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Molecules (Basel, Switzerland) Jun 2024The current study was designed to uncover the chemistry and bioactivity potentials of growing wild in Jordan. In this context, the fresh aerial parts obtained from the...
The current study was designed to uncover the chemistry and bioactivity potentials of growing wild in Jordan. In this context, the fresh aerial parts obtained from the plant material were subjected to hydrodistillation followed by GC/MS analysis. The main components of the HDEO were γ-patchoulene (23.79%), β-dihydro agarofuran (23.50%), α-guaiene (14.11%), and valencene (13.28%). Moreover, the crude thanolic extract was partitioned to afford two main major fractions, the aqueous methanol (BLM) and butanol (BLB). Phytochemical investigation of both fractions, using conventional chromatographic techniques followed by careful inspection of the spectral data for the isolated compounds (NMR, IR, and UV-Vis), resulted in the characterization of five known compounds, including α-spinasteryl (), ethyl arachidate (), ethyl myristate (), quercetin-3--β-d-glucopyranosyl-(1-4")-α-L-rhamnopyranosyl (), and isorhamnetin-3--β-d-glucopyranosyl-(1-4")-α-L-rhamnopyranosyl (). The TPC, TFC, and antioxidant activity testing of both fractions and HDEO revealed an interesting ABTS scavenging potential of the BLB fraction compared to the employed positive controls, which is in total agreement with its high TP and TF contents. Cytotoxic evaluation tests revealed that BLM had interesting cytotoxic effects on the normal breast cell line MDA-MB-231 (ATCC-HTB-26) and the normal dermal fibroblast (ATCC PCS-201-012) and normal African green monkey kidney Vero (ATCC-CCL-81) cell lines. Despite both the BLB and BLM fractions showing interesting AChE inhibition activities (IC = 217.9 ± 5.3 µg/mL and 139.1 ± 5.6 µg/mL, respectively), the HDEO revealed an interestingly high AChE inhibition power (43.8 ± 2.7 µg/mL) that far exceeds the one observed for galanthamine (91.4 ± 5.2 µg/mL). The HDEO, BLM, and BLB exhbitied no interesting antimicrobial activity against , , , , or .
Topics: Jordan; Plant Extracts; Antioxidants; Animals; Bupleurum; Humans; Vero Cells; Phytochemicals; Chlorocebus aethiops; Cell Line, Tumor; Plant Components, Aerial; Gas Chromatography-Mass Spectrometry; Cell Survival; Antineoplastic Agents, Phytogenic
PubMed: 38930796
DOI: 10.3390/molecules29122730 -
Molecules (Basel, Switzerland) Jun 2024Seven new abietane diterpenoids, comprising medusanthol A-G (-, , -) and two previously identified analogs ( and ), were isolated from the hexane extract of the aerial...
Seven new abietane diterpenoids, comprising medusanthol A-G (-, , -) and two previously identified analogs ( and ), were isolated from the hexane extract of the aerial parts of The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds - was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds - and exhibited decreased NO levels at a concentration of 12.5 µM. Compound demonstrated strong activity with an IC of 3.12 µM, and compound had an IC of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.
Topics: Abietanes; Anti-Inflammatory Agents; Animals; Nitric Oxide; Mice; Microglia; Tumor Necrosis Factor-alpha; Plant Extracts; Cell Line; Molecular Structure; Lipopolysaccharides; Plant Components, Aerial
PubMed: 38930790
DOI: 10.3390/molecules29122723 -
Antioxidants (Basel, Switzerland) Jun 2024Scutellarein is a key active constituent present in many plants, especially in Georgi and (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative...
Scutellarein is a key active constituent present in many plants, especially in Georgi and (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative activities. It also is the metabolite of scutellarin, with the ability to relieve LPS-induced acute lung injury (ALI), strongly suggesting that scutellarein could suppress respiratory inflammation. The present study aimed to investigate the effects of scutellarein on lung inflammation by using LPS-activated BEAS-2B cells (a human bronchial epithelial cell line) and LPS-induced ALI mice. The results showed that scutellarein could reduce intracellular reactive oxygen species (ROS) accumulation through inhibiting the activation of NADPH oxidases, markedly downregulating the transcription and translation of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand (CXCL) 8 in LPS-activated BEAS-2B cells. The mechanism study revealed that it suppressed the phosphorylation and degradation of IκBα, consequently hindering the translocation of p65 from the cytoplasm to the nucleus and its subsequent binding to DNA, thereby decreasing NF-κB-regulated gene transcription. Notably, scutellarein had no impact on the activation of AP-1 signaling. In LPS-induced ALI mice, scutellarein significantly decreased IL-6, CCL2, and tumor necrosis factor-α (TNF-α) levels in the bronchoalveolar lavage fluid, attenuated lung injury, and inhibited neutrophil infiltration. Our findings suggest that scutellarein may be a beneficial agent for the treatment of infectious pneumonia by virtue of its anti-oxidative and anti-inflammatory activities.
PubMed: 38929149
DOI: 10.3390/antiox13060710 -
International Journal of Molecular... Jun 2024Acute myeloid leukemia (AML) is an aggressive blood cancer. With low survival rates, new drug targets are needed to improve treatment regimens and patient outcomes....
Acute myeloid leukemia (AML) is an aggressive blood cancer. With low survival rates, new drug targets are needed to improve treatment regimens and patient outcomes. Pseudolaric acid B (PAB) is a plant-derived bioactive compound predicted to interact with cluster of differentiation 147 (CD147/BSG). CD147 is a transmembrane glycoprotein overexpressed in various malignancies with suggested roles in regulating cancer cell survival, proliferation, invasion, and apoptosis. However, the detailed function of PAB in AML remains unknown. In this study, AML cell lines and patient-derived cells were used to show that PAB selectively targeted AML (IC50: 1.59 ± 0.47 µM). Moreover, proliferation assays, flow cytometry, and immunoblotting confirmed that PAB targeting of CD147 resulted in AML cell apoptosis. Indeed, the genetic silencing of CD147 significantly suppressed AML cell growth and attenuated PAB activity. Overall, PAB imparts anti-AML activity through transmembrane glycoprotein CD147.
Topics: Humans; Basigin; Leukemia, Myeloid, Acute; Cell Proliferation; Apoptosis; Cell Line, Tumor; Diterpenes; Cell Survival
PubMed: 38928225
DOI: 10.3390/ijms25126517 -
International Immunopharmacology Jun 2024Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges....
Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.
PubMed: 38924866
DOI: 10.1016/j.intimp.2024.112517 -
Marine Drugs Jun 2024Overwhelming evidence points to an aberrant Wnt/β-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis....
Overwhelming evidence points to an aberrant Wnt/β-catenin signaling as a critical factor in hepatocellular carcinoma (HCC) and cervical cancer (CC) pathogenesis. Dicerandrol C (DD-9), a dimeric tetrahydroxanthenone isolated from the endophytic fungus DHS-48 obtained from mangrove plant via chemical epigenetic manipulation of the culture, has demonstrated effective anti-tumor properties, with an obscure action mechanism. The objective of the current study was to explore the efficacy of DD-9 on HepG2 and HeLa cancer cells and its functional mechanism amid the Wnt/β catenin signaling cascade. Isolation of DD-9 was carried out using various column chromatographic methods, and its structure was elucidated with 1D NMR. The cytotoxicity of DD-9 on HepG2 and HeLa cells was observed with respect to the proliferation, clonality, migration, invasion, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade. We found that DD-9 treatment significantly reduced tumor cell proliferation in dose- and time-dependent manners in HepG2 and HeLa cells. The subsequent experiments in vitro implied that DD-63 could significantly suppress the tumor clonality, metastases, and induced apoptosis, and that it arrested the cell cycle at the G/G phase of HepG2 and HeLa cells. Dual luciferase assay, Western blot, and immunofluorescence assay showed that DD-9 could dose-dependently attenuate the Wnt/β-catenin signaling by inhibiting β-catenin transcriptional activity and abrogating β-catenin translocated to the nucleus; down-regulating the transcription level of β-catenin-stimulated Wnt target gene and the expression of related proteins including -GSK3-β, β-catenin, LEF1, Axin1, -Myc, and CyclinD1; and up-regulating GSK3-β expression, which indicates that DD-9 stabilized the β-catenin degradation complex, thereby inducing β-catenin degradation and inactivation of the Wnt/β-catenin pathway. The possible interaction between DD-9 and β-catenin and GSK3-β protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-β-mediated crosstalk with the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of DD-9 on hepatocellular and cervical cancer.
Topics: Humans; HeLa Cells; Apoptosis; Wnt Signaling Pathway; Cell Proliferation; Hep G2 Cells; beta Catenin; Antineoplastic Agents; Liver Neoplasms; Xanthones; Carcinoma, Hepatocellular; Cell Movement; Uterine Cervical Neoplasms
PubMed: 38921589
DOI: 10.3390/md22060278 -
Marine Drugs Jun 2024The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is , a type of green...
Green Seaweed as a Novel Non-Small Cell Lung Cancer Inhibitor in Overcoming Tyrosine Kinase Inhibitor Resistance: An Analysis Employing Network Pharmacology, Molecular Docking, and In Vitro Research.
The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is , a type of green algae known as green seaweed, seagrapes, or green caviar. This organism stands out because it has great promise for use in medicine, especially in the study of cancer. Through the utilization of computational modeling (in silico) and cellular laboratory experiments (in vitro), the chemical components included in the green seaweed were effectively analyzed, uncovering its capability to treat non-small cell lung cancer (NSCLC). The study specifically emphasized blocking SRC, STAT3, PIK3CA, MAPK1, EGFR, and JAK1 using molecular docking and in vitro. These proteins play a crucial role in the EGFR Tyrosine Kinase Inhibitor Resistance pathway in NSCLC. The chemical Caulersin (C2) included in extract (CRE) has been identified as a potent and effective agent in fighting against non-small cell lung cancer (NSCLC), both in silico and in vitro. CRE and C2 showed a level of inhibition similar to that of osimertinib (positive control/NSCLC drug).
Topics: Humans; Molecular Docking Simulation; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Protein Kinase Inhibitors; Caulerpa; Drug Resistance, Neoplasm; Network Pharmacology; Cell Line, Tumor; Seaweed; Antineoplastic Agents; Plant Extracts; ErbB Receptors; Acrylamides; Tyrosine Kinase Inhibitors
PubMed: 38921583
DOI: 10.3390/md22060272 -
Current Pharmaceutical Design Jun 2024Rhus coriaria L., commonly known as Sumac, is a plant from the Anacardiaceae family that is known for its high phytochemical content. These phytochemicals have the...
BACKGROUND
Rhus coriaria L., commonly known as Sumac, is a plant from the Anacardiaceae family that is known for its high phytochemical content. These phytochemicals have the potential to effectively manage inflammation and oxidative stress. To explore the existing evidence on the impact of Sumac consumption on inflammation and oxidative stress, we conducted a systematic review of randomized controlled trials.
METHODS
We conducted a comprehensive search of Medline/PubMed, Scopus, and Web of Science from inception to August 2023 to identify relevant studies examining the effects of Sumac on biomarkers of inflammation and oxidative stress. The selected studies were assessed for risk of bias using the Cochrane tool.
RESULTS
A total of seven trials were included in this review. Among these trials, three focused on diabetes patients, while the remaining four involved individuals with fatty liver, overweight individuals with depression, and those with polycystic ovary or metabolic syndrome. Five studies reported the effects of Sumac on oxidative stress, with four of them demonstrating a significant reduction in malondialdehyde (MDA) levels and an increase in total antioxidant capacity (TAC) and paraoxonase 1 (PON1). Regarding inflammation, one study reported no significant difference in tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels between the intervention and control groups. The results for high-sensitivity C-reactive protein levels, reported in five trials, were inconsistent.
CONCLUSION
Sumac consumption over time may positively affect oxidative stress, although short-term use shows minimal impact. While one study found no significant effect on IL-6 and TNF-α, hs-CRP levels could decrease or remain unchanged. Further meta-analyses are needed to fully understand Sumac's potential benefits in managing metabolic diseases.
PubMed: 38920072
DOI: 10.2174/0113816128305609240529114411 -
Frontiers in Immunology 2024Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded... (Review)
Review
Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded suboptimal results. ICIs can decrease tumor development by preventing the tumor's immune evasion, presenting cancer patients with a new treatment alternative. The increased use of immune checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, ICIs have demonstrated significant clinical effectiveness in patients with MSI-H CRC, whereas their efficacy is limited in MSS. Acquired resistance can still occur in patients with a positive response to ICIs. This paper describes the efficacy of ICIs currently in the clinical treatment of CRC, discusses the mechanisms by which acquired resistance occurs, primarily related to loss and impaired presentation of tumor antigens, reduced response of IFN-λ and cytokine or metabolic dysregulation, and summarizes the incidence of adverse effects. We posit that the future of ICIs hinges upon the advancement of precise prediction biomarkers and the implementation of combination therapies. This study aims to elucidate the constraints associated with ICIs in CRC and foster targeted problem-solving approaches, thereby enhancing the potential benefits for more patients.
Topics: Humans; Colorectal Neoplasms; Immune Checkpoint Inhibitors; Animals; Drug Resistance, Neoplasm
PubMed: 38919624
DOI: 10.3389/fimmu.2024.1403533 -
Current Pharmaceutical Biotechnology Jun 2024Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are...
INTRODUCTION
Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are still a major clinical issue. Plant extracts have shown cardioprotective effects and reduced the risk of cardiovascular diseases.
METHOD
The current study is intended to explore the cardioprotective effect of ethanolic Moringa oleifera extracts (MOE) leaves loaded into niosomes (MOE-NIO) against DOXinduced cardiotoxicity in rats. MOE niosomes nanoparticles (NIO-NPs) were prepared and characterized by TEM. Seventy male Wistar rats were randomly divided into seven groups: control, NIO, DOX, DOX+MOE, DOX+MOE-NIO, MOE+DOX, and MOE-NIO+DOX. DOX (4 mg/kg, IP) was injected once per week for 4 weeks with daily administration of MOE or MOENIO (250 mg/kg, PO) for 4 weeks; in the sixth and seventh groups, MOE or MOE-NIO (250 mg/kg, PO) was administered one week before DOX injection. Various parameters were assessed in serum and cardiac tissue. Pre and co-treatment with MOE-NIO have mitigated the cardiotoxicity induced by DOX as indicated by serum aspartate aminotransferase (AST), creatine kinase - MB(CK-MB) and lactate dehydrogenase (LDH), cardiac Troponin 1(cTn1) and lipid profile. MOE-NIO also alleviated lipid peroxidation (MDA), nitrosative status (NO), and inflammatory markers levels; myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α) obtained in DOX-treated animals. Additionally, ameliorated effects have been recorded in glutathione content and superoxide dismutase activity. MOE-NIO effectively neutralized the DOXupregulated nuclear factor kappa B (NF-kB) and p38 mitogen-activated protein kinases (p38 MAPK), and DOX-downregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in the heart.
RESULTS
It is concluded that pre and co-treatment with MOE-NIO could protect the heart against DOX-induced cardiotoxicity by suppressing numerous pathways including oxidative stress, inflammation, and apoptosis and by the elevation of tissue antioxidant status.
CONCLUSION
Thus, it may be reasonable to suggest that pre and co-treatment with MOE-NIO can provide a potential cardioprotective effect when doxorubicin is used in the management of carcinoma.
PubMed: 38918977
DOI: 10.2174/0113892010303097240605105013