Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Chemotherapy-induced alopecia negatively impacts the mental health of cancer patients. Topical minoxidil, a widely recommended drug for hair regrowth, causes scalp irritation and contact dermatitis. Oral minoxidil causes multiple cardiovascular and neurological side effects. Cetirizine hydrochloride, an antihistamine with a better safety profile than minoxidil, may stimulate hair follicle activity by modulating prostaglandin levels. Objectives: The present study aimed to develop a cetirizine hydrochloride-loaded emulgel and evaluate its potential, in combination with microneedling, for the treatment of chemotherapy-induced alopecia. Methods: Different emulgel formulations comprising cetirizine HCl, liquid paraffin, carbopol 940, propylene glycol, oleic acid, Tween 20, Span 20 and propylparaben were optimized using central composite design and response surface methodology. Physicochemical evaluation of the prepared emulgel included physical examination, determination of pH, viscosity, spreadability, drug content and stability. Interactions and compatibility among formulation constituents were assessed using In-silico analysis and Fourier transform infrared spectroscopy. In-vitro drug release, ex-vivo permeation and in-vivo hair growth studies were carried out to evaluate the performance efficiency of emulgel. Results: The prepared emulgels exhibited acceptable physicochemical properties and remained stable for 3 months. Constituents were found to be compatible with each other. The optimized formulation F4 released >95% drug at pH 5.5 within 360 minutes. During an ex-vivo study, ~94% of the drug permeated across rat skin within 6 hours following application of emulgel on the microneedle-pretreated skin. In cyclophosphamide-induced alopecia in rats, application of emulgel to microneedle-pierced skin for 15 days promoted hair growth. Conclusion: The prepared cetirizine HCl-loaded emulgel and microneedle combination may be a promising approach to treating chemotherapy-induced alopecia.

Abstract: Background: The pharmaceutical industry is a strategic emerging sector in China, yet its scientific and technological innovation network remains poorly characterized in terms of structural dynamics and evolutionary pathways. Objectives: In the field of scientific and technological innovation in China's pharmaceutical industry, this study systematically sorts out the context of research, reveals the structural characteristics and evolutionary laws of the innovation network and provides references for industrial policy formulation and enterprise strategic layout. Methods: Based on 602 relevant papers collected from the China National Knowledge Infrastructure (CNKI) from 1996 to 2024, VOSviewer and CiteSpace software were comprehensively used to conduct co-occurrence analysis, cluster analysis and burst term detection, so as to construct a multi-dimensional dynamic network model. Results: The number of published papers on scientific and technological innovation in China’s pharmaceutical industry increased, with accelerated growth and greater volatility after 2010. A core author group has initially taken shape, but the participation rate of enterprises is only 8.3%, indicating insufficient industry-university-research collaboration. Research hotspots have expanded from traditional biomedicine to emerging technologies such as artificial intelligence-assisted drug design and mRNA vaccines, with industrial clusters and factor collaboration becoming new focuses. Conclusion: The innovation of the pharmaceutical industry follows a phased evolutionary path of "technology-driven – cluster development – factor collaboration". At present, it is confronted with structural constraints such as inadequate data sharing, unbalanced resource allocation and a shortage of interdisciplinary talents. It is suggested that enterprises’ dominant position in innovation be strengthened, a cross-regional public R and D data platform for the pharmaceutical industry be established, policy incentives shift from project funding to performance-based rewards for innovation alliances and the industry evolve into an adaptive innovation ecosystem.

Abstract: Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease for which targeted therapies remain limited. The Notch signaling pathway has been implicated in T cell differentiation and autoimmune inflammation. Objectives: This study aimed to investigate the therapeutic effects of the Notch signaling antagonist DAPT on autoimmune arthritis in mice and to explore its underlying immunological mechanisms. Methods: A collagen-induced arthritis (CIA) mouse model was established. DAPT (100 ng/kg) or PBS was administered intraperitoneally every other day from day 0 to day 36. Notch pathway activation in CD4+ T cells and synovial tissues was assessed by Western blot and immunohistochemistry. Arthritis severity was evaluated by clinical scoring, radiological examination and histopathology. Th1, Th17 and Treg cell frequencies and absolute numbers in spleen and lymph nodes (LNs) were analyzed by flow cytometry. Plasma cytokine levels were measured by multiplex assay. In-vitro Th17 differentiation assays were performed with DAPT or a Notch agonist. Results: Compared with normal mice, CIA mice showed significant upregulation of NICD expression in CD4+ T cells and synovial tissues. DAPT treatment significantly reduced clinical arthritis scores, joint erosion and cartilage destruction. DAPT also decreased the frequencies and absolute numbers of Th1 and Th17 cells in the spleen and LNs, alongwith reduced plasma levels of IFN-γ and IL-17. In-vitro, DAPT suppressed Th17 differentiation, while Notch agonist enhanced it. Treg cells were not significantly altered by DAPT. Conclusion: The Notch signaling antagonist DAPT ameliorates autoimmune arthritis in mice by suppressing Th1 and Th17 immune responses, highlighting Notch signaling as a potential therapeutic target for RA.

Abstract: Background: Exposure to mercury (Hg) is well-established to induce menstrual cycle disorders and disrupt sex hormone functions. Astragalus species, characterized by their potent antioxidant and anti-apoptotic properties, have shown potential in mitigating these adverse effects by promoting folliculogenesis and restoring hormonal balance. Objectives: This study aimed to evaluate the protective effects of Astragalus microcephalus polysaccharides (APS), both alone and in combination with vitamin E and selenium (Vit E+Se), against ovarian damage and oxidative stress induced by mercuric chloride toxicity in rats. Methods: Thirty-six female Wistar rats were synchronized via vaginal smear and randomly assigned to six groups: Control, Mercury (0.43 mg/kg HgCl2), APS (2.7 g/kg), Vit E+Se, Mercury+APS and Mercury+Vit E+Se. Following a 15-day subacute exposure period, serum levels of estradiol, LH and FSH were measured. Oxidative stress markers and ovarian histopathology were evaluated. Apoptotic and inflammatory pathways were assessed through immunohistochemical staining of Caspase-3, AIF and NF-κB. Results: Hg-induced reductions in hormone levels were significantly restored to near control levels in the APS-treated groups and antioxidant levels were notably elevated in these groups, indicating mitigation of oxidative stress. Furthermore, immunohistochemical analysis revealed a significant reduction in stromal and follicular degeneration and a decrease in apoptotic activity in the ovaries of rats treated with APS. Conclusion: APS exerts a significant protective effect against mercury-induced ovarian toxicity. This protection is mediated through the attenuation of oxidative stress, inflammation and apoptosis, as evidenced by the modulation of Caspase-3, AIF and NF-κB pathways. The results suggest that APS, particularly in synergy with vitamin E and selenium, offers a potential therapeutic strategy for managing heavy metal-induced reproductive damage.

Abstract: Background: Breast cancer (BC) remains a significant global health threat with complex pathogenesis often linked to chemotherapy resistance and inflammatory microenvironments. Histidine triad nucleotide-binding protein 2 (HINT2) is a mitochondrial protein involved in metabolism and immunity, but its specific role in BC and potential as a therapeutic target require further elucidation. Objectives: This study aimed to identify novel therapeutic targets for BC and evaluate the anti-tumor efficacy and molecular mechanisms of Albiflorin (Al), a natural monoterpene glycoside. Methods: Proteomic profiling was performed on BC xenografts in nude mice to identify differentially expressed proteins. In-vivo and in-vitro models (MDA-MB-231 cells) were established to assess the effects of Al (20 mg/kg or 20 µM) on tumor growth, apoptosis and cytokine production. Molecular docking and co-immunoprecipitation (Co-IP) were used to investigate the interactions among HINT2, NLRP3 and Al. Results: HINT2 was significantly upregulated in BC tissues and identified as a primary pro-tumorigenic factor. Co-IP confirmed an endogenous interaction between HINT2 and NLRP3. Al exhibited strong binding affinity to HINT2 (–7.36 kcal/mol) and significantly suppressed tumor volume and weight. Furthermore, Al treatment downregulated the HINT2/NLRP3 axis, reduced inflammatory cytokines (IL-1β, IL-6, TNF-α) and promoted apoptosis by modulating Caspase-3, Bax and Bcl-2 levels. Conclusion: Albiflorin suppresses BC progression by inhibiting the HINT2/NLRP3 signaling pathway, suggesting HINT2 is a viable biomarker and Al a promising therapeutic agent for BC treatment.