Investigating the antiviral activity of Erigeron annuus (L.) pers extract against RSV and examining its active components.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants in the genus Erigeron are known to exhibit antiviral activities, including those against the respiratory syncytial virus (RSV). In traditional medicine Erigeron annuus (L.) Pers (EA) has been used in the treatment of pulmonary diseases and acute infectious hepatitis. AIM OF THIS STUDY: The aim of this study is to determine the optimum extraction method to produce the most potent anti-RSV extract, elucidate its mode and mechanisms of antiviral activity in both in vitro and in vivo models, and identify the chemical structures of the bioactive compounds. MATERIALS AND METHODS: The whole plant of EA was extracted with ethyl acetate, methanol, ethanol, water, aqueous methanol (60, 80% and 100%) and aqueous ethanol (50, 75% and 95%) using maceration, reflux, and ultrasound-assisted extraction methods. The antiviral activities of the extracts were determined in vitro. The in vitro antiviral activities of the extracts were determined using Hep-2 cells. Four in vitro experiments were performed to determine the mode of antiviral activity of the most active extract, ethyl acetate fraction (EAE) of Erigeron annuus whole plant extract prepared by refluxing with 50% ethanol, by examining its ability to inactivate the virus directly, inhibit viral adsorption and penetration, inhibit viral replication and preventive effect. The effect of temperature and duration of treatment on these modes of action was also determined. The antiviral activity of the EAE was also assessed in vivo in a mouse model. The lung index, viral load, and lung tissue histology were measured. qRT-PCR and ELISA studies were performed to determine the expression of key genes (TLR-3 and TLR-4) and proteins (IL-2, IFN-γ, and TNF-α) related to RSV infection. The most active antiviral compound was isolated using chromatography techniques, and its chemical structure was identified through electrospray triple quadrupole mass spectroscopy and nuclear magnetic resonance spectroscopy. RESULTS: The EAE was the most active on RSV. In vitro experiments showed that the antiviral activity of EAE is via direct inactivation, inhibition of entry, and inhibition of the proliferation of the virus. In vivo experiments showed that the EAE effectively inhibited the proliferation of RSV in the lungs and alleviated the lung tissue lesions in RSV-infected mice. The antiviral activity of the EAE is mediated by downregulating the expression of TLR3 and TLR4 in the lung, upregulating the expression of IL-2 and IFN-γ, and downregulating the expression of TNF-α. Apigenin 7-O-methylglucuronide was found to be a major bioactive compound in EAE. CONCLUSIONS: The results of this study confirmed the antiviral activity of EA by inactivating, inhibiting the entry, and inhibiting the proliferation of RSV. The activity is mediated by regulating the immunity and inflammatory mediators. Apigenin 7-O-methylglucuronide is the bioactive compound present in EA.

Revealing binding mechanism of ß-casein to chrysin, apigenin, and luteolin and locating its binding pockets by molecular docking and molecular dynamics.

Revealing the interaction mechanism of proteins with bioactive molecules and the location of their binding pockets is crucial for predicting the structure-function relationship of proteins in drug discovery and design. Despite some published papers on the interaction of ß-casein with small bioactive molecules, the ambiguity of the location and constituent amino acids of ß-casein binding pockets prompted us to identify them by in silico simulation of its interaction with three polyphenols, chrysin, apigenin, and luteolin. Molecular docking revealed that the primary ß-casein binding pocket for chrysin consists of five nonpolar amino acids (Leu73, Phe77, Pro80, Ile89, and Pro196), three polar neutral amino acids (Ser137, Gln138, and Gln197), and two polar charged amino acids (Glu136, and Arg198). For ß-casein/apigenin and ß-casein/luteolin complexes, Asn83 also contributes to forming the pocket. Molecular dynamics provided more details, such as the relative contribution of determinative amino acids and the role of various forces. For example, we found that Glu210, Glu132, and Glu35 are the most destructive residues in the binding of chrysin, apigenin, and luteolin to ß-casein, respectively. Also, we observed that hydrophobic forces mainly stabilize ß-casein/chrysin and ß-casein/apigenin, and polar solvation (including hydrogen bonds) stabilizes ß-casein/luteolin, all by spontaneous processes.

Ca2+-promoted free radical grafting of whey protein to EGCG: As a novel nanocarrier for the encapsulation of apigenin.

Whey protein (WP) is often used as a delivery carrier due to its superior biological activity and nutritional value. Covalent binding of WP to epigallocatechin gallate (EGCG) can significantly improve the performance of WP in encapsulated materials. Nevertheless, the preparation of WP-EGCG covalent complexes still suffers from low grafting rates. Studies have shown that calcium ions (Ca2+) can modify the structure of proteins. We therefore explored the effect of calcium chloride (CaCl2) on the free radical grafting of EGCG and WP. The experimental results showed that the grafting rate of free radicals increased by 17.89% after adding Ca2+. Furthermore, the impact of WP-EGCG-Ca2+ covalent complex on the entrapment efficiency of apigenin (AP) was further examined, and the results revealed that the entrapment rate could reach 93.66% at an apigenin concentration of 0.2 mg/mL. Simulated gastrointestinal digestion showed that WP-EGCG-Ca2+ covalent complex could significantly improve the bioavailability of AP. The study provides new ideas to broaden the application of WP as a carrier for delivering bioactive substances.

Chemopreventive Agents from Nature: A Review of Apigenin, Rosmarinic Acid, and Thymoquinone.

Cancer, a major challenge to global health and healthcare systems, requires the study of alternative and supportive treatments due to the limitations of conventional therapies. This review examines the chemopreventive potential of three natural compounds: rosmarinic acid, apigenin, and thymoquinone. Derived from various plants, these compounds have demonstrated promising chemopreventive properties in in vitro, in vivo, and in silico studies. Specifically, they have been shown to inhibit cancer cell growth, induce apoptosis, and modulate key signaling pathways involved in cancer progression. The aim of this review is to provide a comprehensive overview of the current research on these phytochemicals, elucidating their mechanisms of action, therapeutic efficacy, and potential as adjuncts to traditional cancer therapies. This information serves as a valuable resource for researchers and healthcare providers interested in expanding their knowledge within the field of alternative cancer therapies.

Uncovering SIRT3 and SHMT2-dependent pathways as novel targets for apigenin in modulating colorectal cancer: In vitro and in vivo studies.

Despite significant advances in the treatment of colorectal cancer (CRC), identification of novel targets and treatment options are imperative for improving its prognosis and survival rates. The mitochondrial SIRT3 and SHMT2 have key roles in metabolic reprogramming and cell proliferation. This study investigated the potential use of the natural product apigenin in CRC treatment employing both in vivo and in vitro models and explored the role of SIRT3 and SHMT2 in apigenin-induced CRC apoptosis. The role of SHMT2 in CRC patients' survival was verified using TCGA database. In vivo, apigenin treatment restored the normal colon appearance. On the molecular level, apigenin augmented the immunohistochemical expression of cleaved caspase-3 and attenuated SIRT3 and SHMT2 mRNA expression CRC patients with decreased SHMT2 expression had improved overall and disease-free survival rates. In vitro, apigenin reduced the cell viability in a time-dependent manner, induced G0/G1 cell cycle arrest, and increased the apoptotic cell population compared to the untreated control. Mechanistically, apigenin treatment mitigated the expression of SHMT2, SIRT3, and its upstream long intergenic noncoding RNA LINC01234 in CRC cells. Conclusively, apigenin induces caspase-3-dependent apoptosis in CRC through modulation of SIRT3-triggered mitochondrial pathway suggesting it as a promising therapeutic agent to improve patient outcomes.

Apigenin inhibits proliferation and differentiation of cardiac fibroblasts through AKT/GSK3ß signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge (S. miltiorrhiza) is an important Traditional Chinese herbal Medicine (TCM) used to treat cardio-cerebrovascular diseases. Based on the pharmacodynamic substance of S. miltiorrhiza, the aim of present study was to investigate the underlying mechanism of S. miltiorrhiza against cardiac fibrosis (CF) through a systematic network pharmacology approach, molecular docking and dynamics simulation as well as experimental investigation in vitro. MATERIALS AND METHODS: A systematic pharmacological analysis was conducted using the Traditional Chinese Medicine Pharmacology (TCMSP) database to screen the effective chemical components of S. miltiorrhiza, then the corresponding potential target genes of the compounds were obtained by the Swiss Target Prediction and TCMSP databases. Meanwhile, GeneCards, DisGeNET, OMIM, and TTD disease databases were used to screen CF targets, and a protein-protein interaction (PPI) network of drug-disease targets was constructed on S. miltiorrhiza/CF targets by Search Tool for the Retrieval of Interacting Genes/Proteins (STING) database. After that, the component-disease-target network was constructed by software Cytoscape 3.7. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for the intersection targets between drug and disease. The relationship between active ingredient of S. miltiorrhiza and disease targets of CF was assessed via molecular docking and molecular dynamics simulation. Subsequently, the underlying mechanism of the hub compound on CF was experimentally investigated in vitro. RESULTS: 206 corresponding targets to effective chemical components from S. miltiorrhiza were determined, and among them, there were 82 targets that overlapped with targets of CF. Further, through PPI analysis, AKT1 and GSK3ß were the hub targets, and which were both enriched in the PI3K/AKT signaling pathway, it was the sub-pathways of the lipid and atherosclerosis pathway. Subsequently, compound-disease-genes-pathways diagram is constructed, apigenin (APi) was a top ingredients and AKT1 (51) and GSK3ß (22) were the hub genes according to the degree value. The results of molecular docking and dynamics simulation showed that APi has strong affinities with AKT and GSK3ß. The results of cell experiments showed that APi inhibited cells viability, proliferation, proteins expression of α-SMA and collagen I/III, phosphorylation of AKT1 and GSK3ß in MCFs induced by TGFß1. CONCLUSION: Through a systematic network pharmacology approach, molecular docking and dynamics simulation, and confirmed by in vitro cell experiments, these results indicated that APi interacts with AKT and GSK3ß to disrupt the phosphorylation of AKT and GSK3ß, thereby inhibiting the proliferation and differentiation of MCFs induced by TGFß1, which providing new insights into the pharmacological mechanism of S. miltiorrhiza in the treatment of CF.

Apigenin-6-C-glucoside ameliorates MASLD in rodent models via selective agonism of adiponectin receptor 2.

Adiponectin plays key roles in energy metabolism and ameliorates inflammation, oxidative stress, and mitochondrial dysfunction via its primary receptors, adiponectin receptors -1 and 2 (AdipoR1 and AdipoR2). Systemic depletion of adiponectin causes various metabolic disorders, including MASLD; however adiponectin supplementation is not yet achievable owing to its large size and oligomerization-associated complexities. Small-molecule AdipoR agonists, thus, may provide viable therapeutic options against metabolic disorders. Using a novel luciferase reporter-based assay here, we have identified Apigenin-6-C-glucoside (ACG), but not apigenin, as a specific agonist for the liver-rich AdipoR isoform, AdipoR2 (EC50: 384 pM) with >10000X preference over AdipoR1. Immunoblot analysis in HEK-293 overexpressing AdipoR2 or HepG2 and PLC/PRF/5 liver cell lines revealed rapid AMPK, p38 activation and induction of typical AdipoR targets PGC-1α and PPARα by ACG at a pharmacologically relevant concentration of 100 nM (reported cMax in mouse; 297 nM). ACG-mediated AdipoR2 activation culminated in a favorable modulation of key metabolic events, including decreased inflammation, oxidative stress, mitochondrial dysfunction, de novo lipogenesis, and increased fatty acid ß-oxidation as determined by immunoblotting, QRT-PCR and extracellular flux analysis. AdipoR2 depletion or AMPK/p38 inhibition dampened these effects. The in vitro results were recapitulated in two different murine models of MASLD, where ACG at 10 mg/kg body weight robustly reduced hepatic steatosis, fibrosis, proinflammatory macrophage numbers, and increased hepatic glycogen content. Together, using in vitro experiments and rodent models, we demonstrate a proof-of-concept for AdipoR2 as a therapeutic target for MASLD and provide novel chemicobiological insights for the generation of translation-worthy pharmacological agents.

Optimal harvest period and quality control markers of cultivated Flos Chrysanthemi Indici using untargeted/targeted metabolomics, chemometric analysis and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum Indicum L., is a popular traditional Chinese medicine (TCM) for treatment of inflammatory diseases in China. FCI is also a functional food, and is widely used as herbal tea for clearing heat and detoxicating. AIM OF THE STUDY: To explore quality control markers of FCI based on the optimal harvest period. MATERIALS AND METHODS: First, UPLC-Q-TOF/MS based untargeted metabolomics was applied to explore the chemical profiles of FCIs collected at bud stages (BS), initial stages (IS), full bloom stages (FS) and eventual stages (ES) from eight cultivated regions in China. Subsequently, lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model and carrageenan-induced rat paw edema model were used to confirm the anti-inflammatory effect of FCIs collected at IS/FS. Then, UPLC-PDA targeted metabolomics was used to quantitatively analyze 9 constituents with anti-inflammatory activity (7 flavonoids and 2 phenolic acids) changed significantly (VIP > 4) during flowering stages. Finally, ROC curves combined with PCA analysis based on the variation of 9 active constituents in FCIs from different flowering stages were applied to screen the quality markers of FCI. RESULTS: FCIs at IS/FS had almost same chemical characteristics, but quite different from those at BS and ES. A total of 32 constituents in FCIs including flavonoids and phenolic acids were changed during flowering development. Most of the varied constituents had the highest or higher contents at IS/FS compared with those at ES, indicating that the optimal harvest period of FCI should be at IS/FS. FCI extract could effectively suppress nitric oxide (NO) production in LPS-induced RAW264.7 cells and regulate the abnormal levels of cytokines and PGE2 in carrageenan-induced paw edema model rat. The results of quantitatively analysis revealed that the variation trends of phenolic acids and flavonoids in FCIs were different during flowering development, but most of them had higher contents at IS/FS than those at ES in all FCIs collected from eight cultivated regions, except one sample from Anhui. Finally, linarin, luteolin, apigenin and 3,5-dicaffeoylquinic acid were selected as the Q-markers based on the contribution of their AUC values in ROC and clustering of PCA analysis. CONCLUSIONS: Our study demonstrates the optimal harvest period of FCI and specifies the multi-constituents Q-markers of FCI based on the influence of growth progression on the active constituents using untargeted/targeted metabolomics. The findings not only greatly increase the utilization rate of FCI resources and improve quality control of FCI products, but also offer new strategy to identify the Q-markers of FCI.

Ficus hirta Vahl. ameliorates liver fibrosis by triggering hepatic stellate cell ferroptosis through GSH/GPX4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus hirta Vahl., a traditional Chinese medicine commonly used in the Lingnan region, has been extensively used for liver disease treatment in China. Its notable antioxidant and anti-inflammatory properties have been reported in previous studies. However, its potential effect and underlying mechanism on liver fibrosis remains unclear. AIM OF STUDY: This study was aimed to investigate the effect and its underlying mechanism of Ficus hirta Vahl on liver fibrosis in vitro and in vivo. MATERIALS AND METHODS: The main components of Ficus hirta Vahl in blood were investigated by using UPLC-Q/TOF-MS/MS. Two animal models of liver fibrosis, the CCl4 and MCD induced mice, were used to assess the efficacy of Ficus hirta Vahl on liver fibrosis. Metabolomics was used to detect the level of metabolites in the serum of liver fibrosis mice after Ficus hirta Vahl treatment. Furthermore, the mechanism was validated in vitro using the human liver stellate cell line LX-2. The binding affinities of the active ingredients of Ficus hirta Vahl to the main targets of liver fibrosis were also determined. Finally, we identified the key active ingredients responsible for the treatment of liver fibrosis in vivo. RESULTS: Fibrosis and inflammatory markers were significant down-regulation in both CCl4 and MCD induced liver fibrosis mice after Ficus hirta Vahl administration in a dose-dependent manner. We found that Ficus hirta Vahl may primarily exert its effect on liver fibrosis through the glutathione metabolic pathway. Importantly, the glutathione metabolic pathway is closely associated with ferroptosis, and our subsequent in vitro experiments provided evidence supporting this association. Ficus hirta Vahl was found to modulate the GSH/GPX4 pathway, ultimately leading to the amelioration of liver fibrosis. Moreover, using serum pharmacochemistry and molecular docking, we successfully identified apigenin as a probable efficacious monomer for the management of liver fibrosis and subsequently validated its efficacy in mice with CCl4-induced hepatic fibrosis. CONCLUSION: Ficus hirta Vahl triggered the ferroptosis of hepatic stellate cell by regulating the GSH/GPX4 pathway, thereby alleviating liver fibrosis in mice. Moreover, apigenin is a key compound in Ficus hirta Vahl responsible for the effective treatment of liver fibrosis.

Apigenin improves testosterone synthesis by regulating endoplasmic reticulum stress.

Obesity is a growing epidemic among reproductive-age men, which can cause and exacerbate male infertility by means of associated comorbidities, endocrine abnormalities, and direct effects on the fidelity and throughput of spermatogenesis. A prominent consequence of male obesity is a reduction in testosterone levels. Natural products have shown tremendous potential anti-obesity effects in metabolic diseases. This study aimed to investigate the potential of apigenin (AP) to alleviate testicular dysfunction induced by a high-fat diet (HFD) and to investigate the underlying mechanisms, focusing on endoplasmic reticulum stress (ERS) and testosterone synthesis. A murine model of obesity was established using HFD-fed mice. The effects of AP on obesity, lipid metabolism, testicular dysfunction, and ERS were assessed through various physiological, histological, and molecular techniques. Administration of AP (10 mg/kg) ameliorated HFD-induced obesity and testicular dysfunction in a mouse model, as evidenced by decreased body weight, improved lipid profiles and testicular pathology, and restored protein levels related to testosterone. Furthermore, in vitro studies demonstrated that AP relieved ERS and recovered testosterone synthesis in murine Leydig cells (TM3) treated with free fatty acids (FFAs). It was also observed that AP rescued testosterone synthesis enzymes in TM3 cells, similar to that observed with the inhibitor of the PERK pathway (GSK2606414). In addition, ChIP, qPCR, and gene silencing showed that the C/EBP homologous protein (CHOP) bound directly to the promoter region of steroidogenic STAR and negatively modulated its expression. Collectively, AP has remarkable potential to alleviate HFD-induced obesity and testicular dysfunction. Its protective effects are attributable partly to mitigating ERS and restoring testosterone synthesis in Leydig cells.

Comparison of Anticancer, Antioxidant, Enzyme Inhibitory Effects and Phytochemical Contents between Edible Lettuce (Lactuca sativa) and A New Wild Species (Lactuca anatolica).

In this study, the bioactive components, enzyme inhibitory, antioxidant and anticancer potentials of edible (L. sativa) and a new species (L. anatolica) of Lactuca were evaluated and compared. The quantitative analyzes of the bioactive components of L. sativa (LS) and L. anatolica (LA) were analyzed quantitatively by GC-MS and Orbitrab HPLC-HRMS. Antioxidant, enzyme inhibitory and anticancer properties were analyzed by various assays. In general, LA exhibited more stronger antioxidant properties compared to LS. The extracts showed similar inhibitory effects on these enzymes. It was determined that LS was dominant in terms of linoleic acid (23.71%), while LA contained a high level of α-linolenic acid (31.70%). LA and LS inhibited the viability of A549 and MCF-7 cells in a dose-dependent manner. IC50 values for LA, LS and cisplatin were determined as 120.3, 197.5, 4.3 µg/mL in A549 cell line and 286.2, 472.8, 7.2 µg/mL in MCF-7 cell line, respectively. It was revealed that LA and LS treatment at 50 µg/mL concentrations in A549 cells completely suppressed the colony forming capacity, and treatment with IC50 doses inhibited cell migration, and triggered apoptosis by regulating caspase-3, cPARP, p53 and p21. The findings of this study suggested that these species have significant pharmacological potential.

Apigenin attenuates serum concentrations of TNF-a, interleukin 1b and interleukin 6 in lipopolysaccharide-stimulated rats.

Objective: The use of flavonoids is increasing due to their cost-effectiveness and less adverse reaction. Therefore, the effect of apigenin on lipopolysaccharide (LPS)-induced inflammation was investigated by measuring IL-1b, IL-6, and TNF-a, of serum in the male rats. Materials and Methods: Ninety male wistar rats were divided in 6 groups included; control, sham, dexamethasone 15 mg/kg, intraperitoneally (i.p.), and apigenin (5, 15, and 30 mg/kg, i.p). Thirty minutes after the administration of solvent or apigenin, LPS (30 µg/kg, i.p) was injected. At time intervals of 4, 12 and 24 hr after injection, blood samples were taken and the concentrations of TNF-a, IL-1b and IL-6 were measured by enzyme-linked immunosorbent assay. Results: Compared to the control, apigenin (5 mg/kg) decreased the level of TNF-a, and IL-1b in a period of 24 hr (p<0.05). The concentration of IL-6 decreased significantly by apigenin (15 mg/kg) 24 hr after injection (p<0.05). Apigenin (30 mg/kg) decreased the level of TNF-a, at all three time points (4 hr; p<0.05, 12 hr; p<0.01, and 24 hr; p<0.01), and the level of IL-1b (p<0.01), 24 hr and the level of IL-6 at 4 hr (p<0.05), and 24 hr (p<0.01) after LPS injection. Conclusion: Apigenin can suppress serum inflammatory cytokines, similar to dexamethasone.

Apigenin attenuates indomethacin-induced gastric ulcer in rats: emphasis on antioxidant, anti-inflammatory, anti-apoptotic, and TGF-ß1 enhancing activities.

Gastric ulcer disease is associated with significant morbidity and mortality rates. The most two common causes of the ulcer are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. In the past few decades, a significant decrease in the morbidity and mortality rate has been observed probably due to the discovery of proton pump inhibitors. However, the medications used to treat gastric ulcers impose several nauseous side effects. Therefore, recent studies focus on the use of natural products to treat gastric ulcers. In the current study, gastric ulcer was effectively induced using indomethacin, and the protective effect of apigenin, a potent antioxidant flavonoid, was assessed in comparison to omeprazole. The administration of a single oral indomethacin (50 mg/kg) induced gastric ulcer as manifested by hemorrhagic lesions in the gastric mucosa, increased ulcer index, and histopathological alterations. Indomethacin also increased lipid peroxidation, decreased the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase, increased the immunoreactivity of the inflammatory markers cyclo-oxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB), increased the transcription of the apoptotic marker, Bax, and decreased that of the antiapoptotic Bcl-2. Indomethacin also decreased the immunoreactivity of transforming growth factor-beta 1 (TGF-ß1). On the other hand, pretreatment with apigenin (10 and 20 mg/kg) resulted in a dose-dependent improvement in the macroscopic and microscopic features of the gastric mucosa in a manner comparable to that of omeprazole. The gastroprotective effects of apigenin may be attributed to its anti-inflammatory, anti-antioxidant, and anti-apoptotic activities as well as enhancing the expression of TGF-ß1. Further experimental and clinical research is required to confirm activity of apigenin as anti-ulcer agent.

Mini-encyclopedia of mitochondria-relevant nutraceuticals protecting health in primary and secondary care-clinically relevant 3PM innovation.

Despite their subordination in humans, to a great extent, mitochondria maintain their independent status but tightly cooperate with the "host" on protecting the joint life quality and minimizing health risks. Under oxidative stress conditions, healthy mitochondria promptly increase mitophagy level to remove damaged "fellows" rejuvenating the mitochondrial population and sending fragments of mtDNA as SOS signals to all systems in the human body. As long as metabolic pathways are under systemic control and well-concerted together, adaptive mechanisms become triggered increasing systemic protection, activating antioxidant defense and repair machinery. Contextually, all attributes of mitochondrial patho-/physiology are instrumental for predictive medical approach and cost-effective treatments tailored to individualized patient profiles in primary (to protect vulnerable individuals again the health-to-disease transition) and secondary (to protect affected individuals again disease progression) care. Nutraceuticals are naturally occurring bioactive compounds demonstrating health-promoting, illness-preventing, and other health-related benefits. Keeping in mind health-promoting properties of nutraceuticals along with their great therapeutic potential and safety profile, there is a permanently growing demand on the application of mitochondria-relevant nutraceuticals. Application of nutraceuticals is beneficial only if meeting needs at individual level. Therefore, health risk assessment and creation of individualized patient profiles are of pivotal importance followed by adapted nutraceutical sets meeting individual needs. Based on the scientific evidence available for mitochondria-relevant nutraceuticals, this article presents examples of frequent medical conditions, which require protective measures targeted on mitochondria as a holistic approach following advanced concepts of predictive, preventive, and personalized medicine (PPPM/3PM) in primary and secondary care.

Unveiling the power of flavonoids: A dynamic exploration of their impact on cancer through matrix metalloproteinases regulation.

Cancer stands as a significant contributor to global mortality rates, primarily driven by its progression and widespread dissemination. Despite notable strides in cancer therapy, the efficacy of current treatment strategies is compromised due to their inherent toxicity and the emergence of chemoresistance. Consequently, there is a critical need to evaluate alternative therapeutic approaches, with natural compounds emerging as promising candidates, showcasing demonstrated anticancer capabilities in various research models. This review manuscript presents a comprehensive examination of the regulatory mechanisms governing the expression of matrix metalloproteinases (MMPs) and delves into the potential therapeutic role of flavonoids as agents exhibiting specific anticancer activity against MMPs. The primary aim of this study is to elucidate the diverse functions associated with MMP production in cancer and to investigate the potential of flavonoids in modulating MMP expression to inhibit metastasis.

The In Vitro Antioxidant and Anti-Inflammatory Activities of Selected Australian Seagrasses.

Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (Zostera muelleri, Halodule uninervis, Cymodocea rotundata, Syringodium isoetifolium, and Thalassia hemprichii) from the Great Barrier Reef (QLD, Australia) were thus collected, and their preliminary antioxidant and anti-inflammatory activities were evaluated. From the acetone extracts of five seagrass species subjected to 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging antioxidant assay, the extract of Z. muelleri had the highest activity (half minimal concentration of inhibition (IC50) = 138 µg/mL), with the aerial parts (IC50 = 119 µg/mL) possessing significantly higher antioxidant activity than the roots (IC50 ≥ 500 µg/mL). A human peripheral blood mononuclear cells (PBMCs) assay with bacterial lipopolysaccharide (LPS) activation and LEGENDplex cytokine analysis showed that the aerial extract of Z. muelleri significantly reduced the levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6 by 29%, 74%, and 90%, respectively, relative to the LPS treatment group. The aerial extract was thus fractionated with methanol (MeOH) and hexane fraction, and purification of the MeOH fraction by HPLC led to the isolation of 4-hydroxybenzoic acid (1), luteolin (2), and apigenin (3) as its major constituents. These compounds have been previously shown to reduce levels of TNF-α, IL-1ß, and IL-6 and represent some of the major bioactive components of Z. muelleri aerial parts. This investigation represents the first study of the antioxidant and anti-inflammatory properties of Z. muelleri and the first isolation of small molecules from this species. These results highlight the potential for using seagrasses in treating inflammation and the need for further investigation.

Apigenin: A Bioflavonoid with a Promising Role in Disease Prevention and Treatment.

Apigenin is a powerful flavone compound found in numerous fruits and vegetables, and it offers numerous health-promoting benefits. Many studies have evidenced that this compound has a potential role as an anti-inflammatory and antioxidant compound, making it a promising candidate for reducing the risk of pathogenesis. It has also been found to positively affect various systems in the body, such as the respiratory, digestive, immune, and reproductive systems. Apigenin is effective in treating liver, lung, heart, kidney, neurological diseases, diabetes, and maintaining good oral and skin health. Multiple studies have reported that this compound is capable of suppressing various types of cancer through the induction of apoptosis and cell-cycle arrest, suppressing cell migration and invasion, reduction of inflammation, and inhibiting angiogenesis. When used in combination with other drugs, apigenin increases their efficacy, reduces the risk of side effects, and improves the response to chemotherapy. This review broadly analyzes apigenin's potential in disease management by modulating various biological activities. In addition, this review also described apigenin's interaction with other compounds or drugs and the potential role of nanoformulation in different pathogeneses. Further extensive research is needed to explore the mechanism of action, safety, and efficacy of this compound in disease prevention and treatment.

An In Vivo and In Silico Approach Reveals Possible Sodium Channel Nav1.2 Inhibitors from Ficus religiosa as a Novel Treatment for Epilepsy.

Epilepsy is a neurological disease that affects approximately 50 million people worldwide. Despite an existing abundance of antiepileptic drugs, lifelong disease treatment is often required but could be improved with alternative drugs that have fewer side effects. Given that epileptic seizures stem from abnormal neuronal discharges predominately modulated by the human sodium channel Nav1.2, the quest for novel and potent Nav1.2 blockers holds promise for epilepsy management. Herein, an in vivo approach was used to detect new antiepileptic compounds using the maximum electroshock test on mice. Pre-treatment of mice with extracts from the Ficus religiosa plant ameliorated the tonic hind limb extensor phase of induced convulsions. Subsequently, an in silico approach identified potential Nav1.2 blocking compounds from F. religiosa using a combination of computational techniques, including molecular docking, prime molecular mechanics/generalized Born surface area (MM/GBSA) analysis, and molecular dynamics (MD) simulation studies. The molecular docking and MM/GBSA analysis indicated that out of 82 compounds known to be present in F. religiosa, seven exhibited relatively strong binding affinities to Nav1.2 that ranged from -6.555 to -13.476 kcal/mol; similar or with higher affinity than phenytoin (-6.660 kcal/mol), a known Na+-channel blocking antiepileptic drug. Furthermore, MD simulations revealed that two compounds: 6-C-glucosyl-8-C-arabinosyl apigenin and pelargonidin-3-rhamnoside could form stable complexes with Nav1.2 at 300 K, indicating their potential as lead antiepileptic agents. In summary, the combination of in vivo and in silico approaches supports the potential of F. religiosa phytochemicals as natural antiepileptic therapeutic agents.

Apigenin inhibits tumor angiogenesis by hindering microvesicle biogenesis via ARHGEF1.

Extracellular vesicles are essential for intercellular communication and are involved in tumor progression. Inhibiting the direct release of extracellular vesicles seems to be an effective strategy in inhibiting tumor progression, but lacks of investigation. Here, we report a natural flavonoid compound, apigenin, could significantly inhibit the growth of hepatocellular carcinoma by preventing microvesicle secretion. Mechanistically, apigenin primarily targets the guanine nucleotide exchange factor ARHGEF1, inhibiting the activity of small G protein Cdc42, which is essential in regulating the release of microvesicles from tumor cells. In turn, this inhibits tumor angiogenesis related to VEGF90K transported on microvesicles, ultimately impeding tumor progression. Collectively, these findings highlight the therapeutic potential of apigenin and shed light on its anticancer mechanisms through inhibiting microvesicle biogenesis, providing a solid foundation for the refinement and practical application of apigenin.

Determination of Luteolin and Apigenin in Herbal Teas by Online In-Tube Solid-Phase Microextraction Coupled with LC-MS/MS.

Herbal teas have attracted attention as functional beverages containing luteolin and apigenin, which exhibit antioxidant and anti-inflammatory effects. The objective of this study was to develop a sensitive online automated method to determine these flavones' contents in herbal teas using in-tube solid-phase microextraction (IT-SPME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). These compounds were extracted and concentrated by IT-SPME using a Supel Q PLOT capillary column and then separated and detected within 6 min using a CAPCELL PAK C18 MG III analytical column and a negative electrospray ionization-mode multiple-reaction monitoring system by LC-MS/MS. The detection limits (S/N = 3) for luteolin and apigenin were 0.4 and 0.8 pg mL-1, respectively, and the calibration curves were linear in the range of 2-2000 pg mL-1 with correlation coefficients above 0.9995, and intra-day and inter-day precisions with relative standard deviations below 2.9 and 3.6% (n = 6), respectively. The luteolin and apigenin in herbal tea were quantified using IT-SPME/LC-MS/MS following the acid hydrolysis of their glycosides. Among the 10 herbal teas tested, luteolin was detected in peppermint and sage at concentrations of 375 and 99 µg mL-1, respectively, while apigenin was detected in German chamomile at 110 µg mL-1, which were higher than in the other herbal teas. The method is expected to be a useful method for evaluating the efficacy of luteolin and apigenin in herbal teas as functional beverages.