Pharmaceutical Sciences
Volume:30 Issue: 1, Jan 2024

In recent years, the incidence of cancers, inflammatory diseases, Alzheimer’s disease, glucose metabolism disorder and diabetes has increased alarmingly which demands more research into the discovery of new drug candidates to treat these human diseases. Main phytochemicals from Humulus lupulus L. (hops) have been demonstrated to have positive impacts on human health, and prenylated flavonoids are one of the major groups of bioactive phytochemicals found in this plant. Thus, this review summarizes the role of major prenylated components in hops in human diseases including cancer, inflammation and viral infections. In silico studies of prenylated bioactive compounds against various drug targets such as histone deactylases (HDACs), sirtuins (SIRTs), and acetylcholinesterase (AChE), and the molecular molecular interactions between protein and ligand have also been included. Furthermore, the structure-activity relationships (SAR) studies on these compounds are highlighted. This review concludes that the prenylated phytochemicals from H. lupulus L., including xanthohumol (XN), isoxanthohumol (IXN), 8-prenylnaringenin (8-PN) and 6-prenylnaringenin (6-PN), have promising roles in human health and may contribute to new drug discovery and development.

Phlomoides (L.) Moench belongs to the Lamiaceae family. It has recently undergone significant changes in taxonomy, with many species from Eremostachys and Phlomis added to the genus. The aforementioned species were studied in terms of morphological and phytochemical systematics. Species of Phlomoides are distinguished from Phlomis by their densely bearded upper corolla lip and nutlet. However, Eremostachys and Phlomoides have a lot in common morphologically. Plant chemosystematics present iridoids, phenylethanoids, and furanolabdanes as dominant constituents of Phlomoides species. Long-term traditional uses, such as bone fracture therapy, local analgesic, and wound healing actions, pique researchers' interest in these plants. The species and their secondary metabolites have been implicated in drug discovery by their anti-inflammatory and bone-development properties in vitro, in vivo, and clinically. A review of the taxonomic status based on phytochemical and morphological characteristics, as well as the clinical importance of the Phlomoides genus, is presented in the current study to provide a basis for further investigations.

Cadmium (Cd) is a toxic heavy metal that is known to accumulate in various organs and tissues in the body, including the testes. Exposure to Cd has been shown to cause significant testicular damage, including impaired spermatogenesis and decreased fertility in both humans and animals. This damage is thought to be due to Cd-induced oxidative stress and inflammation, which can lead to cellular damage and apoptosis. Cd has also been shown to disrupt the blood-testis barrier, leading to increased permeability and an altered testicular microenvironment. In addition, Cd exposure has been linked to changes in hormone levels, including decreased testosterone production and altered gonadotropin secretion. Reactive oxygen species (ROS) and an imbalance in the activity of antioxidant enzymes cause oxidative stress. The nuclear factor kappa-B (NF-κB) signaling system, which controls multiple genes involved in inflammatory responses including tumor necrosis factor (TNF-α), is activated by oxidative stress. These effects can contribute to decreased sperm count, motility, and viability. Efforts to reduce exposure to Cd may help to prevent or mitigate the harmful effects on testicular function. This can be achieved through occupational and environmental regulations, as well as public education and awareness programs. In this review, we highlight many of the principal mechanisms included in testicular damage. These pathways could be considered promising targets for the development of potential therapies for a variety of important human diseases.

Hirsutism is characterized by the excessive growth of coarse hair in women, resembling the typical pattern seen in men. It affects between 5 to 10 % of females of reproductive age. Excessive hair growth often leads to significant mental and emotional anguish. Hirsutism is the result of an overabundance of androgens being secreted by the ovaries or adrenal glands. This article offers a comprehensive review of numerous causes that might provoke hirsutism which includes polycystic ovarian syndrome, Cushing syndrome, idiopathic hirsutism, insulin resistance, congenital adrenal hyperplasia, ovarian or adrenal tumors, menopause, and the use of certain drugs. Polycystic ovary syndrome and ovarian tumors are frequent underlying factors of hyperandrogenism, which subsequently results in the development of Hirsutism. Mechanical and cosmetic hair removal methods are viable options for managing hirsutism. This study examines the pharmacological therapies that have proven essential in enhancing the quality of life for patients. These treatments include oral contraceptives, antiandrogen therapy like spironolactone, cyproterone acetate, flutamide, and finasteride, specific insulin-lowering medicines, gonadotrophin-releasing hormone agonists, and topical treatment such eflornithine hydrochloride cream (13.9% w/w cream). This review also explored significance of nanotechnology-based methods like nanostructured lipid carriers, solid lipid nanoparticles, liposomes, cerosomes, and nanogel in enhancing the effectiveness of medications used to treat hirsutism. A comprehensive update has been made to the latest information on clinical studies and patents linked to the treatment of hirsutism.

 The purpose of the current work was to manufacture vitamin A (Vit A) niosome and solid lipid nanoparticle (SLN) using an ultrasonic approach and to evaluate its effect on wound healing.

 The nanoparticles were prepared through an ultrasonication technique and characterized by dynamic light scattering (DLS), and transmission electron microscopy (TEM). Further, the nanoparticles were evaluated for their various parameters such as pH, viscosity, spreadability, stability, in-vitro drug release study, in-vitro cytotoxicity, and in-vivo wound healing.

 TEM confirmed the spherical nature of the Vit A-niosome and SLN. The Vit A formulations (niosome and SLN) were stable in the accelerated stability test (freeze-thaw cycle). Vit A release from the SLN gel and niosome gel was significantly higher (almost 70 and 80%, respectively) than simple Vit A gel. According to the animal study, the wound healing closure in the Vit A niosomal gel and Vit A SLN gel was greater than the other groups during the 21 days after surgery (P < 0.05) and was close to each other over time and on day 21. Based on histological data, wounds treated with Vit A niosome gel and Vit A-SLN gel had more collagen than the other groups. MDA malondialdehyde (MDA, an end-product of lipid peroxidation) significantly decreased in the Vit A-niosome and Vit A-SLN gel group after 21 days, while glutathione peroxidase (GPx), superoxide dismutase (SOD, an endogenous antioxidant), and hydroxyproline levels demonstrated an increase.

 The findings of this study revealed that the prepared Vit A nano-formulations could be used as a possible and safe nano-vesicle for Vit A cutaneous delivery thus potentially opening up new prospects for the treatment of wound disorders.

 The ability of cancer cells to develop multidrug resistance (MDR) is a major challenge in modern chemotherapy. The current generation of commercially available paclitaxel formulations have not been designed to treat resistant tumours. In this study, a nanoemulsion-based delivery system was developed to enhance the efficacy of paclitaxel against resistant breast cancer cells.

 The nanoemulsion was formulated using carvacrol-rich Satureja khuzestanica essential oil. Modification of nanoemulsion was performed by incorporating tocopheryl polyethylene glycol 1000 succinate (TPGS) which could inhibit drug resistance in cancer cells. Fabrication of paclitaxel nanoemulsion was performed by high speed homogenization. The cytotoxicity of prepared formulation against resistant breast cancer cells was investigated by MTT assay. Flow cytometry technique was used for cell cycle arrest analysis and examination of the apoptosis induction ability of prepared nanoemulsion.

 The nanoemulsion had a relatively small mean droplet diameter (93.6 ± 4.2 nm) and good long-term stability. The ability of paclitaxel to inhibit P-gp function in paclitaxel-resistant breast cancer cells (MCF-7/PTX) was synergistically enhanced by administering it within the nanoemulsion. The cytotoxicity of the prepared nanoemulsion on the HUVEC normal cells was much lower than that of MCF-7/PTX cells. Cell cycle analysis utilizing flow cytometry showed that the paclitaxel-loaded nanoemulsion promoted G2-M arrest. Flow cytometry also demonstrated that this nanoemulsion induced apoptosis in MCF-7/PTX cells. Interestingly, apoptosis increased from 20.0% for the free paclitaxel treated group to 85.2 % for the paclitaxel-loaded nanoemulsion treated group.

 This novel paclitaxel nanoemulsion efficiently suppressed the drug resistance of breast cancer cells and induced effective apoptosis in very low concentrations of paclitaxel.

 Tea leaves contain remarkable antioxidant compounds suitable for cosmetics formulation development targeting anti-aging purposes. However, due to its hydrophilicity, it faced the main hurdle, namely the permeation of the potential antioxidant compounds. Nanoemulsion formulation offers the permeation improvement of water-soluble compounds Therefore, this work purposed to formulate and develop the nanoemulsion formulation containing tea leaf extract incorporated into a peel-off mask formulation and an ex-vivo transport study.

 The nanoemulsion formulation was developed according to self-nano emulsification. The optimization process was performed using a design of experiment to define optimized formulation based on quality target product profiles. Dried green tea leaf extract (DGTE) was obtained by lyophilizing the boiled water-based extract. Antioxidant and phenolic content assays were also evaluated. The optimized formulation was incorporated into a hydrogel-based peel-off mask formulation. Permeated polyphenol through a rat skin membrane was carried out along with deposited polyphenols in the skin membrane.

 The results indicated that DGTE had powerful antioxidants with IC50 less than 15 mg/mL. The optimized nanoemulsion comprised 21.62% virgin coconut oil, 48.38% Tween 80, and 30% PEG 400, producing a droplet size of less than 50 nm. The peel-off formulation was successfully formulated along with PVA 10-11% and HPMC 0.25-1% with a drying time of around 30 min. The nanoemulgel peel-off mask formulation played significant roles in enhancing the permeation and deposition in the percutaneous transport using rat skin membrane for roughly 200% and 50%, respectively.

 The nanoemulsion incorporated into a hydrogel-based peel-off mask enhanced the permeation of DGTE polyphenol compounds.

 There is only limited data for solubility of codeine phosphate in binary systems available, which comes with uncertainties about the prediction accuracy of common thermodynamic models.

 This study investigated the codeine phosphate dissolution in N-methyl-2-pyrrolidone(NMP) and ethanol system using shake-flask method and mathematically described generated data by different thermodynamic models. The density as another property was also determined and fitted to the results of the Jouyban-Acree equation. The mean relative deviations were obtained to confirm the model’s accuracy. Moreover, ΔHº, ΔSº, and ΔGº of the dissolution of codeine phosphate in the NMP and ethanol system were calculated using the desired equations at Thm.

 The dissolution process of codeine phosphate was identified as endotherm, the solubility in the binary mixtures was best at higher mass fractions of NMP and finally, the model predictions were deemed as excellent based on a mean relative deviation that was generally below eight percent.

 The results of this study could expand the available solubility database for codeine phosphate.

 Emerging evidence suggests that epigenetic mechanisms contribute to 5-fluorouracil (5-FU) resistance in colorectal cancer (CRC). However, there is limited research on the direct impact of 5-FU on epigenetic alterations in CRC. This study aimed to investigate how 5-FU treatment affects the expression of enzymes involved in epigenome regulation and promoter DNA methylation in human CRC cells.

 The viability of CRC cell lines (SW48, HCT116, LS180, and HT29) was evaluated after 48 hours of 5-FU treatment using MTT assay in both monolayer and hanging drop spheroid cultures. The cells were treated with an IC20 concentration of 5-FU and then the relative expressions of histone deacetylases (HDAC) and DNA methyltransferas1 (DNMT1) in 5-FU-treated and untreated cells were measured by quantitative RT-PCR (qRT-PCR). The status of promoter methylation of selected genes was analyzed using the methylation-specific PCR (MSP) method.

 The 3D cultures of cells were more resistant to 5-FU than their 2D counterparts. The effect of 5-FU on HDAC1 expression was greater in 3D cultures compared to 2D cultures. 5-FU downregulated SIRT1 and DNMT1 in 2D culture of HCT116 and SW48 and upregulated them in 3D cultures of HT29 and LS180 cells. In both monolayer and spheroid cultures, 5-FU downregulated HDAC2 in HCT116, LS180, and HT29 and HDAC4 in HCT116, LS180, and SW48 cells. 5-FU primarily changed promoter methylation in monolayer cultures.

 The epigenetic response to 5-FU is cell line-specific and depends on the culture method. 5-FU modulates epigenome in CRC cells by regulating DNMT1 and HDAC expressions. 3D cultures were found to be considerably more resistant to 5-FU-induced cytotoxicity and promoter DNA methylation changes than 2D cultures. 5-FU downregulated HDAC and DNMT1, particularly in the drug-sensitive cells, and increased the levels of DNMT1 in the drug-resistant cells.

Periprocedural myocardial injury (PMI) after percutaneous coronary intervention (PCI) is a substantial health issue with a high mortality rate. Inflammation and oxidative stress are major contributing factors to PMI. Allopurinol inhibits xanthine oxidase (XO)-induced oxidative stress and has potential cardiovascular benefits.

This randomized clinical trial evaluated 110 patients admitted to elective PCI. Patients were assigned to receive either a 1200 mg loading dose of allopurinol 2 hours before the procedure (n = 55) or the standard pretreatment (n = 55). The creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) levels were measured in both groups at the baseline, 8, and 24 hours after PCI.

There were no significant differences in the CK-MB levels at baseline (P = 0.71), 8 (P = 0.26), and 24 hours (P = 0.88) after PCI between the two groups. No significant changes in the cTnI levels at baseline (P = 0.26), 8 (P = 0.80), and 24 hours (P = 0.89) after the PCI were also noted. The mean difference for CK-MB and cTnI changes was not different between the two groups.

Our study revealed that allopurinol did not reduce cardiac-specific enzymes. Further studies are required to evaluate the impact of allopurinol on preventing PCI-related myocardial injury.

Acute Myeloid Leukemia (AML) is the most common form of acute leukemia among adults. Treatment of acute leukemia has been divided into induction chemotherapy and post-remission therapy. The goal of induction chemotherapy, that consists of anthracycline and cytarabine, is to achieve morphologic complete remission (CR), but the main problem is that it has a high economic burden. Idarubicin is the anthracycline of choice used in AML, while doxorubicin, is mainly used in other types of cancer. The aims of this study were evaluating the use of doxorubicin versus idarubicin in the induction phase for the treatment of AML and analysis the impact of the adoption of this anthracycline in Egypt’s public health system.

A randomized controlled trial was undertaken in 244 patients with AML. A decision tree was developed based on the clinical outcome of the study, safety and efficacy, aiming to get the expected cost of doxorubicin compared with idarubicin in AML management.

In the doxorubicin group, 52.5% had a CR, versus 49.2 % in the idarubicin group (P=0.6). The most common toxicities among the 2 groups were febrile neutropenia, diarrhea and vomiting. Oral mucositis (OM) was higher in the doxorubicin group (70.8% vs 37%, P=0.0001), while invasive fungal infections were greater in the idarubicin group (75% vs 88.7%, P=0.004). Doxorubicin arm had a lower cost than idarubicin arm in treatment success group (39,492 LE vs 44,323 LE).

Doxorubicin provides a treatment option with comparable efficacy, toxicity profile and survival rates at a lower cost compared to the traditional treatment, idarubicin.