Introduction Diabetes mellitus increases the risk of Cardiovascular Diseases (CVDs), highlighting the need for new treatments. Herbal remedies like turmeric (Curcuma longa), with its bioactive compound curcumin, are known for their anticoagulant effects. Cardamom (Elettaria cardamomum) helps lower diastolic blood pressure and inflammatory markers linked to CVDs. Pippali (Piper longum) acts as an anti-inflammatory, analgesic, and bioenhancer. In the current study, acknowledging their properties, these three herbs were combined (Curc+Card+Pip) and conjugated with green-synthesized MgO nanoparticles from curry leaves (Murraya koenigii). The aim was to evaluate the cytotoxicity of the herbal combination with and without MgONPs before employing it as a potential novel therapeutic approach for CVD-related research in diabetes. Methods This case-control study included two groups: a) normoglycemic individuals and b) those with Type 2 Diabetes Mellitus (T2DM). Hydroethanolic extracts were prepared and characterized. Cytotoxicity of Curc+Card+Pip and Curc+Card+Pip+MgONps was assessed using the MTT assay over 24 and 48 hours at concentrations of 100-500 µg/ml. Peripheral Blood Mononuclear Cells (PBMCs) from both groups were used as the primary cell lines. Statistical analysis was conducted using SPSS 26.0 and Excel 2021. Results The MTT assay on PBMCs from Normoglycemic (NG) and T2DM groups with i) Curc+Card+Pip and ii) Curc+Card+Pip+MgONps showed minimal cytotoxicity at concentrations of 100-500 µg/ml. The CC50 order was NG 24 hours >; T2DM 24 hours >; NG 48 hours >; T2DM 48 hours. A significant difference in cell viability was observed between 24 hours (96.45% ± 0.012) and 48 hours (73.62% ± 0.48) at 100 µg/ml in NG (p >; 0.01), while T2DM showed 93.63% ± 0.012 and 68.41% ± 0.048 at 24 and 48 hours, respectively. For NG, Curc+Card+Pip+MgONps exhibited viabilities of 92.75% ± 0.026 and 62.02% ± 0.046 at 24 and 48 hours, respectively, while T2DM showed 90.82% ± 0.018 and 59.44% ± 0.044. Discussion Cytotoxicity increased from 100-500 µg/ml, reducing viability. Cytotoxicity increased at 400-500 µg/ml at 48 hours (p >; 0.001) in both groups and treatments, suggesting that cell tolerance to MgO NPs was similar to that without NPs. The herbal mixture with MgONPs displayed a cytotoxicity pattern similar to that of the mixture without NPs in both groups. Conclusion The CC50 for Cur+Card+Pip without and with NPs was 452 and 410 µg/ml, respectively, within 24 hours, whereas in T2DM patients, the same treatments were found to have CC50 values of 300 and 330 µg/ml, respectively, with and without NPs. The values were the same in the case of T2DM (48 hours), whether it was with or without NPs (CC50 = 240 µg/ml), allowing for future exploration of its anti-inflammatory and antioxidant effects on PBMCs, which could suggest its potential as an alternative therapy for managing CVD in diabetic patients.

Alzheimer’s disease (AD) represents a devastating condition that profoundly impacts the quality of life for both affected individuals and their families. Currently, there is no viable treatment for AD. Conventional drugs for AD provide symptomatic relief by temporarily improving cognitive function or slowing the progression of specific symptoms. These medications do not stop or reverse the underlying neurodegeneration, offering only modest benefits in managing the disease, and often come with unpleasant side effects, making adherence challenging for patients. Natural treatments made from plants have drawn interest for their potential to lessen AD symptoms while having a lesser side-effect profile. Among these, Moringa oleifera (M. oleifera), also referred to as the “miracle tree,” has gained attention for its wide range of health benefits, including antioxidant, anti-inflammatory and neuroprotective properties. By delving into the bioactive compounds underpinning its mechanisms of action, exploring M. oleifera through various omics technologies, and addressing the challenges associated with its standardization, this review provides an in-depth analysis of its potential in AD therapy. This review also highlights the need for further research to unlock the full spectrum of factors that could enhance the efficacy of M. oleifera in combating AD by bridging its phytochemical properties with practical therapeutic applications. Therefore, understanding and harnessing the full therapeutic potential of M. oleifera could pave the way for more effective interventions in AD management.

Background Tuberculosis (TB) is a significant global health challenge due to drug resistance. Furthermore, tuberculous meningitis (TBM), which affects the central nervous system, has a particularly high mortality rate. TBM drugs have low efficacy because of their low blood-brain barrier (BBB) permeability. Many institutions that treat tuberculosis lack the infrastructure to identify specific drug-resistance mutations. The development of drugs with the capability of treating multiple strains would contribute considerably to the advancement of TB control in countries with limited resources. Therefore, there is an urgent requirement for novel therapeutics that can target native and drug-resistant strains. Objective This study aimed to design a novel drug to target native as well as drug-resistant Mycobacterium tuberculosis (MTB) strains associated with pulmonary TB and TBM. Methods RNA Polymerase beta-subunit (rpoB) was chosen because it is a validated target for MTB. Pharmacophore features, core moiety analysis, and docking scores were used for ligand screening. Deep neural networks (DeepFrag) were used for structural optimization, and binding affinity was evaluated using AutoDock Vina. Custom scoring schemes, STWMM for TB and STWMMM for TBM, met the requirements of high binding affinity for multiple targets, optimal pharmacokinetic profiles, and chemical synthesizability. Results M1, M2, and M3 were the molecules with the highest STWMM and STWMMM scores, indicating their potential for TB and TBM therapy. The average binding energy of M1 was -8.83 kcal/mol for native and mutant rpoB. The average binding energy for M2 and M3 was -9.63 and -9.83 kcal/mol, respectively). Conclusion In this study, novel ligands for native and drug-resistant TB and TBM therapy were obtained by multi-target drug design. A major challenge for current therapeutic regimens for TB and TBM is the rise of drug-resistant strains of Mycobacterium tuberculosis and the necessity of distinguishing them from the native strains. The multitargeted ligands developed in this study have the potential to overcome these limitations.

Background: Crop yield is limited by several factors. One of these factors is biotic stress. Among biotic stresses, parasitic plants have the greatest role in reducing plant growth and productivity. On the other hand, the multiple uses of pesticides and herbicides have a negative impact on the environment and agricultural products. As an eco-friendly compound, chitosan stimulates the defense system, increases plant resistance to biotic and abiotics stresses, and increases crop growth and productivity. Methods: In this study, the tomato plant was infected with Cuscuta campestris Yunck and sprayed with chitosan nanoparticles with a molecular weight of 50 kDa for 4 weeks and once a week. Four weeks after the infection, plants biomass, protein concentrations, antioxidant enzyme activity (SOD, CAT, APX, POD), and phenolic metabolism (PAL, PPO, total phenolic components, lignin) were measured. Results: In this study, chitosan application increased biomass in Dodder-infected and non-infected plants. The concentration of soluble proteins also increased. In Dodder-infected plants, the activity of antioxidant enzymes increased and the application of chitosan further increased the activity of these enzymes. Phenol metabolism as a defense mechanism in Dodder-infected plants increased compared to the control and chitosan application intensified phenol metabolism. SDS-PAGE analysis investigated that strong bands are formed in the range of 200 and 60 kDa in chitosan treatments and chitosan-treated infected plants. Conclusion: These bands were also observed in Dodder-infected plants that were not treated with chitosan.

Background: A c rylamide (AA) in food is a public health concern that has attracted scientists’ attention worldwide. Objective: This study was carried out to investigate the efficiency of Moringa oleifera (M. olifera) leaves in the reduction of AA in French fries in vitro and its hepato-protective properties against AA-induced liver toxicity in vivo. Materials and Methods: Total phenolic, flavonoid, tannin contents and antioxidant potential of M. oleifera leaves were evaluated and the phenolic constituents characterized via HPLC. AA content was also monitored in French fries using LC-MS/MS. For in vivo assay, mice were treated with AA alone or in combination with M. oleifera (150 and 250 mg/kg IP). Results: Phytochemical screening showed that gallic acid, ellagic acid, epicatechin, and quercetin were the most abundant phenolic compounds identified. This work also demonstrated a nearly 37% reduction in AA when French fries were soaked in 1% M. oleifera. Moreover, AA-intoxicated mice resulted in a significant (P < 0.05) elevation in the liver enzyme alanine aminotransferase (ALT), which was restored when pre-treated with M. oleifera. Conclusion: This study proved that M. olifera could be effective in reducing AA levels in French fries and that treatment with M. oleifera extract can restore the hepatic damage in AA-intoxicated mice.

Background:Furan, quinoline and triazoles are known for their wide spectrum biologically active molecules. A series of novel furan C-2 quinoline and 1, 2, 4-triazole (FQT) coupled hybrids were designed and synthesized to evaluate for their DNA cleavage and cytotoxic studies.Objectives:In this work we describe the synthesis and biological evaluation of furan C-2 quinoline coupled triazoles exposed for cytotoxic and DNA cleavage study.Methods:The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest) using agarose gelelectrophoresis and the cytotoxic activity were carried out by MTT assay method.Results:The results revealed that, the molecules 7(a-o) did cleave the DNA completely with no trace of fragments at 100 µg concentration, on the other hand, cytotoxic assay was achieved by two different human cancer cell lines (melanoma cell line-A375 and breast cancer cell line MDA-MB 231). Among the synthesized compounds 7a, 7b, 7c and 7k exhibited potent cytotoxic activity with IC50 values ranging from 2.9, 4.0, 7.8 and 5.1 µg/ml against A375 and 6.2, 9.5, 11.3 and 7.3 µg/ml against, MDA-MB 231, respectively.Conclusion:In synthesized compounds 7(a-o) exhibited complete DNA cleavage at 100 µg/ml and the compounds 7a, 7b, 7c and 7k showed very less cytotoxic in nature. The structure activity relationship revealed that, the presence of halogen group/atoms at para position of phenyl ring remarkably enhanced the DNA cleavage and cytotoxic activities among the synthesized compounds.

Tolperisone (2-methyl-1-(4-methylphenyl)-3-piperidin-1-ylpropan-1-one hydro-chloride) was introduced in theclinical practice more than forty years ago and is still evaluated as a widely applicable compound in pathologically elevatedskeletal muscle tone (spasticity) and related pains of different origin. In the present review, basic pharmacodynamiceffects measured on whole animals, analyses of its actions on cell and tissue preparations and molecular mechanism of actionon sodium and calcium channels are summarized as recently significantly new data were reported.

A main target in the treatment of hypertension is the angiotensin-converting enzyme (ACE). This enzyme is responsible for producing angiotensin II, a potent vasoconstrictor. Therefore, one of the targets in the treatment of hypertension is to inhibit ACE activity. Hence, this study’s aim is to use computational studies to demonstrate that the proposed heterocyclic compounds have a molecular affinity for ACE and that, furthermore, these heterocyclic compounds are capable of inhibiting ACE activity, thus avoiding the production of the vasopressor Angiotensin II. All this using computer-aided drug design, and studying the systems, with the proposed compounds, through molecular recognition process and compared with the compounds already on the market for hypertension.

ChemVassa, a new chemical structure search technology, was developed to allow rapid in silico screening ofcompounds for hit and hit-to-lead identification in drug development. It functions by using a novel type of molecular descriptorthat examines, in part, the structure of the small molecule undergoing analysis, yielding its “information signature.”This descriptor takes into account the atoms, bonds, and their positions in 3-dimensional space.For the present study, a database of ChemVassa molecular descriptors was generated for nearly 16 million compounds(from the ZINC database and other compound sources), then an algorithm was developed that allows rapid similaritysearching of the database using a query molecular descriptor (e.g., the signature of atorvastatin, below). A scoring metricthen allowed ranking of the search results.We used these tools to search a subset of drug-like molecules using the signature of a commercially successful statin,atorvastatin (Lipitor™). The search identified ten novel compounds, two of which have been demonstrated to interact withHMG-CoA reductase, the macromolecular target of atorvastatin. In particular, one compound discussed in the results sectiontested successfully with an IC50 of less than 100uM and a completely novel structure relative to known inhibitors. Interactionswere validated using computational molecular docking and an Hmg-CoA reductase activity assay. The rapidityand low cost of the methodology, and the novel structure of the interactors, suggests this is a highly favorable new methodfor hit generation.

Telomeres are protein and DNA complexes located atchromosome ends. Telomeric DNA is composed of a double stranded region of repetitive DNA followed by single-stranded 3' extension of aG-rich sequence. Single-stranded G-rich sequencescan fold into G-quadruplex structures,and molecules that stabilize G-quadruplexes are known to inhibit the enzyme telomerase and disrupt telomere maintenance. Because telomere maintenance is required for proliferation of cancer cells, G-quadruplex stabilizers have become attractive prospects for anticancer drug discovery.However, telomere-targeting G-quadruplex ligands have yet to enter the clinic owing in part to poor pharmacokinetics and target selectivity. Increasing the pharmacophore diversity of G-quadruplex and specifically telomeric-DNA targeting agents should assist in overcoming these shortcomings. In this work, we report the identification and validation ofligands that bind telomeric DNA and induce G-quadruplex formationusing the NCI Diversity Set I, providing validation of anextremely simple, rapid and high-throughput screen using FRET technology. Hits from the screen were validated by examining telomerase inhibition and G-quadruplex inductionusing CD spectroscopy and DNA polymerase stop assays. We show that two known DNA binding molecules, ellipticine derivativeNSC 176327 (apyridocarbazole) and NSC 305831 (an antiparasitic hetero-cyclediamidine referred to as furamidine and DB75),are selective induceG-quadruplex formation in the human telomeric sequence and bind telomeric DNA quadruplexes in the absence of stabilizing monovalent cations with molar ratios(molecule: DNA)of 4:1and 1.5:1, respectively.