Search Results (49)

Background/Objective: Traditionally derived from the dried leaves of Microcos paniculata L., Microctis folium (M. folium) has been employed to manage various inflammatory and metabolic conditions. Despite its reported hypolipidemic potential, the active constituents contributing to this effect and their molecular mechanisms of action remain to be determined. Therefore, this study aimed to systematically identify the active hypolipidemic constituents of M. folium and elucidate their mechanisms of action through an integrated strategy combining chemical profiling, pharmacokinetic screening, network pharmacology, and experimental validation. Methods: UPLC fingerprint and UPLC-QQQ-MS/MS were employed to characterize and quantify the chemical constituents of M. folium. Pharmacokinetic analysis was conducted to identify systemically absorbed compounds. Network pharmacology was applied to predict potential targets and signaling pathways. The lipid-lowering effects were subsequently validated in vitro using an oleic acid/palmitic acid (OA/PA)-induced lipid accumulation model in HepG2 cells and in vivo in a Triton WR-1339-induced hyperlipidemia mouse model. Results: UPLC fingerprint analysis identified 15 common peaks among 21 batches of M. folium, with similarity values ranging from 0.885 to 0.990, indicating good chemical consistency. Eighteen representative compounds were quantified, among which flavone C-glycosides and phenolic acids were predominant. Pharmacokinetic results demonstrated that multiple M. folium’s constituents were absorbed into systemic circulation. Network pharmacology analysis identified 73 potential targets related to hyperlipidemia and highlighted the PI3K-Akt signaling pathway as a key regulatory pathway. In vitro experiments showed that M. folium’s compounds significantly reduced intracellular lipid accumulation and oxidative stress in OA/PA-induced HepG2 cells. Furthermore, in vivo studies demonstrated that vitexin, ferulic acid, isoferulic acid, and N-trans-feruloyltyramine significantly reduced serum and hepatic lipid levels, including TC, TG, and LDL-c, alleviated hepatic steatosis, and improved liver injury and oxidative stress markers in Triton WR-1339-induced hyperlipidemic mice. Conclusions: M. folium exerts significant lipid-lowering effects through multi-component and multi-target mechanisms involving regulation of lipid metabolism and oxidative stress, partly mediated by activation of the PI3K-Akt signaling pathway. These findings provide a scientific basis for the development of M. folium’s natural agents for the treatment of hyperlipidemia. Full article

Amaryllidaceae alkaloids are of notable pharmacological relevance. For instance, galanthamine is used in the treatment of Alzheimer’s disease, while other alkaloids (lycorine, crinine, etc.) derived from Amaryllidaceae plants are also of great interest because they exhibit antitumour, antiviral, antibacterial, antifungal, antimalarial, analgesic and cytotoxic properties. Phenolic acids comprise a group of natural bioactive substances that have commercial value in the cosmetic, food and medicinal industries due to their antioxidant, anticancer, anti-inflammatory and cardioprotective potential. In the present study, the effect of temperature (15, 20, 25 and 30 °C) on Amaryllidaceae alkaloid and phenolic acid biosynthesis in Leucojum aestivum in vitro plant cultures was investigated. The highest diversity of alkaloids (i.e., galanthamine, crinan-3-ol, demethylmaritidine, crinine, 11-hydroxyvitattine, lycorine, epiisohaemanthamine, chlidanthine) was noted in plants cultured at 30 °C. By contrast, ismine and tazettine were only present in plants cultured at 15 °C. Temperatures of 20 °C and 30 °C were found to stimulate galanthamine accumulation. The highest lycorine content was noted in plants grown at temperatures of 15 and 30 °C, and it was negatively correlated with the expression of the gene that encodes the cytochrome P450 96T (CYP96T) enzyme which catalyses a key step in the biosynthesis of different types of Amaryllidaceae alkaloids. This observation may reflect temperature-induced shifts in metabolic flux among different branches of Amaryllidaceae alkaloid biosynthesis. The observed stimulating effect of a 15 °C temperature on the chlorogenic, caffeic, p-coumaric, sinapic, ferulic and isoferulic acid content was in line with the highest expression of a gene that encodes the tyrosine decarboxylase (TYDC) enzyme, which is involved in plant stress response mechanisms. At 30 °C, however, the highest content of the caffeic, vanillic, p-coumaric and isoferulic acids was noted. Full article

Olive pomace (OP), an olive mill byproduct, poses environmental risks if mismanaged due to its high phenolic content, acidic pH, organic load, and electrical conductivity. This study evaluated the impact of olive pomace filtrate (OPF) at varying doses (OP-5, OP-10, OP-15) on broad bean (Vicia faba L.) growth, secondary metabolites, and nutrient accumulation. The highest OPF dose (OP-15) exhibited a clear negative, dose-dependent phytotoxic effect, causing stem discoloration, reduced root growth, necrosis, and chlorosis, while untreated controls showed vigorous growth. This significantly (p < 0.05) reduced leaf development, average number of leaves, and total leaf area, even at the lowest concentration (5%). Consequently, OP-15 reduced dry and fresh biomass by over 50% and shoot/root lengths by up to 61.55% compared to the control. Liquid chromatography mass spectrometry (LC-MS/MS) analysis revealed a positive dose-dependent effect of OPF on beneficial phenol and flavonoid accumulation, with significantly higher amounts of ferulic, isoferulic, caffeic, chlorogenic, and 4-hydroxybenzoic acids, as well as luteolin-4′-rutinoside and 4,7-dihydroxyflavone. OP application significantly (p < 0.05) decreased relative water content and increased electrolyte leakage and malondialdehyde, indicating stress. Furthermore, OP decreased the uptake of K, P, Fe, S, Zn, and Cu. Therefore, the intrinsic phytotoxicity of OPF suggests that mitigation measures are essential before considering environmental application to prevent potential adverse effects on sensitive crops and the wider ecosystem. Full article

Erythrina caffra is a traditional plant used to treat cancer and inflammation. The study aimed to assess and isolate anticancer compounds from E. caffra bark. The plant material was extracted sequentially in n-hexane, dichloromethane, ethyl acetate and methanol. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and 3-(4,5-di methyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to evaluate the crude extracts’ antioxidant and anticancer activities, respectively. Column chromatography was used to purify the potent extracts of the stem bark in order to isolate the bioactive compounds. The crude extracts of the E. caffra bark demonstrated antioxidant and anticancer activity, with the dichloromethane (DCM) extract producing the most favorable activity. Three compounds, namely Hexacosanyl isoferulate, Tetradecyl isoferulate, and 1-Heneicosanol, were detected in fractions from the DCM extract. All the isolated compounds showed significant anticancer potential, with the hydroxycinnamic acid compounds showing better anticancer effects in the cervical (HeLa) and breast cancer (MCF-7) cells. The compounds showed greater activity than even the standard drug, 5-fluorouracil, in the MCF-7 cells, with the tetradecyl isoferulate and hexacosanyl isoferulate fractions having IC₅₀ values of 123.62 and 58.84 µg/mL, respectively. The compounds were observed to be capable of triggering caspase cascade events, leading to apoptotic cell death. Overall, E. caffra extracts contained important bioactive compounds that induced apoptotic cell death in HeLa and MCF-7 tumor cells, warranting further investigations in vitro and in vivo. Full article

This study presents the first comprehensive theoretical investigation of the antioxidant mechanisms of trans-isoferulic acid against hydroperoxyl (HOO^•) radicals in aqueous solution, using the DFT/M062X/6-311+G(d,p)/PCM method. Thermodynamic and kinetic parameters, including reaction energy barriers and bimolecular rate constants, were determined for the three major pathways: hydrogen transfer (HT), radical adduct formation (RAF), and single electron transfer (SET). The results indicate that, at physiological pH, the RAF mechanism is both more exergonic and approximately eight-times faster than HT. At a higher pH, where the phenolate anion dominates, antioxidant activity is enhanced by an additional fast, diffusion-limited SET pathway. Isoferulic acid was also found to effectively chelate Fe²⁺ ions at pH 7.4 and above, forming stable complexes that could inhibit Fenton-type hydroxyl radical generation. Moreover, its strong UV absorption suggests a role in limiting photo-induced free radical formation. These findings not only clarify the antioxidant behavior of isoferulic acid but also provide novel theoretical insights applicable to related phenolic compounds. The compound’s multi-target antioxidant profile highlights its potential as a photoprotective agent in sunscreen formulations. Full article

For the first time, hydroethanolic extracts from Actaea cimicifuga and Actaea erythrocarpa were analyzed using LC-HRMS, HPLC, and spectrometry in this study. Extracts from the above-ground parts of Actaea species exhibited higher concentrations of saponins (up to 248 mg/g of DE), coumarins (up to 162 mg/g of DE), flavonols (up to 32 mg/g of DE), and catechins (up to 11 mg/g of DE) compared to extracts from the underground parts. The concentrations of phenolic acids (up to 112 mg/g of DE) and tannins (up to 202 mg/g of DE) in the underground parts were comparable to or even higher than those in the above-ground parts of the two analyzed species. The concentration of the main metabolites detected was higher in the extract of A. erythrocarpa than that of A. cimicifuga. The metabolite profile of the extracts from both species showed 66 compounds, including chromones, coumarins, phenolic and nitrogenous compounds, fatty acids, and triterpenes. The HPLC analysis of the four extracts revealed that the concentration of caffeic acid (0.74 mg/g of the dry extract [DE]) was the highest in the extract from the underground part of A. erythrocarpa, whereas the extract from the above-ground part of this species showed the highest levels of ferulic (1.16 mg/g of DE) and isoferulic acids (1.49 mg/g of DE) and of hyperoside (13.05 mg/g of DE). The study of biological activity showed that A. erythrocarpa is most promising for further research, with the highest antioxidant activity found in the underground parts of this species (IC₅₀ = 79.7 μg/mL) compared to the above-ground parts (IC₅₀ = 85.8 μg/mL). In addition, the extract from the above-ground part of A. erythrocarpa was found to exhibit the greatest cytotoxic activity among the studied specimens against 3T3-L1, HepG2, and MDA-MB-231 cells. Full article

Background: The colour of tea beverages during processing and storage significantly influences their visual quality. However, natural pink tea products are rare. This study investigated the mechanism behind the pink colouration in the mixed infusion of Biluochun (a green tea) and rosemary. Methods: Infusions of Biluochun (B), rosemary (R), and their mixture (BR), brewed with boiling water for 10 min, were analysed using liquid chromatography-mass spectrometry (LC-MS). Additionally, the pH value and tea pigment content were measured. Results: A total of 134 differential metabolites (DEMs) were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that phenylalanine metabolism and tyrosine metabolism pathways were enriched with abundant DEMs. Some amino acids in BR showed degradation. The content of pelargonin, a compound in the anthocyanin biosynthetic pathway, was significantly elevated in BR compared to that in B and R. DEMs related to fatty acid metabolism were at low levels in BR. Other compounds, such as quercetin, caffeate, rosmarinic acid, and isoferulic acid, were also more abundant in BR. No significant differences in pH value and tea pigment content were found among the three infusions. Conclusions: A model of pink colouration formation in BR was proposed based on the results of this study. Some substances in Biluochun and rosemary were released during the brewing process. Tyrosine was converted into p-coumaric acid, which further reacted to form pelargonin. Pelargonin, an orange-red (pH ≈ 5.0) anthocyanin, was the primary contributor to the pink colouration in BR. Additionally, p-coumaric acid formed co-pigments such as quercetin, caffeic acid, rosmarinic acid, and isovaleric acid. These co-pigments stabilised or enhanced the colour of pelargonin through co-pigmentation. The findings provide a theoretical basis for optimising tea processing techniques and improving quality control in beverage production. Full article

Background: Jujube is a homologous herb of medicine and food, and polyphenols are key in determining the functional effects of jujubes. Methods: In this study, characteristic polyphenols in 15 varieties of Chinese jujubes were investigated based on untargeted metabolomics. Results: The results showed that a total of 79 characteristic polyphenols were identified in the 15 varieties of Chinese jujube, and 55 characteristic polyphenols such as syringetin, spinosin and kaempferol were reported for the first time. Scopoletin (63.94% in LZYZ), pectolinarin (22.63% in HZ) and taxifolin (19.69% in HZ) contributed greatly and presented significant (p < 0.05) differences in the 15 varieties of Chinese jujubes. HZ was characterized by pectolinarin, erianin and wogonoside, while XSHZ, NYDZ and RQHZ, with similar polyphenol profiles, were characterized by (+)-catechin, combretastatin A4 and tectorigenin. JSBZ, HMDZ, TZ, JCJZ and HPZ had similar polyphenol profiles of galangin, isoferulic acid and hydroxysafflor yellow A. Conclusions: Metabolomics is critical in grasping the full polyphenol contents of jujubes, and the differences in the polyphenol profiles and characteristic individual polyphenols of the 15 varieties of Chinese jujubes were well analyzed by principal component analysis (PCA). Full article

Oats are gluten-free cereals rich in dietary fiber, β-glucans, phenolic acids, flavonoids, carotenoids, vitamin E, and phytosterols. They have been used in traditional medicine for centuries to treat hyperacidity, acute pancreatitis, burns, and skin inflammation. This study assessed the nutritional and phenolic profile of oat flour (OF) and ground oat husks (OHs) from white, brown, and black hulled oat genotypes, as well as the antioxidant and antimicrobial activity of their extracts. The extracts were tested on six strains of gastrointestinal tract pathogens. OF samples had, on average, a high protein content (15.83%), fat content (6.27%), and β-glucan content (4.69%), while OH samples were rich in dietary fiber. OHs had significantly higher average total phenolic compounds compared to OF and had twice as high antioxidant capacity. Ferulic acid was predominant in all samples, followed by p-coumaric, isoferulic, vanillic, and syringic acid. The traditionally prepared OH extracts manifested the best bactericidal activity against Listeria monocytogenes, Escherichia coli, and Staphylococcus haemolyticus, while Salmonella typhimurium was the least sensitive to the bactericidal effect of all the investigated samples. Both OF and powdered OHs have potential applications in the functional food industry and pharmacy due to their bioactive compounds, their biological activity, as well as their overall nutritional profile. Full article

The importance of the valorization of industrial by-products has led to increasing research into their reuse. In this research, the innovative by-product okara oat flour, derived from the vegetable beverage industry, was studied. Oat okara sourdough was also produced and evaluated. The microbiological identification and typing involved bacterial and yeast isolates from both flour and sourdough. Untargeted metabolomics allowed the identification of biomarkers of fermented flour, such as phenolic classes, post-fermentation metabolites, fatty acids, and amino acids. The microorganisms most found were Weissella confusa, Enterococcus faecium, Pediococcus pentosaceus, and Pichia kudriavzevii, while Saccharomyces cerevisiae appeared only at the end of the sourdough’s back-slopping. Untargeted metabolomics identified a total of 539 metabolites, including phenolic compounds, lipids, amino acids, and organic acids. An increase in polyphenols released from the food matrix was detected, likely because of the higher bio-accessibility of phenolic metabolites promoted by microbial fermentation. Fermentation led to an increase in isoferulic acid, p-coumaric acid, sinapic acid, and a decrease in amino acids, which can be attributed to the metabolism of lactic acid bacteria. Some key markers of the fermentation process of both lactic acid bacteria and yeast were also measured, including organic acids (lactate, succinate, and propionate derivatives) and flavor compounds (e.g., diacetyl). Two bioactive compounds, such as gamma-aminobutyric acid and 3-phenyl-lactic acid had accumulated at the end of fermentation. Taken together, our findings showed that oat okara flour can be considered an excellent raw material for formulating more sustainable and functional foods due to fermentation promoted by autochthonous microbiota. Full article

Background: Glioblastoma multiforme (GBM) is among the most aggressive and challenging brain tumors, with limited treatment options. Cimicifuga foetida, a traditional Chinese medicine, has shown promise due to its bioactive components. This study investigates the anti-glioma effects of a methanolic extract of C. foetida (CF-ME) in GBM cell lines. Methods: The effects of CF-ME and its index compounds (caffeic acid, cimifugin, ferulic acid, and isoferulic acid) on GBM cell viability were assessed using MTT assays on U87 MG, A172, and T98G cell lines. The ability of CF-ME to induce cell cycle arrest, apoptosis, and autophagy and inhibit metastasis was evaluated using flow cytometry, Western blotting, and functional assays. Additionally, the synergistic potential of CF-ME with temozolomide (TMZ) was explored. Results: CF-ME significantly reduced GBM cell viability in a dose- and time-dependent manner, induced G1 phase cell cycle arrest, promoted apoptosis via caspase activation, and triggered autophagy. CF-ME also inhibited GBM cell invasion, migration, and adhesion, likely by modulating epithelial–mesenchymal transition (EMT) markers. Combined with TMZ, CF-ME further enhanced reduced GBM cell viability, suggesting a potential synergistic effect. However, the individual index compounds of CF-ME exhibited only modest inhibitory effects, indicating that the full anti-glioma activity may result from the synergistic interactions among its components. Conclusions: CF-ME exhibited potent anti-glioma activity through multiple mechanisms, including cell cycle arrest, apoptosis, autophagy, and the inhibition of metastasis. Combining CF-ME with TMZ further enhanced its therapeutic potential, making it a promising candidate for adjuvant therapy in glioblastoma treatment. Full article

Excessive alcohol consumption has led to the prevalence of gastrointestinal ailments. Alleviating gastric disorders attributed to alcohol-induced thinning of the mucus layer has centered on enhancing mucin secretion as a pivotal approach. In this study, foxtail millet bran polyphenol BPIS was divided into two components with MW < 200 D and MW > 200 D by molecular interception technology. Combined with MTT, cell morphology observation, and trypan blue staining, isoferulic acid (IFA) within the MW < 200 D fraction was determined as the effective constituent to mitigate ethanol-induced damage of gastric epithelial cells. Furthermore, a Wistar rat model with similar clinical features to alcohol-induced gastric mucosal injury was established. Then, gastric morphological observation, H&E staining, and assessments of changes in gastric hexosamine content and gastric wall binding mucus levels were carried out, and the results revealed that IFA (10 mg/Kg) significantly ameliorated alcohol-induced gastric mucosal damage. Finally, we applied techniques including Co-IP, molecular docking, and fluorescence spectroscopy and found that IFA inhibited the alcohol-induced downregulation of N-acetylgalactosamintransferase 2 (GALNT2) activity related to mucus synthesis through direct interaction with GALNT2 in gastric epithelial cells, thus promoting mucin synthesis. Our study lays a foundation for whole grain dietary intervention tailored to individuals suffering from alcoholic gastric mucosal injury. Full article

Background and Objectives: Cimicifugae Rhizoma, also known as ‘Sheng ma’ in Madeiran, is a widely used Chinese herbal medicine that has several pharmacological qualities, one of which is its antioxidant activity. Isoferulic acid, a prominent phenolic compound found in Cimicifugae Rhizoma, has potent antioxidant properties. This study was aimed to comprehensively analyze the components in Cimicifugae Rhizoma and rat plasma to evaluate the in vitro antioxidant and anti-inflammatory properties of Cimicifugae Rhizoma extract and Isoferulic acid as potential candidates for developing herbal formulations targeting podocyte injury in diabetic nephropathy for further clinical utilization. Materials and Methods: UPLC/Q-TOF-MS and HPLC were utilized as analytical tools to identify components of Cimicifugae Rhizoma extract or rat plasma after administrating it. MPC5 cells were cultured with H₂O₂ and high glucose and subjected to oxidative stress injury. The CXCL12/CXCR4 system plays a crucial role at certain stages of multiple kidney diseases’ injury. Apoptosis-related and target CXCL12/CXCR4/mTOR/Caspase-3 and Cask protein levels were assessed, and the levels of inflammatory-related factors, motility, morphology, ROS level, and apoptosis in podocytes were tested. Results: A total of 82 and 39 components were identified in the Cimicifugae Rhizoma extract and plasma, and Isoferulic acid content was determined as 6.52 mg/g in the Cimicifugae Rhizoma extract. The Cimicifugae Rhizoma extract (1 μg/mL) and Isoferulic acid (10, 25, 50 μM) considerably decreased high glucose and oxidative-stress-mediated toxicity, impaired mobility and adhesion and apoptotic changes in MPC5 cells, and reversed inflammation response. Moreover, the Cimicifugae Rhizoma extract and Isoferulic acid down-regulated Cask, mTOR, and Caspase-3, while significantly blocking the overactivation of CXCL12/CXCR4 in podocytes stimulated by oxidative stress and high glucose. Conclusions: These results indicate that the renal protective mechanism of the Cimicifugae Rhizoma extract and Isoferulic acid on simulating H₂O₂-induced podocyte injury involves mainly the of CXCL12/CXCR4 pathways and the inactivation of oxidative-stress-mediated apoptotic pathways after comprehensive qualitative and quantitative research by UPLC/Q-TOF-MS and HPLC. These findings provide an important efficacy and ingredient basis for further study on the clinical utilities of Cimicifugae Rhizoma and Isoferulic acid on podocyte and kidney impairment. Full article

This study thoroughly examined the proximate composition, bioactive composition, and in vitro biological activities of three different cultivars of papaya leaf extracts (PLEs) as potential functional ingredients and nutraceuticals. The dark green leaves of three papaya cultivars, Khaek Dam (KD), Holland (H), and Thai Local (L), were used in this study. The protein content of the leaves ranged from 25.96 to 32.18%, the fat content ranged from 7.34 to 11.66%, the carbohydrate content ranged from 5.80 to 17.91%, the moisture content ranged from 6.02 to 6.49%, the ash content ranged from 11.23 to 12.40%, and the fiber content ranged from 23.24 to 38.48%. The L cultivar possessed significantly higher protein and carbohydrate contents, whereas the H cultivar had the highest ash content (p < 0.05). The total phenolic content (TPC) ranged from 113.94 to 173.69 mg GAE/g extract, with the KD cultivar having the highest TPC (p < 0.05). Several metabolic compounds such as phenolic compounds (particularly kaempferol, isorhamnetin, quercetin, ferulic acid, isoferulic acid, salicylic acid, sinapic acid, syringic acid, and vanillin), terpenoids (such as eucalyptol), glycosides, and indole were identified. The PLE from the KD cultivar had the highest levels of DPPH^• inhibition, metal chelation, reducing power, and antidiabetic activity (p < 0.05), suggesting superior biological activity. All three PLEs reduced the proliferation of RAW 264.7 cells in a dose-dependent manner with low nitric oxide formation. These results indicate that the papaya leaf, particularly from the KD cultivar, could be a promising source of functional food ingredients. Full article

Jaggery, a non-centrifugal sugar (NCS), is a naturally produced sweetener and a good source of minerals, essential vitamins and bioactives. Jaggery manufacturing is a continuous heat and mass transfer process which involves various unit operations and in which the effectiveness of juice clarification plays an important role in maintaining the nutritional quality and storage life of jaggery. The major components of nutritional interest in NCSs are minerals and bioactives and they are gaining worldwide attention due to their nutraceutical properties. Hence, there is a need to quantify the nutrients present in NCSs as well as assess their biological absorption and function. This work aims to study the potential flow of materials within a jaggery processing unit by combining sampling, analysis and quantification. Sugarcane juice, clarified juice, scum and jaggery were analyzed for their total sugars, total phenolic and flavonoid content, mineral content and antioxidant potential to clearly understand at which step of jaggery manufacturing nutritional losses take place, if at all. A profiling of phenolic and flavonoid compounds was conducted using liquid chromatography–mass spectroscopy. The total ash content in raw cane juice, scum and jaggery was found to be in the range of 0.1–0.4%, 1–3% and 1–2% (dry basis), respectively. It was found that almost half of the mineral contents from sugarcane juice were lost in scum (p < 0.05). All the mineral elements showed a similar affinity towards scum. However, through liquid chromatography–mass spectroscopy, it was seen that most of the polyphenols (75%) that positively influence human health, such as oryzarol, hydrocinnamic acids, gentisic acid, hydrobenzoic acids, etc., were retained in jaggery. The same could be validated when looking at the total phenolic and flavonoid contents of sugarcane juice, scum and jaggery along with their antioxidant potential. Some unreported phenolics and flavonoids, such as isoferulic acid, prunitrin and maritimetin, which are known to have anti-inflammatory properties, were detected in selected NCS samples. In order to retain maximum mineral content in jaggery and to ensure the removal of appropriate amounts of scum, technological upgrades must be studied and the clarification step must be optimized and standardized. Full article