Phytochemical and antimicrobial evaluation of Miconia burchellii Triana (Melastomataceae).

Four novel triterpenoid saponins, 1α,3ß,23-trihydroxy-olean-12-en-28-oic acid 28-O-ß-glycopyranoside ester (1), 1α,3ß,23-trihydroxy-urs-12-en-28-oic acid 28-O-ß-glycopyranoside ester (2), 3-O-ß-galloyl-1α,23-dihydroxy-olean-12-en-28-oic acid 28-O-ß-glycopyranoside ester (3) and 3-O-ß-galloyl-1α,23-dihydroxy-urs-12-en-28-oic acid 28-O-ß-glycopyranoside ester (4) and two new pentacyclic triterpenoids, 3-O-ß-trans-p-coumaroyl-1α-hydroxy-urs-12-en-28-oic acid (5) and 3-O-ß-cis-p-coumaroyl-1α-hydroxy-urs-12-en-28-oic acid (6), together with six known compounds were isolated from the ethanolic extracts of Miconia burchellii leaves and stem bark. Their structures were established by HR-MS, 1D and 2D NMR and comparison with literature data. Additionally, the antimicrobial activity of the leaves and stem bark extracts and fractions was evaluated using the micro broth dilution technique. The crude extract, the ethyl acetate and methanol fractions of the stem bark were the most active against the tested bacteria, showing growth inhibition of both Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa). To the best of our knowledge, this is the first study to report on the antimicrobial activity of M. burchellii.

Antitumour activity of oleanolic acid: A systematic review and meta­analysis.

Oleanolic acid (OA), a compound known for its potent antitumour properties, has been the subject of investigations in both cell and animal models. Although OA has good biological activity, its low water solubility and bioavailability limit its therapeutic use, and therefore translating the potential of OA into the clinical oncology setting remains challenging. The present systematic review and meta-analysis utilized evidence from animal model studies to gain insights into the antitumour mechanisms of OA to address the gap in understanding, and to provide guidance for future research directions and potential clinical applications. The guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses were applied in the present study and a comprehensive search was conducted across the PubMed/MEDLINE, Web of Science, Cochrane Library and Embase databases, with a cut-off date of June 30, 2023. The primary focus was on randomized controlled trials that used animal models to assess the antitumour effects of OA. The methodological quality appraisal was conducted using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool, and tumour volume and weight served as the principal outcome measures. Data were analysed using the RevMan (version 5.3) and Stata SE11 software packages, with an assessment of heterogeneity conducted using the I2 statistical test, sensitivity analysis conducted using the leave-one-out approach, and evaluation of publication bias performed using Egger's test and funnel plot analysis. The present study demonstrated a significant inhibitory effect of OA intervention on tumour growth and a decrease in tumour weight in animal models. Despite the broad spectrum of antitumour effects exhibited by OA, further investigations are warranted to optimize the dosage and administration routes of OA to maximize its efficacy in clinical cancer treatment.

Cytotoxic potential of new caffeoyl triterpenes from the root of Acosmium diffusissimum (Mohlenbr.) Yakovlev: an in vitro and in silico approach.

Two new caffeoyl triterpenes, cis-lupacosmeol (1) alone and in mixture with trans-lupacosmeol (2), and two known compounds, 16ß-hydroxy-3ß-trans-caffeoyl-olean-12-ene (3) and 16ß-hydroxy-3ß-p-coumaroyl-lup-20(29)-ene (4), were isolated from the roots of Acosmium diffusissimum. The structures were chemically characterised using 1D and 2D NMR, IR spectroscopy, and HRESIMS techniques. Cytotoxicity was evaluated against three different cancer cell lines (MCF-7, HCT-116, SK-MEL-28). Only mixture 2 showed activity against all strains tested, with more pronounced ability to inhibit SK-MEL-28 growth (IC50: 25.45 µg/mL). Molecular docking studies suggested that the cytotoxic activity of 2 was strongly attributed to interactions between cis-lupacosmeol and trans-lupacosmeol, which are present in mixtures used to treat melanoma and exhibit activities towards different molecular targets of importance.

Investigating in vitro anticholinergic potential (anti-AChE and anti-BuChE) of Chaenomeles leaves extracts and its phytochemicals including chlorophylls, carotenoids and minerals.

The goal of this work was to evaluate the chemical constitution and health-promoting potential of 12 varieties of Chaenomeles × superba, speciosa and japonica leaves. Carotenoids, chlorophylls, triterpenes, sugars, polyols and acids were analyzed quantitatively and qualitatively using high pressure liquid chromatography (LC) coupled with mass spectrometry (MS), while the mineral profile was determined using atomic absorption spectroscopy (AAS). Moreover, the in vitro anticholinergic potential (inhibition of acetyl-cholinesterase (AChE) and butyryl-cholinesterase (BuChE)) and antioxidant (ABTS, FRAP, ORAC) capacity were evaluated. For the first time in Chaenomeles genotypes 26 carotenoid derivatives and 22 chlorophyll derivatives were identified. Some varieties contained high amounts of carotenoids and chlorophylls (Ch. × superba 'Colour Trail', 'Nicoline', 'Pink Lady', 'Texas Scarlet'), and triterpenes (Ch. speciosa 'Simonii', 'Rubra', and Ch. × superba 'Colour Trail', 'Nicoline') and showed high ORAC antioxidant (Ch. × superba 'Pink Lady' and Ch. speciosa 'Simonii') and anticholinergic (Ch. speciosa species) activity. The studied leaves also contained sugars (3.1 to 16.5 mg/100 g), organic acids (3.9-8.1 g/100 g), and minerals (Ca, Cu, Fe, K, Mg, Mn, Na, and Zn). In conclusion, Chaenomeles leaves show potential as a new source for the production of nutraceuticals, as well as for medical and/or cosmetic purposes.

Pentacyclic triterpenes as bioactive compounds isolated from Mauritia flexuosa L. f. acting against the Alzheimer's disease.

Alzheimer's disease is a significant concern due to its high prevalence and the limitations of current treatments. In our research, we investigated Mauritia flexuosa, a medicinal plant traditionally used for headaches, to identify active compounds with potential anti-Alzheimer's effects. Three pentacyclic triterpenes were isolated through column chromatography and characterised from the dichloromethane/methanol extract from Mauritia flexuosa (DCMEMf), with (3ß)-3-hydroxy-11-oxours-12-en-28-oic acid (3) showing the highest in vitro activity in the HMC3 and SVG p12 cell lines. Compound 3 inhibited the pharmacological targets NF-κB, PGE2, IDO1, and EGFR with IC50 values of 9.83, 3.86, 1.63 µM, and 49.57 nM, respectively, attributed to a hydroxyl group at the C-3 position of its structure. These findings suggest the potential of these compounds in treating neurological diseases, including headaches, and offer promising prospects for the development of new therapies against Alzheimer's.

Ethnobotanical knowledge and utilization patterns of Burseraceae resins in Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Amid all the Brazilian phytodiversity, in all its shades and shapes, black and white amorphous masses glued to the barks of Burseraceae species stand out as some of the nation's most appreciated plant medicinal resources. Burseraceae resins have been used in all macroregions of Brazil, wherever they occur, for a variety of medicinal purposes. However, despite ongoing interest in them, their cultural and health relevance in the country has been underexamined. AIM OF THE STUDY: This review aimed to illuminate the therapeutic importance and potential of Brazilian Burseraceae by assembling the ethnomedicinal, chemical, and pharmacological data available on its resins used in Brazil. MATERIALS AND METHODS: A search for journal articles documenting local ethnomedicinal uses of Burseraceae resins and reporting chemical and pharmacological data associated with their botanical sources was conducted in ScienceDirect, Google Scholar, and PubMed databases. Books and theses were also appraised for such information. RESULTS: At least 21 Burseraceae taxa, belonging to Protium, Trattinnickia, and Commiphora, are recorded as sources of medicinal resins in Brazil. Protium and Trattinickia yield oleoresins typically rich in mono- and triterpenoids, especially the pentacyclic triterpenoids α- and ß-amyrin. Although Commiphora oleo-gum-resins are expected to differ significantly from Protium and Trattinickia oleoresins by the presence of gum fractions, they often exhibit distinct terpenoid compositional patterns, characterized by a high proportion of sesquiterpenoids and tetracyclic triterpenoids. Burseraceae resins are more frequently cited in the Brazilian ethnomedicinal literature for relieving headaches and healing wounds. Pharmacological evidence corroborates the potential of Burseraceae resins against these and some other conditions and diseases, however, further studies are needed to confirm their efficacy and safety when used topically and through inhalation-the two primary routes of administration explored for them in Brazil. CONCLUSIONS: The present review unearths a consistent, persistent, and cross-cultural pattern of using Burseraceae resins against pain conditions. But to really tap into the Burseraceae's therapeutic potential in Brazil, we first need to address the following gaps: (a) conduct more thorough pharmacological studies, including clinical trials; (b) give more attention to the triterpenoid fraction of Burseraceae oleoresins, not only to essential oils and α- and ß-amyrin; and (c) deepen our understanding of the impact of resin aging on chemical composition.

Cytotoxic activity of callus extract from Vachellia farnesiana (L) Wight & Arn.

The in vitro cultures of Vachellia farnesiana (L) Wight & Arn. have demonstrated cytotoxic activity through callus extract on the HeLa cell line. Explants excised from in vitro-grown seedlings from seeds of two different locations were inoculated on Murashige and Skoog (MS) culture media containing various concentrations of N-6 benzyladenine (BA) or kinetin with 2,4-dichlorophenoxyacetic acid (2,4-D). Optimal efficiency in friable callus induction (100%) was achieved in leaf explants cultured on MS media containing 2.32 µM BA + 13.57 µM 2,4-D. Plant tissues (callus and leaf) were extracted and subjected to quantitative phytochemical analysis, revealing the highest total alkaloid and phenolic content in leaf extracts from Queretaro adult specimens (339.5 ± 20.9 mg atropine equivalents (AE) per g dry extract (DE) and 158.4 ± 12.5 mg gallic acid equivalents (GAE) per g DE, respectively). In contrast, callus cultures exhibited significantly higher total triterpene content (356-381 mg ursolic acid equivalents (UAE) per g DE) compared to leaf extracts (208-243 mg UAE/g DE). Both leaf and callus extracts displayed cytotoxic activity against the HeLa cell line, with a significantly lower half-maximal inhibitory concentration (IC50) for leaf extracts (28-32 µg/mL) compared to callus cultures (43-66 µg/mL), suggesting that alkaloids were primarily responsible for the cytotoxic activity. Furthermore, this study provides valuable insights into the controlled production of bioactive compounds with cytotoxic activity, with callus serving as a rich source.

Acetylation of Oleanolic Acid Dimers as a Method of Synthesis of Powerful Cytotoxic Agents.

Oleanolic acid, a naturally occurring triterpenoid compound, has garnered significant attention in the scientific community due to its diverse pharmacological properties. Continuing our previous work on the synthesis of oleanolic acid dimers (OADs), a simple, economical, and safe acetylation reaction was performed. The newly obtained derivatives (AcOADs, 3a-3n) were purified using two methods. The structures of all acetylated dimers (3a-3n) were determined based on spectral methods (IR, NMR). For all AcOADs (3a-3n), the relationship between the structure and the expected directions of pharmacological activity was determined using a computational method (QSAR computational analysis). All dimers were also tested for their cytotoxic activity on the SKBR-3, SKOV-3, PC-3, and U-87 cancer cell lines. HDF cell line was applied to evaluate the Selectivity Index of the tested compounds. All cytotoxic tests were performed with the application of the MTT assay. Finally, all dimers of oleanolic acid were subjected to DPPH and CUPRAC tests to evaluate their antioxidant activity. The obtained results indicate a very high level of cytotoxic activity (IC50 for most AcOADs below 5.00 µM) and a fairly high level of antioxidant activity (Trolox equivalent in some cases above 0.04 mg/mL).

Olea europaea L. Leaves as a Source of Anti-Glycation Compounds.

High concentrations of advanced glycation end products (AGEs) have been linked to diseases, including diabetic complications. The pathophysiological effects of AGEs are mainly due to oxidative stress and inflammatory processes. Among the proteins most affected by glycation are albumin, the most abundant circulating protein, and collagen, which has a long biological half-life and is abundant in the extracellular matrix. The potential cellular damage caused by AGEs underscores the importance of identifying and developing natural AGE inhibitors. Indeed, despite initial promise, many synthetic inhibitors have been withdrawn from clinical trials due to issues such as cytotoxicity and poor pharmacokinetics. In contrast, natural products have shown significant potential in inhibiting AGE formation. Olea europaea L. leaves, rich in bioactive compounds like oleuropein and triterpenoids, have attracted scientific interest, emphasizing the potential of olive leaf extracts in health applications. This study investigates the anti-glycation properties of two polyphenol-rich extracts (OPA40 and OPA70) and a triterpene-enriched extract (TTP70) from olive leaves. Using in vitro protein glycation methods with bovine serum albumin (BSA)-glucose and gelatin-glucose systems, this study assesses AGE formation inhibition by these extracts through native polyacrylamide gel electrophoresis (N-PAGE) and autofluorescence detection. OPA40 and OPA70 exhibited strong, dose-dependent anti-glycation effects. These effects were corroborated by electrophoresis and further supported by similar results in a gelatin-glucose system. Additionally, TTP70 showed moderate anti-glycation activity, with a synergistic effect of its components. The results support the real possibility of using olive leaf bioproducts in ameliorating diabetic complications, contributing to sustainable bio-economy practices.

Study of Pentacyclic Triterpenes from Lyophilised Aguaje: Anti-Inflammatory and Antioxidant Properties.

Mauritia flexuosa (M. flexuosa), commonly known as Aguaje or Moriche palm, is traditionally recognised in South America for its medicinal properties, particularly for its anti-inflammatory and antioxidant effects. However, the bioactive compounds responsible for these effects have not been thoroughly investigated. This study aims to isolate and characterise pentacyclic triterpenoid compounds from M. flexuosa and to evaluate their therapeutic potential. Using various chromatographic and spectroscopic techniques including Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS), three pentacyclic triterpenoid compounds were successfully isolated. Among them, compound 1 (3,11-dioxours-12-en-28-oic acid) exhibited notable bioactivity, significantly inhibiting the activation of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) (IC50 = 7.39-8.11 µM) and of Nitric Oxide (NO) (IC50 = 4.75-6.59 µM), both of which are key processes in inflammation. Additionally, compound 1 demonstrated potent antioxidant properties by activating the antioxidant enzyme Superoxide Dismutase (SOD) (EC50 = 1.87 µM) and the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) (EC50 = 243-547.59 nM), thus showing its potential in combating oxidative stress. This study is the first to isolate and characterise the three compounds from M. flexuosa, suggesting that compound 1 could be a promising candidate for the development of safer and more effective therapies for inflammatory and oxidative stress-related diseases.

Pharmacological potential of Euphorbia tirucalliL. latex in gastric adenocarcinoma: from an ethnopharmacological perspective into new products.

Products derived from the latex of Euphorbia tirucalli were obtained through hydrolysis and column chromatography, resulting in products rich in triterpenes, ingenol 3-esters (I3E), and other derivatives from hydrolysed latex. These products underwent evaluation for their cytotoxic activity against gastric adenocarcinoma cells (AGS). Triterpene derivatives were synthesised, and the selectivity of each product was assessed. The results were compared with the previously described crude latex. Triterpenes and I3E were analysed in silico for their affinity with the active site of PKCδC1b. The hydrolysed latex (free of I3E) exhibited high cytotoxicity, albeit with reduced selectivity. Triterpenes and acetylated triterpenes were more cytotoxic than I3E, although the latter showed greater selectivity. Euphol benzoates and cinnamates showed no cytotoxicity. I3E demonstrated high affinity for the PKCδC1b. In summary, triterpenes exhibited higher cytotoxicity against AGS cells, while I3E displayed greater selectivity. Hydrolysed latex shows promise as a potential candidate for future gastric cancer treatment.

Getting insights into chemical composition and antiherpetic capability of jujube (Ziziphus jujuba mill.) drupes.

Food plant diversity in bioactive compounds makes them an exploitable resource in the search for effective natural products to prevent or treat viral infections. Therefore, in the framework aimed at studying the antiviral properties of extractive mixtures from fruits (and their waste) grown in the Campania Region (Italy), jujube drupes (Zizyphus jujuba Mill.) were our focus. The drupes were dissected into their peel, pulp and seed parts, each of which was extracted by ultrasound-assisted maceration and further fractionated, thus obtaining, beyond the sugar fraction, a polyphenolic fraction and a lipid fraction. UHPLC-HR MS/MS tools highlighted that the polyphenolic component of the seed was strongly dissimilar from that of the edible parts, being constituted by swertisin and its derivatives. Moreover, the peel mostly accounted for triglycosylated flavonols, whereas the pulp was rich in volatile aromatic glycosides. Among lipids, p-coumaroyl triterpenes mainly characterized the peel. All fractions were screened for their cytotoxicity, and non-toxic concentrations of each extract were tested against herpes simplex virus type 1 (HSV-1) by plaque assays. Molecular tests and Western blot analyses were also carried out. The jujube mixtures, in detail the peel and pulp polyphenolic fractions, and peel lipophilic fraction (the latter enriched mainly in ursane-type triterpenes), showed a marked inhibitory activity against HSV-1 acting in the early stages of viral infection and preventing attachment of the virus to the host cell. The acquired data suggest jujube active mixtures as promising candidates for the prevention and treatment of herpetic lesions.

[Oscillation-static cycle cultivation enhances the synthesis of triterpenes and mycelium activity in Ganoderma lucidum].

Ganoderma lucidum is a precious fungus with both edible and medicinal values and has a long history of medical use. Triterpenes as the main active components endow G. lucidum with anti-tumor, antioxidant, and other pharmacological activities. The present study endeavors to establish a proficient liquid-state fermentation technology for the enhanced production of triterpenes. In view of the limitations inherent in conventional submerged fermentation and oscillation-static two-stage cultivation, this study established an oscillation-static cycle cultivation process and optimized the cultivation conditions by building an artificial neural network model based on genetic algorithms. The cultivation conditions for the high-yield production of triterpenes were optimized as follows: 2.8 days of oscillation, 7.3 days of static cultivation, 0.2 day of oscillation, and 0.3 day of static cultivation. Under these conditions, the content of triterpenes reached 20.82 mg/g. The yield of triterpenes reached 129.09 mg/L, showing a remarkable increase of 324.78% compared with that of the Z10J0 method. Moreover, the established method shortened the cultivation cycle by 10.6 days. The mycelia cultivated under this regimen exhibited commendable anti-tumor and antioxidant activities. This study not only presents an economical liquid-state fermentation approach but also streamlines the fermentation flow, reduces fermentation duration, and effectively ameliorates drawbacks associated with conventional cultivation methods. In addition, this study gives valuable insights into the scaled application of liquid-state fermentation in the high-yield production of triterpenes, which showcases broad prospects.

Exploring the Potential of Oleanolic Acid Dimers-Cytostatic and Antioxidant Activities, Molecular Docking, and ADMETox Profile.

The presented work aimed to explore the potential of oleanolic acid dimers (OADs): their cytostatic and antioxidant activities, molecular docking, pharmacokinetics, and ADMETox profile. The cytostatic properties of oleanolic acid (1) and its 14 synthesised dimers (2a-2n) were evaluated against 10 tumour types and expressed as IC50 values. Molecular docking was performed with the CB-Dock2 server. Antioxidant properties were evaluated with the CUPRAC method. ADMETox properties were evaluated with the ADMETlab Manual (2.0) database. The results indicate that the obtained OADs can be effective cytostatic agents, for which the IC50 not exceeded 10.00 for many tested cancer cell lines. All OADs were much more active against all cell lines than the mother compound (1). All dimers can inhibit the interaction between the 1MP8 protein and cellular proteins with the best results for compounds 2f and 2g with unsaturated bonds within the linker. An additional advantage of the tested OADs was a high level of antioxidant activity, with Trolox equivalent for OADs 2c, 2d, 2g-2j, 2l, and 2m of approximately 0.04 mg/mL, and beneficial pharmacokinetics and ADMETox properties. The differences in the DPPH and CUPRAC assay results obtained for OADs may indicate that these compounds may be effective antioxidants against different radicals.

Antioxidant Extracts from Greek and Spanish Olive Leaves: Antimicrobial, Anticancer and Antiangiogenic Effects.

Olea europaea L. is the most valuable species of the Olea type, and its products offer a wide range of therapeutical uses. The olive tree has been extensively studied for its nourishing qualities, and the "Mediterranean diet", which includes virgin olive oil as a key dietary component, is strongly associated with a reduced risk of cardiovascular disease and various malignancies. Olive leaves, a by-product in the olive harvesting process, are valued as a resource for developing novel phytomedicines. For this purpose, two ethanolic extracts obtained from Olivae folium from Spain (OFS) and Greece (OFG) were investigated. Our findings contribute to a wider characterization of olive leaves. Both extracts displayed important amounts of phenolic compounds and pentacyclic triterpenes, OFG having higher concentrations of both polyphenols, such as oleuropein and lutein, as well as triterpenes, such as oleanolic acid and maslinic acid. The antioxidant capacity is similar for the two extracts, albeit slightly higher for OFG, possibly due to metal polyphenol complexes with antioxidant activity. The extracts elicited an antimicrobial effect at higher doses, especially against Gram-positive bacteria, such as Streptococcus pyogenes. The extract with lower inorganic content and higher content of polyphenols and triterpenic acids induced a strong anti-radical capacity, a selective cytotoxic effect, as well as antimigratory potential on A375 melanoma cells and antiangiogenic potential on the CAM. No irritability and a good tolerability were noted after evaluating the extracts on the in vivo Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Therefore, the present data are suggestive for the possible use of the two types of olive leaf products as high-antioxidant extracts, potentially impacting the healthcare system through their use as antimicrobial agents and as anticancer and anti-invasion treatments for melanoma.

Oleanolic Acid Dimers with Potential Application in Medicine-Design, Synthesis, Physico-Chemical Characteristics, Cytotoxic and Antioxidant Activity.

The present work aimed to obtain a set of oleanolic acid derivatives with a high level of cytotoxic and antioxidant activities and a low level of toxicity by applying an economical method. Oleanolic acid was alkylated with α,ω-dihalogenoalkane/α,ω-dihalogenoalkene to obtain 14 derivatives of dimer structure. All of the newly obtained compounds were subjected to QSAR computational analysis to evaluate the probability of the occurrence of different types of pharmacological activities depending on the structure of the analysed compound. All dimers were tested for cytotoxicity activity and antioxidant potential. The cytotoxicity was tested on the SKBR-3, SKOV-3, PC-3, and U-87 cancer cell lines with the application of the MTT assay. The HDF cell line was applied to evaluate the tested compounds' Selectivity Index. The antioxidant test was performed with a DPPH assay. Almost all triterpene dimers showed a high level of cytotoxic activity towards selected cancer cell lines, with an IC50 value below 10 µM. The synthesised derivatives of oleanolic acid exhibited varying degrees of antioxidant activity, surpassing that of the natural compound in several instances. Employing the DPPH assay, compounds 2a, 2b, and 2f emerged as promising candidates, demonstrating significantly higher Trolox equivalents and highlighting their potential for pharmaceutical and nutraceutical applications. Joining two oleanolic acid residues through their C-17 carboxyl group using α,ω-dihalogenoalkanes/α,ω-dihalogenoalkenes resulted in the synthesis of highly potent cytotoxic agents with favourable SIs and high levels of antioxidant activity.

Isolation of Alpha-Glucosidase Inhibitors from the Panamanian Mangrove Plant Mora oleifera (Triana ex Hemsl.) Ducke.

Panama boasts an expansive mangrove area and stands as one of the most biodiverse countries in America. While mangrove plants have long been utilized in traditional medicine, there are still unstudied species whose potential medicinal applications remain unknown. This study aimed to extract bioactive compounds from Mora oleifera (Triana ex Hemsl.) Ducke, an understudied mangrove species. Through bioassay-guided fractionation of the crude extract, we isolated seven active compounds identified as lupenone (1), lupeol (2), α-amyrin (3), ß-amyrin (4), palmitic acid (5), sitosterol (6), and stigmasterol (7). Compound structures were determined using spectroscopic analyses, including APCI-HR-MS and NMR. Compounds 1-7 displayed concentration-dependent inhibition of the alpha-glucosidase enzyme, with IC50 values of 0.72, 1.05, 2.13, 1.22, 240.20, 18.70, and 163.10 µM, respectively. Their inhibitory activity surpassed acarbose, the positive control (IC50 241.6 µM). Kinetic analysis revealed that all compounds acted as competitive inhibitors. Docking analysis predicted that all triterpenes bonded to the same site as acarbose in human intestinal alpha-glucosidase (PDB: 3TOP). A complementary metabolomic analysis of M. oleifera active fractions revealed the presence of 64 compounds, shedding new light on the plant's chemical composition. These findings suggest that M. oleifera holds promise as a valuable botanical source for developing compounds for managing blood sugar levels in individuals with diabetes.

Ceanothanes Derivatives as Peripheric Anionic Site and Catalytic Active Site Inhibitors of Acetylcholinesterase: Insights for Future Drug Design.

Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system and particularly in the formation of amyloid plaques; therefore, the inhibition of AChE has become one of the most promising strategies for the treatment of AD, particularly concerning AChE inhibitors that interact with the peripheral anionic site (PAS). Ceanothic acid isolated from the Chilean Rhamnaceae plants is an inhibitor of AChE through its interaction with PAS. In this study, six ceanothic acid derivatives were prepared, and all showed inhibitory activity against AChE. The structural modifications were performed starting from ceanothic acid by application of simple synthetic routes: esterification, reduction, and oxidation. AChE activity was determined by the Ellmann method for all compounds. Kinetic studies indicated that its inhibition was competitive and reversible. According to the molecular coupling and displacement studies of the propidium iodide test, the inhibitory effect of compounds would be produced by interaction with the PAS of AChE. In silico predictions of physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of the ceanothane derivatives were performed using the Swiss ADME tool.

Recent advances in the chemistry and biology of oleanolic acid and its derivatives.

The pentacyclic triterpenes represent a significant class of plant bioactives with a variety of structures and a wide array of biological activities. These are biosynthetically produced via the mevalonate pathway although occasionally mixed pathways may also occur to introduce structural divergence. Oleanolic acid is one of the most explored bioactive from this class of compounds and possesses a broad spectrum of pharmacological and biological activities including liver protection, anti-cancer, atherosclerosis, anti-inflammation, antibacterial, anti-HIV, anti-oxidative, anti-diabetic etc. This review provides an overview of the latest research findings, highlighting the versatile medicinal and biological potential of oleanolic and its future prospects.

Inhibition of protein tyrosine phosphatase 1B by serratane triterpenes from Huperzia serrata and their molecular docking study.

During the search for protein tyrosine phosphatase 1B (PTP1B) inhibitory compounds from the natural resources, two new serratane triterpenes, 3-O-dihydro-p-coumaroyltohogenol (1) and 21-O-acetyltohogenol (2), along with four known serratane triterpenes (3-6), were isolated from the whole plant of Huperzia serrata. The chemical structures of compounds 1 and 2 were determined by NMR study, HRMS analysis, and chemical modification. All isolates were evaluated for their PTP1B inhibitory activities. Among the isolates, compounds 1, 3, 5 and 6 exhibit moderate inhibitory activities against PTP1B. Kinetic studies demonstrated that they are competitive inhibitors. Molecular docking studies support these experimental results by showing that compounds 1, 3, 5 and 6 interact with the active site of PTP1B, clarifying the structure-activity relationship. This study suggests that serratane triterpenes from H. serrata have potential as starting skeletons for anti-diabetes or anti-obesity agents.