Current Pharmaceutical Biotechnology - Online First

Gold nanoparticles (GNPs) have garnered significant attention in the biomedicine field due to their exceptional electrical, mechanical, chemical, and optical characteristics. The interaction of these remarkable potentials with biological tissues carries a risk of toxicity. Quercetin (Qur) is a natural flavonoid and exhibits numerous pharmacological impacts, especially anti-inflammatory, anti-apoptotic, and antioxidant.

This investigation aimed to clarify the potential cardiotoxicity induced by different diameters of spherical GNPs as well as to evaluate the possible cardioprotective roles of Qur against the most toxic diameter of GNPs.

Rats were randomly grouped and treated with or without sphere GNPs (10, 20 and 50 nm) and Qur (200 mg/kg b.wt.). Heart and blood samples were collected and subjected to histological, immunohistochemical and biochemical investigations.

When compared to the groups treated with 20 and 50 nm, the 10 nm GNPs dramatically increased the levels of cardiac biomarkers, including Troponin I, Creatine kinase isoenzyme-MB (CK-MB), CK-Total, lactate dehydrogenase (LDH). Histopathologically, 10 nm GNPs exhibited severe cardiomyocytes degenerations, atrophy, disorganization of myocardial fibers, focal hemorrhage, congested blood vessels and interstitial inflammatory cells infiltrations. Immunohistochemically, 10 nm GNPs exhibited strongly positive expressions against anti-caspase-3 antibody confirming extensive apoptosis of cardiomyocytes. However, the majority of these pathological changes were significantly improved upon Qur treatment.

The size of GNPs is crucial to their toxicological impact on cardiac tissues where 10 nm GNPs can induce severe histological damage, potent cytotoxicity, and apoptosis rather than larger particles. Otherwise, pre-co-treatment with Qur revealed a significant cardioprotective effect against GNPs cardiotoxicity.

Urtica dioica (Urticaceae) has outstanding medicinal and pharmacological properties. This investigation was aimed to assess the chemical composition, the total polyphenol and flavonoid content, antioxidant, anti-proliferative, and anti-inflammatory effects of Urtica dioica essential oil (UDEO).

GC/MS analysis was performed to assess the chemical composition, standard antioxidative test, the DPPH assay, the reducing power assay, as well as the anti-proliferative capacities of UDEO against HeLa cell lines using the MTT test. In addition, the anti-inflammatory activities of UDEO were evaluated using paw thickness measurements in rats with carrageenan-induced paw edema and pathologic evaluation of inflammation in paw sections.

GC/MS analysis revealed benzene dicarboxylic acid (14.69%), β-linalool (9.79%), phytol (9.52%), menthol (6.65%), borneol (6.45%), 3-Eicosene (E) (6.10%), 1-8 cineole (5.60%) and camphor (5.36%) as the major components of UDEO.

In vitro results showed that UDEO contained 191 ± 2.04 mg GAE/g of polyphenols and 83.59 ± 4.7 mg CE/g of flavonoids. In addition, the UDEO showed a radical scavenging activity with IC50 = 0.14 ± 0.003 mg/mL and a ferric reducing antioxidant power (FRAP) (optical density = 0.556). A side from the UDEO's antioxidant properties, our findings revealed a reduction in ROS generation in the HeLa cell line. Furthermore, the anti-proliferative activity of UDEO is accompanied by a cytotoxicity effect (IC50 at 3.20 µg ml^-1).

Data from inflammation models revealed that UDEO has an anti-inflammatory effect. The pretreatment with UDEO or Indomethacin (Ind) reduced significantly the volume of edema induced by Carr, the level of C-reactive protein (CRP), the reactive thiobarbituric acid (TBARS), the conjugated dienes (CD), the carbonyl proteins (CP) and the advanced protein oxidation products (AOPP). Furthermore, it restored the hematology parameters such as white blood cells (WBC), lymphocytes (LYM), and platelets (PLT). In addition, it increased the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In UDEO-treated rats, the histopathological examinations of the paws revealed little infiltration of inflammatory cells.

The decrease in paw edema and human cell lines HeLa cytotoxicity showed that UDEO possesses anti-inflammatory and antioxidant properties, which could be attributed to the high amount of phenolic and flavonoid contents.

Inflammation serves as a protective response to combat cellular and tissue damage. There is currently a wide array of synthetic and traditional therapies available for the treatment of inflammatory diseases. However, it is necessary to create a drug delivery system based on nanotechnology that can improve the solubility, permeability, and bioavailability of current treatments. Mesoporous silica nanoparticles (MSNPs) are inorganic materials known for their organised porous interiors, high pore volumes, substantial surface area, exceptional selectivity, permeability, low refractive index, and customisable pore sizes.

This review offers concise insights into the progression of the pathophysiology of inflammation, as well as the inducers, mediators, and effectors that are involved in the inflammatory pathway. This study focuses on the growing significance of MSNPs in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing applications. This review also presents the latest information on the crucial role of MSNPs in delivering herbal medicines for the treatment of inflammation.

A comprehensive literature search was conducted for this aim, utilising the Google Scholar, PubMed, and ScienceDirect databases. A systematic review was undertaken utilising scholarly articles published in peer-reviewed journals from 2000 to 2024.

The inflammatory mediators involved in the pathophysiology of inflammation include platelet-activating factor, lipoxygenase, cyclooxygenase, Interferon-α, interleukin-6, interleukin-1β, matrix metalloproteinases, inducible nitric oxide synthase, nuclear factor-κB, prostaglandins, nitric oxide, and phospholipase A2. MSNPs have the potential to be used in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing. The investigation of the MSNPs of plant-based compounds such as berberine, tetrahydrocannabinol, curcumin, and resveratrol has shown successful results in recent years for the purpose of managing inflammation.

This review demonstrates that MSNPs have a strong potential to play a positive role in delivering synthetic and plant-based therapies for the treatment of inflammatory illnesses.

This study aimed to explore the effects of Jiangu Recipe (JGR) on chondrocyte responses under tert-Butyl hydroperoxide (TBHP)-induced oxidative stress, specifically focusing on apoptosis and extracellular matrix (ECM) degradation.

Chondrocytes were treated with varying JGR concentrations, and cell viability was assessed. The impact of JGR on TBHP-induced apoptosis and protein expression levels of apoptosis-related molecules (Bcl-2, Bax, and cleaved caspase-3) and ECM components (Collagen II, Aggrecan, MMP-13) was evaluated.

JGR exhibited protective effects against oxidative stress in chondrocytes. Moreover, it maintained cell viability under tert-butyl hydroperoxide (TBHP) induction, suppressing apoptosis (Bax, cleaved caspase-3) and enhancing anti-apoptotic Bcl-2. JGR also attenuated extracellular matrix (ECM) degradation, promoting Collagen II and Aggrecan while reducing MMP-13 expression. Investigating endoplasmic reticulum (ER) stress, it was found that JGR downregulated TBHP-induced GRP78, CHOP, ATF4, p-PERK, and p-eIF2α, thus indicating ER stress modulation. SIRT1 played a key role, as JGR upregulated SIRT1, mitigating TBHP-induced downregulation. SIRT1 knockdown reversed JGR's protective effects, highlighting its crucial role in JGR-mediated responses.

Our findings suggest that JGR mitigated TBHP-induced chondrocyte apoptosis and ECM degradation, highlighting its potential therapeutic application in osteoarthritis. Mechanistically, our study highlights that SIRT1 plays a crucial role in mediating the protective effects of JGR against ER stress-induced chondrocyte apoptosis and ECM degradation, providing a foundation for further clinical exploration in managing osteoarthritic conditions.

This study is the first report on the sequence of the transcriptome of Drimia indica, a non-model plant with medicinal properties found in a forest tribal belt, using the Illumina NovaSeq platform. The primary objectives of this study were to elucidate the gene expression profiles in different tissues, identify key regulatory genes and pathways involved in secondary metabolite biosynthesis, and explore the plant's potential pharmacological properties.

The study generated 670087 unigenes from both leaves and roots and identified putative homologs of annotated sequences against UniProt/Swiss-Prot and KEGG databases. The functional annotation of the identified unigenes revealed the secondary metabolite biosynthetic process as the most prominent pathway, with gene enrichment analysis predominantly accounting for secondary metabolite pathways, such as terpenoid, steroid, flavonoid, alkaloid, selenocompound, and cortisol synthesis. The study also identified regulatory genes NAC, Bhlh, WRKY, and C2H2 on the transcriptome dataset.

The functionally annotated unigenes suggested phytocompounds in Drimia indica to have multi-potent properties, such as anti-cancer, anti-inflammatory, and anti-diabetic activities, which has been further validated by GC-MS-based metabolite profiling. Notably, we have identified two novel molecules, di-azo progesterone and 4H-pyran-4-one 2,3-dihydro-3,5-dihydroxy-6-methyl, with potential BCL2 inhibitory anticancer properties, supported by stable binding interactions observed in molecular docking and dynamics simulations. Additionally, an abundance of mono-nucleotide SSR markers has been identified, useful for genetic diversity studies.

This study provides a foundational understanding of the molecular mechanisms in Drimia indica, highlighting its potential as a source for novel therapeutic agents and contributing valuable insights for future pharmacological and agricultural applications. However, further in vivo studies are warranted to confirm these findings and validate their pharmacological efficacy and therapeutic potential. The SSR markers identified also offer valuable tools for molecular genetics, plant breeding, and sustainable drug development.