Current Bioactive Compounds - Volume 20, Issue 4, 2024

Background: Breast cancer was known as the second most common cause of death in the world, natural sources compound derived from milk thistle called silymarin had already shown anticancer properties. Objective: In the present study, silymarin was used to treat MCF7 cells and inhibition of stem cell pluripotency genes, as well as cell proliferation. Methods: MCF7 cells were cultured in the presence of RPMI-1640 medium consisting of various silymarin extract concentrations (10, 100, 500, 1000, 2000, 3000, 4000, and 5000 μg/mL) for 24, 48, and 72 hours. The inhibitory effects of the compound on cellular proliferation were assessed via employing MTT assay techniques. Following confirming apoptosis, the fold changes of OCT4, NANOG and P53 expression were determined by quantitative Real-time PCR. Results: There was a significant difference (p value <0.05) in cell viability when various concentrations of silymarin extract were used for 24, 48, and 72 h in comparison to the control. Real-time- PCR analysis indicated that the expression of OCT4 and NANOG was downregulated while P53 upregulated in compare to untreated control cells (p value <0.05). Conclusion: According to these findings, the silymarin effects on MCF7 cell line and act via modulating OCT4, NANOG, and P53 pathway mediators. Silymarin may introduce this compound as a promising therapeutic compound against MCF7.

Aims: Bixin and norbixin are natural antioxidants used as pigments in the food industry, but their chemical structure makes them susceptible to environmental factors (light, oxygen, and temperature). Background: Nanoencapsulation techniques can improve the stability and solubility of these compounds in addition to reducing particle size which can increase the surface-to-volume ratio and provide many attractive and unique properties to the nanoparticles. Objective: In this study, sodium alginate was used as wall material for the encapsulation of bixin and norbixin in different concentrations (1.25 x 10^-3, 2.5 x 10^-3, 5 x 10-3 and 7.5 x 10^-3 g/g of biopolymer), by emulsification/internal gelation method. Methods: The emulsification/internal gelation method was used to elaborate bixin or norbixinloaded nanospheres. The internal phase of the water-in-oil (W/O) emulsion was prepared with an aqueous solution of sodium alginate (1.5% w/v - 40 mL), 0.12 g of CaCO3, bixin or norbixin pigments, and mechanically stirred for 15 min at 700 rpm. Results: Nanospheres containing the highest concentration of both carotenoids showed better encapsulation efficiency, with 37.86% for bixin and 51.47% for norbixin, and these formulations were used for characterization analyses. The mean size of the nanospheres was 741.9 ± 41.0 nm, 622.9 ± 71.0 nm, and 589.5 ± 99.1 nm for control particles, bixin, and norbixin, respectively. The addition of both carotenoids resulted in particles with a yellow-red color, which demonstrates the encapsulation of natural antioxidants. The thermal analysis results may indicate an increase in the thermal stability of the pigments after encapsulation, in addition, the nanospheres exhibited the ability to scavenge the ABTS⁺ radical. Carotenoids release test in food simulant (95% ethanol) presented a rapid release in the first hours and maintenance of concentration for 10 days. Conclusion: Results showed that these nanospheres could be an alternative to the application of these carotenoid pigments in food matrices and food packaging.

Background: Nuclear enzyme poly (ADP-ribose) polymerase-1 (PARP-1) controls the cell cycle, DNA repair, transcription, and replication processes. In this study, olaparib and rucaparib have been taken as standard drugs for comparison of results. As per previous research data, 1,3,4-Oxadiazole moiety has multidirectional biological activity and shows high activity against cancer. Objective: This study aimed to carry out the in silico ligand-based screening for the identification of hits for PARP1 inhibitors bearing 1,3,4-thiadiazole derivatives using Schrodinger suite 2022-1 and to perform MMGBSA and molecular dynamics simulation for lead molecules. Methods: A total of 32 derivatives of 1,3,4-Oxadiazole were designed with four different acids: phenoxy acetic acid, 1-Naphthoxy acetic acid, 2-Naphthoxy acetic acid, and piperonylic acid. Molecular docking (XP) studies were performed between 4ZZZ.pdb and the designed analogues, and the binding affinity values lay in the range of -8.52 to -3.52 kcal/mol. 2D interactions between the protein and the ligand were observed. Based on the binding affinity values and ADMET results, top 10 analogues were selected for performing MM-GBSA. Results: The dG-bind score of the top compounds varied from -2.30 to -60.67 kcal/mol, and analogue D4 was selected for MD simulation studies for 100ns. Results of Molecular dynamics (MD) studies showed that D4 interacted with amino acid residues, and the ligand-protein interaction stabilized from 58-90ns. The in silico study's findings suggested that the chemicals A1, A3, B1, B2, B3, B4, C1, C6, D1, and D4 might be significantly active against breast cancer with potential therapeutic benefits and are likely to be useful after further development. Conclusion: In conclusion, numerous molecules exhibit a high affinity for PARP-1 when derived from 1,3,4-oxadiazole. The in silico study's findings suggested that the chemicals A1, A3, B1, B2, B3, B4, C1, C6, D1, and D4 might be significantly active against breast cancer with potential therapeutic benefits and are likely to be useful after further development.

Epigenetics deals with the changes in gene expression (no change in the genetic code) concerning certain epigenetic elements in response to the environment. Some of the most common epigenetic examples include DNA methylation, histone modifications, and non-coding RNAs. This field has been extensively applied in forensic studies, particularly to determine types of body fluids, distinguish them from mixed samples, uncovering the biological age of the forensic samples and drug-based studies. Considering recent findings, this review highlights the applications of epigenetics in forensic investigations.

Alzheimer’s disease (AD) is the most common neurodegenerative and progressive disorder that results in damage to memory and alters thinking and behavior, which represent critical problems the world’s aging population is faced with. Clinical symptoms of AD include cognitive decline, loss of memory, emotional and behavioral changes, loss of motor coordination, and mental impairments. Yet, neither a universally accepted diagnosis with respect to its pathogenesis nor an ideal therapy is available for the management of AD. The existing drugs cause many complications and adverse effects. Herbal drugs, supported by an abundance of traditional knowledge, may fulfill the need as they can target the pathogenesis of AD at various destinations, both at the cellular and molecular levels. In recent years, herbal drugs and formulations have been evaluated in preclinical setups, especially involving rat and mouse models of AD, which have shown their memoryenhancing, neuroprotective, and antioxidant activities. Several herbal drugs and phytochemicals have been evaluated for their effectiveness as antioxidative agents to prevent the occurrence of oxidative stress and ROS formation during AD pathogenesis and exhibit antiapoptotic properties by downregulating caspase-3, DNA fragmentation, NF-ΚB, interleukin-1 β (IL1β), and TNF levels. In this paper, we have primarily reviewed herbal remedies that have been recently evaluated as alternative treatments for AD in a preclinical setup, and discussed the role of herbal medicines in the management of AD and advances in their knowledge.

Cancer remains a leading cause of death worldwide, with traditional chemotherapy treatments causing significant side effects. Short synthetic peptides have emerged as a potential alternative due to their unique properties, including selectivity, stability and biocompatibility. Recent research has shown that short peptides can act as effective anticancer agents through their ability to inhibit the COX-2 (Cyclooxegenase-2) enzyme, a key enzyme involved in tumor growth and progression. In particular, short peptides have demonstrated promising results in targeting the tumor microenvironment, disrupting angiogenesis, and inducing apoptosis in cancer cells. This review summarizes the current literature on short peptides as anticancer agents, including their mechanisms of action and future directions for research and development. The results suggest that short peptides hold significant potential as a new class of anticancer agents and warrant further investigation.

Introduction: Etoricoxib is a BCS class II drug with poor aqueous solubility and analgesic and anti-inflammatory properties. Complexation with cyclodextrins is one of the widely used methods, amongst others, for enhancing the solubility and bioavailability of drugs. In current research work, inclusion complexes of etoricoxib using modified forms of cyclodextrin, i.e., captisol were prepared using kneading, evaporation, and freeze-drying methods to improve the solubility and dissolution characteristics. Methods: Etoricoxib inclusion complexes (ratio 1:1) were formulated using kneading, evaporation, and freeze-drying methods. The formulated inclusion complexes were evaluated for phase solubility, equilibrium solubility studies, Fourier transform infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, differential scanning calorimetry studies, in vitro drug release, similarity factor and in vivo studies. Results: The freeze-drying method produced inclusion complexes with the highest equilibrium solubility (ten times that of the pure drug). Fourier transform infrared spectroscopy studies showed no drug-polymer interaction. Differential scanning calorimetry and scanning electron microscopy studies suggested the incorporation of the drug into inclusion complexes of cyclodextrin. In vitro dissolution studies of kneading, evaporation and freeze-drying method inclusion complexes showed 66.53%, 79.13% and 88% drug release, respectively, in 3h, whereas pure drug exhibited 61.77% drug release in 3 h. The f1 value obtained was less than 50, which is indicative of a significant difference in release characteristics of kneading, evaporation and freeze-drying methods with that of the marketed formulation. In vivo studies indicated that inclusion complexes formulated by the freeze-drying method showed better analgesic and anti-inflammatory effects in comparison to formulations prepared by kneading and evaporation methods. Conclusion: It is concluded that the formulation prepared by the freeze-drying method led to a significant enhancement of dissolution and solubility rate of etoricoxib in comparison to the formulation prepared by the kneading method and evaporation method.

Background: Sideritis species were used for the treatment of mental disorders such as Alzheimer’s and dementia traditionally in Turkey. Several in vivo studies report that the mid-polar extract of Sideritis species can develop the brain functions of mice. 2-β-hydroxy manoyl oxide, isolated from ethyl acetate extract of Sideritis perfoliata, was assayed in vitro and in silico on human erythrocytes CA I and CA II. The compound was found to be an activator on two isoenzymes. It has been reported that activators of carbonic anhydrases may be used as a novel approach to treating disorders such as Alzheimer’s and age-related diseases. This study aimed to investigate the activity effect of 2-β-hydroxy manoyl oxide in vitro and in silico on human erythrocytes CA I and CA II (hCA I and hCA II) and to elucidate its pharmacokinetic and physicochemical characteristics. Methods: The test compound was isolated from ethyl acetate extract of Sideritis perfoliata using chromatographic techniques and identified with spectroscopic evidence. Carbonic anhydrase activities were assayed using CO2 substrates. Docking studies were carried out with Molegro Virtual Docker. The compound underwent ADME-Tox prediction by using AdmetSAR and SwissADME software. Results: 2-β-hydroxy manoyl oxide was found to increase the hCA-l and hCAII activity with AC50 values 9 and 19 μM, respectively. These results were further confirmed in silico molecular modeling. It showed favorable pharmacokinetic and physicochemical characteristics as a new drug candidate. Conclusion: These findings demonstrated that 2-β-hydroxy manoyl oxide activated the hCA-l and hCA II. These results provide a novel and alternative activator for the carbonic anhydrase and confirm the traditional usage of the Sideritis perfoliata.

Background: Ruta montana (R. montana) is a medicinal plant with a long history of traditional use in treating ailments. Objective: The present work aims to study the phytochemical composition and to evaluate the biological activities of R. montana L. (Rutacea) extracts. Methods: Bioactive compounds were obtained using solid-liquid extraction using solvents of increasing polarity. The obtained extracts were qualitatively analyzed by liquid chromatography coupled with mass spectrometry (LC-MS). The pharmacological properties of R. montana were also investigated. Antioxidant activity was achieved 'in vitro' using two methods: scavenging of the free radical DPPH and total antioxidant capacity. Antimicrobial activity was evaluated using disc diffusion method on 3 pathogenic bacterial strains (Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus). In addition, cytotoxic activity was determined by the 'Brine shrimp' test. Results: Chemical investigation allowed the identification of 14 phenolic compounds. The identified compounds were mainly phenolic acids, coumarins and flavonoids. The crude extract and the different tested fractions exhibited an interesting antioxidant activity. Chloroform extract was effective against the growth of the tested bacterial strains with zones of inhibition varying between 14 and 18 mm. In contrast, ethyl acetate and butanolic extracts were almost inactive on all of the tested bacterial strains. Furthermore, the crude extract was found to exhibit antibacterial activity with 11 to 11.66 mm of inhibitions zone. No cytotoxic effect was recorded for all the tested extracts up to a concentration of 4000 μg/mL. Conclusion: This work highlights the potent bioactivity and acceptable drug-likeness of this plant, which supports its further uses.