1. |
- Hoa, Hoang Thai, et al.
(författare)
-
Effects of compounds from physalis angulata on fatty acid synthesis and glucose metabolism in HEPG2 cells via the AMP-activated protein kinase pathway
- 2020
-
Ingår i: Natural Product Sciences. - 1226-3907. ; 26:3, s. 200-206
-
Tidskriftsartikel (refereegranskat)abstract
- The ability of the total extract from Physalis angulata; three fractions after partitioning with n-hexane, ethyl acetate (TBE), and water; and four withanolides (compounds 1 – 4) to phosphorylate 5'-adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells was evaluated. The TBE fraction (50 μg/mL) activated p-ACC and p-AMPK expression most strongly. Compounds 1 – 4 (10 μM) upregulated p-ACC expression at different levels. Compound 4 induced the most significant changes in p-AMPK expression, followed by 1 and 2. Sterol regulatory element-binding proteins (SREBPs) play a functional role in the transcriptional regulation of the lipogenic pathway, including fatty acid synthase (FAS) and ACC. The effects of compounds 2 and 4 (10 μM) on FAS and SREBP-1c expression under high glucose conditions (30 mM) in HepG2 cells were evaluated further. Both dose-dependently inhibited FAS and SREBP-1c expression as well as lipid accumulation (1 – 10 μM) were compared to high-concentration glucose control, which upregulated FAS and SREBP-1c. These results suggest that compounds 2 and 4 upregulate AMPK, suppress FAS and SREBP-1c, and have potential effects on glucose and lipid metabolism.
|
|
2. |
- Nguyen, Tra My, et al.
(författare)
-
Effects of Coumarins from Roots of Paramignya scandens (Griff.) Craib on LPS-induced IL-1β and IL-10 Cytokine Production in RAW 264.7 Macrophages
- 2024
-
Ingår i: Natural Product Sciences. - 1226-3907. ; 30:1, s. 30-38
-
Tidskriftsartikel (refereegranskat)abstract
- Based on our previous study, we evaluated the modulatory effects on LPS-induced IL-1β and IL-10 cytokine production in RAW 264.7 macrophages of several medicinal herbs, including P. scandens. The results showed that P. scandens extract showed significant effects on LPS-induced IL-1β and IL-10 cytokine production in RAW 264.7 macrophages. Therefore, in the current research, we focused on the P. scandens sample. Cytokine production effects bioassay-guided isolation of ethyl acetate fraction of 70% ethanol extract from roots of Paramignya scandens (XL) obtained seven coumarins (1–7). Their chemical structures were identified using spectroscopic methods (NMR and MS) and compared with those previously published data to be xanthyletin (1), luvangetin (2), clausenidin (3), nordentatin (4), dentatin (5), clausarin (6), and anisocoumarin E (7). This study represents the first report on the presence of compounds 3, 6, and 7 in the Paramignya genus and compounds 1 and 2 in XL. All isolates (1–7) exhibited significant inhibition of LPS-induced interleukin (IL)-1β production compared to the LPS 5 ng/mL control group, with IL-1β concentrations ranging from 42.77 to 69.76 pg/mL. Additionally, the IL-10 production induced by compounds 1‒7 in LPS-stimulated RAW 264.7 macrophages ranged from 175.98 to 321.56 pg/mL, demonstrating a marked increase as compared to the LPS 5 ng/mL control group. The stimulatory effect on IL-10 production and inhibitory effect on IL-1β production of compounds 1, 2, and 6 gradually increased with the test concentration in both RAW 264.7 macrophages and LPS-induced RAW 264.7 macrophages. Compounds 1, 2, and 6 inhibited IL-1β production in LPS-induced RAW 264.7 macrophages with IC50 values of 10.70 ± 1.18 µM, 8.57 ± 1.05 µM, and 17.43 ± 1.05 µM, respectively. These findings highlight the potential of all the compounds derived from P. scandens roots in inducing IL-1β and IL-10 cytokines activity in LPS-stimulated RAW 264.7 macrophages. The results contributed to expanding the knowledge of the chemistry and bioactivities of P. scandens and provided valuable data for future investigations on this species.
|
|
3. |
- Diep Vu, Thi, et al.
(författare)
-
Identification and Cytotoxic Evaluation of Pregnane Saponins from the Twigs and Leaves of Dregea volubilis
- 2023
-
Ingår i: Chemistry and Biodiversity. - 1612-1872.
-
Tidskriftsartikel (refereegranskat)abstract
- Four new polyhydroxy pregnane glycosides, named volubilosides G−K (3, 5–7), along with three known secondary metabolites, dregeoside Da1 (1), dregeoside Ka1 (2), and volubiloside E (4) were isolated from the twigs and leaves of Dregea volubilis (DV). The chemical structures of these compounds (1–7) were elucidated using spectroscopic techniques (1D and 2D NMR and HR-ESI-MS analyses) and compared with those in the published literature. Compounds (1–7) were evaluated for cytotoxicity against eight cancer cell lines (MB49, K562, MKN-7, HT29, A549, MCF-7, MDA-MB-231, and HepG2), revealing varying levels of cytotoxic effects with IC50 values ranging from 4.29 to 21.05 μM. The results indicated that compounds 1–7 may serve as potential lead compounds for the discovery and development of novel anti-cancer drugs.
|
|
4. |
- Duyen, Nguyen Thi, et al.
(författare)
-
Steroid glycosides isolated from Paris polyphylla var. chinensis aerial parts and paris saponin II induces G1/S-phase MCF-7 cell cycle arrest
- 2022
-
Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215. ; 519
-
Tidskriftsartikel (refereegranskat)abstract
- In our previous research on Vietnamese medicinal plants, we found that the ethanolic extract of the aerial parts of Paris polyphylla var. chinensis exhibited cytotoxic effects in vitro in the MCF-7 human cancer cell line. Here, we used combined chromatographic separations to isolate six compounds including a new steroid glycoside, paripoloside A (3), and five known compounds, from the butanol extract of the aerial parts of P. polyphylla. We unambiguously elucidated their structures based on spectroscopic data (proton and carbon-13 nuclear magnetic resonance, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, correlation spectroscopy, and high-resolution electrospray ionization mass spectroscopy data), and chemical reactions. Among the isolated compounds, paris saponin II (PSII) had the strongest cytotoxic effects against MCF-7 breast cancer cells. Interestingly, PSII significantly increased the expression of p53, p21, p27, and Bax protein levels and significantly suppressed the expression of cyclin D1 and retinoblastoma protein. These data suggest that PSII may induce G1/S phase cell cycle arrest and apoptosis pathway development in MCF-7 cells. Furthermore, the MCF-7 breast cancer cells mechanism of PSII was also investigated using molecular docking. Together, our results demonstrate that isolated compounds from P. polyphylla are promising candidates as breast cancer inhibitors.
|
|
5. |
- Nguyen, Thi Thu, et al.
(författare)
-
Cytotoxic sesquiterpenes and diterpenes from the rhizomes of Curcuma zedoaroides Chaveer. & Tanee
- 2024
-
Ingår i: Biochemical Systematics and Ecology. - 0305-1978. ; 112
-
Tidskriftsartikel (refereegranskat)abstract
- A phytochemical investigation of Curcuma zedoaroides rhizomes resulted in the isolation of ten sesquiterpenes (1–10) and two diterpenes (11−12). The structure of compounds 1–12 was identified as phaeocaulisin E (1), zedoarondiol (2), isozedoarondiol (3), isoprocurcumenol (4), neoprocurcumenol (5), procurcumenol (6), 1-epi-procurcumenol (7), aerugidiol (8), curcumenol (9), curcumenone (10), curcuminol E (11), and zerumin A (12) using MS and NMR methods. Remarkably, all these compounds were found in C. zedoaroides for the first time and their chemotaxonomic significance was also discussed. Moreover, the fractionated extracts of C. zedoaroides (n-hexane, ethyl acetate, and water) were demonstrated to have effects on eight cancer cell lines (A549, MCF-7, HT-29, MB49, HepG2, MDA-MB231, JB6-C141, and K562), exhibiting IC50 values ranging from 5.43 to 11.96 μg/mL. Compounds 1–9 and 11−12 displayed significant activity against five cancer cell lines (A549, MCF-7, MDA-MB231, HL-60, and HepG2), with IC50 values ranging from 3.13 μM to 30.10 μM. The most potent effect was observed in the A549 cell line (IC50: 3.13–13.54 μM).
|
|
6. |
- Brisuda, Antonín, et al.
(författare)
-
Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Partially unfolded alpha-lactalbumin forms the oleic acid complex HAMLET, with potent tumoricidal activity. Here we define a peptide-based molecular approach for targeting and killing tumor cells, and evidence of its clinical potential (ClinicalTrials.gov NCT03560479). A 39-residue alpha-helical peptide from alpha-lactalbumin is shown to gain lethality for tumor cells by forming oleic acid complexes (alpha1-oleate). Nuclear magnetic resonance measurements and computational simulations reveal a lipid core surrounded by conformationally fluid, alpha-helical peptide motifs. In a single center, placebo controlled, double blinded Phase I/II interventional clinical trial of non-muscle invasive bladder cancer, all primary end points of safety and efficacy of alpha1-oleate treatment are reached, as evaluated in an interim analysis. Intra-vesical instillations of alpha1-oleate triggers massive shedding of tumor cells and the tumor size is reduced but no drug-related side effects are detected (primary endpoints). Shed cells contain alpha1-oleate, treated tumors show evidence of apoptosis and the expression of cancer-related genes is inhibited (secondary endpoints). The results are especially encouraging for bladder cancer, where therapeutic failures and high recurrence rates create a great, unmet medical need.
|
|
7. |
- Hien, Tran Thi, et al.
(författare)
-
Bladder cancer therapy without toxicity—A dose-escalation study of alpha1-oleate
- 2020
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 147:9, s. 2479-2492
-
Tidskriftsartikel (refereegranskat)abstract
- Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. Our study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intravesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17 mM) on days 3 to 11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor-bearing mice or healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.
|
|
8. |
- Ho, James C.S., et al.
(författare)
-
Lipid bilayer composition as a determinant of cancer cell sensitivity to tumoricidal protein-lipid complexes
- 2022
-
Ingår i: BioFactors. - : Wiley. - 0951-6433 .- 1872-8081. ; 48:5, s. 1145-1159
-
Tidskriftsartikel (refereegranskat)abstract
- Complexes formed by the alpha1 N-terminal peptide of alpha-lactalbumin and oleic acid (alpha1-oleate) interact with lipid bilayers. Plasma membrane perturbations trigger tumor cell death but normal differentiated cells are more resistant, and their plasma membranes are less strongly affected. This study examined membrane lipid composition as a determinant of tumor cell reactivity. Bladder cancer tissue showed a higher abundance of unsaturated lipids enriched in phosphatidylcholine, PC (36:4) and PC (38:4), and sphingomyelin, SM (36:1) than healthy bladder tissue, where saturated lipids predominated and the lipid extracts from bladder cancer tissue inhibited the tumoricidal effect of the complex more effectively than healthy tissue extracts. Furthermore, unsaturated PC in solution inhibited tumor cell death, and the complex interacted with giant unilamellar vesicles formed by PC, confirming the affinity of alpha1-oleate for fluid membranes enriched in PC. Quartz Crystal Microbalance with dissipation monitoring (QCM-D) detected a preference of the complex for the liquid-disordered phase, suggesting that the insertion into PC-based membranes and the resulting membrane perturbations are influenced by membrane lipid saturation. The results suggest that the membrane lipid composition is functionally important and that specific unsaturated membrane lipids may serve as “recognition motifs” for broad-spectrum tumoricidal molecules such as alpha1-oleate.
|
|
9. |
- Ambite, Inès, et al.
(författare)
-
Active bacterial modification of the host environment through RNA polymerase II inhibition
- 2021
-
Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 131:4
-
Tidskriftsartikel (refereegranskat)abstract
- Unlike pathogens, which attack the host, commensal bacteria create a state of friendly coexistence. Here, we identified a mechanism of bacterial adaptation to the host niche, where they reside. Asymptomatic carrier strains were shown to inhibit RNA polymerase II (Pol II) in host cells by targeting Ser2 phosphorylation, a step required for productive mRNA elongation. Assisted by a rare, spontaneous loss-of-function mutant from a human carrier, the bacterial NlpD protein was identified as a Pol II inhibitor. After internalization by host cells, NlpD was shown to target constituents of the Pol II phosphorylation complex (RPB1 and PAF1C), attenuating host gene expression. Therapeutic efficacy of a recombinant NlpD protein was demonstrated in a urinary tract infection model, by reduced tissue pathology, accelerated bacterial clearance, and attenuated Pol II-dependent gene expression. The findings suggest an intriguing, evolutionarily conserved mechanism for bacterial modulation of host gene expression, with a remarkable therapeutic potential.
|
|
10. |
- Ambite, Ines, et al.
(författare)
-
Molecular determinants of disease severity in urinary tract infection
- 2021
-
Ingår i: Nature Reviews Urology. - : Springer Science and Business Media LLC. - 1759-4812 .- 1759-4820. ; 18:8, s. 468-486
-
Forskningsöversikt (refereegranskat)abstract
- The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of their functions is crucial for strategies to counter microbial aggression with novel treatment and prevention measures. One approach is the use of bacterial molecules that reprogramme the innate immune system, accelerating or inhibiting disease processes. A very different outcome is asymptomatic bacteriuria, defined by low host immune responsiveness to bacteria with attenuated virulence. This observation provides the rationale for immunomodulation as a new therapeutic tool to deliberately modify host susceptibility, control the host response and avoid severe disease. The power of innate immunity as an arbitrator of health and disease is also highly relevant for emerging pathogens, including the current COVID-19 pandemic.
|
|