Current Pharmaceutical Design - Volume 29, Issue 12, 2023

Being an important dietary component, omega-3 (ω-3) fatty acids are essential polyunsaturated fatty acids, which play a crucial role in the normal growth and development of an individual. ω-3 fatty acids have been reported to possess therapeutic activities against several diseases, including cardiovascular, neurological, cancer, etc. Due to the unsaturation, ω-3 fatty acids are highly reactive and prone to oxidation, which is the biggest hurdle in their administration, as oxidation produces a foul smell and reduces their therapeutic efficacy. Although numerous supplementation strategies have been developed to enhance the bioavailability, targeted drug delivery, and therapeutic potential, the rate of compliance is low due to difficulty in swallowing and unpleasant aftertaste. To cope with these problems, several novel drug delivery approaches have been developed, which may be used as an alternative to enhance the effectiveness of ω-3 fatty acids when administered alone or in combination therapy. This review focuses on how novel drug delivery approaches can be used to overcome the ω-3 fatty acids stability issues and how to maximize its therapeutic activity.

Nonalcoholic fatty liver disease (NAFLD) has received worldwide scientific attention because of its rapidly increasing prevalence, and it has emerged as a serious public health problem in end-stage liver disease. Many factors are involved in the multifactorial development and progression of liver disease by influencing multiple signaling and metabolic pathways. Currently, many studies have demonstrated the critical role of microRNA- 21 (miR-21) in NAFLD pathogenesis. In addition, many studies have found that miR-21 is highly expressed in inflammatory bowel disease, which is associated with intestinal barrier dysfunction and altered gut microbiota. In this paper, we focus on the regulatory role of miR-21 in the progression of NAFLD and its effect on the gut microbiota, summarize the involvement of miR-21 through a variety of signaling pathways and metabolic pathways, as well as discuss some predicted miR-21 target genes and miR-21 pathways for future experimental identification.

Flavonoids are secondary metabolites abundantly present in plants and, in most cases, essential contributors to plants bioactivity. They have been studied so far for a range of possible health-beneficial effects, including antioxidant, cardioprotective, and cytotoxic. Therefore, there are data on the antimicrobial potential of a significant number of flavonoids. However, less is known regarding their antivirulence traits. Trending antimicrobial research worldwide has pointed out the promising effects of antimicrobial strategies based on the antivirulence principle, so this review aims to present the newest research regarding the antivirulence effects of flavonoids. Articles on antivirulence flavonoids published from 2015 until now were selected. A range of molecules from this class has been studied up to date, with the most abundant data for quercetin and myricetin, while the most studied organism is Pseudomonas aeruginosa. The antivirulence attributes studied included antibiofilm assessment, followed by data on the inhibition of virulence pigments (pyocyanin, violacein, and staphyloxanthin) and virulence enzyme production (such as sortase A and elastase). Less information is collected on the inhibition of morphological transition, motility, and molecular mechanisms underlying the antivirulence properties of flavonoids and in vivo research. Flavonoids are a group of compounds with a wide range of antivirulence traits and might be further developed into essential parts of novel antimicrobial strategies.

Background: Cognitive dysfunction, such as dementia, is the most common neurological disorder that affects memory, perception, learning, and problem-solving. Emerging evidence suggests that nutritional factors may prevent or accelerate the incidence of neurodegenerative diseases. Objective: This systematic review was designed to evaluate the association between pomegranate treatment and cognitive function. Methods: PubMed, Embase, Google Scholar, and Scopus databases were searched to extract original animal and human studies published until July 2021 without date restrictions. Firstly, 215 studies were retrieved via the search strategy. Irrelevant and duplicated studies were screened out, and critical analysis was used to obtain data. The articles' quality and bias risks were assessed by OHAT and Cochrane Collaboration’s quality assessment tools. Results: Finally, 24 articles (20 animal and 4 randomized controlled trial studies) were included in this review. All included animal and human studies indicated that pomegranate treatment was positively associated with improving specific domains of cognitive function. Conclusion: Our findings demonstrated that pomegranate treatment could improve cognitive function. Therefore, including pomegranate intake during daily life may lower the risk of cognitive impairment at the population level.

Background: Colorectal cancer (CRC) is the most common type of gastrointestinal tumor, but the available pharmacological treatment is insufficient. As a traditional Chinese medicine, the green walnut husks (QLY) exhibit anti-inflammatory, analgesic, anti-bacterial and anti-tumor effects. However, the effects and molecular mechanisms of QLY extracts on CRC were not yet made known. Objective: This study aims to provide efficient and low toxicity drugs for the treatment of CRC. The purpose of this study is to explore the anti-CRC effect and mechanism of QLY, providing preliminary data support for clinical research of QLY. Methods: Western blotting, Flow cytometry, immunofluorescence, Transwell, MTT, Cell proliferation assay, and xenograft model were used to perform the research. Results: In this study, the potential of QLY to inhibit the proliferation, migration invasion and induce apoptosis of the mouse colorectal cancer cell line CT26 in vitro was identified. The xenograft tumor model of CRC noted that QLY suppressed tumor growth without sacrificing body weight in mice. In addition, QLY-induced apoptosis in tumor cells through NLRC3/PI3K/AKT signaling pathway was revealed. Conclusion: QLY regulates the levels of mTOR, Bcl-2 and Bax by affecting the NLRC3/PI3K/AKT pathway to promote apoptosis of tumor cells, suppressing cell proliferation, invasion and migration, and subsequently preventing the progression of colon cancer.

Introduction: This paper aims to reveal the molecular mechanism of resveratrol against oxidative stress and cell injury. The ovarian granulosa-lutein cell injury and apoptosis induced by oxidative stress may be responsible for female luteal phase deficiency. The antioxidant function of resveratrol has been confirmed; however, its effect on the expression of antioxidant enzymes and regulatory mechanisms in ovarian granulosa-lutein cells remains unclear. Objective: This study aimed to investigate the role of the SIRT1/Nrf2/ARE signaling pathway in the effect of resveratrol on the hydrogen peroxide-induced injury of rat ovarian granulosa-lutein cells. Methods: In this study, ovarian granulosa-lutein cells extracted from 3-week female SD rats were treated with 200 μM H2O2 in the presence or absence of 20 μM resveratrol. siRNA-SIRT1 and siRNA-Nrf2 were used to inhibit the expression of SIRT1 and Nrf2, respectively. Cell counting kit 8 (CCK-8), cellular morphology, progesterone secretion, and estradiol were used to evaluate cell injury. Hoechst 33258 staining was used to measure cell apoptosis. DHE staining, DCFH-DA staining, malondialdehyde content, protein carbonyl content, total antioxidant capacity and SOD viability were used to estimate the levels of oxidative stress. Western blot analysis was used to detect the levels of apoptosis-related proteins, and SIRT1/Nrf2/ARE signaling pathway-related proteins. Results: The H2O2 treatment-induced rat ovarian granulosa-lutein cells injury was shown as decreased cell viability, impaired cellular morphology, and decreased levels of progesterone and estradiol. The H2O2 treatment also exacerbated cell apoptosis demonstrated as more apoptotic cells stained by Hoechst staining, decreased level of anti-apoptosis protein Bcl-2 and increased level of pro-apoptosis protein Bax. These effects of cell injury and apoptosis induced by H2O2 can be ameliorated by resveratrol. Resveratrol also alleviated oxidative stress induced by H2O2, supported by decreased superoxide anion and cellular total ROS, decreased malondialdehyde and protein carbonyl levels, and increased total antioxidant capacity and SOD viability. Western blot results demonstrated resveratrol reversed the H2O2-induced decrease in levels of antioxidant enzymes containing ARE sequences and activated SIRT1/Nrf2 pathway. Further treatment by siRNA-Nrf2 suggested resveratrol could not activate the expression of antioxidant enzymes under a condition of inhibition of Nrf2. Conclusion: This study demonstrates that resveratrol attenuated oxidative stress to protect H2O2-induced rat ovarian granulosa-lutein cell injury and apoptosis via SIRT1/Nrf2/ARE signaling pathway.

Background: We recently synthesized a compound in which 5-mercapto-1-methyltetrazole (MM4) was coordinated to tiopronin monovalent (TPN-Au(I)) and reported its cytotoxic activity against human leukemia cells in vitro. Objective: We further synthesized other heterocyclic compounds coordinated with TPN-Au(I) and assessed their cytotoxic activity against hepatocellular carcinoma HepG2 and lung cancer cell line H1299 in vitro. Methods: Seven kinds of compounds were synthesized by introducing a five-membered heterocyclic compound into TPN-Au(I). The number of viable cells was counted by a trypan blue dye exclusion assay. Fluorescence conjugated-Annexin V and propidium iodide were used for the apoptosis analysis. Results: Seven compounds were successfully synthesized. Among these compounds, TPN-Au(I)-MTZ (3- mercapto-1,2,4-triazole), TPN-Au(I)-MMT (2-mercapto-5-methyl-1,3,4-thiadiazole), and TPN-Au(I)-MMTT (2-mercapto-5-methylthio-1,3,4-thiadiazole) effectively suppressed the proliferation and induced apoptosis in HepG2 cells. In addition, TPN-Au(I)-MMTT and TPN-Au(I)-MMT also showed effective cytotoxicity against H1299 cells. Conclusion: The present results showed that introduction of some five-membered heterocyclic compounds, especially MMT and MMTT, to TPN-Au(I) improved the cytotoxicity against solid cancer cells.

Introduction: Patients with left carotid artery atherosclerotic stenosis have an increased ischemic stroke risk. Left carotid stenosis, the most common cause of the transient ischemic attack, is related to a higher risk of acute stroke. Left carotid artery stenosis is also associated with cerebral artery infarction. The significant coronary stenosis promotes ST-segment elevation myocardial infarctions. The severe coronary stenosis plays an important role in development and progression of myocardial infarction. However, the dynamic changes of circulating oxidative stress and inflammatory markers in the carotid stenosis combined with coronary artery stenosis are not clear, and it also remains unknown whether mark of oxidative stress and inflammation are potential therapeutic targets for carotid stenosis combined with coronary artery stenosis. Aim: This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients. Methods: We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2- isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients. Results: Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients. Conclusion: Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.