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International Journal of Molecular... Mar 2019Several plant bioactive compounds have exhibited functional activities that suggest they could play a remarkable role in preventing a wide range of chronic diseases. The... (Review)
Review
Several plant bioactive compounds have exhibited functional activities that suggest they could play a remarkable role in preventing a wide range of chronic diseases. The largest group of naturally-occurring polyphenols are the flavonoids, including apigenin. The present work is an updated overview of apigenin, focusing on its health-promoting effects/therapeutic functions and, in particular, results of in vivo research. In addition to an introduction to its chemistry, nutraceutical features have also been described. The main key findings from in vivo research, including animal models and human studies, are summarized. The beneficial indications are reported and discussed in detail, including effects in diabetes, amnesia and Alzheimer's disease, depression and insomnia, cancer, etc. Finally, data on flavonoids from the main public databases are gathered to highlight the apigenin's key role in dietary assessment and in the evaluation of a formulated diet, to determine exposure and to investigate its health effects in vivo.
Topics: Animals; Apigenin; Chronic Disease; Dietary Supplements; Humans; Molecular Structure; Wound Healing
PubMed: 30875872
DOI: 10.3390/ijms20061305 -
International Journal of Molecular... Jun 2020Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on...
Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 μM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1β, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase [iNOS]), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 μM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human β-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.
Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Apigenin; Cell Line; Cytokines; Extracellular Signal-Regulated MAP Kinases; Filaggrin Proteins; HaCaT Cells; Humans; Immunoglobulin E; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Mast Cells; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; RAW 264.7 Cells; Rats; Receptors, IgE; Signal Transduction; Skin; Skin Diseases; Skin Physiological Phenomena; Tumor Necrosis Factor-alpha
PubMed: 32610574
DOI: 10.3390/ijms21134620 -
Cell Death & Disease Nov 2020Idiopathic pulmonary fibrosis (IPF) is featured with inflammation and extensive lung remodeling caused by overloaded deposition of extracellular matrix. Scutellarin is...
Idiopathic pulmonary fibrosis (IPF) is featured with inflammation and extensive lung remodeling caused by overloaded deposition of extracellular matrix. Scutellarin is the major effective ingredient of breviscapine and its anti-inflammation efficacy has been reported before. Nevertheless, the impact of scutellarin on IPF and the downstream molecular mechanism remain unclear. In this study, scutellarin suppressed BLM-induced inflammation via NF-κB/NLRP3 pathway both in vivo and in vitro. BLM significantly elevated p-p65/p65 ratio, IκBα degradation, and levels of NLRP3, caspase-1, caspase-11, ASC, GSDMD, IL-1β, and IL-18, while scutellarin reversed the above alterations except for that of caspase-11. Scutellarin inhibited BLM-induced epithelial-mesenchymal transition (EMT) process in vivo and in vitro. The expression levels of EMT-related markers, including fibronectin, vimentin, N-cadherin, matrix metalloproteinase 2 (MMP-2) and MMP-9, were increased in BLM group, and suppressed by scutellarin. The expression level of E-cadherin showed the opposite changes. However, overexpression of NLRP3 eliminated the anti-inflammation and anti-EMT functions of scutellarin in vitro. In conclusion, scutellarin suppressed inflammation and EMT in BLM-induced pulmonary fibrosis through NF-κB/NLRP3 signaling.
Topics: Animals; Apigenin; Epithelial-Mesenchymal Transition; Glucuronates; Inflammation; Male; Mice; NF-kappa B; Pulmonary Fibrosis; Transfection
PubMed: 33188176
DOI: 10.1038/s41419-020-03178-2 -
CNS Neuroscience & Therapeutics Nov 2022To investigate the effect of apigenin on fibrous scar formation after mouse spinal cord injury (SCI).
AIM
To investigate the effect of apigenin on fibrous scar formation after mouse spinal cord injury (SCI).
METHODS
The pneumatic impactor strike method was used to establish an SCI model. Mice were intraperitoneally injected with 5 mg/kg or 20 mg/kg apigenin daily for 28 days after SCI. The Basso Mouse Scale (BMS) score, hematoxylin-eosin staining, and immunohistochemical staining were used to assess the effect of apigenin on scar formation and motor function recovery. Western blotting and qRT-PCR were used to detect the expression of fibrosis-related parameters in spinal cord tissue homogenates. NIH-3 T3 cells and mouse primary spinal cord fibroblasts, α-Smooth muscle actin (α-SMA), collagen 1, and fibronectin were used to evaluate apigenin's effect in vitro. Western blotting and immunofluorescence techniques were used to study the effect of apigenin on TGFβ/SMADs signaling.
RESULTS
Apigenin inhibited fibrous scar formation in the mouse spinal cord and promoted the recovery of motor function. It reduced the expression of fibroblast-related parameters and increased the content of nerve growth factor in vivo, decreasing myofibroblast activation and collagen fiber formation by inhibiting TGFβ-induced SMAD2/3 phosphorylation and nuclear translocation in vitro.
CONCLUSION
Apigenin inhibits fibrous scar formation after SCI by decreasing fibrosis-related factor expression through TGFβ/SMADs signaling.
Topics: Actins; Animals; Apigenin; Cicatrix; Collagen; Eosine Yellowish-(YS); Fibronectins; Hematoxylin; Mice; Nerve Growth Factors; Recovery of Function; Signal Transduction; Spinal Cord; Spinal Cord Injuries; Transforming Growth Factor beta
PubMed: 35906830
DOI: 10.1111/cns.13929 -
Biomedicine & Pharmacotherapy =... May 2021Doxorubicin (DOX) is an anthracycline antitumor antibiotic widely utilized in treating various tumors. Nevertheless, the toxicity of DOX toward normal cells limits its...
BACKGROUND AND OBJECTIVE
Doxorubicin (DOX) is an anthracycline antitumor antibiotic widely utilized in treating various tumors. Nevertheless, the toxicity of DOX toward normal cells limits its applicability, with nephrotoxicity considered a major dose-limiting adverse effect. Apigenin (APG), a flavonoid widely distributed in natural plants, has been reported to have antioxidant, anti-inflammatory, and mild tumor-suppressive properties. In this study, we investigated the role of APG in DOX-induced nephrotoxicity and chemotherapeutic efficacy.
METHODS
Male BALB/c mice were administered DOX (11.5 mg/kg) via the tail vein to establish the DOX nephropathy model. After treatment with or without APG (125, 250, and 500 mg/kg) for two weeks, urine, serum, and tissue samples were collected to evaluate proteinuria, serum albumin, serum creatinine (Scr), blood urea nitrogen (BUN), superoxide dismutase (SOD) activity, malondialdehyde (MDA), glutathione (GSH), and pathological changes. Rat renal tubular epithelial cells (NRK52E), murine podocyte cells (MPC5), and murine breast cancer cells (4T1) were utilized to verify the effect of APG on DOX-induced cell injury. An MTT assay was employed to analyze cell viability. Apoptosis was evaluated using a colorimetric TUNEL staining and cleaved caspase-3 protein analysis by western blotting. A reactive oxygen species (ROS)/superoxide (O-) fluorescence probe was employed to determine oxidative injury. Western blotting was used to analyze nephrin, α-smooth muscle actin (α-SMA), collagen I (Col1), fibronectin (FN), and SOD2 expression. The mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), IL-6, NACHT, LRR, PYD domain-containing protein 3 (NLRP3), caspase-1, and IL-1β were tested by reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS
APG ameliorated DOX-elicited renal injuries in both the glomeruli and tubules. The DOX + APG groups had much lower tissue MDA, IL-6, TNF-α, NLRP3, caspase-1, and IL-1β levels and generation of intracellular ROS, but significantly higher SOD activity and GSH levels compared to those of the DOX group. Additionally, APG attenuated DOX-induced morphological changes, loss of cellular viability, and apoptosis in NRK-52E and MPC-5 cells, but not in 4T1 cells.
CONCLUSION
APG has a protective role against DOX-induced nephrotoxicity, without weakening DOX cytotoxicity in malignant tumors. Thus, APG may serve as a potential protective agent against renal injury and inflammatory diseases and may be a promising candidate to attenuate renal toxicity in cancer patients treated with DOX.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibiotics, Antineoplastic; Antioxidants; Apigenin; Apoptosis; Cell Line, Tumor; Doxorubicin; Kidney Diseases; Kidney Function Tests; Kidney Glomerulus; Kidney Tubules; Male; Mice; Mice, Inbred BALB C; Oxidative Stress; Rats; Reactive Oxygen Species
PubMed: 33556877
DOI: 10.1016/j.biopha.2021.111308 -
Redox Biology Nov 2021Although effective drugs have been developed, including 5-fluorouracil (5-FU), advanced colorectal cancer (CRC) shows low therapeutic sensitivity resulting from the...
Although effective drugs have been developed, including 5-fluorouracil (5-FU), advanced colorectal cancer (CRC) shows low therapeutic sensitivity resulting from the development of 5-FU resistance. Thymidylate synthase (TS) is a target protein of 5-FU, and elevated TS lowers the 5-FU sensitivity of CRC cells. Here, we tested the efficacy of several candidate phytochemicals against human CRC-derived HCT116 cells expressing wild-type tumor suppressor protein P53 and HT29 cells expressing mutant P53. Among them, we found that apigenin enhanced the inhibitory effect of 5-FU on cell viability. In addition, apigenin inhibited the upregulation of TS induced by 5-FU. Apigenin also potentiated 5-FU-induced apoptosis of HCT116 cells and enhanced cell cycle disruption. Furthermore, apigenin increased reactive oxygen species production, intracellular and intramitochondrial Ca concentrations, and mitochondrial membrane potential upon cotreatment with 5-FU. Knockdown of forkhead box protein M, a transcription factor modulating 5-FU sensitivity, enhanced the potentiation of apoptosis by apigenin in HCT116 cells. Moreover, apigenin suppressed TS expression and inhibited the viability of 5-FU-resistant HCT116 cells. Therefore, apigenin may improve the therapeutic efficacy of 5-FU against CRC by suppressing TS, but apoptosis induction is mainly dependent on functional P53.
Topics: Antineoplastic Combined Chemotherapy Protocols; Apigenin; Apoptosis; Colorectal Neoplasms; Drug Resistance, Neoplasm; Drug Synergism; Fluorouracil; Humans; Thymidylate Synthase
PubMed: 34562873
DOI: 10.1016/j.redox.2021.102144 -
Nutrients Jan 2023Apigenin is a naturally occurring dietary flavonoid found abundantly in fruits and vegetables. It possesses a wide range of biological properties that exert antioxidant,... (Review)
Review
Apigenin is a naturally occurring dietary flavonoid found abundantly in fruits and vegetables. It possesses a wide range of biological properties that exert antioxidant, anti-inflammatory, anticancer, and antibacterial effects. These effects have been reported to be beneficial in the treatment of atherosclerosis, stroke, hypertension, ischemia/reperfusion-induced myocardial injury, and diabetic cardiomyopathy, and provide protection against drug-induced cardiotoxicity. These potential therapeutic effects advocate the exploration of the cardioprotective actions of apigenin. This review focuses on apigenin, and the possible pharmacological mechanisms involved in the protection against cardiovascular diseases. We further discuss its therapeutic uses and highlight its potential applications in the treatment of various cardiovascular disorders. Apigenin displays encouraging results, which may have implications in the development of novel strategies for the treatment of cardiovascular diseases. With the commercial availability of apigenin as a dietary supplement, the outcomes of preclinical studies may provide the investigational basis for future translational strategies evaluating the potential of apigenin in the treatment of cardiovascular disorders. Further preclinical and clinical investigations are required to characterize the safety and efficacy of apigenin and establish it as a nutraceutical as well as a therapeutic agent to be used alone or as an adjuvant with current drugs.
Topics: Humans; Cardiovascular Diseases; Apigenin; Antioxidants; Atherosclerosis; Anti-Inflammatory Agents
PubMed: 36678254
DOI: 10.3390/nu15020385 -
Frontiers in Bioscience (Landmark... Oct 2023Several antiviral drugs are clinically approved to treat influenza that is a highly prevalent acute respiratory disease. However, emerging drug-resistant virus strains... (Review)
Review
Several antiviral drugs are clinically approved to treat influenza that is a highly prevalent acute respiratory disease. However, emerging drug-resistant virus strains undermine treatment efficacy, highlighting the exigency for novel antiviral drugs to counter these drug-resistant strains. Plants and their derivates have been historically utilized as medicinal remedies, and extensive studies have evidenced the antiviral potential of phytochemicals. Notably, apigenin is a predominant flavonoid with minimal toxicity and substantial therapeutic effects in various disease models. Despite its many anti-inflammatory, anti-oxidant, anti-cancer, anti-bacterial, and other beneficial bioactivities, existing reviews have yet to focus on apigenin's antiviral effects. Therefore, this review elucidates apigenin's therapeutic and antiviral properties and , discussing its mode of action and future prospects. Apigenin's remarkable inhibition by modulating multiple mechanisms against viruses has promising potential for novel plant-derived antiviral drugs and further clinical study developments.
Topics: Humans; Apigenin; Virus Diseases; Neoplasms; Flavonoids; Antiviral Agents
PubMed: 37919082
DOI: 10.31083/j.fbl2810237 -
International Journal of Molecular... Oct 2022Mineralization-competent cells like osteoblasts and chondrocytes release matrix vesicles (MVs) which accumulate Ca and P, creating an optimal environment for apatite...
Mineralization-competent cells like osteoblasts and chondrocytes release matrix vesicles (MVs) which accumulate Ca and P, creating an optimal environment for apatite formation. The mineralization process requires the involvement of proteins, such as annexins (Anx) and tissue-nonspecific alkaline phosphatase (TNAP), as well as low molecular-weight compounds. Apigenin, a flavonoid compound, has been reported to affect bone metabolism, but there are doubts about its mechanism of action under physiological and pathological conditions. In this report, apigenin potency to modulate annexin A6 (AnxA6)- and TNAP-mediated osteoblast mineralization was explored using three cell lines: human fetal osteoblastic hFOB 1.19, human osteosarcoma Saos-2, and human coronary artery smooth muscle cells HCASMC. We compared the mineralization competence, the morphology and composition of minerals, and the protein distribution in control and apigenin-treated cells and vesicles. The mineralization ability was monitored by AR-S/CPC analysis, and TNAP activity was determined by ELISA assay. Apigenin affected the mineral structure and modulated TNAP activity depending on the concentration. We also observed increased mineralization in Saos-2 cells. Based on TEM-EDX, we found that apigenin influenced the mineral composition. This flavonoid also disturbed the intracellular distribution of AnxA6 and TNAP, especially blocking AnxA6 aggregation and TNAP attachment to the membrane, as examined by FM analysis of cells and TEM-gold analysis of vesicles. In summary, apigenin modulates the mineralization process by regulating AnxA6 and TNAP, as well as through various effects on normal and cancer bone tissues or atherosclerotic soft tissue.
Topics: Humans; Alkaline Phosphatase; Annexin A6; Apigenin; Calcification, Physiologic; Osteoblasts
PubMed: 36361965
DOI: 10.3390/ijms232113179 -
Scientific Reports May 2022Apigenin is a dietary polyphenol found abundantly in fruit and vegetables, which sensitizes leukaemia cells to topoisomerase inhibitor agents (e.g., etoposide), and...
Apigenin is a dietary polyphenol found abundantly in fruit and vegetables, which sensitizes leukaemia cells to topoisomerase inhibitor agents (e.g., etoposide), and alkylating agents (e.g., cyclophosphamide), reducing ATP levels and inducing apoptosis; whilst being protective to control haematopoietic stem cells. This study analysed the expression profiles of intrinsic and extrinsic apoptosis-related genes and proteins to help elucidate the mechanisms of action of apigenin when used in combination with etoposide or cyclophosphamide in lymphoid and myeloid leukaemia cell lines (Jurkat and THP-1). Expression of apoptosis-related genes were measured using a TaqMan® Human Apoptosis Array and the StepOne Plus RT-qPCR System, whilst apoptosis-related proteins were determined using a protein profiler™-human apoptosis array and the LI-COR Odyssey Infrared Imaging System. Apigenin when combined with etoposide or cyclophosphamide-induced apoptosis via the mitochondrial pathway, increasing the expression of pro-apoptotic cytochrome c, SMAC/DIABLO, and HTRA2/OMI, which promoted caspase-9 and -3 activation. Targeting anti-apoptotic and/or pro-apoptotic members of the apoptotic pathways is a promising strategy to induce cancer cell death and improve sensitivity to chemotherapy agents. Here the apoptotic pathways induced by apigenin in combination with etoposide or cyclophosphamide were identified within human leukaemia cell lines, such applications could provide combination therapies for the treatment of leukaemia.
Topics: Apigenin; Apoptosis; Apoptosis Regulatory Proteins; Cell Line; Cyclophosphamide; Drug Therapy, Combination; Etoposide; Humans; Leukemia; Mitochondrial Proteins
PubMed: 35614109
DOI: 10.1038/s41598-022-11441-z