Eco-benevolent synthesis of ZnO-NPs and ZnO-MFs from Inula oculus-christi L. (Asteraceae) with effective antioxidant, antimicrobial, DNA cleavage, and decolorization efficiencies.

As a result of the changes occurring globally in recent years, millions of people are facing challenging and even life-threatening diseases such as cancer and the COVID-19 pandemic, among others. This phenomenon has spurred researchers towards developing and implementing innovative and environmentally friendly scientific methods, merging disciplines with significant technological potential, such as nanotechnology with medicinal plants. Therefore, the focus of this research is to synthesize zinc nanoparticles (ZnO-NPs) and microflowers (ZnO-MFs) using extracts of the medicinal plant I. oculus christi prepared in n-hexane and methanol as new bioreduction and capping agents through a simple and environmentally friendly chemical approach. Optical, thermal, and morphological structural analyses of ZnO-NPs and ZnO-MFs were conducted using Ultraviolet-Visible (UV-Vis) spectroscopy, Fourier Transform Infrared (FT-IR) spectroscopy, Thermogravimetric Analysis (TGA), and Field Emission Scanning Electron Microscopy (FE-SEM). Metabolic profiles of extracts from different plant parts were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) and supported by visualization of contents through Principal Component Analysis (PCA), hierarchical cluster analysis heatmaps, and Pearson correlation graphs. Interestingly, ZnO-NPs and ZnO-MFs exhibited strong antioxidant properties and demonstrated particularly potent antimicrobial activity against Micrococcus luteus NRRL B-4375, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231 strains compared to standard antibiotics. Furthermore, ZnO-NPs and ZnO-MFs showed excellent plasmid DNA-cleavage activity of pBR322 with increasing doses. The photocatalytic performance of the synthesized ZnO-NPs and ZnO-MFs was evaluated for methylene blue (MB), congo red (CR), and safranin-O (SO) dyes, demonstrating remarkable color removal efficiency. Overall, the results provide a promising avenue for the green synthesis of ZnO-NPs and ZnO-MFs using I. oculus-christi L. inflorescence and pappus extracts, potentially revolutionizing biopharmaceutical and catalytic applications in these fields.

Alantolactone Induced Apoptosis and DNA Damage of Cervical Cancer through ATM/CHK2 Signaling Pathway.

Traditional Chinese Medicine, known for its minimal side effects and significant clinical efficacy, has attracted considerable interest for its potential in cancer therapy. In particular, Inula helenium L. has demonstrated effectiveness in inhibiting a variety of cancers. This study focuses on alantolactone (ALT), a prominent compound from Inula helenium L., recognized for its anti-cancer capabilities across multiple cancer types. The primary objective of this study is to examine the influence of ALT on the proliferation, apoptosis, cell cycle, and tumor growth of cervical cancer (CC) cells, along with its associated signaling pathways. To determine protein expression alterations, Western blot analysis was conducted. Furthermore, an in vivo model was created by subcutaneously injecting HeLa cells into nude mice to assess the impact of ALT on cervical cancer. Our research thoroughly investigates the anti-tumor potential of ALT in the context of CC. ALT was found to inhibit cell proliferation and induce apoptosis in SiHa and HeLa cell lines, particularly targeting ataxia-telangiectasia mutated (ATM) proteins associated with DNA damage. The suppression of DNA damage and apoptosis induction when ATM was inhibited underscores the crucial role of the ATM/cell cycle checkpoint kinase 2 (CHK2) axis in ALT's anti-tumor effects. In vivo studies with a xenograft mouse model further validated ALT's effectiveness in reducing CC tumor growth and promoting apoptosis. This study offers new insights into how ALT combats CC, highlighting its promise as an effective anti-cervical cancer agent and providing hope for improved treatment outcomes for CC patients.

Characterization of Sesquiterpene Dimers from the Flowers of Inula japonica and the Structural Revisions of Related Compounds.

Sesquiterpene dimers are mainly found in the Asteraceae family. However, conflicting reports on the structures of these compounds can be found in the literature. Herein, we describe ten sesquiterpene dimers isolated from the flowers of Inula japonica, including configurational revisions of japonicone H (1-1), japonicone D (2-1), inulanolide A (4-1), japonicone X (5-1), and inulanolide F (5-2) to compounds 1, 2, 4, and 5, respectively. Five new related metabolites (3 and 6-9) are also described. Application of GIAO NMR/DP4+ analyses and ECD/OR calculations enabled us to revise the absolute configurations of an additional 13 sesquiterpene dimers isolated from plants of the genus Inula. Compounds 1, 2, 4, and 6 exhibited inhibition of nitric oxide production in lipopolysaccharide activated RAW264.7 macrophages with IC50 values of 4.07-10.00 µM.

Ultrasonic extraction of Inula viscosa: Enhancing antioxidant bioactivity and its application in sunflower oil as an antioxidant.

The objective of this study was to optimize the ultrasound-assisted extraction (UAE) of Inula viscosa, focusing on the extraction yield, total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity and to evaluate its antioxidant effect in sunflower oil (SFO) storage. A water-ethanol binary solvent system was applied to extract bioactive components sustainably. Extraction parameters (temperature, time, ethanol concentration, and solvent-to-solid ratio) were optimized using a central composite rotatable design, achieving high accuracy (R2 > 0.974). Optimum conditions were 54 % (v/v) ethanol concentration, 60 °C, 31 min, and a 15 (mL/g) solvent-to-solid ratio resulting in a yield of 24.72 g/g (%), TPC of 489.54 mg gallic acid/g, TFC of 149.81 mg quercetin/g, and IC50 of 18.21 µg/mL. UAE outperformed Soxhlet extraction in yield, bioactive compound composition, and antioxidant capacity. Strong correlations were found between TPC, TFC, and antioxidant capacity, with TFC having a more significant impact. I. viscosa extract was found to be a potent antioxidant and delay the oxidation of SFO during accelerated storage due to peroxide value and oxidative induction time analysis. Microstructural analysis illuminated the structural changes induced by the extraction methods. In conclusion, this study not only optimized UAE of I.viscosa, showing superior efficiency and antioxidant capacity, but also demonstrated the practical application of I.viscosa in enhancing sunflower oil shelf life, thereby providing valuable insights for the field of food engineering and antioxidant research.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells.

Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids 1-5 isolated from Inula britannica flowers were evaluated for their abilities to inhibit sEH with IC50 values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (1-5) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids 1-5 exhibited inhibitory activity in all tests, with compound 3 exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound 3 is a promising natural candidate.

Sesquiterpene Acids and Lactones from Inula Confertiflora with their Antibacterial Activities.

The phytochemical investigation of the leaves of Inula confertiflora, a medicinal plant endemic to Ethiopia, led to the isolation of 15 terpenoids; 1ß-hydroxy-α-costic acid (1), 3α-hydroxycostic acid (2), isotelekin (3), asperilin (4), carabrone (5), carpesioline (6), graveolide (7), inuviscolide (8), 8-epi-inuviscolide (9), 1ß,4ß-dihydroxy-5α(H)-guaia-10(14),11(13)-dien-8α,12-olide (10), isoinuviscolide (11), 4ß,10ß-dihydroxy-5α(H)-1,11(13)-guaidien-8α,12-olide (12), 4ß,10ß-dihydroxy-1ß(H)-5α(H)-guai-11(13)-en-8α,12-olide (13), 4ß,10α-dihydroxy-1ß(H)-5α(H)-guai-11(13)-en-8α,12-olide (14), 4ß,10α-dihydroxy-1α(H)-5α(H)-guai-11(13)-en-8α,12-olide (15). Herein, structural elucidation and full NMR data for compound 1 are presented for the first time. The structures were elucidated using NMR, HRESIMS, and by comparison with literature data. The relative configurations were defined by NOESY correlations and single-crystal X-ray crystallography. Herein, crystallography data of 6 and 7 were reported for the first time. The antibacterial efficacy of some of the isolated compounds was evaluated against two commonly dispersed environmental strains of Escherichia coli and Staphylococcus aureus. Compounds 1, 3, 6, 7, and 8 exhibited moderate antibacterial activities against the tested organisms. The chemotaxonomic significance of compounds is discussed.

Inubritantrimers A-D: Trimerized Sesquiterpenoid [4 + 2] Adducts Featuring a Distinctive Spiro-Polycyclic Scaffold from Inula britannica.

Inubritantrimer A (1), a trace trimerized sesquiterpenoid [4 + 2] adduct featuring an unusual exo-exo type spiro-polycyclic scaffold, together with three new endo-exo [4 + 2] adducts, inubritantrimers B-D (2-4), were discovered from the flowers of Inula britannica. Their structures were elucidated using 1D/2D NMR, X-ray diffraction, and ECD approaches. 1 is characterized as a novel exo-exo trimer, synthesized biogenetically from three sesquiterpenoid monomers, featuring a unique linkage of C-11/C-1', C-13/C-3' and C-13'/C-3″, C-11'/C-1″ through a two-step exo [4 + 2] cycloaddition process. Compounds 1-4 exhibited modest cytotoxicity against breast cancer cells with IC50 values in the range of 5.84-12.01 µM.

Phytochemical characterization and biological activities of Inula viscosa L. Aiton: a promising plant from Turkey.

The methanol extract of Inula viscosa (IVM) was investigated for its antioxidant potential using the DPPH and ABTS radical scavenging as well as iron chelating assays (ICA). The total phenol (TPC) and flavonoid contents (TFC) of IVM were determined using the Folin-Ciocalteu and aluminum trichloride methods, respectively. Antimicrobial activity of different concentrations of I. viscosa methanol extract was investigated by disc diffusion and broth microdilution method. The IVM extract was found to be containing TPC (236.78 ± 7.63 mg GAE/g) and TFC (94.36 ± 1.86 mg QE/g). Antioxidant activity IC50 values for the DPPH, ABTS and ICA assays were found to be 277.7 ± 3.68, 2.44 ± 0.02, and 222.1 ± 0.71 µg/mL, respectively. The MIC values of the IVM on the tested microorganisms ranged from 0.48 to 7.81 mg/mL. Furthermore, IVM extract was demonstrated 18.32 ± 1.37%, 23.06 ± 1.05%, 4.72 ± 0.13%, 15.13 ± 0.37% and 37.64 ± 4.02% inhibition against tyrosinase, α-amylase, α-glucosidase, AChE and BChE, respectively. In the results of LC-MS/MS analysis, acacetin, quercetin, chlorogenic acid and protocatechuic acid were determined as most dominant compounds. These findings suggested that this plant may be a natural resource for creating novel medicinal compounds.

Chemical composition, biological activities, and molecular mechanism of Inula viscosa (L.) bioactive compounds: a review.

Inula viscosa is an herbaceous plant mainly found in Mediterranean regions, predominantly, used in developing countries as a folk remedy for treating numerous diseases using different traditional methods of preparation that includes infusion, decoction, and external application. Researchers have been interested in studying the antioxidant, anti-inflammatory, antifungal, antibacterial, antidiabetic, and antitumor effects of I. viscosa extracts, due to its high countenance of bioactive molecules. The chemical studies of ethanol, methanol, chloroform, aqueous, petroleum ether, dichloromethane, and ethyl acetate extracts from different parts of I. viscosa, growing around the world, and analyzed by different analytical techniques allowed to isolate and identify a great number of secondary metabolites from terpenes, flavonoids, phenylpropanoids, and polyketides, and complementary in vitro and in vivo studies indicated the pharmacological activities of an isolated compound, a mixture, or the crude extract. I. viscosa extracts had a great in vivo potential reducing mice paw, ear, and the severity of pulmonary edema, and the occurrence of skin carcinoma growing; in vitro recent study results showed, in addition, the high antioxidant, α-glucosidase, and α-amylase inhibitory activity, and neuroprotectivity effects; a correlation with the in vivo studies confirming the anti-inflammatory and antitumor proprieties, elucidating some molecular mechanisms: showing that tomentosin reduced pro-inflammatory cytokine secretion (IFNγ, IL-1, IL-2, TNF-α, and IL-6) via the suppression of transcription factor NF-κB and MAP kinase (p38/JNK) activation, and that the two phenolic compounds banaxanthone E and paxanthone inhibited the antiapoptotic protein BCL-2, activating the apoptotic process leading to the antiproliferative effect.

Anti-Fibrosis Effect of Panax ginseng and Inula japonica Formula in Human Pulmonary Fibroblasts.

Panax ginseng Meyer and Inula japonica Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma, and cancer. Although P. ginseng and I. japonica can alleviate pulmonary fibrosis (PF), the anti-fibrosis effect on PF by the combination of two herbal medicines remains unexplored. Therefore, this study explores this combined effect. In conditions that were not cytotoxic, MRC-5 cells underwent treatment using the formula combining P. ginseng and I. japonica (ISE081), followed by stimulation with transforming growth factor (TGF)-ß1, to explore the fibroblast-to-myofibroblast transition (FMT). After harvesting the cells, mRNA levels and protein expressions associated with inflammation and FMT-related markers were determined to evaluate the antiinflammation activities and antifibrosis effect of ISE081. Additionally, the anti-migratory effects of ISE081 were validated through a wound-healing assay. ISE081 remarkably reduced the mRNA levels of interleukin (IL)-6, IL-8, α-smooth muscle actin (SMA), and TGF-ß1 in MRC-5 cells and suppressed the α-SMA and fibronectin expressions, respectively. Furthermore, ISE081 inhibited Smad2/3 phosphorylation and wound migration of MRC-5 cells. Under the same conditions, comparing those of ISE081, P. ginseng did not affect the expression of α-SMA, fibronectin, and Smad2/3 phosphorylation, whereas I. japonica significantly inhibited them but with cytotoxicity. The results indicate that the synergistic application of P. ginseng and I. japonica enhances the anti-fibrotic properties in pulmonary fibroblasts and concurrently diminishes toxicity. Therefore, ISE081 has the potential as a prevention and treatment herbal medicine for PF.

Identification of diverse sesquiterpenoids with anti-fibrotic potential from Inula japonica Thunb.

In the chemical investigation of Inula japonica, a total of 29 sesquiterpenoids (1-29) were obtained, including pseudoguaine-, xanthane-, eudesmane-, and 1,10-secoeudesmane-type compounds, as well as their dimers. Among them, six new dimeric sesquiterpenoids, bisinulains A-F (1-5, 7), characterized by a [4 + 2] biogenetic pathway between different sesquiterpenoid monomers were identified. Additionally, three new monomers named inulaterins A-C (13, 18 and 21) were discovered. The structures of these compounds were determined through analysis of spectroscopic data, X-ray crystallographic data, and ECD experiments. To assess their potential anti-inflammatory activities, the sesquiterpenoid dimers were tested for their ability to inhibit NO production in LPS-stimulated RAW 264.7 cells. Furthermore, the compounds that exhibited anti-inflammatory effects underwent evaluation for their anti-fibrotic potential using a TGF-ß-induced epithelial-mesenchymal transition model in A549 cells. As a result, bisinulain B (2) was screened out to significantly inhibit the production of cytokines involved in pulmonary fibrosis such as NO, α-SMA, collagen I and fibronectin.

Apoptotic and antiproliferative effects of Inula viscosa L. water extract in the expression of microRnas on HCT 116 cell line: an in vitro study.

In this study, the antiproliferative and apoptotic effects of Inula viscosa L. water extract (IVE) on HCT 116 has been examined, and the change in the expression of miRNAs. Phenolic compounds of IVE were determined as µg/g extract using by HPLC-DAD. Quantitative determination of apoptosis, cell viability, IC50 values and miRNAs of the cells were determined during 24, and 48 hours. IVE contain coumarin, rosmarinic acid and chlorogenic acid. According to the findings of our study, the expression of miR-21 and miR-135a1 was upregulated, and miR-145 was downregulated in HCT 116 cells (Control). Additionally, IVE was found to have significant potential in regulating miRNAs, downregulating miR-21, miR-31 and miR-135a1, and upregulating miR-145 in HCT-116 cells. All these results show that the anticancer effect of IVE via regulating miRNAs' expression has been demonstrated for the first time, and may be candidate biomarkers in colorectal cancer.

Dimerized sesquiterpenoid [4 + 2] adducts with ferroptosis-promoting activity from Inula britannica Linn.

Inubritanolides C and D (1 and 2), two exo sesquiterpenoid [4 + 2] adducts with unprecedented interconverting conformations of twist-chair and chair, together with two previously undescribed endo [4 + 2] dimers (3 and 4) were discovered from Inula britannica flowers. Dimers 1 and 2 have an undescribed carbon skeleton comprising of eudesmanolide and guaianolide units with the linkage mode of C-11/C-1' and C-13/C-3' via a Diels-Alder cycloaddition reaction. Their structures were elucidated using 1D/2D NMR, X-ray diffraction, ECD, and variable-temperature NMR experiments. Dimer 2 displayed a strong inhibitory effect on breast cancer cells by promoting lipid ROS production, showing its potential as ferroptosis inducer.

Influence of Inula helenium rhizomes and Matricaria chamomilla inflorescences on the biochemical and physiological parameters in male rats fed a high-fat diet.

Background: Pharmacological correction of a high-fat diet is of great interest to prevent the development of obesity and hypertension. More and more research is being done on the preventive use of medicinal herbs for excess caloric intake. Objective: The aim of this study was to determine the general physiological effect of I. helenium rhizomes and M. chamomilla inflorescences used in the diet of male rats consuming excess amounts of fat and calories in the daily diet. Material and methods: In a 30-day experiment, we determined the effect of I. helenium rhizome and M. chamomilla on the physiological activity and metabolic processes of laboratory rats consuming a high-fat diet. The physical activity was evaluated according to the mass gain of animals and change in the relative mass of the internal organs, and also the functional conditions of the central nervous system. The influence on the metabolic processes was revealed by biochemical and clinical blood analyses. Results: In a laboratory experiment on male rats, it was found that the addition of dry crushed rhizomes of Inula helenium L. and inflorescences of Matricaria chamomilla L. to the diet caused opposite changes in body weight. In the control group, the animals slightly increased their body weight (up to 111.5% of the initial weight by the end of the experiment); the rhizomes of I. helenium caused a decrease in body weight gain (up to 105.5% on the 30th day of the experiment compared to the initial weight); rats fed M. chamomilla inflorescences gained 123.2% of their initial body weight during the month of the experiment. The rhizomes of I. helenium caused an increase in the stomach relative mass. A decrease in the thymus relative weight was observed when animals were fed M. chamomilla inflorescences. The rhizomes of I. helenium stimulated an increase of blood protein concentration (mainly due to globulins), an increase in the alkaline phosphatase activity and cholesterol, and a decrease in the triglycerides concentration. M. chamomilla inflorescences reduced the blood urea concentration and increased the activity of alkaline phosphatase, causing strong changes in fat metabolism. Under the influence of the diet with the addition of M. chamomilla inflorescences, the atherogenic index increased in animals by 6.5 times relatively to the control group (due to a decrease in the concentration of high-density lipoprotein cholesterol and an increase in the concentration of low-density lipoprotein cholesterol, an increase in the total cholesterol concentration). When M. chamomilla was added to the diet, the blood triglycerides concentration in animals decreased sharply and the concentration of leukocytes increased. The concentration of monocytes exceeded the limits of the physiological norm both in the control group and in the group of animals fed on M. chamomilla inflorescences. Conclusions: The results of the studies show the promise for further research of I. helenium rhizomes in the prevention of hypertension and also indicate strong risks when using M. chamomilla inflorescences for preventive purposes during high-fat and hypercaloric diet.

Ethanol Extracts from the Aerial Parts of Inula japonica and Potentilla chinensis Alleviate Airway Inflammation in Mice That Inhaled Particulate Matter 10 and Diesel Particulate Matter.

Air pollution causes various airway diseases. However, many commonly used treatments can have high risks of side effects or are costly. To examine the anti-inflammatory properties of Inula japonica Thunb. and Potentilla chinensis Ser., a mouse model was generated via inhalation of both particulate matter 10 and diesel particulate matter, and 30% ethanol extracts of either I. japonica (IJ) or P. chinensis (PC) and a mixture of both ethanol extracts (IP) were orally administered to BALB/c mice for 12 days. IJ, PC, and IP inhibited immune cell numbers and their regulation in both the bronchoalveolar lavage fluid (BALF) and lungs. These agents suppressed the levels of interleukin (IL)-1α, IL-17, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand (CXCL)-1, and CXCL-2 in BALF, and also inhibited F4/80 and IL-1 receptor-associated kinase (IRAK)-1 in lungs. They reduced the gene expression of TNF-α, CXCL-1, inducible NOS, COX-2, Mucin 5AC, and transient receptor potential cation channel subfamily V member 1 in lungs. These extracts also reduced histopathological changes and inflammatory progression, manifested as decreased cell infiltration, collagen deposition, and respiratory epithelial cell thickness. I. japonica and P. chinensis show potential for development as pharmaceuticals that suppress inflammatory progression and alleviate airway inflammation diseases caused by air pollutants.

Ruptured organosilica nanocapsules immobilized acetylcholinesterase coupled with MnO2 nanozyme for screening inhibitors from Inula macrophylla.

Abnormal expression of acetylcholinesterase (AChE) causes Alzheimer's disease (AD). Inhibiting AChE is a common strategy for reducing the degradation of neurotransmitter acetylcholine, in order to treat early-stage AD. Therefore, it is crucial to screen and explore AChE inhibitors which are safer and cause fewer side effects. Our research is focused on establishing a platform of ruptured organosilica nanocapsules (RONs) immobilized AChE coupled with an MnO2-OPD colorimetric assay, which could monitor AChE activity and screen AChE inhibitors. The fabricated RONs immobilized AChE possessed excellent pH and thermal stability. Huperzine A was introduced into the established platform to evaluate the inhibition kinetics of the immobilized AChE, which promoted its application in the screening of AChE inhibitors. The satisfactory results of enzyme inhibition kinetics proved the feasibility and applicability of the established method. Thus, the proposed platform was applied to screen AChE inhibitors from 14 compounds isolated from Inula macrophylla, and ß-cyclocostunolide (compound 4) demonstrated the best AChE inhibitory activity among these compounds. This work confirms the existence of chemical components that inhibit AChE activity in Inula macrophylla, and provides a new idea for the application of immobilized enzyme-nanozyme in the field of enzyme inhibitor screening.

Targeting PPARγ/ NF-κB Signaling Pathway by Britannin, a Sesquiterpene Lactone from Inula aucheriana DC., in Gastric Cancer.

BACKGROUND: Gastric cancer is one of the most common and deadliest malignancies in the world. Therefore, there is an urgent need to develop new and effective agents to reduce mortality. The plants of genus Inula have gained the attention of researchers worldwide as a rich source of potent medicinal compounds. OBJECTIVE: This study explores the anti-cancer activity of Britannin, a sesquiterpene lactone isolated from Inula aucheriana DC., and its molecular mechanism in gastric cancer cells, AGS and MKN45. METHODS: Cytotoxicity was evaluated through the MTT assay following 24 h, 48 h, and 72 h treatment with different concentrations of Britannin. Apoptosis rate and caspase-3 activity were measured 24 h after treatment by Britannin. . Western blotting was performed to determine the expression of the NF-κB, IκBα, and PPARγ proteins. Moreover, quantitative RT-PCR was applied to measure the expression of NF-κB target genes. RESULTS: We showed that Britannin induced cell growth inhibition and apoptosis in gastric cancer cells. Britannin caused an elevation in mRNA and protein levels of PPARγ. The involvement of PPARγ was more confirmed using GW9662, a PPARγ inhibitor. Suppression of NF-κB was demonstrated by western blot analysis. Down-regulation of MMP-9, TWIST-1, COX-2, and Bcl-2 and up-regulation of Bax were also observed in gastric cancer cells. CONCLUSION: These results imply that activation of the PPARγ signaling pathway through suppression of NF-κB underlies the anti-cancer properties of Britannin in gastric cancer. Therefore, Britannin could be considered as a promising anti-cancer candidate for further evaluation.

Biofilm Inhibition of Inula viscosa (L.) Aiton and Globularia alypum L. Extracts Against Candida Infectious Pathogens and In Vivo Action on Galleria mellonella Model.

The increasing importance of fungal infections has fueled the search for new beneficial alternatives substance from plant extracts. The current study investigates the antifungal and antibiofilm activity of Inula viscosa (L.) Aiton and Globularia alypum (L.) leaves extracts against Candida both in vitro and in vivo. The inhibition of planktonic and sessile Candida albicans and Candida glabrata growth using both leaf extracts are evaluated. Moreover; an in vivo infection model using Galleria mellonella larvae; infected and treated with the extracts are performed. All extracts show fungicidal activity; with a minimum fungicidal concentration (MFC) ranging from 128 to 512 µg mL-1 against the two selected strains of Candida. In particular, the best results are obtained with methanolic extract of I. viscosa and G. alypum with an MFC value of 128 µg mL-1 . The extracts are capable to prevent 90% of biofilm development at minor concentrations ranging from 100.71 ± 2.49 µg mL-1 to 380.4 ± 0.92 µg mL-1 . In vivo, tests on Galleria mellonella larvae show that the extracts increase the survival of the larvae infected with Candida. The attained results reveal that I. viscosa and G. alypum extracts may be considered as new antifungal agents and biofilm inhibiting agents for the pharmaceutical and agro-food field.

Fermentation of Inula britannica using Lactobacillus plantarum SY12 increases of epigallocatechin gallate and attenuates toxicity.

This study aimed to increase epigallocatechin gallate (EGCG) levels and attenuate the toxicity in Inulabritannica by fermentation using Lactobacillus plantarum SY12. The optimal medium was composed of 10 g of I. britannica, 4 g of xylose, 5 g of soytone, and 5 g of beef extract. The predicted value of EGCG was 237.327 µg/mL. To investigate damage in HepG2 cell lines by I. britannica extracts (IE) or fermented I. britannica extracts (FIE), cell viability, mitochondria membrane potential, the expression of apoptosis and autophagy genes, and chemical composition were measured. FIE increased cell viability, regulation of the gene expression (decreased p53, p62, p-ERK 1/2, and p-p38; increased CDK2 and CDK4) compared with IE. These results were explained by an increase in 1,3-dicaffeoylquinic acid and a decrease in 1-O-caffeoylquinic acid, 1-O-acetylbritannilactone, and ergolide in FIE. In conclusion, these results indicated that fermentation can mitigate the toxicity in I. britannica.

The Effects of 1-O-Acetylbritannilactone Isolated from Inula britannica Flowers on Human Neutrophil Elastase and Inflammation of RAW 264.7 Cells and Zebrafish Larvae.

During a search for natural inflammatory inhibitors, 1-O-acetylbritannilactone (ABL), a sesquiterpene lactone, was isolated from the flowers of Inula britannica. ABL significantly inhibited human neutrophil elastase (HNE) with a half-maximal inhibitory concentration (IC50) of 3.2 ± 0.3 µM, thus did so more effectively than the positive control material (epigallocatechin gallate) (IC50 7.2 ± 0.5 µM). An enzyme kinetic study was performed. ABL noncompetitively inhibited HNE with an inhibition constant Ki of 2.4 µM. ABL inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E2 production by RAW 264.7 cells in a dose-dependent manner, as well as the protein-level expression of inducible nitric oxide synthase and cyclooxygenase-2. The anti-inflammatory effect of ABL was confirmed using a transgenic Tg(mpx:EGFP) zebrafish larval model. The exposure of the larvae to ABL inhibited neutrophil recruitment to the site of injury after tail fin amputation.