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Neurochemical Research Mar 2022Apigenin, as a natural flavonoid present in several plants is characterized with potential anticancer, antioxidant, and anti-inflammatory properties. Recent studies...
Apigenin, as a natural flavonoid present in several plants is characterized with potential anticancer, antioxidant, and anti-inflammatory properties. Recent studies proposed that apigenin affects depression disorder through unknown mechanistic pathways. The effects of apigenin's anti-depressive properties on streptozocin-mediated depression have been investigated through the evaluation of behavioral tests, oxidative stress, cellular energy homeostasis and inflammatory responses. The results demonstrated anti-depressive properties of apigenin in behavioral test including forced swimming and splash tests and oxidative stress biomarkers such as reduced glutathione, lipid peroxidation, total antioxidant power and coenzyme Q levels. Apigenin, also, demonstrated its regulatory potency in cellular energy homeostasis and immune system gene expression through inhibiting Nlrp3 and Tlr4 overexpression. Furthermore, failure in energy production as the key factor in various psychiatric disorders was reversed by apigenin modulating effect on AMPK gene expression. Overall, 20 mg/kg of apigenin was recognized as the dose suitable for minimizing the undesirable adverse effects in the STZ-mediated depression model proposed in this study. Our data suggested that apigenin could be able to adjust behavioral dysfunction, biochemical biomarkers and recovered cellular antioxidant level in depressed animals. The surprising results were achieved by raise in COQ level, which could regulate the overexpression of the AMPK gene in stressful conditions. The regulatory effect of apigenin in inflammatory signaling pathways such as Nlrp3, and Tlr4 gene expression was studied at the surface part of the hippocampus.
Topics: Animals; Antioxidants; Apigenin; Depression; Humans; Neuroprotective Agents; Oxidative Stress
PubMed: 34705188
DOI: 10.1007/s11064-021-03473-0 -
Nutrients Mar 2023Progesterone functions as a steroid hormone involved in female reproductive physiology. While some reproductive disorders manifest with symptoms that can be treated by...
Progesterone functions as a steroid hormone involved in female reproductive physiology. While some reproductive disorders manifest with symptoms that can be treated by progesterone or synthetic progestins, recent data suggest that women also seek botanical supplements to alleviate these symptoms. However, botanical supplements are not regulated by the U.S. Food and Drug Administration and therefore it is important to characterize and quantify the inherent active compounds and biological targets of supplements within cellular and animal systems. In this study, we analyzed the effect of two natural products, the flavonoids, apigenin and kaempferol, to determine their relationship to progesterone treatment in vivo. According to immunohistochemical analysis of uterine tissue, kaempferol and apigenin have some progestogenic activity, but do not act in exactly the same manner as progesterone. More specifically, kaempferol treatment did not induce HAND2, did not change proliferation, and induced ZBTB16 expression. Additionally, while apigenin treatment did not appear to dramatically affect transcripts, kaempferol treatment altered some transcripts (44%) in a similar manner to progesterone treatment but had some unique effects as well. Kaempferol regulated primarily unfolded protein response, androgen response, and interferon-related transcripts in a similar manner to progesterone. However, the effects of progesterone were more significant in regulating thousands of transcripts making kaempferol a selective modifier of signaling in the mouse uterus. In summary, the phytoprogestins, apigenin and kaempferol, have progestogenic activity in vivo but also act uniquely.
Topics: Mice; Animals; Female; Progesterone; Kaempferols; Apigenin; Progestins; Uterus
PubMed: 36986136
DOI: 10.3390/nu15061407 -
European Journal of Pharmacology Jul 2023Diabetic nephropathy (DN) is common complication of diabetes. Ferroptosis is an atypical form of iron-dependent modulated necrosis and have been proven to contribute to...
Diabetic nephropathy (DN) is common complication of diabetes. Ferroptosis is an atypical form of iron-dependent modulated necrosis and have been proven to contribute to the progress of diabetic nephropathy. Vitexin, a flavonoid monomer derived from medicinal plants that has various biological activities including anti-inflammatory and anticancer effects, has not been investigated in diabetic nephropathy studies. However, whether vitexin has a protective effect on diabetic nephropathy remains unclear. In this study, the roles and mechanism of vitexin on alleviating DN were explored in vivo and in vitro. The protective effect of vitexin in diabetic nephropathy were evaluated by in vitro and in vivo experiment. In this research, we validated that vitexin protect HK-2 against HG-induced damage. Besides, vitexin pretreatment also reduced fibrosis (Collagen type I Col I, TGF-β1). Furthermore, vitexin inhibited ferroptosis induced by HG, accompanied by changes of morphological, decrease of ROS, Fe and MDA, and increased GSH levels. Meanwhile, vitexin up-regulated the protein expression of GPX4 and SLC7A11 in HG-induced HK-2 cells. Moreover, knockdown of GPX4 by shRNA migrated the protective effect of vitexin on HG-challenged HK-2 and reversed the ferroptosis induced by vitexin. Consistent with in vitro, vitexin alleviated renal fibrosis, damage and ferroptosis in DN rat. In conclusion, our findings revealed that vitexin could alleviate diabetic nephropathy by attenuated ferroptosis via activating GPX4.
Topics: Animals; Rats; Diabetic Nephropathies; Ferroptosis; Apigenin; Collagen Type II; Diabetes Mellitus
PubMed: 37172926
DOI: 10.1016/j.ejphar.2023.175787 -
Current Topics in Medicinal Chemistry 2023Breast cancer is one of the main global diseases with a high mortality rate that mainly affects the female population. Despite the important advances that have been made... (Review)
Review
Breast cancer is one of the main global diseases with a high mortality rate that mainly affects the female population. Despite the important advances that have been made concerning the treatments for this disease, research on less invasive therapies that generate fewer side effects for patients continues to develop. Consequently, researchers have turned their attention to using natural compounds (such as flavonoids) involved in molecular processes implicated in this type of cancer and are studying how these processes can be exploited to develop possible chemotherapies. This review offers a general description of studies on the antiproliferative activity of flavonoids obtained from natural sources for breast cancer treatment and their mechanism of action related to their structural characteristics. Reports were retrieved from electronic databases, such as Web of Science and Scopus using the following keywords: breast cancer, antiproliferative, flavonoids, and structureactivity. Articles published between 2015-2022 related to the topics mentioned above were selected, focusing on the flavonoids apigenin, luteolin, quercetin, and naringenin, as they are the ones with the highest activity and relevance according to the literature found.
Topics: Humans; Female; Flavonoids; Breast Neoplasms; Quercetin; Luteolin; Apigenin
PubMed: 37183471
DOI: 10.2174/1568026623666230512123500 -
Antiviral Research Sep 2020We describe herein that Apigenin, which is a dietary flavonoid, exerts a strong in vitro and in ovo antiviral efficacy against buffalopox virus (BPXV). Apigenin...
We describe herein that Apigenin, which is a dietary flavonoid, exerts a strong in vitro and in ovo antiviral efficacy against buffalopox virus (BPXV). Apigenin treatment was shown to inhibit synthesis of viral DNA, mRNA and proteins, without affecting other steps of viral life cycle such as attachment, entry and budding. Although the major mode of antiviral action of Apigenin was shown to be mediated via targeting certain cellular factors, a modest inhibitory effect of Apigenin was also observed directly on viral polymerase. We also evaluated the selection of drug-resistant virus variants under long-term selection pressure of Apigenin. Wherein Apigenin-resistant mutants were not observed up to ~ P20 (passage 20), a significant resistance was observed to the antiviral action of Apigenin at ~ P30. However, a high degree resistance could not be observed even up to P60. To the best of our knowledge, this is the first report describing in vitro and in ovo antiviral efficacy of Apigenin against poxvirus infection. The study also provides mechanistic insights on the antiviral activity of Apigenin and selection of potential Apigenin-resistant mutants upon long-term culture.
Topics: Animals; Antiviral Agents; Apigenin; Chick Embryo; Chickens; Chlorocebus aethiops; DNA, Viral; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Humans; Vaccinia virus; Vero Cells; Virus Replication
PubMed: 32707051
DOI: 10.1016/j.antiviral.2020.104870 -
Journal of Controlled Release :... Feb 2024Intestinal ischemia reperfusion injury (II/R injury) is a common and intractable pathophysiological process in critical patients, for which exploring new treatments and...
Intestinal ischemia reperfusion injury (II/R injury) is a common and intractable pathophysiological process in critical patients, for which exploring new treatments and mechanisms is of great importance to improve treatment outcomes. Apigenin-7-O-Glucoside (AGL) is a sugar derivative of apigenin natural product with various pharmacological activities to protect against intestinal diseases. In this study, we synthesized two amphiphilic molecules, namely DTPA-N10-10 and mPEG-TK-DA, which can scavenge free radicals and reactive oxygen species (ROS). They were successfully encapsulated AGL through self-assembly, resulting in the formation of multi-site ROS scavenging nanoparticles called PDN@AGL. In vitro and in vivo experiments demonstrated that PDN@AGL could protect intestinal tissues by reducing lipid peroxidation, lowering ROS levels and inhibiting ferroptosis during II/R injury. Furthermore, our study revealed, for the first time, that the regulation of the ATF3/SLC7A11 pathway by PDN@AGL may play a crucial role in mitigating II/R injury. In conclusion, our study confirmed the beneficial effects of PDN@AGL in combating II/R injury through the ATF3/SLC7A11-mediated regulation of ferroptosis and oxidative stress. These findings lay the groundwork for the potential application of PDN@AGL in the treatment of II/R injury.
Topics: Humans; Activating Transcription Factor 3; Amino Acid Transport System y+; Apigenin; Ferroptosis; Nanoparticles; Reactive Oxygen Species; Reperfusion Injury; Intestines
PubMed: 38145659
DOI: 10.1016/j.jconrel.2023.12.038 -
Journal of Integrative Neuroscience May 2023Apigenin has been reported to exhibit anti-inflammatory and anti-oxidative activities. This study aimed to investigate the protective role of Apigenin on...
BACKGROUND
Apigenin has been reported to exhibit anti-inflammatory and anti-oxidative activities. This study aimed to investigate the protective role of Apigenin on chemotherapy-induced peripheral neuropathy (CIPN).
METHODS
CIPN mouse model was established using Paclitaxel treatment. Hot plate and tail prick latency tests were performed to examine the allodynia and hyperalgesia behaviors. Anti-inflammatory and anti-oxidative effects of Apigenin on CIPN were determined by enzyme-linked immunosorbent (ELISA) assay, Western blot, and qRT-PCR. Nuclear recruitment of nuclear factor erythroid 2-related factor 2 (NRF2) was analyzed to evaluate the underlying mechanisms of the protective effects of Apigenin.
RESULTS
Apigenin significantly alleviated CIPN-induced nociceptive behaviors of CIPN mice. It also decreased the TNF-α and IL-1β levels, suppressed oxidative stress and inflammation in the surgical spinal cord tissues. Mechanistically, Apigenin altered the pro-inflammatory and anti-inflammatory phenotypes ratio of microglia through promoting the nuclear recruitment of NRF2 and activating the NRF2/Antioxidant Response Element (ARE) signaling pathway.
CONCLUSIONS
In summary, Apigenin relieves CIPN by regulating microglia activation and polarization, which provides a potential therapeutic strategy for CIPN treatment.
Topics: Mice; Animals; Hyperalgesia; Apigenin; Microglia; NF-E2-Related Factor 2; Peripheral Nervous System Diseases; Anti-Inflammatory Agents; Antineoplastic Agents
PubMed: 37258427
DOI: 10.31083/j.jin2203064 -
Inflammation Oct 2020Astrocytes release biologically active substances that cause inflammation in neurodegenerative diseases. The present study investigated the effects of two flavonoids...
Astrocytes release biologically active substances that cause inflammation in neurodegenerative diseases. The present study investigated the effects of two flavonoids (apigenin and luteolin) on the production of IL-31 and IL-33 in lipopolysaccharide (LPS)-activated astrocytes. Cell viability was investigated using EZ-Cytox assay, mRNA expressions of IL-31 and IL-33 were analyzed by RT-PCR, protein expressions were analyzed by western blot, and cytokine secretion was analyzed by ELISA. Apigenin and luteolin prevented astrocyte activation and inhibited mRNA and protein expression and secretion of IL-31 and IL-33 in the LPS-treated astrocytes. Apigenin's suppression of ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 and IL-33, while luteolin's suppression of JNK, p38, ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 in the astrocytes. Also, luteolin's suppression of ERK, NF-κB, and STAT3 activations inhibited IL-33 production in the activated astrocytes. In addition, apigenin and luteolin also prevented the translocation of activated STAT3 and NF-κB to the nucleus of the activated astrocytes and subsequently affected their DNA binding activities. The results suggest that apigenin and luteolin may have potentials as neuroprotective agents for the treatment of diseases involving astrocyte activation and detrimental production of IL-31 and IL-33.
Topics: Animals; Apigenin; Astrocytes; Cells, Cultured; Cytokines; Dose-Response Relationship, Drug; Drug Delivery Systems; Lipopolysaccharides; Luteolin; MAP Kinase Signaling System; Mice; NF-kappa B; STAT3 Transcription Factor
PubMed: 32462548
DOI: 10.1007/s10753-020-01245-6 -
Journal of Pharmaceutical and... Jan 2022In recent years, deep eutectic solvent (DES) has attracted a great deal of attention as an environmentally friendly solvent and could be used as an alternative to...
In recent years, deep eutectic solvent (DES) has attracted a great deal of attention as an environmentally friendly solvent and could be used as an alternative to conventional solvents. In this study, 34 choline and betaine-based deep eutectic solvents were prepared and investigated the ability to extract apigenin and luteolin from the celery seed. The results showed that DES composed of betaine hydrochloride and propylene glycol had the best extraction efficiency. Using one factor at a time combined with response surface methodology, the optimal conditions of extraction were determined as follows: time of extraction: 19 min, extraction temperature: 75 °C, the water content in solvent: 40% (w/w). Antisolvent (water) combined with distillation was proposed as an efficient method to recover apigenin and luteolin from the DES extract. The relationship between components of DES and solubility of apigenin, luteolin was also established which was the starting point for the prediction of extractability of DES. Molecular dynamics revealed that betaine hydrochloride and propylene glycol could interact with each other by the formation of two types of hydrogen bond while water molecules might play an important role in the ability to dissolve apigenin and luteolin of DES.
Topics: Apigenin; Apium; Luteolin; Seeds; Solvents
PubMed: 34653746
DOI: 10.1016/j.jpba.2021.114406 -
Journal of Environmental Science and... 2023Tetrabromobisphenol A (TBBPA) is a reactive brominated flame retardant widely used in various industrial and household products. This compound is persistent in the...
Tetrabromobisphenol A (TBBPA) is a reactive brominated flame retardant widely used in various industrial and household products. This compound is persistent in the environment and accumulates in living organisms through the food chain, and is toxic to animals and human beings. Studies have shown that TBBPA is toxic to various human cell lines, including neuronal cells. Apigenin is a dietary flavonoid that exhibits various beneficial health effects on biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated the cytoprotective effects of apigenin against TBBPA-mediated cytotoxicity in SK-N-MC cells. Our results demonstrated that treatment of SK-N-MC cells with apigenin increased the cell viability, which was decreased by TBBPA, and reduced apoptosis and autophagy induced by TBBPA. Although we did not observe any change in the levels of IL-1β and nitrite in cultured cells after TBBPA treatment, apigenin was found to decrease the production of these pro-inflammatory mediators. Apigenin decreased the intracellular Ca concentration, NOX4 level, oxidative stress, and mitochondrial membrane potential loss and increased the mitochondrial biogenesis and nuclear Nrf2 levels that were reduced by TBBPA. Finally, apigenin treatment decreased Akt and ERK induction in cells exposed to TBBPA. Based on these results, apigenin could be a promising candidate for designing natural drugs to treat or prevent TBBPA-related neurological disorders.
Topics: Animals; Humans; Reactive Oxygen Species; Apigenin; Oxidative Stress; Neurons; Polybrominated Biphenyls; Flame Retardants
PubMed: 36843298
DOI: 10.1080/10934529.2023.2182581