Pharmacological Analysis Research Articles (Page 1)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and cholinergic dysfunction. This study evaluated the neuroprotective potential of Ficus microcarpa leaf extract via a multidisciplinary approach that integrates phytochemical profiling, in silico analysis, and in vivo validation. LC‒MS analysis revealed key bioactive compounds, including fortunellin, thalsimine, and vocalristine, which are flavonoids, alkaloids, and terpenoids, that are known for their neuroprotective effects. Drug-likeness and toxicity evaluations via SwissADME and ProTox-II revealed favorable pharmacokinetic properties. Network pharmacology and KEGG enrichment analyses identified AChE, APP, and GSK3β as central AD-related targets. Molecular docking (AutoDock 4.2) revealed strong binding affinities of fortunellin (-9.2kcal/mol) and donepezil (-9.0kcal/mol) with AChE, which was supported by active site interactions. Molecular dynamics (200ns, GROMACS) confirmed the complex stability via RMSD, RMSF, SASA, and hydrogen bond analyses. The MM-PBSA calculations further validated the binding stability. In vivo studies revealed that F. microcarpa (100 and 200mg/kg, po) and donepezil (3mg/kg, po) administered for 21 days significantly reversed scopolamine-induced (2mg/kg, ip) memory deficits in Wistar rats, as assessed by the Morris water maze, elevated plus maze, and novel object recognition tests. Biochemical analysis revealed reduced oxidative stress, increased antioxidant enzyme levels, and the restoration of cholinergic function. Histopathological studies revealed that the integrity of the hippocampus was preserved. Overall, these findings support F. microcarpa, particularly fortunellin, as a promising multitarget candidate for AD therapy, meriting further pharmacological investigation.

Exploring the anti-Helicobacter pylori activity and mechanism of Shouhui Tongbian through chemical composition analysis and network pharmacology.

Intervertebral disc degeneration (IVDD) is a complex and multifactorial condition characterized by the progressive deterioration of the intervertebral discs. Ginsenoside Rg1, a bioactive compound isolated from Panax ginseng C.A.Mey., that has demonstrated promising therapeutic potential in the treatment of IVDD. This study employed a multi-faceted approach to investigate the therapeutic effects of ginsenoside Rg1 on IVDD. Initially, histopathology, magnetic resonance imaging (MRI) were performed in clinical IVDD patients. Subsequently, histopathology, safranin green staining, X-ray, and MRI were utilized to evaluate the efficacy of ginsenoside Rg1 in alleviating in a rat model in vivo. Transcriptomics and gene set enrichment analysis (GESA) were conducted, and a network pharmacology visualization of ginsenoside Rg1-ferroptosis key targets-pathways-IVDD was constructed, along with molecular docking of ginsenoside Rg1 and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenoside Rg1 on alleviating IVDD. Additionally, an Hydrogen peroxide (H2O2)-induced degeneration model of nucleus pulposus cells (NP cells) was used to evaluate the efficacy of ginsenoside Rg1 in alleviating IVDD in vitro. Methods including lipid-reactive oxygen species (ROS) detection, enzyme-linked immunosorbent assay (ELISA), FerroOrange staining, and transmission electron microscopy were employed to validate the effect and mechanism of ginsenoside Rg1 on alleviating IVDD in vivo and in vitro. ML385, a nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor, was used to reverse the effect of ginsenoside Rg1 in mitophagy and ferroptosis, respectively. The expression of proteins was assessed on immunochemical, immunofluorescence, and western blotting techniques. Significant ferroptosis was observed in the NP tissue of IVDD patients, with more effects in patients with higher imaging grades. Ginsenoside Rg1 significantly mitigated IVDD in rats and promoted intervertebral disc repair. Network pharmacology and transcriptomics analyses indicated the key targets of ginsenoside Rg1 for the treatment of IVDD, including NRF2, glutathione peroxidase 4 (GPX4), solute carrier family 7a member 11 (SLC7A11), and ferritin light chain 1 (FTL1). Molecular docking exhibited that ginsenoside Rg1 had good binding ability between ginsenoside Rg1 and these ferroptosis key targets. Ginsenoside Rg1 reduced the expression of ROS and malondialdehyde (MDA), decreased Fe2+ content, increased the expression of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and upregulated the expression of ferroptosis key proteins NRF2, GPX4, FTL1, and SLC7A11 in intervertebral disc tissues and NP cells. Treatment with ML385 attenuated the ginsenoside Rg1-induced upregulation of these proteins in NP cells, thereby promoting ferroptosis and reversing the protective effects of ginsenoside Rg1. Ginsenoside Rg1 can mitigate IVDD by inhibiting ferroptosis in NP cells. The NRF2/GPX4 pathway was validated as the key ferroptosis pathway through which ginsenoside Rg1 exerts its therapeutic effects on IVDD.

Lippia nodiflora leaves have been traditionally used by healers in Silent Valley, Palakkad district of Kerala, for treating wounds. This study aimed to scientifically validate the wound-healing potential of the methanol extract of L. nodiflora leaves (MELN) to support its ethnopharmacological claims. Phytochemical profiling using UPLC-QTOF-MS identified key constituents, and network pharmacology analysis revealed potential pathways and targets involved in wound healing. These findings were further supported by molecular docking, in vitro, in vivo, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses. No toxicity was observed in either in vitro or in vivo models. Network pharmacology indicated that MELN may act through the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance pathway. Core compounds such as quercetin, 3-methylherbacetin, eupafolin, 6-hydroxyluteolin 3'-methyl ether 7-sulfate, and syringic acid beta-glucopyranosyl ester likely contribute to the wound-healing activity, as supported by docking studies. RT-qPCR analysis demonstrated upregulation of genes related to cell migration and proliferation. In vitro assays showed enhanced cell proliferation and migration, indicating pro-healing properties. In vivo excision wound models confirmed significant wound closure, complete epithelialization, and improved histopathological features in MELN-treated groups. Overall, this study provides scientific evidence supporting the ethnopharmacological claim of L. nodiflora in wound management and establishes MELN as a potential herbal formulation for wound healing.

Background:Diabetic kidney disease (DKD) is a major cause of end-stage renal disease. Although metformin is widely prescribed, the mechanisms underlying its renoprotective effects remain incompletely understood.Methods:We integrated multi-omics approaches—including network pharmacology, phosphoproteomics, and targeted metabolomics—in both db/db mice (male) and human patients. Analyses were performed on blood and kidney tissue from mice and paired blood/urine samples from DKD patients to identify conserved therapeutic targets and metabolic pathways.Results:Metformin treatment improves glycemic control and renal function (reduced creatinine and urea nitrogen) in DKD mice. Network pharmacology and phosphoproteomic analyses reveal metformin’s engagement with the MAPK pathway, specifically through MAPK1 and MAPK3. Targeted metabolomics identifies four carbohydrate metabolites (mannitol, D-arabitol, D-mannose, and D-xylose) associated with DKD risk in humans. Cross-species validation in mice supports D-Xylose as a potential key biomarker for metformin’s therapeutic effects in DKD, with proximal tubule bicarbonate reclamation and alanine, aspartate and glutamate metabolism as key metabolic pathways.Conclusions:Metformin alleviates DKD through multi-modal mechanisms, modulating the MAPK signaling pathway and carbohydrate metabolites—notably D-xylose. As far as we are aware, these findings provide new mechanistic insights and suggest potential biomarker-driven strategies for DKD management.

Dopamine receptor agonist (DA)-resistant prolactinoma presents a significant clinical challenge, highlighting the need for novel therapeutic strategies. Deguelin is a rotenoid compound derived from several plant species with unique antitumor effects. In this study we investigated the efficacy of deguelin on DA-resistant prolactinoma and elucidated its antitumor mechanisms. We showed that deguelin concentration-dependently inhibited cell viability, proliferation and prolactin secretion, and promoted apoptosis and cell cycle arrest in two prolactinoma tumor cell lines GH3 and MMQ. In CCK-8 assay, the IC50 values of deguelin for GH3 and MMQ were 0.1518 and 0.2381 µM, respectively. Network pharmacology analysis predicted that ornithine decarboxylase (ODC), a rate-limiting enzyme in the de novo synthesis of polyamine and responsible for converting ornithine into putrescine, was the target of deguelin. We demonstrated that deguelin directly interacted with ODC, competitively inhibiting putrescine production, and thereby reducing the levels of active Rac1. Transcriptomic analysis of deguelin-treated GH3 cells identified the PI3K/AKT signaling pathway as a crucial mediator of the action of deguelin with the inhibition of CREB3L1 playing a central role. In GH3 xenograft nude mice, administration of deguelin (4 mg/kg, i.p., every other day for two weeks) significantly inhibited tumor growth with significant reduction in both AKT phosphorylation and CREB3L1 levels in deguelin-treated xenografts. These results suggest that deguelin can be considered a therapeutic option for treating DA-resistant prolactinoma and serve as a basis for developing novel treatment approaches.

Sarcopenia (SP) associated with functional impairment is highly prevalent; however, therapeutic strategies addressing this condition remain limited. Inflammation and oxidative stress are the key contributors. Suitably, formononetin (FMN) offers diverse benefits, including antioxidant, anti-apoptotic, and anti-inflammatory properties. Therefore, this study used network pharmacology to identify 81 potential target genes for FMN to alleviate SP. Serine/threonine-protein kinase 1 (AKT1), epidermal growth factor receptor (EGFR), and sirtuin 1 (SIRT1) as the core targets. Kyoto Encyclopedia of Genes and Genome analysis indicated that FMN primarily affects SP via the interleukin (IL)-17, PI3K-Akt and FoxO signalling pathways. Cell studies revealed that FMN reduces IL-6 release and boosts superoxide dismutase activity, thereby enhancing C2C12 skeletal muscle cell vitality. FMN intervention also enhanced AKT1 and SIRT1 gene and protein expression, decreased muscle-specific RING finger protein-1 gene expression, and increased EGFR protein expression. This suggests its anti-inflammatory and antioxidant effects in dexamethasone-treated C2C12 cells, potentially preventing muscle atrophy by inhibiting protein breakdown. These findings highlight the promising multi-target role and molecular mechanism of FMN in the treatment of SP and suggest future clinical applications.Graphical

Glabridin mitigates osteoarthritis progression through modulation of the PI3K/AKT/FOXO3A autophagy axis.

Ulcerative colitis (UC) is a serious inflammatory bowel disease with a significantly increasing incidence globally. Current treatment options often exhibit unstable efficacy and notable side effects, making the exploration of alternative therapies particularly important. Peucedanum praeruptorum Dunn, a traditional Chinese medicine, contains various bioactive compounds, among which praeruptorin A (PA) has garnered attention for its anti-inflammatory potential. This study aimed to investigate the anti-UC effects of PA in a dextran sulfate sodium (DSS)-induced colitis mouse model and in Caco-2 cells and its underlying mechanisms. Preliminary results indicate that PA alleviates symptoms of DSS-induced ulcerative colitis, significantly reduces the expression of inflammatory factors, decreases colonic apoptosis, and repairs damaged intestinal barrier function in mice. PA also had protective effects on DSS-induced barrier dysfunction and inflammation in Caco-2 cells. Further research demonstrated that PA inhibits the phosphorylation of the STAT-1 and STAT-3 proteins, whereas AG490, an inhibitor of STAT-1 and STAT-3, effectively mimics the intestinal protective effects of PA. In addition, network pharmacology and molecular docking analyses were conducted to further elucidate the molecular targets and mechanisms of PA. These analyses revealed key pathways and potential interactions, supporting the hypothesis that PA exerts its protective effects through the modulation of inflammatory and apoptotic pathways. In summary, these findings support the protective role of PA in ulcerative colitis in vivo and in vitro and suggest its potential as an intervention for the prevention and treatment of this condition.NEW & NOTEWORTHY This study revealed that praeruptorin A (PA) alleviates symptoms of ulcerative colitis in a DSS-induced mouse model, reduces inflammatory factors levels, and promotes intestinal barrier repair in both DSS-induced colitis model mice and Caco-2 cells. The effects of PA are linked to STAT-1 and STAT-3 inhibition, highlighting its potential as a therapeutic intervention.

Cannabigerol (CBG), being one of the non-psychotropic phyto-cannabinoid, has been labelled and recognized to be antioxidant and neuroprotective; it may conceivably hold depression-relieving activity. Consequently, the objective of the present research procedure was to explore the depression-alleviating competence of cannabigerol in both stressed and unstressed mice using computational/in-silico modelling, followed by in-vivo analysis. Target genes for Major Depressive Disorder (MDD) were identified using GeneCards and Swiss Target Prediction, with common targets screened via Venny software. STRING database anal-ysis established protein-protein interactions (PPI), identifying CNR2 (CB2 receptor) as a key target. Molecular docking of CBG with CB2 (PDB ID: 8GUR) showed strong binding, prompting in vivo evaluation. ADME profiling via Schrödinger Maestro v10.5 confirmed CBG's high oral absorption and favorable pharmacokinetics. Male Swiss albino mice underwent chronic unpredictable mild stress (CUMS) for three successive weeks, with CBG (10, 20, 40 mg/kg) and imipramine (15 mg/kg) administered and various behavioral and biochemical parameters being analyzed. Cannabigerol demonstrated maximum oral absorption in ADME predictions using Schrö-dinger's Maestro (v10.5). Wayne diagram illustrated MDD-related targets, with CB2 (CNR2) rank-ings in top targets, based on SwissADME and Venny software analysis. Docking analysis revealed a high binding affinity (-10.53) for CB2, outperforming cannabidiol (-9.56) and comparable to Δ9-THC (-10.11). During in vivo evaluation, CBG (40 mg/kg) and Imipramine 15mg/kg significantly reduced CUMS-induced exalted plasma corticosterone, nitrite quantities, and monoamine oxidase-A action in the brain of stressed mice. Additionally, both treatments substantially reversed the unpre-dictable chronic stress-induced decline in catalase action, demonstrating CBG's possible potential in alleviating depression-like symptoms in mice. Cannabigerol has shown significant depressive alleviating potential in mice exposed to chronic and unpredictable stress regimes, possibly via interaction with cannabinoid receptors as in-dicated by in-silico modelling, which has been validated by our findings of the in-vivo protocol.

Elucidating the therapeutic mechanisms of resveratrol in benign prostatic hyperplasia via an integrated strategy of network pharmacology, multi-omics and molecular biology.

Corilagin alleviates cardiac ischemia-reperfusion injury by inhibiting ferroptosis via PI3K/AKT pathway.

Exploring the alleviating effect and mechanism of the diterpenoid alkaloid Polyschistine D on rheumatoid arthritis based on network pharmacology and non-targeted metabolomics.

Royal jelly acid inhibits NF-κB signaling by regulating H3 histone lactylation to alleviate IgE-mediated mast cell activation and allergic inflammation.

Guilu Erxian glue mitigates spermatogenesis dysfunction through HIF-1α/SLC7A11-mediated ferroptosis inhibition: An integrated metabolomics and network pharmacology study.

Salidroside ameliorates experimental autoimmune neuritis by dually modulating neuroinflammation and immune homeostasis via PI3K/AKT signaling.

Schizandrin ameliorates post-traumatic stress disorder-like behaviors via 5-HT1A receptor in mice.

Combined transcriptomics and network pharmacology to elucidate the mechanisms of rutin in treating ischemic stroke rat.

Multi-omics and experimental validation reveal the mechanism of DanxiaTiaoban decoction in treating atherosclerosis.

Neuroinflammatory mechanism of Volatile oil from Acori graminei Rhizoma in tourette syndrome: GC-MS, network pharmacology and experimental validation.