Gideon F. B. Solre

Hyperlipidemia remains a leading modifiable risk factor for cardiovascular morbidity and mortality. Statins are considered the cornerstone of treatment; however, their adverse effects and limited efficacy in certain patient populations necessitate exploration of novel therapeutic avenues. Epiafzelechin (EZN), a flavanol with established antioxidant and anti‐inflammatory properties, was investigated for its potential role in lipid metabolism using an integrative approach combining network pharmacology, molecular docking, and in vivo validation. Putative EZN targets were predicted through SuperPred, Way2Drug, and PharmMapper, and intersected with hyperlipidemia‐related genes from GeneCards, DisGeNET, and CTD. Overlapping genes were subjected to protein–protein interaction (PPI) mapping, hub gene identification, and pathway enrichment analysis. Molecular docking was conducted to assess the binding affinity of EZN to lipid‐regulating proteins. Therapeutic efficacy of EZN was also evaluated in a TWR‐1339‐induced hyperlipidemic rat model using biochemical assays and real‐time PCR for gene expression profiling. A total of 105 genes were identified, involved in lipid transport, inflammatory signaling, and metabolic regulation. Functional enrichment and PPI analysis highlighted HMGCR, PCSK9, PPAR‐ α , and LDLR as key targets. Docking studies revealed that EZN has strong binding affinities with these targets, supporting the structural feasibility of these interactions. In vivo, EZN treatment significantly reduced total cholesterol, triglycerides, LDL, and VLDL levels, while increasing HDL. Compared with simvastatin, EZN exhibited superior lipid‐lowering effects with a more favorable liver enzyme profile. Gene expression and ELISA analyses indicated downregulation of HMGCR, PCSK9, and APOB, and upregulation of PPAR‐ α , LDLR, and SRB, highlighting its multi‐target modulation of lipid homeostasis. These findings indicate that EZN exerts broad regulatory effects on lipid metabolism through pleiotropic mechanisms and may represent a promising natural candidate for managing hyperlipidemia.

Hyperlipidemia is a major risk factor for cardiovascular disease, highlighting the need for safer and effective therapeutic options. This study evaluated the anti-hyperlipidemic potential of taxifolin (TXF) and its nanoemulsion formulation (TXF-NE) using integrated computational and experimental approaches. Network pharmacology identified 177 common targets between TXF and hyperlipidemia, with enrichment analyses linking these targets to lipid metabolism, cholesterol regulation, and inflammatory pathways. Protein-protein interaction analysis revealed key lipid-regulating genes, including HMGCR as a major hub target. Molecular docking predicted favorable interactions of TXF with several lipid metabolism related proteins, including HMGCR, LDLR, APOB, APOA1, and ACSM2A. The predicted interactions provide structural hypotheses regarding potential TXF protein associations. In-vivo , TXF significantly improved serum lipid profiles and liver function enzymes. Gene expression and protein analyses exhibited downregulation of HMGCR and APOB along with upregulation of LDLR, indicating suppression of cholesterol synthesis, reduced lipoprotein production, and enhanced LDL clearance. Notably, TXF-NE exhibited high drug content and better therapeutic efficacy relative to free TXF, as reflected by greater improvements in lipid parameters. Overall, these findings demonstrate that TXF alleviates hyperlipidemia through a multi-target mechanism, while nanoemulsion-based delivery enhances its therapeutic potential for managing hyperlipidemia and associated hepatic dysfunction.

This study explored the anticancer potential of p‐cymene against hepatocellular carcinoma (HCC) through computational and in vitro approaches. Bioinformatics analysis identified 635 potential targets of p‐cymene, with 216 overlapping HCC‐related proteins. Target interaction networks were constructed using STRING and Cytoscape, revealing key proteins involved in apoptosis, angiogenesis, and tumor progression. Molecular docking was performed using the molecular operating environment software, demonstrating strong binding affinities of p‐cymene with key overlapping HCC targets, including hypoxia‐inducible factor 1‐alpha (HIF1A), B‐cell lymphoma 2 (BCL2), cyclin‐dependent kinase 9 (CDK9), Janus kinase 2 (JAK2), vascular endothelial growth factor (VEGF), mitogen‐activated protein kinase 4 (MAPK4), tumor protein p53 (P53), signal transducer and activator of transcription 3 (STAT3), and caspase‐3 (CASP3). HepG2 cells were treated with increasing concentrations of p‐cymene (5–50 mM), and cytotoxicity was assessed using MTT, crystal violet, and trypan blue exclusion assays. Antioxidant activity was measured by evaluating superoxide dismutase (SOD) and glutathione (GSH) levels. Apoptotic markers, including CASP3, P53, VEGF, and BCL2, were quantified using ELISA. Results showed a dose‐dependent reduction in HepG2 cell viability, with significant cytotoxic effects at higher p‐cymene concentrations (30 and 50 mM). p‐Cymene reduced oxidative stress, evident from increased SOD and GSH levels, and triggered apoptosis, as indicated by increased CASP3 and P53 expression. Additionally, BCL2 and VEGF were downregulated, suggesting inhibition of cell survival and angiogenesis. These findings highlight p‐cymene's multi‐targeted anticancer effects in HCC cells, supporting its further evaluation in in vivo models and potential combination therapies for improved therapeutic outcomes.

Baccaurea ramiflora is a common edible nutritious plant that has been associated with a variety of medicinal attributes. This study investigated the anti‐inflammatory effects of the aqueous extract of B. ramiflora leaves (BrLAE) in a complete Freund's adjuvant (CFA) induced inflammatory model. BrLAE was prepared by the cold maceration process and screened for phytochemical and antioxidant analyses. Inflammation was induced by a single intra‐planter (i.pl.) injection of CFA (100 μL) in the hind paws of male Wistar rats. After 7 days of immunization, paw edema was measured weekly (Day 7–Day 35) by digital plethysmometer and vernier caliper. Animals were daily treated with either methotrexate (MTX) or BrLAE (300, 600, and 1000 mg/kg) from Day 7 to Day 35. At the end of the experimental period, blood and liver samples were collected for the analysis of hematological, biochemical parameters and gene expression, respectively. The findings revealed that BrLAE had significant antioxidant activity and a remarkably high amount of tannins, saponins, flavonoids, phenols along with a trace amount of alkaloids, steroids, and terpinoids. BrLAE significantly reduced paw edema levels and improved hematological (RBC, WBC, Hb, PLT, and ESR) and biochemical (ALT, AST, and CRP) parameters. Moreover, BrLAE prominently downregulated mRNA levels of pro‐inflammatory mediators, such as TNF‐α , IL‐1β , NF‐κB , COX‐2 , PTGDS , mPGES1 , and MMP1 . Molecular docking of the active constituent (Rosmarinic acid) with TNF‐α, NF‐κB, COX‐2, PTGDS, and mPGES1 also supported the experimental findings. These findings highlight that BrLAE possesses robust antioxidant and anti‐inflammatory properties which may be attributed to its inhibitory effects on prostaglandins and cytokines.

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.

This study evaluated the hepatoprotective potential of p-cymene (p-CYM) against two models of liver damage: ethanol (EtOH)-induced hepatocellular injury and diethylnitrosamine-carbon tetrachloride (DEN-CCl ₄ )-induced liver fibrosis (LF). HepG2 cells were treated with p-CYM or silymarin (SIL) before exposure to 10% EtOH in order to induce cellular injury. LF was induced in Sprague–Dawley rats using a single dose of DEN followed by increasing doses of CCl ₄ over 60 days. Rats were treated twice weekly with p-CYM or SIL from day 21 to day 60. Results showed that p-CYM effectively mitigated EtOH-induced cell death in HepG2 cells by enhancing the activity of superoxide dismutase and glutathione reductase. In vivo findings revealed that p-CYM attenuated DEN– CCl ₄ -induced liver damage by preventing weight loss, improving serum biomarkers (e.g., aspartate transaminase, alanine aminotransferase, alkaline phosphatase, and bilirubin), and reducing liver fibrotic changes. It also decreased the expression of pro-inflammatory and pro-fibrotic markers such as TNF-α, IL-1β, IL-6, TGF-β1, COL1A1 , and TIMP-1 . Molecular docking further supported the experimental findings, showing strong interactions between p-CYM and the target proteins. These results indicate that the hepatoprotective effects of p-CYM are likely due to its combined antioxidant, anti-inflammatory, and anti-fibrotic properties.

Ethnopharmacological relevance of Saussurea species for anti-cancer compounds instigated us to develop chemotherapeutic herbal tablets. This study was an ongoing part of our previous research based on the scientific evaluation of Saussurea heteromalla (S. heteromalla) for anti-cancer lead compounds. In the current study, S. heteromalla herbal tablets (500 /800 mg) were designed and evaluated for anti-cancer activity. Arctigenin was found as a bioactive lead molecule with anti-cancer potential for cervical cancer. The in vitro results on the HeLa cell line supported the ethnopharmacological relevance and traditional utilization of S. heteromalla and provided the scientific basis for the management of cervical cancer as proclaimed by traditional practitioners in China. LD50 of the crude extract was established trough oral acute toxicity profiling in mice, wherein the minimum lethal dose was noticed as higher than 1000 mg/kg body weight orally. Chromatographic fingerprint analysis ensured the identity and consistency of S. heteromalla in herbal tablets in terms of standardization of the herbal drug. About 99.15% of the drug (S. heteromalla crude extract) was recovered in herbal tablets (RSD: 0.45%). In vitro drug release profile was found to be more than 87% within 1 h, which was also correlated with different mathematical kinetic models of drug release (r(2) = 0.992), indicating that drug release from matrix tablets into the blood is constant throughout the delivery. The dosage form was found stable after an accelerated stability parameters study which may be used for anti-cervical cancer therapy in the future, if it qualifies successful preclinical investigation parameters.

In this work, polycrystalline BaFe_11.5-xAl_xCo_0.5O₁₉ (0≤x≤2) hexaferrite samples were synthesised by means of the sol–gel technique. Thereafter, the magnetic and structural properties are thoroughly examined. Cell refinement and XRD examination verified a magnetoplumbite hexaferrite arrangement with a space group of P63/mmc for each sample. The parameters ‘a’ and ‘c’ in the lattice fall in value from 5.885 Å to 5.875 Å and from 23.117 Å to 23.049 Å, respectively. Both the average crystallite size and the unit cell volume exhibit a declining trend as the doping level increases. For M-type hexaferrites, the optimal range of c/a values is determined to be 3.923–3.928. X-ray density (d_x) and bulk density (d_b) decline with rising doping contents until x=1.5 doping content, at which point they exhibit an increasing trend. The results showed that as the doping amount increased, the saturation and remanence magnetizations decreased. Coercivity and magnetocrystalline anisotropy are rising together. Both the anisotropy field (H_a) and the anisotropy parameter (B) exhibit a rising trend with doping content. Coercivity of 5.896 kOe, anisotropic applied field of 1.84 kOe, saturation magnetization of 42.68 emu g⁻¹, remanence magnetization of 24.414 (emu/g), and magnetic moment per formula unit-(m_B) of 11.19 μ _B are the best magnetic properties obtained for the BaFe₁₀Al_1.5Co_0.5O₁₉ sample.

Law is the core discipline of society as well as playing a vital role in any organization which is working and exists in the World. International law and trade are the backbones of global organizations. In this present discussion, secondary data was used. Data were obtained from secondary sources, especially from the law discipline research article, and from authentic and reliable sources. In the research article, the law oriented international organizations were the main targeted respondents. The importance of the law is because there are many motivations behind why countries and individuals decide to exchange and carry on with work globally instead of confining themselves in an undertaking to secure homegrown industry. Motivations to exchange incorporate the need to acquire normal assets, items, or administrations, in any case, inaccessible locally; the craving to get similar items more inexpensively than the expense of locally delivered merchandise; the longing to accomplish a monetary advantage by sending out homegrown regular assets, items or administrations which pay for the expense of imports; the longing to assist less beneficial countries with accomplishing advancement; and the need to keep up with military or political partnerships with exchanging countries. The present study gives an outline of international exchanges and business law and the various homegrown and global associations engaged with the guideline of worldwide exchange. It likewise suggests a synopsis of the modalities of the development of an arrangement for the global exchanging of a decent, involving the advantages and entanglements of undertaking worldwide deals.