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Journal of Pharmacopuncture Jun 2024Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past... (Review)
Review
OBJECTIVES
Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of on cognitive function.
METHODS
This study focused primarily on the effects of and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer's disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind 's impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at 's effects on cognitive decline and AD.
RESULTS
According to recent research, and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis.
CONCLUSION
This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of . We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders.
PubMed: 38948308
DOI: 10.3831/KPI.2024.27.2.70 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024This study aims to systematically evaluate the protective role of quercetin (QCT), a naturally occurring flavonoid, against oxidative damage in human endometrial stromal...
OBJECTIVE
This study aims to systematically evaluate the protective role of quercetin (QCT), a naturally occurring flavonoid, against oxidative damage in human endometrial stromal cells (HESCs) induced by hydrogen peroxide (HO). Oxidative stress, such as that induced by HO, is known to contribute significantly to cellular damage and has been implicated in various reproductive health issues. The study is focused on investigating how QCT interacts with specific molecular pathways to mitigate this damage. Special attention was given to the p38 MAPK/NOX4 signaling pathway, which is crucial to the regulation of oxidative stress responses in cellular systems. By elucidating these mechanisms, the study seeks to confirm the potential of QCT not only as a protective agent against oxidative stress but also as a therapeutic agent that could be integrated in treatments of conditions characterized by heightened oxidative stress in endometrial cells.
METHODS
cultures of HESCs were treated with QCT at different concentrations (0, 10, 20, and 40 μmol/L) for 24 h to verify the non-toxic effects of QCT on normal endometrial cells. Subsequently, 250 μmol/L HO was used to incubate the cells for 12 h to establish an HO-induced HESCs injury model. HESCs were pretreated with QCT for 24 h, which was followed by stimulation with HO. Then, CCK-8 assay was performed to examine the cell viability and to screen for the effective intervention concentration. HESCs were divided into 3 groups, the control group, the HO model group, and the HO+QCT group. Intracellular levels of reactive oxygen species (ROS) were precisely quantified using the DCFH-DA fluorescence assay, a method known for its accuracy in detecting and quantifying oxidative changes within the cell. The mitochondrial membrane potential was determined by JC-1 staining. Annexin Ⅴ/PI double staining and flow cytometry were performed to determine the effect of QCT on HO-induced apoptosis of HESCs. Furthermore, to delve deeper into the cellular mechanisms underlying the observed effects, Western blot analysis was conducted to measure the expression levels of the critical proteins involved in oxidative stress response, including NADPH oxidase 4 (NOX4), p38 mitogen-activated protein kinase (p38 MAPK), and phosphorylated p38 MAPK (p-p38 MAPK). This analysis helps increase understanding of the specific intracellular signaling pathways affected by QCT treatment, giving special attention to its potential for modulation of the p38 MAPK/NOX4 pathway, which plays a significant role in cellular defense mechanisms against oxidative stress.
RESULTS
In this study, we started off by assessing the toxicity of QCT on normal endometrial cells. Our findings revealed that QCT at various concentrations (0, 10, 20, and 40 μmol/L) did not exhibit any cytotoxic effects, which laid the foundation for further investigation into its protective roles. In the HO-induced HESCs injury model, a significant reduction in cell viability was observed, which was linked to the generation of ROS and the resultant oxidative damage. However, pretreatment with QCT (10 μmol/L and 20 μmol/L) significantly enhanced cell viability after 24 h (<0.05), with the 20 μmol/L concentration showing the most substantial effect. This suggests that QCT can effectively reverse the cellular damage caused by HO. Furthermore, the apoptosis assays demonstrated a significant increase in the apoptosis rates in the HO model group compared to those in the control group (<0.01). However, co-treatment with QCT significantly reversed this trend (<0.05), indicating QCT's potential protective role in mitigating cell apoptosis. ROS assays showed that, compared to that in the control group, the average fluorescence intensity of ROS in the HO model group significantly increased (<0.01). QCT treatment significantly reduced the ROS fluorescence intensity in the HO+QCT group compared to the that in the HO model group, suggesting an effective alleviation of oxidative damage (<0.05). JC-1 staining for mitochondrial membrane potential changes revealed that compared to that in the control, the proportion of cells with decreased mitochondrial membrane potential significantly increased in the HO model group (<0.01). However, this proportion was significantly reduced in the QCT-treated group compared to that of the HO model group (<0.05). Finally, Western blot analysis indicated that the expression levels of NOX4 and p-p38 MAPK proteins were elevated in the HO model group compared to those of the control group (<0.05). Following QCT treatment, these protein levels significantly decreased compared to those of the HO model group (<0.05). These results suggest that QCT may exert its protective effects against oxidative stress by modulating the p38 MAPK/NOX4 signaling pathway.
CONCLUSION
QCT has demonstrated significant protective effects against HO-induced oxidative damage in HESCs. This protection is primarily achieved through the effective reduction of ROS accumulation and the inhibition of critical signaling pathways involved in the oxidative stress response, notably the p38 MAPK/NOX4 pathway. The results of this study reveal that QCT's ability to modulate these pathways plays a key role in alleviating cellular damage associated with oxidative stress conditions. This indicates not only its potential as a protective agent against cellular oxidative stress, but also highlights its potential for therapeutic applications in treating conditions characterized by increased oxidative stress in the endometrium, thereby offering the prospect of enhancing reproductive health. Future studies should explore the long-term effects of QCT and its clinical efficacy , thereby providing a clear path toward its integration into therapeutic protocols.
Topics: Humans; Hydrogen Peroxide; Oxidative Stress; Female; NADPH Oxidase 4; Quercetin; Endometrium; p38 Mitogen-Activated Protein Kinases; Stromal Cells; Signal Transduction; Reactive Oxygen Species; Apoptosis; Cells, Cultured
PubMed: 38948281
DOI: 10.12182/20240560107 -
PeerJ 2024Ischemic stroke (IS) is a disease with a high mortality and disability rate worldwide, and its incidence is increasing per year. Angiogenesis after IS improves blood...
β-asarone induces viability and angiogenesis and suppresses apoptosis of human vascular endothelial cells after ischemic stroke by upregulating vascular endothelial growth factor A.
Ischemic stroke (IS) is a disease with a high mortality and disability rate worldwide, and its incidence is increasing per year. Angiogenesis after IS improves blood supply to ischemic areas, accelerating neurological recovery. β-asarone has been reported to exhibit a significant protective effect against hypoxia injury. The ability of β-asarone to improve IS injury by inducing angiogenesis has not been distinctly clarified. The experimental rats were induced with middle cerebral artery occlusion (MCAO), and oxygen-glucose deprivation (OGD) model cells were constructed using human microvascular endothelial cell line (HMEC-1) cells. Cerebral infarction and pathological damage were first determined triphenyl tetrazolium chloride (TTC) and hematoxylin and eosin (H&E) staining. Then, cell viability, apoptosis, and angiogenesis were assessed by utilizing cell counting kit-8 (CCK-8), flow cytometry, spheroid-based angiogenesis, and tube formation assays in OGD HMEC-1 cells. Besides, angiogenesis and other related proteins were identified with western blot. The study confirms that β-asarone, like nimodipine, can ameliorate cerebral infarction and pathological damage. β-asarone can also upregulate vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) and induce phosphorylation of p38. Besides, the study proves that β-asarone can protect against IS injury by increasing the expression of VEGFA. experiments affirmed that β-asarone can induce viability and suppress apoptosis in OGD-mediated HMEC-1 cells and promote angiogenesis of OGD HMEC-1 cells by upregulating VEGFA. This establishes the potential for β-asarone to be a latent drug for IS therapy.
Topics: Allylbenzene Derivatives; Anisoles; Apoptosis; Ischemic Stroke; Humans; Vascular Endothelial Growth Factor A; Cell Survival; Animals; Up-Regulation; Rats; Endothelial Cells; Male; Cell Line; Rats, Sprague-Dawley; Neovascularization, Physiologic; Angiogenesis
PubMed: 38948219
DOI: 10.7717/peerj.17534 -
PeerJ 2024PLAUR has been found upregulated in various tumors and closely correlated with the malignant phenotype of tumor cells. The aim of this study was to investigate the...
BACKGROUND
PLAUR has been found upregulated in various tumors and closely correlated with the malignant phenotype of tumor cells. The aim of this study was to investigate the relationship between PLAUR and clear cell renal cell carcinoma (ccRCC) and its potential mechanism of promoting tumor progression.
METHODS
The expression levels and clinical significance of PLAUR, along with the associated signaling pathways, were extensively investigated in ccRCC samples obtained from The Cancer Genome Atlas (TCGA). PLAUR expression in 20 pairs of ccRCC tumor tissues and the adjacent tissues was assessed using qRT-PCR and IHC staining. Additionally, a series of experiments were conducted to investigate the impact of PLAUR suppression on cellular proliferation, migration, invasion, cell cycle progression, and apoptosis in ccRCC. The Western blot analysis was employed to investigate the expression levels of pivotal genes associated with the PI3K/AKT/mTOR signaling pathway.
RESULTS
The expression of PLAUR was significantly upregulated in ccRCC compared to normal renal tissues, and higher PLAUR expression in ccRCC was associated with a poorer prognosis than low expression. The functional investigations demonstrated that knockdown of PLAUR significantly attenuated the proliferation, migration, and invasion capabilities of ccRCC cells. Concurrently, PLAUR knockdown effectively induced cellular apoptosis, modulated the cell cycle, inhibited the EMT process, and attenuated the activation of the PI3K/AKT/mTOR signaling pathway. PLAUR may represent a key mechanism underlying ccRCC progression.
CONCLUSIONS
The involvement of PLAUR in ccRCC progression may be achieved through the activation of the PI3K/AKT/mTOR signaling pathway, making it a reliable biomarker for the identification and prediction of ccRCC.
Topics: Humans; Carcinoma, Renal Cell; TOR Serine-Threonine Kinases; Kidney Neoplasms; Signal Transduction; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Disease Progression; Cell Proliferation; Cell Line, Tumor; Male; Female; Apoptosis; Cell Movement; Middle Aged; Gene Expression Regulation, Neoplastic; Prognosis; Up-Regulation
PubMed: 38948215
DOI: 10.7717/peerj.17555 -
Avicenna Journal of Phytomedicine 2024Baicalin and baicalein are natural flavonoids reported for the first time from Georgi. Recently, attention has been paid to these valuable flavonoids due to their... (Review)
Review
OBJECTIVE
Baicalin and baicalein are natural flavonoids reported for the first time from Georgi. Recently, attention has been paid to these valuable flavonoids due to their promising effects. This paper aims to have a comprehensive review of their pharmacological effects.
MATERIALS AND METHODS
An extensive search through scientific databases including Scopus, PubMed, and ISI Web of Science was established.
RESULTS
According to literature, these compounds have been mainly effective in the treatment of neurological and neurodegenerative diseases, hepatic and cardiovascular disorders, metabolic syndrome, and cancers through anti-inflammatory and antioxidant pathways. Induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for their cytotoxic and antitumor activities. Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms. Inhibiting the development of cardiac fibrosis and reducing inflammation, oxidative stress, and apoptosis are also the mechanisms suggested for cardioprotective activities. Decreasing the accumulation of inflammatory mediators and improving cognitive function and depressive-like behaviours are the main mechanisms for neurological and neurodegenerative activities.
CONCLUSION
The findings suggest the therapeutic potential of baicalin and baicalein. However, complementary research in different and models to investigate their mechanisms of action as well as clinical trials to evaluate their efficacy and safety are suggested.
PubMed: 38948180
DOI: 10.22038/AJP.2023.22307 -
Avicenna Journal of Phytomedicine 2024Astaxanthin (ASX) is a lipid-soluble keto-carotenoid with several biological effects. These effects may benefit polycystic ovarian syndrome (PCOS) patients. Imbalanced...
OBJECTIVE
Astaxanthin (ASX) is a lipid-soluble keto-carotenoid with several biological effects. These effects may benefit polycystic ovarian syndrome (PCOS) patients. Imbalanced apoptosis/anti-apoptosis signaling has been considered the major pathogenesis of PCOS. In a randomized clinical trial, we tested the impact of ASX on the apoptotic pathway in PCOS granulosa cells (GCs). The present study hypothesizes that ASX may improve apoptosis in PCOS patients.
MATERIALS AND METHODS
This trial recruited patients with confirmed PCOS. A total of 58 patients were randomly assigned to take ASX (12 mg) or placebo for 8 weeks. Aspirated follicular fluid (FF) and blood samples were taken from both groups to measure and protein expression. Following FF aspiration, GCs from both groups were obtained; Real-Time PCR and Western blotting were used to evaluate the apoptotic pathway's gene and protein expression levels in GCs..
RESULTS
In GCs analysis, ASX reduced gene and protein expression after 8 weeks compared to placebo(p<0.05). Also, (p>0.05) and (p<0.05) gene expression declined, although the difference was not statistically significant for . Besides,ASX treatment contributed to an elevated gene expression in GCs(p<0.05). In FF and serum analysis, a statistically significant increase was found in concentration in the ASX group (p<0.05). Moreover, a reduction in level was confirmed in both FF and serum of the ASX group; however, this change was not significant in the serum (p>0.05).
CONCLUSION
It seems that ASX consumption among women with PCOS improved serum and FF levels of apoptotic factors and modulated genes and protein expression of the apoptosis pathway in GCs. Nevertheless, further investigations are needed to reveal the potential role of this compound in PCOS treatment.
PubMed: 38948179
DOI: 10.22038/AJP.2023.23111 -
Britannin suppresses MCF-7 breast cancer cell growth by inducing apoptosis and inhibiting autophagy.Avicenna Journal of Phytomedicine 2024Breast cancer is the main reason for cancer-related death in women. Britannin is a sesquiterpene lactone compound derived from with anti-tumor properties. We aimed to...
OBJECTIVE
Breast cancer is the main reason for cancer-related death in women. Britannin is a sesquiterpene lactone compound derived from with anti-tumor properties. We aimed to explore the impacts of britannin on apoptosis and autophagy in MCF-7 breast cancer cell line.
MATERIALS AND METHODS
The cytotoxic influences of britannin on MCF-7 cells were estimated by the MTT method. The expression levels of apoptosis-associated genes such as , , , , and and transcripts of autophagy markers including , , , , , , and were quantified using quantitative real time-PCR (qRT-PCR). Western blotting method was used to evaluate the amount of caspase 3, phosphorylated JAK2, phosphorylated STAT3, ATG1, ATG4, ATG5, Beclin1, and LC-III.
RESULTS
Treatment of MCF-7 cells with various concentrations of britannin remarkably hindered the viability of these cells compared to the controls. This compound significantly elevated the expression of pro-apoptotic caspase-3 but did not influence the levels of anti-apoptotic and . Britannin decreased the levels of phosphorylated forms of JAK2 and STAT3 proteins causing the blockage of the JAK/STAT pathway. Four autophagy factors expressions, including ATG4, ATG5, Beclin1, and LCIII, were reduced due to the effect of britannin on MCF-7 cells.
CONCLUSION
Britannin triggered apoptosis in MCF-7 cells by a mechanism that led to the blockade of the JAK/STAT pathway. Moreover, britannin prohibited autophagy in these cancer cells. This may suggest britannin as an agent for the suppression of breast tumors or as an adjutant for the enhancement of anti-breast cancer drugs effect.
PubMed: 38948174
DOI: 10.22038/AJP.2023.22995 -
Avicenna Journal of Phytomedicine 2024Lead (Pb) poisoning affects multiple organs including the reproductive system. The experiment was performed to explore the protective effect of naringin on testicular...
OBJECTIVE
Lead (Pb) poisoning affects multiple organs including the reproductive system. The experiment was performed to explore the protective effect of naringin on testicular apoptosis, neuronal dysfunction and markers of stress in cockerel chicks.
MATERIALS AND METHODS
Thirty-six cockerel chicks were used for this study, and randomly grouped into six chicks per group viz. control, Pb only (600 ppm), Pb and naringin (80 mg/kg), Pb and Naringin (160 mg/kg), naringin only (80 mg/kg) and naringin only (160 mg/kg), respectively, for eight weeks. Pb was administered via drinking water while naringin was administered via oral gavage. Oxidative stress indices in the brain and testes were assessed, and immunohistochemistry of TNF-α and caspase 3 was done in the brain and testes, respectively.
RESULTS
Lead administration induced inflammatory and testicular apoptosis cascade accompanied with increased oxidative stress and upregulation of brain and testicular antioxidant enzymes in comparison to the control and Pb-only-treated cockerels. Immunohistochemistry showed significant immunoreactivity of testicular caspase 3 and TNF-α in the brain.
CONCLUSION
Treatment of Pb-exposed chickens with naringin offered protection to Pb acetate-induced testicular oxidative stress, apoptosis, and neuroinflammation in cockerel chicks.
PubMed: 38948173
DOI: 10.22038/AJP.2023.22946 -
World Journal of Stem Cells Jun 2024The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging.
BACKGROUND
The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging.
AIM
To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EX) and exogenous mitochondria (mito) protect the lung from ARDS complicated by SS.
METHODS
study, including L2 cells treated with lipopolysaccharide (LPS) and study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EX), 4 (ARDS-SS + mito), and 5 (ARDS-SS + EX + mito), were included in the present study.
RESULTS
study showed an abundance of mito found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels ( < 0.001). The protein levels of inflammation [interleukin (IL)-1β/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EX treatment than without EX treatment, whereas the protein expressions of cellular junctions [occluding/β-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all < 0.0001), whereas arterial oxygen-saturation (SaO%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO% among the groups (all < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all < 0.0001).
CONCLUSION
Combined EX-mito therapy was better than merely one for protecting the lung against ARDS-SS induced injury.
PubMed: 38948095
DOI: 10.4252/wjsc.v16.i6.690 -
Theranostics 2024Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer...
Cancer therapy has moved from single agents to more mechanism-based targeted approaches. In recent years, the combination of HDAC inhibitors and other anticancer chemicals has produced exciting progress in cancer treatment. Herein, we developed a novel prodrug via the ligation of dichloroacetate to selenium-containing potent HDAC inhibitors. The effect and mechanism of this compound in the treatment of prostate cancer were also studied. The concerned prodrug SeSA-DCA was designed and synthesized under mild conditions. This compound's preclinical studies, including the pharmacokinetics, cell toxicity, and anti-tumor effect on prostate cancer cell lines, were thoroughly investigated, and its possible synergistic mechanism was also explored and discussed. SeSA-DCA showed good stability in physiological conditions and could be rapidly decomposed into DCA and selenium analog of SAHA (SeSAHA) in the tumor microenvironment. CCK-8 experiments identified that SeSA-DCA could effectively inhibit the proliferation of a variety of tumor cell lines, especially in prostate cancer. In further studies, we found that SeSA-DCA could also inhibit the metastasis of prostate cancer cell lines and promote cell apoptosis. At the animal level, oral administration of SeSA-DCA led to significant tumor regression without obvious toxicity. Moreover, as a bimolecular coupling compound, SeSA-DCA exhibited vastly superior efficacy than the mixture with equimolar SeSAHA and DCA both and . Our findings provide an important theoretical basis for clinical prostate cancer treatment. Our and results showed that SeSA-DCA is a highly effective anti-tumor compound for PCa. It can effectively induce cell cycle arrest and growth suppression and inhibit the migration and metastasis of PCa cell lines compared with monotherapy. SeSA-DCA's ability to decrease the growth of xenografts is a little better than that of docetaxel without any apparent signs of toxicity. Our findings provide an important theoretical basis for clinical prostate cancer treatment.
Topics: Male; Prostatic Neoplasms; Humans; Animals; Apoptosis; Histone Deacetylase Inhibitors; Cell Line, Tumor; Cell Cycle Checkpoints; cdc25 Phosphatases; Mice; Antineoplastic Agents; Cell Proliferation; Mice, Nude; Selenium; Xenograft Model Antitumor Assays; Prodrugs; Mice, Inbred BALB C
PubMed: 38948069
DOI: 10.7150/thno.92119