Evaluation of the Anti-Cancer Potential of Rosa damascena Mill. Callus Extracts against the Human Colorectal Adenocarcinoma Cell Line

Chemotherapy is an aggressive form of chemical drug therapy aiming to destroy cancer cells. Adjuvant therapy may reduce hazards of chemotherapy and help in destroying these cells when obtained from natural products, such as medical plants. In this study, the potential therapeutic effect of Rosa damascena callus crude extract produced in vitamin-enhanced media is investigated on colorectal cancer cell line Caco-2. Two elicitors, i.e., L-ascorbic acid and citric acid at a concentration of 0.5 g/L were added to the callus induction medium. Callus extraction and the GC–MS analysis of methanolic crude extracts were also determined. Cytotoxicity, clonogenicity, proliferation and migration of Caco-2 colorectal cancer cells were investigated using MTT cytotoxicity, colony-forming, Ki-67 flow cytometry proliferation and Migration Scratch assays, respectively. Our results indicated that L-ascorbic acid treatment enhanced callus growth parameters and improved secondary metabolite contents. It showed the least IC50 value of 137 ug/mL compared to 237 ug/mL and 180 ug/mL in the citric acid-treated and control group. We can conclude that R. damascena callus elicited by L-ascorbic acid improved growth and secondary metabolite contents as well as having an efficient antiproliferative, anti-clonogenic and anti-migratory effect on Caco-2 cancer cells, thus, can be used as an adjuvant anti-cancer therapy

Comparative Study between Curcumin and Nanocurcumin Loaded PLGA on Colon Carcinogenesis Induced Mice

Colorectal cancer is the third most common cancer. Because curcumin (CUR) has anti-inflammatory and anticancer properties, research has been undertaken to indicate that nanocurcumin compounds can be used to treat a variety of cancers. CUR in nanoform has been found to have a stronger effect than conventional CUR. The purpose of this study was to show that CUR-loaded poly lactic-co-glycolic acid nanoparticles (PLGA) (CUR-loaded PLGA) have anti-inflammatory and anticancer effects on colon carcinogenesis in male dimethyl hydrazine (DMH) mice as a comparative study between the nanoform of curcumin and normal curcumin, focusing on the anticancer effect of nanocurcumin. Mice were separated into six groups: No treatment was given to Group I (negative Group-I). Group II was treated with CUR. Group III was treated with CUR-loaded PLGA. Group IV was treated with DMH. Group V received DMH and curcumin. Group VI received DMH and CUR-loaded PLGA. At the conclusion of the trial, the animals were slain (6 weeks). Inflammatory indicators and vascular endothelial growth factor (VEGF) levels all changed significantly in this study, as the following inflammatory markers as TNF showed percent of change compared to the DMH group. Recovery percentage for Groups V and VI, respectively, were 9.18 and 55.31%. In addition, IL1 was 7.45 and 50.37% for Groups V and VI, respectively. The results of IL6 were 4.86 and 25.79% for Groups V and VI, respectively. The vascular endothelial growth factor (VEGF) recovery percent was 16.98 and 45.12% for Groups V and VI, respectively. Following the effect of DMH on colon mucosa shape, the researchers looked at the effect of CUR-loaded PLGA on colon histology. It was shown that CUR-loaded PLGA affects the cell cycle and PCNA expression. We conclude that nanocurcumin is an important anti-inflammatory and cancer-fighting agent

Metallic Porphyrazine Networks: Synthesis, as Well as Thermal and Optical Properties for Accelerating the Oxidation of Thiols to Their Disulfides

A condensation reaction of 2,3,5,6-tetraamino-1,4-benzoquinone 1 with 4,5-Dichloro-3,6-dihydroxy-phthalonitrile 2 produced p-benzoquinone [2,3-b:2,3-b]bis[(5,8-dihydroxybenzopyrazine)-6,7-dinitrile] 3. Utilizing acetic acid with lithium/pentanol, the tetra-nitrile monomer was cyclo-tetramerized, yielding the matching network polymer, tetra p-benzoquinone[2,3-b:2,3-b]. bis[(5,8-dihydroxybenzopyrazino) porphyrazine (2H-Pz) 4a. The equivalent tetra p-benzoquinone[2,3-b:2,3-b]bis[(5,8-dihydroxybenzopyrazino) metallic porphyrazine networks (M-Pz) M = Zn 4b or Ni 4c, were obtained by cyclo-tetramerizing the tetra-nitril monomer 3 using metal salt and quinoline. The synthesized molecules’ elemental analytical results, as well as their IR and NMR spectral data, are consistent with their assigned structures. The prepared compounds have large molecular weights and metal content, indicating that reactions of tetramerization, polymerization, and chelation were all productive. The synthesized porphyrazines were proved to be excellent substrates for oxidizing thiophenol and benzyl thiol to their respective disulfides in atmospheric oxygen. The maximal production of the corresponding disulfides after 15 min was 96 percent for thiophenol and 93 percent for benzyl thiol, respectively

Metallic Porphyrazine Networks: Synthesis, as Well as Thermal and Optical Properties for Accelerating the Oxidation of Thiols to Their Disulfides

A condensation reaction of 2,3,5,6-tetraamino-1,4-benzoquinone 1 with 4,5-Dichloro-3,6-dihydroxy-phthalonitrile 2 produced p-benzoquinone [2,3-b:2,3-b]bis[(5,8-dihydroxybenzopyrazine)-6,7-dinitrile] 3. Utilizing acetic acid with lithium/pentanol, the tetra-nitrile monomer was cyclo-tetramerized, yielding the matching network polymer, tetra p-benzoquinone[2,3-b:2,3-b]. bis[(5,8-dihydroxybenzopyrazino) porphyrazine (2H-Pz) 4a. The equivalent tetra p-benzoquinone[2,3-b:2,3-b]bis[(5,8-dihydroxybenzopyrazino) metallic porphyrazine networks (M-Pz) M = Zn 4b or Ni 4c, were obtained by cyclo-tetramerizing the tetra-nitril monomer 3 using metal salt and quinoline. The synthesized molecules’ elemental analytical results, as well as their IR and NMR spectral data, are consistent with their assigned structures. The prepared compounds have large molecular weights and metal content, indicating that reactions of tetramerization, polymerization, and chelation were all productive. The synthesized porphyrazines were proved to be excellent substrates for oxidizing thiophenol and benzyl thiol to their respective disulfides in atmospheric oxygen. The maximal production of the corresponding disulfides after 15 min was 96 percent for thiophenol and 93 percent for benzyl thiol, respectively

Investigation of the New Inhibitors by Sulfadiazine and Modified Derivatives of α-D-glucopyranoside for White Spot Syndrome Virus Disease of Shrimp by In Silico: Quantum Calculations, Molecular Docking, ADMET and Molecular Dynamics Study

The α-D-glucopyranoside and its derivatives were as the cardinal investigation for developing an effective medication to treat the highest deadly white spot syndrome virus (WSSV) diseases in Shrimp. In our forthcoming work, both computational tools, such as molecular docking, quantum calculations, pharmaceutical kinetics, ADMET, and their molecular dynamics, as well as the experimental trial against WSSV, were executed to develop novel inhibitors. In the beginning, molecular docking was carried out to determine inhibitors of the four targeted proteins of WSSV (PDB ID: 2ED6, 2GJ2, 2GJI, and 2EDM), and to determine the binding energies and interactions of ligands and proteins after docking. The range of binding affinity was found to be between −5.40 and −7.00 kcal/mol for the protein 2DEM, from −5.10 to 6.90 kcal/mol for the protein 2GJ2, from −4.70 to −6.2 kcal/mol against 2GJI, and from −5.5 kcal/mol to −6.6 kcal/mol for the evolved protein 2ED6 whereas the L01 and L03 display the highest binding energy in the protein 2EDM. After that, the top-ranked compounds (L01, L02, L03, L04, and L05), based on their high binding energies, were tested for molecular dynamics (MD) simulations of 100 ns to verify the docking validation and stability of the docked complex by calculating the root mean square deviation (RMSD) and root mean square fluctuation (RMSF). The molecules with the highest binding energy were then picked and compared to the standard drugs that were been applied to fish experimentally to evaluate the treatment at various doses. Consequently, approximately 40–45% cure rate was obtained by applying the dose of oxytetracycline (OTC) 50% with vitamin C with the 10.0 g/kg feed for 10 days. These drugs (L09 to L12) have also been executed for molecular docking to compare with α-D-glucopyranoside and its derivatives (L01 to L08). Next, the evaluation of pharmacokinetic parameters, such as drug-likeness and Lipinski’s principles; absorption; distribution; metabolism; excretion; and toxicity (ADMET) factors, were employed gradually to further evaluate their suitability as inhibitors. It was discovered that all ligands (L01 to L12) were devoid of hepatotoxicity, and the AMES toxicity excluded L05. Additionally, all of the compounds convey a significant aqueous solubility and cannot permeate the blood-brain barrier. Moreover, quantum calculations based on density functional theory (DFT) provide the most solid evidence and testimony regarding their chemical stability, chemical reactivity, biological relevance, reactive nature and specific part of reactivity. The computational and virtual screenings for in silico study reveals that these chosen compounds (L01 to L08) have conducted the inhibitory effect to convey as a possible medication against the WSSV than existing drugs (L09, L10, L11 and L12) in the market. Next the drugs (L09, L10, L11 and L12) have been used in trials

Garlic Alleviates the Injurious Impact of Cyclosporine-A in Male Rats through Modulation of Fibrogenic and Steroidogenic Genes

This work aimed to study the hepato-testicular protective effect of garlic in rats treated with cyclosporine A (CsA). Forty male Westar albino rats were randomly distributed in five groups (8 rats each): control, olive oil, garlic, CsA, and CsA co-treated with garlic. CsA induced an upsurge in the alanine transaminase, aspartate transaminase, and alkaline phosphatase levels and decreased albumin and total protein levels, expression of superoxide dismutase (SOD) gene, serum testosterone, triiodothyronine, and thyroxine levels compared to the control group. Additionally, there was an increase in the cholesterol, triglyceride, and low-density lipoprotein levels and a substantial reduction in the high-density lipoprotein levels compared to the control groups. Histopathological investigation of the liver showed abnormalities like hepatic cell degeneration, congestion of blood vessels, and highly active Kupffer cells in the CsA group. Histopathological examination of testes showed damaged seminiferous tubules, stoppage of the maturation of spermatogonia, and the presence of cells with irregular dense nuclei in the lumina of some tubules. For the groups treated with garlic, mitigation of the damage caused by CsA in the liver and testes, liver function tests, lipid profiles, and hormones was seen along with improved gene expression of SOD and steroidogenesis genes, and decreased gene expression of collagen I-α1 and transforming growth factor-1β. Conclusively, garlic had a positive impact on CsA-induced hepatic and sperm toxicity. It is recommended that garlic should be supplemented in transplant treatments using CsA to alleviate the cyclosporin-induced oxidative injuries and other harmful effects

Interactions of the receptor binding domain of sars-cov-2 variants with hace2: Insights from molecular docking analysis and molecular dynamic simulation

© 2021 by the authors. Licensee MDPI, Basel, Switzerland.Since the beginning of the coronavirus 19 (COVID-19) pandemic in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been evolving through the acquisition of genomic mutations, leading to the emergence of multiple variants of concern (VOCs) and variants of interest (VOIs). Currently, four VOCs (Alpha, Beta, Delta, and Gamma) and seven VOIs (Epsilon, Zeta, Eta, Theta, Iota, Kappa, and Lambda) of SARS-CoV-2 have been identified in worldwide circulation. Here, we investigated the interactions of the receptor-binding domain (RBD) of five SARS-CoV-2 variants with the human angiotensin-converting enzyme 2 (hACE2) receptor in host cells, to determine the extent of molecular divergence and the impact of mutation, using protein-protein docking and dynamics simulation approaches. Along with the wild-type (WT) SARS-CoV-2, this study included the Brazilian (BR/lineage P.1/Gamma), Indian (IN/lineage B.1.617/Delta), South African (SA/lineage B.1.351/Beta), United Kingdom (UK/lineage B.1.1.7/Alpha), and United States (US/lineage B.1.429/Epsilon) variants. The protein-protein docking and dynamics simulation studies revealed that these point mutations considerably affected the structural behavior of the spike (S) protein compared to the WT, which also affected the binding of RBD with hACE2 at the respective sites. Additional experimental studies are required to determine whether these effects have an influence on drug–S protein binding and its potential therapeutic effect

Oral supplementation of policosanol alleviates carbon tetrachloride-induced liver fibrosis in rats

Liver fibrosis is a prevalent liver disease that requires rapid and effective treatment prior to its progression to cirrhosis and liver damage. Recently, several reports have investigated the efficacy of phytotherapy using natural herbal extracts rather than synthetic drugs to treat several liver diseases. Policosanol is a herbal extract used to treat patients with cardiovascular. However, its therapeutic effect on liver fibrosis is still unknown. Therefore, the present study aimed to assess the potential antifibrotic effect of policosanol compared to silymarin and the possible underlying molecular mechanisms. Rats were categorized into four groups; negative control group NCG, the fibrotic group FG, silymarin treated group STG, and policosanol treated group PTG. Serum liver enzymes, oxidative stress markers, angiogenic growth factors, and pro-inflammatory cytokines were measured biochemically. The relative mRNA expressions of liver caspase-3 and alpha-smooth muscle actin (alpha-SMA) were assessed. Immunohistochemical staining was carried out using anti-alpha-SMA, and anti-caspase-3 antibodies. Compared to NCG, the FG group demonstrated a significant decrease in the level of serum liver enzymes GSH, TAC, and SDF. Nevertheless, it demonstrateda significant increase in the level of pro-inflammatory cytokines Il6, TNF; oxidative stress markers NO, MDA, and angiogenic growth factors VEGF and PDGF and the expression of alpha-SMA, and Caspase-3. Interestingly, the values of these measurements were restored to normal levels in the treated groups, particularly the PTG. In conclusion, our data revealed the beneficial effects of co administration of policosanol or silymarin on the fibrotic liver rat model and thus could be a promising natural therapeutic drug

Chemical and Pharmacological Profiling of <i>Wrightia coccinea</i> (Roxb. Ex Hornem.) Sims Focusing Antioxidant, Cytotoxic, Antidiarrheal, Hypoglycemic, and Analgesic Properties

The aim of the study was to conduct phytochemical and pharmacological investigations of Wrightia coccinea (Roxb. ex Hornem.) Sims via several in vitro, in vivo, and in silico models. A total of four compounds were identified and isolated from the methanol extract of the bark and the methanol extract of the seed pulp of W. coccinea through successive chromatographic techniques and were characterized as 3β-acetyloxy-olean-12-en-28-ol (1), wrightiadione (2), 22β-hydroxylupeol (3), and β-sitosterol (4) by spectroscopic analysis. The aqueous fraction of the bark and chloroform fraction of the fruits provided the most potent antioxidant capacity (IC50 = 7.22 and 4.5 µg/mL, respectively) in DPPH free radical scavenging assay compared with the standard ascorbic acid (IC50 = 17.45 µg/mL). The methanol bark extract and the methanol fruit coat extract exerted anti-diarrheal activity by inhibiting 74.55 ± 0.67% and 77.78 ± 1.5% (mean ± SEM) of the diarrheal episode in mice, respectively, after four hours of loading the samples. In the hypoglycemic test, the methanol bark extract and the methanol fruit coat extract (400 mg/kg) produced a significant (p p W. coccinea might be a potential natural source for managing oxidative stress, diarrhea, hyperglycemia, and pain. Further studies are warranted for extensively phytochemical screening and establishing exact mechanisms of action

Molecular Detection of Fluoroquinolone Resistance among Multidrug-, Extensively Drug-, and Pan-Drug-Resistant Campylobacter Species in Egypt

In recent times, resistant foodborne pathogens, especially of the Campylobacter species, have created several global crises. These crises have been compounded due to the evolution of multidrug-resistant (MDR) bacterial pathogens and the emergence of extensively drug-resistant (XDR) and pan-drug-resistant (PDR) strains. Therefore, this study aimed to investigate the development of resistance and the existence of both XDR and PDR among Campylobacter isolates. Moreover, we explored the use of the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) technique for the detection of fluoroquinolone (FQ)-resistant Campylobacter isolates. A total of 120 Campylobacter isolates were identified depending on both phenotypic and genotypic methods. Of note, cefoxitin and imipenem were the most effective drugs against the investigated Campylobacter isolates. Interestingly, the majority of our isolates (75%) were MDR. Unfortunately, both XDR and PDR isolates were detected in our study with prevalence rates of 20.8% and 4.2%, respectively. All FQ-resistant isolates with ciprofloxacin minimum inhibitory concentrations ≥4 µg/mL were confirmed by the genetic detection of gyrA chromosomal mutation via substitution of threonine at position 86 to isoleucine (Thr-86-to-Ile) using the PCR-RFLP technique. Herein, PCR-RFLP was a more practical and less expensive method used for the detection of FQ resistant isolates. In conclusion, we introduced a fast genetic method for the identification of FQ-resistant isolates to avoid treatment failure through the proper description of antimicrobials