Root Morphogenesis of Arabidopsis thaliana Tuned by Plant Growth-Promoting Streptomyces Isolated From Root-Associated Soil of Artemisia annua

In this study, the capacity to tune root morphogenesis by a plant growth-promoting rhizobacterium, Streptomyces lincolnensis L4, was investigated from various aspects including microbial physiology, root development, and root endophytic microbial community. Strain L4 was isolated from the root-associated soil of 7-year plantation of Artemisia annua. Aiming at revealing the promotion mechanism of Streptomyces on root growth and development, this study first evaluated the growth promotion characters of S. lincolnensis L4, followed by investigation in the effect of L4 inoculation on root morphology, endophytic microbiota of root system, and expression of genes involved in root development in Arabidopsis thaliana. Streptomyces lincolnensis L4 is able to hydrolyze organic and inorganic phosphorus, fix nitrogen, and produce IAA, ACC deaminase, and siderophore, which shaped specific structure of endophytic bacterial community with dominant Streptomyces in roots and promoted the development of roots. From the observation of root development characteristics, root length, root diameter, and the number of root hairs were increased by inoculation of strain L4, which were verified by the differential expression of root development-related genes in A. thaliana. Genomic traits of S. lincolnensis L4 which further revealed its capacity for plant growth promotion in which genes involved in phosphorus solubilization, ACC deamination, iron transportation, and IAA production were identified. This root growth-promoting strain has the potential to develop green method for regulating plant development. These findings provide us ecological knowledge of microenvironment around root system and a new approach for regulating root development.

The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer

Artemisinin (ART) is a bioactive molecule derived from the Chinese medicinal plant Artemisia annua (Asteraceae). ART and artemisinin derivatives (ARTs) have been effectively used for antimalaria treatment. The structure of ART is composed of a sesquiterpene lactone, including a peroxide internal bridge that is essential for its activity. In addition to their well-known antimalarial effects, ARTs have been shown recently to resist a wide range of tumors. The antineoplastic mechanisms of ART mainly include cell cycle inhibition, inhibition of tumor angiogenesis, DNA damage, and ferroptosis. In particular, ferroptosis is a novel nonapoptotic type of programmed cell death. However, the antitumor mechanisms of ARTs by regulating ferroptosis remain unclear. Through this review, we focus on the potential antitumor function of ARTs by acting on ferroptosis, including the regulation of iron metabolism, generation of reactive oxygen species (ROS), and activation of endoplasmic reticulum stress (ERS). This article systematically reviews the recent progress in ferroptosis research and provides a basis for ARTs as an anticancer drug in clinical practice.

Barley Seedlings in Response to Salinity and Artemisinin Stress in the Present of Freeze-Thaw Stress

In the Qinghai-Tibet Plateau, both the large daily temperature difference and soil salinization make plants susceptible to abiotic stresses such as freeze-thaw and salinity. Meanwhile, crops in this area could be subjected to the influence of artemisinin, an allelochemical exuded by Artemisia annua. In the context of freeze-thaw and salinity stresses, artemisinin was induced as an allelopathy stress factor to explore the physiological response of highland barley, including the relative electrical conductivity (RC), soluble protein (SP) content, malondialdehyde (MDA) content, antioxidant enzyme activity, and water use efficiency (WUE).There data suggested that artemisinin weakened the self-osmotic adjustment ability of seedlings, reducing the SOD activity in scavenging efficiency of reactive oxygen species, then causing oxidative damage to cell membrane of seedlings, which significantly increases the content of RC and MDA. Artemisinin stress can reduce the WUE of seedlings and weaken the photosynthesis intensity of seedlings as well. In a word, salinity stress and artemisinin respectively showed a synergistic compound relationship with freeze-thaw stress,

In vitro assessment of genotoxic and cytotoxic effects of Artemisia annua L. tincture

The genus Artemisia (fam. Asteraceae) is one of the largest and widely distributed with around 500 species, majority used as aromatic and medicinal plants. Artemisia annua L. is widely used as a dietary spice, herbal tea, as a supplement, and in a non-pharmaceutical form for treatment of malaria and fever. It is orally consumed as capsules, extracts and tinctures and topically applied as an essential oil diluted in lotions and ointments. Artemisinin is the main constituent of Artemisia annua L. extracts. Since the discovery that the artemisinin is efficient in malaria treatment, there is also a growth in consumption of A. annua extracts for antitumour and even recently for antiviral treatments against SARS-CoV-2 infections. This study aimed to investigate genotoxic effect in peripheral blood culture and cytotoxic effects in cancer and normal cell lines, of commercially available A. annua L. tincture in series of dilutions. Both comet and neutral red uptake assays revealed dose-dependent genotoxicity and cytotoxicity of A. annua tincture dilutions. Comet assay revealed significantly increased DNA damage in peripheral blood cells while neutral-red assays showed increase in cytotoxicity (p<0.001) in both normal and cancer cell cultures treated with the lowest extract dilution compared to the highest one applied. Obtained results indicate caution needed in A. annua L. tincture use, especially when poorly diluted.

AaCycTL Regulates Cuticle and Trichome Development in Arabidopsis and Artemisia annua L.

Artemisinin is an important drug for resistance against malaria. Artemisinin is derived from the glandular trichome of leaves, stems, or buds of the Chinese traditional herb Artemisia annua. Increasing the trichome density may enhance the artemisinin content of A. annua. It has been proven that cyclins are involved in the development of trichomes in tomato, Arabidopsis, and tobacco, but it is unclear whether the cyclins in A. annua influence trichome development. In this study, we showed that AaCycTL may regulate trichome development and affect the content of artemisinin. We cloned AaCycTL and found that it has the same expression files as the artemisinin biosynthesis pathway gene. We overexpressed AaCycTL in Arabidopsis, and the results indicated that AaCycTL changed the wax coverage on the surface of Arabidopsis leaves. The trichome density decreased as well. Using yeast two-hybrid and BiFC assays, we show that AaCycTL can interact with AaTAR1. Moreover, we overexpressed AaCycTL in A. annua and found that the expression of AaCycTL was increased to 82–195%. Changes in wax coverage on the surface of transgenic A. annua leaves or stems were found as well. We identified the expression of the artemisinin biosynthesis pathway genes ADS, CYP71AV1, and ALDH1 has decreased to 88–98%, 76–97%, and 82–97% in the AaCycTL-overexpressing A. annua lines, respectively. Furthermore, we found reduced the content of artemisinin. In agreement, overexpression of AaCycTL in A. annua or Arabidopsis may alter waxy loading, change the initiation of trichomes and downregulate trichome density. Altogether, AaCycTL mediates trichome development in A. annua and thus may serve to regulate trichome density and be used for artemisinin biosynthesis.

ATIVIDADE ANTIPARASITÁRIA DA Artemisia annua CONTRA ESPÉCIES DE Leishmania

Introdução: A Artemisia annua é uma planta natural da Ásia e foi introduzida em diversos países ao redor do mundo(1). Conhecida há séculos por suas características medicinais, essa planta pode ser utilizada, por exemplo, na forma de óleo essencial ou pó para auxiliar contra diversas patologias, desde uma simples inflamação até mesmo infecção viral e bacteriana, diabetes e cânceres(1,3,4). O amplo espectro de ação da A. annua se deve ao fato de haver em sua composição metabólitos como artemisinina, flavonóides, terpenóides, cumarinas e saponinas(4). A Artemisia annua possui também ação contra a leishmaniose, uma doença causada por mais de 20 agentes etiológicos intracelulares(4). Transmitida por insetos dos gêneros Phlebotomus e Lutzomyia spp, a leishmaniose é considerada uma doença de preocupação global e se divide em três formas, sendo elas a cutânea, mucocutânea e visceral(2,4). Uma vez que os medicamentos que existem atualmente no mercado possuem graves efeitos colaterais, fez-se necessário o melhor entendimento acerca da ação da Artemisia annua sobre as espécies de Leishmania(4). Objetivos: Este resumo tem como objetivo analisar a ação anti-leishmania da Artemisia annua e em quais formas do parasita essa planta é capaz de atuar. Métodos: Foi realizada uma busca nas plataformas de dados PubMed e Google Acadêmico, e os artigos científicos foram encontrados por meio do descritor “artemisia annua AND leishmania”. Resultados: As folhas da Artemisia annua apresentaram ação contra as amastigotas da Leishmania panamensis, agente etiológico da leishmaniose cutânea, e não foi observada cito e genotoxicidade(4). Além disso, as sementes e folhas da A. annua mostraram atividade contra promastigotas e amastigotas de Leishmania donovani, agente causador da leishmaniose visceral. A ação anti-leishmania ocorreu por meio da ativação da morte celular programada, onde foi possível observar a exteriorização de fosfatidilserina e fragmentos de DNA. Os componentes da A. annua identificados na pesquisa foram a cânfora, n-hexano, acetato de alfa-amirina, β-cariofileno e derivados da artemisinina. Ademais, não foi encontrada citotoxicidade nas células de mamíferos(2,3). Conclusões: Em decorrência do que foi exposto, conclui-se que a Artemisia annua possui componentes com ação anti-leishmania, provocando a morte de amastigotas e promastigotas. Com isso, é necessário que pesquisas continuem sendo realizadas com a A. annua para que mais compostos com potencial contra espécies de Leishmania possam ser identificados e, assim, abordagens terapêuticas mais baratas e seguras possam ser aplicadas em indivíduos infectados por esse parasita.

Marketing and Value Addition of Artemisia Annua Species and Other Potential Medicinal Plants in Southern Ethiopia

Background: Medicinal plants play a pivotal role in the traditional medicine system in Ethiopia. Since the outbreak of the COVID-19 pandemic, domestic demand for medicinal plants has increased, particularly for Artemisia annua species. However, coupled with the secrecy nature in medicinal plant utilization, knowledge regarding marketing and value addition of medicinal plants is lacking in the literature. The objective of the present market study was to investigate the marketing and value addition of Artemisia annua and other major medicinal plants in selected towns of Southern Ethiopia. Methodology: Primary data were collected using questionnaire, focus group discussions, and personal observations with producers and traders. Marketing benefits of the potential medicinal plants were captured by total return and marketing margins. Result: The major medicinal plants in Chencha area were Artemisia annua, Stevia rebaudiana, and Silybum marianum, Echinops kebericho and Silene macrosolen Steud are widely used in Tula and Hawassa; Ocimum tenuiflorum and Ruta graveolens were found in Basha area, while Zehneria scabra was found in Chencha and Basha. The above-mentioned medicinal plants are used to treat various illnesses, while generating income to the local communities. The marketing or profit margins of the value-added products indicated a share of 28.6%, 14.36%, 14.31%, and 42.73% for producers, local collectors, and traders in Arbaminch and Addis Ababa, respectively. Conclusion: Up scaling the cultivation and commercialization of these medicinal plants has the potential to maintain the public health while providing alternative income sources for local communities in Ethiopia. In an effort to capture local value addition of medicinal plants, processing materials, market outlets, and road infrastructures should be improved.

Cytotoxicity of an Innovative Pressurised Cyclic Solid–Liquid (PCSL) Extract from Artemisia annua

Therapeutic treatments with Artemisia annua have a long-established tradition in various diseases due to its antibacterial, antioxidant, antiviral, anti-malaria and anti-cancer effects. However, in relation to the latter, virtually all reports focused on toxic effects of A. annua extracts were obtained mostly through conventional maceration methods. In the present study, an innovative extraction procedure from A. annua, based on pressurised cyclic solid–liquid (PCSL) extraction, resulted in the production of a new phytocomplex with enhanced anti-cancer properties. This extraction procedure generated a pressure gradient due to compressions and following decompressions, allowing to directly perform the extraction without any maceration. The toxic effects of A. annua PCSL extract were tested on different cells, including three cancer cell lines. The results of this study clearly indicate that the exposure of human, murine and canine cancer cells to serial dilutions of PCSL extract resulted in higher toxicity and stronger propensity to induce apoptosis than that detected by subjecting the same cells to Artemisia extracts obtained through canonical extraction by maceration. Collected data suggest that PCSL extract of A. annua could be a promising and economic new therapeutic tool to treat human and animal tumours.

Analysis of the oxidative stress inhibition potentials of Artemisia annua and its bioactive compounds through in vitro and in silico studies

Oxidative stress overwhelms the antioxidant mechanisms of living systems, with active involvement in the pathogenesis of several diseases. Natives of Gangnim in the Plateau State of Nigeria may be unknowingly endowed with some protective advantages against oxidative stress for their habitual consumption of Artemisia annua tea. The antioxidant activities of A. annua extracts were determined using in vitro methods and the inhibitory potentials of twenty-nine (29) bioactive compounds of the plant against oxidative stress target proteins were assessed through molecular docking analysis. These extracts showed significantly high activities in scavenging nitric oxide, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing ferric (Fe3+) to ferrous (Fe2+) iron. Virtually, none of the bioactive compounds binds to the active site of the antioxidant protein targets. Rather, 72.41, 93.10 and 75.86% of these compounds bind with high binding affinity to the activator binding sites of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) respectively. 7,8-dimethylalloxazine (-8.10 kcal/mol) ranked highest as a prospective inhibitor of xanthine oxidase (XOX). The antioxidant activity exhibited by the extracts of the locally cultivated A. annua and the molecular interactions of its bioactive compounds against the protein targets used predict that oxidative stress inhibition could be effectively achieved with these phytochemicals.