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This study aimed to investigate the effect of selected compounds from the group of triterpene sapogenins on model phosphatidylcholine membranes. Two types of biological membrane model systems were used in the work, i.e., liposomes (microelectrophoresis method) and spherical bilayers (interfacial tension method). Each model was modified with the tested sapogenin compounds, and the change in their physicochemical and electrical parameters was analyzed. Parameters characterizing the equilibrium in the membrane of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-oleanolic acid (OA) and DPPC-asiatic acid (AA) were determined). Based on the Young-Laplace equation, the interfacial tensions of spherical lipid bilayers were measured. The formation of 1:1 complexes was assumed in the DPPC-OA and DPPC-AA membrane systems, and the parameters characterizing the interactions in the formed complexes were calculated. Microelectrophoresis was used to study the surface charge density of lipid membranes. These values were obtained from electrophoretic mobility data using Smoluchowsky's equation. The influence of pH on the electrolyte solution and the composition of the membranes was investigated. The results indicate that modifying DPPC membranes with selected triterpene sapogenins, both OA and AA, causes changes in the surface charge density and shifts of the isoelectric point. Data presented in this work, obtained through mathematical derivation and confirmed experimentally, are of great importance for interpreting phenomena occurring in lipid membranes. A quantitative description of equilibria between phosphatidylcholine and sapogenins lets us understand the processes on the membrane surface. The equilibria are particularly significant from the standpoint of cell functioning. Phosphatidylcholine-sapogenin interactions modulate a range of physicochemical properties of membranes, and they are important in the course of the multiple processes involving membranes in the living cell (e.g., transport mechanism)., (© 2024. The Author(s).)

The present work focuses on the fabrication of polyvinyl alcohol-chitosan-loaded oleanolic acid-nanofibers (PVA-CS-OLA-NFs) for bacterial infection. The prepared PVA-CS-OLA-NFs were characterized for contact angle, SEM, AFM, XRD, FTIR, and TGA. The solid-state characterization and in vitro performance evaluation of nanofibers reveal consistent interconnection and diameters ranging from 102 ± 9.5 to 386 ± 11.6 nm. The nanofibers have a flat surface topography and exhibit efficient drug entrapment. Moreover, the in vitro release profile of PVA-CS-OLA-NFs was found to be 51.82 ± 1.49 % at 24 h. Furthermore, the hemocompatibility study showed that the developed PVA-CS-OLA-NFs are non-hemolytic to human blood. The PVA-CS-OLA-NFs demonstrate remarkable antibacterial capabilities, as evidenced by their MBC and MIC values, which range from 128 and 32 μg/mL, against the strains of S. aureus. The in-vivo fluorescence optical imaging showed the sustained PVA-CS-OLA-NFs release at the wound site infected with S. aureus for a longer duration of time. Moreover, the PVA-CS-OLA-NFs showed superior wound healing performance against S. aureus infected wounds compared to the marketed formulation. Further, the laser Doppler imaging system improved oxygen saturation, blood supply, and wound healing by providing real-time blood flow and oxygen saturation information., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mastic is a natural resin produced by Pistacia lentiscus L. (Anacardiaceae) with high medicinal value and have been traditionally used as Uighur imported medicine for centuries. In this study, 16 triterpenoids including seven new noroleanane triterpenoids (1-7), along with nine known oleanane triterpenoids (8-16), were isolated from the mastic. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, UV, ESI-HR-MS and NMR spectroscopy) and singlecrystal X-ray diffraction. Compounds 4-7, 11, 14 and 16 showed strong inhibitory NO production in LPS-induced RAW264.7 cells with IC 50 values 7.44-9.76 μM, respectively (positive control dexamethasone, 9.93±1.17 μM). Furthermore, compounds 3 and 12 significantly inhibited the growth of SW480 cells, compound 3 showed the most pronounced inhibitory effect with an IC 50 of 2.30±0.38 μM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The goal of preparative chromatography is to isolate suitable amounts of compound(s) at the required purity in the most cost-effective way. This study analyses the power of High-performance thin-layer chromatography (HPTLC) guided preparative flash chromatography to separate and isolate bioactive compounds from an olive flower extract for their further characterisation via spectroscopy. The structure and purity of isolated bioactive compounds were assessed using Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Flash chromatography of the olive flower extract successfully isolated pure oleanolic and maslinic acids. Moreover, the flash chromatography of the extract allowed isolation and phytochemical analysis of the most lipophilic fraction of the extract, which was found to contain n-eicosane and n-(Z)-eicos-5-ene, that has not been isolated previously with preparative TLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

The rapid emergence of antibiotic resistance and the scarcity of novel antibacterial agents have necessitated an urgent pursuit for the discovery and development of novel antibacterial agents against multidrug-resistant bacteria. This study involved the design and synthesis of series of novel indole-benzosulfonamide oleanolic acid (OA) derivatives, in which the indole and benzosulfonamide pharmacophores were introduced into the OA skeleton semisynthetically. These target OA derivatives show antibacterial activity against Staphylococcus strains in vitro and in vivo. Among them, derivative c17 was the most promising antibacterial agent while compared with the positive control of norfloxacin, especially against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In addition, derivative c17 also showed remarkable efficacy against MRSA-infected murine skin model, leading to a significant reduction of bacterial counts during this in vivo study. Furthermore, some preliminary studies indicated that derivative c17 could effectively inhibit and eradicate the biofilm formation, disrupt the integrity of the bacterial cell membrane. Moreover, derivative c17 showed low hemolytic activity and low toxicity to mammalian cells of NIH 3T3 and HEK 293T. These aforementioned findings strongly support the potential of novel indole-benzosulfonamide OA derivatives as anti-MRSA agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Although a series of studies confirm the bioactivities of hederagenin and its glycosides, their synergistic effects and potential mechanisms are still worthy of further exploration. This work investigated the synergistic cytotoxicity and in vitro antioxidant activity of hederagenin and hederagenin 28-O-β-d-glucopyranoside (28-Glc-hederagenin). Hederagenin and 28-Glc-hederagenin inhibited HeLa cell growth and their combination further strengthened this effect. The combination of hederagenin and 28-Glc-hederagenin significantly increased the rate of apoptotic cells, suggesting the presence of a synergistic effect between the two substances. This combination also enhanced in vitro antioxidant activity compared with individual treatments. A network pharmacology and molecular docking-based approach was performed to explore the underlying mechanisms of hederagenin and 28-Glc-hederagenin against cervical cancer and oxidant damage. This work identified 18 related Kyoto Encyclopedia of Genes and Genome pathways, 202 related biological process terms, 17 related CC terms, and 35 related molecular function terms and then revealed 30 nodes and 196 edges. Subsequently, two highly connected clusters and the top four targets were identified. Molecular docking showed potent binding affinity of hederagenin and 28-Glc-hederagenin toward core targets associated with both cervical cancer and oxidant damage. This work may provide scientific basis for the combined use of hederagenin and its glycosides as dietary supplements., (© 2024 International Union of Biochemistry and Molecular Biology, Inc.)

From the root barks of a Central African tree Millettia dubia De Wild. (Fabaceae), ten previously undescribed oleanane-type glycosides were isolated by various chromatographic protocols. Their structures were elucidated by spectroscopic methods, mainly 2D NMR experiments and mass spectrometry, as mono- and bidesmosidic glycosides of mesembryanthemoidigenic acid, hederagenin and oleanolic acid. The stimulation of the sweet taste receptor TAS1R2/TAS1R3 by these glycosides was evaluated, and structure/activity relationships were proposed. Two of them showed an agonist effect on TAS1R2/TAS1R3., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In connection with our interest in the phytochemical investigation of Elaeocarpus hainanensis Oliv. (Elaeocarpaceae) growing in Vietnam, two new sulphated oleanane triterpenes were obtained herein and structurally identified. Based on the combination of the extensive 1D-, 2D NMR and HR ESI MS spectroscopic data analysis, their chemical structures have been elucidated as 1 α ,3 β -dihydroxy-olean-18-ene 1-sulphate ( 1 ) and 1 α ,3 β -dihydroxy-olean-12-ene 1-sulphate ( 2 ). Notably, compounds 1 and 2 are corroborating the proposition that triterpenoid sulphates serve as chemosystematic markers of the Elaeocarpus genus. Additionally, all these two new compounds 1 and 2 strongly inhibited α -glucosidase in vitro with the respective IC 50 values of 3.81 ± 0.33 µM and 21.27 ± 0.48 µM, which were significantly better than that obtained from positive control, acarbose (IC 50 247.73 ± 11.85 µM).

Oleanolic acid is an active ingredient from natural products with anti-breast cancer activity. However, the poor solubility in water and low bioavailability have limited its effectiveness in clinic. To improve the anticancer activity of oleanolic acid, we synthesized a novel oleanolic quaternary ammonium (QDT), which, driven by electrostatic interactions, was introduced into heparin and coated with chitosan to obtain a QDT/heparin/chitosan nanoaggregate (QDT/HEP/CS NAs). QDT/HEP/CS NAs showed the negative zeta potential (-35.01 ± 4.38 mV), suitable mean particle size (150.45 ± 0.68 nm) with strip shape, and high drug loading (36 %). The coated chitosan had strong anti-leakage characteristics toward QDT under physiological conditions. More importantly, upon sustained release in tumor cells, QDT could significantly decrease the mitochondrial membrane potential and induce apoptosis of breast cancer cells. Further in vivo antitumor study on 4 T1 tumor-bearing mice confirmed the enhanced anticancer efficacy of QDT/HEP/CS NAs via upregulation of caspase-3, caspase-9 and cytochrome C, which was attributed to the high accumulation in tumor via the enhanced permeability and retention effect. Moreover, QDT/HEP/CS NAs significantly enhanced the biosafety and biocompatibility of QDT in vitro and in vivo. Collectively, the development of QDT/HEP/CS NAs with high antitumor activity, favorable biodistribution and good biocompatibility provided a safe, facile and promising strategy to improve the anti-cancer effect of traditional Chinese medicine ingredients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chemotherapy remains one of the most commonly used strategies in cancer treatment but suffers from damages to healthy tissues and organs. How to precisely co-deliver two or more drugs with different mechanisms of action to the tumors for synergistic function is a challenge for chemotherapy. Herein, Oleanolic acid (OA)-conjugated Hyaluronic acid self-assembled nano-micelles loaded with Doxorubicin (DOX) (HSO NPs/DOX) were constructed for CD44 positive cancer targeted codelivery of DOX and OA. HSO NPs/DOX exhibited reduction triggered drug release under high concentration of glutathione, more efficient uptake by 4T1 breast cancer cells than free DOX leading to higher cytotoxicity, pro-apoptotic, and migration inhibitory activities against 4T1 cells. The ex vivo biodistribution experiment demonstrated more HSO NPs/DOX were accumulated in the tumor tissues than free DOX and less in the non-tumor tissues after injections in 4T1 tumor bearing mice. More importantly, synergistic anti-tumor effects of DOX and OA were obtained using HSO NPs/DOX in 4T1 breast tumor-bearing mice and toxicity of DOX to liver and heart were circumvented through regulating the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Silent Information Regulator 1 (Sirt1) expressions. Taken together, HSO NPs/DOX may become a promising codelivery system for chemotherapeutics in cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B-R (2 - 18), along with six previously described analogs (19 - 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC 50 values of 29.65, 23.41, 18.12 and 26.64 μM, respectively, as compared with the positive control (dexamethasone, IC 50 value: 40.35 μM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX-2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Seven new oleanane-type triterpene saponins, lysimaponins A-G, were isolated from aerial parts of Lysimachia laxa Baudo. Their chemical structures have been elucidated by analysis of spectroscopic and chemical methods. All compounds were evaluated for their antibacterial effects against Microcystis aeruginosa, Vibrio parahaemolyticus, V. harveyi, V. vulinificus, V. cholerae, and V. alginolyticus. All compounds showed potent antibacterial activities against the cyanobacteria M. aeruginosa with IC50 values ranging from 14.4 ± 1.2 to 35.3 ± 2.2 µg/mL. Compounds 1, 2, 4-7 inhibited V. parahaemolyticus with MIC values ranging from 64 to 256 µg/mL. The results suggested that saponins from L. laxa could be potential anti-cyanobacteria agents., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Psoriasis is a chronic, recurrent, and inflammatory skin disease. Topical agents, which can avoid the adverse effects of systemic treatment, are the first-choice therapy for patients with mild-to-moderate psoriasis. Hederacoside C (HSC) with anti-inflammatory properties has been used to treat some inflammatory diseases. We speculated that HSC might also be effective for psoriasis treatment. However, topical application of HSC for psoriasis treatment is challenging because of its low water solubility and poor skin permeability. Therefore, it is important to effectively deliver HSC percutaneously using certain biomaterials. Here we constructed a hydroxypropyl-β-cyclodextrin-coated liposome gel formulation for the loading and percutaneously delivering of HSC, referred to as HSC-Lipo@gel. The characterization, stability, release properties, and mechanical or transdermal features of the HSC-Lipo@gel were evaluated. Its therapeutic potential was also demonstrated using mouse models of IMQ-induced psoriasis. We found that HSC-Lipo@gel effectively improved the skin permeability of HSC with the property of good stability and sustained release. Importantly, HSC-Lipo@gel showed higher efficacy than HSC@gel without liposomes in alleviating psoriatic skin lesions. It attenuated epidermal hyperplasia and suppressed expression of IL-17A, TNF-α, IL-6, and IL-23 in lesional skin. Interestingly, HSC-Lipo@gel reduced the expression of CC chemokine ligand 17 (CCL17), but not CCL22, in the skin. Especially, HSC-Lipo@gel inhibited CCL17 expression by skin dendritic cells while increasing regulatory T cells (Tregs) in both skin and draining lymph nodes of psoriatic mice. Administration of CCL17 resulted in severe skin lesions and reduced CD4 + FoxP3 + Tregs in psoriatic mice previously treated with HSC-Lipo@gel. Finally, HSC or HSC-Lipo also suppressed the CCL17 production by dendritic cells in vitro . Therefore, HSC-Lipo@gel alleviated psoriasiform skin inflammation by increasing cutaneous Tregs via downregulation of the expression of CCL17, but not CCL22. Thus, HSC-Lipo@gel may be a stable, highly permeable, and effective system for topical treatment of psoriasis.

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 (IC 50 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)., Competing Interests: The authors declare no conflicts of interest.

Basidiomycetes with a wide variety of skeletons of secondary metabolites can be expected to be the source of new interesting biological compounds. During our research on basidiomycetes, two new C-29 oxygenated oleanane-type triterpenes (1 and 2) and torulosacid (3), a muurolene type sesquiterpenoid with a five-membered ether ring along with nine known compounds (4-12), were isolated from the MeOH extract of the fruiting bodies of Fuscoporia torulosa. The structures of 1-3 were determined by NMR and HREIMS analysis. Further studies on the stereochemistry of 3 were conducted using X-ray crystallographic analysis and comparison of experimental and calculated ECD spectra. In the antimicrobial assay of isolates, 1, 7, and 9 showed growth inhibitory activity against methicillin-resistant Staphylococcus aureus and other gram-positive strains. Isolation of oleanane type triterpenes from fungi including basidiomycetes, is a unique report that could lead to further isolation of new compounds and the discovery of unique biosynthetic enzymes., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

The effective treatment of acute lung injury (ALI) remains a significant challenge. Patients with ALI demonstrate an abundance of proinflammatory mediators in both bronchoalveolar lavage fluid (BALF) and circulating plasma. Bardoxolone methyl (BM) is a semi-synthetic triterpenoid derived from oleanolic acid, a natural product known for its ability to inhibit proinflammatory signaling. GSDMD is a signaling protein involved in pyroptosis, a form of programmed cell death. It has been reported that its upstream proteins play a role in the pathogenesis of ALI. However, there is currently no research examining whether the effect of BM on the occurrence and development of ALI is associated with changes in GSDMD protein. In this study, we prepared nanostructured lipid carriers loaded with BM and conjugated with anti-PECAM-1 antibody (PECAM@BM NLCs). PECAM@BM NLCs were designed to specifically bind to pulmonary vascular endothelial cells that highly express the PECAM-1 receptors. We also aimed to investigate the protective effects of PECAM@BM NLCs on ALI and elucidate the underlying molecular mechanisms. The results demonstrated that PECAM@BM NLCs accumulated in the lung tissues and significantly alleviated the inflammatory injury of ALI. This was evidenced by the changes in the lung wet/dry ratio, the total protein concentration, proinflammatory cytokines in BALF, and the histopathological progress. Additionally, we elucidated that PECAM@BM NLCs had the ability to inhibit the assembly of NLRP3 inflammasome and pro-caspase-1 complex, thereby suppressing the induction of pyroptosis. This mechanism resulted in the inhibition of N-terminal GSDMD expression and effectively prevented the progression of ALI., Competing Interests: Declaration of Competing Interest We state explicitly that no potential competing interests exist., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Pentacyclic triterpenes have attracted much attention because of their many bioactivities, but their bioaccessibility is low. Oleanolic acid (OA) was used in this study as a typical edible pentacyclic triterpene. In this work, we proposed an OA interfacial delivery model based on W/O Pickering emulsion, and investigated the effects of different oil types on the emulsion properties and OA bioaccessibility of the OA W/O Pickering emulsion interfacial delivery system (EIDS). Medium chain triglyceride (MCT), long chain triglycerides (LCT) and MCT/LCT (1:1, w/w) were selected as carrier oils for the preparation of emulsions, respectively. The results showed that the emulsions formed from LCT had smaller particle sizes, which increased the deformation resistance of the emulsions and exhibited good stability during the simulated in vitro digestion. The extent of free fatty acid (FFA) release during oil digestion was MCT (103.32 ± 3.74 %) > M/L (97.89 ± 2.89 %) > LCT (71.41 ± 6.64 %). Of interest, the bioaccessibility of OA was influenced by the carrier oil: LCT (59.34 ± 2.55 %) > M/L (47.35 ± 6.25 %) > MCT (13.11 ± 1.40 %) ＞ PBS (7.11 ± 1.74 %), and such a difference was mainly attributed to the greater solubilisation of OA in mixed micelles consisting of long-chain fatty acids. In summary, the size of hydrophobic domains in the mixed micelles produced a greater effect than the effect of FFA release on OA bioaccessibility. This study provides a theoretical basis for the interfacial delivery of OA and the enhancement of OA bioaccessibility based on W/O Pickering emulsions with different oil types., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Four new acylated oleanane-type triterpene saponins, symplosaponins A-D (1-4) were successfully isolated from the leaves of Symplocos cochinchinensis (Lour.) S. Moore, alongside with five known compounds (5-9), 2-methoxy-4-prop-1-enylphenyl-1-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (5), and 1-[O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6), 6-O-p-coumaroylsucrose (7), arillatose B (8), and (-)-secoisolariciresinol-O-β-D-glucopyranoside (9). The structures of these compounds were elucidated through spectroscopic methods, comparison with existing data, and chemical methods. Furthermore, all compounds were assessed for their impact on hepatocellular viability using the Resazurin reduction assay. These investigations aimed to explore the potential hepatoprotective properties of isolated compounds. As a result, 1-[O-β-d-xylopyranosyl-(1 → 6)-O-β-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6) and (-)-secoisolariciresinol-O-β-D-glucopyranoside (9) demonstrated statistically significant hepatoprotective activity in a concentration-dependent manner., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Saikosaponin-a (SSa) exhibits antiepileptic effects. However, its poor water solubility and inability to pass through the blood-brain barrier greatly limit its clinical development and application. In this study, SSa-loaded Methoxy poly (ethylene glycol)-poly(ε-caprolactone) (MePEG-SSa-PCL) NPs were successfully prepared and characterized. Our objective was to further investigate the effect of this composite on acute seizure in mice. First, we confirmed the particle size and surface potential of the composite (51.00 ± 0.25 nm and - 33.77 ± 2.04 mV, respectively). Further, we compared the effects of various MePEG-SSa-PCL doses (low, medium, and high) with those of free SSa, valproic acid (VPA - positive control), and saline only (model group) on acute seizure using three different acute epilepsy mouse models. We observed that compared with the model group, the three MePEG-SSa-PCL treatments showed significantly lowered seizure frequency in mice belonging to the maximum electroconvulsive model group. In the pentylenetetrazol and kainic acid (KA) acute epilepsy models, MePEG-SSa-PCL increased both clonic and convulsion latency periods and shortened convulsion duration more effectively than equivalent SSa-only doses. Furthermore, hematoxylin-eosin and Nissl staining revealed considerably less neuronal damage in the hippocampal CA3 area of KA mice in the SSa, VPA, and three MePEG-SSa-PCL groups relative to mice in the model group. Hippocampal gamma-aminobutyric acid-A (GABA-A) receptor and cleaved caspase-3 expression levels in KA mice were significantly higher and lower, respectively, in the three MePEG-SSa-PCL treatment groups than in the model group. Thus, MePEG-SSa-PCL exhibited a more potent antiepileptic effect than SSa in acute mouse epilepsy models and could alleviate neuronal damage in the hippocampus following epileptic seizures, possibly via GABA-A receptor expression upregulation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Natural terpenoid carriers, such as oleanolic acid (OA), can enhance the water solubility and stability of hydrophobic compounds such as curcumin (Cur). However, improving the colloidal stability of nanoparticle emulsions and resolving the redispersion problem of freeze-dried nanoparticle powders remain significant challenges. In this study, we fabricated coassembled oleanolic acid-curcumin nanoparticles (OA/Cur NPs) and applied a polysaccharide surface coating method to improve their colloidal stability and water solubility. The results showed that the optimal ratio of Cur/OA for preparing OA/Cur NPs was 4:10, resulting in a high encapsulation efficiency (EE) of Cur (75.2%). Additionally, TEM, contact angle tests, Turbiscan TOWER optical stability analysis of the polysaccharide-coated OA/Cur NP emulsions and redispersion tests of their lyophilized powders verified the advantages of carboxymethyl chitosan/β-cyclodextrin (CMC/β-CD) coating over other polysaccharides. This study indicated that polysaccharide coating is an effective method for enhancing the colloidal stability, water solubility, and redispersibility of OA/Cur NPs., Competing Interests: Declaration of competing interest All the authors declare that they have no conflicts of interest related to this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

To identify chemical-markers from hot-pressed, cold-pressed, organic-solvent, aqueous-enzymatic and water extracted camellia oils (HPO, CPO, OSO, AEO, WEO). We report a full composition-wide association study based on GC-MS, LC-MS and 1 HNMR. Squalene, β-amyrin and lupeol were potential-markers in distinguishing different oils through GC-MS. Naringenin, FA 18:1 + 10, undecanedioic acid and tridecanedioic acid exhibited were up-regulated in HPO. 16-Hydroxyhexadecanoic acid, octadecanoic acid and 9-hydroxyoctadecadienoic acid were potential-metabolites in CPO. Characteristic-markers in WEO were hydroquinidine and undecanedioic acid. Gallic acid, hydroquinidine, lichesterylic acid and 7,4'-dihydroxyflavone were biomarkers in AEO. Oleic acid, linoleic acid and triacylglycerols may be potential key markers to distinguish AEO from others via 1 HNMR. Finally, Naringenin, gallic acid, kaempferol, 7,4'-dihydroxyflavone, (Z)-5,8,11-trihydroxyoctadec-9-enoic acid and β-amyrin were screened and validate through integration of nonglyceride minor components and trace metabolites. Results provided understanding of chemical diversity for different processed-camellia oils, and proposed a complementary strategy to distinguish different camellia oils for multidimensional perspective., Competing Interests: Declaration of competing interest The authors declare no conflict of interest in this work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Here we report for the first time the entire 13 C-NMR spectral assignments of 119 (out of 127) triterpenoids from the oleo-gum resins of the medicinally important genus Boswellia, which includes the culturally highly valuable Frankincense species. The complete 13 C-NMR resonances of these triterpenoids isolated between 1998 and 2024 and their biological activities are presented. 13 C-NMR spectroscopy is a highly powerful tool for the characterization of these bioactive natural products. The compounds are arranged according to their skeletons, i.e., ursane, oleanane, lupane, dammarane, and tirucallane triterpenes. This review will be a future reference for the identification of these compounds, which have key medicinal properties in the areas of cytotoxicity and inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Liposomes have demonstrated great potential for drug delivery and diabetes treatment. However, hydrolysis by enzymes and emulsification by endogenous bile salts make liposomes unstable in the gastrointestinal tract. In this study, sodium tauroursodeoxycholate (TUDCNa)-based multifunctional bilosomes were designed to address the deficiencies of conventional liposomes. In the designed bilosomes, cholesterol was replaced by TUDCNa, which served as both a membrane stabilizer and an antidiabetic drug. Oleanolic acid (OA) was encapsulated in both conventional liposomes (OA-Ch-Lip) and bilosomes (OA-Tu-Bil) to compare their properties. Firstly, OA-Tu-Bil exhibited similar encapsulation efficiency and drug loading compared to OA-Ch-Lip, but with a smaller particle size. Secondly, OA-Tu-Bil showed better stability than OA-Ch-Lip. Thirdly, bilosomes exhibited prolonged intestinal retention time and improved permeability and oral bioavailability. Fourthly, in type 2 diabetes mellitus (T2DM) mice model, TUDCNa synergized with OA to exhibit the strongest therapeutic effect. In conclusion, TUDCNa have demonstrated the ability to substitute cholesterol in conventional liposomes, it provided a new approach for oral delivery of hypoglycemic drugs, and offered an innovative strategy for combination therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

As an oleanolic acid derivative, CDDO-Me lacks selectivity for tumors. Based on the high reactive oxygen species (ROS) level in cancer cells, compound 4 was selected from 17 new CDDO arylboronate ester derivatives. A preliminary study revealed that 4 displayed the highest selectivity for cancer cells. Furthermore, 4 could be transformed to 4H by ROS to increase its covalent binding ability and antiproliferation effect (IC 50 of 2.11 vs 0.37 μM) in BGC-823 cells. Interestingly, 4 increased ROS levels to induce apoptosis in BGC-823 cells. Moreover, the LD 50 of 4 (91.2 mg/kg) was much greater than that of CDDO-Me (61.7 mg/kg) in ICR mice. A pharmacokinetic study indicated that 4 could be transformed to 4H in vivo. In addition, 4 exhibited a greater tumor inhibition rate (86.2%) than CDDO-Me (51.7%). Overall, the design of 4 provided an effective modification strategy for CDDO to increase the selectivity for cancer cells.

Saikosaponins (SS), which are major bioactive compounds in Radix Bupleuri, have long been used clinically for multicomponent, multitarget, and multipathway therapeutic strategies. Programmed cell death (PCD) induction is among the multiple mechanisms of SS and mediates the anticancer efficacy of this drug family. Although SS show promise for anticancer therapy, the available data to explain how SS mediate their key anticancer effects through PCD (apoptosis, autophagy, ferroptosis, and pyroptosis) remain limited and piecemeal. This review offers an extensive analysis of the key pathways and mechanisms involved in PCD and explores the importance of SS in cancer. We believe that high-quality clinical trials and a deeper understanding of the pharmacological targets involved in the signalling cascades that govern tumour initiation and progression are needed to facilitate the development of innovative SS-based treatments. Elucidating the specific anticancer pathways activated by SS and further clarifying how comprehensive therapies lead to cross-link among the different types of cell death will inspire the clinical translation of SS as cancer treatments., Competing Interests: All the authors declare that there are no conflicts of interest in this work., (© 2024 Xiao and Gao.)

The study investigated Chenopodium berlandieri to analyze its oleanolic acid (OA) content. Response surface methodology with central composite design was used to improve saponin extraction, varying temperature, ethanol, and sample-to-solvent ratio. Best conditions (65 °C, 50% ethanol, 1:10 ratio) yielded 53.45 ± 0.63 mg/g of extract from Huauzontle seeds. Temperature linearly impacted extract yield, while temperature and ethanol influenced total saponin content. Hydrolyzing saponin-rich extracts produced OA-rich extracts. Characterization via HPLC-ELSD and LC-MS identified OA4 as the most concentrated OA saponin (5.54 ± 0.16 mg/g). OA alone reached 2.02 ± 0.12 mg/g. Acid hydrolysis increased OA content by up to 3.27×, highlighting the potential of hydrolyzed Huauzontle extracts as a natural ingredient for various industries due to enhanced OA content., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Plants from the Amaranthaceae family are a source of oleanolic acid (OA)-type saponins with cytotoxic activity. Two known OA-type saponins, calenduloside E and chikusetsusaponin IVa, were isolated from the roots of Chenopodium strictum Roth. Their structures were confirmed using MS and NMR techniques. This constitutes the inaugural report of the saponins in Ch. strictum . Both the isolated saponins and structurally similar compounds, momordin Ic and OA, were compared for their cytotoxicity against various cancer and normal cell lines (including skin, breast, thyroid, gastrointestinal, and prostate panels). Their effects were dose- and time-dependent, varying with the specific cell line and compound structure. A chemometric approach demonstrated the effects of the compounds on the cell lines. The study discusses the structure-activity observations. The key structural elements for potent cytotoxic activity included the free carboxyl group 28COOH in the sapogenin structure (OA) and the presence of a sugar moiety. The monodesmosides with glucuronic acid (GlcA) at the C3 position of OA were generally more cytotoxic than bidesmosides or OA alone. The addition of xylose in the sugar chain modified the activity towards the cancer cells depending on the specific cell line. OA-type saponins with GlcA (particularly calenduloside E and momordin Ic) represent a promising avenue for further investigation as potential anticancer agents.

Triterpene acids are a class of pentacyclic natural carboxylic compounds endowed with a variety of biological activities including antitumor, antimicrobial, and hepatoprotective effects. In this work, several oleanolic acid derivatives were synthesized by structurally modifying them on the C-3 position. All synthesized derivatives were evaluated for possible antibacterial and antiviral activity, and among all the epimers, 6 and 7 demonstrated the best biological activities. Zone-of-inhibition analyses were conducted against two strains, E. coli as a Gram-negative and S. aureus as a Gram-positive model. Subsequently, experiments were performed using the microdilution method to determine the minimum inhibitory concentration (MIC). The results showed that only the derivative with reduced hydrogen bonding ability on ring A possesses remarkable activity toward E. coli . The conversion from acid to methyl ester implies a loss of activity, probably due to a reduced affinity with the bacterial membrane. Before the antiviral activity, the cytotoxicity of triterpenes was evaluated through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Samples 6 and 7 showed less than 50% cytotoxicity at 0.625 and 1 mg/mL, respectively. The antiviral activity against SARS-CoV-2 and PV-1 did not indicate that triterpene acids had any inhibitory capacity in the sub-toxic concentration range.

The Qingfei Paidu decoction (QFPDD) is a widely acclaimed therapeutic formula employed nationwide for the clinical management of coronavirus disease 2019 (COVID-19). QFPDD exerts a synergistic therapeutic effect, characterized by its multi-component, multi-target, and multi-pathway action. However, the intricate interactions among the ingredients and targets within QFPDD and their systematic effects in multiple tissues remain undetermined. To address this, we qualitatively characterized the chemical components of QFPDD. We integrated multi-tissue transcriptomic analysis with GraphDTA, a deep learning model, to screen for potential compound-target interactions of QFPDD in multiple tissues. We predicted 13 key active compounds, 127 potential targets and 27 pathways associated with QFPDD across six different tissues. Notably, oleanolic acid-AXL exhibited leading affinity in the heart, blood, and liver. Molecular docking and molecular dynamics simulation confirmed their strong binding affinity. The robust interaction between oleanolic acid and the AXL receptor suggests that AXL is a promising target for developing clinical intervention strategies. Through the construction of a multi-tissue compound-target interaction network, our study further elucidated the mechanisms through which QFPDD effectively combats COVID-19 in multiple tissues. Our work also establishes a framework for future investigations into the systemic effects of other Traditional Chinese Medicine (TCM) formulas in disease treatment.

Traditional cancer chemotherapy suffers from low efficacy and severe side effects, limiting its use as a first-line treatment. To address this issue, we investigated a novel way to induce lipid peroxidation (LPO), which plays an essential role in ferroptosis and may be useful against cancer cells and tumors. In this study, a pH-responsive synergistic cancer therapy nanoplatform was prepared using CaCO 3 co-loaded with oleanolic acid (OA) and lipoxygenase (LOX), resulting in the formation OLCaP NP. This nanoplatform exhibited good drug release properties in an acidic tumor environment owing to the presence of CaCO 3 . As a result of acidic stimulation at tumor sites, the OLCaP NP released OA and LOX. OA, a chemotherapeutic drug with anticancer activity, is already known to promote the apoptosis of cancer cells, and LOX is a natural enzyme that catalyzes the oxidation of polyunsaturated fatty acids, leading to the accumulation of lipid peroxides and promoting the apoptosis of cancer cells. More importantly, OA upregulated the expression of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), which promoted enzyme-mediated LPO. Based on our combined chemotherapy and nanocatalytic therapy, the OLCaP NP not only had remarkable antitumor ability but also upregulated ACSL4 expression, allowing further amplification of LPO to inhibit tumor growth. These findings demonstrate the potential of this nanoplatform to enhance the therapeutic efficacy against tumors by inducing oxidative stress and disrupting lipid metabolism, highlighting its clinical potential for improved cancer treatment. STATEMENT OF SIGNIFICANCE: This study presents a novel nanoplatform that combines oleanolic acid (OA), a chemotherapeutic drug, and lipoxygenase (LOX), which oxidizes polyunsaturated fatty acids to trigger apoptosis, for targeted cancer therapy. Unlike traditional treatments, our nanoplatform exhibits pH-responsive drug release, specifically in acidic tumor environments. This innovation enhances the therapeutic effects of OA and LOX, upregulating acyl-CoA synthetase long-chain family member 4 expression and amplifying lipid peroxidation to promote tumor cell apoptosis. Our findings significantly advance the existing literature by demonstrating a synergistic approach that combines chemotherapy and nanocatalytic therapy. The scientific impact of this work lies in its potential to improve cancer treatment efficacy and specificity, offering a promising strategy for clinical applications and future research in cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Bone is one of the most prevalent sites of metastases in various epithelial malignancies, including breast cancer and this metastasis to bone often leads to severe skeletal complications in women due to its osteolytic nature. To address this, we devised a novel drug delivery approach using an Alendronate (ALN) functionalized self-assembled porous crystalsomes for concurrent targeting of Oleanolic acid (OA) and ALN (ALN + OA@NCs) to bone metastasis. Initially, the conjugation of both PEG-OA and OA-PEG-ALN with ALN and OA was achieved, and this conjugation was then self-assembled into porous crystalsomes (ALN + OA@NCs) by nanoemulsion crystallization. The reconstruction of a 3D single particle using transmission electron microscopy ensured the crystalline porous structure of ALN + OA@NCs, was well aligned with characteristic nanoparticle attributes including size distribution, polydispersity, and zeta potential. Further, ALN + OA@NCs showed enhanced efficacy in comparison to OA@NCs suggesting the cytotoxic roles of ALN towards cancer cells, followed by augmentation ROS generation (40.81%), mitochondrial membrane depolarization (57.20%), and induction of apoptosis (40.43%). We found that ALN + OA@NCs facilitated inhibiting osteoclastogenesis and bone resorption followed by inhibited osteolysis. In vivo activity of ALN + OA@NCs in the 4 T1 cell-induced tibia model rendered a reduced bone loss in the treated mice followed by restoring bone morphometric markers which were further corroborated bone-targeting effects of ALN + OA@NCs to reduce RANKL-stimulated osteoclastogenesis. Further, In vivo intravenous pharmacokinetics showed the improved therapeutic profile of the ALN + OA@NCs in comparison to the free drug, prolonging the levels of the drug in the systemic compartment by reducing the clearance culminating the higher accumulation at the tumor site. Our finding proposed that ALN + OA@NCs can effectively target and treat breast cancer metastasis to bone and its associated complications., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

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 IC 50 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 IC 50 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.

Natural products have always played an important role in pharmacotherapy, helping to control pathophysiological processes associated with human disease. Thus, natural products such as oleanolic acid (OA), a pentacyclic triterpene that has demonstrated important activities in several disease models, are in high demand. The relevant properties of this compound have motivated re-searchers to search for new analogues and derivatives using the OA as a scaffold to which new functional groups have been added or modifications have been realized. OA and its derivatives have been shown to be effective in the treatment of inflammatory processes, triggered by chronic diseases or bacterial and viral infections. OA and its derivatives have also been found to be effective in diabetic disorders, a group of common endocrine diseases characterized by hyperglycemia that can affect several organs, including the liver and brain. This group of compounds has been reported to exhibit significant bioactivity against cancer processes in vitro and in vivo. In this review, we summarize the bioactive properties of OA and its derivatives as anti-inflammatory, anti-bacterial, antiviral, anti-diabetic, hepatoprotective, neuroprotective, and anticancer agents.

Background: The therapeutic strategies for acute ischemic stroke were faced with substantial constraints, emphasizing the necessity to safeguard neuronal cells during cerebral ischemia to reduce neurological impairments and enhance recovery outcomes. Despite its potential as a neuroprotective agent in stroke treatment, Chikusetsu saponin IVa encounters numerous challenges in clinical application., Result: Brain-targeted liposomes modified with THRre peptides showed substantial uptake by bEnd. 3 and PC-12 cells and demonstrated the ability to cross an in vitro blood-brain barrier model, subsequently accumulating in PC-12 cells. In vivo, they could significantly accumulate in rat brain. Treatment with C-IVa-LPs-THRre notably reduced the expression of proteins in the P2RX7/NLRP3/Caspase-1 pathway and inflammatory factors. This was evidenced by decreased cerebral infarct size and improved neurological function in MCAO rats., Conclusion: The findings indicate that C-IVa-LPs-THRre could serve as a promising strategy for targeting cerebral ischemia. This approach enhances drug concentration in the brain, mitigates pyroptosis, and improves the neuroinflammatory response associated with stroke., (© 2024. The Author(s).)

Three new oleanane-type triterpene saponins, named camphanosides A-C (1-3), along with five known compounds, chikusetsusaponin IVa (4), spinasaponin A 28-O-glucoside (5), (-)-epicatechin (6), (-)-epicatechin 3-O-gallate (7), and (-)-epigallocatechin 3-O-gallate (8) were isolated from the leaves Camellia phanii Hakoda & Ninh. Their structures were established by 1D and 2D-NMR and mass spectral analysis and chemical methods. Moreover, compounds 1-5 were also evaluated for α-glucosidase inhibitory activity. Compounds 1-3 exhibited moderate α-glucosidase inhibitory activity with IC 50 values of 230.7±18.0, 251.4±22.7, and 421.4±25.6 μM, respectively., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

An extensive phytochemical investigation on the rare medicinal plant Semiliquidambar cathayensis (family: Hamamelidaceae) led to the isolation of four new (1-4, named semiliquidacids A-D, respectively) and 25 related known pentacyclic triterpenoids. The new structures with absolute configurations were elucidated by spectroscopic methods, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 represents the first naturally occurring ursane-type triterpenoid featuring an uncommon C-25 formyl group. Compound 4 and oleanolic acid (13) exhibited remarkable inhibitory effects against the ATP-citrate lyase (ACL, an emerging drug target for hyperlipidemia and related metabolic disorders) with IC 50 values of 6.5 and 11.9 μM, respectively. The molecular interaction and binding mode between the bioactive triterpenoids and ACL were elaborated by conducting a molecular docking study. Meanwhile, the chemotaxonomic significance of the isolated triterpenoids has been briefly discussed., Competing Interests: Declaration of competing interest The authors confirm that this article content has no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

An investigation of EtOAc extract from the roots of Paeonia lactiflora yielded three new 30-noroleanane triterpenoids paeonenoides L-N (1-3) and one new oleanane triterpenoid paeonenoide O (4) together with 7 known compounds (5-11). Extensive spectrographic experiments were applied to identify the structures of 1-4, and their absolute configurations were unambiguously determined by theoretical calculations of ECD spectra, as well as the single-crystal X-ray diffraction analysis. Compounds 8, 9 and 10 were isolated from the Paeonia genus for the first time. Moreover, compounds 8, 9 and 11 showed inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with the IC 50 values of 72. 17 ± 4.74, 30.02 ± 2.03 and 28.34 ± 1.85 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Two new triterpenes mayteneri A ( 1 ), mayteneri B ( 2 ), and seven known compounds ( 3-9 ) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3 - 9 were determined by comparison of their spectral with those reported. Compounds 4 - 7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC 50 values of 2.36-3.44  μ M.

Phytochemical study on the roots of Achyranthes bidentata Blume led to the isolation of sixteen compounds including three new ones ( 1-3 ). Their chemical structures were determined as oleanolic acid 28- O - β -D-glucopyranoside-3- O -[ β -D-glucopyranosyl-(1→3)- β -D-galactopyranoside) ( 1 ), methyl (8 Z ,11 Z )-5,6,7-trihydroxytetradeca-8,11-dienoate ( 2 ), methyl (6 E ,11 Z )-5,8,9-trihydroxytetradeca-6,11-dienoate ( 3 ), fulgidic acid ( 4 ), (9 E ,11 E )-13-oxooctadeca-9,11-dienoic acid ( 5 ), (9 Z ,11 E ,15 Z )-13-hydroxyoctadeca-9,11,15-trienoic acid ( 6 ), oleanolic acid 28- O - β -D-glucopyranoside-3- O - α -L-rhamnopyranosyl-(1→4)- β -D-glucuronopyranoside ( 7 ), oleanolic acid 28- O - β -D-glucopyranoside-3- O - β -D - glucopyranosyl-(1→2)-[ α -L-rhamnopyranosyl-(1→3)]- β -D-glucuronopyranoside ( 8 ), oleanolic acid 3- O - β -D - glucopyranosyl-(1→2)-[ α -L-rhamnopyranosyl-(1→3)]- β -D-glucuronopyranoside ( 9 ), oleanolic acid 3- O - α -L-rhamnopyranosyl-(1→3)- β -D-glucuronopyranoside ( 10 ), blumenol C glucoside ( 11 ), citroside A ( 12 ), 6 S ,9 S -roseoside ( 13 ), ginsenoside Rg1 ( 14 ), 20-hydroxyecdysone ( 15 ), and benzyl α -L-rhamnopyranosyl-(1→6)]- β -D-glucopyranoside ( 16 ) by spectroscopic analysis. Compounds 1 , 7 and 11-16 inhibited NO production in LPS-activated RAW264.7 cells with IC 50 values in the range from 28.03 to 54.23 µM (positive control, L-NMMA: IC 50 = 35.52 µM). Compounds 14 and 15 showed anti α -glucosidase activity with IC 50 values of 176.24 and 156.92 µM, respectively, compared with the positive control, acarbose, IC 50 = 160.99 μM.

Oleanolic acid (OA) is a vegetable chemical that is present naturally in a number of edible and medicinal botanicals. It has been extensively studied by medicinal chemists and scientific researchers due to its biological activity against a wide range of diseases. A significant number of researchers have synthesized a variety of analogues of OA by modifying its structure with the intention of creating more potent biological agents and improving its pharmaceutical properties. In recent years, chemical and enzymatic techniques have been employed extensively to investigate and modify the chemical structure of OA. This review presents recent advancements in medical chemistry for the structural modification of OA, with a special focus on the biotransformation, semi-synthesis and relationship between the modified structures and their biopharmaceutical properties.

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 IC 50 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.

This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.

A new flavonolignan, sonyamandin (1) , along with other known compounds was isolated from the aerial parts and seeds extracts of Silybum marianum (milk thistle) collected from Jordan. The known ones are ursolic acid (2) , oleanolic acid (3) , maslinic acid (4), oleic acid (5) , β-sitosterol (6) , β-, sitosteryl glucoside (7), apigenin (8) , kaempferol-3-O-rhamnoside (9) , apigenin-7-O-β-D-glycoside (10) , isosylibin A (11) , isosylibin B (12), and silybin B (13) . The absolute stereochemistry of 1 was confirmed by 2D NMR and CD analysis.

Ursolic acid has gradually attracted much attention due to its unique pharmacological activities and valuable market value in recent years. Currently, ursolic acid is mostly extracted from loquat leaves, but the plant extraction method has low yield and high cost, and chemical synthesis is not readily available, so the biosynthesis method provides a new source for ursolic acid. α-amyrin acts as the main precursor for the synthesis of ursolic acid, and its yield is positively correlated with ursolic acid yield. Oxidosqualene cyclase(OSC) belongs to a multigene family which can catalyze the common precursor 2,3-oxidosqualene to generate different types of triterpene backbones, and plays a decisive role in the synthesis of triterpenoids. However, there are fewer reported key genes catalyzing the synthesis of α-amyrin in medicinal plants, and the yield and proportion of α-amyrin in the catalyzed products have always been a focus of research. In this study, ItOSC2, MdOSC1, AaOSC2 and CrAS, four enzymes capable of catalyzing the production of α-amyrin from 2,3-oxidosqualene, were cloned from Iris tectorum, Malus domestica, Artemisia annua and Catharanthus roseus, subject to sequence alignment and phylogenetic tree analyses, and transformed into Saccharomyces cerevisiae as plasmids. After 7 days of fermentation, the yield and proportions of α-amyrin, β-amyrin and ergosterol were measured. Finally, AaOSC2 with the best ability to catalyze the generation of α-amyrin was filtered out, providing a key gene element for the later construction of engineered yeast strains with high production of α-amyrin and ursolic acid.

Achyranthes bidentata Blume (Amaranthaceae) is an annual or perennial herb widely used as ethnomedicine in Traditional Chinese Medicine for treating fever, cold, ulcers, mensural pain, dementia, and osteoporosis. In the current study, UPLC-IM-Q-TOF-MS/MS-based chemometric approach was adopted for the tentative identification of fifty-six compounds in the extract and fractions of A.bidentata seeds. Further, the chemometric-guided isolation led to the isolation of two previously undescribed oleanane-type triterpenoid saponins, named achyranosides A-B (27 and 30), along with three known compounds (31, 44, and 23) from water fraction of A. bidentata seeds. The structures of new compounds were elucidated based on the detailed analysis of NMR, HR-ESI-MS, FT-IR spectral data, and GC-FID techniques. The isolated compounds in vitro acetylcholinesterase inhibitory activity revealed the promising activity of chikusetsusaponin IVa (23) (IC 50  = 63.7 μM) with mixed type of AChE inhibition in enzyme kinetic studies. Additionally, in silico binding free energy of isolated compounds disclosed the greater stability of enzyme-ligand complex owing to underlying multiple H-bond interactions. Overall, the study demonstrates the effectiveness of a chemometric-guided approach for the phytochemical exploration and isolation of new oleanane-type triterpenoid saponins from A. bidentata seeds., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Euphorbia serpens has been used in central-west region of Argentina in traditional medicine as diuretic plant. The aim of this present study was to evaluate the diuretic activity of E. serpens in-vivo. We used dried aerial parts, and infusions from these were orally administered to Wistar rats. Its effect was evaluated using furosemide as a positive drug and isotonic salt solution as negative control. Their urine output was quantified at several time intervals. The volume of urine excreted and Na + increased significantly, being similar to furosemide. Mannitol, was the main component in aqueous extracts of E. serpens, and the acetone extract showed the presence of Δ 12 - oleanane-type triterpenoids compounds, mainly hederagenin. No toxic effects were observed.

In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N -glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure-activity relationship of 13 oleanane-type natural triterpenoids with respect to the nuclear factor κB (NF-κB) signaling pathway and the expression, intracellular trafficking, and N -glycosylation of the ICAM-1 protein in human lung adenocarcinoma A549 cells. Hederagenin, echinocystic acid, erythrodiol, and maslinic acid, which all possess two hydroxyl groups, decreased the viability of A549 cells. Celastrol and pristimerin, both of which possess an α , β -unsaturated carbonyl group, decreased cell viability but more strongly inhibited the interleukin-1α-induced NF-κB signaling pathway. Oleanolic acid, moronic acid, and glycyrrhetinic acid interfered with N -glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, α -boswellic acid and maslinic acid interfered with the N -glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type N -glycans. Among the oleanane-type triterpenoids tested, α -boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and N -glycosylation of glycoproteins.

Our study aimed at developing polymer micelles that possess redox sensitivity and excellent controlled release properties. 3,3'-dithiodipropionic acid (DTDPA, Abbreviation in synthetic polymers: SS) was introduced as ROS (Reactive oxygen species)response bond and connecting arm to couple hydroxyethyl starch (HES) with oleanolic acid (OA), resulting in the synthesis of four distinct grafting ratios of HES-SS-OA. FTIR (Fourier Transform infrared spectroscopy) and 1 H NMR ( 1 H Nuclear magnetic resonance spectra) were used to verify the triumphant combination of HES-SS-OA. Polymer micelles were found to encapsulate OA in an amorphous form, as indicated by the results of XRD (X-ray diffraction) and DSC (Differential scanning calorimetry). When the OA grafting rate on HES increased from 7.72 % to 11.75 %, the particle size decreased from 297.79 nm to 201.39 nm as the polymer micelles became compact due to enhanced hydrophobicity. In addition, the zeta potential changed from -16.42 mv to -25.78 mv, the PDI (polydispersity index) decreased from 0.3649 to 0.2435, and the critical micelle concentration (CMC) decreased from 0.0955 mg/mL to 0.0123 mg/mL. Results of erythrocyte hemolysis, cytotoxicity and cellular uptake illustrated that HES-SS-OA had excellent biocompatibility and minimal cytotoxicity for AML-12 cells. Disulfide bond breakage of HES-SS-OA in the presence of H 2 O 2 and GSH confirmed the redox sensitivity of the HES-SS-OA micelles and their excellent controlled release properties for OA. These findings suggest that HES-SS-OA can be potentially used in the future as a healthcare drug and medicine for the prevention or adjuvant treatment of inflammation., Competing Interests: Declaration of competing interest All of the authors have declared that no competing interests exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This investigation delves into the inhibitory capabilities of a specific set of triterpenoic acids on diverse isoforms of human carbonic anhydrase (hCA). Oleanolic acid (1), maslinic acid (2), betulinic acid (3), platanic acid (4), and asiatic acid (5) were chosen as representative triterpenoids for evaluation. The synthesis involved acetylation of parent triterpenoic acids 1-5, followed by sequential reactions with oxalyl chloride and benzylamine, de-acetylation of the amides, and subsequent treatment with sodium hydride and sulfamoyl chloride, leading to the formation of final compounds 21-25. Inhibition assays against hCAs I, II, VA, and IX demonstrated noteworthy outcomes. A derivative of betulinic acid, compound 23, exhibited a K i value of 88.1 nM for hCA VA, and a derivative of asiatic acid, compound 25, displayed an even lower K i value of 36.2 nM for the same isoform. Notably, the latter compound displayed enhanced inhibitory activity against hCA VA when compared to the benchmark compound acetazolamide (AAZ), which had a K i value of 63.0 nM. Thus, this compound surpasses the inhibitory potency and isoform selectivity of the standard compound acetazolamide (AAZ). In conclusion, the research offers insights into the inhibitory potential of selected triterpenoic acids across diverse hCA isoforms, emphasizing the pivotal role of structural attributes in determining isoform-specific inhibitory activity. The identification of compound 25 as a robust and selective hCA VA inhibitor prompts further exploration of its therapeutic applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)