, its hepatoprotective property is yet to be scientifically proven. To this effect, the hepatoprotective activity of the polyphenolic-rich fractions (PPRFs) was investigated against acetaminophen (APAP) injured HepG2 cells. The ability of the PPRF to scavenge free radicals was tested against 2,2-diphenyl-1-picrylhydrazyl (DPPH), and [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonicacid)] (ABTS). The ferric ion reducing power (FRAP) was also evaluated as a cell-free antioxidant assay. The hepatoprotective activity was then investigated by observing the effect of PPRFs against APAP-induced reduction in cell viability of HepG2 cells. The concentrations of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and lactate dehydrogenase (LDH) released into the medium were evaluated while the underlying mechanism was further explored through western blot analysis. Thereafter, the isolated PPRFs were identified using UHPLC-QToF-MS. All six fractions of the PPRFs isolated showed significant antioxidant properties that were evident by the effective scavenging of DPPH, ABTS, and higher FRAP. The results indicated that PPRF pretreatments ameliorated APAP-induced hepatocellular injury by significantly inhibiting the leakage of AST, ALT, and LDH into the medium. The most active fractions for hepatoprotection were PPRF4 and PPRF6 with IC50 of 50.243 ± 8.03 and 154.59 ± 1.9 µg/mL, respectively. PPRFs markedly increased activities of liver superoxide dismutase, total antioxidant capacity, and liver glutathione concentration. Both PPRF4 and PPRF6 significantly increased the expression of Nrf2 and translocation. The LC-MS analysis revealed the presence of a wide variety of polyphenolics such as coumarin, ferulic acid, and caffeine among the dominant constituents. In conclusion, this study demonstrates that the isolated PPRFs have potential hepatoprotective activity that may be due to the increased expression of antioxidative genes dependent on Nrf2.

The reluctant visitor: a terpenoid in toxic nectar can reduce olfactory learning and memory in Asian honey bees.

The nectar of the thunder god vine, Tripterygium hypoglaucum, contains a terpenoid, triptolide (TRP), that may be toxic to the sympatric Asian honey bee, Apis cerana, because honey produced from this nectar is toxic to bees. However, these bees will forage on, recruit for, and pollinate this plant during a seasonal dearth of preferred food sources. Olfactory learning plays a key role in forager constancy and pollination, and we therefore tested the effects of acute and chronic TRP feeding on forager olfactory learning, using proboscis extension reflex conditioning. At concentrations of 0.5-10 µg TRP ml-1, there were no learning effects of acute exposure. However, memory retention (1 h after the last learning trial) significantly decreased by 56% following acute consumption of 0.5 µg TRP ml-1 Chronic exposure did not alter learning or memory, except at high concentrations (5 and 10 µg TRP ml-1). TRP concentrations in nectar may therefore not significantly harm plant pollination. Surprisingly, TRP slightly increased bee survival, and thus other components in T. hypoglaucum honey may be toxic. Long-term exposure to TRP could have colony effects but these may be ameliorated by the bees' aversion to T. hypoglaucum nectar when other food sources are available and, perhaps, by detoxification mechanisms. The co-evolution of this plant and its reluctant visitor may therefore likely illustrate a classic compromise between the interests of both actors.

New compounds with antimicrobial activities from Elaeodendron buchananii stem bark.

The plant species Elaeodendron buchananii Loes is widely used in folklore medicine to manage microbial infections in Kenya. Previous studies on the plant fruits and root bark revealed the presence of steroids and terpenoids. The present phytochemical analysis of the plant stem bark has led to the isolation of four new triterpenes characterized as methyl 3ß-acetoxy-11α, 19α, 28-trihydroxyurs-12-en-23-oic acid (1), 3ß, 11α, 19α-trihydroxyurs-12-en-23, 28-dioic acid (2), 3ß-acetoxy-19α, 23, 28-trihydroxyurs-12-ene (3) and 3-oxo-19α, 28-dihydroxyurs-12-en-24-oic acid (4), together with ten known ones (5-14), whose structures were elucidated using spectroscopic techniques. The isolate canophyllol (8) showed promising antibacterial activity against N. meningitides with MIC value of 31.25 µg/ml.

Microtropins Q-W, ent-Labdane Glucosides: Microtropiosides G-I, Ursane-Type Triterpene Diglucoside and Flavonol Glycoside from the Leaves of Microtropis japonica.

Microtropins Q-W, (2S,3R)-2-ethyl-2,3-dihydroxybutyrate of various glucosides and glucose, as well as three ent-labdane diterpenoid glucosides, named microtropiosides G, H and I, an ursane-type triterpene diglucoside and a flavonoid glycoside were isolated from the MeOH extract of the leaves of Microtropis japonica. The structure of microtropioside A, also isolated from the branches of M. japonica, was elucidated spectroscopically in a previous experiment and was found to possess a rare seven-membered oxyrane ring. Its structure was confirmed by X-ray crystallographic analysis of its pentaacetate.

Cytotoxic Triterpenoids from the Stalks of Microtropis triflora.

Bioassay-guided phytochemical investigation of the stalks of Microtropis triflora Merr. & F.L. Freeman led to the isolation of ten triterpenes 1 - 10, including one novel compound 3,24-epoxy-2α,24-dihydroxyfriedelan-29-oic acid (1). Their chemical structures were identified on the basis of spectroscopic analysis, including HR-ESI mass spectrometry, 1D- and 2D-NMR (1 H, 13 C, 1 H,1 H-COSY, HSQC, HMBC, and NOESY), and by comparison with the data reported. The cytotoxicities of compounds 1 - 10 against a panel of cultured human tumor cell lines (Bcap37, SMMC7721, HeLa, CNE) were evaluated. The new compound 1 showed moderate anti-tumor activities with IC50 values of 39.22, 29.24, 23.28, and 68.81 µm/ml, respectively. These results might be helpful for explaining the use of M. triflora in traditional medicine. Triterpenes are characteristic of Microtropis genus and could be useful as potential chemotaxonomic markers.

Employing Two-stage Derivatisation and GC-MS to Assay for Cathine and Related Stimulant Alkaloids across the Celastraceae.

INTRODUCTION: Catha edulis (qat, khat, mirra) is a woody plant species that is grown and consumed in East Africa and Yemen for its stimulant alkaloids cathinone, cathine and norephedrine. Two Celastraceae species, in addition to qat, have been noted for their stimulant properties in ethnobotanical literature. Recent phylogenetic reconstructions place four genera in a clade sister to Catha edulis, and these genera are primary candidates to search for cathine and related alkaloids. OBJECTIVE: Determine if cathine or related alkaloids are present in species of Celastraceae other than Catha edulis. METHODS: Leaf samples from 43 Celastraceae species were extracted in water followed by basification of the aqueous extract and partitioning with methyl-t-butyl ether to provide an alkaloid-enriched fraction. The extract was derivatised in a two-stage process and analysed using GC-MS for the presence of cathine. Related alkaloids and other metabolites in this alkaloid-enriched fraction were tentatively identified. RESULTS: Cathinone, cathine and norephedrine were not detected in any of the 43 Celastraceae species assayed other than Catha edulis. However, the phenylalanine- or tyrosine-derived alkaloid phenylethylamine was identified in five species. Nine species were found to be enriched for numerous sterol- and terpene-like compounds. CONCLUSION: These results indicate that cathine is unique to Catha edulis, and not the compound responsible for the stimulant properties reported in related Celastraceae species. Copyright © 2017 John Wiley & Sons, Ltd.

Denhaminols A-H, dihydro-ß-agarofurans from the endemic Australian rainforest plant Denhamia celastroides.

Eight new dihydro-ß-agarofurans, denhaminols A-H (1-8), were isolated from the leaves of the Australian rainforest tree Denhamia celastroides. The chemical structures of 1-8 were elucidated following analysis of 1D/2D NMR and MS data. The absolute configuration of denhaminol A (1) was determined by single-crystal X-ray crystallography. All compounds were evaluated for cytotoxic activity against the human prostate cancer cell line LNCaP, using live-cell imaging and metabolic assays. Denhaminols A (1) and G (7) were also tested for their effects on the lipid content of LNCaP cells. This is the first report of secondary metabolites from D. celastroides.

Isolation, Structural Modification, and HIV Inhibition of Pentacyclic Lupane-Type Triterpenoids from Cassine xylocarpa and Maytenus cuzcoina.

As a part of our investigation into new anti-HIV agents, we report herein the isolation, structure elucidation, and biological activity of six new (1-6) and 20 known (7-26) pentacyclic lupane-type triterpenoids from the stem of Cassine xylocarpa and root bark of Maytenus cuzcoina. Their stereostructures were elucidated on the basis of spectroscopic and spectrometric methods, including 1D and 2D NMR techniques. To gain a more complete understanding of the structural requirements for anti-HIV activity, derivatives 27-48 were prepared by chemical modification of the main secondary metabolites. Sixteen compounds from this series displayed inhibitory effects of human immunodeficiency virus type 1 replication with IC50 values in the micromolar range, highlighting compounds 12, 38, and 42 (IC50 4.08, 4.18, and 1.70 µM, respectively) as the most promising anti-HIV agents.

[Investigation of metabolites of Triptergium wilfordii on liver toxicity by LC-MS].

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.

Cytotoxic diterpenes from roots of Crossopetalum gaumeri, a Celastraceae species from Yucatan Peninsula.

Four new diterpenes, crossogumerins A-D (1-4) along with six known ones (5-10) were isolated from the root bark of Crossopetalum gaumeri, an endemic medicinal plant from the Yucatan Peninsula. Their structures were elucidated on the basis of 1D and 2D NMR techniques, including HMQC, HMBC, and ROESY experiments. Compounds 1-5, 8-10 were evaluated for cytotoxicity against HeLa (carcinoma of the cervix) and Hep-2 (lung carcinoma) human tumor cells lines and against normal Vero cells (African green monkey kidney) in lag and log phase of growth. Podocarpane diterpenes, crossogumerin B (2) and nimbiol (10), exhibited the highest activity against HeLa cells (IC50 values of 3.1 and 8.1 µM, respectively), but also selectivity on Vero cells (SI 22.6 and 7.5, respectively). The preliminary SAR studies suggest that an epoxy moiety in ring B and a hydrogen bond-donor group strategically positioned in the diterpene core are important requirements for cytotoxicity and selectivity.

Anti-staphylococcal, anti-HIV and cytotoxicity studies of four South African medicinal plants and isolation of bioactive compounds from Cassine transvaalensis (Burtt. Davy) codd.

BACKGROUND: Medicinal plants represent an important opportunity to rural communities in Africa, as a source of affordable medicine and as a source of income. Increased patient awareness about safe usage is important as well as more training with regards to traditional medicine. The aim of this study was to evaluate the ethnomedicinal prowess of some indigenous South African plants commonly used in Eastern Cape Province of South Africa for the treatment of skin and respiratory tract infections, HIV and their toxicity potential. METHODS: Cassine transvaalensis, Vangueria infausta, Croton gratissimus and Vitex ferruginea were tested for antibacterial activities against Staphylococcus aureus and Staphylococcus epidermidis using Kirby-Bauer disk diffusion and minimum inhibition concentration (MIC). Cytotoxic and anti-HIV-1 activities of plants were tested using MTT Assay (3- (Dimethylthiozole-2-yl-2,5-diphenyltetrazolium bromide)) and anti- HIV-1iib assay. In search of bioactive lead compounds, Cassine transvaalensis which was found to be the most active plant extract against the two Staphylocoous bacteria was subjected to various chromatographic. Thin layer chromatography, Column chromatography and Nuclear Magnetic Resonance (NMR), (1H-1H, 13C-13C, in DMSO_d6, Bruker 600 MHz) were used to isolate and characterize 3-Oxo-28-hydroxylbetuli-20(29)-ene and 3,28-dihydroxylbetuli-20(29)-ene bioactive compounds from C. transvaalensis. RESULTS: The four plants studied exhibited bioactive properties against the test isolates. The zones of inhibition ranged between 16 mm to 31 mm for multi-drug resistant staphylococci species. MIC values varied between 0.6 and 0.02 µg/ml. C. gratissimus and C. transvaalensis exhibited the abilities to inhibit HIV-1iib. Two bioactive compounds were isolated from C. transvaalensis. CONCLUSION: Data from this study reveals the use of these plant by traditional healers in the Eastern Cape. Furthermore, C. transvaalensis and C. gratissimus were found to be more active as against HIV-1iib. While C. transvaalensis was most active against the two Staphylococcus bacteria.

Structure, histochemistry and phytochemical profile of the bark of the sobol and aerial stem of Tontelea micrantha (Celastraceae - Hippocrateoideae).

The bark of the underground stem of Tontelea micrantha (Mart. ex. Schult.) A. C. Sm., a native Brazilian Cerrado species, is used in folk medicine for treating kidney ailments. The structures of the underground and the aerial stems were examined and their barks were analyzed for the presence of secondary metabolites. Bark fragments were processed according to conventional techniques in plant anatomy and their chemical compositions examined using histochemical and phytochemical tests, thin layer chromatography, and high-efficiency liquid chromatography. The underground stem is a sobol with unusual cambial activity. Laticifers that secrete terpenoids were present in the cortex and phloem of both organs and can contribute to the identification of the species in field. Druses were present in both barks, but mono-crystals were only observed in the sobol. Tannins, flavonoids, alkaloids, and terpenoids occurred in both types of bark, but carotenoids were only detected in the sobol. The similarities between these two organs indicate that the aerial stem bark has potential medicinal use and represents a plausible alternative to harvesting the sobol, which could contribute to the preservation of natural populations of this species.

Microjaponin, a new dihydroagarofuranoid sesquiterpene from the stem of Microtropis japonica with antituberculosis activity.

A new dihydroagarofuran-based sesquiterpene, microjaponin (1), was isolated from the stem of Microtropis japonica. Its structure was determined by in-depth spectroscopic and mass-spectrometric analyses. Microjaponin (1) exhibited potent in vitro antituberculosis activity, with an MIC value of 12.5 µg/ml against Mycobacterium tuberculosis H37 Rv.

New dihydro-ß-agarofuran sesquiterpenes from Parnassia wightiana wall: isolation, identification and cytotoxicity against cancer cells.

Five new (4-8) and three known (1-3) dihydro-ß-agarofuran sesquiterpene polyesters were isolated from the whole plants of Parnassia wightiana. The structures of all compounds were elucidated through spectroscopic analysis including 2D-NMR and HR-MS. The absolute configuration of these compounds was established by X-ray diffraction analysis, comparison of NOESY spectra and biogenetic means. The cytotoxities of compounds 2-8 were evaluated in vitro against HL-60, SMMC-7721, A549, MCF-7 and SW480 cell lines. Compounds 5-7 exhibited the highest activities with IC50 values of 11.8-30.1 µM in most cases. The SAR revealed that the introduction of hydroxyl group was able to significantly improve the activities of the compounds for most of the cell lines.

Anti-inflammatory triterpenoids from the stems of Microtropis fokienensis.

Three new ursane- and four new oleanane- type triterpenoids 1-7 were isolated, along with six known compounds 8-13, from the methanolic extract of Microtropis fokienensis. All structures were elucidated by mass and NMR spectroscopic methods. The isolates 4-10 and known compounds 14-17 that were previously isolated from this material were evaluated for anti-inflammatory activity based on effects against superoxide anion generation and elastase release by neutrophils in response to fMLP/CB. 11α,30-Dihydroxy-2,3-seco-olean-12-en-2,3-dioic anhydride (7) was the first triterpene anhydride from the genus of Microtropis to have the ring A expanded to a seven-membered ring; it showed significant anti-inflammatory activity against superoxide anion generation and elastase release. Unexpectedly, 30-hydroxy-2,3-seco-lup-20(29)-ene-2,3-dioic acid (17) showed the best effect against superoxide anion generation and elastase release with IC50 values of 0.06±0.01 and 1.03±0.35 µg/mL, respectively. Compound 17 had a dioic acid function, and compound 7 had an anhydride function modification in ring A; both showed promising activity in the target assays.