Optimization, In Vitro and Ex Vivo Assessment of Nanotransferosome Gels Infused with a Methanolic Extract of Solanum xanthocarpum for the Topical Treatment of Psoriasis.

The goal of this investigation is to improve the topical delivery of medicine by preparing and maximizing the potential of a nanotransferosome gel infused with Solanum xanthocarpum methanolic extract (SXE) to provide localized and regulated distribution. Thin-film hydration was used to create SXE-infused nanotransferosomes (SXE-NTFs), and a Box-Behnken design was used to improve them. Phospholipon 90G (X1), cholesterol (X2) and sodium cholate (X3) were chosen as the independent variables, and their effects on vesicle size (Y1), polydispersity index (PDI) (Y2) and the percentage of entrapment efficiency (EE) (Y3) were observed both individually and in combination. For the SXE-NTFs, the vesicle size was 146.3 nm, the PDI was 0.2594, the EE was 82.24 ± 2.64%, the drug-loading capacity was 8.367 ± 0.07% and the drug release rate was 78.86 ± 5.24%. Comparing the antioxidant activity to conventional ascorbic acid, it was determined to be 83.51 ± 3.27%. Ex vivo permeation tests revealed that the SXE-NTF gel (82.86 ± 2.38%) considerably outperformed the SXE gel (35.28 ± 1.62%) in terms of permeation. In addition, it seemed from the confocal laser scanning microscopy (CLSM) picture of the Wistar rat's skin that the rhodamine-B-loaded SXE-NTF gel had a higher penetration capability than the control. Dermatokinetic studies showed that the SXE-NTF gel had a better retention capability than the SXE gel. According to the experimental results, the SXE-NTF gel is a promising and successful topical delivery formulation.

Multi-target mechanism of Solanum xanthocarpum for treatment of psoriasis based on network pharmacology and molecular docking.

Solanum xanthocarpum (SX) has been used to treat a variety of diseases, including skin disorders like psoriasis (PSO). SX possesses many pharmacological activities of anti-inflammatory, anti-cancer, immunosuppressive, and healing qualities. However, the multi-target mechanism of SX on PSO still needs clarity. Materials and methods: The Indian Medicinal Plants, Phytochemicals and Therapeutics (IMPPAT) database and the Swiss Target Prediction online tool were used to find the active phytochemical components and their associated target proteins. OMIM and GeneCards databases were used to extract PSO-related targets. A Venn diagram analysis determined the common targets of SX against PSO. Subsequently, the protein-protein interaction (PPI) network and core PPI target analysis were carried out using the STRING network and Cytoscape software. Also, utilising the online Metascape and bioinformatics platform tool, a pathway enrichment analysis of common targets using the Kyoto Encyclopaedia of Genes and Genome (KEGG) and Gene Ontology (GO) databases was conducted to verify the role of targets in biological processes, cellular components and molecular functions with respect to KEGG pathways. Lastly, molecular docking simulations were performed to validate the strong affinity between components of SX and key target receptors. Results: According to the IMPPAT Database information, 8 active SX against PSO components were active. According to the PPI network and core targets study, the main targets against PSO were EGFR, SRC, STAT3, ERBB2, PTK2, SYK, EP300, CBL, TP53, and AR. Moreover, molecular docking simulations verified the binding interaction of phytochemical SX components with their PSO targets. Last but not least, enrichment analysis showed that SX is involved in several biological processes, including peptidyl-tyrosine phosphorylation, peptidyl-tyrosine modification, and peptidyl-serine modification. The relevant KEGG signalling pathways are the PI3K-AKT signalling pathway, the EGFR tyrosine kinase inhibitor resistance pathway, and the MAPK signalling pathway. Conclusion: The network pharmacology technique, which is based on data interpretation and molecular docking simulation techniques, has proven the multi-target function of SX phytoconstituents.

In-vitro and ex-vivo antidiabetic, and antioxidant activities of Box-Behnken design optimized Solanum xanthocarpum extract loaded niosomes.

One of the most prevalent lifestyle diseases, diabetes mellitus (DM) is brought on by an endocrine issue. DM is frequently accompanied by hyperglycemia, a disease that typically results in an excess of free radicals that stress tissues. The medical community is currently concentrating on creating therapeutic medications with roots in nature to lessen the damage associated with hyperglycemia. Solanum xanthocarpum has a number of medicinal benefits. The investigation aimed to produce and analyze niosomal formulations containing S. xanthocarpum extract (SXE). Niosomes were made by implementing the solvent evaporation process, which was further optimized using Box-Behnken design. Drug release, DPPH assessments, α-amylase inhibition assay, α-glucosidase inhibition assay, and confocal laser scanning microscopy (CLSM) investigation were all performed on the developed formulation (SXE-Ns-Opt). SXE-Ns-Opt displayed a 253.6 nm vesicle size, a PDI of 0.108, 62.4% entrapment efficiency, and 84.01% drug release in 24 h. The rat's intestinal CLSM image indicated that the rhodamine red B-loaded SXE-Ns-Opts had more intestinal penetration than the control. Additionally, the antioxidant effect of the obtained formulation was demonstrated as 89.46% as compared to SXE (78.10%). Additionally, acarbose, SXE, and SXE-Ns-Opt each inhibited the activity of α-amylase by 95.11%, 85.88%, and 89.87%, and also suppressed the enzyme of α-glucosidase by 88.47%, 81.07%, and 85.78%, respectively. To summarise, the establishment of the SXE-Ns-Opt formulation and its characterization demonstrated the legitimacy of the foundation. A promising candidate for the treatment of diabetes mellitus has been shown as in vitro studies, antioxidant against oxidative stress, CLSM of rat's intestine and a high degree of penetration of formulation.

Formulation and Evaluation of Plumbagin-Loaded Niosomes for an Antidiabetic Study: Optimization and In Vitro Evaluation.

Diabetes treatment requires focused administration with quality systemic circulation to determine the optimal therapeutic window. Intestinal distribution through oral administration with nanoformulation provides several benefits. Therefore, the purpose of this study is to create plumbagin enclosed within niosomes using the quality by design (QbD) strategy for efficient penetration and increased bioavailability. The formulation and optimization of plumbagin-loaded niosomes (P-Ns-Opt) involved the use of a Box-Behnken Design. The particle size (PDI) and entrapment efficiency of the optimized P-Ns-Opt were 133.6 nm, 0.150, and 75.6%, respectively. TEM, DSC, and FTIR were used to analyze the morphology and compatibility of the optimized P-Ns-Opt. Studies conducted in vitro revealed a controlled release system. P-Ns-Opt's antioxidant activity, α-amylase, and α-glucosidase were evaluated, and the results revealed a dose-dependent efficacy with 60.68 ± 0.02%,90.69 ± 2.9%, and 88.43 ± 0.89%, respectively. In summary, the created P-Ns-Opt demonstrate remarkable potential for antidiabetic activity by inhibiting oxygen radicals, α-amylase, and α-glucosidase enzymes and are, therefore, a promising drug delivery nanocarrier in the management and treatment of diabetes.

Cytotoxicity and molecular docking analysis of racemolactone I, a new sesquiterpene lactone isolated from Inula racemosa.

CONTEXT: Traditionally, Inula racemosa Hook. f. (Asteraceae) has been reported to be effective in cancer treatment which motivated the authors to explore the plant for novel anticancer compounds. OBJECTIVE: To isolate and characterize new cytotoxic phytoconstituents from I. racemosa roots. MATERIALS AND METHODS: The column chromatography of I. racemosa ethyl acetate extract furnished a novel sesquiterpene lactone whose structure was established by NMR (1D/2D), ES-MS and its cytotoxic properties were assessed on HeLa, MDAMB-231, and A549 cell lines using MTT and LDH (lactate dehydrogenase) assays. Further, morphological changes were analyzed by flow cytometry, mitochondrial membrane potential, AO-EtBr dual staining, and comet assay. Molecular docking and simulation were performed using Glide and Desmond softwares, respectively, to validate the mechanism of action. RESULTS: The isolated compound was identified as racemolactone I (compound 1). Amongst the cell lines tested, considerable changes were observed in HeLa cells. Compound 1 (IC50 = 0.9 µg/mL) significantly decreased cell viability (82%) concomitantly with high LDH release (76%) at 15 µg/mL. Diverse morphological alterations along with significant increase (9.23%) in apoptotic cells and decrease in viable cells were observed. AO-EtBr dual staining also confirmed the presence of 20% apoptotic cells. A gradual decrease in mitochondrial membrane potential was observed. HeLa cells showed significantly increased comet tail length (48.4 µm), indicating broken DNA strands. In silico studies exhibited that compound 1 binds to the active site of Polo-like kinase-1 and forms a stable complex. CONCLUSIONS: Racemolactone I was identified as potential anticancer agent, which can further be confirmed by in vivo investigations.

Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types.

BACKGROUND: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types. Tumors inhibit antitumor response by modulating the immune checkpoint proteins programmed death ligand 1 (PD-L1) and its cognate receptor PD1. The expression of these genes has been implicated in evasion of immune response and resistance to targeted therapies. METHODS: Blood samples were collected from gastric (GC), colorectal (CRC), lung (NSCLC), breast (BC), prostate cancer (PC) patients, and a healthy control group. ctRNA was purified from fractionated plasma, and following reverse transcription, levels of PD-L1 expression were analyzed using qPCR. RESULTS: PD-L1 expression was detected in the plasma ctRNA of all cancer types at varying frequencies but no PD-L1 mRNA was detected in cancer-free individuals. The frequencies of PD-L1 expression were significantly different among the various cancer types but the median relative PD-L1 expression values were not significantly different. In 12 cases where plasma and tumor tissue were available from the same patients, there was a high degree of concordance between expression of PD-L1 protein in tumor tissues and PD-L1 gene expression in plasma, and both methods were equally predictive of response to nivolumab. CONCLUSIONS: PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. These results pave the way for further studies aimed at determining whether monitoring the levels of PD-L1 mRNA in blood can identify patients who are most likely to benefit from the conventional treatment.