Irfan Anjum

Interstitial cystitis (IC) is an adverse event associated with the use of cyclophosphamide (CYP), an alkylating anticancer agent, caused by oxidative stress and excessive production of proinflammatory cytokines. The bladder becomes overactive. This study aims to evaluate linalool’s ability to treat CYP-induced IC. To induce IC, a 150 mg/kg intraperitoneal (i.p.) dose of CYP was administered to female Sprague Dawley rats on days 1, 4, and 7. To assess the protective potential of linalool, macroscopic evaluation, nociception response, Evans blue dye test, and the role of antioxidant and inflammatory mediators were investigated. Linalool is an acyclic monoterpene tertiary alcohol. It makes up almost 70% of the terpenoids found in flower fragrances. In this study, oral linalool at doses of 25, 50, and 100 mg/kg significantly reduced inflammation (P < 0.05). Compared to the CYP-treated group, linalool markedly increased mRNA expression (P < 0.05) of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH), and interleukin-10 (IL-10) levels, while decreasing mRNA expression of inducible nitrous oxide synthase (iNOS), tissue growth factor-β1 (TGF-β1), and tissue necrosis factor-α (TNF-α). The anti-inflammatory and antioxidant properties of linalool were further confirmed by molecular docking with specific protein targets. Linalool reduced CYP-induced bladder overactivity by blocking muscarinic 3 (M₃) receptors, ATP-sensitive potassium channels, calcium channels, and the cyclooxygenase (COX) enzyme, without affecting beta-adrenergic receptors. Thus, by reducing oxidative stress, inflammation, and bladder smooth muscle hyperexcitability, our results demonstrate that linalool offers significant protection against CYP-induced IC. Therefore, in CYP-based chemotherapy regimens, linalool presents as a potential adjuvant drug.

This study evaluates the hepatoprotective effects of Carduus marianus in a paracetamol‐induced hepatotoxicity model using Wistar rats. Wistar rats were divided into six groups and treated with varying doses (100, 200, and 300 mg/kg) of C. marianus 12× aqueous solution after hepatotoxicity induction. Serum biomarkers for liver function (ALT and AST), lipid profiles, renal indicators, oxidative stress markers, and inflammatory mediators were measured. Phytochemical screening revealed alkaloids, glycosides, carbohydrates, saponins, phenols, and flavonoids, with oleic acid as the major component. Gas chromatography–mass spectrometry (GC–MS) identified oleic acid as the predominant constituent (62.96%). Treatment significantly improved liver biomarkers, lipid profiles, and renal function ( p < 0.001) across all doses, alongside notable reductions in oxidative stress markers and inflammatory mediators ( p < 0.001). These results highlight the potential of C. marianus as a promising therapeutic agent for managing liver health.

Interstitial cystitis is a fierce syndrome affecting the quality of life of thousands of individuals around the globe. It causes immense pain in the bladder and associated viscera along with inflammation-like lesions. The current medicinal and pharmacological research focuses on the protective and curative effects of phytochemicals in several ailments. Phytochemicals derived from many medicinal plants have shown potent outcomes in protection against various pathological conditions including interstitial cystitis. This review has summarized the insights of in vitro and in vivo studies regarding the effects of phytochemicals in fading the inflammation in bladder tissue and exhibiting a protective effect on the urothelium. Hemorrhagic cystitis is a common manifestation in patients undergoing chemotherapy with cyclophosphamide and related alkylating agents. Sodium 2-mercaptoethane sulfonate (Mesna) has traditionally been employed in clinical practice to counter cyclophosphamide-induced cystitis in humans. However, cyclophosphamide has been employed in developing animal models of interstitial cystitis in in vivo studies. Phytochemicals including quercetin, beta-caryophyllene, curcumol, boswellic acid, caftaric acid, some flavonoids and other secondary metabolites being a consequential component of numerous medicinal plants, have displayed a significant reduction in the levels of proinflammatory cytokines including TNF-α, NFĸB, IL-1β, NLRP3 inflammasome, IL-6, IL-2, matrix metalloproteinases etc. Uroprotective outcomes of these phytochemicals have been found to result in diminished oxidative stress and restoration of glutathione, superoxide dismutase, and related proteins in the inflamed bladder tissue. Many in vivo studies involving cyclophosphamide-induced interstitial cystitis have confirmed these findings. The coupling of phytotherapy with novel drug delivery systems such as nanoparticles, liposomes, nanotubes, quantum dots, etc. can help translate these beneficial effects of phytochemicals into clinical practice. Further investigations of these phytochemicals can provide intuition regarding the development of newer drug molecules having exclusive activity for attenuating interstitial cystitis.

Citronellol (CT) is a naturally occurring lipophilic monoterpenoid which has shown anticancer effects in numerous cancerous cell lines. This study was, therefore, designed to examine CT's potential as an anticancer agent against glioblastoma (GBM). Network pharmacology analysis was employed to identify potential anticancer targets of CT. A comprehensive data mining was carried out to assess CT and GBM‐associated target genes. Protein–protein interaction network was constructed to identify hub genes and later GO and KEGG enrichment analysis was performed to elucidate the possible mechanism. Human glioblastoma cell line “SF767” was used to confirm in silico findings. MTT, crystal violet, and trypan blue assays were performed to assess the cytotoxic effects of various concentrations of CT. Subsequently, ELISA and qPCR were performed to analyze the effects of CT on proapoptotic and inflammatory mediators. In silico findings indicated that CT differentially regulated proapoptotic and inflammatory pathways by activating caspase‐3 and 8 and inhibiting nuclear factor‐kappa B (NF‐κB), tumor necrosis factor‐α, Janus kinase 2 (JAK2). Molecular docking also demonstrated strong binding affinities of CT with the above‐mentioned mediators when compared to 5‐fluorouracil or temozolomide. In SF767 cell line, CT displayed dose‐dependent cytotoxic and antioxidant effects, and upregulation of annexin‐V, caspase‐3, and 8 along with downregulation of inflammatory modulators. In a nutshell, it can be concluded from these findings that CT possesses robust anticancer activity which is mediated via differential regulation of caspase‐3, JAK2, and NF‐κB pathways.

Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.

Diabetes, a global health concern, poses increasing mortality risks. The pathogenesis of diabetes involves multiple mechanisms, with oxidative stress being one of the key contributors. As synthetic drugs have various side effects, which can be minimized by using herbal plants. This study focuses on the In vitro antioxidant potential, α-amylase inhibition potential, identification of bioactive compounds, and hub genes in diabetes treatment mechanism by using C. tinctorius Extraction of C. tinctorious lead and flower was performed using different solvents (Distilled water, methanol, chloroform, and Dimethyl ether). After extraction different concentrations range from 25–200 mg/mL) was made and checked against activities. The antioxidant potential was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic contents (TPC), and total antioxidant capacity (TAC) assays, while antidiabetic activity was evaluated through α-amylase inhibition assay. Phytochemicals was identified by GC–MS analysis, followed by ADMET screening and network pharmacology analysis using Swiss Target Prediction, Gene Card, DesGeNet, DAVID, STRING, Cytoscape, and drug revitalization databases. Results revealed positive correlations with DPPH, TAC, and TPC. Methanol extract exhibited the highest inhibitory concentration. Screening of 46 compounds was performed by studying their pharmacokinetic properties which revealed 9 compounds effective against 204 diabetes targets. Moreover, their network analysis identified four hub genes, including AKT1, JUN, EGFR, and MMP9. These genes found highly associated with drugs like Colchicine and Serotobenine. Revitalization analysis also highlighted four genes (EGFR, PTGS2, AKT1, and MMP9) strongly correlated with FDA-approved drugs. The study suggests C. tinctorius methanol extract is a potential source for novel drugs. Graphical Abstract

Iron deficiency anemia is a global health concern, affecting around 2 billion people. Oral iron therapy often causes severe gastro‐intestinal issues. Eruca sativa, member of the Brassicaceae family, is valued in traditional medicine and renowned for its rich iron and vitamin C content. This study aims to evaluate the anti‐anemic properties of E. sativa extract in vivo and identify its compounds targeting anemia mechanisms using network pharmacology. Thirty‐two Sprague–Dawley rats (200 ± 250 g) were split into two distinct groups, iron‐deficient and iron‐sufficient. Three different doses (200, 400, and 800 mg/kg) of aqueous extract of E. sativa were checked against anemia by studying hematological, oxidative stress, and histopathological parameters. GC–MS analysis of E. sativa revealed its phytochemical profile, followed by ADME screening. Network pharmacology explored targets related to iron deficiency anemia, with oral bioavailability and drug likeness assessment for compounds. The administration of extracts significantly improved various blood parameters, including osmotic fragility, Hb, RBCs, MCV, PCV, and alkaline phosphatase; catalase activity; and histopathological parameters such as liver in both iron‐deficient and iron‐sufficient rats (p < .001). Seventy‐nine compounds were identified in E. sativa aqueous extract, with only six of them found to be bioavailable and drug‐like against multiple targets. Gene ontology and pathway analysis revealed their diverse molecular, biological, and cellular functions. One gene EGFR was found to have functional association with ID anemia, suggesting potential for using E. sativa extracts. The study concludes that E. sativa extract has potential for iron deficiency anemia treatment, offering hope for future pharmaceutical interventions.

6-Methoxyflavone (6-MOF) is a flavonoid that has been reported to be a GABA-A receptor agonist and reverses cisplatin-induced hyperalgesia and allodynia. Considering the varied neuropharmacological profile of 6-MOF, this study was intended to determine the pharmacological effects of 6-MOF on locomotion, anxiety, novel object recognition (NOR), depression, spatial memory, socialization behavior, nest-building behavior, and depression in various groups of mice. Selected groups of mice were injected with 25, 50, and 75 mg/kg 6-MOF. Using HPLC-UV, the frontal cortex, striatum, and hippocampus of the sacrificed mice were analyzed for the levels of vitamin C, dopamine, serotonin, noradrenaline, adenosine, and its metabolites. Statistical analysis showed significant results in socialization behavior and elevated plus maze with 75 mg/kg. In Y-maze, NOR 6-MOF showed significant results at all three doses, while in tail suspension test (TST), 50 and 75 mg/kg showed significant results; however, no statistical significance was observed in nest-building behavior; 50 and 75 mg/kg 6-MOF showed significant results in the Morris water maze. 6-MOF raised vitamin C levels in the frontal cortex and hippocampus. Serotonin, dopamine, and nor-adrenaline levels were raised in the hippocampus and striatum. It has also imparted region-specific neuroprotection by improving adenosine and its metabolite levels. In silico studies performed using PyRx have shown that the minimum binding energy of 6-MOF with antioxidant enzyme is −7.1 k/cal/mol. The binding energy showed that 6-MOF was successfully docked with an anti-oxidant enzyme. In conclusion, in silico and behavioral studies showed that 6-MOF can be a potential candidate for the treatment of cognitive decline, anxiety, and depression.