Current Pharmaceutical Design - Online First

The Xianling Gubao capsule (XLGB), a traditional Chinese medicine formulation approved by the China Food and Drug Administration, has been effectively used to treat two common medical conditions: osteoarthritis (OA) and osteoporosis (OP). However, due to the complex ingredients, the molecular mechanisms underlying its therapeutic effects for OA and OP remain unknown.

This study identified XLGB-related therapeutic target genes and pathways for OA and OP by using bioinformatics and network pharmacology. Molecular docking assessed the interactions between core genes and compounds, while quantitative real-time PCR and Western blotting analyses validated the mRNA and protein expression of key target genes.

Bioinformatics analysis identified 473 unique genes common to OA and OP. Network pharmacology analysis identified 30 intersecting genes as the principal target genes for anti-OA and anti-OP effects. Ten hub genes were identified using protein-protein interaction as potential therapeutic targets. These genes were related to transcription regulation and enriched in certain signaling pathways, such as interleukin-17 and tumor necrosis factor. Molecular docking analysis revealed danshenxinkun B to exhibit a strong affinity for Ptgs2, Fos, and Tnfaip3, while miltirone displayed a strong affinity for Ptgs2. The experimental results have been verified using cellular experiments.

This study showed Ptgs2, Fos, and Tnfaip3 to be mainly enriched in interleukin-17 and tumor necrosis factor signaling pathways. Moreover, danshenxinkun B and miltirone significantly modulated the expression levels of these genes.

This study has demonstrated that danshenxinkun B and miltirone may be pivotal agents in treating OA and OP by down-regulating the expressions of Ptgs2, Fos, and Tnfaip3.

Hepatitis C virus (HCV) remains a major global health challenge, driving chronic hepatitis C (CHC) progression to severe liver diseases, including hepatocellular carcinoma (HCC). Direct-acting antivirals (DAAs) have transformed HCV treatment by achieving high sustained virological response (SVR) rates. However, limitations such as resistance, reinfection, and restricted accessibility emphasize the urgent need for novel therapeutic approaches. Among HCV therapeutic targets, the NS3/4A protease is critical for viral replication and immune evasion, positioning it as a prime focus for innovative drug discovery.

A comprehensive computational approach was adopted to evaluate flavonoids, natural compounds with known antiviral and anticancer properties, as potential inhibitors of the HCV NS3/4A protease. A curated flavonoid library was subjected to virtual screening using molecular docking techniques. Top-ranked flavonoids were further assessed based on binding affinity, dissociation constants, and key protein-ligand interactions. Pharmacokinetic profiling, molecular dynamics simulations, MM/PBSA energy calculations, and principal component analysis were performed to validate the most promising candidate.

The top ten scoring flavonoids demonstrated strong binding affinities and stable interactions with key catalytic residues of the NS3/4A protease. CID 100943380 emerged as the most promising candidate, exhibiting favorable pharmacokinetic properties and sustained stability throughout molecular dynamics simulations. MM/PBSA and PCA analyses further confirmed its robust binding and conformational stability.

The findings highlight flavonoids as promising inhibitors of NS3/4A protease, supporting their potential for further antiviral development.

This investigation identifies 10 flavonoids with high potential as NS3/4A protease inhibitors, providing a basis for future biological validation and safer drug development.

Sepsis-induced acute lung injury (S-ALI) is one of the diseases with a very high fatality rate. However, the traditional Chinese medicine compound Buzhong Yiqi Decoction (BZYQD) has an excellent effect in the treatment of S-ALI. Nevertheless, its mechanism of action is still unclear. In this study, we explored the molecular mechanisms of S-ALI injury treated with buzhong yiqi decoction through network pharmacology, in combination with in vivo experimental validation.

Traditional Chinese medicine system pharmacology (TCMSP) database was used to screen thechemical composition of BZYQD and its action targets; Multiple databases were used to collect target genesfor-S-ALI, including OMIM, TTD, GeneCards, and DrugBank; The STRING database was used for the protein-protein interaction (PPI) analysis of the common targets of the BZYQD and the S-ALI; The DAVID databasewas used for GO and KEGG analysis; molecular docking was used to detect the binding capacity of corecomponents and targets. HE staining was used to visualize the pathology of lung tissue in each group; ELISA wasused to detect the levels of inflammatory factors (IL-1β, IL-6, IL-8, NF-κB and TNF-α) and oxidative stressrelatedfactors (LDH, CK-MB, SOD, GSH-Px); The qPCR and Western blot were used to examine the mRNAand protein expression of IL-1β, IL-6, TNF-α NF-κB, p-NF-κB, PI3K, p-PI3K, AKT, and IKKα.

113 chemical components and 226 targets were screened from BZYQD; 9059 S-ALI-related geneswere screened out, with a total of 228 intersecting targets between BZYQD and S-ALI. Stigmasterol, quercetin, and isorhamnetin are the core components of BZYQD, PPI analysis shows that AKT1, IL6, TNF, andIL1B are the core targets of BZYQD for treating S-ALI, and molecular docking results show that the corecomponents have high binding activity with the target; Enrichment analysis shows that these core targets arerelated to the TNF signaling pathway. In vivo experimental studies have found that BZYQD can improve thedegree of inflammatory infiltration and edema in lung tissue of S-ALI model mice, reduce the expression ofIL-6, IL-1β, IL-8, TNF-α, LDH, CK-MB, and NF-κB in serum (P0.05), as well as the mRNA and proteinexpression of IL-6, IL-1β, TNF-α, NF-κB, p-NF-κB, PI3K, p-PI3K, AKT, and IKKα in lung tissue (P0.05),and levels of SOD and GSH-Px were increased (P0.05).

The action targets of the main chemical components of BZYQD are TNF, AKT, and IL6. Thesetargets can promote the activation of PI3K and TNF pathways and mediate the occurrence of inflammationand oxidative stress, which provides inspiration for the treatment of S-ALI. However, the results of this study still need to be verified in combination with in vitro approaches.

This study suggests that the mechanism of BZYQD in treating S-ALI may be achieved by inhibiting the TNF and PI3K signaling pathway and reducing inflammation and oxidative stress levels.

Diabetic neuropathy (DN) is a common complication of diabetes with limited therapeutic options. Given its complex pathophysiology involving oxidative stress, inflammation, and impaired nerve function, there is increasing interest in complementary therapies. This review aims to summarize the potential use of natural oils, both as dietary supplements and topical agents, for the prevention and management of DN.

A systematic literature search was conducted using databases such as SciFinder and PubMed for studies published from 1988 to January 2024. The search employed keywords including “diabetic neuropathy,” “natural oils,” and “bioactive constituents.” Relevant studies involving preclinical and clinical evaluation of natural oils or their active compounds in DN were selected, analyzed, and categorized based on the type of oil, mode of application, and mechanism of action.

Several natural oils of plant and animal origin demonstrated protective and therapeutic effects against DN in both animal models and limited clinical settings. Their beneficial effects were attributed to anti-inflammatory and antioxidant properties, enhanced nerve conduction velocity, and modulation of vascular and neurotrophic factors. Both oral and topical applications contributed to symptom improvement.

Due to the involvement of various signalling pathways and complex pathophysiology, DN has long been a condition with few acceptable treatment options. Although several natural oils have demonstrated activity against DN, very few clinical studies have been conducted to explore their therapeutic potential fully.

Natural oils represent a potential complementary strategy for managing DN. However, more rigorous clinical investigations are essential to confirm their safety, efficacy, and translational value.

The zebrafish (Danio rerio), which lives in tropical freshwater, is thought to be one of the best animal models for studying drugs and their effects. This model is unique for its fast growth, clear embryos, genetic similarity to humans, and low cost for experiments. Literature-based data were gathered and shared so that future researchers in the field of pharmacology could get an idea of what kind of work could be done.

Journal sources like Scopus, Springer, MDPI, and PubMed were used. Seventy-four research papers from 2000 to 2025 were reviewed, but some from before 2020 were added because they were more scientifically sound. Articles about fish that aren't zebrafish were left out.

In order to perform preclinical investigations of several ailments, including diabetes, cancer, cardiovascular disease, and neurological disorders, researchers are using zebrafish as an animal model. The reason behind its use is its similar genetic pattern, similar physiology, rapid development, and optical transparency.

Researchers have found heart-healthy phospholipids, antitumor peptides, and anti-diabetic chemicals in zebrafish models, which makes them a great way to study human pathophysiology. In vivo studies using zebrafish are also easy to expand and cost-effective.

The emerging zebrafish model is indispensable for translational investigation. This model works as a bridge connecting in vitro assays to mammalian models. The present article is an attempt to showcase the current perspective on the pharmacological model in view of drug discovery involving zebrafish.