Pharmaceutical Sciences
Volume:29 Issue: 3, Jul 2023

Wound healing is a complicated, organised process that includes numerous phases that connect diverse cellular events and activate several intracellular molecular pathways in injured cells and tissues. Delay in wound healing owing to high levels of oxidative stress is a major difficulty in various metabolic illnesses, including diabetes mellitus. Several therapeutic wound dressing materials and methods, such as hyperbaric oxygen treatment and negative pressure wound therapy, have been developed to speed up wound healing and restore cellular homeostasis. A significant advance has been made in locating transcriptional regulators involved in wound healing. The redox-sensitive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is the major regulator of antioxidant defence regulation, inducing the expression of cytoprotective genes and increasing the generation of antioxidants that scavenge free radicals. Activators of Nrf2 have been shown to reduce oxidative stress and improve wound healing in a variety of pathophysiological situations, including diabetes and its consequences such as diabetic foot ulcers, chronic kidney disease, and diabetic nephropathy. Several therapeutic chemicals have been discovered to alleviate oxidative stress and consequently increase cell proliferation. Angiogenesis results in tissue healing through activating the transcription factor Nrf2. This review focuses on the role of Nrf2-mediated antioxidant gene expression in diabetic wound healing.

The overcomplicated and elusive pathophysiology with unclear etiology, have been the main driving force of the medical scientists all over the world to develop a predictive, reliable, robust and reproducible simulation model of arthritis. This review highlights osteoarthritis and rheumatoid arthritis with distinct conditions pertaining to each type of disease. The advances in various in vitro and in vivo experimental models of osteoarthritis and rheumatoid arthritis have been presented along with their pros and cons for antiarthritic drug discovery and formulation development. Additionally, the ethical issues to be considered while selecting animal models and handling them have been covered briefly. The current status quo on clinical trials of antiarthritic therapeutic interventions has also been covered.

3D printing is a novel approach in the pharmaceutical field, but its usage has not been fully established. This method can promote drug therapy and overcome some traditional treatment challenges in different ways that are discussed in this paper. “One-size-fits-all”, Large-scale production, and less patient and physician acceptability are some limitations that we will encounter in traditional therapy. Three-dimensional printing of pharmaceutical products is a versatile technology that needs specific attention. Droplet-based, extrusion-based, and laser-assisted 3D printers are three main techniques that can be used in this field. The limitations and advantages of this method have been discussed, highlighting potential innovative pathways towards the possibility of drug carriers’ usage in ink formulas. The administration pathway of drug-loaded composites is another critical issue in drug treatment strategies that have been discussed here. Oral drug delivery as a convenient method of systemic drug administration with significant patient preference is introduced as the most prevalent pathway that has been studied about 3D printed medicines. Finally, essential ethics and future directions of 3D printing in the pharmaceutical and healthcare industries are outlined.

Phytopharmaceuticals or herbal drugs have a significant therapeutic impact on healthcare systems. Though herbal extracts and their active constituents show excellent pharmacological in vitro effects, they still have indigent in vivo biological effects because of their considerable molecular weight and low lipid solubility, leading to low systemic availability. Phytosome is a novel approach for overcoming the drawbacks of conventional delivery methods of herbal actives. The phospholipids, mainly phosphatidylcholine, form a bond with herbal extracts or actives, forming a herb-lipid complex. The encapsulation of herbal actives with phospholipid allows an effective tool for the delivery to the affected area with enhanced pharmacological effect. Moreover, the amphiphilic nature of the phospholipid provides a good hydrophilic-lipophilic balance, thereby improving a better dissolution profile in the lipid-rich membranes of the gastrointestinal tract. This review focuses on the various phytosome nanocarriers to improve herbal medication bioavailability and uptake—recent trends in their industrial applicability, and applications in clinical management for various diseases, including other challenges.

The development of multidrug resistance (MDR) is a major barrier to achieving effective chemotherapy in cancer. Studies have shown that epithelial ovarian cancer initially responds to platinum-based therapy, however, the recurrent type is often resistant to treatment and is associated with high mortality. Fucoxanthin, a natural component found in marine algae, possesses various pharmacologic properties. This study evaluated the cytotoxicity and resistance reversal activity of fucoxanthin on multidrug resistance-associated protein 2 (MRP2)- overexpressing, cisplatin-resistant ovarian cancer cells (A2780RCIS) and their parental cells (A2780).

Cell viability was evaluated in the presence of different concentrations of fucoxanthin or cisplatin or fucoxanthin/cisplatin combination using the MTT assay. Propidium iodide staining and subG1 analysis were used to evaluate fucoxanthin potential for cell cycle modification and apoptosis induction in cancer cell lines.

The results showed that fucoxanthin was able to cause similar toxicity in both cell lines via apoptosis induction. Co-treatment of cells with cisplatin (3.125 to 100 µM) and nontoxic concentrations of fucoxanthin (1 and 2.5 µM) did not reverse resistance to cisplatin in A2780RCIS cells.

Although fucoxanthin was not able to modify cisplatin resistance in ovarian cancer cells, it was equally effective in inducing apoptosis and death in both A2780 and A2780RCIS cells, indicating it is not an MRP2 substrate.

 MicroRNAs (miRNAs) can play essential roles in the modulation of cancer cell growth, survival, and resistance to chemotherapy. Thus, we hypothesized that restoration of miR-451a-5p (a tumor suppressor) might affect sensitivity to chemotherapeutics in breast cancer cells.

 For this purpose, malignant breast cancer cells (MDA-MB-231) were transfected with miR-451a-5p mimic and exposed with carboplatin. Then, the apoptotic rate was evaluated by flow cytometry and DAPI staining (apoptosis), q-RT-PCR (expression levels of caspase-3, caspase-8, MMP9, ROCK, vimentin, c-Myc genes). Moreover, the proliferation and migration of cancer cells were assessed by MTT (cell viability) and wound healing assay. The western blot assay was used for protein expression of PTEN, AKT, and P-AKT.

 Our findings demonstrated that a combination of miR-451a-5p restoration with carboplatin administration could additionally induce apoptosis, repress the proliferation and migration, and also increase PTEN protein expression with no significant alteration on the AKT/P-AKT protein expressions in the breast cancer cells. The present data was analyzed using GraphPad Prism 6 software by non-parametric one-way ANOVA and t-test.

 In conclusion, it seems that overexpression of miR-451a can enhance the chemosensitivity of breast cancer cells to carboplatin therapy. Thus, it may shed new light on miR-451a management of breast cancer chemoresistance and may be a beneficial strategy for future cancer therapy. However, further studies, particularly in other signaling pathways, should be required.

 Osteoarthritis (OA) is the most common disease of joints. The management of OA is challenging due to the efficacy and safety of treatments. In recent decades, traditional herbal medicines have been introduced for treatment of disease. Delphinium denudatum Wall. (Jadwar) is a medicinal herb with a long-lasting usage in traditional Persian medicine for joint diseases. The present study aimed to investigate the effect of Jadwar on pain and symptoms of knee OA.

 In this randomized double-blind placebo-controlled trial, 104 patients with knee OA were randomly assigned into two groups of intervention and control. While the intervention group received one Jadwar capsule (500 mg) twice a day for four weeks, the control group received placebo capsules. The primary outcomes, including pain, stiffness, and physical activity were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire and the Visual Analogue Scale (VAS) at baseline two and four weeks after the intervention.

 Ninety-four participants completed the study. Considering the time of interaction, after four weeks, data analysis revealed a significant decrease in the VAS score (37.23±12.58 vs. 57.87±13.21), total WOMAC score (24.83±9.70 vs. 49.17±12.89), WOMAC pain score (7.19±2.90 vs. 12.40±4.46), stiffness (2.06± 0.845 vs. 4.11±1.14), and physical function (15.57±7.25 vs. 32.66±9.78) in the intervention group compared to the control group (P<0.0001 for all outcomes). Additionally, no serious adverse effects were reported.

 Jadwar can be suggested as a safe medicinal plant for knee OA because it can relieve the pain and symptoms of OA.

 Type 2 diabetes mellitus (T2DM) is a prevalent disease with metabolic consequences. Lower levels of adiponectin and higher levels of leptin were reported in T2DM. This study aimed to evaluate the effect of menaquinone-7 (MK-7) supplementation on adiponectin and leptin in overweight/obese T2DM patients.

 Sixty men and women with T2DM and 27 ≤ body mass index < 35 kg/m2 , participated in this double-blind placebo-controlled randomized clinical trial for 12 weeks. The subjects were allocated into intervention (200 µg/day MK-7) or placebo groups. Three-day food records, anthropometrics and physical activity were assessed and fasting blood samples were collected at the pre- and post-intervention. Serum adiponectin, leptin, fasting blood sugar (FBS) and fasting insulin (FI) were measured and adiponectin to leptin ratio (A/L ratio) was calculated.

 MK-7 decreased fasting blood sugar (P: 0.018) and fasting insulin (P: 0.012), according to a within group analysis of the 45 patients who finished the research. Fasting blood sugar (P: 0.024) and leptin levels (P: 0.032) were lower in the MK-7 group, but there were no significant changes between the groups in terms of adiponectin or the adiponectin to leptin (A/L) ratio.

 Current study showed that MK-7 supplementation could lead to significant reduction in leptin and FBS, but it has no effect on the adiponectin and A/L ratio in overweight/ obese T2DM patients.

 We assessed the potential efficacy of Coenzyme Q10 (CoQ10) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).

 Seventy STEMI patients who presented ≤12 hours after the onset of symptoms and were scheduled for PPCI were randomly assigned to the standard treatments plus CoQ10 or placebo. In the intervention group, CoQ10, as an oral capsule at a dose of 400 mg, was loaded immediately before PPCI and continued at 200 mg twice daily for 28 days. The control group received a matching placebo, similarly. The study endpoints were the proportion of patients with complete myocardial reperfusion, defined as thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade (MBG) 3 at the end of PPCI, the proportion of patients with complete ST-segment elevation resolution (≥70%) assessed 60 minutes after PPCI, the plasma levels of creatine kinase myocardial band isoenzyme (CK-MB) and troponin I (TnI) at 12, 24, 48, and 72 hours after PPCI, and left ventricular ejection fraction (LVEF) at day 28.

 The study groups were comparable regarding baseline clinical and procedural characteristics. The proportion of patients with TIMI flow grade 3, MBG 3, and complete ST resolution after completion of PPCI was similar between the groups. Whereas at all-time points after PPCI (12, 24, 48, and 72 hours), the plasma levels of CK-MB and TnI were significantly lower in the CoQ10 group than in the control group. Further, at day 28, CoQ10-treated patients exhibited better LVEF than placebo-treated patients, and the proportion of patients with LVEF less than 50% was lower in the intervention group than in the control group.

 Our study provided evidence that CoQ10 supplementation might reduce myocardial ischemia-reperfusion injury after PPCI and help to preserve left ventricular function. However, further studies are required to validate these results.

 According to the poison center data for most countries, more than thousands of people’s exposure to aspirin or salicylate-containing products. So, this work aimed was to offer a rapid colorimetric method for monitoring aspirin concentration in exhaled breath condensate (EBC).

 A method based on a redox reaction catalyzed by nanoparticles was validated for the analysis of aspirin. 3,3 ,5,5 –Tetramethyl benzidine /H2 O2 and sodium dodecyl sulfate modified silver nanoparticles were used as the redox reagents and catalyst, respectively.

 Detection mechanism of aspirin using this system is based on the inhibitory effect of aspirin on the signal intensity of the colorimetric systems. Since the decrement in signal intensity was proportional to aspirin level, a colorimetric method was proposed for its quantification in EBC samples. This method shows a linear relationship with aspirin concentration in the range of 10‒250 mg.L−1 with a relative standard deviation of < 3.5%.

 This method has great potential for aspirin determination due to some features such as high reliability, and fast response time.

 Minoxidil is an antihypertensive agent and vasodilator which may help to promote local blood flow thus hastening the closure of excisional skin wounds. Corticosteroids may down-regulate wound healing. This work aims to develop and characterize nanofiber-eluting dexamethasone and minoxidil and investigate their effect on wound healing in a rat model.

 Minoxidil and dexamethasone-loaded wound dressings were developed and characterized with scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). In vitro, drug release studies were performed for 12 days. To model the wound-healing activity of the developed formulations, excisional wounds were created on the dorsal section of male rats.

 All the electrospun wound dressing nanofibers displayed smooth structures and surfaces without drug crystals. Histological results of Hematoxylin & Eosin and Masson’s trichrome staining indicate wound healing suppression in the dexamethasone-treated group and good healing activity in the minoxidil-treated group. Here we identified that the application of topical minoxidil can be effective for wound healing probably driven by the anagen hair growth while dexamethasone suppresses collagen production and prevents scar formation.

 The findings suggest that this minoxidil and dexamethasone wound dressing can potentially be developed as a new treatment modality in the clinic to accelerate wound healing while preventing scar formation.

 Screening medicinal plants for their biological activities and phytochemicals is important for finding safe and potent new compounds for therapeutic use. The current investigation was conducted in extracts of Lebanese A. squamosa (leaves and bark) to evaluate the antioxidant, anticancer, and anti-inflammatory activities.

 Seven extracts were prepared by ultrasound-assisted extraction (UAE) or microwave-assisted extraction (MAE), and using various solvents. The evaluation of antioxidant activity was done using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the anticancer activity assessed on the colon cancer HCT116 cell line was determined by water-soluble tetrazolium-1 (WST-1) viability assay. Finally, the anti-inflammatory activity was investigated by measuring the secreted amounts of prostaglandin E2 (PGE2) and interleukin 6 (IL-6) using.

 The total phenolic contents were in the range between 27.3 to 179.5 mg GAE/g of plant extract, while total flavonoid contents were between 8.3 to 150.8 mg RE/g of plant extract. DPPH assay showed high antioxidant activity for the methanolic extracts obtained by UAE in both natural dried leaves and bark with IC50 values of 9.3 and 12.6 μg.mL-1, respectively. For WST-1 assay, methanolic extracts obtained by UAE showed a potent anti-proliferative effect against the HCT116 cell line with IC50 values ranged from 0.18 to 0.88 μg.mL-1. Also, the western blot assay suggested that these extracts may inhibit the proliferation of the HCT 116 cell line by causing cell cycle arrest through activation of the p21 pathway. Significant anti-inflammatory activity was observed due to the decrease in the secretion of IL-6 in lipopolysaccharide (LPS)-stimulated THP-1 cells.

 Therefore, the present study revealed that the dried leaves and bark of Lebanese A. squamosa methanolic extracts obtained by UAE possess effective bioactivities, and thus hold the potential application in the pharmacological field.