Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Chronic non-atrophic gastritis is a common digestive system disease with a high incidence. While Traditional Chinese Medicine (TCM) offers unique therapeutic approaches, the specific combined efficacy of Woxuan needling and Xiangsha Liujunzi decoction warrants further clinical investigation. Objectives: To explore the effect of Woxuan needling combined with Xiangsha Liujunzi decoction on traditional Chinese medicine syndromes in patients with chronic non-atrophic gastritis. Methods: Convenience sampling was used to select 120 patients with chronic gastritis admitted to Jiangxi Province Hospital of Integrated Chinese and Western Medicine between 1 January 2022 and 1 January 2023. According to the order of enrolment, they were divided into an observation group and a control group using a random number table. The control group received basic drug treatment combined with Xiangsha Liujunzi decoction, whereas the observation group received Woxuan needling in addition to the control treatment. Results: Compared with the control group, the levels of stomach burning, abdominal distension or dull pain, loose stools, fatigue, shortness of breath and poor appetite were significantly lower in the observation group after treatment (p < 0.05). The serum pepsinogen level, gastroscopy score and gastrointestinal symptom rating scale score were also lower, whereas the gastrin level was higher in the observation group (p < 0.05). Conclusion: Treating patients with chronic non-atrophic gastritis with Woxuan needling combined with Xiangsha Liujunzi decoction can improve clinical symptoms and enhance therapeutic efficacy.

Abstract: Background: Tibial transverse osteotomy (TTO) is a promising but limited surgical option for diabetic foot (DF). Berberine, a natural compound from Coptis chinensis, exhibits anti-inflammatory and pro-angiogenic effects relevant to metabolic diseases. Objectives: This study aimed to evaluate whether adjunctive berberine enhances the therapeutic outcomes of TTO in DF patients and to explore its potential association with the platelet-derived growth factor-B (PDGF-B)/PDGF receptor-β (PDGFRβ) signaling pathway. Methods: This was a prospective, single-center, randomized, placebo-controlled, parallel-group, blinded trial. Of 200 screened DF patients, 96 eligible participants (Wagner grade 2–4) scheduled for TTO were randomized 1:1 to receive either TTO plus local berberine injections (n=48) or TTO plus local saline placebo (n=48). An additional non-randomized diabetic reference group (n=10) and healthy control group (n=10) were included for exploratory cellular studies only. The primary outcome was the total effective rate of ulcer healing at 3 months. Secondary outcomes included changes in Ankle-Brachial Index (ABI), ulcer area, Visual Analogue Scale (VAS) pain score and serum inflammatory markers (hs-CRP, IL-6). Exploratory outcomes comprised serum VEGF, bFGF and PDGF-B levels, as well as fibroblast apoptosis in wound tissue. Results: All 96 randomized participants completed the 3-month follow-up, with no dropouts. The berberine group demonstrated a significantly higher total effective rate than the surgery-alone group (87.5% vs. 68.8%; risk difference, 18.7%; 95% CI, 1.2% to 36.2%; P < 0.05). At 3 months, the berberine group also showed greater improvements in ABI (mean difference, 0.13; 95% CI, 0.08 to 0.18; P < 0.01) and ulcer healing rate (mean difference, 16.7%; 95% CI, 9.5% to 23.9%; P < 0.01), along with more significant reductions in hs-CRP and IL-6. Berberine treatment was associated with reduced fibroblast apoptosis in wound tissue (mean difference, -1.10%; 95% CI, -1.56% to -0.64%; P = 0.001) and lower protein expression of PDGF-B and PDGFRβ. No severe adverse events related to berberine injections were reported. Conclusion: In DF patients undergoing TTO, adjunctive local berberine therapy significantly improves the total effective rate and promotes ulcer healing, with benefits associated with reduced inflammation and fibroblast apoptosis and downregulation of the PDGF-B/PDGFRβ pathway. These findings are correlative and require further mechanistic validation. Larger multi-center trials are needed to confirm efficacy and safety.

Abstract: Background: Cardiomyocyte apoptosis plays a critical role in ventricular remodeling and heart failure following acute myocardial infarction (AMI). The Rho kinase signaling pathway is known to be involved in this pathological process. Butylphthalein, a compound with neuroprotective effects, may exert cardioprotective effects by regulating this pathway. Objective: This study aims to investigate the effects of butylphthalein on hemodynamic parameters and cardiomyocyte apoptosis in a rat model of AMI and to explore whether these effects are mediated through the Rho kinase signaling pathway. Methods: Fifty SD rats were randomly divided into five groups: Sham, AMI model, butylphthalein, fasudil (a Rho kinase inhibitor) and combination therapy. AMI was induced by ligation of the left anterior descending coronary artery. Two weeks post-surgery, hemodynamic parameters—including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximal rate of rise and fall of ventricular pressure (±dp/dtmax)—were measured. Cardiomyocyte apoptosis was assessed using TUNEL staining. The expression levels of Bcl-2, Bax, RhoA, ROCK1 and the p-MYPT1/MYPT1 ratio were detected by Western blot. Results: Rats in the AMI model group exhibited significant hemodynamic impairment and increased cardiomyocyte apoptosis. Compared with the model group, butylphthalein treatment significantly improved LVSP and ±dp/dtmax, reduced LVEDP, decreased the number of TUNEL-positive cells, upregulated Bcl-2 expression, downregulated Bax expression and suppressed the expression of RhoA/ROCK1 and the p-MYPT1/MYPT1 ratio (all P<0.05). The combination of butylphthalein and fasudil resulted in enhanced therapeutic effects, suggesting a synergistic inhibition of Rho kinase activity. Conclusion: Butylphthalein attenuates cardiomyocyte apoptosis and improves cardiac function in rats with AMI, likely through inhibition of the Rho kinase signaling pathway. These findings support its potential as a therapeutic agent for AMI.All experiments were performed on male Sprague-Dawley rats (n=50).

Abstract: Background: Epithelial-mesenchymal transition (EMT) is involved in colorectal cancer (CRC) pathogenesis. Curcumin (CUR) is widely used in the treatment of CRC. Polystyrene nanoparticles (PS-NPS) have a high specific affinity and have an inhibitory effect on cell proliferation. Therefore, the purpose of this study is to investigate the mechanism of inhibition of EMT in colorectal cancer mice by preparing curcumin polystyrene nanoparticles (CUR-PS-NPS). Objective: This study aimed to construct CUR-PS-NPS and investigate their mechanism in inhibiting CRC EMT via the miR-186/PI3K/AKT/Twist axis. Method: CUR-PS-NPS were prepared and characterized. In-vivo, CRC model mice (Balb/c, male) were divided into four groups: sham-operated control (PC), CRC model (CRC), low-dose CUR-PS-NPS (Cur-PS-NPS-L), and high-dose CUR-PS-NPS (Cur-PS-NPS-H). After intraperitoneal injection, tumor volume, EMT marker proteins and changes in miR-186 and the PI3K/AKT/Twist pathway were measured. In-vitro, human normal colonic epithelial cells (NCM460) were used to validate miR-186 interference and SW480 cells were co-transfected with a PI3K inhibitor to clarify the specific mechanism by which CUR-PS-NPS inhibit EMT. Results: In CRC mice intervened with CUR-PS-NPS, the tumor volume was reduced by 50%, the expression of mir-186 was up-regulated by 2.5 times, the phosphorylation level of PI3K/AKT was decreased by 40%, the expression of  Twist protein was down-regulated by 35% and the expression of the EMT marker E-cadherin was increased. The expressions of N-cadherin, Vimentin and Snail decreased significantly. Conclusion: CUR-PS-NPS can effectively delay the EMT process of CRC by up-regulating mir-186, inhibiting the PI3K/AKT signaling pathway and the expression of Twist. This discovery provides a new strategy for targeted therapy based on nanocarriers and its application potential in clinical practice can be further explored in the future.

Abstract: Background: Fine particulate matter (PM2.5) induces lung inflammation through pathways involving receptor for advanced glycation end-products (RAGE), S100A9 and nuclear factor-kappa B (NF-κB). Xing Su San and Sang Xing Tang are traditional Chinese medicine formulas used for respiratory disorders associated with cool-dry and warm-dry conditions, respectively. Objectives: To investigate whether treatment with these formulas is associated with reduced expression of RAGE, S100A9 and NF-κB in lung tissue of rats exposed to PM2.5 under simulated warm-dry and cool-dry conditions. Methods: Forty male Wistar rats were divided into five groups (n=8 each): blank control, warm-dry model, cool-dry model, Sang Xing Tang treatment and Xing Su San treatment. Exposed groups received PM2.5 (500 µg/m³, 3 hours/day, 28 days) under warm-dry (20°C, 33% humidity) or cool-dry (8°C, 33% humidity) conditions. Treatment groups received oral gavage of Sang Xing Tang (8.5 g/kg) or Xing Su San (12.5 g/kg) before exposure. RAGE messenger RNA was measured by reverse transcription quantitative polymerase chain reaction, NF-κB p65 protein by Western blot and S100A9 by immunohistochemistry. Results: Both PM2.5 exposure conditions were associated with significantly increased RAGE (2.8-fold and 2.5-fold), NF-κB p65 (2.4-fold and 2.2-fold) and S100A9-positive cells (3.45% and 3.13%) compared to controls (0.82%; all P < 0.05). Sang Xing Tang treatment was associated with reduced markers in the warm-dry model (RAGE: 1.6-fold; NF-κB: 1.5-fold; S100A9: 2.25%). Xing Su San treatment was associated with reduced markers in the cool-dry model (RAGE: 1.5-fold; NF-κB: 1.4-fold; S100A9: 2.08%; all P < 0.05). Conclusion: Xing Su San and Sang Xing Tang attenuate PM2.5-induced upregulation of RAGE, S100A9 and NF-κB in rat lung tissue in a pattern-specific manner. These hypothesis-generating findings provide preliminary evidence warranting further mechanistic validation.