Search Results (91)

The flowers of Sophora japonica L. (SJF) and Robinia pseudoacacia L. (RPF) are edible and similar in appearance. The chemical constituents of SJF and RPF were compared by UPLC-Q-TOF-MS/MS and HPLC analysis in this study. A total of 29 and 19 constituents were identified in SJF and RPF, respectively. Flavonoid glycosides were the main constituents found in both flowers. The main aglycon moieties found in SJF were quercetin, kaempferol and isorhamnetin, whereas acacetin and kaempferol were the main ones found in RPF. Additionally, the content of flavonoids in SJF was significantly higher than that in RPF, as determined by HPLC. Rutin was the most dominant flavonoid in SJF with a content range of 72.31~88.15 mg/g, followed by quercetin (13.05~20.30 mg/g). Kaempferol-di(rhamnoside)-hexoside was the most dominant flavonoid in RPF with a content range of 25.94~30.00 mg/g. The distinct flavonoid profiles indicated the chemical non-equivalence of SJF and RPF. Therefore, RPF should not be considered a direct substitute for SJF in herbal medicine without further pharmacological and clinical validation. Full article

Cancer ranks as one of the top causes of death worldwide, and the World Health Organisation (WHO) estimates an increase of up to 55% in cases over the next 15 years, reaching 300 million cases worldwide. Current approaches to the treatment of cancer, such as chemotherapy and radiation therapy, have been used with continuous significant advancements. However, these conventional methods have harmful side effects that can last a lifetime. Today, there is growing interest in developing alternative cancer therapies from natural products or complementary medicine. One of the natural sources that has shown promise as an anticancer agent is honey, which has long been applied as a complementary medicine, and its beneficial health effects on various diseases in both animal and human models have been widely studied. Malaysian honey, such as Tualang, pineapple, Gelam, Kelulut, and Acacia, possesses a rich composition of phytochemicals, including polyphenols and flavonoids, which are reported to have promising anticancer properties. Examples of the phytochemicals highlighted in this review are phenolic acid, syringic acid, salicylic acid, p-coumaric acid, gallic acid, benzoic acid, caffeic acid, chrysin and its derivatives, kaempferol, fisetin, catechin, apigenin, quercetin, acacetin, pinocembrin, pinobanksin, hesperetin, naringenin, vitexin, isoorientin, xanthohumol, and galangin. This review highlights the anticancer mechanisms and molecular pathways of the phytochemicals found in Malaysian honey, focusing on their antioxidant effects, induction of mitochondrial-mediated apoptosis, inhibition of angiogenesis and metastasis, and suppression of cancer cell proliferation. The findings of various studies published in the past five years are collated to understand their mechanisms of action. Full article

The escalating threat of antibiotic resistance, particularly from Staphylococcus aureus (S. aureus), has become a critical challenge in both public health and animal husbandry. The extensive use of conventional antibiotics in livestock production accelerates the emergence of resistant strains, heightening risks to food safety and human health. Although plant-derived bioactive compounds are increasingly recognized as promising alternatives to synthetic antimicrobials, the mechanisms underlying their efficacy—and the potential for synergistic action among different plant parts—remain poorly understood. In particular, the antibacterial interactions among extracts from different tissues of Cyperus esculentus L. (C. esculentus), a plant rich in flavonoids and phenolics, have yet to be systematically evaluated. Here, we investigated the antibacterial properties and mechanisms of ethanol extracts from the tubers, stems–leaves and their mixture of C. esculentus against S. aureus. Using Oxford cup diffusion assays, scanning electron microscopy (SEM), bacterial growth kinetics, and untargeted metabolomics, we assessed both phenotypic inhibition and metabolic disruption. The mixed extract exhibited the strongest antibacterial effect, producing a 26.15 mm inhibition zone—approximately 7% greater than that of single-part extracts—and induced cell wall rupture and disintegration as observed by SEM. Growth curve analyses revealed time-dependent bacterial suppression, while metabolomic profiling identified 845 differential metabolites, indicating disturbances in amino acid, lipid, and nucleotide metabolism. Flavonoids such as acacetin, diosmetin, naringenin, and silybin A were identified as principal active compounds contributing to these effects. Full article

Background: Acacetin, a naturally occurring flavone present in various plants, is known as a promising drug candidate for cardiovascular disorders. Our previous study demonstrated that acacetin ameliorates atherosclerosis through endothelial cell protection; however, its pharmacological effects on vascular smooth muscle cells (VSMCs) remain unexplored. This study investigates the therapeutic potential of acacetin against lysophosphatidylcholine (LysoPC)-induced VSMC injury and elucidates the underlying molecular mechanisms. Methods and Results: Multiple biochemical techniques were employed in the present study. The results showed that acacetin significantly attenuated LysoPC-induced apoptosis and reactive oxygen species (ROS) generation in cultured VSMCs. Western blot analysis revealed that the cytoprotection of acacetin was associated with upregulated expression of antioxidant defense proteins, including nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), NADPH quinone oxidoreductase 1 (NQO-1), and superoxide dismutase 1 (SOD1). Nrf2 silencing completely abolished these protective effects. Mechanistically, siRNA-silencing of Sirtuin 1 (Sirt1) abrogated acacetin-induced modulation of the Nrf2/Keap1/p62 signaling. In vivo validation using aortic tissues from high-fat-diet-fed ApoE^−/− mice confirmed that acacetin effectively suppressed VSMC apoptosis and ROS overproduction associated with restoring the downregulated Sirt1 expression levels. Conclusions: These findings establish a novel mechanistic paradigm wherein acacetin confers protection against LysoPC-induced VSMC apoptosis and oxidative stress through Sirt1-dependent activation of the Nrf2/p62 signaling pathway, suggesting that acacetin is a promising therapeutic drug candidate for atherosclerotic plaque stabilization. Full article

Chrysanthemum (Chrysanthemum morifolium Ramat.) has been recognized as both a food and medicinal substance in China since 2002 and possesses antioxidant, anti-inflammatory, antibacterial, and immunomodulatory activities. Previous studies suggest that Chrysanthemum may alleviate skin lesions resembling atopic dermatitis (AD); however, its underlying mechanisms remain unclear. In this study, we integrated network pharmacology and machine learning to systematically explore the potential mechanisms of Chrysanthemum in AD treatment. Four algorithms—Random Forest (RF), Lasso regression with cross-validation (LassoCV), Elastic Net (EN), and Extreme Gradient Boosting (XGB)—were compared, among which the XGB model achieved the best performance (accuracy = 0.9393). Further analysis identified 15 optimal features, two core targets (PTGS2 and MMP9), and one critical pathway (NF-κB signaling). To experimentally validate these findings, HaCaT keratinocytes were co-stimulated with TNF-α and IFN-γ to establish an in vitro inflammatory model, and co-treatment with three major flavonoids from Chrysanthemum—Acacetin, Diosmetin, and Chryseriol—significantly suppressed cytokine-induced COX-2 overexpression and reduced NF-κB p65 phosphorylation, confirming their inhibitory effects on NF-κB activation. These results were consistent with molecular docking and dynamics simulations, which demonstrated that these flavonoids, along with celecoxib, could stably bind to COX-2, thereby enhancing system stability and reducing residue fluctuations at the binding interface, revealing the molecular basis by which Chrysanthemum alleviates AD and supporting its modernization and therapeutic potential. Full article

Acacetin, a naturally occurring flavonoid, has attracted increasing attention due to its broad anticancer potential. In vitro and in vivo studies using diverse tumor models have demonstrated that acacetin modulates oncogenic signaling, suppresses angiogenesis, and induces apoptosis and other regulated cell death pathways. With the rising demand for multi-target therapeutics, network pharmacology and molecular docking have emerged as powerful tools to unravel the complex molecular mechanisms of phytochemicals. Unlike previous reviews that have mainly focused on single pathways or limited cancer contexts, this review emphasizes novelty by integrating network pharmacology with molecular docking and explicitly linking these computational predictions to experimental validation, thereby identifying epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), and the serine/threonine kinase AKT (also known as protein kinase B (PKB) as central experimentally supported targets. This integrative framework maps acacetin’s multi-target anticancer mechanisms and clarifies its translational opportunities for future therapeutic development. Full article

In this study, an in vitro co-culture system of Castilleja tenuiflora and its host, Baccharis conferta, was used, and the impact of their interaction on specialized metabolite content was analyzed. After 4 weeks of co-culture, haustoria formation was verified through environmental scanning electron and confocal microscopy, confirming the successful establishment of the plant–plant interaction. Shoot height and biomass of the aerial part of the hemiparasite were not affected significantly by co-culture. However, root biomass increased by 53% compared to individually grown plants. Co-culture significantly reduced the host’s root length without negatively affecting its overall growth or survival. Phytochemical profile alterations were observed in both species. For C. tenuiflora, the lignans sesamin and eudesmin are proposed as differentially accumulated metabolites, while in B. conferta, the caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, and the flavonoid acacetin were expressed differently. The development and chemical profiles of B. conferta and C. tenuiflora change when they grow in a co-culture because of the host–parasite interaction. Here, we report the feasibility of using a hemiparasite–host system to investigate more profound research questions. Future biotechnological applications of this system include elucidating the genetic regulators involved in haustorium formation, as well as optimizing environmental and physiological conditions to enhance its biosynthetic capacity for the production of specialized metabolites with therapeutic value. Full article

The capitula of Chrysanthemum indicum Linné or C. morifolium Ramatuelle (Kikuka in Japanese) are included in several formulae of Kampo medicines (traditional Japanese medicines), such as Chotosan, which is used for headache and dizziness. Luteolin, the principal constituent of C. indicum, has antioxidant and anti-inflammatory activities. However, the effects of other flavonoids on this crude drug have not yet been thoroughly investigated. To evaluate and compare anti-inflammatory effects, we used primary cultured rat hepatocytes, which produce proinflammatory mediators, such as nitric oxide (NO) and proinflammatory cytokines, in response to interleukin (IL)-1β. Eight derivatives of 5,7-dihydroxyflavone were purified and identified in the ethyl acetate-soluble fraction of a C. indicum capitulum extract: luteolin (Compound 1), apigenin (2), diosmetin (3), 5,7-dihydroxy-3′,4′,5′-trimethoxyflavone (4), acacetin (5), eupatilin (6), jaceosidin (7), and 6-methoxytricin (8). Luteolin is the most abundant compound in this fraction. All compounds significantly suppressed NO production in hepatocytes, with apigenin and acacetin showing the greatest efficacy. The comparison of the IC₅₀ values of the inhibition of NO production suggests that substitutions by hydroxyl and methoxy groups at the C-3′ and C-4′ positions of 5,7-dihydroxyflavone may be at least essential for the suppression of NO production. In hepatocytes, acacetin and luteolin decreased the levels of mRNAs encoding inducible nitric oxide synthase (iNOS), proinflammatory cytokines, including tumor necrosis factor, IL-6, and type 1 IL-1 receptor, which regulates inflammatory responses. Based on the comparison of the IC₅₀ values and the content, luteolin, jaceosidin, and diosmetin may be responsible for the anti-inflammatory effects of C. indicum capitula. Full article

The application of non-thermal (cold) plasmas is considered an environmentally friendly method that could affect plant metabolism and cellular development or can be used for the commercial production of natural products that cannot be chemically synthesized. In the present study, the non-embryogenic callus of iris (Iris reichenbachii Heuff.) was treated with a Radio Frequency (RF) plasma needle device using He as a working gas. We investigated short-term (up to seven days) and long-term (up to one year) changes on morphological, physiological and biochemical levels. An increased production of O₂⁻ and H₂O₂ was observed in the callus tissue after plasma treatment. The enzymes SOD and CAT represented the frontline in the antioxidant defense against reactive oxygen species (ROS) produced during the first hour of treatment, while POX was the leading antioxidant enzyme seven days after plasma treatment. Significant long-term morphological changes were observed in the calli due to the increased mitotic activity of the plant cells. In addition, three flavonoids (naringenin, apigenin and acacetin) and two isoflavonoids (irisolidone and irilone) were detected only in the plasma-treated tissue even one year after plasma treatment. The present study emphasizes the application of the plasma technique to promote meristematic activity and stimulate the production of specialized metabolites in iris calli. Full article

Chrysanthemum species represent an economically important group of flowering plants. Many species also present a medicinal interest, notably for the treatment of inflammatory pathologies. This is the case for Chrysanthemum boreale Makino, endemic to Japan and widespread in Eastern Asia. This perennial plant has long been used in folk medicine to treat inflammatory diseases and bacterial infections. An extensive review of the scientific literature pertaining to C. boreale has been performed to analyze the origin of the plant, its genetic traits, the traditional usages, and the properties of aqueous or organic plant extracts and essential oils derived from this species. Aqueous extracts and the associated flavonoids, such as acacetin and glycoside derivatives, display potent antioxidant activities. These aqueous extracts and floral waters are used mainly as cytoprotective agents. Organic extracts, in particular those made from methanol or ethanol, essentially display antioxidant and anti-inflammatory properties useful to protect organs from oxidative damage. They can be used for neuroprotection. Essential oils from C. boreale have been used as cytoprotective or antibacterial agents. The main bioactive natural products isolated from the plant include flavonoids such as acacetin and related glycosides (notably linarin), and diverse sesquiterpene lactones (SLs). Among monomeric SLs, cumambrins and borenolide are the main products of interest, with cumambrin A targeting covalently the transcription factor NF-κB to regulate proinflammatory gene expression to limit osteoclastic bone resorption. The dimeric SL handelin, which is characteristic of C. boreale, exhibits a prominent anti-inflammatory action, with a capacity to target key proteins like kinase TAK1 and chaperone Hsp70. A few other natural products isolated from the plant (tulipinolide, polyacetylenic derivatives) are discussed. Altogether, the review explores all medicinal usages of the plant and the associated phytochemical panorama, with the objective of promoting further botanical and chemical studies of this ancestral medicinal species. Full article

Biflavonoids are a unique subclass of dietary polyphenolic compounds known for their diverse bioactivities. Despite these benefits, these biflavonoids remain largely underexplored due to their limited natural availability and harsh conditions required for their synthesis, which restricts broader research and application in functional foods and nutraceuticals. To address this gap, we synthesized a library of rare biflavonoids using a radical–nucleophile coupling reaction previously reported by our group. The food grade coupling reaction under weakly alkaline water at room temperature led to isolation of 28 heterocoupled biflavones from 11 monomers, namely 3′,4′-dihydroxyflavone, 5,3′,4′-trihydroxyflavone, 6,3′,4′-trihydroxyflavone, 7,3′,4′-trihydroxyflavone, diosmetin, chrysin, acacetin, genistein, biochanin A, and wogonin. The structures of the dimers are characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectroscopy (HRMS). In addition, we evaluated the antioxidant potential of these biflavones using a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay and the DPPH value ranges between 0.75 to 1.82 mM of Trolox/mM of sample across the 28 synthesized dimers. Additionally, a three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis was conducted to identify structural features associated with enhanced antioxidant activity. The partial least squares (PLS) regression QSAR model showed acceptable r² = 0.936 and q² = 0.869. Additionally, the average local ionization energy (ALIE), electrostatic potential (ESP), Fukui index (F-), and electron density (ED) were determined to identify the key structural moiety that was capable of donating electrons to neutralize reactive oxygen species. Full article

Background: Horwoodia dicksoniae Turrill. (Brassicaceae) and Stipa capensis Thunb. (Poaceae) are commonly grown in the eastern region of Saudi Arabia. Methods: This study evaluated the antibacterial and antifungal potential of these plants. H. dicksoniae extract was further subjected to antioxidant, anticancer, GC-MS, LC-MS/MS, and in silico analyses. Results: H. dicksoniae extract presented a higher antimicrobial efficiency than S. capensis extract by effectively inhibiting the growth of Staphylococcus aureus, Escherichia coli, Proteus vulgaris, Bacillus subtilis, and Candida albicans. H. dicksoniae ethanolic extract also demonstrated promising antioxidant and anticancer properties against the human colon cancer cell line HCT-116. GC-MS analysis revealed the presence of 12 natural compounds in the H. dicksoniae extract, whereas LC-MS/MS analysis revealed 19 different compounds in negative ion mode and 25 in positive ion mode. Furthermore, the presence of bioactive compounds in the H. dicksoniae extract, such as flavonoids (acacetin and hesperetin) and caffeic acid, confirmed the observed antibacterial, antifungal, antioxidant, and anticancer activities. Molecular docking revealed promising interactions between various bioactive compounds and target proteins associated with antimicrobial, antioxidant, and anticancer activities. Conclusions: This study is the first to report GC-MS and LC-MS/MS analyses of H. dicksoniae ethanolic extract. The findings provide valuable insights into the potential mechanisms and therapeutic applications of the identified bioactive compounds. Thus, the present work can serve as a platform for the isolation of natural compounds from H. dicksoniae extract, which may play a significant role in the discovery and design of new drugs for the treatment of human diseases. Full article

Background: Skin aging is a complex biological process affected by internal and external factors that disrupt the skin structure, especially in sun-exposed areas. Elastin and collagen in the dermis layer, responsible for the skin’s resistance and elasticity, have been the main subject of research. Since tyrosinase (TYR) is an enzyme found in different organisms and plays an essential role in melanogenesis, inhibitors of this enzyme have been the target mechanism for skin-bleaching product research. Methods: We selected the plant species Cotinus coggygria Scop., Garcinia mangostana L., Pistacia vera L., Vitis vinifera L., and propolis, which exhibited activity against a minimum of three target enzymes—elastase, collagenase, and TYR—in our previous screening study to find the suitable raw material for a cosmetic product. In the current research, the extracts from these samples were tested through a cell-free enzyme assay using validated elastase, collagenase, and TYR inhibition kits. We also performed the safety and efficacy tests of the selected extracts with 2D/3D cell culture methods. Results: Our data revealed the propolis extract among the tested ones displayed remarkable anti-inflammatory activity in the 2D (NF-κB induction: 10.81%) and 3D assays. Cotinus coggygria leaf and Garcinia mangostana shell extracts exhibited anti-inflammatory activity in the 2D luciferase reporter assay via TNFα addition. C. coggygria leaf, V. vinifera (grape) seed, and propolis extracts were selected for testing in 3D cell culture methods based on the 2D cytotoxicity results with cell viability values of 54.75%, 93.19%, and 98.64% at 34.25 µg/mL, respectively. The general phytochemical profiles of these three extracts were examined in terms of 53 phenolic compounds with LC-MS/MS, revealing that quinic acid, epicatechin, and acacetin were the dominant phenolics among the tested ones. Conclusions: It is the first study conducted to evaluate the use of the extracts indicated above in cosmetics by employing procedures involving 3D cell culture. Full article

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a pulmonary disease with high mortality associated with inflammation. During the development of ALI/ARDS, macrophages usually polarize toward M1 pro-inflammatory macrophages, promoting the inflammatory response in ALI/ARDS and aggravating lung tissue damage. Natural compounds with anti-inflammatory activity have achieved excellent results in the treatment of ALI/ARDS through different regulatory modes, including macrophage polarization. Of note, flavonoid, brevilin A, and tetrahydropalmatine play an important role in the treatment of ALI/ARDS by modulating the phenotypic polarization of macrophages and their pro-inflammatory cytokine expression in innate immune cells of the lung. Flavonoids are a kind of naturally occurring polyphenol compound, which has antioxidant and anti-inflammatory activities. Studies have found that some flavonoids can alleviate ALI/ARDS through inhibiting the expression of inflammatory cytokines in macrophages. Among them, 5-methoxyflavone, acacetin, grape seed proanthocyanidins, and luteolin can also regulate macrophage polarization. Therefore, the in-depth exploration of the regulatory mechanism of macrophages can lay the foundation for the application of flavonoids in alleviating inflammation-related lung injury. This review focuses on the macrophage polarization effects of different natural compounds and their potential anti-inflammatory mechanisms in the treatment of ALI/ARDS. Full article

Plant polyphenols have significant importance due to their potential health benefits. Polygala major Jacq. is commonly found in Asia and has a long history of use in traditional medicine. This study investigated the extraction of polyphenols from the leaves and flowers of P. major Jacq. using various solvents (acetone, ethanol, and methanol) and employing two extraction methods: maceration and ultrasonication. Significant amounts of total phenolics were detected in all conditions, measuring between 26.69 and 48.51 mg GAE/g dry matter, with the highest concentration found in the ultrasonicated ethanol extract from the leaves. Compared to the other solvents, acetone was particularly effective in extracting flavonoids from the leaves. The antioxidant activities ranged from 0.65 to 0.86 mg TE/g dry matter, as determined by the DPPH radical scavenging activity method. The leaf extract displayed antibacterial activity against Bacillus cereus, Pseudomonas aeruginosa, and Staphylococcus aureus, while the flower extract had no antibacterial activity. UV-Vis spectroscopy and FTIR analysis confirmed the presence of polyphenols in the extracts. According to LCMS analyses, a total of 67 compounds were identified in the leaves and flowers, including several that are pharmaceutically significant, such as eupatorin, sinensetin, acacetin, ombuin, vanillic acid, sinapic acid, apigenin, naringenin, and luteolin. Full article