Current Pharmaceutical Design - Volume 29, Issue 43, 2023

Polyphenols and flavonoids, naturally occurring compounds found abundantly in plants, have gained considerable attention in recent years due to their potential health benefits. Research exploring their bioactive properties has revealed promising therapeutic applications in various diseases. This article aims to provide a comprehensive overview of the intricate journey from academic laboratory discoveries to the availability of polyphenols and flavonoids as drugs on pharmacy shelves. It was shown that the transformation of these natural compounds into effective therapies is a promising avenue for enhancing human health. Yet, fully realizing this potential necessitates sustained scientific exploration, cross-disciplinary collaboration, and continued investment in research and development. This article underscores the importance of sustained collaboration and investment as key pillars of progress towards innovative and effective therapies

Aim: Alzheimer’s disease (AD) has been identified as a progressive brain disorder associated with memory dysfunction and the accumulation of β-amyloid plaques and neurofibrillary tangles of Τ protein. Mitochondria is crucial in maintaining cell survival, cell death, calcium regulation, and ATP synthesis. Mitochondrial dysfunction and linked calcium overload have been involved in the pathogenesis of AD. CRM2 (Collapsin response mediator protein-2) is involved in endosomal lysosomal trafficking as well as autophagy, and their reduced level is also a primary culprit in the progression of AD. In addition, Cholinergic neurotransmission and neuroinflammation are two other mechanisms implicated in AD onset and might be protective targets to attenuate disease progression. The microbiota-gut-brain axis (MGBA) is another crucial target for AD treatment. Crosstalk between gut microbiota and brain mutually benefitted each other, dysbiosis in gut microbiota affects the brain functions and leads to AD progression with increased AD-causing biomarkers. Despite the complexity of AD, treatment is only limited to symptomatic management. Therefore, there is an urgent demand for novel therapeutics that target associated pathways responsible for AD pathology. This review explores the role of different mechanisms involved in AD and possible therapeutic targets to protect against disease progression.Background: Amidst various age-related diseases, AD is the most deleterious neurodegenerative disorder that affects more than 24 million people globally. Every year, approximately 7.7 million new cases of dementia have been reported. However, to date, no novel disease-modifying therapies are available to treat AD.Objective: The aim of writing this review is to highlight the role of key biomarker proteins and possible therapeutic interventions that could play a crucial role in mitigating the ongoing prognosis of Alzheimer’s disease.Materials and Methods: The available information about the disease was collected through multiple search engines, including PubMed, Science Direct, Clinical Trials, and Google Scholar.Results: Accumulated pieces of evidence reveal that extracellular aggregation of β-amyloid plaques and intracellular tangles of Τ protein are peculiar features of perpetuated Alzheimer’s disease (AD). Further, the significant role of mitochondria, calcium, and cholinergic pathways in the pathogenesis of AD makes the respiratory cell organelle a crucial therapeutic target in this neurodegenerative disease. All currently available drugs either delay the clinical damage to cells or temporarily attenuate some symptoms of Alzheimer’s disease.Conclusion: The pathological features of AD are extracellular deposition of β-amyloid, acetylcholinesterase deregulation, and intracellular tangles of Τ protein. The multifactorial heterogeneity of disease demands more research work in this field to find new therapeutic biological targets.

Coronavirus disease 2019 is a global pandemic, particularly affecting individuals with pre-existing lung conditions and potentially leading to pulmonary fibrosis. Age and healthcare system limitations further amplify susceptibility to both diseases, especially in low- and middle-income countries. The intricate relationship between Coronavirus disease 2019 and lung cancer highlights their clinical implications and the potential for early detection through biosensor techniques involving hedgehog and mucin signaling. This study highlights the connection between Coronavirus disease 2019 and lung cancer, focusing on the mucosa, angiotensin- altering enzyme 2 receptors, and their impact on the immune system. It details the inflammatory mechanisms triggered by Coronavirus disease 2019, which can result in pulmonary fibrosis and influence the cancer microenvironment. Various cytokines like Interleukins-6 and Tumor Necrosis Factor-alpha are examined for their roles in both diseases. Moreover, the review delves into the Hedgehog signaling pathways and their significance in lung cancer, particularly their influence on embryonic cell proliferation and tissue integrity. Mucin signaling is another vital aspect, highlighting the diverse mucin expression patterns in respiratory epithelial tissues and their potential as biomarkers. The review concludes with insights into diagnostic imaging techniques like chest computed tomography, Positron Emission Tomography and Computed Tomography, and Magnetic Resonance Imaging for early lung cancer detection, emphasizing the crucial role of biosensors in identifying specific biomarkers for early disease detection. This review provides a comprehensive overview of the clinical impact of Coronavirus disease 2019 on lung cancer patients and the potential for biosensors utilizing hedgehog and mucin signaling for early detection. It underscores the ongoing need for research and innovation to address these critical healthcare challenges.

Artemisinin (ART) has been found to exert anti-tumor activity by regulating the cell cycle, inducing apoptosis, inhibiting angiogenesis and tumor invasion and metastasis. Its derivatives (ARTs) can regulate the expression of drug-resistant proteins and reverse the multidrug resistance (MDR) of tumor cells by inhibiting intracellular drug efflux, inducing apoptosis and autophagy of tumor cells, thus enhancing the sensitivity of tumor cells to chemotherapy and radiotherapy. Recent studies have shown that nanodrugs play an important role in the diagnosis and treatment of cancer, which can effectively solve the shortcomings of poor hydrophilicity and low bioavailability of ARTs in the human body, prolong the in vivo circulation time, improve the targeting of drugs (including tumor tissues or specific organelles), and control the release of drugs in target tissues, thereby reducing the side effect. This review systematically summarized the latest research progress of nano-strategies of ARTs to enhance the efficiency of MDR reversal in breast cancer (BC) from the following two aspects: (1) Chemicals encapsulated in nanomaterials based on innovative anti-proliferation mechanism: non-ABC transporter receptor candidate related to ferroptosis (dihydroartemisinin/DHA analogs). (2) Combination therapy strategy of nanomedicine (drug-drug combination therapy, drug-gene combination, and chemical-physical therapy). Self-assembled nano-delivery systems enhance therapeutic efficacy through increased drug loading, rapid reactive release, optimized delivery sequence, and realization of cascade-increasing effects. New nanotechnology methods must be designed for specific delivery routines to achieve targeting administration and overcome MDR without affecting normal cells. The significance of this review is to expect that ART and ARTs can be widely used in clinical practice. In the future, nanotechnology can help people to treat multidrug resistance of breast cancer more accurately and efficiently.

Background: Growth differentiation factor-10 (GDF-10), a member of the TGF-β superfamily, plays a crucial role in cell proliferation and differentiation. In some tumors, GDF-10 can act as a tumor suppressor to inhibit tumor progression, but its role in posterior squamous cell carcinoma has not been reported yet. Methods: The aim of this study was to investigate the effect of GDF-10 on the epithelial-mesenchymal transition of laryngeal squamous cell carcinoma, and to provide new ideas for future targets in the treatment of laryngeal squamous carcinoma. Results: The effect of GDF-10 on tumor growth was detected; bioinformatics analysis was performed to predict the downstream targets of GDF-10, and RT-PCR and western blot were performed to detect the expression levels of target genes and proteins, respectively. Conclusion: Our findings support that GDF-10 can inhibit the proliferation, migration, and invasion, and promote apoptosis of laryngeal carcinoma AMC-HN-8 cells. GDF-10 inhibits the EMT of laryngeal carcinoma through LRP4 and thus inhibits the progression of laryngeal carcinoma.

Background: A number of studies demonstrate the efficacy of ribavirin against various cancer types in in vitro and in vivo models. However, ribavirin induces the development of multiple side effects, suggesting a high demand for ribavirin analogues with improved therapeutic indexes. Objective: This study was focused on the analysis of ribavirin, its aglycon 1,2,4-triazole-3-carboxamide, and several of its derivatives activities in blood cancer cells in vitro. Methods: Four 1,2,4-triazole-3-carboxamide derivatives were designed and synthesized. Antiproliferative effects were evaluated in chronic myeloid leukemia cells Ц#154;562 and acute lymphoblastic leukemia cells CCRF-SB as well as in the cells of whole blood mononuclear fraction of healthy volunteers by cell counting using the trypan blue exclusion method. Cell cycle distribution and apoptosis under the influence of the compounds were analyzed by flow cytometry with PI staining, and then apoptosis data were confirmed by Western blot analysis for PARP1 and caspase-3 cleavage. Results: We demonstrated the significant antiproliferative effect of 5-(tetrahydropyran-2-yl)-1,2,4-triazole-3- carboxamide and 1-(tetrahydropyran-2-yl)-1,2,4-triazol-3-carboxamide in leukemia cell lines in vitro in comparison to non-transformed monocytes, providing the rationale for further studies of 1,2,4-triazole-3-carboxamide derivatives as anti-leukemia drugs. Conclusion: These results implied that the 1,2,4-triazole-3-carboxamide derivatives exhibited their antiproliferative activities by induction of cell cycle arrest. Consequently, 5-(tetrahydropyran-2-yl)-1,2,4-triazole-3-carboxamide and 1-(tetrahydrofuran-2-yl)-1,2,4-triazol-3-carboxamide may present antimetabolites with potential anticancer efficacy.

Background: Antibiotics have led to significant advancements in medicine. Unfortunately, they were faced with the emergence of pathogen resistance. According to the World Health Organization, antimicrobial resistance has been declared one of humanity's top ten global public health threats. The risk of those bacteria is not only from their being resistant to multi-antibiotics but also from their ability to form biofilms, which can be 1,000 times more resistant than planktonic bacteria.Method: This study used rational design to hybridize two antimicrobial peptides, aiming to enhance their efficacy and stability with reduced toxicity.Results: The MY8 novel peptide was designed from the parent peptides BMAP-27 and CAMP 211-225. Some amino acid modifications were introduced to the hybrid peptide to improve its physicochemical properties guided by several software. Its antimicrobial activity has been studied against gram-negative and gram-positive strains, which showed broad-spectrum activity with MIC values against planktonic bacteria ranging from 0.125 to 25 μM. In contrast, 25-200 μM were needed to eradicate biofilms. Moreover, the MY8 peptide showed synergism with four conventional antibiotics., It also showed reduced toxicity against mammalian cells and a slight hemolysis tendency towards erythrocytes.Conclusion: The design of the MY8 peptide was successful, resulting in a novel, potent, broad-spectrum antimicrobial peptide with reduced toxicity and possible synergism with conventional antibiotics.

Objective: Inflammation is a well-described factor in the pathophysiology of type 2 diabetes mellitus (DM), which has been a suspect in the alteration of correlations between CRP and leptin in patients with type 2 DM.Aim: This study aimed to show the effect of vitamin C as an antioxidant on the correlation of the serum levels of C-reactive protein (CRP) and leptin in patients with type 2 DM.Methods: We recruited 70 patients with longstanding T2DM and randomly assigned them into two groups; one received 500 mg/day of vitamin C, and the other received a placebo for eight weeks. Both groups were matched regarding baseline characteristics such as age, gender, weight, and diabetic medications.Results: Out of 70 individuals, 57 participants were left in the study. After eight weeks of follow-up, leptin level was significantly increased in the Vitamin C group (MD = 3.48 change = 24%, p-value = 0.001) but did not change in the placebo group. Other markers such as Fasting plasma glucose, HbA1c, Creatinine, uric acid, Urea, cholesterol, HDL, LDL, TG, AST, ALT, insulin, and CRP did not significantly change in both groups (p value > 0.05). The significant changes in the leptin level among the vitamin C group also remained after controlling for age, BMI, Blood pressure (BP), Triglyceride (TG), and cholesterol. Also, the correlation between serum CRP and leptin became significant in the vitamin C group after eight weeks of follow-up but not in the placebo group. (rs = 0.730, p < 0.001 vs. rs = 0.286, p-value = 0.266 in placebo group).Conclusion: This study shows vitamin C can restore CRP-leptin correlation in patients with type 2 diabetes and increase serum leptin levels. More studies are needed to clarify the mechanism of this restoration.Clinical Trial Registration Number: IRCT20160811029306N1.