Background: Doxorubicin (DOX) is a very powerful chemotherapy drug. However, its severe toxicity and potential for resistance development limit its application. Withania somnifera L. Dunal (WIT) has therapeutic capacities, including anti-inflammatory, antioxidant, and anticancer activities. This study investigates the preventative benefits of a standardized WIT extract against DOX-induced renal damage in vivo. We also investigate the synergistic effects of combining WIT and DOX to improve therapeutic efficacy in breast cancer cells (MCF7-ADR). Methods: This study employed an animal model where rats were administered 300 mg/kg/day of WIT orally for a duration of 14 days. Rats received DOX injections at a dose of 5 mg/kg, for a total of 15 mg, on the 6th, 8th, and 10th days. Results: Present results revealed that WIT reduced DOX-induced increase levels of blood urea and creatinine and the activity of kidney injury molecule-1. WIT also reduced renal tissue damage, oxidative stress, and levels of pro-inflammatory markers. WIT alleviated the effects of DOX on nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and sirtuin 1 in the renal tissues. WIT modulated nuclear factor-κB activity and decreased apoptotic indicators. Furthermore, WIT improves DOX’s capacity to kill drug-resistant MCF7-ADR cells by arresting the cell cycle and promoting apoptosis. Chemical analysis of WIT root extract revealed 34 distinct compounds, including alkaloids, withanolides, flavanones, and fatty acids. Conclusions: These constituents synergistically contribute to WIT’s antioxidant, anti-inflammatory, and anti-apoptotic properties. In addition, they confirm its ability to reduce systemic toxicity while improving treatment efficacy.

Sugiol, a natural compound with anticancer properties, has shown promise in various cancer types, but its potential in preventing gastric cancer remains uncertain. In this study, we aimed to examine the inhibitory effect of sugiol on human gastric cancer cell proliferation. Our findings demonstrate that sugiol effectively suppresses the proliferation of SNU-5 human gastric cancer cells, leading to apoptotic cell death. We assessed the chemo-preventive potential of sugiol via an MTT assay and confirmed the induction of oxidative stress using the H2DCFDA fluorescent dye. Treatment with sugiol at concentrations higher than 25 µM for 24 h resulted in an increase in intracellular levels of reactive oxygen species (ROS). This elevation of ROS levels inhibited cell-cycle progression and induced cell-cycle arrest at the G1 phase. Furthermore, our study revealed that sugiol reduces the viability and proliferation of SNU-5 cells in a dose-dependent manner. Importantly, ADME and toxicity analyses revealed that sugiol was effective and nontoxic at low doses. In parallel, we utilized the Swiss target prediction tool to identify potential targets for sugiol. Enzymes and nuclear receptors were identified as major targets. To gain insights into the molecular interactions, we performed structure-based molecular docking studies, focusing on the interaction between sugiol and STAT3. The docking results revealed strong binding interactions within the active site pocket of STAT3, with a binding affinity of −12.169 kcal/mole. Sugiol’s -OH group, carbonyl group, and phenyl ring demonstrated hydrogen-bonding interactions with specific residues of the target protein, along with Vander Waals and hydrophobic interactions. These data suggest that sugiol has the potential to inhibit the phosphorylation of STAT3, which is known to play a crucial role in promoting the growth and survival of cancer cells. Targeting the dysregulated STAT3 signaling pathway holds promise as a therapeutic strategy for various human tumors. In combination with interventions that regulate cell cycle progression and mitigate the DNA damage response, the efficacy of these therapeutic approaches can be further enhanced. The findings from our study highlight the antiproliferative and apoptotic potential of sugiol against human gastric cancer cells (SNU-5). Moreover, the result underpins that sugiol’s interactions with STAT3 may contribute to its inhibitory effects on cancer cell growth and proliferation. Further research is warranted to explore the full potential of sugiol as a therapeutic agent and its potential application in treating gastric cancer and other malignancies characterized by dysregulated STAT3 activity.

The coast of the Red Sea in Jeddah City is home to a unique microbial community that has adapted to extreme environmental conditions. Therefore, it is essential to characterize the microbial community in this unique microbiome to predict how environmental changes will affect it. The aim of this study was to conduct metagenomic sequencing of 16S rRNA and ITS rRNA genes for the taxonomic classification of the microbial community in soil samples associated with the halophytic plants Tamarix aphylla and Halopeplis perfoliata. Fifteen soil samples were collected in triplicate to enhance robustness and minimize sampling bias. Firstly, to identify novel microbial candidates, the gDNAs were isolated from the saline soil samples surrounding each plant, and then bacterial 16S (V3–V4) and fungal ITS1 regions were sequenced utilizing a high-throughput approach (next-generation sequencing; NGS) on an Illumina MiSeq platform. Quality assessment of the constructed amplicon libraries was conducted using Agilent Bioanalyzer and fluorometric quantification methods. The raw data were processed and analyzed using the Pipeline (Nova Lifetech, Singapore) for bioinformatics analysis. Based on the total number of readings, it was determined that the phylum Actinobacteriota was the most prevalent in the soil samples examined, followed by the phylum Proteobacteria. Based on ITS rRNA gene analysis, the alpha and beta fungal diversity in the studied soil samples revealed that the fungal population is structured into various groups according to the crust (c) and/or rhizosphere (r) plant parts. Fungal communities in the soil samples indicated that Ascomycota and Basidiomycota were the two most abundant phyla based on the total amount of sequence reads. Secondly, heat-map analysis of the diversity indices showed that the bacterial alpha diversity, as measured by Shannon, Simpson, and InvSimpson, was associated with soil crust (Hc and Tc enclosing H. perfoliata and T. aphylla, respectively) and that the soil rhizosphere (Hr and Tr) was strongly correlated with bacterial beta diversity. Finally, fungal-associated Tc and Hc samples clustered together, according to observations made using the Fisher and Chao1 methods, and Hr and Tr samples clustered together according to Shannon, Simpson, and InvSimpson analyses. As a result of the soil investigation, potential agents that have been identified could lead to innovative agricultural, medical, and industrial applications.

Although praziquantel (PZQ) is the main antischistosomal drug currently in use, concerns remain regarding incomplete reversal of schistosomiasis-induced pathology and the emergence of drug resistance. This study evaluates the combined effect of PZQ with safranal, a bioactive saffron constituent, on Schistosoma mansoni-induced pathology in mice. Male CD1 Swiss albino mice were exposed to 60 S. mansoni cercariae and, at week 9 post-infection, were treated with PZQ (500 mg/kg orally for two consecutive days), safranal (50 mg/kg/day), or both, for three weeks. The animals were sacrificed at week 11 post-infection. Worm and egg burdens, liver histopathology, fibrotic markers, oxidative stress, and inflammatory cytokines were assessed. Combined PZQ + safranal therapy significantly reduced adult worm counts and hepatic and intestinal egg loads compared to PZQ alone. All treatments decreased liver index (hepatomegaly), with the combination treatment providing the best intervention. Histological analyses revealed significantly reduced granuloma size and hepatic necrosis post-treatment, particularly in the combination group. The levels of proinflammatory cytokines (TNF-α, IL-1β) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10) were significantly lowered in treated mice, most notably with the combination treatment. Oxidative stress was also markedly attenuated, and infected mice exhibited elevated malondialdehyde and depleted antioxidant enzymes (SOD, CAT, GSH). Interestingly, PZQ and/or safranal restored antioxidant status and reduced lipid peroxidation, with the combination being most effective. Furthermore, collagen deposition and expression of hepatic fibrotic markers α-smooth muscle actin (α-SMA), TGF-β1, and matrix metalloproteinase-9 were most effectively suppressed by combined therapy. To conclude, safranal enhances PZQ’s antischistosomal efficacy and confers additive protection against Schistosoma-induced liver fibrosis.