Effects Of Apigenin Research Articles

Pharmacodynamic interaction profile of apigenin with diclofenac in an experimental model of inflammation in rats

Objectives: Chronic use of non-steroidal anti-inflammatory drugs(NSAID’s) is often limited by their side effect, necessitating the development of safer therapeutic alternatives. Apigenin, A plant flavonoid, has shown potential in enhancing the efficacy of NSAIDs while potentially reducing their adverse effects. This study aimed to evaluate the synergistic effects of apigenin combined with a subtherapeutic dose of diclofenac on inflammation in a rat model, to determine whether such a combination can improve anti-inflammatory effectiveness and reduce the drug dose required. Materials and Methods: A total of 42 Wistar albino rats were randomised into seven groups to receive various treatments including control (normal saline), standard diclofenac (100 mg/kg), three doses of apigenin (10, 20 and 40 mg/kg), a subtherapeutic dose of diclofenac (50 mg/kg) and a combination of apigenin (20 mg/kg) with diclofenac (50 mg/kg). Inflammation was induced using carrageenan, and paw volume was measured at multiple time points to assess oedema. The percentage change from baseline paw volume and percentage protection against paw oedema was calculated for each group. Results: The study found that the combination of 20 mg/kg apigenin with 50 mg/kg diclofenac significantly enhanced the anti-inflammatory response, achieving a peak reduction in paw volume of up to 49.66% at 3 h post-administration. This was superior to the responses seen with apigenin or diclofenac alone, where the maximal dose of apigenin (40 mg/kg) only managed a peak reduction of 28.18%, and the standard dose of diclofenac (100 mg/kg) reached a peak inhibition of 66.66% at 6 h. The subtherapeutic dose of diclofenac (50 mg/kg), used alone, showed a lower peak effect of 21.47% at 3 h. These results underscore the enhanced efficacy of the combination therapy, potentially allowing for lower doses of diclofenac while maintaining effective anti-inflammatory action. Conclusion: The findings suggest that combining apigenin with diclofenac enhances anti-inflammatory responses, supporting the potential of flavonoid-NSAID combinations as more effective and safer anti-inflammatory therapies. Future studies should explore the long-term effects and mechanisms of action to fully understand the benefits and limitations of such combinations in managing chronic inflammation.

Protective Effects of Apigenin in Neurodegeneration: An update on the Potential Mechanisms

Protective Effects of Apigenin in Neurodegeneration: An update on the Potential Mechanisms

Apigenin Induces Apoptosis and Inhibits Migration in Human Cholangiocarcinoma Cells

Cholangiocarcinoma (CCA) is a rare and highly aggressive cancer of the biliary tract, associated with poor clinical outcomes due to late diagnosis, extensive metastasis, drug resistance, and limited treatment options. Apigenin, a natural flavonoid, has been found to exhibit anticancer properties in several types of human cancer cells. Therefore, apigenin may be relevant to developing chemotherapeutic agents for cancer treatment. In this study, we examined the effects of apigenin on cell viability, cell cycle distribution, apoptosis, and cell migration in human CCA cell lines (KKU-M055) under in vitro conditions. The results demonstrate that apigenin significantly suppressed specific CCA cell proliferation by inducing cell cycle arrest at the G2/M phase and promoting cell apoptosis in KKU-M055 cells while exhibiting low toxicity in immortalized MMNK1 cells. Apigenin enhanced apoptotic features, including nuclear fragmentation and the loss of mitochondrial membrane potential. Furthermore, apigenin induced the apoptosis of KKU-M055 cells in both extrinsic and intrinsic pathways by activating caspase-8, -9, and -3/7. Moreover, apigenin inhibited KKU-M055 migration. Our study suggests apigenin as a promising candidate for treating CCA, and these findings provide theoretical support for the further development and potential application of apigenin in clinical CCA therapy.

Apigenin enhancing oxidative resistance and proteostasis to extend lifespan via PTEN-mediated AKT signalling pathway.

Aging is a complicated process, featuring the progressive deterioration of physiological functions and a heightened susceptibility to diseases including neurodegenerative disorders, cardiovascular diseases, and cancer. Apigenin, a flavonoid existing in various plants, has attracted attention due to its potential role in anti-aging. In this investigation, the potential effect of apigenin on extending lifespan in Saccharomyces cerevisiae (yeast) and Drosophila melanogaster (flies) was explored. The results indicate that apigenin significantly extends both replicative and chronological life duration in yeast, as well as longevity in male and female flies. Apigenin treatment also improves resistance to oxidative stress in both organisms, as manifested by enhanced survival, decreased reactive oxygen species (ROS) levels and upregulation of antioxidant enzymes. Furthermore, apigenin activates crucial elements of the proteostasis network (PN), such as upregulation of proteostasis-related enzymes activity and genes expression. Network analysis revealed that apigenin affects aging conserved in the longevity-regulating pathway. Notably, Pten is a hub target in flies. Apigenin regulated DmPten at both mRNA and protein expression level while modulating downstream targets, including the phosphorylation of AKT and associated signalling pathways. In a high-sucrose diet (HSD) model, Apigenin treatment extended lifespan, reduced hemolymph glucose levels, enhanced Pten expression, suppressed AKT phosphorylation, and modulated the phosphorylation status of S6K and expression of DmFoxo. These results demonstrate that apigenin could serve as a longevity research object and potential therapeutic drug for promoting health and longevity through its antioxidant and proteostatic properties.

The therapeutic potential of apigenin against atherosclerosis.

Apigenin is a natural flavonoid abundantly found in fruits, vegetables, and medicinal plants. It possesses protective effects against cancer, metabolic syndrome, dyslipidemia, etc. Atherosclerosis, a chronic immune-mediated inflammatory disease, is the underlying cause of coronary heart disease, stroke, and myocardial infarction. Numerous in vivo and in vitro studies have shown a protective effect of apigenin against atherosclerosis, attributed to its antioxidant and anti-inflammatory properties, as well as its antihypertensive effect and regulation of lipid metabolism. This study aimed to review the effects and mechanisms of apigenin against atherosclerosis for the first time. Apigenin displays encouraging results, and this review confirms the potential value of apigenin as a candidate medication for atherosclerosis.

CD38 Coordinates with NF-κB to Promote Cochlear Inflammation in Noise-Induced Hearing Loss: the Protective Effect of Apigenin.

Noise exposure is one of the most common causes of sensorineural hearing loss. Although many studies considered inflammation to be a major contributor to noise-induced hearing loss, the process of cochlear inflammation is still unclear. Studies have found that activation of the NF-κB signaling pathway results in the accumulation of macrophages in the inner ear plays an important role in hair cell damage. In this study, tandem mass tag (TMT) technique was used to analyze the changes in basilar membrane proteome expression before and after acoustic injury. After noise exposure, the nicotinamide adenine dinucleotide (NAD) metabolism level was decreased, and the NF-κB signaling pathway was activated. The expression of CD38, the main NAD hydrolase in mammals, may directly lead to inflammation onset. Then, anakinra, an IL-1 receptor blocker, and apigenin, a CD38 inhibitor, were administered to animals to protect against noise-induced hearing loss. Our results showed that anakinra had little influence on the hearing threshold shift, while apigenin significantly reduce the threshold shift of hearing by inhibiting the expression of NF-κB and CD38 can be a promising target for protecting against noise-induced hearing loss.

A systems biology-based study to assess the effects of TNF-alpha ± apigenin in triple-negative breast cancer cell line

Triple-negative breast cancer (TNBC) is a type of breast cancer that lacks estrogen, progesterone, and HER2 receptors. Various treatment methods are available for breast cancer, but therapies with minimal toxic side effects are particularly important. This study computationally investigates the impact of apigenin, a compound used in traditional Chinese medicine, on the TNBC cell line. The GSE120550 dataset was retrieved from the NCBI-GEO database. BRB-ArrayTools were used for pre- and post-processing to identify significantly differentially expressed genes. Additionally, the DAVID web server was utilized to analyze three main components:"biological process," "cellular component," and "molecular function," along with the KEGG signaling pathway. Finally, a Venn diagram was employed to thoroughly investigate the number of shared genes among 15 groups derived from 6 compared sample sets. The primary analysis of 6 pairs of samples revealed significant differentially expressed genes (DEGs), which were prioritized using the TOPPgene web server. These identified genes, playing key roles in inhibiting the progression of BC, are involved in various signaling pathways. Protein-protein interaction network analysis highlighted the biomarkers associated with the inhibitory effects of apigenin across the 15 sets derived from the 6 sample pairs. The findings of this study confirm the inhibitory effects of apigenin, with no toxic side effects, on patients with TNBC. This natural compound holds promise for future therapeutics and novel drug designs.

Efficacy and Safety of Natural Apigenin Treatment for Alzheimer's Disease: Focus on In vivo Research Advancements.

Alzheimer's Disease (AD) is the most common dementia in clinics. Despite decades of progress in the study of the pathogenesis of AD, clinical treatment strategies for AD remain lacking. Apigenin, a natural flavonoid compound, is present in a variety of food and Chinese herbs and has been proposed to have a wide range of therapeutic effects on dementia. To clarify the relevant pharmacological mechanism and therapeutic effect of apigenin on animal models of AD. Computer-based searches of the PubMed, Cochrane Library, Embase, and Web of Science databases were used to identify preclinical literature on the use of apigenin for treating AD. All databases were searched from their respective inception dates until June 2023. The meta-analysis was performed with Review manager 5.4.1 and STATA 17.0. Thirteen studies were eventually enrolled, which included 736 animals in total. Meta-analysis showed that apigenin had a positive effect on AD. Compared to controls, apigenin treatment reduced escape latency, increased the percentage of time spent in the target quadrant and the number of plateaus traversed; apigenin was effective in reducing nuclear factor kappa-B (NF-κB) p65 levels; apigenin effectively increased antioxidant molecules SOD and GSH-px and decreased oxidative index MDA; for ERK/CREB/BDNF pathway, apigenin effectively increased BDNF and pCREB molecules; additionally, apigenin effectively decreased caspase3 levels and the number of apoptotic cells in the hippocampus. The results show some efficacy of apigenin in the treatment of AD models. However, further clinical studies are needed to confirm the clinical efficacy of apigenin.

Neuroprotective effects of Apigenin on prenatal Valproic acid-induced autism spectrum disorder in rats

Valproic acid (VPA) demonstrates teratogenic effects during pregnancy. Prenatal exposure to VPA may result in autism spectrum disorder (ASD) -like phenotypes. Apigenin, a natural flavonoid, has been shown to have neuroprotective impacts due to its antioxidant properties. This study aimed to investigate the protective effects of apigenin in prenatal Valproic acid-induced autism in rats. Female rats (220–240g, 2-3 months) received a single dose of VPA (600mg/kg, i.p.) on the 12.5th day of gestational. The male offspring were given oral apigenin (50mg/kg, p.o.) or the vehicle for 30 days. Behavioral tests, biochemical assessments for oxidative stress markers and pro-inflammatory cytokines were performed. VPA-treated rats exhibited increased anxiety-like behavior, and repetitive behavior. Social interaction was reduced, and detection of the novel object was impaired. Also, VPA-treated rats have shown higher levels of oxidative stress malondialdehyde (MDA) and lower GPX and superoxide dismutase (SOD) levels. Furthermore, IL-6 and TNF-α increased in the prefrotalcortex decreased. On the other hand, apigenin-treated rats restored the cognitive consequences and lowered oxidative stress and inflammation in the prefrotalcortex. ConclusionChronic apigenin treatment restored the behavioral and biochemical abnormalities caused by prenatal VPA exposure.

The Effect of Apigenin on Renal Damage Induced by Aristolochic Acid I and the Involvement of Nrf2/HO-1 Pathway

Background Aristolochic acid is naturally found in plants of the Aristolochiaceae family and possesses antitumor, anti-infection, and anti-inflammatory properties. Purpose This study investigated the protective effect of apigenin (API) on aristolochic acid I (AAI)-induced renal damage in mice and its underlying mechanisms. Methods Male C57BL/6J mice were assigned to the control group, model group, and API low, medium, and high-dose groups (10, 20, 40 mg/kg). On the 5th day, 2 h after administration, except for the control group, all other groups were intraperitoneally injected with AAI (10 mg/kg). Following final administration, 24-h urinary protein levels, serum creatinine (Scr), and blood urea nitrogen (BUN) levels were assessed along with hematoxylin–eosin (HE) staining of kidneys and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, as well as analysis of malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Results When compared with the model group, mice in API treatment groups exhibited significantly reduced 24-h urinary protein levels and serum levels of Scr and BUN ( p < 0.05) with an improvement in renal tissue histopathological changes and cell apoptosis as well as decreased MDA and increased SOD and GSH-Px ( p < 0.05). Tumor necrosis factor alpha protein (TNF-α)/interleukin (IL)-1β/IL-6 levels showed a reduction ( p < 0.05). Nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were upregulated, while NF-κB/Cleaved Caspase-3 were downregulated ( p < 0.01). Conclusion API protects against renal damage induced by AAI possibly through Nrf2/HO-1 pathway, which in turn inhibits oxidative stress damage, inflammatory responses, and cell apoptosis.

Apigenin Improves Ovarian Dysfunction Induced by 4-Vinylcyclohexene Diepoxide via the AKT/FOXO3a Pathway.

Perimenopausal syndrome is a significant issue that disturbs women's metabolism, mood and quality of life. Apigenin (4',5,7-trihydroxyflavone) is a natural flavonoid that exhibits antioxidant, anti-inflammatory and anticancer effects. The present study aims to investigate the effect of apigenin on perimenopausal syndrome by combining bioinformatics analysis with in vivo experiments. The mouse model with perimenopausal syndrome was established using 4-vinylcyclohexene diepoxide (VCD) treatment. Apigenin alleviated VCD-induced disorder of estrous cycle and shrinkage of ovarian tissue. The reduction of anti-Muller hormone and the increase of follicle stimulation hormone and luteinizing hormone triggered by VCD were reversed by apigenin in a dose-dependent manner. Apigenin suppressed the VCD-induced decrease of primordial, primary, secondary and antral follicle number in ovarian tissue. Oxidative stress in ovarian tissue was activated by VCD treatment through increasing the reactive oxygen species production. High concentration of apigenin significantly reversed the alteration induced by VCD. Apigenin alleviated VCD-induced cell apoptosis through regulating Bax, Bcl-2, cleaved PARP1 and caspase-3. Furthermore, the phosphorylation of AKT and FOXO3a was inhibited by VCD and activated by apigenin in a dose-dependent manner. Collectively, apigenin effectively mitigates the ovarian dysfunction through suppressing oxidative stress and apoptosis via the AKT/FOXO3a signaling pathway.

Apigenin as a Promising Agent for Enhancing Female Reproductive Function and Treating Associated Disorders.

Apigenin is an organic flavonoid abundant in some plants such as parsley, chamomile, or celery. Recently, it has been investigated for several of its pharmacological characteristics, such as its ability to act as an antioxidant, reduce inflammation, and inhibit the growth of cancer cells. The purpose of this review is to provide a summary of the existing knowledge regarding the effects of apigenin on female reproductive systems and its dysfunctions. Apigenin can influence reproductive processes by regulating multiple biological events, including oxidative processes, cell proliferation, apoptosis, cell renewal and viability, ovarian blood supply, and the release of reproductive hormones. It could stimulate ovarian folliculogenesis, as well as ovarian and embryonal cell proliferation and viability, which can lead to an increase in fertility and influence the release of reproductive hormones, which may exert its effects on female reproductive health. Furthermore, apigenin could inhibit the activities of ovarian cancer cells and alleviate the pathological changes in the female reproductive system caused by environmental pollutants, harmful medications, cancer, polycystic ovarian syndrome, ischemia, as well as endometriosis. Therefore, apigenin may have potential as a biostimulator for female reproductive processes and as a therapeutic agent for certain reproductive diseases.

Evaluating the potential effects of apigenin on memory, anxiety, and social interaction amelioration after social isolation stress.

Vigorous research confirmed the anti-inflammatory, antioxidant, and antidementia effects of apigenin (Api). The present study evaluated the beneficial impacts of Api administration on behaviour, brain-derived neurotrophic factor (BDNF), Interleukin 6 (IL-6), oxidative stress, and inflammation induced by social isolation (SI) stress in rats. For this purpose, rats underwent a 28-day SI period followed by a 4-week oral Api treatment (50 mg/kg/day, PO). On Day 56, behaviour tests were performed, including an elevated plus maze (EPM), Morris water maze (MWM), and three-chamber social tests. The oxidative stress markers, IL-6, and BDNF levels were measured in the hippocampus. Our results showed that SI stress caused an increase in anxiety and a decrease in spatial memory, sociability, and social preference index. In addition, SI stress increased hippocampal levels of IL-6 and malondialdehyde (MDA) content, whereas it reduced the hippocampal BDNF level and superoxide dismutase (SOD) activities. Our study indicated that Api attenuates anxiety and causes improvements in spatial memory and social interaction. These desirable effects of Api might be related to amelioration in the BDNF level, IL-6, and oxidative stress biomarkers in the hippocampus.

An Investigation of Pharmacokinetic Interaction of Vericiguat with Apigenin based on a Newly Developed Ultra-performance Liquid Chromatography-tandem Mass Spectrometry Assay.

Vericiguat, as a new stimulator of soluble guanylate cyclase (s- GC), was recently approved as a first-in-class treatment for reducing risks in patients with ejection fraction less than 45 percent and heart failure (HF) in the USA. The main aim of the present experiment was to establish an acceptable, sensitive assay based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for quantitatively analyzing the plasma concentration levels of vericiguat in rats, and to further evaluate the effect of apigenin on the metabolism of vericiguat in vivo. In sample processes, acetonitrile was finally chosen for quickly precipitating protein. The levels of vericiguat in plasma were analyzed by a Xevo TQ-S triple quadrupole tandem mass spectrometry (Milford, MA, USA) in a positive ion mode. The scope of the calibration standard for vericiguat ranged from 0.5 to 1000 ng/mL, where a great linearity was acceptable. The lower limit of quantification (also called LLOQ) of vericiguat presented the sensitivity of this assay was evaluated as low as 0.5 ng/mL. Additionally, selectivity, accuracy and precision, extraction recovery, matrix effect, and stability were all verified. Subsequently, this approach also supported to assess the plasmatic concentrations of vericiguat from an interaction survey on herb-- drug, in which oral administration of apigenin (20 mg/kg) obviously increased the plasmatic levels of vericiguat and altered the pharmacokinetics of vericiguat in rats. These results would help us to further understand the pharmacokinetic properties of vericiguat when co-administration with apigenin, and to avoid unexpected clinical risks in the future.

Apigenin Ameliorates H2O2-Induced Oxidative Damage in Melanocytes through Nuclear Factor-E2-Related Factor 2 (Nrf2) and Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (Akt)/Mammalian Target of Rapamycin (mTOR) Pathways and Reducing the Generation of Reactive Oxygen Species (ROS) in Zebrafish

Background: Apigenin is one of the natural flavonoids found mainly in natural plants, as well as some fruits and vegetables, with celery in particular being the most abundant. Apigenin has antioxidant, anti-tumor, anti-inflammatory, and anticancer effects. In this research, we attempted to further investigate the effects of apigenin on the mechanism of repairing oxidative cell damage. The present study hopes to provide a potential candidate for abnormal skin pigmentation disorders. Methods: We used 0.4 mM H2O2 to treat B16F10 cells for 12 h to establish a model of oxidative stress in melanocytes, and then we gave apigenin (0.1~5 μM) to B16F10 cells for 48 h, and detected the expression levels of melanin synthesis-related proteins, dendritic regulation-related proteins, antioxidant signaling pathway- and Nrf2 signaling pathway-related proteins, autophagy, and autophagy-regulated pathways by immunoblotting using Western blotting. The expression levels of PI3K/Akt/mTOR proteins were measured by β-galactosidase staining and Western blotting for cellular decay, JC-1 staining for mitochondrial membrane potential, and Western blotting for mitochondrial fusion- and mitochondrial autophagy-related proteins. Results: Apigenin exerts antioxidant effects by activating the Nrf2 pathway, and apigenin up-regulates the expression of melanin synthesis-related proteins Tyr, TRP1, TRP2, and gp100, which are reduced in melanocytes under oxidative stress. By inhibiting the expression of senescence-related proteins p53 and p21, and delaying cellular senescence, we detected the mitochondrial membrane potential using JC-1, and found that apigenin improved the reduction in mitochondrial membrane potential in melanocytes under oxidative stress, and maintained the normal function of mitochondria. In addition, we further detected the key regulatory proteins of mitochondrial fusion and division, MFF, p-DRP1 (S637), and p-DRP1 (S616), and found that apigenin inhibited the down-regulation of fusion-associated protein, p-DRP1 (S637), and the up-regulation of division-associated proteins, MFF and p-DRP1 (S616), due to oxidative stress in melanocytes, and promoted the mitochondrial fusion and ameliorated the imbalance between mitochondrial division and fusion. We further detected the expression of fusion-related proteins OPA1 and Mitofusion-1, and found that apigenin restored the expression of the above fusion proteins under oxidative stress, which further indicated that apigenin promoted mitochondrial fusion, improved the imbalance between mitochondrial division and fusion, and delayed the loss of mitochondrial membrane potential. Apigenin promotes the expression of melanocyte autophagy-related proteins and the key mitochondrial autophagy proteins BNIP3L/Nix under oxidative stress, and activates the PINK1/Parkin signaling pathway by up-regulating the expression of autophagy-related proteins, as well as the expression of PINK1 and Parkin proteins, to promote melanocyte autophagy and mitochondrial autophagy. Conclusions: Apigenin exerts anti-melanocyte premature aging and detachment effects by promoting melanin synthesis, autophagy, and mitochondrial autophagy in melanocytes, and inhibiting oxidative cell damage and senescence.

Apigenin With Protective Effect Against Oxidative Injury to Skeletal Muscle Cells via Activation of the Nrf-2HO-1 Pathway

Human skeletal muscle would suffer from an oxidative injury caused by long-term training or exhaustive exercise. It is important to scavenge oxygen free radicals in due course to reduce oxidative damage to human skeletal muscle cells (HSKMC) by some means. Apigenin, as an effective antioxidant, is likely to protect HSKMC against oxidative injury. In this study, tert-butyl hydroperoxide (t-BHP) was used to induce oxidative injured HSKMC. Then, we studied the protective effect of apigenin on cell viability, oxidative stress status, and the expression of antioxidation-related proteins and tried to understand the mechanisms driving these effects. Results show that the cellular viability of HSKMC could be obviously improved by apigenin treatment at the concentration of 80 μM. Pretreatment with celery resulted in the activity of related enzymes approaching normal levels, and decrease the release of malondialdehyde and the level of intracellular reactive oxygen species in HSKMC. The Nuclear factor E2-related factor (Nrf2) signaling pathway could also be activated by apigenin. Therefore, apigenin could attenuate t-BHP induced oxidative injury in HSKMC through enhancement of the activities of related antioxidant enzymes by activating the Nrf2 pathway.

Apigenin inhibits lipid metabolism of hepatocellular carcinoma cells by targeting the histone demethylase KDM1A

BackgroundThe development of cancer is accompanied by metabolic reprogramming, and the liver serves as a central hub for lipid transportation. Apigenin, a plant-derived flavonoid, demonstrates potent anticancer properties across various cancer types and exhibits promising potential as a therapeutic agent for cancer treatment. However, there are limited studies focusing on the downstream targets of apigenin. Moreover, there are few reports on the impact of apigenin in lipid metabolism within liver cancer cells. PurposeThe objective is to elucidate the metabolic mechanism underlying the inhibitory effect of apigenin on liver cancer progression, search for downstream targets and provide reliable data support for the clinical trials of apigenin. MethodsAnticancer effects of apigenin were detected at cellular and molecular levels in vitro, and downstream targets of apigenin, especially metabolic pathway genes, were analyzed by transcriptome. Next, the downstream target of apigenin was verified and the biological function of the downstream target was examined. Finally, the downstream target of apigenin was further verified by restoring target gene expression. ResultsCellular molecular experiments showed that Apigenin inhibited the proliferation, migration, invasion and lipid metabolism of hepatocellular carcinoma (HCC) cells. Transcriptome analysis showed apigenin widely regulates histone demethylase, particularly histone H3K4 lysine demethylase 1A (KDM1A). Apigenin treatment inhibited the expression of KDM1A protein and mRNA levels in liver cancer cells, molecular docking predicted the interaction between apigenin and KDM1A. Furthermore, downregulation KDM1A inhibited the proliferation and lipid metabolism of HCC cells, in the same way, overexpressing KDM1A promoted proliferation of HCC cells. Finally, restoring KDM1A expression partially attenuated the effects of apigenin on lipid metabolism in HCC cells. ConclusionIn conclusion, our study provides compelling evidence that apigenin inhibits liver cancer progression and elucidates its mechanism of action in regulating lipid metabolism. Specifically, we find that apigenin suppresses the progression of HCC cells by downregulating genes involved in lipid metabolism. Additionally, our results indicate that KDM1A acts as a downstream target of apigenin in the inhibition of lipid metabolism in HCC. These findings offer experimental support for the potential use of apigenin as a therapeutic agent for liver cancer, highlighting its relevance in future clinical applications.

Enhancing therapy with nano-based delivery systems: exploring the bioactive properties and effects of apigenin.

Apigenin, a potent natural flavonoid, has emerged as a key therapeutic agent due to its multifaceted medicinal properties in combating various diseases. However, apigenin's clinical utility is greatly limited by its poor water solubility, low bioavailability and stability issues. To address these challenges, this review paper explores the innovative field of nanotechnology-based delivery systems, which have shown significant promise in improving the delivery and effectiveness of apigenin. This paper also explores the synergistic potential of co-delivering apigenin with conventional therapeutic agents. Despite the advantageous properties of these nanoformulations, critical challenges such as scalable production, regulatory approvals and comprehensive long-term safety assessments remain key hurdles in their clinical adoption which must be addressed for commercialization of apigenin-based formulations.

Radiation-induced Testicular Damage in Mice: Protective Effects of Apigenin Revealed by Histopathological Evaluation.

Radiation exposure poses a significant threat to reproductive health, particularly the male reproductive system. The testes, being highly sensitive to radiation, are susceptible to damage that can impair fertility and overall reproductive function. The study aims to investigate the radioprotective effects of apigenin on the testis through histopathological evaluation. This research involved utilizing a total of 40 mice, which were randomly divided into eight groups of five mice each. The groups were categorized as follows: A) negative control group, B, C, and D) administration of apigenin at three different doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) respectively, E) irradiation group, and F, H, and I) administration of apigenin at three different doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) in combination with irradiation. The irradiation procedure involved exposing the mice to a 2Gy X-ray throughout their entire bodies. Subsequently, histopathological assessments were conducted seven days after the irradiation process. The findings indicated that radiation exposure significantly impacted the spermatogenesis system. This research provides evidence that administering apigenin to mice before ionizing radiation effectively mitigated the harmful effects on the testes. Apigenin demonstrated radioprotective properties, positively influencing various parameters, including the spermatogenesis process and the presence of inflammatory cells within the tubular spaces. Apigenin can provide effective protection for spermatogenesis, minimize the adverse effects of ionizing radiation, and safeguard normal tissues.

Dietary apigenin ameliorates obesity-related hypertension through TRPV4-dependent vasorelaxation and TRPV4-independent adiponectin secretion

BackgroundObesity-related hypertension is a major cardiovascular risk factor. Apigenin, a natural flavonoid in celery, induces vascular dilation via endothelial transient receptor potential channel vanilla 4 (TRPV4) channels. This study aimed to explore apigenin's potential to alleviate obesity-related hypertension in mice and its underlying mechanisms. MethodsThe C57BL/6 and TRPV4 knockout mice were fed a high-fat diet and subjected to dietary intervention with apigenin. Body weight and tail blood pressure of the mice were measured during the feeding. Vascular reactivity was assessed through a DMT wire myograph systems in vitro. The distribution and expression of adiponectin and pro-inflammatory markers in brown fat were detected. Injecting adeno-associated eight (AAV8) viruses into brown adipose tissue (BAT) to determine whether adiponectin is indispensable for the therapeutic effect of apigenin. Palmitic acid (PA) was used in mouse brown adipocytes to examine the detailed mechanisms regulating adiponectin secretion. ResultsApigenin improved vasodilation and reduced blood pressure in obese mice, effects partly blocked in TRPV4 knockout. It also reduced weight gain independently of TRPV4. Apigenin increased adiponectin secretion from BAT; knockdown of adiponectin weakened its benefits. Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing adiponectin expression. ConclusionsOur study indicates that dietary apigenin is suitable as a nonpharmaceutical intervention for obesity-related hypertension. In mechanism, in addition to improving vascular relaxation through the activation of endothelial TRPV4 channels, apigenin also directly alleviated adipose inflammation and increased adiponectin levels by inhibiting CD38.