Exploring the Role of Apigenin in Neuroinflammation: Insights and Implications.

Neuroinflammation, a hallmark of various central nervous system disorders, is often associated with oxidative stress and neuronal or oligodendrocyte cell death. It is therefore very interesting to target neuroinflammation pharmacologically. One therapeutic option is the use of nutraceuticals, particularly apigenin. Apigenin is present in plants: vegetables (parsley, celery, onions), fruits (oranges), herbs (chamomile, thyme, oregano, basil), and some beverages (tea, beer, and wine). This review explores the potential of apigenin as an anti-inflammatory agent across diverse neurological conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease), cancer, cardiovascular diseases, cognitive and memory disorders, and toxicity related to trace metals and other chemicals. Drawing upon major studies, we summarize apigenin's multifaceted effects and underlying mechanisms in neuroinflammation. Our review underscores apigenin's therapeutic promise and calls for further investigation into its clinical applications.

Scutellarin activates IDH1 to exert antitumor effects in hepatocellular carcinoma progression.

Isochlorate dehydrogenase 1 (IDH1) is an important metabolic enzyme for the production of α-ketoglutarate (α-KG), which has antitumor effects and is considered to have potential antitumor effects. The activation of IDH1 as a pathway for the development of anticancer drugs has not been attempted. We demonstrated that IDH1 can limit glycolysis in hepatocellular carcinoma (HCC) cells to activate the tumor immune microenvironment. In addition, through proteomic microarray analysis, we identified a natural small molecule, scutellarin (Scu), which activates IDH1 and inhibits the growth of HCC cells. By selectively modifying Cys297, Scu promotes IDH1 active dimer formation and increases α-KG production, leading to ubiquitination and degradation of HIF1a. The loss of HIF1a further leads to the inhibition of glycolysis in HCC cells. The activation of IDH1 by Scu can significantly increase the level of α-KG in tumor tissue, downregulate the HIF1a signaling pathway, and activate the tumor immune microenvironment in vivo. This study demonstrated the inhibitory effect of IDH1-α-KG-HIF1a on the growth of HCC cells and evaluated the inhibitory effect of Scu, the first IDH1 small molecule agonist, which provides a reference for cancer immunotherapy involving activated IDH1.

Apigenin Suppresses Innate Immune Responses and Ameliorates Lipopolysaccharide-Induced Inflammation via Inhibition of STING/IRF3 Pathway.

The stimulator of interferon genes (STING) signaling pathway is crucial for the pathogenesis of autoimmune and inflammatory disorders, including acute lung injury (ALI). Apigenin (4[Formula: see text],5,7-trihydroxyflavone) is a natural flavonoid widely found in fruits, vegetables, and Chinese medicinal herbs that exhibits a range of pharmacological effects, such as antibacterial and anti-inflammatory activities. However, the efficacy of apigenin in STING pathway-mediated diseases remains unclear. Accordingly, this study screened Chinese medicines to identify potent agents that reduced the synthesis of type I interferons (IFNs). The results revealed apigenin as a potent compound with low cytotoxicity that markedly reduced the synthesis of type I IFNs in response to STING pathway agonists. Besides, apigenin markedly suppressed innate immune responses triggered by the STING agonist SR-717. Mechanistically, apigenin downregulated IFN beta 1 (IFNB1) expression mediated by the STING pathway via dose-dependent inhibition of STING expression, reduction of dimerization, nuclear translocation of phosphorylated IRF3, and disruption of the association between STING and IRF3. Moreover, apigenin effectively mitigated pathological pulmonary inflammation and lung edema in lipopolysaccharide (LPS)-induced ALI in mice. Apigenin further strongly attenuated the hallmarks of immoderate inflammation (interleukin (IL)-6, IL-1[Formula: see text], and tumor necrosis factor [Formula: see text]) and innate immune responses (IFNB1, C-X-C motif chemokine ligand 10, and IFN-stimulated gene 15) by preventing the activation of the STING/IRF3 pathway both in vitro and in vivo. Importantly, SR-717 significantly reversed the inhibitory effects of apigenin in LPS-induced THP1-BlueTM ISG macrophages. Collectively, apigenin effectively alleviated innate immune responses and mitigated inflammation in LPS-induced ALI via inhibition of the STING/IRF3 pathway. These findings suggest the potential of apigenin as a prophylactic and therapeutic candidate for managing STING-mediated diseases.

Vitexin enhances radiosensitivity of mouse subcutaneous xenograft glioma by affecting the miR-17-5p/miR-130b-3p/PTEN/HIF-1α pathway.

PURPOSE: Vitexin can cooperate with hyperbaric oxygen to sensitize the radiotherapy of glioma by inhibiting the hypoxia-inducible factor (HIF)-1α. However, whether vitexin has a direct radiosensitization and how it affects the HIF-1α expression remain unclear. This study investigated these issues. METHODS: The SU3 cells-inoculated nude mice were divided into control, radiation, and vitexin + radiation groups. The vitexin + radiation-treated mice were intraperitoneally injected with 75 mg/kg vitexin daily for 21 days. On the 3rd, 10th, and 17th days during the vitexin treatment, the radiation-treated mice were locally irradiated with 10 Gy, respectively. In vitro, the microRNA (miR)-17-5p or miR-130b-3p mimics-transfected SU3 cells were used to examine the effects of vitexin plus radiation on expression of miR-17-5p- or miR-130b-3p-induced radioresistance-related pathway proteins. The effects of vitexin on miR-17-5p and miR-130b-3p expression in SU3 cells were also evaluated. RESULTS: Compared with the radiation group, the tumor volume, tumor weight, and expression of HIF-1α, vascular endothelial growth factor, and glucose transporter-1/3 proteins, miR-17-5p, and miR-130b-3p in tumor tissues in the vitexin + radiation group decreased, whereas the expression of phosphatase and tensin homolog (PTEN) protein increased. After treatment of miR-17-5p or miR-130b-3p mimics-transfected SU3 cells with vitexin plus radiation, the PTEN protein expression also increased, the HIF-1α protein expression decreased correspondingly. Moreover, vitexin decreased the miR-17-5p and miR-130b-3p expression in SU3 cells. CONCLUSION: Vitexin can enhance the radiosensitivity of glioma, and its mechanism may partly be related to the attenuation of HIF-1α pathway after lowering the inhibitory effect of miR-17-5p and miR-130b-3p on PTEN.

Food therapy of scutellarein ameliorates pirarubicin­induced cardiotoxicity in rats by inhibiting apoptosis and ferroptosis through regulation of NOX2­induced oxidative stress.

Pirarubicin (THP) is one of the most commonly used antineoplastic drugs in clinical practice. However, its clinical application is limited due to its toxic and heart­related side effects. It has been reported that oxidative stress, inflammation and apoptosis are closely associated with cardiotoxicity caused by pirarubicin (CTP). Additionally, it has also been reported that scutellarein (Sc) exerts anti­inflammatory, antioxidant, cardio­cerebral vascular protective and anti­apoptotic properties. Therefore, the present study aimed to investigate the effect of food therapy with Sc on CTP and its underlying molecular mechanism using echocardiography, immunofluorescence, western blot, ROS staining, and TUNEL staining. The in vivo results demonstrated that THP was associated with cardiotoxicity. Additionally, abnormal changes in the expression of indicators associated with oxidative stress, ferroptosis and apoptosis were observed, which were restored by Sc. Therefore, it was hypothesized that CTP could be associated with oxidative stress, ferroptosis and apoptosis. Furthermore, the in vitro experiments showed that Sc and the NADPH oxidase 2 (NOX2) inhibitor, GSK2795039 (GSK), upregulated glutathione peroxidase 4 (GPX4) and inhibited THP­induced oxidative stress, apoptosis and ferroptosis. However, cell treatment with the ferroptosis inhibitor, ferrostatin­1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2­induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP.

Rational design of mitochondria-targeted fluorescent biosensors for in vivo elucidation of the interaction between breast cancer metastasis and mitochondrial autophagy.

Breast cancer lung metastases (BCLM) are a major cause of high mortality in patients. The shortage of therapeutic targets and rapid drug screening tools for BCLM is a major challenge at present. Mitochondrial autophagy, which involves the degradation of proteins associated with cancer cell aggressiveness, represents a possible therapeutic approach for the treatment of BCLM. Herein, four fluorescent biosensors with different alkyl chains were designed and synthesized to monitor mitochondrial autophagy. Among them, PMV-12 demonstrated the highest sensitivity to viscosity variance, the least impact on polarity, and the longest imaging time. The introduction of the C12-chain made PMV-12 anchored in the mitochondrial membrane without being disturbed by changes of the mitochondrial membrane potential (MMP), thereby achieving the long-term monitor in situ for mitochondrial autophagy. Mitochondria stained with PMV-12 induced swelling and viscosity increase after treating with apigenin, which indicated that apigenin is a potential mitochondrial autophagy inducer. Apigenin was subsequently verified to inhibit cancer cell invasion by 92%. Furthermore, PMV-12 could monitor the process of BCLM in vivo and evaluate the therapeutic effects of apigenin. This work provides a fluorescent tool for elucidating the role of mitochondrial autophagy in the BCLM process and for anti-metastatic drug development.

Apigenin's Therapeutic Potential Against Viral Infection.

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 in vitro and in vivo, 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.

Biostimulated-sesame sprout extracts as potential agents against Leishmania mexicana.

Leishmania mexicana is one of the causal agents of cutaneous leishmaniasis. Current antileishmanial chemotherapeutics have demonstrated adverse side effects; thus, alternative treatments are needed. In this study, we performed in silico and in vitro analyses of the leishmanicidal potential of the most abundant phenolic compounds identified in black sesame sprouts biostimulated with Bacillus clausii. The molecular docking analysis showed strong interactions (binding free energies between -6.5 and -9.5 kcal/mol) of sesaminol 2-O-triglucoside, pinoresinol dihexoside, isoverbascoside, and apigenin with the arginase, leishmanolysin, cysteine peptidase B, and pyruvate kinase leishmanial enzymes. Furthermore, almost all phenolic compounds interacted with the active site residues of L. mexicana enzymes. In vitro, the B. clausii-biostimulated sprout phenolic extracts and apigenin inhibited the growth of promastigotes with IC50 values of 0.08 mg gallic acid equivalent/mL and 6.42 µM (0.0017 mg/mL), respectively. Additionally, in the macrophage infection model, cells treated with B. clausii-biostimulated sprout phenolic extracts and infected with L. mexicana exhibited significantly (P < 0.05) reduced nitric oxide production and decreased parasite burden. Altogether, our study provides important data related to high efficacy and less toxic natural antileishmanial candidates against promastigotes of L. mexicana.

The interaction between apigenin and PKM2 restrains progression of colorectal cancer.

Apigenin, a flavonoid that widely existed in vegetables and fruits, possesses anticarcinogenic, low toxicity, and no mutagenic properties, suggesting that apigenin is a potential therapeutic agent for tumors. However, the underlying anti-cancer molecular target of apigenin is still unclear. Therefore, to reveal the direct target and amino acid site of apigenin against colorectal cancer is the focus of this study. In the present study, the results proved that the anti-CRC activity of apigenin was positively correlated with pyruvate kinase M2 (PKM2) expression, characterized by the inhibition of cell proliferation and increase of apoptotic effects induced by apigenin in LS-174T cells of knock down PKM2. Next, pull-down and MALDI-TOF/TOF analysis determined that apigenin might interact directly with PKM2 in HCT-8 cells. Further, the study confirmed that lysine residue 433 (K433) was a key amino acid site for PKM2 binding to apigenin. Apigenin restricted the glycolysis of LS-174T and HCT-8 cells by targeting the K433 site of PKM2, thereby playing an anti-CRC role in vivo and in vitro. Meanwhile, apigenin markedly attenuated tumor growth without any adverse effects. Taken together, these findings reveal that apigenin is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC.

The effect of Apigenin on glycometabolism and cell death in an anaplastic thyroid cancer cell line.

AIMS AND BACKGROUND: A more pronounced characteristic of cancer cells is the energy dependence on glucose, which mitigated by glucose transporters. The comprehension of the regulatory mechanisms behind the Warburg effect holds promise for developing therapeutic interventions for cancers. Studies are lacking which targeted the GLUTs for treatment of malignancy of thyroid tumors. In our current investigation, we have undertaken this study to determine the potential of Apigenin, plant derived flavonoid in modulating tumor apoptosis by targeting GLUTs expression in SW1736 cell line of anaplastic thyroid carcinoma. MATERIAL METHODS: Flow cytometry with propidium iodide staining was used to determine cell apoptosis. For glucose uptake detection, the "GOD-PAP" enzymatic colorimetric test was used to measure the direct glucose levels inside the cells. To determine the expression of GLUT1 and GLUT3 mRNA in the SW1736 cell line qRT-PCR was employed. Protein levels of GLUT1 and GLUT3 in the SW1736 cell line were detected with western blotting. Also, the scratch wound healing assay was conducted for cell migration. RESULTS: According to qRT-PCR analysis, the levels of GLUT1 and GLUT3 mRNA were lower in the group that received Apigenin relative to the control group. The Apigenin treatment of SW1736 cells decreased protein expression of the GLUT1 and GLUT3 levels in conformity to qRT-PCR. The scratch assays revealed that Apigenin treatment of cancer cell lines inhibited cell migration as compared to control. CONCLUSION: These findings demonstrate the possibility of targeting the glucose facilitators' pathway for making thyroid cancer cells more susceptible to programmed cell death.

Synergism Antiproliferative Effects of Apigenin and Naringenin in NSCLC Cells.

Non-small cell lung cancer (NSCLC) is one of the leading cancer killers. Apigenin (Api) and Naringenin (Nar) are natural bioactive substances obtained in various vegetables and fruits, possessing anti-tumor effects across multiple studies. This study investigated the latent synergistic antiproliferative functions of Api and Nar in A549 and H1299 NSCLC cells. Cell viability was determined after incubating with different concentrations of Api, Nar, or the combination of Api and Nar (CoAN) for 24 h. Analysis using the CompuSyn software revealed that the CI value of each combined dose was < 1, depicting that the two drugs had a synergistic inhibitory effect. The CoAN (A:N = 3:2) group with the lowest CI value was selected for subsequent experiments. The IC50 of CoAN (A:N = 3:2) was used to determine the cell cycle, the expression ratio of Bax to Bcl2, Caspase 3 activity, and mitochondrial function to assess oxidative stress and apoptosis. The results established that CoAN treatment caused significant cytotoxicity with cell cycle arrest at G2/M phases. Furthermore, CoAN significantly enhanced mitochondria dysfunction, elevated oxidative stress, and activated the apoptotic pathway versus Api or Nar alone groups. Thus, the CoAN chemotherapy approach is promising and deserves further research.

Vitexin ameliorated diabetic nephropathy via suppressing GPX4-mediated ferroptosis.

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-ß1). Furthermore, vitexin inhibited ferroptosis induced by HG, accompanied by changes of morphological, decrease of ROS, Fe2+ 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.

Apigenin Alleviates Allodynia and Hyperalgesia in a Mouse Model of Chemotherapy-Induced Peripheral Neuropathy via Regulating Microglia Activation and Polarization.

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-1ß 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.

Insights into Pharmacological Potential of Apigenin through Various Pathways on a Nanoplatform in Multitude of Diseases.

Apigenin is a natural polyphenolic compound widely distributed as a glycoside in fruits and vegetables. Apigenin belongs to BCS class II with low solubility, which leads to poor absorption and bioavailability. It is mostly absorbed from the small intestine and extensively metabolized through glucuronidation and sulfation processes. Apigenin is known for its antioxidant and anti-inflammatory properties. It is also used as a chemopreventive drug in the management of various cancers. Pharmacological effects of apigenin have a wide range, from neuroprotective to treating renal disorders. Apigenin is non-toxic in nature and acts through various pathways (JAK/STAT, Wnt/ß-catenin, MAPK/ERK, PI3K/Akt, and NF-κB) to exert its therapeutic efficacy. Numerous formulations have been researched to enhance the bioavailability and pharmacological effects of apigenin. Combinatorial therapies are also researched to minimize the side-effects of chemotherapeutic drugs. The review presents pharmacokinetic and pharmacodynamic aspects of apigenin. Apigenin is safe for the treatment and management of numerous diseases. It can be easily incorporated into nanoformulation alone or in combination with other active ingredients to widen the therapeutic window. This review intends to help in drug optimization and therapeutic efficacy maximization for future studies.

Concurrent induction of apoptosis and necroptosis in apigenin­treated malignant mesothelioma cells: Reversal of Warburg effect through Akt inhibition and p53 upregulation.

A high dependence on aerobic glycolysis, known as the Warburg effect, is one of the metabolic features exhibited by tumor cells. Therefore, targeting glycolysis is becoming a very promising strategy for the development of anticancer drugs. In the present study, it was investigated whether pre­adaptation of malignant mesothelioma (MM) cells to an acidic environment was associated with a metabolic shift to the Warburg phenotype in energy production, and whether apigenin targets acidosis­driven metabolic reprogramming. Cell viability, glycolytic activity, Annexin V­PE binding activity, reactive oxygen species (ROS) levels, mitochondrial membrane potential, ATP content, western blot analysis and spheroid viability were assessed in the present study. MM cells pre­adapted to lactic acid were resistant to the anticancer drug gemcitabine, increased Akt activation, downregulated p53 expression, and upregulated rate­limiting enzymes in glucose metabolism compared with their parental cells. Apigenin treatment increased cytotoxicity, Akt inactivation and p53 upregulation. Apigenin also reduced glucose uptake along with downregulation of key regulatory enzymes in glycolysis, increased ROS levels with loss of mitochondrial membrane potential, and downregulated the levels of complexes I, III and IV in the mitochondrial electron transport chain with intracellular ATP depletion, resulting in upregulation of molecules mediating apoptosis and necroptosis. Apigenin­induced alterations of cellular responses were similar to those of Akt inactivation by Ly294002. Overall, the present results provide mechanistic evidence supporting the anti­glycolytic and cytotoxic role of apigenin via inhibition of the PI3K/Akt signaling pathway and p53 upregulation.

From traditional medicine to modern oncology: Scutellarin, a promising natural compound in cancer treatment.

Natural substances are increasingly being used as cancer treatments. Scutellarin, as a flavonoid, recently has been identified in a Chinese herbal extract called Erigeron breviscapus (Vant.). Scutellarin is being researched for its potential benefits due to the discovery that it possesses a variety of biological effects, such as neuroprotective, anti-bacterial, and anti-viral properties. In addition to these biological functions, scutellarin has also been found to have anti-tumor properties. The underlying mechanisms of scutellarin's anticancer activity involve its ability to inhibit various signaling pathways, such as Jak/STAT, ERK/AMPK, and Wnt/ß-catenin. Additionally, scutellarin activates intrinsic and extrinsic apoptotic pathways, which causes the death of tumor cells, interrupts the cell cycle, and promotes its arrest. By limiting metastasis, angiogenesis, drug resistance, and other tumorigenic processes, scutellarin also reduces the aggressiveness of tumors. Despite its promising anticancer activity, scutellarin faces several challenges in its clinical development, including poor solubility, bioavailability, and pharmacokinetic properties. Therefore, it has been suggested that certain modifications can enhance the pharmacogenetic capabilities of scutellarin to decrease its limited water solubility. In conclusion, scutellarin represents a potential candidate for cancer treatment and further studies are needed to explore its clinical utility and optimize its therapeutic potential.

Deciphering the modulatory role of apigenin targeting oncogenic pathways in human cancers.

Cancer is a complicated malignancy controlled by numerous intrinsic and extrinsic pathways. There has been a significant increase in interest in recent years in the elucidation of cancer treatments based on natural extracts that have fewer side effects. Numerous natural product-derived chemicals have been investigated for their anticancer effects in the search for an efficient chemotherapeutic method. Therefore, the rationale behind this review is to provide a detailed insights about the anticancerous potential of apigenin via modulating numerous cell signaling pathways. An ingestible plant-derived flavonoid called apigenin has been linked to numerous anticancerous potential in numerous experimental and biological studies. Apigenin has been reported to induce cell growth arrest and apoptotic induction by modulating multiple cell signaling pathways in a wider range of human tumors including those of the breast, lung, liver, skin, blood, colon, prostate, pancreatic, cervical, oral, and stomach. Oncogenic protein networks, abnormal cell signaling, and modulation of the apoptotic machinery are only a few examples of diverse molecular interactions and processes that have not yet been thoroughly addressed by scientific research. Thus, keeping this fact in mind, we tried to focus our review towards summarizing the apigenin-mediated modulation of oncogenic pathways in various malignancies that can be further utilized to develop a potent therapeutic alternative for the treatment of various cancers.

Apigenin: A Therapeutic Agent for Treatment of Skin Inflammatory Diseases and Cancer.

The skin is the main barrier between the body and the environment, protecting it from external oxidative stress induced by ultraviolet rays. It also prevents the entrance of infectious agents such as viruses, external antigens, allergens, and bacteria into our bodies. An overreaction to these agents causes severe skin diseases, including atopic dermatitis, pruritus, psoriasis, skin cancer, and vitiligo. Members of the flavonoid family include apigenin, quercetin, luteolin, and kaempferol. Of these, apigenin has been used as a dietary supplement due to its various biological activities and has been shown to reduce skin inflammation by downregulating various inflammatory markers and molecular targets. In this review, we deal with current knowledge about inflammatory reactions in the skin and the molecular mechanisms by which apigenin reduces skin inflammation.

Pharmacological and Molecular Insight on the Cardioprotective Role of Apigenin.

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.

Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach.

Hepatocellular carcinoma (HCC) is a leading cause of death globally. Even though the progressive invention of some very potent therapeutics has been seen, the success is limited due to the chemotherapeutic resistance and recurrence in HCC. Advanced targeted treatment options like immunotherapy, molecular therapy or surface-engineered nanotherapeutics could offer the benefits here owing to drug resistance over tumor heterogenicity. We have developed tumor-sensing phosphorothioate and amino-modified aptamer (AS1411)-conjugated stealth nanoliposomes, encapsulating with apigenin for precise and significant biodistribution of apigenin into the target tumor to exploit maximum bio-therapeutic assistances. The stable aptamer functionalized PEGylated nanoliposomes (Apt-NLCs) had an average vesicle size of 100-150 nm, a smooth surface, and an intact lamellarity, as ensured by DLS, FESEM, AFM, and Cryo-TEM. This study has specified in vitro process of optimum drug (apigenin) extrusion into the cancer cells by nucleolin receptor-mediated cellular internalization when delivered through modified AS1411 functionalized PEGylated nanoliposomes and ensured irreversible DNA damage in HCC. Significant improvement in cancer cell apoptosis in animal models, due to reduced clearance and higher intratumor drug accumulation along with almost nominal toxic effect in liver, strongly supports the therapeutic potential of aptamer-conjugated PEGylated nanoliposomes compared to the nonconjugated formulations in HCC. The study has established a robust superiority of modified AS1411 functionalized PEGylated nanoliposomes as an alternative drug delivery approach with momentous reduction of HCC tumor incidences.