Pakistan journal of pharmaceutical sciences最新文献

Inflammatory response is a key for the emergence and progression of diabetic kidney disease (DKD). Studies have proved that Agrimonia pilosa Ledeb (APL) as a traditional Chinese herbal medicine has strong anti-oxidant and anti-inflammatory effects, but how APL plays on DKD hasn't been reported. This work explored the effects and potential regulatory mechanism of APL in DKD, aiming to inspire new ideas for developing novel drugs for DKD. DKD mice were induced by streptozotocin (STZ) and treated with APL extract of different concentrations by gavage. Blood glucose, blood lipids, renal function and histopathological examination were performed using blood glucose meter and biochemical analyzer, HE staining, PAS staining and immunohistochemistry separately. Subsequently, Western blot and ELISA were used to determine the expression of inflammatory factors and JNK/p38 pathway proteins in mice kidney tissue. The results showed that APL concentration-dependently reduced blood glucose and lipid levels in DKD mice, alleviated kidney injury and reduced the expression of fibrotic factors and inflammatory factors in kidney tissue. In addition, APL also effectively inhibited the expression of the JNK/p38 pathway proteins. It can be speculated that APL may alleviate pathological damage and inflammatory response in DKD by inhibiting the JNK/p38 signaling pathway.

This study aimed to enrich flavonoids from Euphorbia hirta L. (E. hirta) extracts, and the enrichment parameters were optimized by adsorption and desorption tests. The HPD-300 resin was chosen after a comparison of the flavonoids from E. hir15ta's adsorption and desorption capabilities on nine different types of macro porous resin. The optimal enrichment for purification of E. hirta extracts were determined as sample concentration of 3.0mg/mL, pH of 2.0 and a desorption solvent of 50% ethanol. The optimal dynamic parameters were loading 2.5 BV of sample at a feeding flow rate of 2 BV/h, cleaning the column with 5 BV of water and then eluting 50.0% ethanol at a 2 BV/h elution flow rate using 5 BV of eluent. Following a single treatment cycle with HPD-300 resin, the product's total flavonoid content rose from 6.32% to 28.8%, with an 80.01% recovery yield. Then, 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and hydroxyl radical scavenging ability were used to evaluate the antioxidant properties of the purified flavonoids. The main chemical components of purified flavonoids from E. hirta are astragalin, quercetin-3β-D-glucoside, 9,16-dioxo-10,12,14-octadeca-trienoic acid and gallic acid. The results showed that purified flavonoids from E. hirta had a strong antioxidant effect, which indicated that it represented a valuable natural antioxidant source.

Atherosclerosis (AS), as the main pathophysiological basis of coronary heart disease, can develop into carotid atherosclerotic plaque (CAP) through intimal inflammation, necrosis, fibrosis and calcification. However, there are few reports on the clinical drug selection of CAP. The aim of this study was to explore the effects of atorvastatin and ezetimibe on CD147, HIF-1, MMP-2 and VEGF in CAP under the guidance of IVUS, so as to provide basis for CAP of the best drug. 32 male New Zealand rabbits were divided into the control group, the model group, the atorvastatin group and the ezetimibe group randomly. The levels of serum LDL-C and MMP-2 have a significant decrease in atorvastatin group and ezetimibe group (P <0.05). The level of serum CD147 has a significant decrease in ezetimibe group (P <0.05). The average OD value of HIF-1 in atorvastatin group decreased significantly (P <0.05). The relative expression of CD147 and VEGF decreased significantly in atorvastatin group (P <0.05). There were different degrees of fibrous plaque and lipid plaque in model group, atorvastatin group and ezetimibe group. There exists a significant decline of CD147, HIF-1, MMP-2 and VEGF by atorvastatin in plaque, but the effect of ezetimibe is not obvious.

Imiquimod, known for its immune-modulating properties, has emerged as a potential anti-cancer agent. The U87 glioblastoma cell line, known for its high malignancy and poor prognosis, presents a significant challenge in neuro-oncology. Targeting the STAT-3/NF-κB pathways offers a promising therapeutic strategy for glioblastoma treatment. Imiquimod potentially inhibits these oncogenic signaling routes to suppress U87 cell proliferation and migration. We investigated the effect of imiquimod (IMQ) on U87 cell growth using CCK-8 and cell scratch assays. Western blotting analyzed protein levels of STAT-3, p-STAT-3, NF-κB and p-NF-κB, while flow cytometry assessed U87 cell apoptosis rates. ELISA detected cellular inflammatory factor levels. In vivo experiments further evaluated IMQ's impact on U87 cell growth. Findings suggest that IMQ suppresses U87 cell growth and movement, inhibits STAT-3 and NF-κB phosphorylation and accelerates apoptosis. ELISA assays indicated that IMQ reduced local inflammation. Adding a STAT-3 inhibitor yielded similar effects to IMQ, altering cell proliferation, migration and apoptosis. Overall, IMQ appears to inhibit U87 cell proliferation and migration, inducing programmed cell death through STAT-3 modulation.

Chronic wounds are a common and difficult problem in clinics. It is of great significance to develop effective and economical methods to treat chronic wounds. The present study aimed to investigate the effects of liposomal gel loaded with Pro-xylane intermediate on chronic wounds. Rat models of chronic wounds were created and verified. The pro-xylane intermediate (C-β-D-xylopyranoside-n-propan-2-one, PXYI) were encapsulated with liposomes and the liposomes containing PXYI were mixed with Pluronic F-127 gel to obtain PXYI liposomal gel (PXYI-LG). PXYI-LG has been applied to the rat's chronic wounds. The therapeutic effects were evaluated by wound healing rate and wound healing time. Additionally, Alamar Blue was used to detect the effect of PXYI on the proliferation of human skin fibroblasts (HF) and human immortalized epidermal cells (HaCaT). It was not found that PXYI alone could promote the proliferation of HF and HaCaT. From the 12^th to the 32^nd day, the wound healing rate of PXYI-LG group were significantly higher than that of the normal saline (NS) group (P <0.05). The number of days when the wound healing rate reached 90% was significantly shorter in the PXYI-LG group (21.8 ±1.8) than in the NS group (28.4 ±1.6) (P < 0.01). In summary, the results demonstrate that the PXYI-LG can promote chronic wound healing.

Ligusticum chuanxiong Hort (CR) is the dried rhizome of Ligusticum belongs to the Umbelliferae family. The present study aimed to assess the antidiarrheal effects of ethanol extracts of CR (CR ext.). The mice were administered castor oil to induce diarrhea and the antidiarrheal effects of CR ext (250, 500 and 1000mg/kg) were assessed in vivo. The potential effect of CR ext (0.01-10 mg/mL) was examined on isolated rabbit jejunum smooth muscle in vitro. CR ext exhibited antidiarrheal effects at a dose ranging from 500 to 1000 mg/kg (P <0.01). CR ext (0.01-10 mg/mL) relaxed the smooth muscles in a dose-dependent manner and its median effective concentration (EC₅₀) was 0.55 mg/mL (0.46-0.67, n = 6) (P<0.05; P <0.01). It alleviated jejunal contraction induced by ACh/K+ (60 mM) and EC₅₀ values were 0.35 mg/mL (0.34-0.37) and 0.11 mg/mL (0.10-0.12), respectively. Similar to the effect of verapamil, CR ext shifted the concentration-response curve of CaCl₂ downward to the right. The CR ext exhibits a notable antidiarrheal effect and can inhibit intestinal contraction. This mechanism of action may be based on its ability to inhibit Ca²⁺ channels.

Dengue is an important arboviral infection worldwide for which presently there is no specific medicine. Evidence suggests there are four serotypes of dengue virus (DENV1-4), of which DENV 2 is considered to cause the most sever dengue. Therefore, this study was aimed to develop the new uridine derivatives (NUDs) against dengue virus (DENV 2). In current study 2-(3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-4-((substituted cyclohexa-2,5-dienylidene)methyl)-1,2,4-triazine-3,5(2H,4H)-dione (2a-f), were obtained via reaction of substituted uridine (1) and different aromatic aldehydes separately. Synthesized NUDs were further characterized using FTIR, 1H & 13C-NMR, mass and element analysis data. Characterized NUDs were assessed for their inhibition potential against DENV 2. Synthesized NUDs were also evaluated for their cytotoxicity towards Vero cells by MTT assay method. This investigation successfully synthesized NUDs 2a-f and reported their high inhibitory activity against DENV 2. The synthesized NUDs exhibited negligible cytotoxicity. High anti-viral activity against DENV 2 serotype and least/no cytotoxicity of NUDs suggests their importance in the treatment of dengue. Present study recommends that in future these NUDs must be investigated for their clinical importance to establish them as a choice for dengue treatment.

Bombax ceiba, an ethnomedically useful plant belonging to the Bombacaceae family, is traditionally used to treat various ailments. With the increase of interest in herbal remedies globally, it is imperative to scientifically validate the phytochemical profiling to ensure therapeutic utility and safety. The present study was designed to comprehensively analyze the phytochemical composition of Bombax ceiba seeds oil to provide evidence for its medicinal uses. The recommended standard Soxhlet extraction method was used to isolate the oil from the seeds. Its chemical profile, physicochemical parameters and antioxidant potential were characterized. The GC-MS analysis revealed the presence of 31 diverse phytoconstituents including vital terpenoids, ketones, esters, alcohols, aliphatic acids, and other compounds in minor quantities which are known to possess wide pharmaceutical applications. The key unsaturated fatty acids identified with nutritional and therapeutic benefits were oleic, linoleic, palmitoleic, arachidonic and docosahexaenoic acids. The high iodine value of 67.832g I/100g indicates a high degree of unsaturation. Although the DPPH assay showed minimal antioxidant activity, the myriad of bioactive components confers significant pharmacological utility to Bombax ceiba seeds oil. By providing in-depth phytochemical insights, this research work validates this oil's traditional and other medicinal uses, which can be further explored for newer ethnomedicine development.

The present work aimed to use the methanol extracts of Croton bonplandianus (Cb) and Tithonia diversifolia (Td) and the synergistic activity of Croton bonplandianus and Tithonia diversifolia (CbTd) for the phytochemical screening, anti-microbial, anti-oxidant and anti-inflammatory activities. Phytochemical screening was done by the standard protocols. In vitro antimicrobial, antioxidant and anti-inflammation, were assayed by using disc diffusion, total antioxidant activity, DPPH method, HRBC (human red blood cells) membrane stabilization and anti-protein denaturation tests. The synergistic approach of the two plants showed potent antimicrobial, antioxidant and anti-inflammation activity. In vitro antibacterial activity was done against Pseudomonas aeroginosa, Escherichia coli, Bacillus subtilis and Staphylococcus aureus at different concentrations. The maximum zone of inhibition (21 mm) was observed in the combinatorial approach. The maximum inhibition of free radicals is observed in CbTd with a low IC₅₀, i.e., 7.64 mg/ml, followed by Cb with an IC₅₀ value of 11.8mg/ml and Td with an IC₅₀ of 28.3 mg/ml. The percentage inhibition of hemolysis and protein denaturation is high in CbTd (93% and 69%). The experimental analysis reveals the effectiveness of the synergistic effect of these plants with anti-microbial, anti-oxidant and anti-inflammatory activity, further it can be used in the formulations against infectious human pathogens.

Artemisia absinthium, renowned for its medicinal properties, boasts a wealth of biologically active compounds, rendering it indispensable for extracting chemicals from its aerial parts using Soxhlet extraction. Through diverse chromatography methods, fractions Ia and IIb were isolated, revealing numerous phenolics. XTT tests on cell cultures demonstrated that MCF-7 cancer cells treated with fatty acids exhibited significantly lower survival rates than the control group, with IC50 values of 43.24 and 347.2, respectively. Fraction Ia exhibited dose-dependent effects on cell viability, inhibiting MCF7 breast cancer cell proliferation by 76.4%, 67.08% and 48.98% at doses of 5, 10 and 20µg/mL, respectively, while exerting minimal impact on the healthy cell line WI38, with percentages of 97.82%, 95.49% and 91.52%, respectively. Similarly, fraction IIb significantly impeded MCF7 cell growth at doses of 5, 10 and 20µg/mL, with percentages of 66.12%, 47.05% and 33.26%, respectively, yet demonstrated negligible effects on WI38 cells, with percentages of 98.80%, 96.73% and 95.55%, respectively. Notably, fraction IIb exhibited selective toxicity towards breast cancer cells, indicating the potential of A. absinthium plant extracts in breast cancer treatment.