Search Results (50)

Agro-industrial residues such as prickly pear peel represent an underutilized source of bioactive compounds. However, comparative evidence on green extraction versus biotransformation strategies remains limited. This study evaluated solid-state fermentation (SSF), ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE) for tannin recovery from Opuntia ficus-indica peel. SSF using Aspergillus niger significantly enhanced condensed tannins (>50 mg/g) and hydrolyzable tannins (~7 mg/g), outperforming UAE and MAE. This improvement was associated with fungal-mediated cell wall degradation and metabolic transformation. SSF extracts also showed superior antioxidant activity (DPPH, ABTS, and FRAP) and exclusive antimicrobial activity against Escherichia coli (4.5 mm inhibition zone). HPLC analysis revealed increased phenolic diversity, with rhamnetin as the predominant metabolite. These findings demonstrate that SSF is not only an extraction method but also a biotransformation strategy that enhances both the yield and functionality of phenolic compounds. This approach supports the sustainable valorization of agro-industrial residues within a circular bioeconomy framework. Full article

The genus Tamarix L. includes several species widely used in traditional medicine for their therapeutic properties. This study aims to evaluate the bioactive potential of Tamarix gallica extracts from Western Algeria using an integrated in vitro and in silico approach. GC–MS analysis with BSTFA derivatization was performed to characterize the chemical profile of the methanolic fraction. In addition, total phenolic, flavonoid, and tannin contents were determined in methanolic extracts of leaves and stems. The biological activities were assessed using antioxidant (DPPH, ABTS, β-carotene, FRAP, O-phenanthroline, and cupric reducing assays), antimicrobial, antidiabetic, and anti-Alzheimer in vitro assays. Molecular docking was conducted to evaluate the inhibitory potential of selected flavonoids against α-amylase, acetylcholinesterase, and butyrylcholinesterase. Results revealed a rich metabolite profile dominated by long-chain aliphatic alcohols (including hentriacontan-12-ol), phytosterols (β-sitosterol), fatty acids, phenolic derivatives, and sugar alcohols. The extracts exhibited strong antioxidant activity (IC₅₀ = 1.34 ± 0.43 and 12.32 ± 0.36 μg·mL⁻¹), significant antimicrobial effects against the tested pathogens, and notable antidiabetic and anticholinesterase activities (IC₅₀ = 78.65 ± 1.43 and 98.37 ± 1.07 μg·mL⁻¹). Molecular docking analysis supported these findings, showing strong binding affinities of quercetin and rhamnetin toward the target enzymes. Overall, T. gallica exhibits promising multifunctional bioactivities with potential pharmaceutical relevance. Full article

Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are major global health burdens that share interconnected pathological mechanisms involving impaired insulin signaling, metabolic stress, and chronic neuroinflammation. This study applied an integrative systems biology and atomistic simulation framework to investigate bioactive compounds from Caesalpinia sappan L. targeting shared molecular regulators linking AD and T2DM. Network topology analysis identified four central hub genes, STAT3, SRC, HSP90AA1, and TP53, representing key regulatory nodes involved in inflammatory signaling, kinase regulation, proteostasis, and cellular stress responses. Compound-specific interaction analysis revealed distinct target preferences among phytochemical subclasses. Protosappanin B showed strong binding toward both STAT3 and HSP90α, whereas flavonols including quercetin and rhamnetin exhibited high affinity for SRC, and the chalcone derivative sappanchalcone preferentially interacted with TP53. Atomistic molecular dynamics simulations and MM-PBSA calculations supported stable protein ligand interactions and favorable binding energetics, while density functional theory analysis indicated electronic properties consistent with sustained intermolecular interactions. Collectively, these findings suggest that structurally distinct subclasses of C. sappan phytochemicals converge on complementary regulatory hubs within the shared AD and T2DM molecular network, supporting coordinated multi-target modulation of interconnected inflammatory, kinase signaling, proteostasis, and cellular stress pathways underlying AD–T2DM comorbidity. Full article

Flavonols are dietary polyphenols whose biological activity is influenced by structural modifications such as O-methylation. This study compared two quercetin derivatives, isorhamnetin (3′-O-methylquercetin) and rhamnetin (7-O-methylquercetin). Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays. Cyclooxygenase-2 (COX-2) inhibitory activity was assessed in vitro and supported by molecular docking simulations. In vivo effects included developmental toxicity, behavioral assessment, and locomotor responses in a 6-hydroxydopamine (6-OHDA) model. The results demonstrated that rhamnetin exhibited significantly stronger radical-scavenging and reducing activity in DPPH, ABTS, and FRAP assays, whereas no significant differences were observed in the CUPRAC assay. Isorhamnetin showed stronger COX-2 inhibition, with docking results suggesting a different mode of binding when analyzing possible interactions with enzyme active site. In zebrafish larvae, rhamnetin showed lower observable developmental toxicity within the tested concentration range, whereas isorhamnetin induced developmental abnormalities at higher concentrations. Both flavonols attenuated 6-OHDA-associated locomotor deficits and modulated antioxidant enzyme activity under oxidative stress conditions. In conclusion, our findings indicate that the position of O-methylation influences flavonol antioxidant properties, COX-2 interactions, and organism-level responses. Full article

Soil salinization poses a major constraint to global agriculture. Apocynum venetum, a salt-tolerant halophyte, provides an effective model for investigating salt-adaptive strategies; however, the temporal dynamics of its tolerance-associated genes and metabolites remain unclear. In this study, integrated transcriptomics, metabolomics (UHPLC-MS), physiological assays, and weighted gene co-expression network analysis (WGCNA) were conducted to characterize early (7-day) and late (18-day) responses to 200 mM NaCl stress. NaCl stress significantly reduced chlorophyll content while increasing Na⁺ accumulation, MDA levels, antioxidant enzyme activities (SOD and CAT), and total flavonoid content. Early responses (NaCl7) were marked by accumulation of ferulic acid, rhamnetin, and 3,4-dihydrocoumarin, with activation of plant hormone (ABA, auxin, zeatin) and MAPK signaling pathways. Late responses (NaCl18) exhibited increased accumulation of scopoletin, formononetin, and caffeyl-alcohol, with enrichment of phenylpropanoid biosynthesis, glutathione metabolism, and photosynthesis-related pathways. WGCNA identified early-response hub genes, including AOC, MAPKKK17/18, CYP98A, and CCoAOMT, coordinating stress signaling and antioxidant metabolism. Late stress responses involved genes like CPK, GST, CYCD3, and ARF, modulating calcium signaling and ROS detoxification. Genes shared across phases included CYP90C1, HD-ZIP, HSP20, and PP2C, regulating protein stabilization and stress signaling. These findings reveal a two-phase salt tolerance strategy in A. venetum, integrating early signaling and late metabolic adaptation. Full article

Cancer remains a major global public health concern, driving the need for innovative therapeutic agents with intensified efficacy and safety. Growth factor receptors (GFRs), often overexpressed in cancer cells and critical in regulating cell proliferation, survival, and tumor progression, represent key targets for cancer therapy. Halophytic plants like Salicornia spp. are known for their diverse bioactive compounds with notable pharmacological properties. This study comprehensively evaluated the anti-cancer potentials of phytochemicals derived from Salicornia herbacea and Salicornia brachiata using molecular docking and ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) profiling. A total of 37 bioactive compounds from Salicornia spp. were screened against HER1, HER2, and HER4 receptors. Among them, 3,5-di-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, myricetin, quercetin, stigmasterol, kaempferol, isorhamnetin, rhamnetin, and hesperitin featured strong predicted binding affinities to the HER1, HER2, and HER4 growth factor receptors, comparable to those of standard anti-cancer drugs such as gefitinib and dovitinib. Further pharmacokinetic assessments, including bioavailability and toxicity analyses, identified compounds with favorable drug-likeness properties and minimal toxicity risks, except for myricetin and quercetin. These findings underscore the potential of Salicornia-derived phytochemicals as promising candidates for the development of safe, novel, and effective anti-cancer agents targeting GFRs, contributing to the advances in precision oncology, pending further validation through in vitro and/or in vivo experiments. Full article

Snakebite is a significant global public health challenge, and the limited application of antivenom has driven the exploration of novel therapies. Combination therapy using small-molecule drugs targeting phospholipases A₂ (PLA2) and metalloproteinases (SVMP) in venom shows great potential. Although Rhamnetin and RXP03 exhibit notable anti-phospholipase and anti-metalloproteinase activities, respectively, their antiophidic potential remains poorly explored. This study aims to evaluate the inhibitory effects of Rhamnetin and RXP03 on snake venom toxicity. Methodologically, we conducted in vitro enzymatic assays to quantify PLA₂/SVMP inhibition, murine models of envenomation (subcutaneous/intramuscular venom injection) to assess local tissue damage and systemic toxicity, and histopathological/biochemical analyses. In vitro experiments demonstrated that Rhamnetin effectively inhibited PLA₂ activity while RXP03 showed potent suppression of SVMP activity, with their combination significantly reducing venom-induced hemorrhagic activity. In murine models, the combined therapy markedly alleviated venom-triggered muscle toxicity and ameliorated oxidative stress. Furthermore, the combination enhanced motor performance and survival rate in mice, improved serum biochemical parameters, corrected coagulation disorders, and attenuated pathological damage in liver, kidney, heart, and lung tissues. This research demonstrates that dual-targeted therapy against metalloproteinases and phospholipases in snake venom can effectively prevent a series of injuries caused by snake venom. Collectively, the combined application of Rhamnetin and RXP03 exhibits significant inhibitory effects on a variety of venom-induced toxicities, providing pharmacological evidence for the development of antivenom therapies. However, the efficacy validation in this study was limited to murine models, and there is a discrepancy with clinical needs for delayed treatment in real-world envenomation scenarios. Despite these limitations, the findings provide robust preclinical evidence supporting the Rhamnetin–RXP03 combination therapy as a cost-effective, broad-spectrum antivenom strategy. Future studies are required to optimize dosing regimens and evaluate clinical translatability. Full article

This study evaluated the antioxidant capacity of the oxidation products of three flavonols using oxygen radical absorbance capacity—fluorescein assay (ORAC-FL), oxygen radical absorbance capacity—pyrogallol red assay (ORAC-PGR), and the cellular antioxidant activity (CAA) assay in human dermal fibroblast (HFF) cells, with 2,2’-azobis(2-amidinopropane) dihydrochloride (AAPH) as a free radical generator under controlled pH and solvent conditions. At pH 2 in a polar aprotic solvent, BZF-OH (benzofuranone-OH) compounds were formed, while methoxylated analogs were obtained at pH 7 in a polar protic solvent. The products generated at pH 2 exhibited significantly higher antioxidant capacities, demonstrating the influence of the reaction environment on modulating antioxidant properties. The antioxidant activity was observed to reflect the combined action of the flavonol precursor and its oxidation products. This led to the proposal of the Gross Antioxidant Capacity (GAC) concept to integrate the contribution of all generated species. Since chemical assays such as ORAC do not fully capture the complexity of biological systems, they should be complemented with cellular approaches for a more accurate evaluation. Additionally, BZF-OH compounds were analyzed as potential cyclooxygenase-2 (COX-2) inhibitors through docking and molecular dynamics simulations, where BZF-Quer-OH showed binding affinities comparable to celecoxib, a selective COX-2 inhibitor. These findings were complemented by an analysis of COX-2 expression in RAW 264.7 cells treated with lipopolysaccharide (LPS), where treatment with the antioxidants significantly inhibited COX-2 expression. In the case of the oxidation products, only the oxidation product of rhamnetin showed a reduction in COX-2 expression compared to the LPS-treated control. Together, these results highlight that flavonol-derived oxidation products not only retain significant antioxidant capacity but may also possess anti-inflammatory properties, opening new perspectives for the development of innovative therapies targeting oxidative stress and chronic inflammation. Full article

Secondary metabolites such as flavonoids bring a range of biological properties to natural products, making them potential candidates for the pharmaceutical industry. Piptadenia stipulacea (Benth.) Ducke is well known in Brazil as Jurema Branca, and yet few studies have investigated its biological and phytochemical properties. This study aimed to characterize and evaluate the biological properties of ethanolic extract obtained from the bark of Jurema Branca. Characterization was performed by qualitative phytochemistry, HPLC, and mass spectroscopy. The antibacterial properties were investigated by microdilution method, cytotoxicity by MTT method, biocompatibility testing with human erythrocytes was performed, and antioxidant properties were investigated using DPPH and ABTS radical scavenging. The phytochemical tests demonstrated that rhamnetin and luteolin were the main constituents of the extract. This is the first report of these compounds in this species. The extract presented activity against Staphylococcus aureus (MIC = 500 µg/mL) and demonstrated activity against human colorectal adenocarcinoma (HCT-116), prostate adenocarcinoma (PC-3), and acute myeloid leukemia (HL-60) cell lines with IC₅₀ of 37.96, 37.6, and 27.82 µg/mL, respectively, for this Piptadenia genus. Additionally, the extract presented excellent biocompatibility and antioxidant activity (IC₅₀ = 956.7 and 147.2 µg/mL in DPPH and ABTS methods, respectively). These results are novel for the Piptadenia genus and pave the way for further evaluations regarding the biological importance of this species. Full article

Background/Objectives: Rhamnetin 3-O-α-rhamnoside (ARR) is a major flavonoid of the herb Loranthus tanakae Franch. & Sav., which has been used for treating liver diseases in China. However, the protective effect of ARR on the liver has not been reported. Methods: Zebrafish larvae were used as a visual animal model, and liver injury was induced by thioacetamide (TAA) for an acute liver injury (ALI) model. The hepatoprotective activity of ARR was evaluated by assessing liver morphology, liver function indices, oxidative stress, and the mRNA expression levels of inflammation-related genes in the zebrafish model. Additionally, the ROS level, inflammatory factors, and protein expression related to the IKKβ/NF-κB signaling pathway were measured to investigate a potential mechanism of ARR in HepG2 cells. Results: ARR ameliorated TAA-induced growth retardation, reduced liver injury phenotypes, and decreased oxidative stress in the zebrafish. ARR was also able to lower ROS levels in HepG2 cells, effectively inhibit the overactivation of the IKKβ/NF-κB signaling pathway in pathological conditions, inhibit NF-κB p65 translocation from the cytoplasm to the nucleus, and reduce the release of intracellular inflammatory factors. Conclusions: ARR showed significant protective activity against TAA-induced liver injury in in vivo and in vitro models, and its potential mechanism was closely related to the IKKβ/NF-κB signaling pathway. Full article

Flavonoids are a class of polyphenolic secondary metabolites found in plants. Due to their ubiquity in our daily dietary intake and their major anti-oxidative, anti-inflammatory and anti-mutagenic activities, they have been a major focus of wide-ranging research for the past two decades. Mass spectrometry combined with liquid chromatography is one of the most popular techniques for the analysis of flavonoids. In this study, high-resolution accurate mass electrospray tandem mass spectrometry was used to study 30 flavonoids in both positive and negative ionisation modes. From the data obtained, common losses were summarised and compiled. Dominating neutral losses were tabulated. The radical loss of CH₃· was observed in flavonoids containing methoxy groups and three key diagnostic product ions were identified. These were m/z 153 (indicative of two OH groups on ring A) m/z 167 (indicative of one OH and one methoxy group on ring A) and m/z 151 (a flavanol, with no ketone oxygen but two OH groups on ring A). These will be useful in structural elucidation of unknown flavonoids and flavonoid metabolites. Energy breakdown graphs were utilised to distinguish between three pairs of structural isomers, and to help rationalise proposed fragmentation pathways. Lastly, a competition of loss of CH₃· and methane was reported for rhamnetin and isorhamnetin in the negative ion mode for the first time. Proposed fragmentation pathways were given to rationalise the differences in peak intensities for this competitive process. Full article

Nature provides us with a rich source of compounds with a wide range of applications, including the creation of innovative drugs. Despite advancements in chemically synthesized therapeutics, natural compounds are increasingly significant, especially in cancer treatment, a leading cause of death globally. One promising approach involves the use of natural inhibitors of checkpoint kinase 2 (Chk2), a critical regulator of DNA repair, cell cycle arrest, and apoptosis. Chk2’s activation in response to DNA damage can lead to apoptosis or DNA repair, influencing glycolysis and mitochondrial function. In cancer therapy, inhibiting Chk2 can disrupt DNA repair and cell cycle progression, promoting cancer cell death and enhancing the efficacy of radiotherapy and chemotherapy. Additionally, Chk2 inhibitors can safeguard non-cancerous cells during these treatments by inhibiting p53-dependent apoptosis. Beyond oncology, Chk2 inhibition shows potential in treating hepatitis C virus (HCV) infections, as the virus relies on Chk2 for RNA replication in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), in which DNA damage plays a crucial role. Plant-derived Chk2 inhibitors, such as artemetin, rhamnetin, and curcumin, offer a promising future for treating various diseases with potentially milder side effects and broader metabolic impacts compared to conventional therapies. The review aims to underscore the immense potential of natural Chk2 inhibitors in various therapeutic contexts, particularly in oncology and the treatment of other diseases involving DNA damage and repair mechanisms. These natural Chk2 inhibitors hold significant promise for revolutionizing the landscape of cancer treatment and other diseases. Further research into these compounds could lead to the development of innovative therapies that offer hope for the future with fewer side effects and enhanced efficacy. Full article

The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into pharmaceuticals is Tripleurospermum inodorum (L.) Sch. Bip., also known as Tripleurospermum perforatum (Merat.) M. This plant has been shown to possess various biological activities, including anti-inflammatory, antimicrobial, and antimycotic activities, among others. However, a review of the current literature reveals a paucity of studies investigating the chemical composition of the herb Tripleurospermum inodorum (L.) Sch. Bip. This study presents the development of a method for obtaining an extract of the herb Tripleurospermum inodorum (L.) Sch. Bip. enriched with flavonoids, harvested before flowering and butonization. This study focused on determining the optimal conditions for extraction, including the concentration of the extractant (ethanol), extraction time, raw material/extractant ratio, extraction frequency, complexation reaction time, amount of aluminum chloride solution, and amount of diluted acetic acid. The results indicate that herbs harvested during this specific period exhibited a higher flavonoid content compared to those collected during butonization and flowering. Moreover, this study demonstrated that the flavonoid content could exceed 7% mg REq/100 g D.W. through a one-hour extraction process. Furthermore, the flavonoid content was found to be 7.65 ± 0.03 mg REq/100 g D.W. following a three-minute ultrasound-assisted extraction process, followed by thermal extraction. A qualitative analysis identified a variety of phenolic compounds in the extract, such as chlorogenic acid, 5-O-p-coumaroylquinic acid, 1-O-p-coumaroylquinic acid, luteolin-7-glucoside, quercetin-3-glucoside, luteolin-7-rutinoside, 3,5-O-dicaffeoylquinic acid, quercetin-3-O-malonylglucoside, apigenin-7-glucoside, luteolin-3-malonylglucoside, cynarin, rhamnetin-3-(O-dimethyl rhamnosyl glucosylglucoside), and luteolin. Moreover, this study demonstrated the antimicrobial, anti-inflammatory, anticoagulant, anti-aggregation, and antioxidant activities of the aqueous alcoholic extract from T. inodorum herb (ETIH) against pathogens such as Staphylococcus aureus, Escherichia coli, and Candida albicans. Additionally, the extract exhibited comparable anti-inflammatory effects on diclofenac sodium. These findings contribute to the understanding of the potential pharmacological applications of the developed herb extract. Full article

NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3–V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation. Full article

Sea buckthorn (Hippophaë rhamnoides L.), as one of the Elaeagnaceae family, has the significant function of anti-tumor, anti-inflammation, anti-oxidation, and other physiological activities. High hydrostatic pressure (HHP) extraction has the advantages of being easy and efficient, while maintaining biological activity. In this study, sea buckthorn flavonoid (SBF) was extracted with HHP and purified sea buckthorn flavonoid (PSBF) was isolated by AB-8 macroporous resin column. HPLC analysis was used to quantified them. In addition, the effect of anti-allergy in RBL-2H3 cells by SBF, PSBF, and their flavonoid compounds was evaluated. The results demonstrate the conditions for obtaining the maximum flavonoid amount of SBF: 415 MPa for 10 min, 72% ethanol concentration, and a liquid to solid ratio of 40 mL/g, which increased the purity from 1.46% to 13.26%. Both SBF and PSBF included rutin, quercitrin, quercetin, isorhamnetin, and kaempferol. In addition, quercitrin, kaempferol, and SBF could regulate Th1/Th2 cytokine balance. Moreover, extracellular Ca²⁺ influx was reduced by quercitrin and PSBF. Furthermore, rutin, quercetin, iso-rhamnetin, and SBF could also inhibit P-p38 and P-JNK expression, thereby suppressing the phosphorylation of the MAPK signaling pathways. Overall, SBF is effective for relieving food allergy and might be a promising anti-allergic therapeutic agent. Full article