Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Suaeda fruticosa is a widely distributed plant in Pakistan which has been traditionally used as a remedy for constipation, dyspnoea, headache, nausea, neurosis and vertigo. Objectives: The present study aimed to scientifically validate the traditionally claimed medicinal properties of Suaeda fruticosa. Methods: The experiment involved the preparation of a 70% ethanolic extract of Suaeda fruticosa (Sf.Cr), which was tested ex-vivo in an isolated rabbit jejunum preparation for spasmolytic activity. Moreover, the crude extract was tested on isolated tracheal and aorta preparations to evaluate the effects. Results: Sf.Cr dose-dependently relaxed the jejunum and inhibited K⁺(80 mM)-induced contractions with EC₅₀ value of 0.229 mg/ml and 0.095 mg/ml, respectively. Further, the Sf.Cr caused a rightward shift in Ca2+ concentration response curves (CRCs), similar to verapamil. So, calcium channel-blocking and anticholinergic actions were responsible for the antispasmodic (anti-diarrhoeal) effect. Sf.Cr produced inhibition of carbachol (1 µM)- and K⁺(80 mM)-induced contractions in isolated rabbit tracheal tissues with EC₅₀ values of 0.8339 mg/ml and 1.022 mg/ml, respectively. Sf. Cr also completely abolished the Phenylephrine (1 µM)- and K+(80 mM)-induced constrictions in isolated rabbit aortic rings, with EC50 values of 0.9448 mg/ml and 0.2026 mg/ml, respectively. Molecular docking against calmodulin (PDB ID: 6M7H) showed that 3-hydroxy-2-quinolinone attained the highest glide score (-6.742 kcal.mol⁻¹), establishing hydrogen bonding and Pi–Pi stacking interactions with MET124 and PHE92, surpassing the binding affinity of the standard drug verapamil (-5.464 kcal.mol⁻¹). SwissADME profiling showed that all identified phytoconstituents complied with Lipinski’s rule of five, exhibited high gastrointestinal absorption and were predicted to cross the blood-brain barrier, supporting their oral bioavailability as drug candidates. Conclusion: These findings collectively established Sf.Cr as a source of non-specific calcium channel-blocking phytochemicals with potential for developing antispasmodic, bronchodilator, and vasorelaxant agents.

Abstract: Background: Ulcerative colitis is a relapsing inflammatory bowel disease driven by dysregulated immunity, epithelial barrier injury and microbial imbalance. Current therapies remain limited by relapse, adverse effects and incomplete response. Quercetin has anti-inflammatory and barrier-protective activities and ERK-MMP signaling may link inflammation to mucosal tissue damage. Objectives: To evaluate whether the protective effects of quercetin in experimental ulcerative colitis (UC) are associated with modulation of ERK-MMP signaling, while avoiding causal overinterpretation beyond the animal and cellular evidence. Methods: A dextran sulfate sodium (DSS)-induced mouse model and a lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage inflammatory model were used. Mice were allocated to the control, UC model and low-, medium- and high-dose quercetin groups. Disease activity index (DAI; unitless), colon length, histopathology, inflammatory cytokines and ERK/MMP-related molecules were evaluated by histological staining, ELISA, qRT-PCR and western blotting. In-vitro, quercetin was compared with the ERK phosphorylation inhibitor U0126 and an agonistic stimulus to explore pathway-related associations. The study was exploratory and did not include genetic rescue experiments or human validation. Results: In DSS-treated mice, medium- and high-dose quercetin were associated with improved colon morphology, reduced DAI scores and partial restoration of colon length. Quercetin decreased pro-inflammatory cytokine expression and increased IL-10 expression. In both mouse colon tissues and LPS-stimulated RAW264.7 cells, quercetin was associated with reduced ERK1/2 activation and lower MMP-3 and MMP-9 expression, together with partial recovery of TIMP expression. These molecular changes were directionally consistent with the effects observed after ERK inhibition in-vitro. Conclusion: Quercetin showed protective effects in experimental UC models and these effects may be associated with modulation of the ERK-MMP signaling axis. Further pathway-specific rescue experiments, pharmacokinetic studies and human-relevant models are required before this mechanism can be considered definitive or clinically translatable.

Abstract: Background: Laxatives are the mainstay for pediatric functional constipation (FC), yet response factors need more real-world research. Objectives: This study investigated factors associated with laxative treatment response in children with functional constipation. Methods: Retrospective data were screened from 103 pediatric FC patients receiving polyethylene glycol treatment (The First Hospital of Qinhuangdao, Feb 2023–Nov 2025). After exclusion, 100 cases were included and divided into the responder group (n=68) and the non-responder group (n=32). The primary outcome measures included the Pediatric Constipation Score (PCS), the Bristol Fecal Morphology Scale (BSFS) and defecation frequency. Secondary endpoints included the incidence of abdominal pain, incidence of bloating, average daily dietary fiber intake, average daily water intake and average daily physical activity. A logistic regression analysis was conducted to identify independent risk factors associated with treatment response. Results: The baseline clinical characteristics of both groups were well-balanced (all P > 0.05). Post-treatment evaluation showed that the PCS score in the responder group decreased more significantly compared to the non-responder group (P<0.001). Meanwhile, increases in bowel movement frequency and BSFS scores were more pronounced in the responder cohort (all P<0.001). Compared to the non-responder group, the responder group also had lower incidences of abdominal pain and distension (all P<0.05). In terms of lifestyle-related indicators, the responder group had significantly higher daily average dietary fiber intake, average daily water intake and average daily physical activity levels (all P<0.001). Results from logistic regression analysis indicated that high baseline PCS scores, elevated incidence of abdominal pain, insufficient dietary fiber intake, low daily water intake and inadequate physical activity emerged as independent risk factors for poor laxative response in pediatric FC patients (all P<0.05). Conclusion: Laxative response in pediatric FC is affected by several factors, such as severe constipation, poor diet, low activity and abdominal pain.

Abstract: Background: Surgical excision of uterine fibroids triggers acute inflammation, impacting postoperative recovery. Propofol anesthesia may modulate this response. Chicoric acid possesses anti-inflammatory properties, but its perioperative utility remains unexplored. Objectives: To investigate whether preoperative chicoric acid enhances the anti-inflammatory effect of propofol in a mouse model of myomectomy and to explore the involvement of the p38 MAPK/NF-κB/IL-1β axis. Methods: A human uterine fibroid xenograft mouse model was established using CB-17 SCID mice. Mice underwent simulated myomectomy under propofol or ketamine anesthesia, with or without preoperative chicoric acid (50 mg/kg, 7 days). Controls included sham and model groups. The p38 MAPK/NF-κB agonist LPS and the IL-1β blocker Rilonacept were used to probe mechanisms. Inflammatory cytokines (MSD), pathway protein expression (Western blot), and uterine histopathology (H&E) were assessed 12h post-surgery. Results: Propofol anesthesia significantly inhibited surgery-induced p38 MAPK/NF-κB activation and reduced levels of inflammatory cytokines compared with the model group. Preoperative cholic acid further suppressed this pathway and enhanced the anti-inflammatory effect beyond that of propofol alone. LPS reversed chicoric acid's effects, confirming the involvement of the pathway. Unexpectedly, Rilonacept did not enhance but rather reversed the anti-inflammatory effect of chicoric acid, suggesting complex, compensatory interactions within a cytokine network. Conclusion: Preoperative chicoric acid augments propofol's anti-inflammatory effect during myomectomy by inhibiting the p38 MAPK/NF-κB pathway. However, the paradoxical effect of IL-1β blockade reveals unforeseen complexity in the perioperative cytokine network, warranting further investigation into the multitarget effects of chicoric acid and potential network-compensation mechanisms.

Abstract: Background: Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with rising incidence. The role of LINC01116 in PTC progression and its underlying mechanisms remain unclear. Objectives: To investigate LINC01116 expression in PTC, evaluate its prognostic significance and explore its functional role in regulating bone marrow mesenchymal stem cell (BMSC) apoptosis. Methods: This was a cross-sectional observational study with a prognostic cohort component.Serum samples from 60 PTC patients and 30 healthy controls were analyzed by RT-qPCR. Prognostic value was assessed using Kaplan-Meier survival analysis and Cox regression. In vitro, LINC01116 expression was manipulated in PTC cells and BMSCs using three independent siRNAs and pcDNA3.1 overexpression plasmids. Cell proliferation was evaluated by CCK-8 and colony formation assays, migration by Transwell assays and apoptosis by flow cytometry and Western blot analysis of Bcl-2, cleaved caspase-3 and cleaved caspase-9. Rescue experiments using siRNA-resistant LINC01116 were performed to confirm specificity. Results: LINC01116 was significantly upregulated in serum from PTC patients compared with healthy controls (P < 0.001). High LINC01116 expression correlated with advanced TNM stage and predicted reduced disease-free survival (HR=2.067, P=0.026) and overall survival (HR=2.081, P=0.024), serving as an independent prognostic factor. Knockdown of LINC01116 inhibited PTC cell proliferation and migration, while overexpression enhanced these effects. Mechanistically, LINC01116 suppressed BMSC apoptosis by upregulating Bcl-2 and downregulating cleaved caspase-3/9. Knockdown of LINC01116 induced opposite effects. Rescue experiments confirmed that restoring LINC01116 expression partially reversed knockdown-induced phenotypes (50-60% reversal), demonstrating functional specificity. Conclusion: LINC01116 is significantly upregulated in PTC and serves as an independent prognostic biomarker. It promotes tumor progression by inhibiting BMSC apoptosis through modulation of the Bcl-2/caspase pathway. These findings provide new insights into PTC pathogenesis and suggest LINC01116 as a potential therapeutic target.