Antiangiogenic Properties Research Articles

Determination of resveratrol in nanoformulations using UV-spectroscopy: forced degradation and drug entrapment

Abstract Dietary polyphenols from plant sources play an important role in the human diet. They have various biological effects, such as protein kinase inhibition, antibacterial, anticancer, antiulcer, antiarthritic, and anti-angiogenic properties. Among the various phenolic chemicals found in plants, resveratrol (trans-3,5,4′-trihydroxystilbene) (RVT) is a non-flavonoid polyphenolic compound that has been extensively studied for its health-promoting advantages, including its anti-cancer, neuroprotective, anti-inflammatory, antioxidant, and cardio-protective activities. Considering its potential in pharmaceutical nanoformulations, a rapid, economical, sensitive, and robust UV spectrophotometric method was developed and validated. The proposed method was developed in phosphate buffer at pH 7.4 to estimate the RVT content in the pharmaceutical nanoformulation. The method was developed at a reported wavelength of 306 nm. The developed method was validated according to ICH Q2A (R1) guidelines and was applied for the estimation of RVT in prepared nanoformulations. The method showed exceptional linearity in the range of (1–6) μg mL−1 with a coefficient of determinant value of 0.9998. The study proves that the developed method is linear, precise, sensitive, robust, reproducible, and accurate. This method can be applied for the estimation of RVT in nanoformulations and other bulk dosage forms.

Anti-angiogenic Potential of Trans-chalcone in an In Vivo Chick Chorioallantoic Membrane Model: An ATP Antagonist to VEGFR with Predicted Blood-brain Barrier Permeability.

Glioblastoma multiforme (GBM) is characterized by massive tumorinduced angiogenesis aiding tumorigenesis. Vascular endothelial growth factor A (VEGF-A) via VEGF receptor 2 (VEGFR-2) constitutes majorly to drive this process. Putting a halt to tumordriven angiogenesis is a major clinical challenge, and the blood-brain barrier (BBB) is the prime bottleneck in GBM treatment. Several phytochemicals show promising antiangiogenic activity across different models, but their ability to cross BBB remains unexplored. We screened over 99 phytochemicals having anti-angiogenic properties reported in the literature and evaluated them for their BBB permeability, molecular interaction with VEGFR-2 domains, ECD2-3 (extracellular domains 2-3) and TKD (tyrosine kinase domain) at VEGF-A and ATP binding site, cell membrane permeability, and hepatotoxicity using in silico tools. Furthermore, the anti-angiogenic activity of predicted lead Trans-Chalcone (TC) was evaluated in the chick chorioallantoic membrane. Out of 99 phytochemicals, 35 showed an efficient ability to cross BBB with a probability score of > 0.8. Docking studies revealed 30 phytochemicals crossing benchmark binding affinity < -6.4 kcal/mol of TKD with the native ligand ATP alone. Out of 30 phytochemicals, 12 showed moderate to low hepatotoxicity, and 5 showed a violation of Lipinski's rule of five. Our in silico analysis predicted TC as a BBB permeable anti-angiogenic compound for use in GBM therapy. TC reduced vascularization in the CAM model, which was associated with the downregulation of VEGFR-2 transcript expression. The present study showed TC to possess anti-angiogenic potential via the inhibition of VEGFR-2. In addition, the study predicted TC to cross BBB as well as a safe alternative for GBM therapy, which needs further investigation.

Anticancer Effects of the Novel Pyrazolyl-Urea GeGe-3.

In a screen of over 200 novel pyrazole compounds, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl)ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a potential anticancer compound. GeGe-3 displays potent anti-angiogenic properties through the presumptive targeting of the protein kinase DMPK1 and the Ca2+-binding protein calreticulin. We further explored the anticancer potential of GeGe-3 on a range of established cancer cell lines, including PC3 (prostate adenocarcinoma), SKMEL-28 (cutaneous melanoma), SKOV-3 (ovarian adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MDA-MB231, SKBR3, MCF7 (breast adenocarcinoma), A549 (lung carcinoma), and HeLa (cervix epithelioid carcinoma). At concentrations in the range of 10 μM, GeGe-3 significantly restricted cell proliferation and metabolism. GeGe-3 also reduced PC3 cell migration in a standard wound closure and trans-well assay. Together, these results confirm the anticancer potential of GeGe-3 and underline the need for more detailed pre-clinical investigations into its molecular targets and mechanisms of action.

Novel synthesis of trans-ferulic acid loaded tragacanth-chitosan nanoformulations and evaluation of their biological activities

Trans-ferulic acid, is one of the many biologically significant bioactive components of Datura. It has wide range of potential applications in the food industry, health, and cosmetics industries. Trans-ferulic acid possess myriad properties like anti-inflammatory, anti-aging, antiangiogenic, anticancer, antimicrobial, and antioxidant properties. To exploit its antioxidant and anti-inflammatory properties, first of all, trans-ferulic acid loaded tragacanth/chitosan nanoparticles (TFA loaded TGCA-NPs) were synthesized by ionic gelation method using tragacanth and chitosan as polymers. Tragacanth used to encapsulate the trans-ferulic acid is a polysaccharide gum, which is used all over the world in industries ranging from the food industry to healthcare systems due to its availability, affordability, non-toxicity, and environmental friendliness. The synthesized nanoparticles were then characterized by using techniques like FTIR, UV–Vis Spectroscopy, SEM and TEM. The particle size of nanoparticles thus obtained ranged from 105 nm to 250 nm. SEM micrograph of nanoparticles showed tiny rod-like structures, which appear to be coated on the polymer. TEM images showed somewhat sphere-shaped nanoparticles with a projecting rod-like structure that might be due to the trans-ferulic acid encapsulation in tragacanth-chitosan polymer. Decent antimicrobial activity of synthesized nanoparticles was observed against pathogenic bacteria named Staphylococcus aureus. Hemocompatibility of trans-ferulic acid loaded tragacanth-chitosan nanoparticles was also examined. The antioxidant activity was evaluated by DPPH radical scavenging assay, in which synthesized nanoparticles showed 41.62 % radical scavenging activity. For in-vitro anti-inflammatory activity Human Red Blood Cell membrane stabilization method (HRBC method) was used, and the results showed higher protection by the synthesized nanoparticles in comparison to the pure trans-ferulic acid and blank nanoparticles.

Evaluation of Anti-angiogenic Activity of Iraqi Mesembryanthemum cordifolium using rat aorta ring assay

New blood vessels are produced during angiogenesis, which is necessary in both normal and abnormal physiological and pathologic states. The use of non-toxic plant extracts that inhibit angiogenesis might lead to more focus on the use of natural sources as a pivotal therapeutic agent in the treatment of many diseases and malignancies. Mesembryanthemum cordifolium is belongs to the Aizoaceae family and commonly known as the Heartleaf Ice Plant or Tiny Sun Rose. The plant was cultivated in the city of al Diwaniyah. No previous research has been conducted on this plant and its antiangiogenic properties. Hence, this research aimed to assess the antiangiogenic capacity of the Iraqi M. cordifolium. For this study, male albino rats aged 12 to 14 weeks were used. With a Soxhlet apparatus, the defatted plant components were extracted in 85 % methanol for 12 h. Subsequently, each fraction was fractionated using petroleum ether, chloroform and ethyl acetate and each fraction underwent phytochemical analysis. Rat aortic rings were infused with 100 ?g/mL of each plant component and placed in a growth medium. In addition, the dose-response relationship was assessed for the most active fraction at 6 different concentrations ranging from 6.25 ?g/mL to 100 ?g/mL. Compared to the negative control (1 % DMSO), the results demonstrated that fractions of M. cordifolium inhibit the growth of blood vessels in a dose-dependent manner; chloroform demonstrates the most potent effect. The results indicate that the chloroform fraction derived from M. cordifolium has a good ability to limit blood vessel development. This makes it a viable option for future investigation as an angiogenesis inhibitor.

The Past and Future of Angiogenesis as a Target for Cancer Therapy and Prevention.

Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. After this concept was established in the 1970s, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy, prevention, and interception and recently investigated substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, β blockers, renin-angiotensin-aldosterone inhibitors, carnitines, and biguanides, are reviewed.

A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways.

Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.

Harnessing Plant Flavonoids to Fight Pancreatic Cancer.

This review draws on the last fifteen years (2009-2024) of published data to summarize the potential effect of plant flavonoids on pancreatic carcinogenesis and discuss the possible mechanisms of action to establish their applicability as anti-cancer agents. This review found that the plant flavonoids with anti-pancreatic cancer activity mainly include chalcones, dihydrochalcones, flavanols, flavanones, flavones, isoflavonoids, flavonols, isoflavones, and flavanonols. Most of these flavonoids have anti-proliferative, pro-apoptotic, cell cycle arrest, anti-angiogenic, anti-inflammatory, anti-epithelial-mesenchymal transition, and anti-metastatic properties. Some flavonoids can also regulate autophagy, immune and glucose uptake in the context of pancreatic cancer. Several molecules and signaling pathways are associated with the pharmacological activities of plant flavonoids, including AMP-activated protein kinase, mitogen-activated protein kinases, phosphatidylinositol-3-kinase/protein kinase B, nuclear factor-κB, signal transducer, and activator of transcription 3, Smad3, epidermal growth factor receptor, and vascular endothelial growth factor. This review provides strong evidence that plant flavonoids have potential against pancreatic carcinogenesis in experimental animals through various pharmacological mechanisms. They are a promising resource for use as adjuvant anti-cancer therapy. However, randomized controlled clinical trials with those flavonoids are needed.

PLA2-MjTX-II from Bothrops moojeni snake venom exhibits antimetastatic and antiangiogenic effects on human lung cancer cells

Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.

New Study on the Effect of Scopoletin and Silver Nanoparticles of Fenugreek Extract as Pancreatic Cancer Inhibition Agents

Pancreatic cancer is a highly aggressive and lethal form of cancer with limited treatment options. Therefore, exploring novel therapeutic strategies is crucial to improve patient outcomes. Researchers are currently investigating the potential therapeutic effects of scopoletin and silver nanoparticles on various diseases, including pancreatic cancer. Specifically, they have synthesized and characterized silver nanoparticles using fenugreek extract and tested different concentrations of these nanoparticles and scopoletin to determine their anti-cancer and anti-angiogenic properties. The aim is to identify the most effective dose that can reduce the levels of cyclooxygenase-2 (COX-2) and lactate dehydrogenase (LDH), which are markers associated with cancer progression. The study was performed in a laboratory setting, dividing the samples into three separate groups. The first group, known as the control group, consisted of 30 samples from healthy individuals of both genders, aged between 23 and 45 years. The second group included 30 male and female patients aged between 45 and 65 years, with stage II pancreatic cancer. Lastly, the third group comprised 30 male and female patients with stage III pancreatic cancer, aged between 52 and 79 years. This study found that, compared to the control group, patients with stage IΙ and stage IΙΙ pancreatic cancer experienced the greatest decrease in enzyme concentration at the concentration of the nanoparticle solution 2 ppm where the Cyclooxygenas-2 enzyme concentrations values were 2.43±0.22ng/ml, 3.04±0.31ng/ml and 1.59±0.06ng/ml, respectively. As for the concentration of the enzyme Lactate dehydrogenase, it was 1.20±0.02ng/ml, 1.14±0.02ng/ml and 0.85±0.18ng/ml respectively. Also, as compared to the control 1.97±0.17ng/ml, 1.72±0.10ng/ml, and 1.22±0.07ng/ml, the concentration of the scopoletin compound solution 8ppm results in the best reduction in COX-2 enzyme concentration As for the concentration of the enzyme LDH, it was 0.93±0.07 ng/ml, 0.97±0.11 ng/ml and 0.71±0.10 ng/ml In individuals with stage IΙ and stage IIΙ PC. The results of this research demonstrate that scopoletin compounds and Ag-NPs derived from Fenugreek extract function as anti-cancer and anti-angiogenesis agents by reducing the levels of cyclooxygenase-2 (COX-2) and lactate dehydrogenase (LDH) enzymes in the blood serum of individuals with stage II and stage III pancreatic carcinoma in Iraq.

Effect of Lupeol on the Expression of Neuro Inflammatory Signalling Molecules in Brain Tissues of High Fat Diet and Sucrose Fed Type-2 Diabetic Rats

Lupeol has anti- inflammatory, antimicrobial, anti-protozoal, anti-proliferative, anti-invasion, anti-angiogenic and cholesterol-lowering properties. However, the mechanisms underlying the effect of lupeol on neuroinflammatory signalling molecules have not yet been identified. The study was designed to study the effect of lupeol on the expression of inflammatory signalling molecules in brain tissue of high-fat diet and sucrose-fed type-2 diabetic rats. Adult male albino rats of Wistar 150–180 days old with 180–200 g body weight (b.wt) were divided into four groups of six rats each. Group I: Control (vehicle-treated): Group II: High fat diet-induced type-2 diabetic rats; Group III: Type-2 diabetic rats treated with lupeol (25 mg/kg b.wt/day) orally for 30 days and Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg, b.wt/day orally for 30 days. After 30 days of treatment, the animals were anaesthetized, and brain tissue was dissected and used for the assessment of mRNA expression analysis. Type-2 diabetic animals showed a significant increase (p&lt;0.05) in TNF-α and IL-6 mRNA levels in brain tissue in high-fat diet-induced type-2 diabetic animals. However, lupeol treatment, effectively reduced (p&lt;0.05) the neuroinflammatory signaling molecules (TNF- α and IL-6 mRNA) showing that lupeol has significant role over the control of neuroinflammatory signaling. Our present findings clearly show that lupeol has a significant role in reducing neuroinflammation via the downregulation of TNF-α and IL-6 in brain tissues and hence, lupeol can be a potential natural drug for the treatment of diabetic neuropathy.

Marine-derived antimicrobial peptide piscidin-1 triggers extrinsic and intrinsic apoptosis in oral squamous cell carcinoma through reactive oxygen species production and inhibits angiogenesis

Cancer of the head and neck encompasses a wide range of cancers, including oral and oropharyngeal cancers. Oral cancer is often diagnosed at advanced stages and has a dismal prognosis. Piscidin-1, a marine antimicrobial peptide (AMP) containing approximately 22 amino acids, also exhibits significant anticancer properties. We investigated the possible anti-oral cancer effects of piscidin-1 and clarified the mechanisms underlying these effects. We treated the oral squamous cell carcinoma cell lines OC2 and SCC4 with piscidin-1. Cell viability and the expression of different hallmark apoptotic molecules, including reactive oxygen species (ROS), were tested using the appropriate MTT assay, flow cytometry and western blotting assays, and human umbilical vein endothelial cell (HUVEC) wound healing, migration, and tube formation (angiogenesis) assays. Piscidin-1 increases cleaved caspase 3 levels to induce apoptosis. Piscidin-1 also increases ROS levels and intensifies oxidative stress in the endoplasmic reticulum and mitochondria, causing mitochondrial dysfunction. Additionally, it decreases the oxygen consumption rates and activity of mitochondrial complexes I–V. As expected, the antioxidants MitoTEMPOL and N-acetylcysteine reduce piscidin-1–induced ROS generation and intracellular calcium accumulation. Piscidin-1 also inhibits matrix metalloproteinase (MMP)-2/-9 expression in HUVECs, affecting migration and tube formation angiogenesis. We demonstrated that piscidin-1 can promote apoptosis via both intrinsic and extrinsic apoptotic pathways and findings indicate that piscidin-1 has anti-proliferative and anti-angiogenic properties in oral cancer treatment. Our study on piscidin-1 thus provides a basis for future translational anti-oral cancer drug research and a new theoretical approach for anti-oral cancer clinical research.

Off-label use of intravitreal bevacizumab: A global conundrum.

Bevacizumab is a monoclonal, humanized, full-length antibody targeting vascular endothelial growth factor(VEGF-A), known for its anti-angiogenic properties. The off-label use of bevacizumab has stirred legal, financial, industrial, and ethical complexities. With its potential to treat diverse ocular conditions, this commentary delves into the multifaceted dimensions of bevacizumab's off-label utilization, encompassing clinical trials, regulatory frameworks, safety considerations, comparative effectiveness, and economic implications.

Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.

Cannabidiol Inhibits Epithelial Ovarian Cancer: Role of Gut Microbiome.

Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.

Stack-AAgP: Computational prediction and interpretation of anti-angiogenic peptides using a meta-learning framework

Background:Angiogenesis plays a vital role in the pathogenesis of several human diseases, particularly in the case of solid tumors. In the realm of cancer treatment, recent investigations into peptides with anti-angiogenic properties have yielded encouraging outcomes, thereby creating a hopeful therapeutic avenue for the treatment of cancer. Therefore, correctly identifying the anti-angiogenic peptides is extremely important in comprehending their biophysical and biochemical traits, laying the groundwork for uncovering novel drugs to combat cancer. Methods:In this work, we present a novel ensemble-learning-based model, Stack-AAgP, specifically designed for the accurate identification and interpretation of anti-angiogenic peptides (AAPs). Initially, a feature representation approach is employed, generating 24 baseline models through six machine learning algorithms (random forest [RF], extra tree classifier [ETC], extreme gradient boosting [XGB], light gradient boosting machine [LGBM], CatBoost, and SVM) and four feature encodings (pseudo-amino acid composition [PAAC], amphiphilic pseudo-amino acid composition [APAAC], composition of k-spaced amino acid pairs [CKSAAP], and quasi-sequence-order [QSOrder]). Subsequently, the output (predicted probabilities) from 24 baseline models was inputted into the same six machine-learning classifiers to generate their respective meta-classifiers. Finally, the meta-classifiers were stacked together using the ensemble-learning framework to construct the final predictive model. Results:Findings from the independent test demonstrate that Stack-AAgP outperforms the state-of-the-art methods by a considerable margin. Systematic experiments were conducted to assess the influence of hyperparameters on the proposed model. Our model, Stack-AAgP, was evaluated on the independent NT15 dataset, revealing superiority over existing predictors with an accuracy improvement ranging from 5% to 7.5% and an increase in Matthews Correlation Coefficient (MCC) from 7.2% to 12.2%.

Discovery of novel thiophene-3-carboxamide derivatives as potential VEGFR-2 inhibitors with anti-angiogenic properties

VEGFR-2 is an attractive target for the development of anti-tumor drugs and plays a crucial role in tumor angiogenesis. This study reports a series of novel thiophene-3-carboxamide derivatives based on PAN-90806 as VEGFR-2 inhibitors, among which compound 14d exhibits excellent anti-proliferative activity against HCT116, MCF7, PC3, and A549 cell lines, and has effective VEGFR-2 inhibitory activity with an IC50 value of 191.1 nM. Additionally, CETSA results indicated that VEGFR-2 was a relevant target of compound 14d in the cell lines, and compound 14d could also inhibit VEGFR-2 protein phosphorylation in A549 cell line. Furthermore, compound 14d inhibited colony formation, cell migration, and HUVECs tube formation in a dose-dependent manner. The mechanism by which 14d induced cancer cell death involves blocking the cell cycle, increasing ROS production, inducing apoptosis, and dose-dependently reducing the levels of phosphorylated ERK and MEK. Molecular docking and molecular dynamics simulations had shown that compound 14d could stably bind to the active site of VEGFR-2. These results confirmed that compound 14d might be a promising lead compound for anti-angiogenesis.

Harnessing silk fibroin microparticles for metformin delivery: A novel approach to treating corneal neovascularization

Corneal neovascularization (CV) poses significant challenges in ophthalmology, often leading to impaired vision and discomfort. Silk fibroin microparticles have emerged as promising candidates for drug delivery applications, owing to their biocompatibility, biodegradability, and controlled release characteristics. In the current research, metformin-loaded silk microparticles were developed, and their potential for treating corneal neovascularization was evaluated. Silk microparticles were prepared using silk fibroin and polyvinyl alcohol (PVA) at various weight ratios, facilitating phase separation to create a porous structure conducive to drug loading. Metformin (MT), a widely used antidiabetic agent with potential anti-angiogenic properties, was incorporated into the silk microparticles at different concentrations. The formulation termed TB (0.3 % MT loaded Microparticles) emerged as the most promising candidate was identified through comprehensive in vitro evaluations. In in vitro cytotoxicity studies, it was determined that all formulations provided cell viability above 80%, however, in permeability studies and encapsulation efficiency studies, TB was determined to be more effective than other formulations. TB demonstrated a particle size of approximately 8.9 ± 3.6 μm and an encapsulation efficiency of 96.3 ± 2.1%. In vitro release studies revealed that TB exhibited a burst release of 62% within the initial two days, followed by sustained release over a period of 14 days, consistent with Peppas-Sahlin kinetics. Mathematical modeling further corroborated the diffusion mechanism underlying drug release from TB microparticles. In vivo studies on rats and histochemical analyzes on corneas showed that TB exhibited efficacy comparable to dexamethasone, a standard treatment for CV, despite being administered once daily. Histological analyses of corneal tissues revealed reduced neovascularization and inflammation in the TB-treated group, underscoring its therapeutic potential. Overall, our findings highlight the promise of metformin-loaded silk fibroin microparticles as a novel therapeutic approach for managing CV, offering sustained drug release and enhanced efficacy in treating this challenging ocular condition.

Analysis of the Anticancer Mechanism of OR3 Pigment from Streptomyces coelicolor JUACT03 Against the Human Hepatoma Cell Line Using a Proteomic Approach.

This study assessed OR3 pigment, derived from Streptomyces coelicolor JUACT03, for its anticancer potential on HepG2 liver cancer cells and its safety on HEK293 normal cells. OR3 induced apoptosis and inhibited HepG2 cell proliferation, confirmed by caspase activation, Sub-G1 phase cell cycle arrest, and reduced colony formation. Proteomic analysis revealed altered expression of proteins associated with ribosomal function, mRNA processing, nuclear transport, proteasome activity, carbohydrate metabolism, chaperone function, histone regulation, and vesicle-mediated transport. Downregulation of proteins in MAPKAP kinase1, EIF2, mTOR, and EIF4 pathways contributed to apoptosis and cell cycle arrest. Changes in c-MYC, FUBP1 target proteins and upregulation of Prohibitin-1 (PHB1) were also noted. Western blot analysis supported alterations in eIF2, mTOR, and RAN pathways, including downregulation of RAB 5, c-MYC, p38, MAPK1, and MAPK3. OR3 exhibited significant anti-angiogenic activity in the in ovo CAM assay. In summary, OR3 demonstrated strong anticancer effects, inducing apoptosis, hindering proliferation, and displaying antiangiogenic properties. These findings highlight OR3's potential as an anticancer drug candidate, warranting further in vivo exploration.

Origin, occurrence, pharmaceutical, analytical, and various pharmacological studies on Swarna bhasma (~incinerated gold ash): A synoptic review

Swarna (~gold) is categorized under the Sara loha varga (~noble metals) and is said to be superior to all other metals. Almost all ancient Ayurveda classics have indicated the therapeutic utilities of Swarna. However, compiled information on various aspects of this metal is not available, considering which, an attempt has been made to screen and compile information from available literature. The data have been compiled from different Ayurveda classical texts. Research articles published on Swarna bhasma (~incinerated gold ash) have also been referred for information. This precious metal is advocated to be used in therapeutics after converting it into fine powders through processing specified classical pharmaceutical procedures. The published information reiterated the therapeutic applications of Swarna bhasma referred in the classical literature. Swarna bhasma exhibited anticataleptic, antidepressant, antianxiety, antioxidant, antiarthritic, and antiangiogenic properties. It has shown significant effects on memory enhancing and improving learning abilities too.