Skin anti-aging potential of Launaea procumbens extract: Antioxidant and enzyme inhibition activities supported by ADMET and molecular docking studies.

Aging is a natural process that occurs in all living organisms. Particularly, the skin embodies aging since it serves as a barrier between the body and its surroundings. Previously, we reported the wound healing effect of Launaea procumbens and identified compounds therein. The study aims to explore the skin anti-aging properties of the plant extract. To that effect, the antioxidant potential of L. procumbens methanolic extract (LPM) was assessed using two complementary DPPH and FRAP assays. The enzyme inhibitory effect of the extract on collagenase, elastase, hyaluronidase, and tyrosinase was evaluated to assess the direct skin anti-aging effects. Similarly, the anti-inflammatory activity was evaluated to explore the indirect anti-aging effects via the assessment of extract inhibitory effects on cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). In addition, ADMET and molecular docking studies were performed to explore the interaction mechanisms of identified compounds in LPM with target enzymes. LPM demonstrated significant antioxidant activity in DPPH (IC50 = 29.08 µg/mL) and FRAP (1214.67 µM FeSO4/g extract) assays. Plant extract showed significant inhibition of collagenase, elastase, hyaluronidase, and tyrosinase (IC50 = 52.68, 43.76, 31.031, and 37.13 µg/mL, respectively). The extract demonstrated significant COX-2 and 5-LOX inhibition capacity with IC50 values of 8.635 and 10.851 µg/mL, respectively. The molecular docking study revealed the high potential of the identified compounds to bind to the active sites of enzymes crucially involved in the skin aging process. ADMET analysis of the compounds revealed their good absorption, distribution, and metabolism profiles, and they were found to be safe as well. Study findings suggest L. procumbens as a promising source for the development of natural skin anti-aging and antioxidant compounds. This, in turn, may facilitate its incorporation into cosmetic formulations after further investigation.

Overcoming the imatinib-resistant BCR-ABL mutants with new ureidobenzothiazole chemotypes endowed with potent and broad-spectrum anticancer activity.

The design of kinase inhibitors targeting the oncogenic kinase BCR-ABL constitutes a promising paradigm for treating chronic myeloid leukaemia (CML). Nevertheless, the efficacy of imatinib, the first FDA-approved targeted therapy for CML, is curbed by the emergence of resistance. Herein, we report the identification of the 2-methoxyphenyl ureidobenzothiazole AK-HW-90 (2b) as a potent pan-BCR-ABL inhibitor against imatinib-resistant mutants, particularly T315I. A concise array of six compounds 2a-f was designed based on our previously reported benzothiazole lead AKE-5l to improve its BCR-ABLT315I inhibitory activity. Replacing the 6-oxypicolinamide moiety of AKE-5l with o-methoxyphenyl and changing the propyl spacer with phenyl afforded 2a and AK-HW-90 (2b) with IC50 values of 2.0 and 0.65 nM against BCR-ABLT315I, respectively. AK-HW-90 showed superior anticancer potency to imatinib against multiple cancer cells (NCI), including leukaemia K-562. The obtained outcomes offer AK-HW-90 as a promising candidate for the treatment of CML and other types of cancer.

Comprehensive analysis of malabar tamarind fruit rind total extract: HPTLC fingerprinting, in-silico exploration of its metabolites for SARS-cov-2 omicron spike protein, antibacterial and antidiabetic potentials with in vitro evaluation of antidiabetic and antioxidant activities.

Malabar tamarind tropical fruit, scientifically known as Garcinia gummi-gutta, is indigenous to Southeast Asia. In this work, the total methanolic extract of the Malabar fruit rind was examined by HPTLC fingerprinting, with quantitative evaluation of the total phenolics and flavonoids. Library of previously reported natural metabolites was utilized to demonstrate their affinity for specific target sites, they were evaluated against Omicron SARS-CoV-2 mainly it's Spike Protein, bacterial tyrosinase, and antidiabetic targets such α-glucosidase, pancreatic lipase and also α-amylase enzymes. The molecular docking revealed that the Guttiferone R possessed the highest binding affinity toward the Omicron Spike Protein with a stable binding mode, -8.67 kcal/mol binding energy and a 1.07 Å RMSD value compared to reference, Azithromycin, which has -8.90 kcal/mol binding affinity and a 1.20 Å RMSD value. On the other hand, the identified polyphenolic compounds; Vitexin, Prunin, Naringin, Hinokiflavone, Kaempherol-3-O-rutinoside, Gallic acid, Naringenin, and Catechin, showed remarkable antidiabetic activity by strong inhibitory activity against α-glucosidase and notable activity against α-amylase compared with acarbose as reference. According to antibacterial activity, the identified compounds showed low affinity with weak activity against screened bacterial strains. In-vitro evaluation of Tamarind antioxidant and antidiabetic potentials, it exhibited a free radical-scavenging potential with 71.75 % retardation and α-glucosidase, α-amylase and pancreatic lipase inhibitor activities with an IC50 of 391.3 ± 26.27, 95.03 ± 0.03 and 0.01043 ± 0.0004 µg/mL, respectively that emphasize the molecular docking study. The findings imply that Malabar tamarind fruit rind possess antioxidant, antidiabetic, antibacterial and antiviral activities.

Integrating Chemical Profiling, In Vivo Study, and Network Pharmacology to Explore the Anti-inflammatory Effect of Pterocarpus dalbergioides Fruits and Its Correlation with the Major Phytoconstituents.

The purpose of this study is to explore the anti-inflammatory activity of Pterocarpus dalbergioides fruit extract (PFE) and the underlying mechanism. Chemical profiling using ultraperformance liquid chromatography/mass spectrometry identified 28 compounds in PFE (12 flavonoids, 5 fatty acids, 4 phenolic compounds, 3 alkaloids, 2 sesquiterpenes, and 2 xanthophylls). PFE (2 g/kg) significantly inhibited carrageenan-induced rat paw edema after 4 h of administration (42% inhibition). A network-based strategy and molecular docking studies were utilized to uncover the anti-inflammatory mechanism. Out of the identified compounds, 16 compounds with DL ≥ 0.18 and F ≥ 30% were selected using bioavailability (F) and drug-likeness (DL) metrics. The network analysis revealed that 90 genes are considered key targets for the selected compounds and linked to the anti-inflammatory effect. Among all compounds, linoleic acid was found to be the top-most active constituent as it targets maximum genes. Four targets (TNF, IL6, AKT1, and CCL2) among the top 10 genes were found to be the main target genes that may contribute to the anti-inflammatory potential of PFE. Furthermore, KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis revealed that PFE might regulate inflammation through five pathways: neuroactive ligand-receptor interaction, lipid and atherosclerosis, fluid shear stress and atherosclerosis, TNF signaling pathway, and rheumatoid arthritis. The docking study predicted the significant binding affinity between the top four active constituents (linoleic acid, 9-octadecenoic acid, 11,12,13-trihydroxy-9-octadecenoic acid, and rhamnetin-3-O-rhamnoside) and the selected target proteins (TNF and AKT1). The findings highlight PFE as a promising drug lead for controlling inflammation.

Simultaneous green TLC determination of nirmatrelvir and ritonavir in the pharmaceutical dosage form and spiked human plasma.

Quantitative analysis of pharmaceutical compounds up to Nano gram levels is highly recommended to introduce feasible and sensitive tool for determination of the compounds in the pharmaceutical and biological samples. Nirmatrelvir plus ritonavir was recently approved in the US, the UK and Europe as a new co-packaged dosage form for the treatment of COVID-19. The objective of this work was to develop a more sensitive TLC method based on using ß-cyclodextrin as a chiral selector additive in the mobile phase for simultaneous determination of nirmatrelvir and ritonavir in pure form, pharmaceutical formulation and spiked human plasma. The analysis procedures were developed using TLC aluminum silica gel plates and methanol-water- 2% urea solution of ß-cyclodextrin (40:10:.5, by volume) as a mobile phase with UV detection at 215 nm. The developed method was successfully applied over a linearity range of 10-50 ng/band for both nirmatrelvir and ritonavir. The method was validated for limits of detection and quantitation, accuracy, precision, specificity, system suitability, and robustness. Furthermore, the eco-friendliness of the proposed method was assessed using the analytical eco-scale and the green analytical procedure index. The described method exhibited compliance with green analytical chemistry principles based on common green metric values.

The Influence of a Nanoemulsion of Cardamom Essential Oil on the Growth Performance, Feed Utilization, Carcass Characteristics, and Health Status of Growing Rabbits under a High Ambient Temperature.

Recently, nanotechnology approaches have been employed to enhance the solubility, availability, and efficacy of phytochemicals, overcoming some industrial obstacles and natural biological barriers. In this regard, 120 clinically healthy growing V-line rabbits (5 weeks old) reared during the summer season were divided randomly into four equal experimental groups (30 rabbits each). The first group received a basal diet without the supplementation of the nanoemulsion of cardamom essential oil (NCEO) (0 g/kg diet) and served as a control (NCEO 0). The other groups were given diets containing NCEO at levels of 150 (NCEO 150), 300 (NCEO 300), and 600 (NCEO 600) mg/kg diet, respectively. The growth performance (higher LBW and ADG), feed utilization (lower FCR), dressing percentage, and relative weight of the liver were improved significantly in the NCEO-treated groups compared to the control group. Moreover, the dietary treatment significantly decreased the rectum temperature and respiration rate, minimizing the 350 and 325 mg NECO/kg diets. The erythrocyte count, hematocrit, and hemoglobin concentration were significantly increased (p < 0.05), while white blood cells were significantly diminished (p = 0.0200) in the NCEO300 and NCEO600 groups compared to the control group. Treatment with 300 or 600 mg NCEO/kg significantly increased the blood serum total protein and albumin compared to the control group. Meanwhile, the liver enzymes (AST and ALT), uric acid, and creatinine concentrations decreased significantly in the NCEO300 group compared to the control group. The concentrations of triglycerides and total cholesterol were reduced significantly by the dietary treatment. The total antioxidant capacity, dismutase activity, and glutathione concentration were significantly higher, while the malondialdehyde and protein carbonyl levels were significantly lower in the NCEO300 group than in the control. The inflammatory responses and immunity statuses were improved in the blood serum of the NCEO-treated rabbits compared to the control. Heat-stress-induced pathological perturbations in renal/hepatic tissues and NCEO co-treatment successfully re-established and recovered near-control renal-hepatic morphology. In conclusion, a dietary supplementation of NCEO (300 mg/kg) could effectively enhance growing rabbits' growth indices, feed efficiency, redox balance, immunity, and inflammatory responses during the summer.

Lactoferrin: Antimicrobial impacts, genomic guardian, therapeutic uses and clinical significance for humans and animals.

Lactoferrin (LF) is a protein found in several bodily fluids, such as milk. This protein has a diverse range of functions and is evolutionarily conserved. Lactoferrin is a multifunction protein with distinct biological abilities affecting mammals' immune structures. Reports indicated that the daily uptake of LF from dairy products is unsatisfactory in detecting further health-promoting abilities. Research has shown that it protects against infection, mitigates cellular senescence, and improves nutritional quality. Additionally, LF is being studied as a potential treatment for various diseases and conditions, including gastrointestinal issues and infections. Studies have also demonstrated its effectiveness against various viruses and bacteria. In this article, we'll look closer at the structure of LF and its various biological activities, including its antimicrobial, anti-viral, anti-cancer, anti-osteoporotic, detoxifying, and immunomodulatory properties. More specifically, the protective effect of LF against oxidative DNA damage was also clarified through its ability to abolish DNA damaging issues without interfacing with host genetic material. Fortification with LF protects mitochondria dysfunction syndromes via sustaining redox status and biogenesis and suppressing apoptosis and autophagy singling. Additionally, we'll examine the potential benefits of lactoferrin and provide an overview of recent clinical trials conducted to examine its use in laboratory and living models.