Unveiling the multifaceted antiproliferative efficacy of Cichorium endivia root extract by dual modulation of apoptotic and inflammatory genes, inducing cell cycle arrest, and targeting COX-2.

Chicory (Cichorium endivia L. divaricatum) is a renowned medicinal plant traditionally used for various ailments, yet the pharmacological potential of its roots, particularly in terms of antitumor activity, remains elusive. In the present study, we explore, for the first time, the metabolomic profile of ethanolic extract from Cichorium endivia roots (CIR) and further unveil its antiproliferative potential. The untargeted phytochemical analysis UPLC/T-TOF-MS/MS identified 131 metabolites in the CIR extract, covering acids, amino acids, flavonoids, alkaloids, nucleotides, and carbohydrates. The antiproliferative activity of the CIR extract was tested in 14 cancer cell lines, revealing significant cytotoxicity (IC50: 2.85-29.15 µg mL-1) and a high selectivity index. Among the cells examined, the CIR extract recorded the most potent antiproliferative activity and selectivity toward HepG2 and Panc-1 cells, with an IC50 of 2.85 µg mL-1 and 3.86 µg mL-1, respectively, and SI > 10. Insights into the mode of action of the antiproliferative activity revealed that CIR extract induces cell arrest in the S phase while diminishing cell distribution in the G0/G1 and G2/M phases in HepG-2 and Panc-1 cells. Flow cytometric and RT-PCR analysis revealed that the CIR extract significantly triggers apoptosis and modulates the expression of pro-apoptotic and anti-apoptotic genes. Furthermore, the CIR extract exhibited a pronounced anti-inflammatory activity, as evidenced by down-regulating key cytokines in LPS-induced RAW 264.7 cells and selectively inhibiting the COX-2 enzyme. Finally, the CIR extract showed a robust total antioxidant capacity, together with potent free radicals and metal scavenging properties, highlighting its role in alleviating oxidative stress. Taken together, this study highlights the multifaceted therapeutic potential of CIR extract as a natural-based antitumor supplement.

Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study.

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund's complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.

Therapeutic strategy of biological macromolecules based natural bioactive compounds of diabetes mellitus and future perspectives: A systematic review.

High blood glucose levels are a hallmark of the metabolic syndrome known as diabetes mellitus. More than 600 million people will have diabetes by 2045 as the global prevalence of the disease continues to rise. Contemporary antidiabetic drugs reduce hyperglycemia and its consequences. However, these drugs come with undesirable side effects, so it's encouraging that research into plant extracts and bioactive substances with antidiabetic characteristics is on the rise. Natural remedies are preferable to conventional anti-diabetic drugs since they are safer for the body, more affordable and have fewer potential adverse effects. Biological macromolecules such as liposomes, niosomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions and metallic nanoparticles are explored in this review. Current drug restrictions have been addressed, and the effectiveness of plant-based antidiabetic therapies has enhanced the merits of these methods. Plant extracts' loading capacity and the carriers' stability are the primary obstacles in developing plant-based nanocarriers. Hydrophilic, hydrophobic, and amphiphilic drugs are covered, and a brief overview of the amphipathic features of liposomes, phospholipids, and lipid nanocarriers is provided. Metallic nanoparticles' benefits and attendant risks are highlighted to emphasize their efficiency in treating hyperglycemia. Researchers interested in the potential of nanoparticles loaded with plant extracts as antidiabetic therapeutics may find the current helpful review.

Synthesis and Characterization of Graphene Oxide/Polyethylene Glycol/Folic Acid/Brucine Nanocomposites and Their Anticancer Activity on HepG2 Cells.

Background: Liver cancer is the sixth most prevalent form of cancer and the second major cause of cancer-associated mortalities worldwide. Cancer nanotechnology has the ability to fundamentally alter cancer treatment, diagnosis, and detection. Objective: In this study, we explained the development of graphene oxide/polyethylene glycol/folic acid/brucine nanocomposites (GO/PEG/Bru-FA NCs) and evaluated their antimicrobial and anticancer effect on the liver cancer HepG2 cells. Methodology: The GO/PEG/Bru-FA NCs were prepared using the co-precipitation technique and characterized using various techniques. The cytotoxicity of the GO/PEG/Bru-FA NCs was tested against both liver cancer HepG2 and non-malignant Vero cells using an MTT assay. The antimicrobial activity of the GO/PEG/Bru-FA NCs was tested against several pathogens using the well diffusion technique. The effects of GO/PEG/Bru-FA NCs on endogenous ROS accumulation, apoptosis, and MMP levels were examined using corresponding fluorescent staining assays, respectively. The apoptotic protein expressions, such as Bax, Bcl-2, and caspases, were studied using the corresponding kits. Results: The findings of various characterization assays revealed the development of GO/PEG/Bru-FA NCs with face-centered spherical morphology and an agglomerated appearance with an average size of 197.40 nm. The GO/PEG/Bru-FA NCs treatment remarkably inhibited the growth of the tested pathogens. The findings of the MTT assay evidenced that the GO/PEG/Bru-FA NCs effectively reduced the HepG2 cell growth while not showing toxicity to the Vero cells. The findings of the fluorescent assay proved that the GO/PEG/Bru-FA NCs increased ROS generation, reduced MMP levels, and promoted apoptosis in the HepG2 cells. The levels of Bax, caspase-9, and -3 were increased, and Bcl-2 was reduced in the GO/PEG/Bru-FA NCs-treated HepG2 cells. Conclusion: The results of this work demonstrate that GO/PEG/Bru-FA NCs suppress viability and induce apoptosis in HepG2 cells, indicating their potential as an anticancer candidate.

Chitosan biopolymer functionalized with graphene oxide and titanium dioxide with Escin metallic nanocomposites for anticancer potential against colon cancer.

Our study produced GO-TiO2-chitosan-escin nanocomposites (GTCEnc), characterized them using physical and biological methods, and evaluated their potential as cancer treatment candidates. Standard protocols were used to produce GTCEnc. Nanocomposites are created using XRD, FTIR, UV-Vis, and PL spectroscopy analysis. The morphology and ultrastructure of nanocomposites were investigated using SEM and TEM. Nanocomposites containing TiO2, GO, chitosan, and escin nanostructures were characterized using diffraction, microscopy, and spectroscopy; the antimicrobial activity of GTCEnc was investigated. Various methods were used to test the anticancer activity of GTCEnc against COLO 205 cell lines, including MTT, EtBr/AO, DAPI, JC-1, Annexin-V/FITC, cell cycle analysis, and activation of pro-apoptotic markers, such as caspase-3, -8, and -9. The nanocomposites were cytotoxic to COLO 205 cells, with an IC50 of 22.68 µg/mL, but not to 293T cells. In cells treated with nanomaterials, cytotoxicity, nuclear damage, apoptosis induction, and free radical production were significantly increased. Our finding suggests that GTCEnc has potent anticancer and antibacterial activity in vitro because of its unique nanocomposite properties and antibacterial and anticancer activity in vitro. Additional research is required to understand the clinical efficacy of these nanocomposites.

An application of carbohydrate polymers-based surface-modified gold nanoparticles for improved target delivery to liver cancer therapy - A systemic review.

Gold nanoparticles have been broadly investigated as cancer diagnostic and therapeutic agents. Gold nanoparticles are a favorable drug delivery vehicle with their unique subcellular size and good biocompatibility. Chitosan, agarose, fucoidan, porphyran, carrageenan, ulvan and alginate are all examples of biologically active macromolecules. Since they are biocompatible, biodegradable, and irritant-free, they find extensive application in biomedical and macromolecules. The versatility of these compounds is enhanced because they are amenable to modification by functional groups like sulfation, acetylation, and carboxylation. In an eco-friendly preparation process, the biocompatibility and targeting of GNPs can be improved by functionalizing them with polysaccharides. This article provides an update on using carbohydrate-based GNPs in liver cancer treatment, imaging, and drug administration. Selective surface modification of several carbohydrate types and further biological uses of GNPs are focused on.

Carbohydrate polymers-based surface modified nano delivery systems for enhanced target delivery to colon cancer - A review.

Carbohydrate polymers-based surface-modified nano-delivery systems have gained significant attention in recent years for enhancing targeted delivery to colon cancer. These systems leverage carbohydrate polymers' unique properties, such as biocompatibility, biodegradability, and controlled release. These properties make them suitable candidates for drug delivery applications. Nano-delivery systems loaded with bioactive compounds are well-studied for targeted colorectal cancer delivery. However, those drugs' target reach is still limited in various nano-delivery systems. To overcome this limitation, surface modification of nanoparticles with carbohydrate polymers like chitosan, pectin, alginate, and guar gum showed enhanced target-reaching capacity along with enhanced anticancer efficacy. Recently, a chitosan-decorated PLGA nanoparticle was constructed with tannic acid and vitamin E and showed long-term release of specific targets along with higher anticancer efficacy. Similarly, Chitosan-conjugated glucuronic acid-coated silica nanoparticles loaded with capecitabine were studied against colon cancer and found to be the pH-responsive controlled release of capecitabine with higher anticancer efficacy. Surface-modified carbohydrate polymers have promising potential for improving colon cancer target delivery. By leveraging the unique properties of these polymers, such as surface modification, pH responsiveness, mucoadhesion, controlled drug release, and combination therapy, researchers are working toward developing more effective and targeted treatment strategies for colon cancer.