[Water use characteristics and the mechanism of water uptake in two typical sand-fixing species in Mu Us sandy land]. / æ¯›ä¹Œç´ å ¸åž‹å›ºæ²™æ¤ç‰©çš„æ°´åˆ†åˆ©ç”¨ç‰¹æ€§ä¸Žå¸æ°´æœºåˆ¶.

Understanding water absorption mechanisms of sand-fixing plants is important for the rational establishment of plant community structures, thereby providing a scientific basis for desertification control and the efficient utilization of water resources in sandy areas. Based on the hydrogen and oxygen isotopic compositions of precipi-tation, soil water, xylem water, and groundwater, coupled with soil water-heat dynamics, annual water consumption characteristics of vegetation, using the multi-source linear mixing model (IsoSource), we analyzed the differences in water sources between Salix psammophila and Artemisia ordosica, during winter and the growing season. We further examined the effects of groundwater depth (2 m and 10 m), soil freezing-thawing, and drought on their water utilization to elucidate water absorption mechanisms of those species. The results showed that: 1) During soil freezing-thawing period (January to March), S. psammophila mainly utilized soil water in 60-120 cm depths below the frozen layer (69.1%). In the green-up season (April and May), soil water from the 0-60 cm layers could satisfy the water demand of S. psammophila (30.9%-87.6%). During the dry period of the growing season (June), it predominantly utilized soil water at the depth of 120-160 cm (27.4%-40.8%). Over the rainy season (July and September), soil water in 0-60 cm depths provided 59.8%-67.9% of the total water required. A. ordosica, with shallow roots, could not utilize soil water after complete freezing of root zone but could overwinter by storing water in rhizomes during autumn. During the growing season, it primarily relied on 0-40 cm soil layer (23.4%-86.8%). During the dry period, it mainly utilized soil water from 40-80 cm and 80-160 cm soil layers, with utilization rates of 14.6%-74.4% and 21.8%-78.2%, respectively. 2) With decreasing groundwater depth, vegetation shifted its water absorption depth upward, with water source of S. psammophila transitioning from 120-160 cm to 60-160 cm layers, while A. ordosica shifted water absorption depth from 80-160 cm to 0-40 cm. S. psammophila's utilization of soil water is influenced by transpiration, adopting an "on-demand" approach to achieve a balance between water supply and energy conservation, whereas A. ordosica tends to utilize shallow soil water, exhibiting a higher depen-dence on water sources from a single soil layer.

[Environmental regulation of water use efficiency in Artemisia ordosica in Mu Us Sandy Land: From leaf to ecosystem]. / æ¯›ä¹Œç´ æ²™åœ°é»‘æ²™è’¿æ°´åˆ†åˆ©ç”¨æ•ˆçŽ‡çŽ¯å¢ƒè°ƒæŽ§:从叶片到生态系统.

Water use efficiency (WUE) is a key indicator for predicting the impacts of climate change on ecosystem carbon and water cycles. Most studies have explored the changes in the response environment of WUE at a particular scale. Few studies have examined how WUE responds to environments at multiple scales, thus limiting our in-depth understanding of the cross-scale carbon and water cycles. In this study, we measured photosynthesis and transpiration in situ periodically and continuously from June to October 2022 in a community dominated by Artemisia ordosica in Mu Us Sandy Land, and analyzed the seasonal variations in WUE at leaf, canopy, and ecosystem scales. The results showed there were significant seasonal variations in leaf water use efficiency (WUEL), canopy water use efficiency (WUET), and ecosystem water use efficiency (WUEE). WUEL was large in June and small in both August and September, ranging from 0.73-2.98 µmol·mmol-1. Both WUET and WUEE were lowest in June and highest in July and August, ranging from 0.10-7.00 and 0.06-6.25 µmol·mmol-1. WUEL was significantly negatively correlated with stomatal conductance. WUET was significantly positively correlated with canopy conduc-tance and soil water content, and negatively correlated with vapor pressure deficit (VPD). There was a significant positive correlation between WUEE and soil water content (SWC10) in 10 cm soil depth. The structural equation model showed that SWC10 and air temperature affected net photosynthetic rate and transpiration rate by modifying stomatal conductance, and thus affecting WUEL. VPD and SWC10 affected WUET by altering transpiration. SWC10, air temperature, and VPD affected WUEE by regulating ecosystem gross primary productivity. The modelling of carbon and water cycles should thoroughly consider the path and intensity of the effect of environmental factors on WUE at multiple scales.

Integrated multi-omics analysis reveals genes involved in flavonoid biosynthesis and trichome development of Artemisia argyi.

Artemisia argyi is an herbaceous plant of the genus Artemisia. Its young and mature leaves are used as food and medicine, respectively. Glandular trichomes (GTs) are distributed on the leaf surface in A. argyi and are generally considered the location of flavonoid biosynthesis and accumulation. However, the mechanism of flavonoid biosynthesis and accumulation in A. argyi remains unclear. In this study, the coregulatory genes involved in flavonoid biosynthesis and trichome development in this species were screened and evaluated, and the biosynthetic pathways for key flavonoids in A. argyi were uncovered. AaMYB1 and AaYABBY1 were screened using weighted gene co-expression network analysis, and both genes were then genetically transformed into Nicotiana tabacum L. cv. K326 (tobacco). Simultaneously, AaYABBY1 was also genetically transformed into Arabidopsis thaliana. The total flavonoid and rutin contents were increased in tobacco plants overexpressing AaMYB1 and AaYABBY1, and the expression levels of genes participating in the flavonoid synthesis pathway, such as PAL, FLS, and F3H, were significantly up-regulated in plants overexpressing these genes. These results indicated that AaMYB1 and AaYABBY1 promote flavonoid biosynthesis in tobacco. Furthermore, compared to that in the wild-type, the trichome density was significantly increased in tobacco and A. thaliana plants overexpressing AaYABBY1. These results confirm that AaYABBY1 might be involved in regulating trichome formation in A. argyi. This indicates the potential genes involved in and provides new insights into the development of trichome cellular factories based on the "development-metabolism" interaction network and the cultivation of high-quality A. argyi.

The Extracts Derived from Artemisia japonica Thunb. Leaves Mitigate Oxidative Stress and Inflammatory Response Induced by LPS in RAW264.7 Cells through Modulation of the Nrf2/HO-1 Signaling Pathway.

Artemisia japonica Thunb. has been used as a traditional Chinese medicine and a vegetable for thousands of years in China. However, there are few reports on the chemical composition and biological activity of its leaves. Thus, this study aimed to evaluate the chemical composition, antioxidant and anti-inflammatory effects of water extracts of A. japonica leaves and their underlying mechanisms. A total of 48 compounds were identified in the water extract using UPLC-QTOF-MS2 analysis, with phenolic acids, particularly chlorogenic acid compounds, being the predominant components. The ethyl acetate fraction (EAF) contained most of the total phenolic content (385.4217 mg GAE/g) and displayed superior antioxidant capacity with the IC50DPPH•, IC50ABTS•+, and OD0.5reducing power at 10.987 µg/mL, 43.630 µg/mL and 26.883 µg/mL, respectively. Furthermore, EAF demonstrated potent antioxidant and anti-inflammatory effects in LPS-induced RAW264.7 cells by upregulating the Nrf2/HO-1 signal pathway. These findings highlight that A. japonica leaves possess remarkable abilities to mitigate inflammation and oxidative stress, suggesting their potential utilization as medicinal agents and food additives for promoting human health.

Analysis of root volatiles and functional characterization of a root-specific germacrene A synthase in Artemisia pallens.

MAIN CONCLUSION: The study demonstrated that Artemisia pallens roots can be a source of terpene-rich essential oil and root-specific ApTPS1 forms germacrene A contributing to major root volatiles. Davana (Artemisia pallens Bess) is a valuable aromatic herb within the Asteraceae family, highly prized for its essential oil (EO) produced in the aerial parts. However, the root volatile composition, and the genes responsible for root volatiles have remained unexplored until now. Here, we show that A. pallens roots possess distinct oil bodies and yields ~ 0.05% of EO, which is primarily composed of sesquiterpenes ß-elemene, neryl isovalerate, ß-selinene, and α-selinene, and trace amounts of monoterpenes ß-myrcene, D-limonene. This shows that, besides aerial parts, roots of davana can also be a source of unique EO. Moreover, we functionally characterized a terpene synthase (ApTPS1) that exhibited high in silico expression in the root transcriptome. The recombinant ApTPS1 showed the formation of ß-elemene and germacrene A with E,E-farnesyl diphosphate (FPP) as a substrate. Detailed analysis of assay products revealed that ß-elemene was the thermal rearrangement product of germacrene A. The functional expression of ApTPS1 in Saccharomyces cerevisiae confirmed the in vivo germacrene A synthase activity of ApTPS1. At the transcript level, ApTPS1 displayed predominant expression in roots, with significantly lower level of expression in other tissues. This expression pattern of ApTPS1 positively correlated with the tissue-specific accumulation level of germacrene A. Overall, these findings provide fundamental insights into the EO profile of davana roots, and the contribution of ApTPS1 in the formation of a major root volatile.

Plant morphology, secondary metabolites and chlorophyll fluorescence of Artemisia argyi under different LED environments.

Different light spectra from light-emitting diodes (LEDs) trigger species-specific adaptive responses in plants. We exposed Artemisia argyi (A. argyi) to four LED spectra: white (the control group), monochromatic red light (R), monochromatic blue light (B), or a mixture of R and B light of photon flux density ratio is 3 (RB), with equivalent photoperiod (14 h) and light intensity (160 µmol s-1 m-2). R light accelerated photomorphogenesis but decreased biomass, while B light significantly increased leaf area and short-term exposure (7 days) to B light increased total phenols and flavonoids. HPLC identified chlorogenic acid, 3,5-dicaffeoylquinic acid, gallic acid, jaceosidin, eupatilin, and taxol compounds, with RB and R light significantly accumulating chlorogenic acid, 3,5-dicaffeoylquinic acid, and gallic acid, and B light promoting jaceosidin, eupatilin, and taxol. OJIP measurements showed that B light had the least effect on the effective quantum yield ΦPSII, with higher rETR(II), Fv/Fm, qL and PIabs, followed by RB light. R light led to faster photomorphology but lower biomass than RB and B lights and produced the most inadaptability, as shown by reduced ΦPSII and enlarged ΦNPQ and ΦNO. Overall, short-term B light promoted secondary metabolite production while maintaining effective quantum yield and less energy dissipation.

Essential oil from Artemisia argyi alleviated liver disease in zebrafish (Danio rerio) via the gut-liver axis.

The popularity of intensive fish farming has led to the emergence of fish diseases characterized by hepatobiliary syndrome. Artemisia argyi (A. argyi) essential oils have anti-inflammatory and anti-oxidant effects. However, their alleviating effects and mechanism on liver disease in fish are still unclear. Thus, adult zebrafish were used to construct an animal model to observe histopathological damages, determine biochemical parameters and expression of inflammatory cytokines and mRNAs in the PPAR-γ/NF-κB pathway, and conduct 16 S sequencing of intestinal microbiota. The results found that after treatment with A. argyi essential oil, the histopathological damage caused by ethanol was relieved; the CAT, SOD, and GSH levels were remarkably elevated, while the MDA level was obviously lowered (P < 0.05); the expression levels of IL-10 and IFN-γ mRNAs were enhanced, but the levels of IL-1ß, IL-6, PPAR-γ, NF-κB, and TNF-α mRNAs were reduced (P < 0.05) relative to the EtOH group. A. argyi essential oil remarkably attenuated the damage to intestinal tissue structure, and elevated the levels of Muc2, ZO-1, Claudin-1, and Occludin mRNA (P < 0.05). Sequencing of the gut flora showed that A. argyi essential oil significantly altered the composition of gut microbes compared with the EtOH group. In addition, KEGG and COG analyses also showed significant (P < 0.05) changes in acetate cycling metabolism in the EtOH group, catechol 2, 3-dioxygenase and nitroreductase were significantly increased (P < 0.001), and lipid metabolism and terpenoid synthesis were significantly elevated (P < 0.001) in A. argyi essential oil group. The results indicate that A. argyi essential oil could effectively relieve ethanol-caused histopathological damage of livers by modulating the composition of gut microbiota, thus inhibiting the level of IL-1ß and mRNAs in the PPAR-γ/NF-κB pathway, increasing the IL-10 level, reducing the oxidative stress. This may offer a rationale for further research on the rationality of A. argyi as a substitute for feed antibiotics in aquaculture.

Microbial Transformation of the Sesquiterpene Lactone, Vulgarin, by Aspergillus niger.

The biotransformation of vulgarin (1), an eudesmanolides-type sesquiterpene lactone obtained from Artemisia judaica, by the microorganism, Aspergillus niger, was carried out to give three more polar metabolites; 1-epi-tetrahydrovulgarin (1α,4α-dihydroxy-5αH,6,11ßH-eudesman-6,12-olide (2), 20% yield, 1α,4α-dihydroxyeudesm-2-en-5αH,6,11ßH-6,12-olide (3a), 10% yield, and C-1 epimeric mixture (3a, b), 4% yield, in a ratio of 4:1, 3a/3b. The structures of vulgarin and its metabolites were elucidated by 1 and 2D NMR spectroscopy in conjunction with HRESIMS. Metabolites (3a) and (3b) are epimers, and they are reported here for the first time as new metabolites obtained by biotransformation by selective reduction at C-1. Vulgarin and its metabolites were evaluated as anti-inflammatory agents using the human cyclooxygenase (COX) inhibitory assay. The obtained data showed that (1) exhibited a good preferential inhibitory activity towards COX-2 (IC50 = 07.21 ± 0.10) and had a moderate effect on COX-1 (IC50 = 11.32 ± 0.24). Meanwhile, its metabolite (3a) retained a selective inhibitory activity against COX-1 (IC50 = 15.70 ± 0.51). In conclusion, the results of this study revealed the necessity of the presence α, ß unsaturated carbonyl group in (1) for better COX-2 inhibitory activity. On the other hand, the selectivity of (1) as COX-1 inhibitor may be enhanced via the reduction of C-1 carbonyl group.

Metabolomic and transcriptomic analyses provide insights into variations in flavonoids contents between two Artemisia cultivars.

BACKGROUND: Plants in the genus Artemisia are rich in active ingredients and specialized metabolites. Many of these compounds, especially flavonoids, have potential medicinal and nutritional applications, and are of growing interest to scientists due to their wide range of pharmacological and biological activities. Artemisia cultivars are commonly used as raw materials for medicine, food, and moxibustion in China. However, most of the metabolites produced by Artemisia species have not been identified, and few studies have addressed differences in active compounds between species and cultivars. RESULTS: We here investigated two Artemisia cultivars, 'Nanyangshiyong' (NYSY) and 'Nanyangyaoyong' (NYYY), which are commonly used in foods and moxibustion, respectively. NYSY and NYYY were confirmed to be Artemisia argyi cultivars. Total flavonoids contents and antioxidant activities were higher in NYYY than in NYSY. A total of 882 metabolites were identified in the samples; most of the potentially medicinally active compounds, especially flavonoids (e.g., flavone, flavonol, isoflavone, and anthocyanin), were up-regulated in NYYY compared to NYSY. Furthermore, most of the genes related to flavonoids biosynthesis were up-regulated in NYYY. Correlation analysis was used to identify putative members of transcription factor families that may regulate genes encoding key flavonoids biosynthesis enzymes. CONCLUSIONS: We found that the antioxidant activities and flavonoids contents significantly varied between two Artemisia cultivars of the same species. We also uncovered metabolomic and transcriptomic evidence of the molecular phenomena underlying those differences in flavonoids contents between the two Artemisia cultivars. This study provides a wealth of data for future utilization and improvements of Artemisia cultivars, and highlights a need to study the specific metabolite profiles of plants that are used in foods and medicines.

Moisturizing and Antioxidant Effects of Artemisia argyi Essence Liquid in HaCaT Keratinocytes.

Artemisia argyi essence liquid (AL) is an aqueous solution extracted from A. argyi using CO2 supercritical fluid extraction. There have been few investigations on the aqueous solution of A. argyi extracted via CO2 supercritical fluid extraction. This study aimed to explore the moisturizing and antioxidant effects of AL and to clarify the potential mechanism underlying those effects. Expression levels of skin moisture-related components and the H2O2-induced oxidative stress responses in human keratinocyte cells were measured via quantitative RT-qPCR, Western blot, and immunofluorescence. Our results showed that AL enhanced the expression of AQP3 and HAS2 by activating the EGFR-mediated STAT3 and MAPK signaling pathways. In addition, AL can play an antioxidant role by inhibiting the NF-κB signaling pathway and activating the Nrf2/HO-1 signaling pathway, consequently increasing the expression of antioxidant enzymes (GPX1, SOD2) and decreasing the production of reactive oxygen species (ROS). This study revealed that AL could be used as a potential moisturizing and antioxidant cosmetic ingredient.

Recent Trends on Production Sources, Biosynthesis Pathways and Antiviral Efficacies of Artemisinin: A Candidate Phytomedicine against SARS-CoV-2.

BACKGROUND: Artemisinin is a lactone sesquiterpenoid with an endo-peroxide bridge in the 1, 2, 3-trioxane structure employed for the treatment and management of lethal viral diseases. In the current review, emphasis has been given on the production of artemisinin from natural sources with biosynthesis pathways and potential antiviral activity. METHODS: A wide-ranging inquiry on artemisinin was made electronically on the basis of articles published in peer-reviewed journals, abstracts, published in conference proceedings, government reports, preprints, books, Master's and Ph.D. theses, etc. The research was carried out in different International scientific databases like Academic Search, Biological Abstracts, BIOSIS, BioOne Previews, CabDirect, Cochrane Library, Pubmed/Medline, GeoRef, Google Scholar, JSTOR, Journal Citation Reports, Mendeley, Publons, Researchgate, Scopus, SciELO, Springer Link, Science Direct, Web of Science, Taylor and Francis with particular keywords. RESULTS: The evidence reviewed here indicates that out of the hundreds of species of the genus Artemisia mentioned in the literature, only 37 Artemisia species are reported to possess artemisinin naturally in their extracts with variable concentrations. This review further discusses the biosynthesis pathways and antiviral activities of artemisinin and its derivatives which have been used against more than 12 viral disease categories. CONCLUSION: On the whole, it is concluded that the primary natural sources of artemisinin and its derivatives are the Artemisia plants with antiviral activity, which are essential candidates for drug development against SARS-CoV-2 mainly from those Artemisia species screened for SARS-CoV- 2 infection.

Ursonic acid from Artemisia montana exerts anti-diabetic effects through anti-glycating properties, and by inhibiting PTP1B and activating the PI3K/Akt signaling pathway in insulin-resistant C2C12 cells.

Artemisia is one of the largest genera in the plant family Asteraceae and has long been used in traditional medicine for its antitussive, analgesic, antihypertensive, antitoxic, antiviral, antimalarial, and anti-inflammatory properties. However, the anti-diabetic activity of Artemisia montana has not been broadly studied. The goal of this study was to determine whether extracts of the aerial parts of A. montana and its main constituents inhibit protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase activities. We isolated nine compounds from A. montana including ursonic acid (UNA) and ursolic acid (ULA), which significantly inhibited PTP1B with IC50 values of 11.68 and 8.73 µM, respectively. In addition, UNA showed potent inhibitory activity against α-glucosidase (IC50 = 61.85 µM). Kinetic analysis of PTP1B and α-glucosidase inhibition revealed that UNA was a non-competitive inhibitor of both enzymes. Docking simulations of UNA demonstrated negative binding energies and close proximity to residues in the binding pockets of PTP1B and α-glucosidase. Molecular docking simulations between UNA and human serum albumin (HSA) revealed that UNA binds tightly to all three domains of HSA. Furthermore, UNA significantly inhibited fluorescent AGE formation (IC50 = 4.16 µM) in a glucose-fructose-induced HSA glycation model over the course of four weeks. Additionally, we investigated the molecular mechanisms underlying the anti-diabetic effects of UNA in insulin-resistant C2C12 skeletal muscle cells and discovered that UNA significantly increased glucose uptake and decreased PTP1B expression. Further, UNA increased GLUT-4 expression level by activating the IRS-1/PI3K/Akt/GSK-3 signaling pathway. These findings clearly demonstrate that UNA from A. montana shows great potential for treatment of diabetes and its complications.

Sesquiterpenes from Artemisia princeps regulate inflammatory responses in RAW 264.7 macrophages.

Four sesquiterpenoids were isolated from an ethyl acetate-soluble fraction of A. princeps ethanolic extract: seco-tanapartholide B (5-epi-seco-tanapartholide A) (1), 4-epi-seco-tanapartholide A (2), 11,13-dehydrodesacetylmatricarin (3) and desacetylmatricarin (4). Compounds 1 - 3 dose-dependently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. These compounds also decreased mRNA and protein expression levels of inducible NO synthase and cyclooxygenase-2 as well as mRNA levels of pro-inflammatory cytokines (interleukin-1ß and tumour necrosis factor-α) in LPS-stimulated RAW 264.7 macrophages. Moreover, compound 3 effectively enhanced the expression of heme oxygenase-1 (HO-1) in macrophages in the presence or absence of LPS. Additionally, the exocyclic methylene of α-methylene-γ-lactone moiety of compound 3 was found to be essential for the activation of the NF erythroid 2-related factor 2 (Nrf2)/HO-1 pathway. Here, we firstly report the isolation of compounds 3 and 4 from A. princeps and the anti-inflammatory activity of compound 3 by up-regulation of Nrf2/HO-1 pathway.

Cultivated Artemisia rupestris L. polysaccharide CARP2 as an adjuvant for influenza vaccines to prolong immune responses.

In the study, the adjuvant features of the immunoregulatory polysaccharide component CARP2 isolated from cultivated Artemisia rupestris L. for influenza virus vaccine (IVV) and the mechanism responsible for its action in DCs were further explored. CARP2 showed a typical absorbance peak of polysaccharides in spectral analysis. At two doses of CARP2-adjuvanted IVV, IgG, hemagglutination inhibition (HI) titers, and effector/memory T cells were generated and lasted for 275 days without adverse events. CARP2 primed rapid HI and IgG, IgG2a/IgG1 ratio, splenocyte proliferation, and cytotoxic T lymphocyte (CTL), and facilitated the generation of INF-γ and IL-4 by activating DCs and regulatory T cells (Tregs). Additionally, CARP2 achieved the ten-fold dose-sparing effect. In vitro, CARP2 stimulated DCs to prime the production of Th1/Th2 cytokines and CCR7 and activated MyD88-dependent pathway by upregulating the expressions of TLR4, MyD88, TRAF-6, and p65. In contrast, MyD88, TRAF-6, and NF-κB inhibitors partially blocked the effect through reducing related cytokines and proteins. Overall, CARP2 promoted IVV efficacy, which was involved in the modulation of Th1/Th2 responses and shifted toward Th1-polarizing response via TLR4/MyD88/TRAF/NF-κB activation in DCs.

Inhibition of Synaptic Glutamate Exocytosis and Prevention of Glutamate Neurotoxicity by Eupatilin from Artemisia argyi in the Rat Cortex.

The inhibition of synaptic glutamate release to maintain glutamate homeostasis contributes to the alleviation of neuronal cell injury, and accumulating evidence suggests that natural products can repress glutamate levels and associated excitotoxicity. In this study, we investigated whether eupatilin, a constituent of Artemisia argyi, affected glutamate release in rat cortical nerve terminals (synaptosomes). Additionally, we evaluated the effect of eupatilin in an animal model of kainic acid (KA) excitotoxicity, particularly on the levels of glutamate and N-methyl-D-aspartate (NMDA) receptor subunits (GluN2A and GluN2B). We found that eupatilin decreased depolarization-evoked glutamate release from rat cortical synaptosomes and that this effect was accompanied by a reduction in cytosolic Ca2+ elevation, inhibition of P/Q-type Ca2+ channels, decreased synapsin I Ca2+-dependent phosphorylation and no detectable effect on the membrane potential. In a KA-induced glutamate excitotoxicity rat model, the administration of eupatilin before KA administration prevented neuronal cell degeneration, glutamate elevation, glutamate-generating enzyme glutaminase increase, excitatory amino acid transporter (EAAT) decrease, GluN2A protein decrease and GluN2B protein increase in the rat cortex. Taken together, the results suggest that eupatilin depresses glutamate exocytosis from cerebrocortical synaptosomes by decreasing P/Q-type Ca2+ channels and synapsin I phosphorylation and alleviates glutamate excitotoxicity caused by KA by preventing glutamatergic alterations in the rat cortex. Thus, this study suggests that eupatilin can be considered a potential therapeutic agent in the treatment of brain impairment associated with glutamate excitotoxicity.

Ethyl Acetate Extract from Artemisia argyi Prevents Liver Damage in ConA-Induced Immunological Liver Injury Mice via Bax/Bcl-2 and TLR4/MyD88/NF-κB Signaling Pathways.

BACKGROUND: Immunological liver injury (ILI) is a common liver disease and lacks potent drugs for treatment. Artemisia argyi Lévl. et Vant. (A. argyi), a medicinal and edible homologous plant usually used in diet therapy to cure various liver diseases, provides a great option for the prevention of ILI. PURPOSE: To investigate the effect that ethyl acetate extract of A. argyi (AaEA) on Concanavalin A (ConA)-induced ILI and the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. METHODS: The chemical components of AaEA were studied by LC-MS. In animal experiments, the positive control group was administrated diammonium glycyrrhizinate (DIG, 100 mg/kg), while different doses of AaEA groups (AaEA-H, AaEA-M, AaEA-L) were pretreated with AaEA 2.00, 1.00, and 0.50 g/kg, respectively, by intragastric for seven days, once every day. Then, ConA (12.00 mg/kg) was used through tail intravenous injection to establish the ILI model. The blood samples and livers were collected to test the degree of liver dysfunction, inflammation, oxidative stress, histopathological changes, and cell apoptosis. Real-time PCR and Western blotting analysis were used to explain the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. RESULTS: The way in which AaEA prevents liver damage in immunological liver injury (ILI) mice caused by ConA was investigated for the first time. Pretreatment with AaEA reduced the expression of ALT, AST, and inflammatory factors (TNF-α and IFN-γ). Meanwhile, AaEA also reduced MDA levels but upregulated the contents of IL-4, SOD, and GSH-px, alleviating oxidative stress induced by ILI. Western blotting and real-time PCR analysis demonstrated that AaEA could regulate the expression level and relative mRNA expression of key proteins on Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. Finally, 504 components from AaEA were identified by LC-MS analysis, mainly including flavones, phenolic acids, and terpenoids with anti-inflammatory and liver protective activities, which highlights the potential of AaEA for diet treatment of ILI. CONCLUSION: AaEA can work against ConA-induced ILI in mice by regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways, which has the potential to be a great strategy for the prevention of ILI.

Alleviating effects of essential oil from Artemisia vulgaris on enteritis in zebrafish via modulating oxidative stress and inflammatory response.

Artemisia vulgaris (A. vulgaris) is a traditional Chinese medicine widely distributed in China and contains many bioactive compounds with pharmacological effects. However, the anti-inflammatory effects and mechanism of essential oil from A. vulgaris on enteritis in fish are still unclear. In this study, in order to elucidate the underlying mechanism of essential oil from A. vulgaris on zebrafish enteritis, zebrafish were used for establishing animal models to observe the histopathological changes of intestines, determine the activities of immune-related enzymes and oxidative stress indicators, and the mRNA expression of genes in MyD88/TRAF6/NF-KB signaling pathways. The results showed that different doses of A. vulgaris essential oil could effectively alleviate zebrafish enteritis in a dose- and time-dependent manner by improving the intestinal histopathological damage, decreasing the intestinal oxidative stress, repairing the intestinal immune ability, changing the expression levels of IL-1ß, IL-10 and genes in MyD88/TRAF6/NF-κB pathway. In addition, co-treatment with oxazolone and MyD88 inhibitor could alleviate the morphological damage, the induction of oxidative stress, and the levels of immune-related enzymes and the mRNA expression of genes in MyD88/TRAF6/NF-κB signaling pathway. Moreover, essential oil from A. vulgaris had more significantly therapeutic effects on enteritis of male zebrafish than that of female zebrafish. This result will clarify the therapeutic effect and anti-inflammatory mechanism of essential oil from A. vulgaris on zebrafish enteritis, and provide a theoretical basis for further research on the rationality of A. vulgaris to replace feed antibiotics.

Artemisia argyi extract ameliorates IL-17A-induced inflammatory response by regulation of NF-κB and Nrf2 expression in HIG-82 synoviocytes.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that results in joint destruction and disability in the adult population. RA is characterized by the accumulation and proliferation of fibroblast-like synoviocytes. Many pro-inflammatory mediators are associated with RA, such as interleukin (IL)-1ß, IL-6, IL-17, cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB). Furthermore, IL-17 upregulates the production of other pro-inflammatory mediators, including IL-1ß and IL-6, and promotes the recruitment of neutrophils in RA. Artemisia argyi, a traditional Chinese herbal medicine, is used for the treatment of diseases associated with inflammation and microbial infections. In this study, synoviocytes (HIG-82) were treated with varying doses of A. argyi extract (AAE) following IL-17A stimulation. Proliferation of the IL-17A-stimulated cells was increased compared to that of the non-stimulated control cells. However, cell proliferation decreased significantly in a dose-dependent manner following AAE treatment. Treatment of IL-17A-stimulated cells with AAE resulted in decreased levels of phosphorylated (p)-NF-κB, p-IκB-α, and COX-2. Enzyme-linked immunosorbent assay results showed that IL-1ß and IL-6 levels were increased in the IL-17A-stimulated group but decreased in the AAE treatment group. Additionally, we found that AAE facilitated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and promoted its nuclear translocation, thereby inducing the expression of heme oxygenase-1. Moreover, AAE did not attenuate IL-17A-induced inflammatory mediator production in the presence of ML385, an Nrf2-specific inhibitor. These results suggest that the downregulation of expression of pro-inflammatory cytokines and the transcription factor NF-κB by AAE may be a potential therapeutic strategy for reducing inflammation associated with RA.

In Silico Evaluation of Bioactive Compounds of Artemisia pallens Targeting the Efflux Protein of Multidrug-Resistant Acinetobacter baumannii (LAC-4 Strain).

Acinetobacter baumannii (A. baumannii) is one of the major representative aetiologies of recalcitrant nosocomial infections. Genotypic and phenotypic alterations in A. baumannii have resulted in a significant surge in multidrug resistance (MDR). Of all the factors responsible for the development of antimicrobial resistance (AMR), efflux protein pumps play a paramount role. In pursuit of a safe alternative for the prevention and control of A. baumannii infections, bioactive compounds from the aerial parts of the medicinal plant Artemisia pallens were studied. GC-MS analysis of the ethanol extract of A. pallens detected five major compounds: lilac alcohol A, spathulenol, lilac alcohol C, n-hexadecanoic acid, and vulgarin. In silico examinations were performed using the Schrödinger suite. Homology modelling was performed to predict the structure of the efflux protein of A. baumannii-LAC-4 strain (MDR Ab-EP). The identified bioactive compounds were analysed for their binding efficiency with MDR Ab-EP. High binding efficiency was observed with vulgarin with a glide score of -4.775 kcal/mol and stereoisomers of lilac alcohol A (-3.706 kcal/mol) and lilac alcohol C (-3.706 kcal/mol). Our molecular dynamic simulation studies unveiled the stability of the ligand-efflux protein complex. Vulgarin and lilac alcohol A possessed strong and stable binding efficiency with MDR Ab-EP. Furthermore, validation of the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the ligands strongly suggested that these compounds could serve as a lead molecule in the development of an alternate drug from A. pallens.