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The aim of this study was to examine the effects of triterpenes from Pleiocarpa pycnantha leaves on the induction of apoptotic signalling in human cells. The molecular mechanisms of triterpenes isolated from P. pycnantha leaves were investigated in vitro on HeLa, MCF-7, HT-29, and KMST-6 cells. The compounds activated several markers associated with apoptosis, viz., phosphatidylserine translocation, caspase activation, oxidative stress, and topoisomerase I inhibition. Compounds 1 and 5 were non-selective, whereas compounds 2, 3, and 4 showed potential as cancer-specific agents by selectively inducing apoptosis only on cancer cells. Theoretical studies on the interactions of compound 1 with caspases -3 and -9 and topoisomerase I were carried out through a molecular docking study and illustrated that compound 1 had an equal binding affinity with the caspases and topoisomerase I comparable to that of camptothecin. The cellular pathway activated by these compounds was dependent on the compound and the cell type.

Background: Subarachnoid hemorrhage (SAH) is a life -threatening cerebrovascular disease, where early brain injury (EBI) stands as a primary contributor to mortality and unfavorable patient outcomes. Neuronal ferroptosis emerges as a key pathological mechanism underlying EBI in SAH. Targeting ferroptosis for therapeutic intervention in SAH holds significant promise as a treatment strategy., Methods: SAH model was induced via intravascular puncture and quantitatively assessed the presence of neuronal ferroptosis in the early phase of SAH using FJC staining, Prussian blue staining, as well as malondialdehyde (MDA) and glutathione (GSH) measurements. Hyaluronic acid-coated ursolic acid nanoparticles (HA-PEG-UA NPs) were prepared using the solvent evaporation method. We investigated the in vivo distribution of HA-PEG-UA NPs in SAH model through IVIS and fluorescence observation, and examined their impact on short-term neurological function and cortical neurological injury. Finally, we assessed the effect of UA on the Nrf-2/SLC7A11/GPX4 axis via Western Blot analysis., Results: We successfully developed self-assembled UA NPs with hyaluronic acid to target the increased CD44 expression in the SAH-afflicted brain. The resulting HA-PEG-UA NPs facilitated delivery and enrichment of UA within the SAH-affected region. The targeted delivery of UA to the SAH region can effectively inhibit neuronal ferroptosis, improve neurological deficits, and prognosis in mice. Its mechanism of action is associated with the activation of the Nrf-2/SLC7A11/GPX4 signaling pathway., Conclusions: Brain-targeted HA-PEG-UA NPs was successfully developed and hold the potential to enhance SAH prognosis by limiting neuronal ferroptosis via modulation of the Nrf-2/SLC7A11/GPX4 signal., (© 2024. The Author(s).)

New Ursolic Acid (UA) conjugates were synthesized using optimized synthetic protocols through the molecular hybridization approach at C-3 and C-28. This resulted in the targeted molecules being produced in good yields. Some of the synthesized conjugates showed significantly relevant bioactivity against mammalian cells and in animal models of cancers. Selected UA conjugates were tested against bladder and breast cancer cell lines. The conjugates showed moderate to significantly enhanced antiproliferative activities against Triple Negative Breast Cancer (TNBC; MDA-MB 231), which is an aggressive tumor making up about 10-15 % of all breast cancers and bladder (T24 and 5637) cancer cell lines. These properties were superior to the parent UA. Among all the synthesized compounds, 18 c and 18 d have exhibited promising antiproliferative and cytotoxic properties against all tested cancer cell lines. However, 18 d has proved to be exceptionally selective for cancer cell lines, showing more cytotoxicity towards them than normal epithelial cells (MCF-12A). Compound 18 d has demonstrated cytotoxicity against tumor cells, including those intrinsically resistant to chemotherapy drugs such as 2-difluoro-deoxy cytidine (Gemcitabine). The activity of the UA conjugates on tumor cells was mediated by multiple cytotoxic mechanisms, including drug-induced cytotoxic autophagy and programmed cell death, indicating a novel possibility of combination therapy., (© 2024 Wiley-VCH GmbH.)

Ursolic acid (UA), a pentacyclic triterpene, exhibits diverse pharmacological effects, including potential treatment for allergic diseases. It downregulates thymic stromal lymphopoietin (TSLP) and disrupts mast cell signaling pathways. However, the exact molecular mechanism by which UA interferes with mast cell action remains unclear. Therefore, the current study aimed to uncover molecular entities underlying the effect of UA on mast cells and its potential antipruritic effect, specifically investigating its modulation of key molecules such as TRPV4, PAR2, and MRGPRX2, which are involved in TSLP regulation and sensation. Calcium imaging experiments revealed that UA pretreatment significantly suppressed MRGPRX2 activation (and its mouse orthologue MrgprB2), a G protein-coupled receptor predominantly expressed in mast cells. Molecular docking predictions suggested potential interactions between UA and MRGPRX2/MrgprB2. UA pretreatment also reduced mast cell degranulation through MRGPRX2 and MrgprB2-dependent mechanisms. In a dry skin mouse model, UA administration decreased tryptase and TSLP production in the skin, and diminished TSLP response in the sensory neurons. While PAR2 and TRPV4 activation enhances TSLP production, UA did not inhibit their activity. Notably, UA attenuated compound 48/80-induced scratching behaviors in mice and suppressed spontaneous scratching in a dry skin model. The present study confirms the effective inhibition of UA on MRGPRX2/MrgprB2, leading to reduced mast cell degranulation and suppressed scratching behaviors. These findings highlight the potential of UA as an antipruritic agent for managing various allergy- or itch-related conditions., Competing Interests: Declaration of competing interest The authors state no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context: Melanoma is one of the cancers with the highest mortality rate for its ability to metastasize. Several targets have undergone investigation for the development of drugs against this pathology. One of the main targets is the kinase BRAF (RAF, rapidly accelerated fibrosarcoma). The most common mutation in melanoma is BRAFV600E and has been reported in 50-90% of patients with melanoma. Due to the relevance of the BRAFV600E mutation, inhibitors to this kinase have been developed, vemurafenib-OMe and dabrafenib. Ursolic acid (UA) is a pentacyclic triterpene with a privileged structure, the pentacycle scaffold, which allows to have a broad variety of biological activity; the most studied is its anticancer capacity. In this work, we reported the interaction profile of vemurafenib-OMe, dabrafenib, and UA, to define whether UA has binding capacity to BRAFWT, BRAFV600E, and BRAFV600K. Homology modeling of BRAFWT, V600E, and V600K; molecular docking; and molecular dynamics simulations were carried out and interactions and residues relevant to the binding of the inhibitors were obtained. We found that UA, like the inhibitors, presents hydrogen bond interactions, and hydrophobic interactions of van der Waals, and π-stacking with I463, Q530, C532, and F583. The ΔG of ursolic acid in complex with BRAFV600K (- 63.31 kcal/mol) is comparable to the ΔG of the selective inhibitor dabrafenib (- 63.32 kcal/mol) in complex to BRAFV600K and presents a ΔG like vemurafenib-OMe with BRAFWT and V600E. With this information, ursolic acid could be considered as a lead compound for design cycles and to optimize the binding profile and the selectivity towards mutations for the development of new selective inhibitors for BRAFV600E and V600K to new potential melanoma treatments., Methods: The homology modeling calculations were executed on the public servers I-TASSER and ROBETTA, followed by molecular docking calculations using AutoGrid 4.2.6, AutoDockGPU 1.5.3, and AutoDockTools 1.5.6. Molecular dynamics and metadynamics simulations were performed in the Desmond module of the academic version of the Schrödinger-Maestro 2020-4 program, utilizing the OPLS-2005 force field. Ligand-protein interactions were evaluated using Schrödinger-Maestro program, LigPlot + , and PLIP (protein-ligand interaction profiler). Finally, all of the protein figures presented in this article were made in the PyMOL program., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ursolic acid (UA) has demonstrated significant immunomodulatory and hepatoprotective effects; however, the underlying mechanisms remain unclear. This study aims to analyze the impact of UA on the gut microbiome, metabolome, and liver transcriptome, investigate UA's role in maintaining gut immune homeostasis and liver health, and evaluate the potential contributions of gut microbes and their metabolites to these beneficial effects. Our findings indicate that UA enhances immune balance in the jejunum, fortifies intestinal barrier function, and promotes overall gut health. UA modulates the intestinal microbiota and its metabolic processes, notably increasing the abundance of beneficial bacteria such as Odoribacter and Parabacteroides , along with their metabolites, including ornithine and lactucin. Additionally, UA inhibits the expression of interleukin-1 receptor 1 ( IL1R1 ) and calcium (Ca 2+ ) voltage-gated channel auxiliary subunit beta 2 ( CACNB2 ) while enhancing the synthesis pathways of retinol and ascorbic acid, thereby exerting a protective influence on liver function. In summary, UA enhances intestinal immune homeostasis and promotes liver health, with these advantageous effects potentially mediated by beneficial bacteria ( Odoribacter and Parabacteroides ) and their metabolites (ornithine and lactucin).

The efficacy of single chemotherapy drugs in cancer treatment is often limited. Combining administration targeting multiple targets has emerged as an effective strategy to improve cancer treatment. Ursolic acid, a triterpenoid compound in various natural foods, was identified as a novel inhibitor of lung cancer specific target TMEM16A. The IC 50 of ursolic acid on the whole-cell current of TMEM16A was 13.85 ± 1.64 μM. Molecular dynamics simulations and site-directed mutagenesis experiments indicated the binding sites of ursolic acid on TMEM16A as L381, R535, E623, and C625. Ursolic acid significantly inhibited the proliferation and migration of LA795 cells, while promoting cancer cell apoptosis. Mechanistic studies revealed that ursolic acid inhibited lung cancer through the MAPK and EMT pathways, and induced DNA and membrane damage. Next, a degradable and self-repairing hydrogel drug-loading system was designed to enhance the targeting effect of the ursolic acid and cisplatin drug combination. In vivo experiments showed that the hydrogel-loaded ursolic acid and cisplatin enhanced the antitumor activity and reduced the toxicity. This study presents a novel approach of multi-target combination therapy using ursolic acid and cisplatin, combined with the targeted delivery capability of the hydrogel system, which significantly improves the therapeutic efficacy in lung cancer., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ursolic acid (UA), a triterpenoid found in plants, has many health benefits for liver function. However, understanding how UA intervenes in alcohol-induced ferroptosis remains unclear because of the lack of research. This study explored the protective effects of UA on alcohol-induced liver injury and further elucidated its mechanism of action. Using a mouse model, acute liver injury was induced via high-dose alcohol gavage, and UA's protective effects were assessed by analyzing serum and liver indicators. The results indicated that UA has a significant protective effect against alcohol-induced liver injury in mice. UA significantly decreased serum ALT, AST, TC, and TG levels. Histopathological examination revealed that UA significantly ameliorated liver damage. UA increased ADH, ALDH, and CYP2E1 enzyme expression levels and alleviated alcohol-induced oxidative damage by regulating alcohol metabolism. Moreover, UA increased SOD and GSH-Px levels and lowered the MDA levels in the liver. Furthermore, UA regulated ACC expression by activating the LKB1/AMPK pathway, thereby inhibiting lipid synthesis and peroxidation. UA also upregulated the expression of GPX4 and SLC7A11 in the liver and exerted hepatoprotective effects by inhibiting alcohol-induced ferroptosis. Additionally, 16S rRNA amplicon sequencing showed that excessive alcohol consumption significantly affected the composition of the mouse gut microbiota, with UA intervention proving to be beneficial for improving gut microbiota imbalance. We also validated the protective effects of UA on alcohol-treated HepG2 cells at the cellular level. In summary, these results revealed that UA can alleviate alcoholic liver injury by inhibiting oxidative stress-mediated ferroptosis and regulating gut microbiota. These findings suggest that UA may serve as a functional component in the prevention of alcoholic liver disease.

Candida auris, a pathogenic fungus, has posed significant challenges to conventional medical treatments due to its increasing resistance to antifungal agents. Consequently, due to their promising pharmacological properties, there is a compelling interest in exploring novel bioactive compounds, such as phytosterols and triterpenes. This study aimed to conduct virtual screening utilizing computational methods, including ADMET, molecular docking, and molecular dynamics, to assess the activity and feasibility of phytosterols extracted from Cryptostegia grandiflora as potential therapeutic agents. Computational predictions suggest that compounds bearing structural similarities to Fsp 3 -rich molecules hold promise for inhibiting enzymes and G protein-coupled receptor (GPCR) modulators, with particular emphasis on ursolic acid, which, in its conjugated form, exhibits high oral bioavailability and metabolic stability, rendering it a compelling drug candidate. Molecular docking calculations identified ursolic acid and stigmasterol as promising ligands. While stigmasterol displayed superior affinity during molecular dynamics simulations, it exhibited instability, contrasting with ursolic acid's slightly lower affinity yet sustained stability throughout the dynamic assessments. This suggests that ursolic acid is a robust candidate for inhibiting the FKBP12 isomerase in C. auris. Moreover, further investigations could focus on experimentally validating the molecular docking predictions and evaluating the efficacy of ursolic acid as an FKBP12 isomerase inhibitor in models of C. auris infection., 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.)

Achyranthes aspera is renowned for its rich medicinal properties since the Ayurvedic era. This plant is known for the presence of experimentally validated anticancer compounds like oleanolic acid (OA) and ursolic acid (UA). Our study involved sequencing the RNA from the root tissue of A. aspera to elucidate the genes responsible for synthesizing these two critical secondary metabolites. Through RNA-Seq analysis, we assembled approximately 167,698 transcripts, averaging 847 base pairs in length, with an N50 value of 1509 bp. From this data, we mapped 604 sequences involved in the metabolism of terpenoids and polyketide pathways. Among them, 241 transcripts were mapped to the triterpenoid biosynthesis pathway, which included 127 transcripts involved in OA and UA biosynthesis. From these transcripts, we identified 22 full-length genes coding for all the 21 enzymes required for OA and UA biosynthesis. Identifying these full-length genes will lead to a better understanding of the pathway and adopting genetic engineering approaches., 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.)

Background: The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury., Materials and Methods: RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury., Results: In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased., Conclusion: In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Peng et al.)

Ursolic acid (UA) and its derivatives have garnered significant attention due to their extensive pharmacological activity. UA is a pentacyclic triterpenoid found in a variety of plants, such as apples, rosemary, thyme, etc., and it possesses a range of pharmacological properties. Researchers have synthesized various derivatives of UA through structural modifications to enhance its potential pharmacological properties. Various in vitro and in vivo studies have indicated that UA and its derivatives possess diverse biological activities, such as anticancer, antifungal, antidiabetic, antioxidant, antibacterial, anti-inflammatory and antiviral properties. This review article provides a review of the biological activities of UA and its derivatives to show their valuable therapeutic properties useful in the treatment of different diseases, mainly focusing on the relevant structure-activity relationships (SARs), the underlying molecular targets/pathways, and modes of action.

Triple negative breast cancer (TNBC) represents the most aggressive and heterogenous disease, and combination therapy holds promising potential. Here, an enzyme-responsive polymeric prodrug with self-assembly properties was synthesized for targeted co-delivery of paclitaxel (PTX) and ursolic acid (UA). Hyaluronic acid (HA) was conjugated with UA, yielding an amphiphilic prodrug with 13.85 mol% UA and a CMC of 32.3 μg/mL. The HA-UA conjugate exhibited ∼14 % and 47 % hydrolysis at pH 7.4 and in tumor cell lysate. HA-UA/PTX NPs exhibited a spherical structure with 173 nm particle size, and 0.15 PDI. The nanoparticles showed high drug loading (11.58 %) and entrapment efficiency (76.87 %) of PTX. Release experiments revealed accelerated drug release (∼78 %) in the presence of hyaluronidase enzyme. Cellular uptake in MDA-MB-231 cells showed enhanced uptake of HA-UA/PTX NPs through CD44 receptor-mediated endocytosis. In vitro, HA-UA/PTX NPs exhibited higher cytotoxicity, apoptosis, and mitochondrial depolarization compared to PTX alone. In vivo, HA-UA/PTX NPs demonstrated improved pharmacokinetic properties, with 2.18, 2.40, and 2.35-fold higher AUC, t 1/2 , and MRT compared to free PTX. Notably, HA-UA/PTX NPs exhibited superior antitumor efficacy with a 90 % tumor inhibition rate in 4T1 tumor model and low systemic toxicity, showcasing their significant potential as carriers for TNBC 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 Elsevier Ltd. All rights reserved.)

Inhibitor of growth 5 (ING5) has been reported to be involved in the malignant progression of cancers. Ursolic acid (UA) has shown remarkable antitumor effects. However, its antitumor mechanisms regarding of ING5 in hepatocellular carcinoma (HCC) remain unclear. Herein, we found that UA significantly suppressed the proliferation, anti-apoptosis, migration and invasion of HCC cells. In addition, ING5 expression in HCC cells treated with UA was obviously downregulated in a concentration- and time-dependent manner. Additionally, the pro-oncogenic role of ING5 was confirmed in HCC cells. Further investigation revealed that UA exerted antitumor effects on HCC by inhibiting ING5-mediated activation of PI3K/Akt pathway. Notably, UA could also reverse sorafenib resistance of HCC cells by suppressing the ING5-ACC1/ACLY-lipid droplets (LDs) axis. UA abrogated ING5 transcription and downregulated its expression by reducing SRF and YY1 expression and the SRF-YY1 complex formation. Alb/JCPyV T antigen mice were used for in vivo experiments since T antigen upregulated ING5 expression by inhibiting the ubiquitin-mediated degradation and promoting the T antigen-SRF-YY1-ING5 complex-associated transcription. UA suppressed JCPyV T antigen-induced spontaneous HCC through inhibiting ING5-mediated PI3K/Akt signaling pathway. These findings suggest that UA has the dual antitumoral functions of inhibiting hepatocellular carcinogenesis and reversing sorafenib resistance of HCC cells through targeting ING5, which could serve as a potential therapeutic strategy for HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Fungal endophytes are a known warehouse of bioactive compounds with multifarious applications. In the present investigation two compounds, β-Sitosterol (1) and ursolic acid (2), were isolated from Alternaria alternata , an endophytic fungus associated with Morus alba Linn for the first time. The structure of the compounds was elucidated on the basis of comprehensive spectral analysis (UV, IR, 1 H-, 13 C- and 2D-NMR, as well as HRESI-MS). In the in vitro alpha amylase inhibitory assay both compounds (1) and (2) show potent antidiabetic activity. In support, Docking studies indicate significant binding affinity of the isolated compounds. Hence from the present study, it can be concluded that endophytic fungi in Morus alba Linn can find use in antidiabetic drug development in the medicinal industry.Communicated by Ramaswamy H. Sarma.

Background: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease that affects multiple organs and cause a wide range of severe clinical manifestations, including lupus nephritis (LN), which is a major risk factor for morbidity and mortality in individual with SLE. Ursolic acid (UA) is a natural compound with favorable anti-inflammatory properties and has been employed to treat multiple disease, including inflammatory diseases, diabetes, and Parkinson's disease. However, its therapeutic potential on LN and the underlying mechanisms remains unclear., Purpose: This aim of this study was to investigate the impact of UA on LN and its underlying mechanism., Methods: MRL/lpr lupus-prone mouse model was used and UA was administered orally for 8 weeks. Dexamethasone was used as a positive control. After 8 weeks of administration, the spleen-to-body-weight ratio, renal function, urine albumin excretion, cytokines levels, and the deposition of immune complex were measured. The primary mouse glomerular mesangial cells (GMCs) and SV40-MES-13 were stimulated by lipopolysaccharide (LPS), either alone or in combination with nigericin, to establish an in vitro model. The activation of NLRP3 inflammasome were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence., Results: Our results revealed that UA prominently alleviated LN in MRL/lpr lupus-prone mice, leading to a significant reduction in proteinuria production, infiltration of immune cells infiltration, and histopathological damage in the renal tissue. In addition, UA exerted inhibitory effects on the secretion of IL-1β, IL-18, and caspase-1, pyroptosis, and ASC speck formation in primary mouse GMCs and SV40-MES-13 cells. Furthermore, UA facilitated the degradation of NLRP3 by suppressing SUMO1-mediated SUMOylation of NLRP3., Conclusion: UA possess a therapeutical effect on LN in MRL/lpr mice by enhancing the degradation of NLRP3 through inhibition of SUMO1-mediated SUMOylation of NLRP3. Our findings provide a basis for proposing UA as a potential candidate for the treatment of LN., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Oligospermia is one of the most common reasons for male infertility which is troubling numerous couples of child-bearing age. This investigation scrutinizes the implications and mechanistic underpinnings of ursolic acid's effect on busulfan-induced oligospermia in mouse models., Methods: A singular intraperitoneal injection of busulfan at a dosage of 30 mg/kg induced oligospermia. Two weeks subsequent to this induction, mice were subjected to various dosages of ursolic acid (10, 30, and 50 mg/kg body weight, respectively) on a daily basis for four consecutive weeks. Following this treatment period, a meticulous analysis of epididymal sperm parameters, encompassing concentration and motility, was conducted using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels, including testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde), were gauged employing specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between the oligospermia-induced group and the various ursolic acid treatment groups were identified through RNA sequencing analysis., Results: The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice., Competing Interests: The authors declare there are no competing interests., (©2024 Dong et al.)

Ursolic acid (UA), which has many biological properties such as anti-cancer, anti-inflammatory and antioxidant, and regulates some pharmacological processes, has been isolated from the flowers, leaves, berries and fruits of many plant species. In this work, UA was purified from the methanol-chloroform crude extract of Nepeta species ( N. aristata , N. baytopii , N. italica , N. trachonitica , N. stenantha ) using a silica gel column with chloroform or ethyl acetate solvents via bioactivity-guided isolation. The most active sub-fractions were determined under bioactivities using antioxidant and DNA protection activities and enzyme inhibitions. UA was purified from these fractions and its structure was elucidated by NMR spectroscopy techniques. The highest amount of UA was found in N. stenantha (8.53 mg UA/g), while the lowest amount of UA was found in N. trachonitica (1.92 mg UA/g). The bioactivities of UA were evaluated with antioxidant and DNA protection activities, enzyme inhibitions, kinetics and interactions. The inhibition values (IC 50 ) of α-amylase, α-glucosidase, urease, CA, tyrosinase, lipase, AChE, and BChE were determined between 5.08 and 181.96 µM. In contrast, K i values of enzyme inhibition kinetics were observed between 0.04 and 0.20 mM. In addition, K i values of these enzymes for enzyme-UA interactions were calculated as 0.38, 0.86, 0.45, 1.01, 0.23, 0.41, 0.01 and 2.24 µM, respectively. It is supported that UA can be widely used as a good antioxidant against oxidative damage, an effective DNA protector against genetic diseases, and a suitable inhibitor for metabolizing enzymes.Communicated by Ramaswamy H. Sarma.

Background/aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD., Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings., Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression., Conclusion: Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

To investigate the efficacy of Ursolic acid in alleviating neuropathic pain in rats with spinal nerve ligation (SNL), the SNL rat model was surgically induced. Different concentrations of Ursolic acid and manipulated target mitogen-activated protein kinase 1 (MAPK1) were administered to the SNL rats. Fecal samples were collected from each group of rats for 16S rDNA analysis to examine the impact of gut microbiota. Molecular docking experiments were conducted to assess the binding energy between Ursolic acid and MAPK1. In vivo studies were carried out to evaluate the expression of inflammatory factors and signaling pathways in spinal cord and colon tissues. Ursolic acid was found to have a beneficial effect on pain reduction in rats by increasing plantar withdrawal latency (PWL) and paw withdrawal threshold (PWT). Comparing the Ursolic acid group with the control group revealed notable differences in the distribution of Staphylococcus, Allobaculum, Clostridium, Blautia, Bifidobacterium, and Prevotella species. Network pharmacology analysis identified MAPK1 and intercellular adhesion molecule-1 (ICAM1) as common targets for Ursolic acid, SNL, and neuropathic pain. Binding sites between Ursolic acid and these targets were identified. Additionally, immunofluorescent staining showed a decrease in GFAP and IBA1 intensity in the spinal cord along with an increase in NeuN following Ursolic acid treatment. Overexpression of MAPK1 in SNL rats led to an increase in inflammatory factors and a decrease in PWL and PWT. Furthermore, MAPK1 counteracted the pain-relieving effects of Ursolic acid in SNL rats. Ursolic acid was found to alleviate neuropathic pain in SNL rats by targeting MAPK1 and influencing gut microbiota homeostasis., 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.)

Ursolic acid (UA), a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices and medicinal plants, has various biological effects such as reducing inflammation, protecting cells from damage, and preserving brain function. However, its impact on ferroptosis in cancer stem‑like cells remains unexplored. The present study investigated the effect of UA on MDA‑MB‑231 and BT‑549 cell‑derived triple‑negative breast CSCs (BCSCs) and its potential ferroptosis pathway. The effects of ferroptosis on BCSCs were demonstrated by the detection of ferroptosis‑related indexes including the intracellular level of glutathione, malondialdehyde, reactive oxygen species and iron. The effects of UA on the biological behaviors of BCSCs were analyzed by Cell Counting Kit‑8, stemness indexes detection and mammosphere formation assay. The mechanism of UA induction on BCSCs was explored by reverse transcription‑quantitative PCR and western blotting. BALB/c‑nude mice were subcutaneously injected with MDA‑MB‑231‑derived BCSCs to establish xenograft models to detect the effects of UA in vivo . The results revealed that BCSCs have abnormal iron metabolism and are less susceptible to ferroptosis. UA effectively reduces the stemness traits and proliferation of BCSCs in spheroids and mice models by promoting ferroptosis. It was observed that UA stabilizes Kelch‑like ECH‑associated protein 1 and suppresses nuclear factor erythroid‑related factor 2 (NRF2) activation. These findings suggested that the ability of UA to trigger ferroptosis through the inhibition of the NRF2 pathway could be a promising approach for treating BCSCs, potentially addressing metastasis and drug resistance in triple‑negative breast cancer (TNBC). This expands the clinical applications of UA and provides a theoretical basis for its use in TNBC treatment.

Objective: To unveil the pathological changes associated with demyelination in schizophrenia (SZ) and its consequential impact on interstitial fluid (ISF) drainage, and to investigate the therapeutic efficacy of ursolic acid (UA) in treating demyelination and the ensuing abnormalities in ISF drainage in SZ., Methods: Female C57BL/6J mice, aged 6-8 weeks and weighing (20±2) g, were randomly divided into three groups: control, SZ model, and UA treatment. The control group received intraperitoneal injection (ip) of physiological saline and intragastric administration (ig) of 1% carboxymethylcellulose sodium (CMC-Na). The SZ model group was subjected to ip injection of 2 mg/kg dizocilpine maleate (MK-801) and ig administration of 1% CMC-Na. The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801. The treatment group received UA pretreatment via ig administration for one week, followed by a two-week drug intervention for all the three groups. Behavioral assessments, including the open field test and prepulse inhibition experiment, were conducted post-modeling. Subsequently, changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions. Immunofluorescence analysis was employed to examine alterations in aquaporin 4 (AQP4) polarity distribution in the brain and changes in protein expression. Myelin reflex imaging using Laser Scanning Confocal Microscopy (LSCM) was utilized to study modifications in myelin within the mouse brain. Quantitative data underwent one-way ANOVA, followed by TukeyHSD for post hoc pairwise comparisons between the groups., Results: The open field test revealed a significantly longer total distance [(7 949.39±1 140.55) cm vs . (2 831.01±1 212.72) cm, P < 0.001] and increased central area duration [(88.43±22.06) s vs . (56.85±18.58) s, P =0.011] for the SZ model group compared with the controls. The UA treatment group exhibited signifi-cantly reduced total distance [(2 415.80±646.95) cm vs . (7 949.39±1 140.55) cm, P < 0.001] and increased central area duration [(54.78±11.66) s vs . (88.43±22.06) s, P =0.007] compared with the model group. Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the startle reflex in the model group relative to the controls ( P < 0.001 for both), with the treatment group displaying significant improvement ( P < 0.001 for both). Myelin sheath analysis indicated significant demyelination in the model group, while UA treatment reversed this effect. Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thalamus in the model group relative to the controls [(13.93±3.35) mm 2 vs . (2.79±0.94) mm 2 , P < 0.001 for diffusion area; (2.48±0.38) mm 2 vs . (0.05±0.12) mm 2 , P < 0.001 for reflux area], with significant impairment of drainage in brain regions. The treatment group demonstrated significantly reduced tracer diffusion and reflux areas [(7.93±2.48) mm 2 vs . (13.93±3.35) mm 2 , P < 0.001 for diffusion area; (0.50±0.30) mm 2 vs . (2.48±0.38) mm 2 , P < 0.001 for reflux area]. Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls [(3 663.88±733.77) μm 2 vs . (13 354.92±4 054.05) μm 2 , P < 0.001]. The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression [(11 104.68±3 200.04) μm 2 vs . (3 663.88±733.77) μm 2 , P < 0.001]., Conclusion: UA intervention ameliorates behavioral performance in SZ mice, Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function. The underlying mechanism may involve the improvement of demyelination and ISF drainage dysregulation in SZ mice.

The glomerular podocyte, a terminally differentiated cell, is crucial for the integrity of the glomerular filtration barrier. The re-entry of podocytes into the mitotic phase results in injuries or death, known as mitotic catastrophe (MC), which significantly contributes to the progression of diabetic nephropathy (DN). Furthermore, P62-mediated autophagic flux has been shown to regulate DN-induced podocyte injury. Although previous studies, including ours, have demonstrated that ursolic acid (UA) mitigates podocyte injury by enhancing autophagy under high glucose conditions, the protective functions and potential regulatory mechanisms of UA against DN have not been fully elucidated. For aiming to investigate the regulatory mechanism of podocyte injuries in DN progression, and the protective function of UA treatment against DN progression, we utilized db/db mice and high glucose (HG)-induced podocyte models in vivo and in vitro, with or without UA administration. Our findings indicate that UA treatment reduced DN progression by improving biochemical indices. P62 accumulation led to Murine Double Minute gene 2 (MDM2)-regulated MC in podocytes during DN, which was ameliorated by UA through enhanced P62-mediated autophagy. Additionally, the overexpression of NF-κB p65 or TNF-α abolished the protective effects of UA both in vivo and in vitro . Overall, our results provide strong evidence that UA could be a potential therapeutic agent for DN, regulated by inhibiting podocyte MC through the NF-κB/MDM2/Notch1 pathway by targeting autophagic-P62 accumulation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ultraviolet B (UVB) exposure can contribute to photoaging of skin. Cornus officinalis is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the Cornus officinalis extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of Cornus officinalis . The effect of COE on UVB damage was assessed using Caenorhabditis elegans . The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of C. elegans exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the skn-1 downstream gene and the extension of the lifespan in skn-1 mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in C. elegans via the SKN-1/Nrf2 pathway.

Tuberculosis (TB) stands as the second most prevalent cause of global human mortality from infectious diseases. In 2022, the World Health Organization documented an estimated number of global TB cases reaching 7.5 million, which causes death for 1.13 million patients. The continuous growth of drug-resistant TB cases due to various mutations in the Mycobacterium tuberculosis (MTB) strain, raises the urgency of the exploration of novel anti-TB treatments. Ursolic acid (UA) is a natural pentacyclic triterpene found in various plants that has shown potential as a novel anti-TB agent. This review aims to provide an overview of the therapeutic prospects of UA against MTB, with a particular emphasis on in silico, in vitro, and in vivo studies. Various mechanisms of action of UA against MTB are briefly recapped from in silico studies, such as enoyl acyl carrier protein reductase inhibitors, FadA5 (Acetyl-CoA acetyltransferase) inhibitors, tuberculosinyl adenosine transferase inhibitors, and small heat shock protein 16.3 inhibitor. The potential of UA to overcome drug resistance and its synergistic effects with existing antituberculosis drugs are briefly explained from in vitro studies using a variety of methods, such as Microplate Alamar Blue Assay, Mycobacteria Growth Indicator Tube 960 and Resazurin Assays, morphological change evaluation using transmission electron microscopy, and in vivo studies using BALB/C infected with multi drug resistant clinical isolates. Besides its promising mechanism as an antituberculosis drug, its complex chemical composition, limited availability and supply, and lack of intellectual property are also reviewed as those are the most frequently occurring challenges that need to be addressed for the successful development of UA as novel anti-TB agent., Competing Interests: 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., (© 2024 Pitaloka et al.)

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens accountable to developing skin cancers. Recently, we reported that exposure to benzo[a]pyrene (B[a]P), a common PAH, causes epigenetic and metabolic alterations in the initiation, promotion and progression of non-melanoma skin cancer (NMSC). As a follow-up investigation, this study examines how dietary triterpenoid ursolic acid (UA) regulates B[a]P-driven epigenetic and metabolic pathways in SKH-1 hairless mice. Our results show UA intercepts against B[a]P-induced tumorigenesis at different stages of NMSC. Epigenomic cytosines followed by guanine residues (CpG) methyl-seq data showed UA diminished B[a]P-mediated differentially methylated regions (DMRs) profiles. Transcriptomic RNA-seq revealed UA revoked B[a]P-induced differentially expressed genes (DEGs) of skin cancer-related genes, such as leucine-rich repeat LGI family member 2 (Lgi2) and kallikrein-related peptidase 13 (Klk13), indicating UA plays a vital role in B[a]P-mediated gene regulation and its potential consequences in NMSC interception. Association analysis of DEGs and DMRs found that the mRNA expression of KLK13 gene was correlated with the promoter CpG methylation status in the early-stage comparison group, indicating UA could regulate the KLK13 by modulating its promoter methylation at an early stage of NMSC. The metabolomic study showed UA alters B[a]P-regulated cancer-associated metabolisms like thiamin metabolism, ascorbate and aldarate metabolism during the initiation phase; pyruvate, citrate and thiamin metabolism during the promotion phase; and beta-alanine and pathothenate coenzyme A (CoA) biosynthesis during the late progression phase. Taken together, UA reverses B[a]P-driven epigenetic, transcriptomic and metabolic reprogramming, potentially contributing to the overall cancer interception against B[a]P-mediated NMSC., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Ursolic acid and uvaol are naturally occurring triterpenoids that exhibit a broad spectrum of pharmacological activities, including cytotoxicity. However, a primary challenge in the development of ursane-type pentacyclic triterpenoids for pharmacological use is their poor aqueous solubility, which can impede their effectiveness as therapeutics agents. In this study, we present the facile synthesis of ursolic acid monodesmosides and uvaol bidesmosides, incorporating naturally occurring and water-soluble pentoses and deoxyhexose sugar moieties of opposite d- and l-configurations at the C3 or C3/C28 positions of the ursane core. The twenty synthetic saponins were evaluated in vitro for their cytotoxicity against lung carcinoma (A549) and colorectal adenocarcinoma (DLD-1) cell lines. Notably, all the bidesmosidic uvaol saponins were shown to be cytotoxic as compared to their non-cytotoxic parent triterpenoid. For each series of ursane-type saponins, the most active compounds were 3-O-α-l-arabinopyranosyl ursolic acid (3h) and 3,28-di-O-α-l-rhamnopyranosyl uvaol (4f), showing IC 50 values in the low micromolar range against A549 and DLD-1 cancer lines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andre Pichette reports financial support was provided by Canadian Institutes of Health Research. Jean Legault reports financial support was provided by Canadian Institutes of Health Research. Charles Gauthier reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Charles Gauthier reports financial support was provided by Quebec Health Research Fund. If there are other authors, they 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.)

Glutaminase is an important target that is often over-expressed in neurodegenerative and lifestyle-related diseases but few effective inhibitors of this enzyme have yet reached clinical trials. Three compounds isolated from fresh leaves of Diospyros kaki Thunberg, ursolic acid ( 1 ), rotungenic acid ( 2 ) and barbinervic acid ( 3 ), were identified by analyzing their NMR and MS spectral data and comparison of these with reported data. The IC 50 values of 1 - 3 and 6-diazo-5-oxo-L-norleucine (DON) as control were 775, 13, 14, and 434 μM, respectively. Compounds 2 and 3 showed higher glutaminase inhibitory activities than DON. Compounds 2 and 3 may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting glutaminase. This is the first report on glutaminase inhibitory activities of 2 and 3 .

3-nitropropionic acid (3-NPA), a toxic metabolite produced by mold, is mainly found in moldy sugarcane. 3-NPA inhibits the activity of succinate dehydrogenase that can induce oxidative stress injury in cells, reduce ATP production and induce oxidative stress in mouse ovaries to cause reproductive disorders. Ursolic acid (UA) has a variety of biological activities and is a pentacyclic triterpene compound found in many plants. This experiment aimed to investigate the cytotoxicity of 3-NPA during mouse oocyte in vitro maturation and the protective effects of UA on oocytes challenged with 3-NPA. The results showed that UA could alleviate 3-NPA-induced oocyte meiotic maturation failure. Specifically, 3-NPA induced a decrease in the first polar body extrusion rate of oocytes, abnormal distribution of cortical granules, and an increase in the proportion of spindle abnormalities. In addition, 3-NPA caused mitochondrial dysfunction and induced oxidative stress, including decreases in the GSH, mitochondrial membrane potential and ATP levels, and increases in the ROS levels, and these effects led to apoptosis and autophagy. The addition of UA could significantly improve the adverse effects caused by 3-NPA. In general, our data show that 3-NPA affects the normal development of oocytes during the in vitro culture, and the addition of UA can effectively repair the damage caused by 3-NPA to oocytes., 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. The Graphical abstract is created using Figdraw (www.figdraw.com)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ursonic acid (UNA) is a natural pentacyclic triterpene found in some medicinal plants and foods. The reproductive protective effect of UNA was evaluated in a mouse model of oligozoospermia induced by busulfan (BUS) at 30 mg/kg b.w.. The mice were initially divided into groups with UNA concentrations of 10, 30, 50, 100 mg/kg. Subsequently, based on sperm parameters, the optimal concentration of 50 mg/kg was identified. As a control, an additional group was supplemented with ursolic acid at a concentration of 50 mg/kg. The results indicated that BUS caused the loss of spermatogenic cells in testis, the decrease of sperm in epididymis, the disorder of testicular cytoskeleton, the decrease of serum sex hormones such as testosterone which induced an increase in feedback of androgen receptor and other testosterone-related proteins, the increase of malondialdehyde and reactive oxygen species levels and the increase of ferroptosis in testis while UNA successfully reversed these injuries. High-throughput sequencing revealed that UNA administration significantly upregulated the expression of genes associated with spermatogenesis, such as Tnp1, Tnp2, Prm1, among others. These proteins are crucial in the histone to protamine transition during sperm chromatin remodeling. Network pharmacology analysis reveals a close association between UNA and proteins related to the transformation of histones to protamine. Molecular docking studies reveal that UNA can interact with the ferroptosis-inhibiting gene SLC7A11, thereby modulating ferroptosis. Taken together, UNA alleviated BUS-induced oligozoospermia by regulating hormone secretion, mitigating oxidative stress and promoting recovery of spermatogenesis by inhibiting the ferroptosis., 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.)

Cognitive deficits are the main outcome of neurological disorders whose occurrence has risen over the past three decades. Although there are some pharmacologic approaches approved for managing neurological disorders, it remains largely ineffective. Hence, exploring novel nature-based nutraceuticals is a pressing need to alleviate the results of neurodegenerative diseases, such as Alzheimer's disease (AD) and other neurodegenerative disorders. Some triterpenoids and their derivates can be considered potential therapeutics against neurological disorders due to their neuroprotective and cognitive-improving effects. Betulin (B), betulinic acid (BA), and ursolic acid (UA) are pentacyclic triterpenoid compounds with a variety of biological activities, including antioxidative, neuroprotective and anti-inflammatory properties. This review focuses on the therapeutic efficacy and probable molecular mechanisms of triterpenoids in damage prevention to neurons and restoring cognition in neurodegenerative diseases. Considering few studies on this concept, the precise mechanisms that mediate the effect of these compounds in neurodegenerative disorders have remained unknown. The findings can provide sufficient information about the advantages of these compounds against neurodegenerative diseases.

Background: Chemotherapies target the PfEMP-1 and PfPKG proteins in Plasmodium falciparum, the parasite that causes malaria, in an effort to prevent the disease's high fatality rate. This work identified the phytochemical components of Nauclea latifolia roots and docked the chemical compounds against target proteins, and examined the in vivo antiplasmodial effect of the roots on Plasmodium berghei-infected mice., Methods: Standard protocols were followed for the collection of the plant's roots, cleaning, and drying of the roots, extraction and fraction preparation, assessment of the in vivo antiplasmodial activity, retrieval of the PfEMP-1 and PfPKG proteins, GCMS, ADME, and docking studies, chromatographic techniques were employed to separate the residual fraction's components, and the Swis-ADME program made it possible to estimate the drug's likeness and pharmacokinetic properties. The Auto Dock Vina 4.2 tool was utilized for molecular docking analysis., Results: The residual fraction showed the best therapeutic response when compared favorably to amodiaquine (80.5%) and artesunate (85.1%). It also considerably reduced the number of parasites, with the % growth inhibition of the parasite at 42.8% (D2) and 83.4% (D5). Following purification, 25 compounds were isolated and characterized with GCMS. Based on their low molecular weights, non-permeation of the blood-brain barrier, non-inhibition of metabolizing enzymes, and non-violation of Lipinski's criteria, betulinic and ursolic acids were superior to chloroquine as the best phytochemicals. Hence, they are lead compounds., Conclusion: In addition to identifying the bioactive compounds, ADME, and docking data of the lead compounds as candidates for rational drug design processes as observed against Plasmodium falciparum target proteins (PfEMP-1 and PfPKG), which are implicated in the pathogenesis of malaria, the study has validated that the residual fraction of N. latifolia roots has the best antiplasmodial therapeutic index., (© 2024. The Author(s).)

Ursolic acid (UA), a natural pentacyclic triterpenoid, is known to exhibit various biological activities and anticancer effects. However, the underlying anticancer mechanism is not fully understood to date. The present study aimed to investigate the antimetastatic effect of UA through ADP‑ribosylation factor like GTPase 4C (ARL4C) in colon cancer. A lung metastasis model of colon cancer in nude mice was established through tail vein injection. A Cell Counting Kit‑8 assay was used to investigate the proliferation of colon cancer cells. Transwell assays were used to detect cell migration and invasion. The expression levels of proteins including ARL4C, matrix metallopeptidase 2 (MMP2), phosphorylated (p)‑AKT and p‑mTOR were measured using western blot analysis. Immunohistochemistry was used to determine the protein expression level in tissues. ARL4C ubiquitination levels were analysed using immunoprecipitation and western blotting. The results indicated that UA inhibits the metastasis of colon cancer in vivo and in vitro . The expression of ARL4C in human colon cancer tissue was significantly higher than that in adjacent tissues and its high expression level was associated with lymph node metastases and tumour stage. UA treatment significantly decreased ARL4C and MMP2 protein levels and inhibited the AKT/mTOR signalling pathway. Overexpression of ARL4C reversed the inhibitory effect of UA on the invasion and migration of HCT‑116 and SW480 cells, as well as the expression and secretion of MMP2 protein. In addition, UA and an AKT signalling pathway inhibitor (LY294002) induced the ubiquitination of the ARL4C protein, which was reversed by a proteasome inhibitor (MG‑132). Collectively, it was revealed in the present study that UA served as a novel solution to relieve colon cancer metastasis by inducing the ubiquitination‑mediated degradation of ARL4C by modulating the AKT signalling pathway. Thus, UA may be a promising treatment option to prolong the survival of patients with colon cancer metastasis.

The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination of curcumin (CURC) and ursolic acid (UA). We investigate this combination using a systematic review process to assess the most likely mechanistic pathway and human testing in prostate cancer. We used the PRISMA statement to screen titles, abstracts, and the full texts of relevant articles and performed a descriptive analysis of the literature reviewed for study inclusion and consensus of the manuscript. The most common molecular and cellular pathway from articles reporting on the pathways and effects of CURC ( n  = 173) in prostate cancer was NF-κB ( n  = 25, 14.5%). The most common molecular and cellular pathway from articles reporting on the pathways and effects of UA ( n  = 24) in prostate cancer was caspase 3/caspase 9 ( n  = 10, 41.6%). The three most common molecular and cellular pathway from articles reporting on the pathways and effects of both CURC and UA ( n  = 193) in prostate cancer was NF-κB ( n  = 28, 14.2%), Akt ( n  = 22, 11.2%), and androgen ( n  = 19, 9.6%). Therefore, we have identified the potential synergistic target pathways of curcumin and ursolic acid to involve NF-κB, Akt, androgen receptors, and apoptosis pathways. Our review highlights the limited human studies and specific effects in prostate cancer., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pterocephali Herba (PH), the dried whole plant of Pterocephalus hookeri, is a Tibetan medicine commonly used to treat rheumatoid arthritis (RA). Iridoids, triterpenoids, flavonoids and phenylpropanoids are the major groups of bioactive constituents from PH. However, only ursolic acid and oleanolic acid, two unspecific triterpenoid components, are used as markers for the quality control of PH in Chinese Pharmacopoeia. Herein, an UPLC-TQ-MS/MS integrating SIR and MRM mode method for simultaneously quantifying 18 components, i.e., 9 iridoids, 3 triterpenoids, 3 phenylpropanoids, 2 flavonoids and quinic acid, in PH was developed and validated, and was used to evaluate 10 batches of PH samples from different origins. Hierarchical cluster analysis (HCA) was used to show the clustering of PH samples, while spearman correlation analysis was adopted to evaluate the correlation between ursolic acid/oleanolic acid and other quantified components. It was found that the established method was sensitive, precise, and accurate enough for the simultaneous quantification of 18 analytes in PH samples. Significant differences were found among the contents of 18 components in PH samples, no apparent clustering of the quality of PH samples was found to be related to its origins, and the contents of ursolic acid/oleanolic acid were only significantly correlated to the content of sylvestroside I, dipsanoside B, dipsanoside A in PH. Our results suggested that the newly established multi-components quantitative method is an improved approach for quality evaluation of PH samples. Furthermore, the holistic quality was inconsistent among PH samples, and ursolic acid/oleanolic acid alone could not indicate the holistic quality variation trend of PH., 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 Elsevier B.V. All rights reserved.)

Background: There is a critical need for the discovery of novel and effective antibacterial or anticancer molecules., Objectives: Amine-linked ursolic acid-based hybrid compounds were prepared in good yields in the range of 60-68%., Methods: Their molecular structures were successfully confirmed using different spectroscopic methods including 1 H/ 13 C NMR, UHPLC-HRMS and FTIR spectroscopy. The in vitro cytotoxicity of some of these hybrid molecules against three human tumour cells, such as MDA-MB23, MCF7, and HeLa was evaluated using the MTT colorimetric method., Result: Their antibacterial efficacy was evaluated against eleven bacterial pathogens using a serial dilution assay. Majority of the bacterial strains were inhibited significantly by compounds 17 and 24, with the lowest MIC values in the range of 15.3-31.25 μg/mL. Compound 16 exhibited higher cytotoxicity against HeLa cells than ursolic acid, with an IC 50 value of 43.64 g/mL., Conclusion: The in vitro antibacterial activity and cytotoxicity of these hybrid compounds demonstrated that ursolic acid-based hybrid molecules are promising compounds. Further research into ursolic acid-based hybrid compounds is required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The chemical transformation of ursolic acid (UA) into novel C-3 aryl ester derivatives and in vitro and silico assessment of their antitubercular potential., Background: UA is a natural pentacyclic triterpenoid with many pharmacological properties. Semisynthetic UA analogs have demonstrated enhanced anticancer, antimalarial, and antifilarial properties in our previous studies., Methods: The C-30 carboxylic group of previously isolated UA was protected, and various C-3 aryl ester derivatives were semi-synthesized. The agar dilution method was used to evaluate the in vitro antitubercular efficacy of Mycobacterium tuberculosis (Mtb) H 37 Ra. In silico docking studies of the active derivative were carried out against Mtb targets, catalase peroxidase (PDB: 1SJ2), dihydrofolate reductase (PDB: 4M2X), enoyl-ACP reductase (PDB: 4TRO), and cytochrome bc1 oxidase (PDB: 7E1V)., Results: The derivative 3-O-(2-amino,3-methyl benzoic acid)-ethyl ursolate (UA-1H) was the most active among the eight derivatives (MIC1 2.5 μg/mL) against Mtb H 37 Ra. Also, UA-1H demonstrated significant binding affinity in the range of 10.8-11.4 kcal/mol against the antiTb target proteins, which was far better than the positive control Isoniazid, Ethambutol, and co-crystallized ligand (HEM). Moreover, the predicted hit UA-1H showed no inhibition of Cytochrome P450 2D6 (CYP2D6), suggesting its potential for favorable metabolism in Phase I clinical studies., Conclusion: The ursolic acid derivative UA-1H possesses significant in vitro antitubercular potential with favorable in silico pharmacokinetics. Hence, further in vivo assessments are suggested for UA-1H for its possible development into a secure and efficient antitubercular drug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Ursolic acid (UA) has an important biological role in the fight against fat accumulation, insulin resistance, obesity and inflammation. Therefore, in the current review and meta-analysis work, we investigate the effects of UA (dosage range is 50.94 to 450 mg/day) on cardiometabolic risk factors. Materials & methods: After searching the studies up to February 2023, six articles were included in the study. Results: The pooled effect size showed that UA supplementation didn't significantly change body weight, body mass index, waist circumference, body fat percentage, lean body mass, systolic blood pressure, diastolic blood pressure, fasting blood glucose, insulin, triglyceride and high-density lipoprotein compared with control groups. Conclusion: UA supplementation had no significant effect on the cardiometabolic risk factors in adults.

Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing need for alternative strategies that can address multiple hallmarks concomitantly. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has recently emerged as a promising candidate for multitargeted cancer therapy. This review aims to summarize the current knowledge on the anticancer properties of UA, focusing on its ability to modulate various cancer hallmarks. The literature reveals that UA exhibits potent anticancer effects through diverse mechanisms, including the inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment. Additionally, UA has demonstrated promising activity against different cancer types (e.g., breast, lung, prostate, colon, and liver) by targeting various cancer hallmarks. This review discusses the molecular targets and signaling pathways involved in the anticancer effects of UA. Notably, UA has been found to modulate key signaling pathways, such as PI3K/Akt, MAPK/ERK, NF-κB, and Wnt/β-catenin, which play crucial roles in cancer development and progression. Moreover, the ability of UA to destroy cancer cells through various mechanisms (e.g., apoptosis, autophagy, inhibiting cell growth, dysregulating cancer cell metabolism, etc.) contributes to its multitargeted effects on cancer hallmarks. Despite promising anticancer effects, this review acknowledges hurdles related to UA's low bioavailability, emphasizing the need for enhanced therapeutic strategies.

Ursolic acid (UA) is a pentacyclic triterpenoid, which exhibits many biological activities, particularly in anti-cardiovascular and anti-diabetes. The further application of UA is greatly limited due to its low bioavailability and poor water solubility. Up to date, various UA derivatives have been designed to overcome these shortcomings. In this paper, the authors reviewed the development of UA derivatives as the anti-diabetes anti-cardiovascular reagents., (© 2023 John Wiley & Sons Ltd.)

Pentacyclic triterpenes is a natural amphipathic product which possess a rigid backbone and several polar functional groups such as hydroxyl, carbonyl and carboxyl groups. The amphipathic character makes it easy to realize self-assemble into complex nano structure and therefore attract extensive attention due to the simple synthetic processes and renewable raw materials. Hence, a novel Ursolic acid-based hydrogel was prepared successfully via a simple self-assembly of triterpenoid derivative in methanol by capture water molecule in air. The resulting hydrogel show a porous morphology and good elasticity including strong heat resistance. Based on the characteristic above, the hydrogel showed a good iodine adsorption capacity and can removal 75.0% of the iodine from cyclohexane solution and 66.3% from aqueous solution within 36 h. Data analysis indicate that all the iodine adsorption process are dominated by chemisorption and belongs to the multi-site adsorption on heterogenous surfaces. In addition, the obtained hydrogel also possesses a good recyclability which can maintain more than 82% of its capacity after 5 cycles. The simple preparation method and easily available raw materials endow it a great potential in future pollutant treatment., 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 Elsevier Inc. All rights reserved.)

The world is currently facing a global challenge against neoplastic diseases. Chemotherapy, hormonal therapy, surgery, and radiation therapy are some approaches used to treat cancer. However, these treatments are frequently causing side effects in patients, such as multidrug resistance, fever, weakness, and allergy, among others side effects. As a result, current research has focused on phytochemical compounds isolated from plants to treat deadly cancers. Plants are excellent resources of bioactive molecules, and many natural molecules have exceptional anticancer properties. They produce diverse anticancer derivatives such as alkaloids, terpenoids, flavonoids, pigments, and tannins, which have powerful anticancer activities against various cancer cell lines and animal models. Because of their safety, eco-friendly, and cost-effective nature, research communities have recently focused on various phytochemical bioactive molecules. Ursolic acid (UA) and its derivative compounds have anti-inflammatory, anticancer, apoptosis induction, anti-carcinogenic, and anti-breast cancer proliferation properties. Ursolic acid (UA) can improve the clinical management of human cancer because it inhibits cancer cell viability and proliferation, preventing tumour angiogenesis and metastatic activity. Therefore, the present article focuses on numerous bioactivities of Ursolic acid (UA), which can inhibit cancer cell production, mechanism of action, and modulation of anticancer properties via regulating various cellular processes.

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO 2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC 50 17.90 ± 1.2 μg/mL; LC 50 26.73 ± 1.2 μg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity., (© 2023 John Wiley & Sons Ltd.)

Ursolic acid (UA) is a pentacyclic triterpenoid widely found in in medicinal plants, edible plants, fruits, and flowers. The great interest in this bioactive compound is related to the positive effects in human health. However, its limited solubility, moderate biological activity and poor bioavailability limit the potential and further applications of UA. Here, we explored the efficacy of MeON-Glycosides of UA in inhibiting tumor cell proliferation. A number of compounds showed significant antitumor activity against tested five cancer cell lines. Among them, compound 2a exhibited the most potent activity against HepG2 cells with IC 50 values of 3.1 ± 0.5 μM. Especially, compound 2a could induce HepG2 cells apoptosis and reduce mitochondrial membrane potential. Western blot analysis showed that compound 2a up-regulated Bax, cleaved caspase-3/9, cleaved PARP levels and down-regulated Bcl-2 level of HepG2 cells. These results indicated that compound 2a could obviously induce the apoptosis of HepG2 cells. At the same time, compound 2a significantly decreased the expression of p-AKT and p-mTOR, which indicated that compound 2a might exert its cytotoxic effect by targeting PI3K/AKT/mTOR signaling pathway. Moreover, the in silico ADME predictions showed that compound 2a has improved water solubility and other properties. Thus, compound 2a may be a promising antitumor candidate, which may be potentially used to prevent or treat cancers., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

In this study, methanol, ethanol, methanol-dichloromethane (1 : 1, v/v), acetone, ethyl acetate, diethyl ether, and chloroform extracts of lavender (Lavandula stoechas L. subsp. stoechas) were prepared by maceration, and the ursolic acid contents in the extracts were determined quantitatively by HPLC analyses. The present results show that the methanol-dichloromethane (1 : 1, v/v) solvent system is the most efficient solvent system for the extraction of ursolic acid from the plant sample with the highest yield (2.22 g/100 g plant sample). In the present study, a new practical method for the isolation of ursolic acid from polar extracts was also demonstrated for the first time. The inhibition effects of the extracts and ursolic acid were also revealed on α-glycosidase, acetylcholinesterase, butyrylcholinesterase, and human carbonic anhydrase I and II enzymes by determining IC 50 values for the first time. The extracts and ursolic acid acted as potent antidiabetic agents by strongly inhibiting the α-glycosidase activity, whereas they were found to be very weak neuroprotective agents. In view of the present results, L. stoechas and its major metabolite, ursolic acid, can be recommended as a herbal source to control postprandial blood sugar levels and prevent diabetes by delaying the digestion of starch in food., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Cuticular wax has been reported to play an essential role in resisting pathogens in various fruits. This study investigated the antifungal ability of the components in blueberry cuticular wax. We showed that the cuticular wax of blueberry inhibited the growth of Botrytis cinerea and ursolic acid (UA) was the key antifungal compound. UA inhibited B. cinerea growth in vitro and in vivo. Furthermore, UA increased extracellular conductivity and cellular leakage in B. cinerea, deformed the mycelial morphology, and destroyed cell ultrastructure. We also demonstrated that UA stimulated the accumulation of reactive oxygen species (ROS) and inactivated ROS scavenging enzymes. These results indicate that UA may exert antifungal effects against B. cinerea by disrupting cell membrane integrity. Thus, UA has significant potential as an agent for the control of gray mold in blueberry., 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 Ltd.)

Viscum album L. (mistletoe) is a semiparasitic plant of the Santalaceae family. A valuable group of bioactive compounds in mistletoe are triterpene acids (TTAs), which possess anti-inflammatory and anticancer properties. Parrotia persica and Carpinus betulus are the most common hosts of mistletoe in the Hyrcanian forests of Iran. This study was performed to compare the content of oleanolic acid (OA), betulinic acid (BA), and ursolic acid (UA) in the mistletoe foliage (stems and leaves) from P. persica and C. betulus in various seasons for the first time. The results showed that OA was the prevailing TTA in all samples, while UA was found in none of them. The maximum amount of OA (12.38 mg/g dry weight [DW]) and BA (1.68 mg/g DW) was detected in V. album from P. persica in summer. The minimum amount of OA (5.58 mg/g DW) and BA (0.72 mg/g DW) was observed in that growing on C. betulus in winter. However, the mistletoe from C. betulus showed the greatest level of OA in spring (9.06 mg/g DW) and BA in summer and autumn (0.92 and 0.97 mg/g DW, respectively). The data collected in this study complement existing research on this subject from around the world., (© 2023. The Author(s).)

Background: Jatyadi taila (JT) is a well-known Ayurvedic wound-healing product, comprising 16 different medicinally important plants, including Curcuma longa, Terminalia chebula, and Jasminum officinale., Objective: The proposed work discusses the development and validation of the green and economical stability-indicating HPTLC method for quantification of the key marker phytoconstituents, curcumin (CUR), gallic acid (GA), and ursolic acid (UA), from JT., Method: Quality standard parameters for JT were determined following standard procedures. The marker constituents CUR, GA, and UA were resolved from JT using toluene-ethyl acetate-formic acid (6:2:1, v/v/v) as the mobile phase and subsequently derivatized to estimate UA. The developed plates were subjected to HPTLC-MS analysis. All constituents were subjected to forced degradation to determine the proposed technique's stability-indicating property and the accelerated stability studies of marketed formulation and marker constituents. Greenness evaluation of the method was aided by the AGREE methodology., Results: The Rf values of CUR, GA, and UA were found to be 0.60 and 0.60; 0.27 and 0.28; and 0.74 and 0.77 from reference standard and oil samples respectively, when analyzed at 366 nm, 290 nm, and 366 nm, respectively. HPTLC-MS was carried out to verify the active constituents present in JT. The constituents followed first-order degradation kinetics. The quantity of CUR, GA, and UA in JT was reduced at the end of accelerated stability studies. The developed approach was validated in compliance with the International Conference on Harmonization (ICH) Q2 (R2) guideline., Conclusions: Among the chosen key markers, GA was highly unstable during forced degradation. JT should be stored at a controlled temperature using more protective packaging material to ensure its quality and efficacy., Highlights: The developed method can be used as a quality control tool for JT as it can be used to determine the stability of the key marker compounds the herbal formulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Plants produce biologically active metabolites that have been utilised to cure a variety of severe and persistent illnesses. There is a possibility that understanding how these bioactive molecules work would allow researchers to come up with better treatments for diseases including malignancy, cardiac disease and neurological disorders. A triterpene called ursolic acid (UA) is a pentacyclic prevalent triterpenoid found in fruits, leaves, herbs and blooms. The biological and chemical aspects of UA, as well as their presence, plant sources and biosynthesis, and traditional and newer technologies of extraction, are discussed in this review. Because of its biological function in the creation of new therapeutic techniques, UA is a feasible option for the evolution and medical management of a wide range of medical conditions, including cancer and other life threatening diseases. Despite this, the substance's poor solubility in aquatic environments makes it unsuitable for medicinal purposes. This hurdle was resolved in many different ways. The inclusion of UA into various pharmaceutical delivery approaches was found to be quite effective in this respect. This review also describes the properties of UA and its pharmacokinetics, as well as therapeutic applications of UA for cancer, inflammatory and cardiovascular diseases, in addition to its anti-diabetic, immunomodulatory, hepatoprotective and anti-microbial properties. Some of the recent findings related to novel nano-sized carriers as a delivery system for UA and the patents related to the applications of UA and its various derivatives are covered in this review. The analytical study of UA, oleanolic acid and other phytoconstituents by UV, HPLC, high-performance thin-layer chromatography and gas chromatography is also discussed. In the future, UA could be explored in vivo using various animal models and, in addition, the regulatory status regarding UA needs to be explored. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

From the methanol extract of the leaves of Aralia dasyphylla Miq. (Araliaceae), ten triterpenoids including five ursane-type triterpenoids, ursolic acid ( 1 ), 3- O - α -l-arabinopyranosyl ursolic acid ( 2 ), ursolic acid 28- O - β -D-glucopyranosyl ester ( 3 ), 3- O -[ β -D-glucopyranosyl (l→3)]- α -L-arabinopyranosyl ursolic acid ( 4 ), and matesaponin 1 ( 5 ), and five oleanane-type triterpenoids, elatoside E ( 6 ), elatoside F ( 7 ), 3- O -[ β -D-glucopyranosyl (l→3)]- α- L-arabinopyranosyl oleanolic acid ( 8 ), 3- O - α -L-arabinopyranosyl oleanolic acid ( 9 ) and oleanolic acid 28- O - β -D-glucopyranosyl ester ( 10 ) were isolated. Their structures were elucidated based on 1D-, 2D-NMR and ESI-MS spectra as well as by comparison with those reported in the literature. All isolated compounds were evaluated in vitro for their cytotoxic activities against three human cancer cell lines (HepG2, LU-1 and RD) and in silico by molecular docking studies on human glucose transporter 1 (hGLUT1) protein. The triterpenoids 2 , 4 , 6 , 8 and 9 exhibited good growth inhibition of HepG2 and LU-1 cancer cell lines with IC 50 values in the range 1.76 - 7.21 (μM). The oleanane type triterpenoid 8 was the highest cytotoxic compound to inhibit all the tested cancer cell lines with IC 50 values of 2.73 ± 0.12, 1.76 ± 0.11, 2.63 ± 0.10 μM, respectively. The in silico molecular docking study results showed that compounds 4 and 6 had the highest binding affinity. Compounds 1 - 10 were evaluated for their in silico ADMET of absorption, distribution, metabolism, excretion and oral toxicity parameters. Compounds 6 , 8 , 9 and 10 from A. dasyphylla are potential hGLUT1 inhibitors and worth of further investigation for the prevention or treatment of diabetes and cancer.Communicated by Ramaswamy H. Sarma.