Anti-MRSA and cytotoxic activities of different solvent extracts from Artemisia herba-alba grown in Shubak, Jordan.

Background: Globally, resistance to antimicrobial drugs is a major hazard to public health. Infections that were once easily treatable with antibiotics are becoming harder to control, leading to prolonged illnesses, increased mortality rates, and higher healthcare costs. Aim: This study intended to assess the antimicrobial, specifically the anti-Methicillin resistant Staphylococcus aureus (MRSA), and anticancer properties of different extracts obtained from A. herba-alba (AHA). Methods: The antibacterial tests of AHA were performed on two Gram-negative bacterial strains (Escherichia coli and Klebsiella pneumonia), two Gram-positive bacterial strains (Methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus aureus). Initial screening for antibacterial activities was conducted using the well diffusion technique. Subsequently, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined through the broth-dilution assay. The anticancer test was carried out in vitro on a human colorectal carcinoma cell line (HCT-116) using MTT assay. Results: Among all extracts, n-hexane extract of AHA was the most effective against S. aureus with the highest inhibition zone (24.67 mm ± 0.58) compared to standard antibiotic (erythromycin, 24.00 mm) followed by the methanolic extract against MRSA (24.00 mm ± 1.73). The methanol extract of AHA showed the highest antibacterial activity against MRSA. The results of MIC and MBC of the AHA methanol extract against MRSA were 1.17 ± 1.09 and 9.375 ± 0.0 mg/ml, respectively, demonstrating therapeutically significant antibacterial activity. Ethyl acetate extract has no antibacterial activity against E. coli and K. pneumonia. The findings indicated that the methanol extract of AHA exhibited the highest efficacy against the colorectal carcinoma cell line (HCT-116), with an IC50 value of 126.61 ± 13.35 µg/ml. Conclusion: These findings suggest that the methanol extract of AHA could be considered as a potential agent to serve as a source of antibacterial and anticancer compounds.

Differential Anti-Fibrotic and Remodeling Responses of Human Dermal Fibroblasts to Artemisia sp., Artemisinin, and Its Derivatives.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant Artemisia annua L. is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria. A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia teas reduced fibroblast viability 4 d post-treatment in up to 80% of their respective controls. After 4 d of treatment, AS DHA and Artemisia teas downregulated ACTA2 up to 10 fold while ART had no significant effect, and AM increased viability by 10%. MMP1 and MMP3 were upregulated by AS, 17.5 and 32.6 fold, respectively, and by DHA, 8 and 51.8 fold, respectively. ART had no effect, but A. annua and A. afra teas increased MMP3 5 and 16-fold, respectively. Although A. afra tea increased COL3A1 5 fold, MMP1 decreased >7 fold with no change in either transcript by A. annua tea. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone but was less effective than A. afra. Immunofluorescent staining for smooth-muscle α-actin (α-SMA) correlated well with the transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts, with evidence also of remodeling of fibrotic ECM.

Anti-inflammatory discovery of sesquiterpenoids and a jasmonic acid derivative from Artemisia stolonifera.

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.

Chemical composition of Artemisia argyi essential oil and its antifungal activity against dermatophytes by inhibiting oxidative phosphorylation and causing oxidative damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Dermatophytes are notorious pathogens capable of infecting various mammals skin, posing serious threats to human health and overall life quality worldwide. Artemisia argyi has been recorded and applied for over a thousand years to treat skin itching. Although it has the potential to be developed as a plant-based antifungal agent, it's antifungal activity and action mechanism of active ingredients are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the chemical composition, antifungal activity against skin fungi, and potential mechanisms of Artemisia argyi essential oil (AEO). MATERIALS AND METHODS: The chemical composition of AEO was analyzed by gas chromatography-mass spectrometry (GC-MS) firstly. Flat growth restraint and double half dilution tests was performed to evaluate AEO antifungal activity against Microsporum gypseum, Trichophyton mentagrophytes, and Trichophyton rubrum. And then, the physiological mechanism of AEO inhibiting dermatophytes was systematically explored through scanning electron microscopy, relative conductivity, membrane leakage, ROS content, and antioxidant enzyme activity. Finally, the main pathways were screened through transcriptome sequencing, while the related genes expression levels and enzyme activity were validated. RESULTS: Monoterpenes and sesquiterpenoids were the most highly representative class of AEO. AEO had powerful antifungal activity against M. gypseum, T. mentagrophytes, and T. rubrum, with minimum inhibitory concentration (MIC) values of 0.6, 1.2, and 1.2 µL/mL, respectively. Moreover, AEO can also damage the cell membrane integrity of T. mentagrophytes, resulting in cellular extravasation of intracellular substances. Transcriptome analysis revealed that the main target of AEO is to inhibit electron transfer and oxidative phosphorylation during respiration, ultimately leading to obstruction of normal ATP synthesis and energy metabolism in mitochondria. And a large amount of ROS will generate due to the incompletely catalysis of oxygen under mitochondrial complexes. Coupled with the decrease of antioxidant enzyme (SOD, POD) activity, excessive accumulation of ROS will cause serious oxidative damage to cells and eventually exhibiting antifungal activity against dermatophytes. CONCLUSIONS: The present study demonstrated that Artemisia argyi was a valuable source of active compounds with antifungal activity. These findings support AEO as a potential agent to inhibit dermatophytes and prevent related dermatophytoses.

Physiology and transcriptome analysis of Artemisia argyi adaptation and accumulation to soil cadmium.

The soil pollution caused by cadmium (Cd) poses a significant threat to the environment. Therefore, identifying plants that can effectively remediate Cd-contaminated soils is urgently needed. In this study, physiological, cytological, and transcriptome analyses were performed to comprehensively understand the changes in Artemisia argyi under Cd stress. Physiological and cytological analyses indicated that A. argyi maintained normal growth with intact cell structure under Cd stress levels up to 10 mg/kg. Cytological analysis showed that Cd precipitation in leaf cells occurred in the cytoplasm and intercellular spaces. As the levels of Cd stress increased, proline accumulation in leaves increased, whereas soluble protein and soluble sugar initially increased, followed by a subsequent decline. The translocation factor was above 1 under 0.6 mg/kg Cd stress but decreased when it exceeded this concentration. Transcriptome analyses revealed several crucial Cd-influenced pathways, including amino acid, terpenoid, flavonoid, and sugar metabolisms. This study not only proved that A. argyi could enrich Cd in soil but also revealed the response of A. argyi to Cd and its resistance mechanisms, which provided insight into the cleaner production of A. argyi and the remediation of Cd-contaminated soil.

In vivo antimalarial efficacy of Artemisia afra powder suspensions.

BACKGROUND: A global death toll of 608,000 in 2022 and emerging parasite resistance to artemisinin, the mainstay of antimalarial chemotherapy derived from the Chinese herb Artemisia annua, urge the development of novel antimalarials. A clinical trial has found high antimalarial potency for aqueous extracts of A. annua as well as its African counterpart Artemisia afra, which contains only trace amounts of artemisinin. The artemisinin-independent antimalarial activity of A. afra points to the existence of other antimalarials present in the plant. However, the publication was retracted due to ethical and methodological concerns in the trial, so the only evidence for antimalarial activity of A. afra is built on in vitro studies reporting efficacy only in the microgram per milliliter range. HYPOTHESIS: Our study aims to shed more light on the controversy around the antimalarial activity of A. afra by assessing its efficacy in mice. In particular, we are testing the hypothesis that A. afra contains a pro-drug that is inactive in vitro but active in vivo after metabolization by the mammalian host. METHODS: Plasmodium berghei-infected mice were treated once or thrice (on three consecutive days) with various doses of A. afra, A. annua, or pure artemisinin. RESULTS: Aqueous powder suspensions of A. annua but not A. afra showed antimalarial activity in mice. CONCLUSION: Our experiments conducted in mice do not support the pro-drug hypothesis.

Phytochemical Analysis, Antimicrobial Screening and In Vitro Pharmacological Activity of Artemisia vestita Leaf Extract.

Artemisia vestita Wall. Ex Besser is a folklore medicinal plant that belongs to Asteraceae family and a treasure trove of drugs. The aim of this research study was to investigate the phytoconstituents, antimicrobial activity, antioxidant, anti-inflammatory, cytotoxicity and wound healing potential of A. vestita leaf extract (ALE). Phytochemical analysis of the ALE was carried out by Soxhlet extraction and GCMS (gas chromatography-mass spectrometry) analysis. Antimicrobial activity was performed by the agar well diffusion method against selected bacterial and fungal strains. Free radical scavenging potential was evaluated by DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (Ferric reducing antioxidant power) assays. Anti-inflammatory activity was performed by enzyme inhibition assay-COXII. The cytotoxicity of ALE on HaCaT cells was studied via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. An in vitro scratch assay was performed for the evaluation of the wound healing property of ALE. It showed satisfactory antimicrobial activity against Staphylococcus aureus (14.2 ± 0.28 mm), Escherichia coli (17.6 ± 0.52 mm), Bacillus subtilis (13.1 ± 0.37 mm), Streptococcus pyogenes (17.3 ± 0.64 mm), Proteus mirabilis (9.4 ± 0.56 mm), Aspergillus niger (12.7 ± 0.53 mm), Aspergilus flavus (15.3 ± 0.25 mm) and Candida albicans (17.6 ± 0.11 mm). In ALE, 36 phytochemicals were detected by GCMS analysis, but 22 were dominant. Moreover, the ALE was effective in scavenging free radicals with different assays and exhibited reasonable anti-inflammatory activity. The MTT assay revealed that ALE had a cytotoxic effect on the HaCaT cells. The scratch assay showed 94.6% wound closure (after 24 h incubation) compared to the positive control Cipladine, which is remarkable wound healing activity. This is the first report on the wound healing property of A. vestita, which can serve as a potential agent for wound healing and extends knowledge on its therapeutic potential.

Chemical profiles and bioactivities of polyphenolic extracts of Lavandula stoechas L., Artemisia dracunculus L. and Ocimum basilicum L.

This study assessed the chemical profiles and bioactivities of the infusions, decoctions and hydroethanolic extracts of tarragon, basil and French lavender. The extracts were chemically characterised (HPLC-DAD-ESI/MS) and their bioactivities were evaluated in vitro. All extracts revealed antimicrobial, antifungal and antioxidant properties. French lavender extracts showed higher total phenolic content, regardless of the extraction method used, and antioxidant and antitumour capacities, but no anti-inflammatory action. All basil and two of the tarragon extracts revealed anti-inflammatory power. Thus, tarragon, basil and French lavender extracts may be considered for inclusion in foods, as preservatives or functional ingredients. Nonetheless, further studies must be conducted to evaluate the pharmacokinetic parameters of the bioactive compounds.

Artificial aging conditions for Artemisia argyi leaves based on quality-inflammation-quality marker transformation.

BACKGROUND: Appropriate conditions for storage of Artemisia argyi leaves reduce irritation during treatment and increase the active ingredient content. Naturally aged A. argyi leaves (≥1 year) are optimal for moxibustion; however, this process is time-consuming and costly. A comprehensive understanding of the conditions for artificial aging of A. argyi leaves and the mechanism of quality-marker conversion are required to guarantee A. argyi quality and moxibustion efficacy. OBJECTIVE: To identify the optimal conditions for artificial aging of A. argyi leaves and clarify the mechanism of quality-marker conversion. METHOD: Gas chromatography (GC), high-performance liquid chromatography (HPLC), colorimeter (CD), and near-infrared spectroscopy (NIRS) were used to determine the chemical composition of A. argyi leaves before and after artificial and natural (1 year) aging and to determine the optimal artificial aging conditions. The effects of both artificially and naturally aged A. argyi leaves were then evaluated in a mouse model of ulcerative colitis (UC). The main chemical components of aged A. argyi leaves were then analyzed to determine quality-markers and the transformation mechanism. RESULTS: Comprehensive analysis of volatile and non-volatile components, color values, and characteristic near-infrared spectra revealed that the quality of artificially aged A. argyi leaves was similar to that of naturally aged A. argyi leaves. In the mouse model, artificially and naturally aged A. argyi leaves not only improved the symptoms of UC with the same therapeutic effects, but also safeguarded the barrier of the colonic mucosa and prevented the release of colitis-related substances. In addition, the content of caffeic acid converted from L-phenylalanine in A. argyi leaves increased during the aging process. CONCLUSION: Conditions for artificial aging of A. argyi leaves were identified for the first time, and the equivalent efficacy of artificially aged A. argyi leaves and naturally aged A. argyi leaves for improving UC was confirmed. This method for artificial aging of A. argyi leaves not only reduces the time and cost associated with this process, but also provides technical support to ensure the quality and stability of artificially aged A. argyi leaves. In addition, caffeic acid was identified as a potential quality-marker for establishing standards and specifications for aging A. argyi leaves for the first time, and its possible transformation mechanism was preliminarily elucidated.

Artemyriantholides A-K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity.

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.

Artemisia herba-alba: antioxidant capacity and efficacy in preventing chronic arthritis in vivo.

Arthritis is a debilitating condition impacting the quality of life for millions worldwide, characterized by pain and inflammation. Understanding the mechanisms of arthritis and developing effective treatments are crucial. This study investigated the hydroethanolic extract of Artemisia herba-alba for its protective potential against arthritis hallmarks, oxidative stress, and lipid peroxidation in vitro. It also assessed its in vivo anti-arthritic activity. The phytochemical analysis identified various compounds within the extract, with high concentrations of polyphenols and flavonoids. These compounds are associated with numerous health benefits, making A. herba-alba a potential source of valuable phytochemicals. A. herba-alba demonstrated a notable effect in body weight loss, paw edema, and arthritic severity. Histopathological examination revealed structural improvements in bone and muscle tissues, emphasizing its therapeutic potential in managing chronic arthritis. Furthermore, while these findings are promising, further studies are necessary to delve deeper into the mechanisms underlying the observed hematological changes and to gain a more comprehensive understanding of the in vivo results. This research sets the stage for continued exploration, ultimately aiming to unlock the full potential of A. herba-alba in addressing chronic arthritis and enhancing the lives of those affected by this condition.

Transplanted sagebrush "wildlings" exhibit higher survival than greenhouse-grown tubelings yet both recruit new plants.

BACKGROUND: Land uses such as crop production, livestock grazing, mining, and urban development have contributed to degradation of drylands worldwide. Loss of big sagebrush (Artemisia tridentata) on disturbed drylands across the western U.S. has prompted massive efforts to re-establish this foundational species. There has been growing interest in avoiding the severe limitations experienced by plants at the seed and seedling stages by instead establishing plants from containerized greenhouse seedlings ("tubelings"). In some settings, a potential alternative approach is to transplant larger locally-collected plants ("wildlings"). We compared the establishment of mountain big sagebrush (A. tridentata ssp. vaseyana) from tubelings vs. wildlings in southeastern Idaho. A mix of native and non-native grass and forb species was drill-seeded in a pasture previously dominated by the introduced forage grass, smooth brome (Bromus inermis). We then established 80 m x 80 m treatment plots and planted sagebrush tubelings (n = 12 plots, 1200 plants) and wildlings (n = 12 plots, 1200 plants). We also established seeded plots (n = 12) and untreated control plots (n = 6) for long-term comparison. We tracked project expenses in order to calculate costs of using tubelings vs. wildlings as modified by probability of success. RESULTS: There was high (79%) tubeling and low (10%) wildling mortality within the first year. Three years post-planting, chance of survival for wildlings was significantly higher than that of tubelings (85% and 14% respectively). Despite high up-front costs of planting wildlings, high survival rates resulted in their being < 50% of the cost of tubelings on a per-surviving plant basis. Additionally, by the third year post-planting 34% of surviving tubelings and 95% of surviving wildlings showed evidence of reproduction (presence / absence of flowering stems), and the two types of plantings recruited new plants via seed (3.7 and 2.4 plants, respectively, per surviving tubeling/wildling). CONCLUSIONS: Our results indicate that larger plants with more developed root systems (wildlings) may be a promising avenue for increasing early establishment rates of sagebrush plants in restoration settings. Our results also illustrate the potential for tubelings and wildlings to improve restoration outcomes by "nucleating" the landscape via recruitment of new plants during ideal climate conditions.

Chemical Composition of Essential Oils from Natural Populations of Artemisia scoparia Collected at Different Altitudes: Antibacterial, Mosquito Repellent, and Larvicidal Effects.

The current study aimed to evaluate the presence of chemical variations in essential oils (EOs) extracted from Artemisia scoparia growing at different altitudes and to reveal their antibacterial, mosquito larvicidal, and repellent activity. The gas chromatographic-mass spectrometric analysis of A. scoparia EOs revealed that the major compounds were capillene (9.6-31.8%), methyleugenol (0.2-26.6%), ß-myrcene (1.9-21.4%), γ-terpinene (1.5-19.4%), trans-ß-caryophyllene (0.8-12.4%), and eugenol (0.1-9.1%). The EO of A. scoparia collected from the city of Attock at low elevation was the most active against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa bacteria (minimum inhibitory concentration of 156-1250 µg/mL) and showed the best mosquito larvicidal activity (LC50, 55.3 mg/L). The EOs of A. scoparia collected from the high-altitude areas of Abbottabad and Swat were the most repellent for females of Ae. aegypti and exhibited repellency for 120 min and 165 min, respectively. The results of the study reveal that different climatic conditions and altitudes have significant effects on the chemical compositions and the biological activity of essential oils extracted from the same species.

The Essential Oil Compositions of Ambrosia acanthicarpa Hook., Artemisia ludoviciana Nutt., and Gutierrezia sarothrae (Pursh) Britton & Rusby (Asteraceae) from the Owyhee Mountains of Idaho.

As part of our interest in the volatile phytoconstituents of aromatic plants of the Great Basin, we have obtained essential oils of Ambrosia acanthicarpa (three samples), Artemisia ludoviciana (12 samples), and Gutierrezia sarothrae (six samples) from the Owyhee Mountains of southwestern Idaho. Gas chromatographic analyses (GC-MS, GC-FID, and chiral GC-MS) were carried out on each essential oil sample. The essential oils of A. acanthicarpa were dominated by monoterpene hydrocarbons, including α-pinene (36.7-45.1%), myrcene (21.6-25.5%), and ß-phellandrene (4.9-7.0%). Monoterpene hydrocarbons also dominated the essential oils of G. sarothrae, with ß-pinene (0.5-18.4%), α-phellandrene (2.2-11.8%), limonene (1.4-25.4%), and (Z)-ß-ocimene (18.8-39.4%) as major components. The essential oils of A. ludoviciana showed wide variation in composition, but the relatively abundant compounds were camphor (0.1-61.9%, average 14.1%), 1,8-cineole (0.1-50.8%, average 11.1%), (E)-nerolidol (0.0-41.0%, average 6.8%), and artemisia ketone (0.0-46.1%, average 5.1%). This is the first report on the essential oil composition of A. acanthicarpa and the first report on the enantiomeric distribution in an Ambrosia species. The essential oil compositions of A. ludoviciana and G. sarothrae showed wide variation in composition in this study and compared with previous studies, likely due to subspecies variation.

Composition and antimicrobial activity of Rosmarinus officinalis L. and Artemisia monosperma L. leaf essential oils and methanolic extracts from plants grown in normal and saline habitats in Egypt.

The present work aimed to investigate the effect of salinity in natural habitats in Egypt on the main secondary metabolites of Rosmarinus officinalis L. and Artemisia monosperma L. plants compared to plants grown at normal conditions. Plants grown under salinity were collected from Egyptian Western Coastal region habitats irrigated with underground water. Results showed that salinity increased the essential oil percentage of R. officinalis L. by 52.7% and A. monosperma L by 0.29% in addition to the total phenolics and flavonoids content in dry leaves compared to control plants. GC/MS analysis of rosemary essential oils revealed that salinity decreased the amount of some major oil monoterpenes component as verbenone, with a slight effect on 1,8 cineole and increased Camphor, endo- Boreneol, and linalool in addition to the appearance of new specific components such as Chrysanthenone monoterpene ketone and Caryophyllene sesquiterpene, while, in the case of Artemisia, the GC/MS showed that Artemisia ketone, Camphor, ß -phellandrene monoterpenes andα-Bisabolol sesquiterpenewere the major oil components; salinity decreased Camphor and ß -phellandrene content and increased artemisia ketone and α-Bisabolol oil content. About 11 new oil constituents were detected such as ( +)-2-Bornanone and Sesquisabinene hydrate. Mineral ions (N, K+, Ca+2, P, and Mg+2) uptake by R. officinalis and A. monosperma decreased in plants grown under salinity, while Na content increased compared to corresponding controls. Results demonstrated that both plants could tolerate the high salinity level in natural Western Coastal region soil which promoted more production of valuable secondary metabolites. The antimicrobial effect of R. officinalis L. and A. monosperma L. leaf methanolic extracts, results showed that R. officinalis extracts had an inhibitory response against all tested gram-positive and negative bacteria, in addition to the yeast (Candida albicans), whereas there was no any inhibitory effect concerning A. monosperma L extract on the tested species.

Yinchen gongying decoction mitigates CCl4-induced chronic liver injury and fibrosis in mice implicated in inhibition of the FoxO1/TGF-ß1/ Smad2/3 and YAP signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis (LF) is a common reversible consequence of chronic liver damage with limited therapeutic options. Yinchen Gongying decoction (YGD) composed of two homologous plants: (Artemisia capillaris Thunb, Taraxacum monochlamydeum Hand.-Mazz.), has a traditionally application as a medicinal diet for acute icteric hepatitis. However, its impact on LF and underlying mechanisms remain unclear. AIM OF THE STUDY: This study aims to assess the impact of YGD on a carbon tetrachloride (CCl4) induced liver fibrosis and elucidate its possible mechanisms. The study seeks to establish an experimental foundation for YGD as a candidate drug for hepatic fibrosis. MATERIALS AND METHODS: LC-MS/MS identified 11 blood-entry components in YGD, and network pharmacology predicted their involvement in the FoxO signaling pathway, insulin resistance, and PI3K-AKT signaling pathway. Using a CCl4-induced LF mouse model, YGD's protective effects were evaluated in comparison to a positive control and a normal group. The underlying mechanisms were explored through the assessments of hepatic stellate cells (HSCs) activation, fibrotic signaling, and inflammation. RESULTS: YGD treatment significantly improved liver function, enhanced liver morphology, and reduced liver collagen deposition in CCl4-induced LF mice. Mechanistically, YGD inhibited HSC activation, elevated MMPs/TIMP1 ratios, suppressed the FoxO1/TGF-ß1/Smad2/3 and YAP pathways, and exhibited anti-inflammatory and antioxidant effects. Notably, YGD improved the insulin signaling pathway. CONCLUSION: YGD mitigates LF in mice by modulating fibrotic and inflammatory pathways, enhancing antioxidant responses, and specifically inhibiting FoxO1/TGF-ß1/Smad2/3 and YAP signal pathways.

Artemisia capillaris Thunb. Polysaccharide alleviates cholestatic liver injury through gut microbiota modulation and Nrf2 signaling pathway activation in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional Chinese medicine (TCM) theory, cholestasis belongs to category of jaundice. Artemisia capillaris Thunb. has been widely used for the treatment of jaundice in TCM. The polysaccharides are the one of main active components of the herb, but its effects on cholestasis remain unclear. AIM OF THE STUDY: To investigate the protective effect and mechanism of Artemisia capillaris Thunb. polysaccharide (APS) on cholestasis and liver injury. MATERIALS AND METHODS: The amelioration of APS on cholestasis was evaluated in an alpha-naphthyl isothiocyanate (ANIT)-induced mice model. Then nuclear Nrf2 knockout mice, mass spectrometry, 16s rDNA sequencing, metabolomics, and molecular biotechnology methods were used to elucidate the associated mechanisms of APS against cholestatic liver injury. RESULTS: Treatment with low and high doses of APS markedly decreased cholestatic liver injury of mice. Mechanistically, APS promoted nuclear translocation of hepatic nuclear factor erythroid 2-related factor (Nrf2), upregulated downstream bile acid (BA) efflux transporters and detoxifying enzymes expression, improved BA homeostasis, and attenuated oxidative liver injury; however, these effects were annulled in Nrf2 knock-out mice. Furthermore, APS ameliorated the microbiota dysbiosis of cholestatic mice and selectively increased short-chain fatty acid (SCFA)-producing bacteria growth. Fecal microbiota transplantation of APS also promoted hepatic Nrf2 activation, increased BA efflux transporters and detoxifying enzymes expression, ameliorated intrahepatic BA accumulation and cholestatic liver injury. Non-targeted metabolomics and in vitro microbiota culture confirmed that APS significantly increased the production of a microbiota-derived SCFA (butyric acid), which is also able to upregulate Nrf2 expression. CONCLUSIONS: These findings indicate that APS can ameliorate cholestasis by modulating gut microbiota and activating the Nrf2 pathway, representing a novel therapeutic approach for cholestatic liver disease.

Divergence of 10 satellite repeats in Artemisia (Asteraceae: Anthemideae) based on sequential fluorescence in situ hybridization analysis: evidence for species identification and evolution.

Artemisia is a large genus encompassing about 400 diverse species, many of which have considerable medicinal and ecological value. However, complex morphological information and variation in ploidy level and nuclear DNA content have presented challenges for evolution studies of this genus. Consequently, taxonomic inconsistencies within the genus persist, hindering the utilization of such large plant resources. Researchers have utilized satellite DNAs to aid in chromosome identification, species classification, and evolutionary studies due to their significant sequence and copy number variation between species and close relatives. In the present study, the RepeatExplorer2 pipeline was utilized to identify 10 satellite DNAs from three species (Artemisia annua, Artemisia vulgaris, Artemisia viridisquama), and fluorescence in situ hybridization confirmed their distribution on chromosomes in 24 species, including 19 Artemisia species with 5 outgroup species from Ajania and Chrysanthemum. Signals of satellite DNAs exhibited substantial differences between species. We obtained one genus-specific satellite from the sequences. Additionally, molecular cytogenetic maps were constructed for Artemisia vulgaris, Artemisia leucophylla, and Artemisia viridisquama. One species (Artemisia verbenacea) showed a FISH distribution pattern suggestive of an allotriploid origin. Heteromorphic FISH signals between homologous chromosomes in Artemisia plants were observed at a high level. Additionally, the relative relationships between species were discussed by comparing ideograms. The results of the present study provide new insights into the accurate identification and taxonomy of the Artemisia genus using molecular cytological methods.

Artemdubosides A-G, seven unusual polyacetylenes from Artemisia dubia var. subdigitata and their antihepatoma activity.

Artemdubosides A-E (1-5), the first examples of natural polyacetylenes substituted by 6'-O-crotonyl ß-glucopyranoside, and artemdubosides F-G (6-7) that were two unusual polyacetylenes featuring a 6'-O-acetyl ß-glucopyranoside moiety, were isolated from Artemisia dubia var. subdigitata. Their structures were elucidated based on the spectral data including HRESIMS, UV, IR, 1D and 2D NMR, and ECD calculations. Antihepatoma assay suggested that compound 1 exhibited activity against HepG2, Huh7, and SK-Hep-1 cells with inhibitory ratios of 77.1%, 90.8%, and 73.1% at 200.0 µM, respectively.

Artemisia argyi extracts overcome lapatinib resistance via enhancing TMPRSS2 activation in HER2-positive breast cancer.

Breast cancer stands as the predominant malignancy and primary cause of cancer-related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti-cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib-responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib-resistant HER2-positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes.