Search Results (18)

Background/Objectives: Necroptosis is a critical process in the pathogenesis of myocardial ischemia–reperfusion injury (MIRI). Tilianin (Til), a natural flavonoid glycoside derived from Dracocephalum moldavica L., exhibits significant therapeutic potential in cardiovascular diseases. However, its efficacy and mechanisms in mitigating necroptosis-induced MIRI remain incompletely understood. This study aimed to elucidate the molecular mechanisms by which Til regulates cardiomyocyte necroptosis to alleviate MIRI. Methods: A rat model of MIRI was established by ligating the left anterior descending coronary artery. Necroptosis in H9c2 cardiomyocytes was induced by oxygen–glucose deprivation/reoxygenation (H/R) combined with Z-VAD-FMK. Myocardial infarct size was assessed using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Histopathological injury in cardiac tissue was examined by hematoxylin–eosin (HE) staining. Fluorescent probes were used to detect reactive oxygen species (ROS) and mitochondria. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method was used to predict the binding energy between Til and RIP3. Furthermore, RIP3 overexpression and knockdown, along with inhibition of the downstream protein CaMKII, were used to further investigate the mechanism. Results: Til treatment significantly reduced MIRI in rats, decreased myocardial infarct size, histopathological injury, and regulated myocardial enzyme levels. Til pretreatment effectively inhibited necroptosis in H9c2 cells induced by H/R and Z-VAD-FMK, as evidenced by reduced necroptosis rates, decreased inflammatory cytokine release, improved mitochondrial function, and suppressed phosphorylation of the necroptosis marker MLKL. Molecular docking and dynamics simulation demonstrated stable binding of Til to RIP3, which was verified through Western blot. The protective effects of Til on necroptosis were reversed by RIP3 overexpression. Furthermore, the CaMKII inhibitor KN93 abolished Til’s effect on mitochondria. Conclusions: Til alleviates MIRI by targeting RIP3 to inhibit the necroptosis pathway and mPTP opening. These findings provide a new therapeutic strategy for MIRI and necroptosis-related diseases. Full article

Artemisia dracunculus L., commonly known as tarragon, is a popular culinary herb and a valuable source of bioactive extracts and phytocompounds. Its wide distribution across regions of the Northern Hemisphere demonstrates the species’ high adaptability to diverse growing conditions and has led to the development of chemoraces that differ in chemical composition. North Asian populations of A. dracunculus remain poorly studied, and plants growing in Siberia have not yet been examined. Given the vast areas occupied by tarragon, the species is a promising candidate for industrial use. Liquid chromatography–mass spectrometry (LC–MS) profiling identified 80 compounds in Siberian tarragon samples, including hydroxycinnamates (HCys), coumarins, flavonoid aglycones (FlAs), and glycosides (FlGs). Among these, 62 phenolics were reported for the first time as A. dracunculus metabolites, highlighting the uniqueness of the North Asian accessions, particularly in their diversity of flavone O-glycosides and methylated flavanone aglycones. The highest levels of HCy, FlA, and FlG were 21.84, 52.53, and 54.44 mg/g, respectively, yielding a total phenolic content of 128.81 mg/g in the dry plant material—a high value. The concentrations of certain compounds exceeded 1%, making tarragon a noteworthy source of rare metabolites, including naringenin 7-O-methyl ester, thermopsoside, tilianin, and naringenin 7,4′-di-O-methyl ester. Thus, the existing knowledge of the chemical profile of tarragon has been expanded by new data on phenolic compounds from the North Asian populations of the species, which may be used to develop new A. dracunculus varieties with improved metabolic profiles and bioactive properties. Full article

This study offers a detailed assessment of the polyphenolic composition and antioxidant, anti-inflammatory, and cardioprotective properties of lyophilized extracts derived from the aerial parts of Agastache mexicana and Agastache scrophulariifolia. The polyphenolic content was determined through the quantification of total polyphenols, flavonoids, and caffeic acid derivatives, complemented by LC-MS profiling. The antioxidant activity was evaluated in vitro using DPPH and FRAP assays, while the in vivo antioxidant and anti-inflammatory effects were investigated in a rat model of turpentine-oil-induced acute inflammation. Cardioprotective potential was assessed in a separate rat model of isoprenaline-induced myocardial infarction. Phytochemical analysis revealed a complex polyphenolic profile for both species, with tilianin and rosmarinic acid identified as predominant compounds. In the DPPH assay, both extracts exhibited marked radical scavenging activity (IC₅₀: 65.91 ± 1.21 μg/mL for A. mexicana; 68.64 ± 2.48 μg/mL for A. scrophulariifolia). In the in vivo assays, the administration of the extracts significantly decreased pro-oxidant biomarkers (TOS, OSI, MDA, NO) and enhanced antioxidant markers (TAC, SH groups). Furthermore, the extracts led to a significant reduction in serum levels of GOT, GPT, and CK-MB in rats subjected to myocardial injury, supporting their cardioprotective efficacy. Overall, the results suggest that A. mexicana and A. scrophulariifolia represent promising natural sources of polyphenolic compounds with potential therapeutic value in oxidative-stress-related inflammatory and cardiovascular disorders. Full article

Tilianin (Til), a flavonoid glycoside, is well-known for its therapeutic promise in treating inflammatory disorders. Its poor water solubility and permeability limit its clinical applicability. In order to overcome these restrictions, an antisolvent precipitation and ultrasonication technique was used to prepare amorphous tilianin nanocrystals (Til NCs). We have adjusted the organic solvents, oil-to-water ratio, stabilizer composition, and ultrasonic power and time by combining single-factor and central composite design (CCD) methodologies. The features of Til NCs were characterized using powder X-ray diffraction (PXRD), scanning calorimetry (DSC), and transmission electron microscopy (TEM). Specifically, the optimized Til NCs were needle-like with a particle size ranging from 90 to 130 nm. PVA (0.3%, w/v) and TPGS (0.08%, w/v) stabilized them well. For at least two months, these Til NCs stayed amorphous and showed an impressive stability at 4 °C and 25 °C. Remarkably, Til NCs dissolved almost 20 times faster in simulated intestinal fluid (SIF) than they did in crude Til. In RAW264.7 cells, Til NCs also showed a better cellular absorption as well as safety and protective qualities. Til NCs were shown to drastically lower reactive oxygen species (ROS), TNF-α, IL-1β, and IL-6 in anti-inflammatory experiments, while increasing IL-10 levels and encouraging M1 macrophages to adopt the anti-inflammatory M2 phenotype. Our results highlight the potential of amorphous Til NCs as a viable approach to improve Til’s anti-inflammatory effectiveness, solubility, and dissolving rate. Full article

The aim of this work was to evaluate the vasorelaxant and antihypertensive effects of a standardized precipitate of the hydroalcoholic extract from Agastache mexicana (PPAm), comprising ursolic acid, oleanolic acid, acacetin, luteolin and tilianin, among others. In the ex vivo experiments, preincubation with L-NAME (nonspecific inhibitor of nitric oxide synthases) reduced the relaxation induced by PPAm; nevertheless, preincubation with indomethacin (nonspecific inhibitor of cyclooxygenases) did not generate any change in the vasorelaxation, and an opposed effect was observed to the contraction generated by CaCl₂ addition. Oral administration of 100 mg/kg of PPAm induced a significant acute decrease in diastolic (DBP) and systolic (SBP) blood pressure in spontaneously hypertensive rats, without changes in heart rate. Additionally, PPAm showed a sustained antihypertensive subacute effect on both DBP and SBP for 10 days compared to the control group. On the other hand, human umbilical vein cells treated with 10 µg/mL of PPAm showed a significant reduction (p < 0.05) in intracellular adhesion molecule-1, compared to the control, but not on vascular cell adhesion molecule-1. In conclusion, PPAm induces a significant antihypertensive effect in acute- and subacute-period treatments, due to its direct vasorelaxant action on rat aortic rings through NO production and Ca²⁺ channel blockade. Full article

Many studies have examined how various cultivation methods and elicitors elevate target crop values. Post-harvest treatments, such as the drying method, may alter the final product’s characteristics. We investigated the effect of nutrient solution concentration during the hydroponic cultivation and drying method (cold air drying and freeze drying) after harvesting Agastache rugosa Kuntze, an herb used for folk medicine and as a deodorant, spice, and tea in East Asia. To explore the properties of A. rugosa, we determined its growth parameters, secondary metabolites, and photoprotective effects. We observed the highest growth and yields in A. rugosa grown under 4.0 dS·m⁻¹ electrical conductivity (EC) conditions. However, the EC 2.0 group showed higher antioxidative properties than those grown in EC 1.5 and 4.0 conditions. Drying conditions varied the content and ratios of major active compounds (rosmarinic acid, tilianin, and acacetin) in A. rugosa. Cold air drying caused rosmarinic acid transmutation to tilianin and acacetin, and tilianin showed a stronger positive correlation with antioxidative and photoprotective activities than rosmarinic acid. The increased tilianin content in cold-air-dried A. rugosa accompanied the improved photoprotective effects in dermal cell lines. This study reveals the effects of cultivation and drying methods in A. rugosa production, and proposes alternate industrial production techniques. Full article

This scoping review aimed to summarize the effects of natural products targeting phosphoinositide-3-kinases/serine/threonine kinase (PI3K/AKT) in myocardial ischemia-reperfusion injury (MIRI). The review details various types of natural compounds such as gypenoside (GP), gypenoside XVII (GP-17), geniposide, berberine, dihydroquercetin (DHQ), and tilianin which identified to reduce MIRI in vitro and in vivo by regulating the PI3K/AKT signaling pathway. In this study, 14 research publications that met the inclusion criteria and exclusion criteria were shortlisted. Following the intervention, we discovered that natural products effectively improved cardiac functions through regulation of antioxidant status, down-regulation of Bax, and up-regulation of Bcl-2 and caspases cleavage. Furthermore, although comparing outcomes can be challenging due to the heterogeneity in the study model, the results we assembled here were consistent, giving us confidence in the intervention’s efficacy. We also discussed if MIRI is associated with multiple pathological condition such as oxidative stress, ERS, mitochondrial injury, inflammation, and apoptosis. This brief review provides evidence to support the huge potential of natural products used in the treatment of MIRI due to their various biological activities and drug-like properties. Full article

Agastache rugosa, otherwise called Korean mint, has a wide range of medicinal benefits. In addition, it is a rich source of several medicinally valuable compounds such as acacetin, tilianin, and some phenolic compounds. The present study aimed to investigate how the Tartary buckwheat transcription factor AtMYB12 increased the primary and secondary metabolites in Korean mint hairy roots cultured under light and dark conditions. A total of 50 metabolites were detected by using high-performance liquid chromatography (HPLC) and gas chromatography–time-of-flight mass spectrometry (GC-TOFMS). The result showed that the AtMYB12 transcription factor upregulated the phenylpropanoid biosynthesis pathway genes, which leads to the highest accumulation of primary and secondary metabolites in the AtMYB12-overexpressing hairy root lines (transgenic) than that of the GUS-overexpressing hairy root line (control) when grown under the light and dark conditions. However, when the transgenic hairy root lines were grown under dark conditions, the phenolic and flavone content was not significantly different from that of the control hairy root lines. Similarly, the heat map and hierarchical clustering analysis (HCA) result showed that most of the metabolites were significantly abundant in the transgenic hairy root cultures grown under light conditions. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) showed that the identified metabolites were separated far based on the primary and secondary metabolite contents present in the control and transgenic hairy root lines grown under light and dark conditions. Metabolic pathway analysis of the detected metabolites showed 54 pathways were identified, among these 30 were found to be affected. From these results, the AtMYB12 transcription factor activity might be light-responsive in the transgenic hairy root cultures, triggering the activation of the primary and secondary metabolic pathways in Korean mint. Full article

Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1β, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1β, IL-8 and MMP9. Full article

Cardiovascular disorders (CVDs) are the leading risk factor for death worldwide, and research into the processes and treatment regimens has received a lot of attention. Tilianin is a flavonoid glycoside that can be found in a wide range of medicinal plants and is most commonly obtained from Dracocephalum moldavica. Due to its extensive range of biological actions, it has become a well-known molecule in recent years. In particular, numerous studies have shown that tilianin has cardioprotective properties against CVDs. Hence, this review summarises tilianin’s preclinical research in CVDs, as well as its mechanism of action and opportunities in future drug development. The physicochemical and drug-likeness properties, as well as the toxicity profile, were also highlighted. Tilianin can be a natural lead molecule in the therapy of CVDs such as coronary heart disease, angina pectoris, hypertension, and myocardial ischemia, according to scientific evidence. Free radical scavenging, inflammation control, mitochondrial function regulation, and related signalling pathways are all thought to play a role in tilianin’s cardioprotective actions. Finally, we discuss tilianin-derived compounds, as well as the limitations and opportunities of using tilianin as a lead molecule in drug development for CVDs. Overall, the scientific evidence presented in this review supports that tilianin and its derivatives could be used as a lead molecule in CVD drug development initiatives. Full article

Plants of the genus Wikstroemia are traditionally used in China to treat various inflammatory diseases. The purpose of this study was to isolate the components of Wikstroemia ganpi (Siebold & Zucc.) Maxim., to evaluate their anti-atopic activities and to identify candidates with anti-atopic therapeutics. A total of 24 compounds were isolated by bioassay-guided separation, including one novel compound, which was tilianin 5-methyl ether. The anti-atopic activities of the isolated compounds were determined using TNF-α-treated RBL-2H3 cells and HaCaT cells. The mRNA expressions of IL-4, IL-6, GM-CSF, G-CSF and TRPV1 were reduced by luteolin 7-methyl ether. The study shows that the luteolin 7-methyl ether isolated from W. ganpi is a potential therapeutic agent for the treatment of atopic dermatitis. Full article

Agastache rugosa, or Korean mint, is an herb used as a spice, food additive and traditional medicinal ingredient. It has desirable effects, such as its antibacterial, antifungal and antioxidant properties. A. rugosa contains many phenolic compounds studied for their various health benefits, with the primary components being tilianin. A. rugosa extract (ARE), which was extracted with ethanol and freeze-dried, contained 21.14 ± 0.15 mg/g of tilianin with a total polyphenol content of 38.11 ± 0.88 mg/g. Next, the antiadipogenic effect of A. rugosa and tilianin was clarified using 3T3-L1 cells, which differentiate into adipocytes and develop lipid droplets. 3T3-L1 cells were treated with ARE or tilianin and lipid accumulation (%) was calculated through oil red O staining. Tilianin elicited dose-dependent decrease in lipid accumulation (% of positive control) (30 μM 92.10 ± 1.19%; 50 μM 69.25 ± 1.78%; 70 μM 54.86 ± 1.76%; non-differentiation 18.10 ± 0.32%), assessed by oil-red-O staining, whereas ARE treatments caused consistent diminution in lipid accumulation regardless of dose (100 μM 86.90 ± 4.97%; 200 μM 87.25 ± 4.34%; 400 μM 88.54 ± 2.27%; non-differentiation 17.96 ± 1.30%), indicating that both compounds have anti-obesity effects on adipocytes. Treatment with ARE lowered the mRNA (PPARγ; C/EBPα; FABP4; SREBP1; ACC; FAS) and protein (PPARγ; C/EBPα; SREBP1) levels of adipogenesis and lipogenesis-related factors. Tilianin showed a greater effect on the mRNA levels compared with ARE. Thus, tilianin and ARE may have anti-adipogenic and anti-lipogenic effects on 3T3-L1 cells and be possible candidates of obesity-related supplements. Full article

Edible flowers have been used in the food and beverage industries because of their high nutritional value, flavor, and scent. For the storage of edible flowers used in these industries, drying is a necessity to store the materials more easily and prevent the damage of metabolites in the flowers. However, drying may affect metabolite retention because drying conditions can differ according to the various methods. In this study, Agastache rugosa flowers were dried using four different methods (oven drying at 25 ± 1 °C, 50 ± 1 °C, 80 ± 1 °C, and freeze drying) and primary and secondary metabolites were analyzed using high-performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). Freeze-dried flower samples contained higher levels of carotenoids (lutein, 13Z-β-carotene, β-carotene, and 9Z-β-carotene) and phenolics (rosmarinic acid, ferulic acid, and sinapic acid). Contrarily, the 80 °C oven-dried flower samples contained higher levels of most amino acids and flavonoids (including acacetin and tilianin) and at 25 °C and 50 °C contained higher levels of carbohydrates. Therefore, freeze-drying is a suitable method for retaining carotenoids and phenolics. In contrast, oven drying at 50 °C was highly recommended to retain amino acids and flavonoids. Full article

This study aimed to determine the optimal indole-3-acetic acid (IAA) concentration in a nutrient solution to increase the bioactive compounds while enhancing the plant growth of A. rugosa grown hydroponically. Twenty-eight-day-old plants were transplanted in a plant factory for 32 days. The plants were subjected to various IAA concentrations (10⁻¹¹, 10⁻⁹, 10⁻⁷, and 10⁻⁵ M) from 8 days after transplanting, and the control treatment (without IAA). Shoot and root fresh weights were effectively improved under 10⁻⁷ and 10⁻⁹ IAA treatments. Leaf gas exchange parameters were increased under 10⁻⁷ and 10⁻⁹ IAA treatments. Four of the IAA treatments, except 10⁻¹¹ IAA treatment, significantly increased the rosmarinic acid (RA) concentration, as well as the tilianin concentration was significantly increased at all IAA treatments, compared with that of the control. Especially, the tilianin concentration of the 10⁻¹¹ IAA treatment was significantly (1.8 times) higher than that of the control. The IAA treatments at 10⁻⁵ and 10⁻⁷ significantly raised the acacetin concentrations (1.6- and 1.7-times, respectively) compared to those of the control. These results suggested that 10⁻⁷ concentration of IAA in a nutrient solution was effective for enhancing plant growth and increasing bioactive compounds in A. rugosa, which offers an effective strategy for increasing phytochemical production in a plant factory. Full article

Plants respond to root temperature stresses by producing antioxidants as a defense mechanism. Since a number of these are phytochemicals with enhancing effects on human health, we examined the effects of 4 root-zone temperature (RZT) treatments (10, 20, 28, and 36 °C) on plant growth and the main bioactive compound concentrations in each organ of Agastache rugosa plants. We aimed to determine the optimal RZT treatment to increase bioactive compound concentrations with no deleterious effects on plant growth. Four-week-old seedlings were grown in a plant factory for 32 days. Nine plant growth parameters, namely, shoot and root fresh weights, stem and root lengths, leaf length and leaf width, leaf area, and shoot and root dry weights were significantly decreased at 10 and 36 °C compared with other treatments. A similar pattern was observed for the chlorophyll content and leaf gas exchange parameters. Of all the RZT treatments, RZT at 28 °C produced the significantly greatest accumulation of two major bioactive compounds, namely, rosmarinic acid (RA) and tilianin contents per the A. rugosa plant, and had no adverse effects on the overall growth of A. rugosa. This supports the use of 28 °C RZT to successfully improve the bioactive compounds with no adverse influence on plant growth or yield. Full article