Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis.

The objective of this study was to probe the effect and mechanism of Szechwan Lovage Rhizome (Chuanxiong, CX) extract on renal function (RF) and inflammatory responses (IRs) in acute pyelonephritis (APN) rats infected with Escherichia coli (E. coli). Fifteen SD rats were randomized to intervention, model and control groups. Rats in the control were fed normally without treatment, rats in the APN model were infected with E. coli, and rats in the intervention group were intragastrically administered CX extract after infection with E. coli. HE staining detected pathological changes in the kidney tissues in rats. Levels of renal function indexes and inflammatory factors (IFs) were measured by ELISA and an automatic biochemical analyzer. Besides, levels of IL-6/signal transducer and activator of transcription 3 (STAT3) pathway-related genes in rat kidney tissue were detected by qRT-PCR and western blot. the experimental results showed that IL-1ß, IL-8, TNF-α and RF levels were the highest in the model group and the lowest in the control group, with those of the intervention group in between (P<0.05). Besides, the IL-6/STAT3 axis was markedly activated in the model group but inhibited in the intervention group (P<0.05). Subsequently, activated IL-6/STAT3 signal promoted IFs (IL-1ß, IL-8 and TNF-α) and RF (BUN, Scr, ß2-MG and UA), but this effect was offset after CX treatment (P<0.05). In conclusion, CX extract could improve RF and inhibit IRs of APN rats infected with E. coli by inhibiting the IL-6/STAT3 axis, which may be a new choice for APN treatment in the future.

Influence of Elicitation and Drying Methods on Anti-Metabolic Syndrome, and Antimicrobial Properties of Extracts and Hydrolysates Obtained from Elicited Lovage (Levisticum officinale Koch).

This research aims to investigate the influence of elicitation and drying methods (natural, convection, microwave, and freeze-drying), with jasmonic acid (JA) and yeast extract (YE) on the biological activity of extracts and hydrolysates from lovage (Levisticum officinale Koch) leaves. The results indicate that the highest TPC was determined for hydrolysates obtained from JA-elicited microwave-dried lovage (24.96 mg/gDW). The highest ACE and lipase inhibitory activity was noted for PBS extract obtained from JA-elicited lovage after microwave drying (EC50 = 0.16 and 0.12 mg/mL, respectively). Ethanolic extract from JA-elicited lovage after freeze-drying was characterized by the highest α-amylase inhibitory activity (EC50 = 3.92 mg/mL) and the highest α-glucosidase inhibitory activity (EC50 = 1.43 mg/mL) was noted for hydrolysates from control plants subjected to freeze-drying. The highest antimicrobial activity towards C. albicans yeasts was observed for microwave ethanolic extracts with minimal inhibition (MIC) and lethal (MLC) concentrations of 0.625 and 1.25 mg/mL, respectively.

Uncovering the multi-level response of Glycine max L. to the application of allelopathic biostimulant from Levisticum officinale Koch.

The interest expressed by the agriculture in the category of innovative biostimulants is due to the intensive search for natural preparations. Our study is the first ever to report a complex approach to the use of allelopathic extracts from Levisticum officinale Koch. roots in soybean cultivation, includes analyses of morphological observations, and analyses of biochemical indicators. Hot method of aqueous extraction was applied. The extracts were administered via foliar application and soil treatment. Lovage extracts had high contents of polyphenolic compounds and rich micro- and macroelemental composition. The infusions did not contain gibberellic acid and indole-3-acetic acid but the abscisic acid and saccharose, glucose, and fructose were found. The extracts modified soybean plant physiology, as manifested by changes in biometric traits. Plants responded positively by increased yield. Seeds from the treated plants had higher contents of micro- and macroelements, as well as total concentrations of lipids (with a slight decrease in protein content). In addition, they featured changes in their amino acid profile and fatty acid composition. The application of allelopathic biostimulant caused increased concentrations of isoflavones and saponins. The natural biostimulants from Levisticum officinale may become a valuable tool in the sustainable agriculture.

The effect of Apium graveolens L., Levisticum officinale and Calendula officinalis L. on cell viability, membrane integrity, steroidogenesis, and intercellular communication in mice Leydig cells in vitro.

Several plants have the potential to protect essential reproductive processes such as spermatogenesis or steroidogenesis, however, effective concentrations and main mechanisms of action are still unknown. This in vitro study was aimed to assess the effects of Apium graveolens L., Levisticum officinale, and Calendula officinalis L. extracts on the structural integrity, functional activity and gap junctional intercellular communication (GJIC) in mice Leydig cells. TM3 cells were grown in the presence of experimental extracts (37.5; 75; 150 and 300 µg/ml) for 24 h. For the present study, high-performance liquid chromatography analysis was used to quantify flavonoids or phenolic acids. Subsequently, Leydig cell viability was assessed by alamarBlue assay, while the cell membrane integrity was detected by 5-carboxyfluorescein diacetate-acetoxymethyl ester. The level of steroid hormones production was determined by enzyme-linked immunosorbent assay. Additionally, GJIC was assessed by scalpel loading/dye transfer assay. According to our results, Apium graveolens L. significantly increased the viability and cell membrane integrity at 75 µg/ml (109.0±4.3%) followed by a decline at 300 µg/ml (89.4±2.3%). In case of Levisticum officinale and Calendula officinalis L. was observed significant decrease at 150 µg/ml (88.8±11.66%; 87.4±6.0%) and 300 µg/ml (86.2±9.3%; 84.1±4.6%). Furthermore, Apium graveolens L. significantly increased the progesterone and testosterone production (75 and 150 µg/ml) however, Levisticum officinale and Calendula officinalis L. significantly reduced steroid hormones synthesis at 150 and 300 µg/ml. Finally, the disturbance of GJIC was significantly affected at 300 µg/ml of Levisticum officinale (82.5±7.7%) and Calendula officinalis L. (79.8±7.0%). The balanced concentration ratio may support the Leydig cell function, steroidogenesis as well as all essential parameters that may significantly improve reproductive functions.

Neuroprotective effects of Levisticum officinale on LPS-induced spatial learning and memory impairments through neurotrophic, anti-inflammatory, and antioxidant properties.

Levisticum officinale (Apiaceae) has been identified as a medicinal plant in traditional medicine, with the anti-inflammatory, antioxidant, and anticholinesterase activities. The present study aims to evaluate the effects of Levisticum officinale extract (LOE) on lipopolysaccharide (LPS)-induced learning and memory deficits and to examine its potential mechanisms. LOE was administered to adult male Wistar rats at doses of 100, 200, and 400 mg kg-1 for a week. Later, LPS was intraperitoneally injected at a dose of 1 mg kg-1 to induce neuroinflammation, and treatment with LOE continued for 3 more weeks. Behavioral, biochemical, and molecular analyses were performed at the end of the experiment. Moreover, quantitative immunohistochemical assessments of the expression of Ki-67 (intracellular proliferation marker) in the hippocampus were performed. The results revealed that LPS injection caused spatial memory impairment in the rats. Daily LOE treatment at applied doses for 4 weeks attenuated spatial learning and memory deficits in LPS-injected rats. Furthermore, LPS significantly increased the mRNA expression level of interleukin-6 in the hippocampus, which was accompanied by decreased brain-derived neurotrophic factor (BDNF) mRNA expression levels. Moreover, LPS increased the levels of malondialdehyde, reduced the antioxidant enzyme activities of catalase and superoxide dismutase in the hippocampus, and impaired neurogenesis. However, pre-treatment with LOE at a dose of 100 mg kg-1 significantly reversed the LPS-induced changes, and improved neurogenesis. In conclusion, the beneficial effect of LOE on the improvement of learning and memory could be attributed to its anti-inflammatory and antioxidant activities, along with its ability to increase BDNF expression and neurogenesis in the hippocampus.

Chemical and bioactive characterization of the aromatic plant Levisticum officinale W.D.J. Koch: a comprehensive study.

Aromatic plants have been used since antiquity as seasoning ingredients to impart unique flavours to foods, and also as folk medicines, and are currently used as a source of several compounds of interest for different industries. Lovage (Levisticum officinale W.J.D. Koch) is an aromatic plant from the Apiaceae family with a strong flavour that has long been used in culinary products, in traditional medicine and by the food industry. Despite its significance and relevance, apart from its composition in volatile compounds, there is a scarcity of information about this plant species. To the best of our knowledge, this study documents for the first time the nutritional value and composition in fatty acids, organic acids and tocopherols of the edible aerial part of lovage, evidencing a low caloric value, a predominance of polyunsaturated fatty acids, mainly α-linolenic acid, oxalic acid as the most abundant organic acid and α-tocopherol as the most abundant vitamin E isoform. The essential oil was mainly characterised by the presence of monoterpenes, showing also a high abundance of phthalides. In addition, a total of 7 phenolic compounds were identified in the decoction and hydroethanolic extracts, which showed interesting antioxidant properties and bacteriostatic activity, particularly against Gram-positive bacteria. Only the decoction showed cytotoxicity against a tumoral cell line (HepG2).

Antioxidative and Potentially Anti-inflammatory Activity of Phenolics from Lovage Leaves Levisticum officinale Koch Elicited with Jasmonic Acid and Yeast Extract.

The effect of elicitation with jasmonic acids (JA) and yeast extract (YE) on the production of phenolic compounds as well as the antioxidant and anti-inflammatory properties of phenolic extracts of lovage was evaluated. The analysis of phenolic compounds carried out with the UPLC-MS technique indicated that rutin was the dominant flavonoid, while 5-caffeoylquinic acid was the main component in the phenolic acid fraction in the lovage leaves. The application of 10 µM JA increased the content of most of the identified phenolic compounds. The highest antioxidant activities estimated as free radical scavenging activity against ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and reducing power were determined for the sample elicited with 10 µM JA, while this value determined as iron chelating ability was the highest for the 0.1% YE-elicited lovage. The 0.1% and 1% YE elicitation also caused significant elevation of the lipoxygenase (LOX) inhibition ability, while all the concentrations of the tested elicitors significantly improved the ability to inhibit cyclooxygenase 2 (COX2) (best results were detected for the 10 µM JA and 0.1% YE2 sample). Thus, 0.1% yeast extract and 10 µM jasmonic acid proved to be most effective in elevation of the biological activity of lovage.

Hydroalcoholic Extract of Levisticum officinale Increases cGMP Signaling Pathway by Down-Regulating PDE5 Expression and Induction of Apoptosis in MCF-7 and MDA-MB-468 Breast Cancer Cell Lines

Background: This study aimed to investigate Levisticum officinale hydroalcoholic extract (LOHE) effect on both cGMP signaling pathway and phosphodiesterase 5 (PDE5) gene expression pattern and to examine the role of LOHE in apoptosis induction of MCF-7 and MDA-MB-468 cell lines. Methods: The half maximal inhibitory concentration (IC50) of LOHE was examined in both cell lines using the MTT assay. Using IC50 values of LOHE on both cells, the type of cell death was detected by flowcytometric analysis. The values of PDE5 and cGMP were evaluated by real-time PCR and ELISA methods, respectively. Results: The IC50 values were measured as 150 µg/ml for MDA-MB-468 and 200 µg/ml for MCF-7. At 12 hour of treatment, a significant decrease in the PDE5 expression and maximum increase in the amount of intracellular cGMP were observed (p < 0.05). However, these effects were more noticeable in MDA-MB-468 triple-negative cells. Conclusion: Our data suggest that LOHE extract could be a potential source for new strategies towards targeting both PDE5 and cGMP signaling pathways.

The hepatoprotective effects of aquatic extract of Levisticum officinale against paraquat hepatocyte toxicity.

Paraquat is extensively used as a strong nitrogen-based herbicide for controlling weeds in agriculture. This herbicide is extremely toxic to humans and induces multiorgan failure due to accumulation in the cells. So far, many instances of fatal poisoning have been reported. Paraquat is metabolized primarily in the liver. Accordingly, the effects of aquatic Levisticum officinale extract on biochemical factors and oxidative status were evaluated in hepatocytes exposed to paraquat in this study. The results showed that paraquat-induced hepatocyte destruction is mediated by reactive oxygen species (ROS) production. The aquatic extracts of Levisticum officinale (100, 200, and 300µg/mL) could prevent lipid peroxidation and reduction in the potential of mitochondrial membranes (P<0.05). The antioxidants, ROS scavengers (mannitol, dimethyl sulfoxide, and α-tocopherol), and mitochondrial permeability transition pore-sealing agent (carnitine) inhibited the effects of paraquat. The pore-sealing compound inhibited hepatotoxicity, indicating that paraquat induces cell death via mitochondrial pathways. Hepatic cell death due to paraquat could be prevented by hepatocyte pretreatment with aquatic Levisticum officinale extracts, antioxidants, and ROS scavengers; therefore, oxidative stress might directly reduce the mitochondrial membrane potential. In conclusion, paraquat hepatotoxicity may be associated with oxidative stress and maintained by the disruption of mitochondrial membrane potential. Levisticum officinale aquatic extract, presumably due to its strong antioxidant properties, could protect against the destructive effects of paraquat on rat hepatocytes.

Development of SCAR Markers Based on Improved RAPD Amplification Fragments and Molecular Cloning for Authentication of Herbal Medicines Angelica sinensis, Angelica acutiloba and Levisticum officinale.

Molecular cloning from DNA fragments of improved RAPD amplification of Angelica sinensis, Angelica acutiloba and Levisticum officinale, provided novel sequence-characterized amplified region (SCAR) markers A13, A23, A1-34 and A1-0 whose sequences were deposited in the GenBank database with the accession numbers KP641315, KP641316, KP641317 and KP641318, respectively. By optional PCR amplification, the SCAR markers A13 and A23 are Levisticum officinale-specific, whereas the SCAR marker A1-34 is Angelica acutiloba-specific, and the SCAR marker A1-0 is Angelica sinensis-specific. These diagnostic SCAR markers may be useful for genetic authentications, for ecological conservation of all three medicinal plants and as a helpful tool for the genetic authentication of adulterant samples.

Chlorogenic acid in raw materials for the production of chicory coffee.

BACKGROUND: Chicory coffee is produced from traditional raw materials. Other materials are added to improve its aroma. The aim of this study was to test new raw materials with a high content of chlorogenic acid (CGA) as the criterion for their selection. This acid is degraded in the course of roasting and is a source of phenolic compounds affecting coffee aroma. For this reason, contents of CGAs were analyzed in traditional and new materials before and after roasting and compared with the chemicals formed in the roasted pure standard of chlorogenic acid (5-CQA). RESULTS: It was shown that the novel raw materials contained considerable amounts of 5-CQA, frequently higher than in traditional chicory. The roasting process caused significant losses of 5-CQA in the tested raw materials, amounting to 55-91%. In turn, the analysis of volatile compounds in roasted materials showed the presence of certain phenolic and heterocyclic compounds that were also formed as degradation products of the pure 5-CQA chemical standard. CONCLUSION: Novel raw materials, mainly chokeberry, artichoke and lovage, are rich sources of CGAs, particularly 5-CQA. Their application in the production of chicory coffee may result in an increased content of primarily phenolic compounds in its aroma.

Chemical Composition and antiproliferative activity of essential oil from the leaves of a medicinal herb, Levisticum officinale, against UMSCC1 head and neck squamous carcinoma cells.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a challenging disease with a high mortality rate. Natural products represent a valuable source for the development of novel anticancer drugs. We investigated the cytotoxic potential of essential oil from the leaves of a medicinal plant, Levisticum officinale (lovage) on head and neck squamous carcinoma cells (HNSCC). MATERIALS AND METHODS: Cytotoxicity of lovage essential oil was investigated on the HNSCC cell line, UMSCC1. Additionally, we performed pharmacogenomics analyses. RESULTS: Lovage essential oil extract had an IC50 value of 292.6 µg/ml. Genes involved in apoptosis, cancer, cellular growth and cell cycle regulation were the most prominently affected in microarray analyses. The three pathways to be most significantly regulated were extracellular signal-regulated kinase 5 (ERK5) signaling, integrin-linked kinase (ILK) signaling, virus entry via endocytic pathways and p53 signaling. CONCLUSION: Levisticum officinale essential oil inhibits human HNSCC cell growth.