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1.
Int J Mol Sci ; 23(15)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35955957

RESUMO

Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50-60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of marine-derived triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B dose-dependently decreased the viability of both cell lines, with a significant reduction in OC2 cells at ≥0.1 µM at 24 and 48 h, and in SCC4 cells at ≥1 µM at 24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells were significantly observed at 20 µM of stellettin B at 48 h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were increased, whereas p62 was decreased. At 20 µM at 48 h, the expression levels of the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were significantly increased and mitogen-activated protein kinase (MAPK) signaling pathways were activated. Further investigation using the autophagy inhibitor 3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell death and autophagy. Overall, our findings show that stellettin B induces the ER stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of OSCC cells.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Triterpenos , Apoptose , Autofagia , Carcinoma de Células Escamosas/tratamento farmacológico , Estresse do Retículo Endoplasmático , Humanos , Neoplasias Bucais/tratamento farmacológico , Transdução de Sinais , Triterpenos/farmacologia
2.
Molecules ; 27(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35956820

RESUMO

Five new triterpenoids, oenotheralanosterols C-G (1-5), with seven known triterpenoidcompounds, namely 2α,3α,19α-trihydroxy-24-norurs4,12-dien-28-oic acid (6), 3ß,23-dihydroxy-1-oxo-olean-12-en-28-oic acid (7), remangilone C (8), knoxivalic acid A (9), termichebulolide (10), rosasecotriterpene A (11), androsanortriterpene C (12), were extracted and separated from the dichloromethane part of Oenothera biennis L. The anti-pulmonary fibrosis activities of all the compounds against TGF-ß1-induced damage tonormal human lung epithelial (BEAS-2B) cells were investigated in vitro. The results showed that compounds 1-2, 6, 8, and 11 exhibited significant anti-pulmonary fibrosis activities, with EC50 values ranging from 4.7 µM to 9.9 µM.


Assuntos
Oenothera biennis , Triterpenos , Fibrose , Humanos , Estrutura Molecular , Extratos Vegetais/farmacologia , Triterpenos/farmacologia
3.
Molecules ; 27(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35956824

RESUMO

Propolis is very popular for its beneficial health properties, such as antimicrobial activity and antioxidant effects. It is one of the most long-serving traditional medicines to mankind due to its interesting chemical diversity and therapeutic properties. The detailed chemical information of propolis samples is very necessary to guarantee its safety and for it to be accepted into health care systems. The phenolic profile of the hydroethanolic extract was determined using HPLC-DAD, and the antioxidant was evaluated using five complementary methods. Triterpenoids were isolated using column chromatography and characterized using 1H NMR and 13C NMR. The effects of the extract and the isolated compounds on quorum sensing mediated processes and biofilm formation in bacteria were evaluated. Protocatechic acid (40.76 ± 0.82 µg/g), 4-hydroxybenzoic acid (24.04 ± 0.21 µg/g), vanillic acid (29.90 ± 1.05 µg/g), quercetin (43.53 ± 1.10 µg/g), and luteolin (4.44 ± 0.48 µg/g) were identified and quantified. The extract showed good antioxidant activity in the DPPH•, ABTS•+, CUPRAC, and metal chelating assays, and this antioxidant effect was confirmed by cyclic voltammetry. 27-Hydroxymangiferonic acid (1), Ambolic acid (2), and Mangiferonic acid (3) were isolated from anti-quorum sensing activity at MIC, and it was indicated that the most active sample was the extract with inhibition diameter zone of 18.0 ± 1.0 mm, while compounds 1, 2, and 3 had inhibition zones of 12.0 ± 0.5 mm, 9.0 ± 1.0 mm, and 12.3 ± 1.0 mm, respectively. The samples inhibited the P. aeruginosa PA01 swarming motility at the three tested concentrations (50, 75, and 100 µg/mL) in a dose-dependent manner. The propolis extract was able to inhibit biofilm formation by S. aureus, E. coli, P. aeruginosa, C. albicans, and C. tropicalis at MIC concentration. Compound 1 proved biofilm inhibition on S. aureus, L. monocytogenes, E. faecalis, E. coli, and C. tropicalis at MIC and MIC/2; compound 2 inhibited the formation of biofilm at MIC on S. aureus, E. faecalis, E. coli, S. typhi, C. albicans, and C. tropicalis; and compound 3 inhibited biofilm formation on E. faecalis, E. coli, C. albicans, and C. tropicalis and further biofilm inhibition on E. coli at MIC/4 and MIC/8. The studied propolis sample showed important amounts of cycloartane-type triterpene acids, and this indicates that there can be significant intra-regional variation probably due to specific flora within the vicinity. The results indicate that propolis and its compounds can reduce virulence factors of pathogenic bacteria.


Assuntos
Própole , Triterpenos , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Bactérias , Biofilmes , Camarões , Candida albicans , Misturas Complexas/farmacologia , Escherichia coli , Pradaria , Testes de Sensibilidade Microbiana , Fenóis/farmacologia , Própole/química , Própole/farmacologia , Pseudomonas aeruginosa , Staphylococcus aureus , Triterpenos/farmacologia
4.
Gen Physiol Biophys ; 41(4): 263-274, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35938960

RESUMO

Platycodin D (PD) is a triterpenoid saponin, a major bioactive constituent of the roots of Platycodon grandiflorum, which is well known for possessing various pharmacological properties. However, the anti-cancer mechanism of PD in bladder cancer cells remains poorly understood. In the current study, we investigated the effect of PD on the growth of human bladder urothelial carcinoma cells. PD treatment significantly reduced the cell survival of bladder cancer cells associated with induction of apoptosis and DNA damage. PD inhibited the expression of inhibitor of apoptosis family members, activated caspases, and induced cleavage of poly (ADP-ribose) polymerase. PD also increased the release of cytochrome c into the cytoplasm by disrupting the mitochondrial membrane potential while upregulating the expression ratio of Bax to Bcl-2. The PD-mediated anti-proliferative effect was significantly inhibited by pre-treatment with a pancaspase inhibitor, but not by an inhibitor of necroptosis. Moreover, PD suppressed the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, and the apoptosis-inducing effect of PD was further enhanced by a PI3K inhibitor. In addition, PD increased the accumulation of reactive oxygen species (ROS), whereas N-acetyl cysteine (NAC), an ROS inhibitor, significantly attenuated the growth inhibition and inactivation of the PI3K/Akt/mTOR signaling caused by PD. Furthermore, NAC significantly suppressed apoptosis, DNA damage, and decreased cell viability induced by PD treatment. Collectively, our findings indicated that PD blocked the growth of bladder urothelial carcinoma cells by inducing ROS-mediated inactivation of the PI3K/Akt/mTOR signaling.


Assuntos
Carcinoma de Células de Transição , Saponinas , Triterpenos , Neoplasias da Bexiga Urinária , Apoptose , Humanos , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinase/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Triterpenos/farmacologia , Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
5.
Int J Mol Sci ; 23(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35955423

RESUMO

Triterpenes are a diverse group of natural compounds found in plants. Soyasapogenol B (SoyB) from Arachis hypogaea (peanut) has various pharmacological properties. This study aimed to elucidate the pharmacological properties and mechanisms of SoyB in bone-forming cells. In the present study, 1-20 µM of SoyB showed no cell proliferation effects, whereas 30-100 µM of SoyB increased cell proliferation in MC3T3-E1 cells. Next, osteoblast differentiation was analyzed, and it was found that SoyB enhanced ALP staining and activity and bone mineralization. SoyB also induced RUNX2 expression in the nucleus with the increased phosphorylation of Smad1/5/8 and JNK2 during osteoblast differentiation. In addition, SoyB-mediated osteoblast differentiation was not associated with autophagy and necroptosis. Furthermore, SoyB increased the rate of cell migration and adhesion with the upregulation of MMP13 levels during osteoblast differentiation. The findings of this study provide new evidence that SoyB possesses biological effects in bone-forming cells and suggest a potentially beneficial role for peanut-based foods.


Assuntos
Arachis , Triterpenos , Autofagia , Diferenciação Celular , Linhagem Celular , Necroptose , Ácido Oleanólico/análogos & derivados , Osteoblastos/metabolismo , Saponinas , Triterpenos/metabolismo , Triterpenos/farmacologia
6.
Hum Exp Toxicol ; 41: 9603271221111333, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35786050

RESUMO

As a pentacyclic triterpenoid compound, Ursolic acid (UA) broads range of biological effects. CXCL12 is a ligand for CXCR4 and CXCR7 proteins on thyroid cancer cells. Here we examined the effects of UA on the proliferation, migration and invasion of papillary thyroid carcinoma (PTCs) in a dose-manner. In addition, UA can reduce the expression levels of CXCR4 and CXCR7 in PTCs. In addition to this direct anticancer pathway, studies have shown that UA can play an anticancer role by affecting the secretion of CXCL12 in cancer-associated fibroblasts (CAFs). After treated with UA, normal fibroblasts and CAFs culture medium (CM) showed differential CXCL12 expression levels. We prepared fibroblast conditioned medium according to the intervention of UA, then cultured TPC-1 and B-CPAP cells with differential CM, and detected significant differences in the proliferation, migration and invasion of cancer cells. Our findings uncovered an indirect anticancer mechanism of UA. This cancer chemopreventive properties is expected to make UA a clinically useful chemopreventive agent.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias da Glândula Tireoide , Triterpenos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Movimento Celular , Proliferação de Células , Quimiocina CXCL12/farmacologia , Humanos , Receptores CXCR , Receptores CXCR4 , Câncer Papilífero da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Triterpenos/farmacologia
7.
Int J Mol Sci ; 23(14)2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35887090

RESUMO

Triterpenic acids are phytocompounds with a widespread range of biological activities that have been the subject of numerous in vitro and in vivo studies. However, their underlying mechanisms of action in various pathologies are not completely elucidated. The current review aims to summarize the most recent literature, published in the last five years, regarding the mechanism of action of three triterpenic acids (asiatic acid, oleanolic acid, and ursolic acid), corelated with different biological activities such as anticancer, anti-inflammatory, antidiabetic, cardioprotective, neuroprotective, hepatoprotective, and antimicrobial. All three discussed compounds share several mechanisms of action, such as the targeted modulation of the PI3K/AKT, Nrf2, NF-kB, EMT, and JAK/STAT3 signaling pathways, while other mechanisms that proved to only be specific for a part of the triterpenic acids discussed, such as the modulation of Notch, Hippo, and MALAT1/miR-206/PTGS1 signaling pathway, were highlighted as well. This paper stands as the first part in our literature study on the topic, which will be followed by a second part focusing on other triterpenic acids of therapeutic value.


Assuntos
Ácido Oleanólico , Triterpenos , Anti-Inflamatórios , Ácido Oleanólico/farmacologia , Fosfatidilinositol 3-Quinases , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Triterpenos/uso terapêutico
8.
J Med Chem ; 65(14): 10014-10044, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35801495

RESUMO

In this study, 70 new seco-lupane triterpene derivatives were designed, synthesized, and characterized, and their in vitro anticancer activities were evaluated. Structure-activity relationship studies showed that most compounds inhibited the growth of a variety of tumor cells in vitro. With the extension of alkyl chains, the activity of azole compounds gradually increased while that of indole compounds first increased and then decreased. Moreover, all indole derivatives showed stronger anticancer activity than azole derivatives. In addition, compound 21 showed the strongest inhibitory effect on HepG2 cells with an IC50 value of 0.97 µM. Mechanistic studies showed that compound 21 coregulates the cell death process by inducing ferroptosis and regulating the cell cycle. In conclusion, compound 21 can be used as a ferroptosis inducer and cycle blocker to regulate the HepG2 death process, and it has the potential to become an effective new drug for the treatment of hepatocellular carcinoma.


Assuntos
Antineoplásicos , Ferroptose , Triterpenos , Antineoplásicos/farmacologia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/farmacologia , Imidazóis/farmacologia , Indóis/farmacologia , Estrutura Molecular , Triterpenos Pentacíclicos/farmacologia , Sulfonamidas , Tiofenos , Triterpenos/farmacologia
9.
Bioorg Chem ; 127: 106012, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35830756

RESUMO

Extensive phytochemical investigation on the methanol extract of the inflorescences, twigs, and leaves of Brucea javanica led to the isolation and identification of 27 triterpenoids, including 21 previously undescribed ones, named brujavanoids A-U (1-21). Their structures were determined based on comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Of these compounds, brujavanoid A (1) represents the first apotirucallane-type triterpenoid with a novel 19(10 â†’ 9)abeo motif, and brujavanoids B and C (2-3) are the first apotirucallane-type triterpenoids with a rarely occurring 14-hydorxy-15,16-epoxy fragment. All the isolates were evaluated for their anti-inflammatory effect in an LPS-activated RAW264.7 cells model. Furthermore, the most active one, brujavanoid E (5), can suppress the transcriptional expression of typical pro-inflammatory mediators and inhibit the nuclear translocation of NF-κB p65 in the LPS- activated RAW264.7 cells.


Assuntos
Brucea , Triterpenos , Anti-Inflamatórios/farmacologia , Brucea/química , Brucea javanica , Lipopolissacarídeos/farmacologia , Triterpenos/química , Triterpenos/farmacologia
10.
Bioorg Chem ; 127: 106013, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35841667

RESUMO

In the present study, six new cucurbitane type compounds, including three triterpenoids hemsleyacins P-R (6-7, 13) and three cucurbitane-type triterpenoid glycosides hemsleyaosides L-N (15-17), along with seventeen known cucurbitacin analogues were separated from the root tuber of Hemsleya penxianensis and elucidated based on NMR and HRESIMS. Then, 23 analogues of three types, namely, polyhydroxy-type (I) (1-7), monohydroxy-type (II) (8-13), and glycosides-type (III) (14-23), were assessed for their antitumor activity and structure-activity relationship analysis (SAR). We determined temozolomide (TMZ)-resistant GBM cell was the most sensitive to the tested compounds, and found hemsleyaoside N (HDN) displayed the best antineoplastic potency. Furthermore, we confirmed the anti-glioma activity of HDN in patient-derived recurrent GBM strains, GBM organoid (GBO) and orthotopic nude mouse models. Investigations exploring the mechanism made clear that HDN induced synchronous activation of UPR and MAPK signaling, which triggered deadly ER stress and apoptosis. Taken together, the potent antitumor activity of HDN warrants further comprehensive evaluation as a novel anti-glioma agent.


Assuntos
Cucurbitaceae , Glioma , Triterpenos , Animais , Apoptose , Linhagem Celular Tumoral , Cucurbitaceae/química , Resistencia a Medicamentos Antineoplásicos , Glioma/tratamento farmacológico , Glioma/patologia , Glicosídeos/química , Glicosídeos/farmacologia , Camundongos , Triterpenos/química , Triterpenos/farmacologia
11.
Cytokine ; 157: 155947, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35780710

RESUMO

BACKGROUND: Ursolic acid (UA) is a pentacyclic triterpenoid compound with a wide range of anti-tumor, anti-inflammatory, hypotensive and other pharmacological effects. Here, the biological roles and regulatory mechanisms of UA in influenza A virus (IAV)-treated A549 cells were investigated. METHOD: The cytotoxic impacts of UA on A549 cells with or without IAV treatment were determined using MTT and LDH assays. The inflammatory responses and oxidative stress of IAV-treated A549 cells were measured by RT-qPCR, ELISA, DCFH-DA probe, and colorimetric assays. A dual luciferase assay was carried out to validate the molecular interaction between miR-34c-5p and TLR5. Promoter methylation was detected by MSP experiment. Methylation-related proteins were quantified by western blot. Virus replication was assessed by TCID50 and western blot assays. RESULTS: UA significantly ameliorated IAV-triggered cell injury and inflammatory response, virus replication and oxidative stress by elevating cell viability, ROS level and the activities of SOD and GSH-Px but reducing the LDH, MDA, and TCID50 values and the expression of virus-related proteins (NP) and cytokines (TNF-α, IL-1ß, IL-6, and IL-18). Moreover, UA promoted miR-34c-5p expression by repressing DNMTs-mediated methylation. TLR5 was verified to be a direct target of miR-34c-5p and could be downregulated by UA. Rescue experiments revealed that silencing miR-34c-5p diminished the regulatory roles of UA in IAV-treated A549 cells. CONCLUSION: Our data elucidated that UA attenuated IAV-triggered inflammatory responses and oxidative stress in A549 cells by regulating the miR-34c-5p/TLR5 axis, suggesting that UA plays a protective role in IAV-induced pneumonia.


Assuntos
Antineoplásicos , Vírus da Influenza A , MicroRNAs , Triterpenos , Células A549 , Antineoplásicos/uso terapêutico , Apoptose , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo , Receptor 5 Toll-Like/metabolismo , Triterpenos/farmacologia , Triterpenos/uso terapêutico
12.
Biomed Res Int ; 2022: 7382130, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845929

RESUMO

Methods: Data from TCMSP and GEO databases were utilized to identify targets for Celastrol on DCM. The relationship between the major targets and conventional glycolipid metabolism was obtained with Spearman correlation analysis. Experiments on animals were conducted utilizing healthy control (HC), low-dose Celastrol interventions (CL), and no intervention groups (NC), all of which had 8 SD rats in each group. To study alterations in signaling molecules, RT-PCR was performed. Results: There were 76 common targets and 5 major targets for Celastrol-DCM. Celastrol have been found to regulate AGE-RAGE, TNF, MAPK, TOLL-like receptors, insulin resistance, and other signaling pathways, and they are closely linked to adipocytokines, fatty acid metabolism, glycolipid biosynthesis, and glycosylphosphati-dylinositol biosynthesis on DCM. These five major targets have been found to regulate these pathways. Experiments on rats indicated that P38 MAPK was considerably elevated in the cardiac tissue from rats in the CL and NC groups compared to the HC group, and the difference was statistically significant (P < 0.01). Significant differences were seen between the CL and NC groups in P38 MAPK levels, with a statistical significance level of less than 0.05. Conclusion: Celastrol may play a role in reversing energy remodeling, anti-inflammation, and oxidative stress via modulating p38 protein expression in the MAPK pathway, which have been shown in the treatment of DCM.


Assuntos
Triterpenos , Animais , Glicolipídeos , Farmacologia em Rede , Triterpenos Pentacíclicos , Ratos , Ratos Sprague-Dawley , Triterpenos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética
13.
Int Heart J ; 63(4): 755-762, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35831147

RESUMO

Ursolic acid (UA) has been reported to possess several biological benefits, such as anti-cancer, anti-inflammation, antibacterial, and neuroprotective functions. This study detects the function and molecular mechanism of UA in H9c2 cells under hypoxia and reoxygenation (H/R) conditions.Under H/R stimulation, the effects of UA on H9c2 cells were examined using ELISA and western blot assays. The Comparative Toxicogenomics Database was employed to analyze the target molecule of UA. Small interfering RNA was used to knock down CXCL2 expression, further exploring the function of CXCL2 in H/R-induced H9c2 cells. The genes related to the nuclear factor-kappa B (NF-κB) pathway were assessed using western blot analysis.Significant effects of UA on H/R-induced H9c2 cell damage were observed, accompanied by reduced inflammation and oxidative stress injury. Additionally, the increased level of CXCL2 in H/R-induced H9c2 cells was reduced after UA stimulation. Moreover, CXCL2 knockdown strengthened the beneficial effect of UA on H/R-induced H9c2 cells. HY-18739, an activator of the NF-κB pathway, can increase CXCL2 expression. Moreover, the increased levels of p-P65 NF-κB and p-IκBα in H/R-induced H9c2 cells were remarkably attenuated by UA treatment.In summary, the results indicated that UA may alleviate the damage of H9c2 cells by targeting the CXCL2/NF-κB pathway under H/R conditions.


Assuntos
NF-kappa B , Triterpenos , Anti-Inflamatórios/farmacologia , Apoptose , Quimiocina CXCL2/metabolismo , Quimiocina CXCL2/farmacologia , Humanos , Hipóxia/metabolismo , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Triterpenos/metabolismo , Triterpenos/farmacologia
14.
Sci Rep ; 12(1): 9370, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672366

RESUMO

Medicinal plants are in use of humankind since ancient and still they are playing an important role in effective and safer natural drug delivery systems. Acacia nilotica (native of Egypt) commonly known as babul belongs to family Fabaceae, widely spread in India, Sri Lanka and Sudan. Being a common and important plant, using in many ways from fodder (shoots and leaves to animals) to dyeing (leather coloration) to medicine (root, bark, leaves, flower, gum, pods). The present study is focused on investigating the natural chemistry and important biological activities of the plant. Employing bioassay guided fractionation coupled with TLC and column chromatography, a pure fraction named AN-10 was isolated from ethyl acetate fraction of crude methanol extract which identified as "Betulin (Lupan-3ß,28-diol)" by Liebermann-Burchard test and structure elucidation by UV-Vis, NMR and MS techniques. A battery of in vitro biological assays for antioxidant, anti-inflammatory and anticancer were performed and betulin showed excellent potential in all assays. It was found that the inhibitory potential in all assays were dose dependent manner and after a range of concentration, the activities get leveled off with no further increase in activity.


Assuntos
Acacia , Triterpenos , Acacia/química , Animais , Casca de Planta/química , Extratos Vegetais/química , Triterpenos/análise , Triterpenos/farmacologia
15.
Biochim Biophys Acta Biomembr ; 1864(10): 183993, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35724740

RESUMO

Triterpene glycosides are a diverse group of plant secondary metabolites, consisting of a sterol-like aglycon and one or several sugar groups. A number of triterpene glycosides show membranolytic activity, and, therefore, are considered to be promising antimicrobial drugs. However, the interrelation between their structure, biological activities, and target membrane lipid composition remains elusive. Here we studied the antifungal effects of four Panax triterpene glycosides (ginsenosides) with sugar moieties at the C-3 (ginsenosides Rg3, Rh2), C-20 (compound K), and both (ginsenoside F2) positions in Saccharomyces cerevisiae mutants with altered sterol plasma membrane composition. We observed reduced cytostatic activity of the Rg3 and compound K in the UPC2-1 strain with high membrane sterol content. Moreover, LAM gene deletion reduced yeast resistance to Rg3 and digitonin, another saponin with glycosylated aglycon in the C-3 position. LAM genes encode plasma membrane-anchored StARkin superfamily-member sterol transporters. We also showed that the deletion of the ERG6 gene that inhibits ergosterol biosynthesis at the stage of zymosterol increased the cytostatic effects of Rg3 and Rh2, but not the other two tested ginsenosides. At the same time, in silico simulation revealed that the substitution of ergosterol with zymosterol in the membrane changes the spatial orientation of Rg3 and Rh2 in the membranes. These results imply that the plasma membrane sterol composition defines its interaction with triterpene glycoside depending on their glycoside group position. Our results also suggest that the biological role of membrane-anchored StARkin family protein is to protect eukaryotic cells from triterpenes glycosylated at the C-3 position.


Assuntos
Citostáticos , Ginsenosídeos , Triterpenos , Ergosterol , Ginsenosídeos/metabolismo , Ginsenosídeos/farmacologia , Saccharomyces cerevisiae/genética , Esteróis , Açúcares , Triterpenos/farmacologia
16.
Bioorg Chem ; 125: 105924, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35687940

RESUMO

The semisynthesis of novel derivatives of lupeyl palmitate and 3ß-palmitoyloxy-olean-12-ene by introduction of a pyrazine at C-2 / C-3 and modifications of the relatively unexplored C-30 position of lupeol derivatives was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. The derivatives 7, 10 and 11 significantly inhibited the tumor cell lines U251, K562, HCT-15, MCF-7 and SKLU-1, and compounds 7 and 11 were more active (IC50 25.4 ± 2.0 µM and 7.1 ± 0.4 µM, respectively) than the positive control (etoposide (IC50 31.5 ± 2.2 µM) in the tumor line PC-3. Introduction of the pyrazine at C-2 / C-3 in compounds 1 and 2 or modification at C-30 of compound 1 decreased the anti-inflammatory activity in the TPA-induced mouse ear edema. Following the results of the PASS online evaluation of the potential biological activity of the natural compounds and their derivatives, the inhibition of pNF-κB translocation to the prostate cancer (PC-3) cell nucleus was investigated and the binding mode of compounds 7, 10 and 11 with the human NF-κB receptor was explored by a molecular docking study. These derivatives bound directly or close to the amino acids that form the DNA recognition site. The ADMET physicochemical parameters of the fifteen compounds were further analyzed in silico using Molinspiration calculations indicating the potential of compounds 7, 10 and 11 for further investigation.


Assuntos
Antineoplásicos , Triterpenos , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Triterpenos Pentacíclicos/farmacologia , Pirazinas , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacologia
17.
Med Oncol ; 39(8): 118, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35674939

RESUMO

We investigated the antitumor effects of oleanolic acid (OA) and ursolic acid (UA) on adult T-cell leukemia cells. OA and UA dose-dependently inhibited the proliferation of adult T-cell leukemia cells. UA-treated cells showed caspase 3/7 and caspase 9 activation. PARP cleavage was detected in UA-treated MT-4 cells. Activation of mTOR and PDK-1 was inhibited by UA. Autophagosomes were detected in MT-4 cells after UA treatment using electron microscopy. Consistently, mitophagy was observed in OA- and UA-treated MT-4 cells by confocal microscopy. The mitochondrial membrane potential in MT-4 cells considerably decreased, and mitochondrial respiration and aerobic glycolysis were significantly reduced following UA treatment. Furthermore, MT-1 and MT-4 cells were sorted into two regions based on their mitochondrial membrane potential. UA-treated MT-4 cells from both regions showed high activation of caspase 3/7, which were inhibited by Z-vad. Interestingly, MT-4 cells cocultured with sorted UA-treated cells showed enhanced proliferation. Finally, UA induced cell death and ex vivo PARP cleavage in peripheral blood mononuclear cells from patients with adult T-cell leukemia. Therefore, UA-treated MT-4 cells show caspase activation following mitochondrial dysfunction and may produce survival signals to the surrounding cells.


Assuntos
Antineoplásicos Fitogênicos , Leucemia-Linfoma de Células T do Adulto , Ácido Oleanólico , Triterpenos , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucócitos Mononucleares/metabolismo , Mitocôndrias/metabolismo , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Triterpenos/metabolismo , Triterpenos/farmacologia
18.
Molecules ; 27(11)2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35684557

RESUMO

Betulin is the most popular of the known triterpenoids of the lupan series. It has valuable pharmacological properties. It exhibits antibacterial, antiviral, antitumor, hypolipidemic and other types of activity. The prospects of using betulin in medicine, pharmacology, and veterinary medicine require the development of effective methods for obtaining it from waste from the woodworking industry. Therefore, the question arises of the need to develop a technology for isolating and purifying triterpenoids from birch bark in large quantities. This review contains a variety of methods for the isolation of betulin. The advantages and disadvantages of the proposed methods are described. The following methods are considered: vacuum sublimation after preliminary alkaline; vacuum pyrolysis; supercritical extraction with carbon dioxide or mixtures of carbon dioxide with various solvents; extraction with organic solvents. Also, the method of microwave is described, it is activation on the example of the Kyrgyz birch (Betula kirghisorum), this is an endemic species that has not been studied before, growing on the territory of the Republic of Kazakhstan.


Assuntos
Betula , Triterpenos , Dióxido de Carbono/química , Casca de Planta/química , Solventes , Triterpenos/química , Triterpenos/farmacologia
19.
Molecules ; 27(11)2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35684565

RESUMO

BACKGROUND: Poria cocos (P. cocos) is an important medicinal fungus in traditional Chinese medicine. Poria acid (PA), a triterpenoid compound, is an effective component of traditional Chinese medicine P. cocos. This experiment investigated the anti-gastric cancer biological activity of PA in vitro. METHODS: The effect of PA on the viability of gastric cancer cells was detected by the thiazolyl blue (MTT) assay. Cell adhesion assays were used to detect changes in the adhesion of cells treated after PA (0, 20, 40, and 80 µmol/L). The ability of cell invasion and migration were detected by Transwell assays and wound healing assays. A high-content imaging system was used to dynamically record the motility of the gastric cancer cells after PA (0, 20, 40, and 80 µmol/L) treatment. Western blotting was used to detect the expression of epithelial-mesenchymal transformation (EMT), invasion and migration related proteins. RESULTS: The MTT assay showed that the proliferation of gastric cancer cells was significantly inhibited after PA treatment. Cell adhesion experiments showed that the adhesion of gastric cancer cells was significantly decreased after PA treatment. Compared with the control group, the wound healing area of the gastric cancer cells treated with different concentrations of PA decreased. The Transwell assay showed that the number of gastric cancer cells passing through the cell membrane were significantly reduced after PA treatment. In addition, after PA treatment, the cells' movement distance and average movement speed were significantly lower than those of the control group. Finally, PA can significantly alter the expression of EMT-related proteins E-cadherin, N-cadherin, and Vimentin and decreased the expressions of metastasis-related proteins matrix metalloproteinase (MMP) 2, MMP-9 and tissue inhibition of matrix metalloproteinase (TIMP)1 in the gastric cancer cells. CONCLUSIONS: Triterpenoids from P. cocos have significant biological activity against gastric cancer, and the mechanism may be involved in the process of epithelial-mesenchymal transformation.


Assuntos
Neoplasias Gástricas , Triterpenos , Wolfiporia , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Triterpenos/farmacologia , Wolfiporia/química
20.
Phytochemistry ; 201: 113258, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35654136

RESUMO

Six undescribed abietane-type diterpenoids (tripterydinoids A-F) and five undescribed oleanane-type triterpenoids (tripterytrinoids A-E) were obtained and determined from the stem and branch of Tripterygium wilfordii Hook. f. (Celastraceae). Tripterydinoids A-C possessed the abietane-type diterpenoid skeleton with rare 8, 9-epoxy ring. The structures of undescribed compounds were established by extensive spectroscopic studies [HRESIMS, 1D/2D-NMR and electronic circular dichroism (ECD) calculation]. The absolute configurations of tripterydinoids A, B, E and tripterytrinoid A were defined by X-ray crystallographic analyses. Bioactivity screening indicated that tripterydinoids A-C exhibited potent inhibitory effects against NO release in LPS-activated RAW 264.7 macrophages with IC50 values of 6.93, 4.46 and 2.98 µM, respectively. Meanwhile, tripterydinoids A-D and tripterytrinoids B, C showed moderate and selective cytotoxicities against five human tumor cell lines (A375, Huh7, MCF-7, HCT-116 and NCI-H460).


Assuntos
Diterpenos , Triterpenos , Abietanos/química , Abietanos/farmacologia , Linhagem Celular Tumoral , Diterpenos/farmacologia , Humanos , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Tripterygium/química , Triterpenos/farmacologia
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