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Molecules (Basel, Switzerland) Apr 2023This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects... (Review)
Review
This review article describes studies published over the past five years on the combination of polyphenols, which are the most studied in the field of anticancer effects (curcumin, quercetin, resveratrol, epigallocatechin gallate, and apigenin) and chemotherapeutics such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, etc. According to WHO data, research has been limited to five cancers with the highest morbidity rate (lung, colorectal, liver, gastric, and breast cancer). A systematic review of articles published in the past five years (from January 2018 to January 2023) was carried out with the help of all Web of Science databases and the available base of clinical studies. Based on the preclinical studies presented in this review, polyphenols can enhance drug efficacy and reduce chemoresistance through different molecular mechanisms. Considering the large number of studies, curcumin could be a molecule in future chemotherapy cocktails. One of the main problems in clinical research is related to the limited bioavailability of most polyphenols. The design of a new co-delivery system for drugs and polyphenols is essential for future clinical research. Some polyphenols work in synergy with chemotherapeutic drugs, but some polyphenols can act antagonistically, so caution is always required.
Topics: Polyphenols; Curcumin; Resveratrol; Antioxidants; Drug Therapy, Combination
PubMed: 37175156
DOI: 10.3390/molecules28093746 -
The Kaohsiung Journal of Medical... Jul 2021The present study aimed to investigate the role of apigenin and the molecular mechanism of miR-152-5p and bromodomain containing 4 (BRD4) in the proliferation, invasion,...
The present study aimed to investigate the role of apigenin and the molecular mechanism of miR-152-5p and bromodomain containing 4 (BRD4) in the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of cervical carcinoma cells. Quantitative real-time PCR was used to detect the transfection efficiency and the expression of miR-152-5p and BRD4. Western blotting was conducted to evaluate the protein level of BRD4, E-cadherin, N-cadherin, and MMP9. Luciferase reporter assay was performed to confirm whether miR-152-5p bound to BRD4. MTT and Transwell invasion assay were applied to determine the cell proliferation and invasion, respectively. MiR-152-5p was downregulated and BRD4 was upregulated in cervical carcinoma tissue. Besides, miR-152-5p could directly bind to BRD4 in Hela and CaSki cells. In addition, apigenin inhibited proliferation, invasion, and EMT of Hela and CaSki cells by regulating miR-152-5p/BRD4 axis. Apigenin suppresses proliferation, invasion, and induced EMT of cervical carcinoma cells by regulation of miR-152-5p/BRD4 axis.
Topics: Apigenin; Carcinoma; Cell Cycle Proteins; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; MicroRNAs; Neoplasm Invasiveness; Nuclear Proteins; Tetrazolium Salts; Thiazoles; Transcription Factors; Uterine Cervical Neoplasms
PubMed: 33611824
DOI: 10.1002/kjm2.12370 -
International Journal of Molecular... May 2023Cancer is a widespread but dangerous disease that can strike anyone and is the second 1leading cause of death worldwide. Prostate cancer, in particular, is a prevalent... (Review)
Review
Cancer is a widespread but dangerous disease that can strike anyone and is the second 1leading cause of death worldwide. Prostate cancer, in particular, is a prevalent cancer that occurs in men, and much research is being done on its treatment. Although chemical drugs are effective, they have various side effects, and accordingly, anticancer drugs using natural products are emerging. To date, many natural candidates have been discovered, and new drugs are being developed as drugs to treat prostate cancer. Representative candidate compounds that have been studied to be effective in prostate cancer include apigenin, acacetin and tangeretin of the flavone family among flavonoids. In this review, we look at the effects of these three flavones on prostate cancer cells via apoptosis in vitro and in vivo. Furthermore, in addition to the existing drugs, we suggest the three flavones and their effectiveness as natural anticancer agents, a treatment model for prostate cancer.
Topics: Male; Humans; Flavones; Flavonoids; Apoptosis; Apigenin; Antineoplastic Agents; Prostatic Neoplasms
PubMed: 37298192
DOI: 10.3390/ijms24119240 -
Molecules (Basel, Switzerland) Mar 2023The overall purpose of this study was to investigate the mechanism of macrophage polarization on chondrocyte injury in osteoarthritis and the protective effect of...
OBJECTIVE
The overall purpose of this study was to investigate the mechanism of macrophage polarization on chondrocyte injury in osteoarthritis and the protective effect of apigenin on chondrocytes in osteoarthritis.
METHOD
Primary chondrocytes were isolated from the knee cartilage of three-day-old mice, and cells positive for Alsine blue staining and type II collagen immunocytochemical staining were identified and used in followup experiments. Transwell coculture was performed. Chondrocytes were inoculated in the inferior compartment, and macrophages were inoculated in the upper compartment. The experimental groups were the N group, LPS group, and LPS+ apigenin group. The effect of macrophage polarization on chondrocyte inflammation and the protective effect of apigenin on chondrocytes were verified by the drug administration. Real-time quantitative PCR (qPCR) and Western blot were used to detect the expression of RNA and protein. Experimental OA was induced by modified Hulth surgery in mice. Modified Hulth surgery was performed on the mouse's right knee to induce experimental osteoarthritis in mice, with the nonoperative right knee serving as an ipsilateral control. The mice were randomly assigned to three groups (six mice per group): the sham group, the modified Hulth group, and the modified Hulth + apigenin group. Animals were given gavage for four weeks. The protective effect of apigenin on articular cartilage was verified by histological staining and immunohistochemical analysis.
RESULTS
Histological staining showed that apigenin had a protective effect on cartilage degeneration induced by modified Hulth surgery. The PCR results showed that apigenin significantly reduced the expression levels of IL-1, IL-6, MMP3, and MMP13 in the articular cartilage of OA mice, and it had a protective effect on articular cartilage. Apigenin reduced the levels of IL-1, IL-6, TNF-α, and IL-12 in macrophages and increased the levels of MG-L1, MG-L2, ARG-1, and IL-10, which can inhibit the M1 polarization of macrophages and promote M2 polarization. In the coculture system, apigenin decreased the protein levels of TRPM7, P-mTOR, BAX, and c-caspase3 in macrophages, while significantly increasing the protein levels of Bcl2. The levels of IL-1, IL-6, MMP13, TNF-α, P38, JNK, and ERK phosphorylation were reduced in chondrocytes.
CONCLUSION
Apigenin alleviates cartilage injury in OA mice induced by modified Hulth. Apigenin inhibits chondrocyte inflammation through the MAPK pathway. Apigenin alleviates macrophage-polarization-induced inflammatory response and chondrocyte apoptosis in the macrophage-chondrocyte coculture system through the TRPM7-mTOR pathway.
Topics: Mice; Animals; Matrix Metalloproteinase 13; Apigenin; TRPM Cation Channels; Tumor Necrosis Factor-alpha; Interleukin-6; Lipopolysaccharides; Disease Models, Animal; Osteoarthritis; Inflammation; Cartilage, Articular; Chondrocytes; Macrophages; TOR Serine-Threonine Kinases; Interleukin-1
PubMed: 37049677
DOI: 10.3390/molecules28072915 -
Molecules (Basel, Switzerland) Jun 2024Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores...
Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores apigenin's capacity to modulate cancer cell viability, emphasizing its roles beyond its minimal antioxidant activity attributed to its basic molecular structure devoid of hydroxyl groups. We investigated apigenin's effects on two breast cancer cell lines, estrogen-dependent MCF-7 and non-estrogen-dependent MDA-MB-231 cells. Our findings reveal that apigenin exerts a dose-dependent cytotoxic and anti-migratory impact on these cells. Interestingly, both apigenin and doxorubicin-a standard chemotherapeutic agent-induced lipid droplet accumulation in a dose-dependent manner in MDA-MB-231 cells. This phenomenon was absent in MCF-7 cells and not evident when doxorubicin and apigenin were used concurrently, suggesting distinct cellular responses to these treatments that imply that their synergistic effects might be mediated through mechanisms unrelated to lipid metabolism. A further chemoinformatics analysis indicated that apigenin and doxorubicin might interact primarily at the level of ATP-binding cassette (ABC) transporter proteins, with potential indirect influences from the AKT and MYC signaling pathways. These results highlight the importance of understanding the nuanced interactions between apigenin and conventional chemotherapeutic drugs, as they could lead to more effective strategies for cancer treatment. This study underscores apigenin's potential as a modulator of cancer cell dynamics through mechanisms independent of its direct antioxidant effects, thereby contributing to the development of flavonoid-based adjunct therapies in cancer management.
Topics: Humans; Apigenin; Doxorubicin; Breast Neoplasms; Female; Cell Line, Tumor; Cell Survival; MCF-7 Cells; Cell Movement; Signal Transduction; Cell Proliferation; Drug Synergism
PubMed: 38893482
DOI: 10.3390/molecules29112603 -
Molecules (Basel, Switzerland) Mar 2023Flavones such as 7,8-dihydroxyflavone (tropoflavin), 5,6,7-trihydroxyflavone (baicalein), 3',4',5,6-tetrahydroxyflavone (luteolin), 3,3',4',5,5',7-hexahydroxyflavone... (Review)
Review
Flavones such as 7,8-dihydroxyflavone (tropoflavin), 5,6,7-trihydroxyflavone (baicalein), 3',4',5,6-tetrahydroxyflavone (luteolin), 3,3',4',5,5',7-hexahydroxyflavone (myricetin) 4',5,7-trihydroxyflavone (apigenin), and 5,7-dihydroxyflavone (chrysin) are important both for their presence in natural products and for their pharmacological applications. However, due to their chemical characteristics and their metabolic processes, they have low solubility and low bioavailability. Knowledge about the physicochemical properties of nanocarriers and the possible mechanisms of covalent and non-covalent interaction between nanoparticles (NPs) and drugs is essential for the design of nanocarriers to improve the bioavailability of molecules with pharmacological potential, such as tropoflavin, baicalein, luteolin, myricetin, apigenin, and chrysin. The parameters of characterization of some NPs of these flavones, such as size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), and % release/time, utilized in biomedical applications and the covalent and non-covalent interactions existing between the polymeric NPs and the drug were analyzed. Similarly, the presence of functional groups in the functionalized carbon nanotubes (CNTs), as well as the effect of pH on the % adsorption of flavonoids on functionalized multi-walled carbon nanotubes (MWCNT-COOH), were analyzed. Non-covalent interaction mechanisms between polymeric NPs and flavones, and covalent interaction mechanisms that could exist between the NPs and the amino and hydroxyl functional groups, are proposed.
Topics: Flavones; Nanotubes, Carbon; Apigenin; Luteolin; Flavonoids
PubMed: 36985836
DOI: 10.3390/molecules28062864 -
Bioengineered Feb 2022The COVID-19 new variants spread rapidly all over the world, and until now scientists strive to find virus-specific antivirals for its treatment. The main protease of...
The COVID-19 new variants spread rapidly all over the world, and until now scientists strive to find virus-specific antivirals for its treatment. The main protease of SARS-CoV-2 (M) exhibits high structural and sequence homology to main protease of SARS-CoV (93.23% sequence identity), and their sequence alignment indicated 12 mutated/variant residues. The sequence alignment of SARS-CoV-2 main protease led to identification of only one mutated/variant residue with no significant role in its enzymatic process. Therefore, M was considered as a high-profile drug target in anti-SARS-CoV-2 drug discovery. Apigenin analogues to COVID-19 main protease binding were evaluated. The detailed interactions between the analogues of Apigenin and SARS-CoV-2 M inhibitors were determined as hydrogen bonds, electronic bonds and hydrophobic interactions. The binding energies obtained from the molecular docking of M with Boceprevir, Apigenin, Apigenin 7-glucoside-4'-p-coumarate, Apigenin 7-glucoside-4'-trans-caffeate and Apigenin 7-O-beta-d-glucoside (Cosmosiin) were found to be -6.6, -7.2, -8.8, -8.7 and -8.0 kcal/mol, respectively. Pharmacokinetic parameters and toxicological characteristics obtained by computational techniques and Virtual ADME studies of the Apigenin analogues confirmed that the Apigenin 7-glucoside-4'-p-coumarate is the best candidate for SARS-CoV-2 M inhibition.
Topics: Amino Acid Sequence; Antiviral Agents; Apigenin; Bioengineering; COVID-19; Computer Simulation; Coronavirus 3C Proteases; Cysteine Proteinase Inhibitors; Drug Evaluation, Preclinical; Glucosides; Humans; Molecular Docking Simulation; Phytotherapy; Protein Domains; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35048792
DOI: 10.1080/21655979.2022.2027181 -
International Journal of Biological... 2023Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced...
Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced cardiomyopathy, the underlying mechanisms remain incompletely understood. Since apigenin beneficially regulates various aspects of mitochondrial function and dynamics, we asked whether apigenin improves heart function in mice with Dox-induced cardiomyopathy by regulating the mitochondrial unfolded protein response (UPR). Co-administration of apigenin significantly restored heart function, reduced myocardial swelling, inhibited cardiac inflammation, increased cardiac transcription of UPR-related genes, and promoted cardiomyocyte survival in Dox-treated mice. In turn, blockade of UPR abolished the mito- and cytoprotective effects of apigenin, evidenced by decreased ATP production, suppressed mitochondrial antioxidant capacity, and increased apoptosis, in Dox-treated, cultured HL-1 cardiomyocytes. Furthermore, apigenin treatment prevented Dox-induced downregulation of Sirt1 and Atf5 expression, and the beneficial effects of apigenin were completely nullified in knockout (KO) mice or after siRNA-mediated knockdown . We thus provide novel evidence for a promotive effect of apigenin on UPR via regulation of the Sirt1/Atf5 pathway. Our findings uncover that apigenin seems to be an effective therapeutic agent to alleviate Dox-mediated cardiotoxicity.
Topics: Mice; Animals; Apigenin; Sirtuin 1; Myocytes, Cardiac; Cardiotoxicity; Cardiomyopathies; Mice, Knockout; Doxorubicin; Apoptosis; Oxidative Stress
PubMed: 37928261
DOI: 10.7150/ijbs.85204 -
BMC Ophthalmology Jul 2023Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to...
BACKGROUND
Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism.
METHODS
Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay.
RESULTS
HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway.
CONCLUSIONS
Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.
Topics: Humans; Proto-Oncogene Proteins c-akt; MicroRNAs; Phosphatidylinositol 3-Kinases; Apigenin; Signal Transduction; Endothelial Cells; Diabetic Retinopathy; Cell Proliferation; PTEN Phosphohydrolase
PubMed: 37415101
DOI: 10.1186/s12886-023-03046-5 -
Frontiers in Pharmacology 2022The initial responses to standard chemotherapies among prostate cancer (PCa) patients are usually significant, while most of them will finally develop drug resistance,... (Review)
Review
The initial responses to standard chemotherapies among prostate cancer (PCa) patients are usually significant, while most of them will finally develop drug resistance, rendering them with limited therapies. To discover new regimens for the treatment of PCa including resistant PCa, natural products, the richest source of bioactive compounds, can serve as a library for screening and identifying promising candidates, and flavones such as apigenin and genistein have been used in lab and clinical trials for treating PCa over decades. In this mini-review, we take a look into the progress of apigenin and genistein, which are isomers, in treating PCa in the past decade. While possessing very similar structure, these two isomers can both target the same signaling pathways; they also are found to work differently in PCa cells. Given that more combinations are being developed and tested, genistein appears to be the more promising option to be approved. The anticancer efficacies of these two flavones can be confirmed by and studies, and their applications remain to be validated in clinical trials. Information gained in this work may provide important information for new drug development and the potential application of apigenin and genistein in treating PCa.
PubMed: 35359832
DOI: 10.3389/fphar.2022.851589