Current Pharmaceutical Biotechnology - Online First

Drug and chemical nephrotoxicity is a common cause of kidney disorders. This systematic review aimed to evaluate the recent progress in applying nano-curcumins (nano-CURs) to prevent and mitigate drug and chemical-induced nephrotoxicity, highlighting their underlying protective mechanisms and therapeutic potential.

A comprehensive search of experimental and clinical studies was conducted in various databases, including Web of Science, PubMed/MEDLINE, Scopus, Embase, and Cochrane Library. The studies were analyzed for improvements in bioavailability, mechanisms of action, and outcomes in reducing kidney damage. After extracting the data and entering it into an Excel sheet, the essential information and the related knowledge on consequences and mechanisms were collected. The collected information was discussed and analyzed.

The antioxidant property of nano-CURs in dealing with nephrotoxicity is one of their most critical nephroprotective properties. They also exhibit potent anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects. Moreover, nano-CURs improve mitochondrial function, modulate kidney biochemical markers, modulate electrolyte imbalance, reduce endoplasmic reticulum (ER) stress, and improve kidney histopathological changes and autophagy, offering protection against nephrotoxicity induced by various drugs and chemicals. Nano-CURs significantly improve histopathological changes. Animal models have demonstrated reduced oxidative stress, inflammation, and apoptosis, causing improved renal function and histological outcomes.

Nano-CURs have shown promising nephroprotective effects in experimental studies. However, these results have not been significant in clinical trial studies. Future research should focus on clinical trials and optimizing formulations for broader therapeutic applications.

Alzheimer's disease poses a major challenge as a widespread and fatal neurodegenerative disorder, primarily affecting the elderly population worldwide.

This study aimed to assess the potential protective and therapeutic effects of virgin olive oil and tiger nut essential oil on Alzheimer's dementia in male rats while also analyzing serum biomarker gene expression profiles in both Alzheimer's and control groups.

Rats were fed basal diets supplemented with 5% virgin olive oil or tiger nut essential oil, along with high-fat meals containing trans fats, butter (25%), margarine (25%), and hydrogenated shorten oils (25%) to evaluate lipid profiles and serum biomarkers. Gene expression analysis revealed a significant upregulation of acetylcholinesterase, P53, BCL2, Mouse ICAM-1, PSEN, and BACE genes in the Alzheimer's disease group compared to controls. Real-time PCR analysis also identified inflammatory biomarkers and Alzheimer's disease-associated risk factors in high-fat diet-treated, virgin olive oil-treated, and control samples.

The study found significant correlations between serum biomarker levels, lipid profiles, and dietary treatments. The activities of acetylcholinesterase, glutathione, catalase, and superoxide dismutase differed notably between virgin olive oil and tiger nut essential oil treatments. High-fat dietary treatments resulted in substantial increases in serum lipid profiles due to trans-fat intake compared to the control group. Overall, both virgin olive oil and tiger nut essential oil demonstrated cognitive enhancement and potential therapeutic effects against Alzheimer's disease symptoms induced by trans-fat feeding, including inhibition of acetylcholines-terase activity, reduction of amyloid-beta accumulation, and mitigation of inflammation.

The study suggests that serum biomarker gene expression profiles could serve as valuable indicators for differentiating between Alzheimer’s disease, virgin olive oil, and dietary treatments. Both virgin olive oil and tiger nut essential oil demonstrated protective effects, enhancing cognitive function and offering therapeutic potential against AD symptoms. These effects were achieved through the reduction of inflammation, the inhibition of AChE activity, and the reduction of amyloid-beta accumulation.

Given the high mortality associated with Cirrhotic Portal Hypertension (CPH) worldwide, this study investigates the mechanism by which baicalin (BA), known for its beneficial effects on cirrhosis, alleviates CPH.

The CPH model was established in Sprague-Dawley (SD) rats, followed by 4-week oral administration of 30 and 60 mg/kg/day BA. SD rats were randomly assigned to four groups (n=6/group): Con, Model, BA-30, and BA-60. Portal vein smooth muscle cells (PVSMCs, extracted from SD rats, n=6) were incubated with 5, 10 and 20 μmol/L BA. The levels of liver function indicators and von Willebrand factor (vWF) were determined by biochemical and immunohistochemical analyses, respectively. The portal pressure (PP) was examined. The liver fibrosis was detected by Sirius red staining. The levels of fibrosis-, angiogenesis- and proliferation-related indicators, zinc fingers and homeoboxes 2 (ZHX2), and matrix metallopeptidase 14 (MMP14) were quantified by Western blot. The levels of and interaction between ZHX2 and MMP14 were separately measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The proliferation and migration of PVSMCs were assessed by EdU staining and scratch test, respectively.

BA up-regulated ZHX2 and down-regulated MMP14 (P<0.001). BA concentration-dependently suppressed liver fibrosis, PP, and angiogenesis in the liver tissue, as well as PVSMC proliferation and migration, while enhancing liver function (P<0.05). Further, according to the GRNdb database and luciferase reporter assay, ZHX2 is bound with the promoter of MMP14. ZHX2 could suppress the MMP14 level (P<0.001). ZHX2 silencing reversed the effects of BA treatment on the proliferation and migration of PVSMCs, whereas MMP14 silencing could further offset the role of ZHX2 silencing in the BA-treated PVSMCs (P<0.05).

BA up-regulates ZHX2 to reduce the level of MMP14 and alleviate CPH. Understanding the mechanisms of BA in CPH may provide a foundation for novel interventions to attenuate CPH.

Selenium is an important trace element that plays crucial roles in metabolism, immune function, and antioxidant defense. As an antioxidant, selenium helps to alleviate postpartum uterine inflammation and promotes uterine recovery. However, the exact mechanism underlying the role of selenium in postpartum uterine recovery is not fully understood.

This study aimed to identify the underlying mechanism and examine how selenium enhances postpartum uterine healing.

Female ICR mice aged 8 weeks were classified into five groups: control, postpartum model, low-dose selenium (100 nm), medium-dose selenium (200 nm), and high-dose selenium (400 nm). Endometrial morphology was evaluated by hematoxylin and eosin (H&E) staining. Oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and malondialdehyde (MDA), and inflammatory factors, including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), were measured using commercially available kits. GPX1, GPX4, and nuclear factor erythroid 2-related factor 2 (NRF2) expression were determined using real-time PCR and WB.

We found damage and bleeding points in the endometrium and destruction of the ultrastructure of endometrial cells in the postpartum model group; however, mice treated with a high dose (400 nm) of selenium showed alleviated levels of pathological alteration in the endometrium. In addition, the levels of MDA in the postpartum mice group increased, while the SOD, CAT, and GPX levels decreased; however, changes in these oxidative stress markers were reversed after selenium treatment. For inflammatory factors, high levels of TNF-α and IL-1β were observed in postpartum mice, whereas they were decreased in selenium-treated groups. GPX1, GPX4, and NRF2 expression were reduced in postpartum model mice, but upregulated in selenium-treated mice.

Selenium supplementation ameliorated postpartum uterine oxidative stress and inflammation and promoted uterine recovery via the GPX1/GPX4/NRF2 pathway in mice.

Metabolic syndrome encompasses conditions such as diabetes mellitus (DM), which has become increasingly prevalent. Chemically synthesized medications are commonly used to mitigate the effects of DM and its complications; however, these often result in undesirable side effects, including weight gain, digestive issues, and heart failure.

This review highlights the therapeutic potential of bioactive compounds and anti-diabetic plants that possess proven anti-diabetic properties. Focusing on phytomedicines also explores their possible mechanisms of action and positions this work relative to current reviews in the field.

A comprehensive literature analysis was conducted, emphasizing the therapeutic potential of bioactive compounds in anti-diabetic plants. Databases such as PubMed, Scopus, and Google Scholar were thoroughly searched to identify studies investigating the anti-diabetic properties and mechanisms of action of plant-derived bioactive compounds. Inclusion criteria focused on studies evaluating the pharmacological effects of herbal medicines, plant extracts, and isolated bioactive compounds on diabetes management.

Therapeutic plants, as sources of anti-diabetic compounds, offer significant advantages. They are affordable, exhibit minimal or no adverse effects, and do not necessitate strict dietary restrictions or intense exercise regimens. The integrated insights underscore the potential of phytomedicines to address limitations in current diabetes management strategies.

The unique focus on phytomedicines positions this review as a valuable resource for researchers and clinicians. Detailing mechanisms and evidence supporting the efficacy of these compounds, guides the development of innovative strategies for identifying and utilizing bioactive compounds in effective diabetes management.

Diet-related chronic diseases, such as cardiovascular diseases, obesity, diabetes, autoimmune diseases and cancer, are largely preventable with a healthy diet and lifestyle. Therefore, searching for dietary supplements rich in antioxidant and anti-inflammatory phytochemicals for the prevention and/or management of diet-related chronic diseases is an important strategy for controlling these diseases to reduce healthcare costs and sustain development.

The aim of the current research was to prepare dietary supplements from avocado fruit pulp [AFPDS] and evaluate their potential against various diet-related chronic diseases through in-vitro , in-vivo , and molecular docking studies.

Volatile compounds of avocado pulp were evaluated, and the total phenolic compounds, fatty acids, and phytosterols profiles of the AFPDS were determined.

D-limonene, methyl propanoate, isobutyl propanoate and pentanol were the principal volatile compounds in the avocado pulp. Total phenolic and flavonoids were present in the AFPDS by 9.65 mg GAE/g and 6.87 mg CE/g, respectively. Chlorogenic acid and cinnamic acid were the major and minor identified phenolic compounds in AFPDS, respectively. Oleic acid [75.06%] and β-Sitosterol [2.19%] were the highest fatty acid and phytosterol present in AFPDS, respectively. AFPDS recorded anti-inflammatory activity against nitric oxide [NO] production in RAW264.7 macrophages by 98.2µg/ml [IC50] and 164.8µg/ml [IC90]. AFPDS showed significant anti-inflammatory activity against carrageenan-induced rat paw edema. AFPDS showed antioxidant activity against DPPH and ABTS by 8.67 mg TE/g and 6.14 mg TE/g. AFPDS possessed anti-cancer activity against MCF7 and HPG2 at10.8µg/ml and 40.5µg/ml, respectively. AFPDS exhibited anti-diabetic activity as an inhibitor of α-amylase and α-glucosidase by26.35±0.77μg/ml and 0.55±0.163mg/ml, respectively. Molecular docking studies revealed high binding affinity of different active compounds present in AFPDS with cyclooxygenase-2, glutathione peroxidase, α-glucosidase and B-cell lymphoma-extra-large proteins.

AFPDS can be considered a new agent for the prevention and treatment of diet-related chronic diseases, such as diabetes and cancer, due to its anti-inflammatory, antioxidant, anticancer, and anti-diabetic activities, as demonstrated through in-vivo , in-vitro , and molecular docking studies.

Atherosclerosis (AS) is caused by the endothelium injury associated with oxidative stress. Previous studies have shown that the Phlegm-Eliminating and Stasis-Transforming Decoction (Huayu Qutan Decoction, HYQTD) has mitochondrial protective function. The objective of this research was to explore how HYQTD drug-containing serum (HYQTD-DS) could potentially protect mitochondrial energy production in endothelial cells (ECs) from injury caused by hydrogen peroxide (H2O2)-induced oxidative damage in AS through SIRT1/PGC-1α/ Nrf2 pathway.

After preparation of containing serum, the cells were divided into various categories, such as control group, H2O2 group (an oxidative damage model), HYQTD group, Selisistat (EX527, a SIRT1 inhibitor) combined with H2O2 group, and EX527 combined with HYQTD group. The evaluation of oxidative stress involved measuring reactive oxygen species (ROS) and malondialdehyde (MDA) generation, as well as Superoxide Dismutase (SOD) activity. Mitochondrial function and ultrastructure were measured by Transmission electron microscopy (TEM), mitochondrial membrane potential (MMP), rate of oxygen consumption (OCR), respiratory chain complex activities, and ATP production. The key proteins and gene levels in the SIRT1/PGC-1α/Nrf2 pathway was quantified by quantitative real-time PCR (RT-PCR) and Western blotting analysis.

We found oxidative stress, mitochondrial damage, and mitochondrial energy disorder in H2O2-induced ECs. However it indicated a marked reversal after pretreated with HYQTD-DS. Mechanistically, EX527 induced increased oxidative stress, worse mitochondrial dysfunction, and less ATP synthesis.

We demonstrated that HYQTD-DS attenuated oxidative stress, improved mitochondrial function, and up-regulated mitochondrial ATP synthesis by activating SIRT1/PGC-1α/Nrf2 pathway-induced mitochondrial biogenesis and its downstream NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDV2).

This study evaluated the renoprotective effects of p-Coumaric acid nanoparticles (PCNPs) in nephropathic rats.

Six groups of male Albino Wistar rats were randomly assigned. Group 1 was the control, while Group 2 received 45 mg/kg of streptozotocin (STZ) to induce diabetic nephropathy. Groups 3, 4, and 5 received STZ (45 mg/kg) along with PCNPs at doses of 20, 40, and 80 mg/kg, respectively. Group 6 received 80 mg/kg of PCNPs without STZ. Body weight, blood glucose, insulin, hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) levels were measured. Blood urea, serum creatinine, kidney antioxidant enzymes, and lipid peroxidation levels were also analyzed. Histological and immunohistochemical studies of kidney tissues were performed.

PCNPs (80 mg/kg) significantly reduced serum glucose, creatinine, and urea levels while increasing insulin levels and antioxidant activity in the kidneys. Histological analysis revealed that nephropathic rats exhibited cellular damage, including shrinkage of Bowman’s capsule and lesions in the kidneys, along with degeneration in the Islets of Langerhans in the pancreas. PCNPs treatment restored these morphological alterations in the pancreas, liver, and kidneys to near-normal. Furthermore, nephropathic rats had elevated IL-6 and TNF-α expression in the renal tubules and glomeruli, which was reduced following PCNPs treatment.

The findings suggest that PCNPs exhibit antihyperglycemic, antioxidant, anti-glycation, and renoprotective effects in STZ-induced diabetic nephropathy.

Prostate cancer is an androgen-dependent malignancy, and the use of androgen deprivation therapies frequently results in treatment resistance, relapse, and the development of aggressive castration-resistant tumors. Patchouli alcohol, a tricyclic sesquiterpene derived from Pogostemon cablin of the Labiatae family, has demonstrated potential in modulating inflammatory responses and tumor progression. This study aimed to investigate the mechanisms through which patchouli alcohol influences inflammatory pathways associated with prostate cancer using bioinformatics and experimental validation.

Differentially Expressed Genes (DEGs) were identified from the GSE46602 dataset, containing 36 prostate cancer and 14 normal prostate biopsy samples, using the GEO2R tool (adjusted P < 0.05). Functional annotation was performed using GO and KEGG databases, while PPI networks were constructed via STRING and Cytoscape. Key hub genes were identified. To validate the bioinformatics findings, qPCR and Western blotting were employed to confirm the differential expression of selected hub genes in DU145 prostate cancer cells treated with patchouli oil.

Bioinformatic analysis revealed 71 DEGs, including 35 upregulated and 36 downregulated genes. Thirteen hub genes were identified (DCK, APRT, ADK, KCNK9, ADSL, PKM, KCNK3, S100A10, ENTPD2, PKLR, ARHGEF38, TPK1, and AK5), which were enriched in pathways, such as MAPK, PI3K-Akt, Ras, and Rap1. Experimental validation confirmed the upregulation of DCK, APRT, KCNK9, ADSL, PKM, S100A10, ENTPD2, PKLR, ARHGEF38, and AK5, and the downregulation of ADK, KCNK3, and TPK1 at both the mRNA and protein levels.

Patchouli alcohol appears to influence multiple hub genes associated with prostate cancer progression through its modulation of key cellular signaling and metabolic pathways. These findings support its potential role as a therapeutic agent for prostate cancer.

This study aimed to comprehensively investigate the molecular landscape of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.

GSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB, cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR, and cell proliferation assay were employed in this study.

Analysis of the GSE79973 dataset identified 300 differentially expressed genes (DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using protein-protein interaction network analysis. Subsequent validation across The Cancer Genome Atlas (TCGA) datasets confirmed their up-regulation in GC tissues compared to normal controls. Promoter methylation analysis revealed decreased methylation levels of these hubs in GC tissues, suggesting their potential role in tumorigenesis. Mutational analysis using cBioPortal showcased frequent mutations in these genes, particularly FN1, further highlighting their significance in GC pathogenesis. Survival analysis indicated their correlation with reduced overall survival rates among GC patients, supported by the development of a robust prognostic model. Prediction of hub-associated miRNAs and gene enrichment analysis provided insights into their regulatory mechanisms and downstream pathways, implicating their involvement in extracellular matrix remodeling and cell migration. Drug sensitivity analysis revealed correlations between hub gene expression and drug response, while RT-qPCR validation confirmed their up-regulation in clinical GC samples. Finally, functional assays demonstrated the impact of FN1 knockdown on cellular proliferation, colony formation, and wound healing capacities.

Overall, this study elucidates the crucial role of COL1A1, COL1A2, CHN1, and FN1 in GC pathogenesis and underscores their potential as diagnostic markers and therapeutic targets.

Iron oxide nanozyme was synthesized from the fruit peel extract of pomegranate, which served as a reducing agent during the green synthesis. The scavenging of reactive oxygen species is often accompanied by immunomodulation following antiproliferative effects due to the crosstalk between the proteins involved in the inter-related signaling pathways.

In the current study, the green synthesized nanozyme was studied for its ability to induce apoptosis in breast cancer cell lines. The free radical scavenging effect of the nanozyme was reflected as an extension of its intrinsic endogenous enzyme-mimicking property.

The cell cycle analysis revealed that the cell death induced by nanozyme mainly affected the G0/G1 phase. The expression of RelA/p65 and the inflammatory mediators affected by the nanozyme established the role of the Fe3O4 nanozyme in immunomodulation along with its antiproliferative activity.

This is the first report on the antiproliferative and immunomodulatory activities expressed by the biomimetic iron oxide nanozyme.

The increasing prevalence of antibiotic-resistant bacteria necessitates exploring nanotechnology as a potential solution for microbial elimination.

This study aimed to investigate the antimicrobial and antioxidant effects of silver nanoparticles synthesized using aqueous extract from the Ephedra gerardiana (E. gerardiana) plant (EG@AgNPs).

Optimal synthesis conditions, including silver nitrate concentration, time, and temperature, were determined. Characterization of EG@AgNPs was conducted, which was followed by antimicrobial assessment against eight bacterial strains and one fungal strain. Additionally, the antioxidant properties of EG@AgNPs were evaluated using the DPPH method.

XRD analysis confirmed EG@AgNPs synthesis. DLS analysis revealed a hydrodynamic diameter of 22 nm. FT-IR analysis confirmed the presence of functional groups from the E. gerardiana plant extract in EG@AgNPs. FESEM and TEM images depicted spherical nanoparticles ranging in size from 10 to 20 nm. Antimicrobial investigations using the broth microdilution method demonstrated that E. gerardiana plant extract at 7.5 mg/ml inhibited only Streptococcus mutans and Candida albicans growth, with no antimicrobial effects observed at lower concentrations. However, EG@AgNPs significantly enhanced the antimicrobial properties of the E. gerardiana plant extract. Notably, these nanoparticles exhibited the most significant effect on E. coli and the least on S. salivaris, with MIC value of 125 and 2000 µg/ml, respectively. Furthermore, they inhibited C. albicans growth at a concentration of 62.5 μg/ml. An assessment of the antioxidant properties of EG@AgNPs indicated a significant increase in antioxidant activity.

The E. gerardiana plant extract has emerged as a promising option for silver nanoparticle synthesis. These nanoparticles have been found to exhibit potent antimicrobial properties against Gram-positive and Gram-negative bacterial species, as well as C. albicans. Additionally, they have demonstrated antioxidant properties.