Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: viral fever is a common acute infectious disease among infants and young children. Oseltamivir, a first-line antiviral drug, has limitations in inflammation regulation. In contrast, Evodia Rutaecarpa (E. Rutaecarpa) has been proven to exert antipyretic effects in traditional Chinese medicine. Objectives: This study, for the first time, systematically evaluated the efficacy of topical E. Rutaecarpa acupoint preparation plus Oseltamivir in treating viral fever in infants and young children. Methods: In this retrospective analysis, we included 60 pediatric cases between the ages of 6 months and 3 years and assigned them 1:1 according to propensity score matching (PSM): a combined group (topical E. Rutaecarpa acupoint application + oral Oseltamivir) and a control group (oral Oseltamivir alone). The treatment course lasted for 5 days. The main outcome measure was antipyretic time and the secondary outcome measures included changes in body temperature at different time points, serum inflammatory factors (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6], interleukin-1β [IL-1β], high-sensitivity C-reactive protein [hs-CRP]) levels, treatment comfort score (TCS), sleep quality index (SQI), adverse reactions and parents' satisfaction. Results: The antipyretic time was found to be shorter in the combined group than in the control group. Besides, the combined therapy led to markedly milder body temperature fluctuations at 24 hours and 48 hours, as well as greater decreases in serum inflammatory markers (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), compared to Oseltamivir monotherapy. Additionally, improved TCS and PSQI scores were found in pediatric patients receiving E. Rutaecarpa + Oseltamivir, together with superior parental satisfaction (P<0.01). The two groups showed no notable difference in the incidence of adverse reactions, with no added burden on liver and kidney functions with the combination therapy. Conclusion: Topical E. Rutaecarpa preparation exerts a three-dimensional effect of "acupoint stimulation‒transdermal drug delivery‒systemic anti-inflammation", synergizing with oral Oseltamivir. This combined therapy demonstrates greater advantages in rapidly reducing fever, regulating inflammation and improving patient comfort.

Abstract: Background: Patients’ self-perceived awareness of drug–drug interactions (DDIs) and drug–food interactions (DFIs) is important for medication safety, yet interaction-related counseling remains limited. Objectives: To assess patients’ self-perceived awareness of DDIs/DFIs and identify sociodemographic correlates of insufficient awareness in tertiary outpatient pharmacies of southern Saudi Arabia. Methods: A cross-sectional survey was conducted at two tertiary hospitals over six months. Adults ≥18 years attending outpatient pharmacies were recruited via consecutive sampling. A structured, self-administered questionnaire, refined by expert review, collected data on demographics, awareness, attitudes and behaviors. Insufficient self-perceived awareness was defined a priori as a moderate, weak, or very weak rating on a five-point Likert scale. Internal consistency was assessed via Cronbach’s alpha. Associations were examined using χ² with Cramer’s V and multivariable logistic regression estimated adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results: Of 401 patients approached, 353 consented; after excluding 12 records aged <18 years, 341 participants (52.8% female) formed the analytic sample. Overall, 22.3% (95% CI 18.2–27.0) reported insufficient awareness. Counseling on DDIs (7.6%) and DFIs (6.2%) was uncommon; DDIs (54.0%) and DFIs (51.3%) were the most frequent unclear topics. A two-item attitudinal subscale showed acceptable internal consistency (α = 0.75). After adjustment, only older age remained an independent predictor (aOR ≥51 vs 18–40 = 8.33, 95% CI 3.10–22.40), while education was not (aOR 1.11, 0.57–2.16). Conclusion: Insufficient self-perceived awareness of DDIs/DFIs was substantial. Older age, rather than education, was the only independent correlate, suggesting the unadjusted education association may be age-confounded. Targeted, age-sensitive pharmacist-led counseling may improve medication safety. Findings are exploratory given reliance on a self-perceived measure.

Abstract: Background: Oral heat-clearing and detoxifying Chinese patent medicines (CPMs) are frequently added to conventional therapy for pediatric acute upper respiratory tract infection (AURTI), but comparative evidence among products is sparse. Objectives: To compare adjunctive oral CPMs, prioritizing time to fever resolution and to assess total effective rate, cough resolution and adverse events. Methods: Eight databases and grey-literature sources were searched from inception to 31 May 2026. Eighteen studies were synthesized qualitatively; ten studies contributed to quantitative analyses. Two loop-enabling trials were added: One head-to-head comparison of Xiaoer Chiqiao Qingre Granules (CQ) with Lianhua Qingwen Granules (LHQW) and one LHQW-plus-conventional-therapy comparison. Loop-specific direct-versus-indirect inconsistency was assessed. Results: The CT-CQ-LHQW triangle formed one closed loop. No statistically detectable inconsistency was found for total effective rate (inconsistency factor 1.06, 95% CI 0.86-1.31; P=0.583) or adverse events (0.13, 95% CI 0.003-5.27; P=0.283), although the safety interval was very wide. The consistency-model RRs versus conventional therapy were 1.24 (95% CI 1.12-1.38) for LHQW and 1.18 (95% CI 1.07-1.32) for CQ. Pairwise analyses favored adjunctive CPMs for fever and cough resolution, with substantial heterogeneity. Conclusion: A real closed loop permits a limited consistency check, but certainty remains very low because only one loop was available, safety events were sparse and clinical and outcome definitions varied. Product rankings remain exploratory. Registration: The review was not prospectively registered. Funding: None.

Abstract: Background: Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases and lacks effective targeted therapy. Traditional Chinese medicine formulas, such as Xinbao Pill, have shown potential cardiovascular benefits; however, their molecular mechanisms are not yet fully understood. Objectives: This study aimed to systematically explore the multi-compound, multi-target mechanism of Xinbao Pill in the treatment of HFpEF using a network pharmacology approach. Methods: Active ingredients of Xinbao Pill were identified from the TCMSP database according to predefined pharmacokinetic criteria. Three GEO datasets (GSE180065, GSE240400 and GSE269053) were analyzed to identify differentially expressed genes associated with HFpEF. Elastic Net regression was used to refine the intersecting targets. Molecular docking and 100 ns all-atom molecular dynamics simulations were used to predict and validate the structural stability of compound-target interactions. Results: A total of 32 active compounds were identified. Differential expression analysis identified 1,368 HFpEF-related genes across the three datasets, including 23 overlapping targets. Elastic Net regression further selected 11 key genes (Clk1, Comt, Drd2, Ephx2, Fgr, Hcn2, Mme, Pparg, Ptgds, Slc27a1, Vdr). Molecular docking predicted strong binding affinities for several compound-target pairs, including Withanolide D-VDR (-12.0 kcal/mol) and 12-Deoxywithastramonolide-EPHX2 (-11.5 kcal/mol). Molecular dynamics simulations confirmed the structural stability of both top-ranked complexes over 100 ns, with low RMSD values and well-defined free energy minima. Conclusions: This in-silico study identified candidate targets and bioactive compounds that may be associated with the potential effects of the Xinbao Pill in HFpEF. The identified key targets and compounds may serve as promising candidates for further experimental validation and therapeutic development.

Abstract: Background: The genus Allium is a chemically diverse source of bioactive secondary metabolites, yet wild populations remain unevenly studied. Wild Allium ampeloprasum L. from Cyprus is underexplored despite evidence that the species contains phenolic, flavonoid and organosulfur constituents with diverse bioactivity. This study provides a locality-specific phytochemical and in-vivo evaluation of its methanolic bulb extract (AAB). Objectives: To characterise AAB and assess its acute toxicity, antinociceptive and local anti-inflammatory activity in Wistar albino rats. Methods: Dried bulb powder (50.0 g) was macerated in methanol, yielding 2.906 g extract (5.812%). Constituents were quantified by LC-MS/MS and screened using SwissADME and ProTox-III. Acute toxicity followed the two-phase Lorke design using 12 rats. Three independent efficacy cohorts (25 rats each; n = 5/group) received distilled water, AAB at 125, 250 or 500 mg/kg, or piroxicam 20 mg/kg. Antinociception was assessed by writhing, hot-plate and formalin tests and local anti-inflammatory activity by formalin-induced paw oedema. Biochemical, haematological, ESR and CRP measurements were performed after the final 5-h paw oedema assessment. Results: Thirteen constituents were quantified, with caffeic acid and trans-ferulic acid showing the highest relative abundances. No mortality occurred up to 5000 mg/kg, although transient clinical signs were observed. AAB reduced writhing by 45.8%, 69.5% and 91.5% at 125, 250 and 500 mg/kg, respectively (adjusted p = 0.0035, p < 0.0001 and p < 0.0001). Hot-plate latency increased significantly only at 500 mg/kg (adjusted p = 0.0067). Paw licking decreased at all concentrations in both formalin phases (adjusted p < 0.0001), with late-phase inhibition of 85.71-95.71%. Paw oedema inhibition at 5-h was 66.67-71.11%. Post-oedema blood analyses showed selected biochemical changes without a consistent concentration-related pattern. Conclusion: AAB demonstrated antinociceptive and local anti-inflammatory activity in rat models. Absence of mortality does not establish safety; further standardisation, mechanistic investigation and longer-duration toxicity studies are required.