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Cold stress, a major abiotic factor, positively modulates the synthesis of artemisinin in Artemisia annua and influences the biosynthesis of other secondary metabolites. To elucidate the changes in the synthesis of secondary metabolites under low-temperature conditions, we conducted dynamic transcriptomic and metabolite quantification analyses of A. annua leaves. The accumulation of total organic carbon (TOC) in leaves under cold stress provided ample precursors for secondary metabolite synthesis. Short-term exposure to low temperature induced a transient increase in jasmonic acid synthesis, which positively regulates the artemisinin biosynthetic pathway, contributing to artemisinin accumulation. Additionally, transcripts of genes encoding key enzymes and transcription factors in both the phenylpropanoid and artemisinin biosynthetic pathways, including PAL, C4H, ADS, and DBR2, exhibited similar expression patterns, suggesting a coordinated effect between these pathways. Prolonged exposure to low temperature sustained high levels of phenylpropanoid synthesis, leading to significant increases in lignin, flavonoids, and anthocyanin. Conversely, the final stage of the artemisinin biosynthetic pathway is inhibited under these conditions, resulting in elevated levels of dihydroartemisinic acid and artemisinic acid. Collectively, our study provides insights into the parallel transcriptional regulation of artemisinin and phenylpropanoid biosynthetic pathways in A. annua under cold stress. [ABSTRACT FROM AUTHOR]

Simple Summary: Artemisia annua residue (AR), as the byproduct of the industrial extraction of artemisinin, contains rich nutrients and active ingredients, which have the potential to replace dietary corn or soybean meal and improve the production performance and intestinal health of livestock. This study found that dietary AR supplementation could increase serum antioxidant capacity, immunity, and intestinal barrier function to improve the growth performance of weaned piglets. Additionally, AR at an appropriate amount of 2.08~4.24% also improved the intestinal microbial structure, metabolic phenotypes, and short-chain fatty acid (SCFA) production, which benefits piglets by improving intestinal status and alleviating weaning stress. This contribution is theoretically and practically relevant because these findings can be applied in the livestock industry to alleviate weaning stress and improve intestinal health. Moreover, developing AR as a new feed material can broaden the comprehensive exploitation and utilization of Artemisia annua resources, improve the economic benefits, and relieve the shortage of feed resources and environmental pollution. Artemisia annua residue (AR), as the byproduct of industrial extraction of artemisinin, contains rich nutrients and active ingredients. This study was conducted to determine the effects of AR as an unconventional feed material on growth performance, immunity, and intestinal health in weaned piglets. Thirty-two piglets weaned at 21 days (7.53 ± 0.31 kg average BW) were fed with a corn–soybean basal diet (BD) and a basal diet with 1% (LAR), 2% (MAR), and 4% (HAR) AR diets for 28 days. AR diets increased the serum IgA and complement component 3 levels, superoxide dismutase activity, and villus height in the duodenum (p < 0.05). The MAR group increased the ADG, serum total protein, and mRNA expression levels of Claudin-1 in the duodenum and zonula occludens-1 (ZO-1) and the mucin 2 (MUC2) in the colon, as well as colonic Romboutsia and Anaerostipes abundances, and decreased the Proteobacteria abundance (p < 0.05). To sum up, dietary AR supplementation may enhance growth performance by improving serum immunoglobulin and antioxidant enzyme activity, intestinal morphology, tight junction protein expression, and gut microbiota of weaned piglets. Regression analysis showed that the optimal AR supplemental level for growth performance, immunity, antioxidant ability, and intestinal health of weaned piglets was 2.08% to 4.24%. [ABSTRACT FROM AUTHOR]

Artemisia annua is an essential aromatic medicinal plant endemic to China. Here, essential oil was extracted from wild A. annua from Ningxia, China. GC-MS analysis showed that A. annua essential oil was dominated by artemisia ketone, a characteristic compound accounting for 31.26%, followed by eucalyptol (14.89%), camphor (8.69%), myrcene (8.25%) and α-pinene (6.65%). The overall antioxidative potential represented by DPPH and ATBS free radical scavenging rates was weak. The essential oil exhibited good bactericidal activities against Escherichia coli and Staphylococcus aureus and fungicidal activities against Trichophyton rubrum and Epidermophyton floccosum. The minimum inhibitory and microbicidal concentrations were 0.02 mg/mL and 5.12 mg/mL for both bacteria, 0.315% and 2.5% for E. floccosum, and 0.625% and 5% for T. rubrum. The results suggest that A. annua essential oil may be an antimicrobial adjuvant to be applied in pharmaceutical and cosmetic industries. [ABSTRACT FROM AUTHOR]

Background: A large number of available substances were retained in artemisinin residual materials, and they can be extracted through further separation and purification for further utilization. Methods: Purification and bioguided separation, including silica gel column chromatography (SGCC) and high-pressure liquid chromatography (HPLC), were utilized to isolate scopoletin, an acaricidal compound, from residual materials of Artemisia annua after extraction of artemisinin (RMAAEA). A methanol crude extract was prepared and subjected to chromatographic purification. Results: A total of 20 groups were obtained. The 17th, 8th, and 18th groups showed stronger acaricidal activity against Tetranychus cinnabarinus than other groups. The 17th group was isolated by further HPLC and divided into three parts: 17-1 (16.21%, w/w), 17-2 (5.31%, w/w), and 17-3 (77.64%, w/w). The LC50 value at 48 h after treatment against T. cinnabarinus was 181.3, 701.1, and 101.5 mg·L−1. Conclusion: The combined elements of 17-3 after purification was determined as scopoletin. Its industrial process with 900 kg of residual materials finally obtained 1.23 kg of pure scopoletin. [ABSTRACT FROM AUTHOR]

Dihydroartemisinin (DHA), a compound extracted from the herbal medicine Artemisia annua , has shown promise as a clinical treatment strategy for colorectal cancer. However, its clinical use is hindered by its low water solubility and bioavailability. A pH/glutathione (GSH) dual-responsive nano-herb delivery system (PMDC NPs) has been developed for the targeted delivery of DHA, accompanied by abundant carbon monoxide (CO) release. Due to the passive enhanced permeability and retention (EPR) effect and active targeting mediated by pHCT74 peptide binding to overexpressed α-enolase on colorectal cancer cells, the pHCT74/MOF-5@DHA&CORM-401 nanoparticles (PMDC NPs) exhibited specific targeting capacity against colorectal cancer cells. Once reaching the tumor site, the pH/GSH dual-responsive behavior of metal-organic framework-5 (MOF-5) enabled the rapid release of cargo, including DHA and CORM-401, in the acidic tumor microenvironment. Subsequently, DHA stimulated CORM-401 to release CO, which facilitated ROS-induced ferroptosis and apoptosis, leading to immunogenic cell death (ICD) and a sustained antitumor response through the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Overall, PMDC NPs enhanced the bioavailability of DHA and exhibited outstanding therapeutic effectiveness both in vitro and in vivo , indicating their potential as a promising and feasible alternative for synergistic treatment with immunotherapy and gas therapy in the clinical management of colorectal cancer. The nano-herb delivery system (PMDC NPs) integrated chemotherapy, immunotherapy, and gas therapy to effectively inhibit colorectal cancer through the mechanisms of ferroptosis, apoptosis, and immunogenic cell death. [Display omitted] • A novel tumor microenvironment-modulated nano-herb delivery system (PMDC NPs) effectively inhibited the growth and recurrence of colorectal cancer. • PMDC NPs exhibited superior efficacy in facilitating oxidative stress-induced apoptosis and ferroptosis. • PMDC NPs can trigger immunogenic cell death and elicit a long-lasting antitumor response. • PMDC NPs exhibited significant synergistic antitumor therapeutic effects, offering a promising approach for combating colorectal cancer. [ABSTRACT FROM AUTHOR]

The degradation of ecosystem functions caused by the allelopathic effects of invasive plants is one of the major environmental problems in the world today. In this study, we used highland barley seedlings as experimental materials to explore the physiological effects of freeze-thaw and artemisinin single and multiple stresses, so as to provide a theoretical basis for the scientific planting, management and environmental problems caused by Artemisia annua L. The key results showed that under the same artemisinin concentration stress, compared with the non-freeze-thaw group, the net photosynthetic rate of plateau barley seedlings decreased by 8.35–40.41%, the soluble sugar content decreased by 21.04–29.83%, and the malondialdehyde (MDA) content decreased by 22.57–43.25% (P < 0.05), and the soluble protein content did not change significantly, and the superoxide dismutase (SOD) activity decreased first and then increased, and the SOD activity was the lowest when the artemisinin concentration was 50 mg/L. We hypothesized that SOD activity decreased first and then increased, possibly due to the initial inhibition of enzyme activity by the decrease in temperature, and the accumulation of superoxide in plant cells. Over time, the temperature rises, and the barley seedlings gradually adapt to the environmental changes, while the temperature rises and the SOD enzyme activity increases to break down excess superoxide in the cells. Under the combined stress of freeze-thaw and artemisinin, barley seedlings showed high cold resistance, and artemisinin with a concentration of less than 10 mg/L had a certain effect on the growth of barley seedlings, which could reduce the harm of freeze-thaw to barley seedlings and improve the stress resistance of barley seedlings. Artemisinin at concentrations below 10 mg/L exhibited antagonistic effect when used in combination with freeze-thaw. When the artemisinin concentration was higher than 10mg/L, it would lead to barley seedling cell damage, and high artemisinin concentration showed incomplete synergistic effect with freeze-thawing. [ABSTRACT FROM AUTHOR]

In order to study the insecticidal activity components and preliminary mechanism of the petroleum ether extract from Artemisia annua against Mythimna separata, the insecticidal activity of different fractions and main components were measured by insect immersion method. The petroleum ether extract was separated by column chromatography and analyzed by gas chromatography-mass spectrometry to determine its chemical components, and the target enzyme and metabolic enzyme activities in the body of Mythimna separata were measured for the active components. The results showed that the petroleum ether extract of Artemisia annua was separated by silica gel column chromatography, and 27 fractions were obtained, of which fraction 8 showed the best contact toxicity. According to gas chromatography-mass spectrometry, the main compounds were tridecane, 4-quinolinecarboxaldehyde, caryophyllene oxide, linoleic acid ethyl ester, linolenic acid ethyl ester with contents of 7.9%, 72.8%, 3.6%, 2.4%, 3.1%, respectively. The lethal concentration of 50% (LC50 ) of above 5 compounds on the 7th day were 7.9, 2.5, 3.6, 5.4 and 1.5 mg•mL-1, respectively, which indicated that ethyl linolenic acid had significant contact toxicity against M. separata. On the 7th day of treatment with 1.5 mg•mL-1 linolenic acid ethyl ester, the scanning electron microscopy results showed that the wax layer structure in the surface of M. separata were loosely, the wax layer particles disappeared significantly, and the wax flower gap increased. And the acetylcholinesterase (AChE) and carboxylesterase (CarE) of M. separata treated with 1.5 mg•mL-1 linolenic acid ethyl ester showed first activation and then inhibition, Na+-K+-ATPase showed inhibition over time, and catalase (CAT) showed first inhibition and then activation. To sum up, the linolenic acid ethyl ester was the main active compound of A. annua, which provided reference for the development of new plant-based insecticides and biological control of M. separata and the development and utilization of A.annua resources. [ABSTRACT FROM AUTHOR]

Background: Herbal therapy for healing disease has many advantages than drugs. This study investigates the protective efficacy of Artemisia annua (Art) and Echinacea pupurea (Ech) extracts against 7, 12-dimethylbenz (α) anthracene (DMBA) toxicity. Results: DMBA-treated rats showed a significant increase in the level of serum ALT, AST, LDH and CKMB, also reduction in body weight gain (BWG) ℅, HB, WBCs, RBCs and platelet counts, in addition to histopathological and ultrastructural alterations. Rats treated with Art or Ech after DMBA showed little improvements in the biochemical, hematological, histopathological, ultrastructural and molecular docking results than before DMBA. Conclusions: This study suggested the ameliorative effect of Ech and Art due to their antioxidant properties, but Ech and Art were more effective if they are given before than after DMBA administration and the marked effect against DMBA toxicity with Ech before DMBA exposure. Also, the molecular docking, molecular properties descriptors, and pharmacoinformatic studies of constituents of extract from Artemisia annua L. and Echinacea purpurea L. exhibited that all studied compounds have better ADMET and physicochemical properties, especially compounds extract from Echinacea purpurea L. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be among the leading causes of mortality in Africa including Uganda, with the emergence of parasite resistance to the first-line therapeutics (Artemisinin- based Combination Therapy). To find new therapeutics, this study has reported an in vivo antimalarial efficacy of combinations of Artemisia annua (Aa), Vernonia amygdalina (Va), and Microglossa pyrifolia (Mp) in mice model using factorial design. Methods: The Aa and Va were extracted by hot infusion, and Mp by cold maceration using distilled water. The dry extracts were screened for different phytochemicals, and later subjected to in vivo antimalarial activity using Peter's 4-day suppressive test. The 23 factorial design used Aa, Va, and Mp aqueous extracts as independent variables at two levels (-1 and 1), and the percentage chemo suppression and survival time as response variables. The data was analyzed using Design Expert 13 and GraphPad Prism employing ANOVA linear regression modelling and t-test respectively. Results: All the extracts had alkaloids, phenols, saponins, terpenoids, cardiac glycosides, tannins, steroids, and carbohydrates. The various combinations showed chemo suppression from 41.5 to 91.0% and survival time of 19 to 23 days. The first three combinations having lower levels of Aa (200 mg/kg) exhibited higher chemo suppression (> 90%) compared to Artemisinin-Lumefantrine positive control at 4 mg/kg with 87.5%. Lower levels of Aa in the combinations contributed to high chemo suppression while higher levels of Va prolonged survival times. Interactions between Aa and Mp showed higher chemo suppression, and that between Aa and Va increased survival time. An optimized prediction of 94.4% chemo suppression was made by the ANOVA model at lower levels of Aa and Va, and a higher level of Mp, which is similar to an experimental run which gave a response of 90. 6%. Conclusion: An optimum combination of the three plants as a natural herbal antimalarial therapy was obtained using factorial design, and it offers an alternative to first line Artemisinin based Combination Therapy (ACTs) as parasite resistance looms. This combination could be further developed into a standard phytopharmaceutical and subjected to Randomized Controlled Trials (RCTs). [ABSTRACT FROM AUTHOR]

The 2015 Nobel Prize in Physiology or Medicine was awarded due to the isolation of the active ingredient of artemisinin, a sesquiterpene lactone, from the plant Artemisia annua L. and proving its effectiveness in the treatment of malaria, and the chemical contents and biological activities of other Artemisia L. species aroused great interest. In this study, it was aimed to investigate the chemical content of essential oils obtained by hydrodistillation from the aerial parts of seven Artemisia species (A. abrotanum L., A. absinthium L., A. annua L., A. austriaca Jacq., A. chamaemelifolia Vill., A. incana (L.) Druce, A. tournefortiana Rchb.) growing in different regions of Turkiye and to evaluate their antimicrobial activities. The essential oils were analyzed by GC and GC-MS. The main components are chrysanthenone (55.9%) for A. abrotanum, sabinyl acetate (23.0%) for A. absinthium, artemisia ketone (53.7%) for A. annua, camphor (34.2%) for A. austriaca, selin-11-en-4-a-ol (29.1%) for A. chamaemelifolia, camphor (29.7%) for A. incana, and (Z)-ß-farnesene (71.5%) for A. tournefortiana. In vitro antimicrobial activity of essential oils against five microorganisms (Bacillus subtilis, Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, Pseudomonas aeruginosa) was investigated using the microdilution method. The highest activity against all species was observed in A. incana essential oil. Staphylococcus aureus was found to be the most sensitive bacteria to all essential oils. [ABSTRACT FROM AUTHOR]

Background: Artemisia annua, a plant with antiviral potential, has shown promise against various viral infections, yet its mechanisms of action are not fully understood. This study explores A. annua's antiviral effects using network pharmacology and molecular docking, focusing on key active compounds and their interactions with viral protein targets, particularly within the JAK-STAT signaling pathway—a critical mediator of immune responses to viral infections. Methods: From the TCMSP database, we identified eight active compounds and 335 drug targets for A. annua, with 19 intersecting targets between A. annua compounds and viral proteins. A protein–protein interaction (PPI) network highlighted 10 key hub genes, analyzed further through Gene Ontology (GO) and KEGG pathways to understand their immune and antiviral roles. ADMET properties of the active compound Patuletin (MOL004112) were assessed, followed by 200 ns molecular dynamics simulations to examine its stability in complex with JAK2. Results: PPI analysis identified JAK2, MAPK3, MAPK1, JAK1, PTPN1, HSPA8, TYK2, RAF1, MAPT, and HMOX1 as key hub genes, with JAK2 emerging as a critical regulator of immune and antiviral pathways. ADMET analysis confirmed Patuletin's favorable pharmacokinetic properties, and molecular dynamics simulations showed a stable Patuletin-JAK2 complex, with FEL analysis indicating minimal disruption to JAK2's intrinsic flexibility. Conclusions: These findings highlight JAK2 as a promising target in the antiviral activity of A. annua compounds, particularly Patuletin, supporting its potential as an antiviral agent and providing a foundation for further research on A. annua's therapeutic applications. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are crucial in regulating secondary metabolite production in plants, but their role in artemisinin (ART) biosynthesis, a key anti-malarial compound from Artemisia annua, remains unclear. Here, by investigating high-artemisinin-producing (HAP) and lowartemisinin-producing (LAP) genotypes, we found that the final artemisinin content in A. annua is influenced by the quantity of the precursor compounds. We report on RNA deep sequencing in HAP and LAP genotypes. Based on the application of a stringent pipeline, 1419 novel lncRNAs were identified. Moreover, we identified 256 differentially expressed lncRNAs between HAP and LAP. We then established correlations between lncRNAs and artemisinin biosynthesis genes in order to identify a molecular framework for the differential expression of the pathway between the two genotypes. Three potential lncRNAs (MSTRG.33718.2, MSTRG.30396.1 and MSTRG.2697.4) linked to the key artemisinin biosynthetic genes (ADS: Amorpha-4,11-diene synthase, DXS: 1-deoxy-D-xylulose-5-phosphate synthase, and HMGS: 3-hydroxyl-3-methyglutaryl CoA synthase) were detected. Importantly, we observed that up-regulation of these lncRNAs positively modulates the target artemisinin biosynthetic genes, potentially leading to high artemisinin biosynthesis in HAP. In contrast, BAS (beta-amyrin synthase), which is involved in the artemisinin competing pathway, was strongly down-regulated in HAP compared to LAP, in line with the expression pattern of the linked lncRNA MSTRG.30396.1. By identifying and characterizing lncRNAs that are potentially linked to the regulation of key biosynthetic genes, this work provides new insights into the complex regulatory networks governing artemisinin production in A. annua. Such findings could pave the way for innovative approaches in metabolic engineering, potentially enhancing artemisinin yields and addressing challenges in sustainable production. [ABSTRACT FROM AUTHOR]

Essential oils (EOs) are reported to be natural pesticides, but their use to protect crops is very limited due to EOs' high instability and great volatility. Nanovectors represent a very smart alternative, and in this study, EOs from Artemisia annua (AEO) and Salvia fruticosa (SEO) were formulated into microemulsions and tested against Fusarium verticillioides. The EOs were extracted by steam distillation and analyzed by GC–MS. The main constituents of AEO were camphor, artemisia ketone, and 1,8-cineole; the main constituents of SEO were 1,8-cineole, camphor, α-pinene, and β-pinene. Artemisia ketone and 1,8-cineole were used to calculate the recovery and chemical stability of the microemulsions. The microemulsions were loaded with 10 mg/mL of EOs, and the recoveries were 99.8% and 99.6% for AEO and SEO, respectively. The sizes of the lipid phases were 255.3 ± 0.6 nm and 323.7 ± 2.3 nm for the AEO and SEO microemulsions, respectively. Activity against F. verticillioides was tested using amphotericin B as the positive control. F. verticillioides was very susceptible to both EOs. When loaded in the microemulsions, AEO and SEO remained very active at a dose of 1.4 and 1.2 mg, with a 99.99% reduction of F. verticillioides. The findings suggest AEO and SEO microemulsions are suitable carriers for the protection of crops against F. verticillioides. [ABSTRACT FROM AUTHOR]

In the last years, the research on the sweet wormwood (Artemisia annua L.) has increasingly become the focus of oncology science. The bioactive ingredient of the plant is artemisinin, which has been proven to be effective in the treatment of malaria. At the same time, Hungarian and international research groups are also investigating the plant, with the research aimed at the treatment of malignant cancer. In Europe, the therapeutic use of medicinal plants against tumours is realized in relatively few countries, in contrast, phytotherapy research in Asia reports results with a significant therapeutic effect. The aim of our work was to investigate the antioxidant effect of Artemisia annua. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Oxygen radical absorbance capacity (ORAC) laboratory assays proved that the parts of the herb show a significant antioxidant effect, while the seed and the extracted bioactive ingredient artemisinin have no antioxidant capacity at all. On the other hand, aqueous extracts made from leafy shoots showed promising antioxidant capacity values DPPH 10.48 ±0.46. Due to its bitter taste index 1548, it can be used in premixed feed e.g. for piglets. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of water extracts of Artemisia annua L. (WEAA) on rumen immune and antioxidative indexes, fermentation parameters and microbial diversity in lambs. A total of 32 3-month-old Dorper × Han female lambs having comparable body weights (24±0.09 kg) were selected and were randomly assigned to four treatments, with eight repetitions for each treatment. The basal diet, consisting of 45% concentrate and 55% forage, was solely provided to the control group. For the other treatment groups, the basal diet was supplemented with WEAA at dosages of 500, 1000, and 1500 mg/kg diet, respectively. Rumen tissue samples were collected for the analysis of immune and antioxidative parameters, as well as related gene expression. Rumen fluid samples were collected to assess rumen fermentation parameters on days 30 and 60 and to evaluate the microbiota on day 60. Results showed that WEAA supplementation linearly or quadratically increased the content of sIgA, IL-4, IL-2 and the gene expression level of MyD88, IκB-α, IL-4, COX-2, iNOS in rumen tissue (p < 0.05), as well as the bacteria negatively associated with IL-6 (g_ [Eubacterium] _cellulosolvens_group). Furthermore, the addition of WEAA linearly or quadratically increased rumen T-SOD, GSH-Px (p < 0.05) and the gene expression level of Nrf2, SOD2, GSH-Px, HO-1 (p < 0.05), and decreased the rumen concentration of malondialdehyde (MDA) and gene expression level of Keap1 (p < 0.05), as well as the bacteria positively associated with T-AOC, T-SOD and GSH-Px (g_Lachnospiraceae_NK3A20_group, g_Saccharofermentans, g__Marvinbryantia, g_unclassified_f_Eggerthellaceae). The supplementation of WEAA caused the concentration of microprotein (MCP), total volatile fatty acids (TVFA), propionate to increase either linearly or quadratically, while reducing the concentration of NH3-N and the acetate/propionate ratio (A:P) in rumen fluid (p < 0.05). The addition of WEAA linearly or quadratically increased the abundance of Actinobacteriota, Cyanobacteria and Lachnospiraceae_NK3A20_group (p < 0.10), and g__Lachnospiraceae_NK3A20_group, g_Saccharofermentans, g_Marvinbryantia, g_Bifidobacterium were significantly abundant as specific microflora in the 1000 mg/kg WEAA supplementation group. In conclusion, dietary inclusion of 1000 mg/kg WEAA improved the rumen immune function, antioxidant status, rumen fermentation, and composition of rumen microbes in lambs. [ABSTRACT FROM AUTHOR]

Abstract Cold stress, a major abiotic factor, positively modulates the synthesis of artemisinin in Artemisia annua and influences the biosynthesis of other secondary metabolites. To elucidate the changes in the synthesis of secondary metabolites under low-temperature conditions, we conducted dynamic transcriptomic and metabolite quantification analyses of A. annua leaves. The accumulation of total organic carbon (TOC) in leaves under cold stress provided ample precursors for secondary metabolite synthesis. Short-term exposure to low temperature induced a transient increase in jasmonic acid synthesis, which positively regulates the artemisinin biosynthetic pathway, contributing to artemisinin accumulation. Additionally, transcripts of genes encoding key enzymes and transcription factors in both the phenylpropanoid and artemisinin biosynthetic pathways, including PAL, C4H, ADS, and DBR2, exhibited similar expression patterns, suggesting a coordinated effect between these pathways. Prolonged exposure to low temperature sustained high levels of phenylpropanoid synthesis, leading to significant increases in lignin, flavonoids, and anthocyanin. Conversely, the final stage of the artemisinin biosynthetic pathway is inhibited under these conditions, resulting in elevated levels of dihydroartemisinic acid and artemisinic acid. Collectively, our study provides insights into the parallel transcriptional regulation of artemisinin and phenylpropanoid biosynthetic pathways in A. annua under cold stress.

Abstract Background Malaria continues to be among the leading causes of mortality in Africa including Uganda, with the emergence of parasite resistance to the first-line therapeutics (Artemisinin- based Combination Therapy). To find new therapeutics, this study has reported an in vivo antimalarial efficacy of combinations of Artemisia annua (Aa), Vernonia amygdalina (Va), and Microglossa pyrifolia (Mp) in mice model using factorial design. Methods The Aa and Va were extracted by hot infusion, and Mp by cold maceration using distilled water. The dry extracts were screened for different phytochemicals, and later subjected to in vivo antimalarial activity using Peter’s 4-day suppressive test. The 23 factorial design used Aa, Va, and Mp aqueous extracts as independent variables at two levels (-1 and 1), and the percentage chemo suppression and survival time as response variables. The data was analyzed using Design Expert 13 and GraphPad Prism employing ANOVA linear regression modelling and t-test respectively. Results All the extracts had alkaloids, phenols, saponins, terpenoids, cardiac glycosides, tannins, steroids, and carbohydrates. The various combinations showed chemo suppression from 41.5 to 91.0% and survival time of 19 to 23 days. The first three combinations having lower levels of Aa (200 mg/kg) exhibited higher chemo suppression (> 90%) compared to Artemisinin-Lumefantrine positive control at 4 mg/kg with 87.5%. Lower levels of Aa in the combinations contributed to high chemo suppression while higher levels of Va prolonged survival times. Interactions between Aa and Mp showed higher chemo suppression, and that between Aa and Va increased survival time. An optimized prediction of 94.4% chemo suppression was made by the ANOVA model at lower levels of Aa and Va, and a higher level of Mp, which is similar to an experimental run which gave a response of 90. 6%. Conclusion An optimum combination of the three plants as a natural herbal antimalarial therapy was obtained using factorial design, and it offers an alternative to first line Artemisinin based Combination Therapy (ACTs) as parasite resistance looms. This combination could be further developed into a standard phytopharmaceutical and subjected to Randomized Controlled Trials (RCTs).

Artemisinin is a truly fascinating drug in many ways. Since the unrestrained procedure of its detection, as an antimalarial drug, artemisinin has received a great deal of consideration. Recently, application of artemisinin-based combination therapy has been broadly applied for treating numerous ailments. Moreover, as an antimalarial compound, artemisinin and its associated compounds have abundant healing efficacy and can be repurposed for additional symptoms, like autoimmune infections, cancer, and viral contaminations. Recently a number of studies have highlighted the significance of the artemisinin-related compounds in SARS-CoV-2 treatment. The current review purposes to present a concise account of the history of the antiviral and antimalarial prodrugs—Artemisinin, from the Artemisia species. It is followed by its antiviral, antimalarial prospective, chemical nature and extraction procedure, photochemistry, mechanism of action, and its clinical trials and patents, and accentuates the significance of the mechanistic studies concerned for therapeutic results, both in viral and malarial circumstances.

درمنه خزری (کاسنیان)، گونه‌­ای با پتانسیل دارویی بالا است. هدف از این مطالعه، مشخص کردن ویژگی‌های رویان­‌شناختی درمنه خزری با تمرکز بر تکوین دانه گرده و تخمک به منظور کمک به جایگاه سیستماتیکی این گونه بود. به این منظور، از میکروسکوپ نوری و الکترونی نگاره برای توصیف تکوین گل استفاده شد. با توجه به نتایج، شکل‌­گیری دیواره بساک در گونه مذکور از نوع دو­لپه‌­ای، لایه مغذی بساک چند­هسته‌­ای و از نوع ترشحی بود. تتراد میکروسپورها از دو نوع تتراگونال و تتراهدرال و دانه­‌های گرده در هنگام شکوفایی دوسلولی، سه‌منفذی و ریزخاردار بودند. تخمک از نوع واژگون، تک‌­پوست‌ه­ای و کم‌­خورش و آرکئوسپور تک‌­سلولی بود. تترادهای مگاسپور T شکل و خطی مشاهده شد. مگاسپور قطب سفتی طبق الگوی تک‌­اسپوری و علف ­‌هفت‌­بند به کیسه‌رویانی هشت هسته‌­ای نمو یافت. لقاح از نوع سفت­‌زامی (porogamous) و تکوین آندوسپرم در این گونه از نوع سلولی بود. برخی از ویژگی‌­های رویان­‌زایی کاسنیان، Calyceraceae و Goodeniaceae نیز در این مقاله آورده شده است. مقایسه نشان داد که ویژگی­‌های رویان‌­زایی شواهد آشکاری برای جداسازی این تیره‌­های خویشاوند ارایه می‌­دهد. در نتیجه بررسی حاضر، نگارندگان پیشنهاد می‌­کنند که مطالعات سیستماتیک روی جنس درمنه و جنس­‌های مشابه فقط روی تزیینات دانه گرده نبوده و لازم است مراحل تکوین بساک و دانه گرده نیز مورد بررسی قرار گیرد. به علاوه، مطالعات کیسه­‌رویانی شاید بتواند تفاوت‌­های نهان سیستماتیکی بین آرایه­‌های مختلف را نیز آشکار سازد.

Abstract Background Transcription factors (TFs) of plant-specific SHORT INTERNODES (SHI) family play a significant role in regulating development and metabolism in plants. In Artemisia annua, various TFs from different families have been discovered to regulate the accumulation of artemisinin. However, specific members of the SHI family in A. annua (AaSHIs) have not been identified to regulate the biosynthesis of artemisinin. Results We found five AaSHI genes (AaSHI1 to AaSHI5) in the A. annua genome. The expression levels of AaSHI1, AaSHI2, AaSHI3 and AaSHI4 genes were higher in trichomes and young leaves, also induced by light and decreased when the plants were subjected to dark treatment. The expression pattern of these four AaSHI genes was consistent with the expression pattern of four structural genes of artemisinin biosynthesis and their specific regulatory factors. Dual-luciferase reporter assays, yeast one-hybrid assays, and transient transformation in A. annua provided the evidence that AaSHI1 could directly bind to the promoters of structural genes AaADS and AaCYP71AV1, and positively regulate their expressions. This study has presented candidate genes, with AaSHI1 in particular, that can be considered for the metabolic engineering of artemisinin biosynthesis in A. annua. Conclusions Overall, a genome-wide analysis of the AaSHI TF family of A. annua was conducted. Five AaSHIs were identified in A. annua genome. Among the identified AaSHIs, AaSHI1 was found to be localized to the nucleus and activate the expression of structural genes of artemisinin biosynthesis including AaADS and AaCYP71AV1. These results indicated that AaSHI1 had positive roles in modulating artemisinin biosynthesis, providing candidate genes for obtaining high-quality new A. annua germplasms.

Breast cancer has become the most prevalent malignancy among women, and it is estimated to comprise over 30% of all cancer cases diagnosed in women. This study evaluates the antitumor effects of a green-synthesized Fe3O4/CeO2 nanocomposite, utilizing Artemisia annua L. extract, against breast cancer. The viability assay was carried out using 100 to 1000 µg/mL of the as-prepared nanocomposites. The BALB/c mice were injected with 4T1 breast cancer cells and subsequently treated with 5 mg/kg body weight of the synthesized nanocomposites through intraperitoneal injection for two weeks. The in vitro studies on the cell viability and cytotoxicity of Fe3O4/CeO2 nanocomposites demonstrated superior effectiveness of the green-synthesized sample (AFC) compared to the chemically produced variant (FC) against 4T1 cells. Treatment with AFC significantly reduced tumor size in 4T1-injected BALB/c mice compared to untreated control. The IC50 results for FC (890.16 µg/mL) and AFC (490.21 µg/mL) corroborated these findings. Notably, the biointerface provided by the phytomolecules from A. annua extract played a crucial role in enhancing the cytotoxic effects of the nanocomposite. This research highlights the potential of green-synthesized Fe3O4/CeO2 nanocomposites as a safe and effective nanomedicine for targeting cancer cells while minimizing adverse effects on healthy cells. [ABSTRACT FROM AUTHOR]

Artemisia annua (A. annua) is a yearly plant that belongs to the Asteraceae family, exhibiting diverse biological activities, such as antipyretic and haemostatic, as well as known for its potential in disease prevention and treatment. The plant contains multiple compounds with proven anticancer properties, which have been proven by both preclinical and clinical studies conducted to validate the anticancer activity. As a result, this study was carried out to assess the prediction of mutagenicity, carcinogenicity, hepatotoxicity, and overall toxicity of phenolic compounds in A. annua using in silico methods. The test processes were carried out using Protox II, Vega QSAR software, and the pkCSM website for analysis. The physicochemical properties of the active compounds were evaluated using Lipinski's Rule of Five, including factors like LogP, molecular weight (MW), number of hydrogen bond donors (HBDs), hydrogen bond acceptors (HBAs), rotatable bonds (ROTB), and topological surface area (TPSA). From thirty-six compounds, there were twenty-nine compounds that met the Lipinski requirement and were predicted not hepatotoxic. About nineteen compounds act as mutagenic and carcinogenic. The prediction results for acute oral toxicity were three compounds, namely quercetin (the most toxic) with an LD50 value of 159 mg/kg (classified as toxic if swallowed), isofraxidin and esculetin were 423 and 945 mg/kg, respectively classified as harmful effects if swallowed. From this study, isofraxidin and esculetin are safer than quercetin and have potential cancer treatments. [ABSTRACT FROM AUTHOR]

Background and Aim: The emergence of multidrug-resistant Staphylococcus aureus (MRSA) strains poses a significant threat to healthcare settings. Although various studies have explored alternative antibiotics, discovering novel therapeutic agents remains crucial. This study aimed to synthesize green silver nanoparticles (AgNPs) as bactericidal agents, identify a multidrug-resistant isolate of Staphylococcus aureus, and explore their biofilm formation ability. To estimate the role of phyto-AgNPs in the perfection of immune markers and healing hepatic lesions in vivo. Materials and Methods: The clinical isolate of MRSA was identified using 16S rRNA New green AgNPs derived from Artemisia annua extract were synthesized. The nanoparticles (NPs) were characterized, and their minimum inhibitory concentration was estimated for fighting MRSA biofilm. A study was conducted on rats to evaluate the effect of new NPs on their immune response to MRSA infection. Results: The new clinical isolate of MRSA RM-Ph8 was identified by molecular phylogenetic analysis as S. aureus, and 16S rRNA sequence analysis confirmed that the new strain was similar to S. aureus with 98.12% identity with accession number OQ421819. The FTIR of the new phyto-AgNPs displayed different functional groups that work as reducing silver nitrate agents. Transmission electron microscopy and scanning electron microscopy images showed spherical particles with an average diameter of 6-28 nm smaller. The chemical method led to complete cell destruction of the multidrug strain within 24 h. Biofilm formation showed that the new MRSA clinical strain was strongly adherent (88%). Notably, the phyto-AgNPs exhibited significant bactericidal activity against the new MRSA strain, with an MIC of up to 50 mg/mL. Moreover, phyto-AgNPs significantly decreased reversed MRSA-induced liver and kidney function impairment, with improvement in both the histopathological lesions and immune histochemical expression of tumor necrosis factor-a and inducible nitric oxide synthase at p < 0.05 compared with the untreated group. Conclusion: Green AgNPs are a promising therapeutic approach against multidrug-resistant bacterial infections, surpassing the effectiveness of conventional antibiotics. [ABSTRACT FROM AUTHOR]

Soil moisture movement reveals the hydrological environment and irrigation characteristics of plants, which is very important and basic hydrological problem. A soil moisture movement algorithm based on cellular automata suitable for greenhouse was proposed to simulate the lateral flow and vertical penetration of soil water in different soil layers. Artemisia annua was used as an experimental plant, and two numerical simulations were set up to determine the minimum water replenishment and the degree of upward soil modification. To verify the performance of the model, corn was used as an experimental plant for application simulation. The numerical simulation results show that the effect of only water for plant cells is superior to soil cells, and the disturbance behavior of the underlying soil layer should be minimized during the cultivation process. The average MAE/RMSE of all soil layers is 0.86/1.06 and in deep layer (50 cm and 60 cm) is 0.53/0.64. It shows the model has a certain prediction and simulation ability, especially in deep soil layers. The proposed algorithm can simply calculate soil flow, set the minimum water replenishment, and evaluate the water replenishment efficiency, which can provide a theoretical reference for the water replenishment and soil replacement scheme. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) by biological synthesis have many advantages. Among them, herbs attract wide attention due to their unique medicinal effects. In this paper, the water/alcohol/ether extracts of dried or fresh Artemisia annua were used as reducing agents and stabilizers to synthesize AgNPs. Water is a highly polar solvent that can effectively extract polar compounds such as phenolic profile, which possesses strong reducing properties and enables the reduction of Ag+ to AgNPs. The prepared AgNPs were characterized using ultraviolet–visible (UV–vis) absorption spectra, X‐ray diffraction (XRD), Fourier transform infrared (FT‐IR) spectroscopy, transmission electron microscopy (TEM), and zeta potential analysis. The AgNPs prepared from the water extracts of dried Artemisia annua have obvious bacteriostatic effects on six common aquatic pathogens and have a wide application prospect in aquaculture. The inhibition zone against Vibrio anguillarum is up to 16.88 mm. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Vibrio anguillarum are 1.09 µg/mL and 2.17 µg/mL, respectively, which is lower than most published reports. [ABSTRACT FROM AUTHOR]

Introduction: Thus far, the impact of kaolin mining activities on the surrounding native plants and rhizosphere microecology has not been fully understood. Methods: In this study, we used 16S rRNA high-throughput sequencing to examine the impact of kaolin mining on the rhizosphere bacterial communities and functions of three local plant species: Conyza bonariensis, Artemisia annua, and Dodonaea viscosa. Results: The results showed that kaolin mining significantly reduced the diversity of rhizosphere bacteria in these plants, as indicated by the Shannon, Simpson, Chao1, and observed species indices (p < 0.05). Kaolin mining had an impact on the recruitment of three rhizosphere bacteria native to the area: Actinoplanes, RB41, and Mycobacterium. These bacteria were found to be more abundant in the rhizosphere soil of three local plants than in bulk soil, yet the mining of kaolin caused a decrease in their abundance (p < 0.05). Interestingly, Ralstonia was enriched in the rhizosphere of these plants found in kaolin mining areas, suggesting its resilience to environmental stress. Furthermore, the three plants had different dominant rhizosphere bacterial populations in kaolin mining areas, such as Nocardioides, Pseudarthrobacter, and Sphingomonas, likely due to the unique microecology of the plant rhizosphere. Kaolin mining activities also caused a shift in the functional diversity of rhizosphere bacteria in the three local plants, with each plant displaying different functions to cope with kaolin mining-induced stress, such as increased abundance of the GlpM family and glucan-binding domain. Discussion: This study is the first to investigate the effects of kaolin mining on the rhizosphere microecology of local plants, thus contributing to the establishment of soil microecological health monitoring indicators to better control soil pollution in kaolin mining areas. [ABSTRACT FROM AUTHOR]

Plants adapt to cold stress through a tightly regulated process involving metabolic reprogramming and tissue remodeling to enhance tolerance within a short timeframe. However, the precise differences and interconnections among various organs during cold adaptation remain poorly understood. This study employed dynamic transcriptomic and metabolite quantitative analyses to investigate cold adaptation and subsequent de-adaptation in Artemisia annua, a species known for its robust resistance to abiotic stress. Our findings revealed distinct expression patterns in most differentially expressed genes (DEGs) encoding transcription factors and components of the calcium signal transduction pathway within the two organs under cold stress. Notably, the long-distance transport of carbon sources from source organs (leaves) to sink organs (roots) experienced disruption followed by resumption, while nitrogen transport from roots to leaves, primarily in the form of amino acids, exhibited acceleration. These contrasting transport patterns likely contribute to the observed differences in cold response between the two organs. The transcriptomic analysis further indicated that leaves exhibited increased respiration, accumulated anti-stress compounds, and initiated the ICE-CBF-COR signaling pathway earlier than roots. Differential expression of genes associated with cell wall biosynthesis suggests that leaves may undergo cell wall thickening while roots may experience thinning. Moreover, a marked difference was observed in phenylalanine metabolism between the two organs, with leaves favoring lignin production and roots favoring flavonoid synthesis. Additionally, our findings suggest that the circadian rhythm is crucial in integrating temperature fluctuations with the plant's internal rhythms during cold stress and subsequent recovery. Collectively, these results shed light on the coordinated response of different plant organs during cold adaptation, highlighting the importance of inter-organ communication for successful stress tolerance. [ABSTRACT FROM AUTHOR]

Artemisinin‐based combinational therapies (ACTs) constitute the first line of malaria treatment. However, due to its trichome‐specific biosynthesis, low concentration, and poor understanding of regulatory mechanisms involved in artemisinin biosynthesis and trichome development, it becomes very difficult to meet the increased demand for ACTs. Here, we have reported that a bHLH transcription factor, AaMYC2‐type, plays an important role in regulating GST development and artemisinin biosynthesis in Artemisia annua. AaMYC2‐type encodes a protein that is transcriptionally active and localised to the nucleus. It is prominently expressed in aerial parts like leaves, stems, inflorescence and least expressed in roots. AaMYC2‐type expression is significantly increased under different hormonal treatments. In transgenic overexpression lines, AaMYC2‐type OE, a significant increase in the expression of trichome development and artemisinin biosynthesis genes was observed. While in knockdown lines, Aamyc2‐type, expression of trichome development and artemisinin biosynthesis genes were significantly reduced. Yeast one‐hybrid assay clearly shows that the AaMYC2‐type directly binds to the E‐boxes in the promoter regions of ADS and CYP71AVI. The SEM microscopy depicted the number of trichomes elevated from 11 mm−2 in AaMYC2‐type OE lines to 6.1 mm−2 in Aamyc2‐type. The final effect of the alteration in biosynthetic and trichome developmental genes was observed in the accumulation of artemisinin. In the AaMYC2‐type OE, the artemisinin content was 12 mg g−1DW, which was reduced to 3.2 mg g−1DW in the Aamyc2‐type. Altogether, the above findings suggest that the AaMYC2‐type play a dual regulating role in controlling both trichome developmental and artemisinin biosynthetic genes. [ABSTRACT FROM AUTHOR]

Target identification is one of the crucial tasks in drug research and development, as it aids in uncovering the action mechanism of herbs/drugs and discovering new therapeutic targets. Although multiple algorithms of herb target prediction have been proposed, due to the incompleteness of clinical knowledge and the limitation of unsupervised models, accurate identification for herb targets still faces huge challenges of data and models. To address this, we proposed a deep learning-based target prediction framework termed HTINet2, which designed three key modules, namely, traditional Chinese medicine (TCM) and clinical knowledge graph embedding, residual graph representation learning, and supervised target prediction. In the first module, we constructed a large-scale knowledge graph that covers the TCM properties and clinical treatment knowledge of herbs, and designed a component of deep knowledge embedding to learn the deep knowledge embedding of herbs and targets. In the remaining two modules, we designed a residual-like graph convolution network to capture the deep interactions among herbs and targets, and a Bayesian personalized ranking loss to conduct supervised training and target prediction. Finally, we designed comprehensive experiments, of which comparison with baselines indicated the excellent performance of HTINet2 (HR@10 increased by 122.7% and NDCG@10 by 35.7%), ablation experiments illustrated the positive effect of our designed modules of HTINet2, and case study demonstrated the reliability of the predicted targets of Artemisia annua and Coptis chinensis based on the knowledge base, literature, and molecular docking. [ABSTRACT FROM AUTHOR]

The emergence of resistance to current antimalarial drugs poses a significant challenge in the fight against malaria. This study aimed to investigate the in vivo antiplasmodial potential of the aqueous extract of fresh and dried leaves of A3 in Plasmodium berghei‐infected (P. berghei) mice. A 4‐day suppressive test was conducted, with infected BALB/c mice receiving artesunate and A3 extracts. The results showed that the tested doses of A3 attenuated the elevation of parasitemia induced by P. berghei, particularly at the dose of 400 mg/kg, and improved hematological indices. Computational techniques, including molecular docking, binding free energy calculations, and ADMET predictions, identified several bioactive compounds in A3 with promising inhibitory potential against lysyl‐tRNA synthetases and Dihydrofolate reductase (DHFR), the crucial enzymes targeted by antimalarial drugs. In this paper, Friedelin, Bauerenol, Epifriedelanol, Alpha‐Amyrenone, Stigmasterol, and beta‐Amyrin acetate were top‐ranked, having docking scores from −10.6 to −9.9 kcal/mol, compared with the −9.4 and −7.1 kcal/mol demonstrated by artesunate and chloroquine, respectively, as standard ligands. Also, it was shown that docking score from the Lysyl‐tRNA protein target (4YCV) ranged from −9.5 to −7.8 kcal/mol in comparison to artesunate (8.1 kcal/mol) and chloroquine (5.6 kcal/mol). The results suggest that the identified compounds in A3 could serve as potential candidates for the development of new anti‐malarial agents. [ABSTRACT FROM AUTHOR]

Artemisia annua L. is the main source of artemisinin, an antimalarial drug. High diversity of morphological characteristics and artemisinin contents of A. annua has affected the stable production of artemisinin while efficient discrimination method of A. annua strains is not available. The complete chloroplast (cp) genomes of 38 A. annua strains were assembled and analyzed in this study. Phylogenetic analysis of Artemisia species showed that distinct intraspecific divergence occurred in A. annua strains. A total of 38 A. annua strains were divided into two distinct lineages, one lineage containing widely-distributed strains and the other lineage only containing strains from northern China. The A. annua cp genomes ranged from 150, 953 to 150, 974 bp and contained 131 genes, and no presence or absence variation of genes was observed. The IRs and SC junctions were located in rps19 and ycf1, respectively, without IR contraction observed. Rich sequence polymorphisms were observed among A. annua strains, and a total of 60 polymorphic sites representing 14 haplotypes were identified which unfolding the cpDNA heteroplasmy of A. annua. In conclusion, this study provided valuable resource for A. annua strains identification and provided new insights into the evolutionary characteristics of A. annua. [ABSTRACT FROM AUTHOR]

Summary Artemisinin, the well‐known natural product for treating malaria, is biosynthesised and stored in the glandular‐secreting trichomes (GSTs) of Artemisia annua. While numerous efforts have clarified artemisinin metabolism and regulation, the molecular association between artemisinin biosynthesis and GST development remains elusive. Here, we identified AaMYC3, a bHLH transcription factor of A. annua, induced by jasmonic acid (JA), which simultaneously regulates GST density and artemisinin biosynthesis. Overexpressing AaMYC3 led to a substantial increase in GST density and artemisinin accumulation. Conversely, in the RNAi‐AaMYC3 lines, both GST density and artemisinin content were markedly reduced. Through RNA‐seq and analyses conducted both in vivo and in vitro, AaMYC3 not only directly activates AaHD1 transcription, initiating GST development, but also up‐regulates the expression of artemisinin biosynthetic genes, including CYP71AV1 and ALDH1, thereby promoting artemisinin production. Furthermore, AaMYC3 acts as a co‐activator, interacting with AabHLH1 and AabHLH113, to trigger the transcription of two crucial enzymes in the artemisinin biosynthesis pathway, ADS and DBR2, ultimately boosting yield. Our findings highlight a critical connection between GST initiation and artemisinin biosynthesis in A. annua, providing a new target for molecular design breeding of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Diabetic mellitus (DM) is characterized by hyperglycaemia and defective macromolecular metabolism, arising from insulin resistance or lack of insulin production. The present study investigates the potential of artemisinin, a sesquiterpene lactone isolated from Artemisia annua, to exert anti-diabetic and antioxidant effects through modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway. Our computational analyses demonstrated a high binding affinity of artemisinin with proteins belonging to the PI3K/AKT signalling cascade. α-Amylase and α-glucosidase studies revealed a notable increase in inhibition percentages with artemisinin treatment across concentrations ranging from 10 to 160 µM. A similar significant (p < 0.05) dose-dependent inhibition of free radicals was observed for the in vitro anti-oxidant assays. Further, toxicological profiling of artemisinin in the in vivo zebrafish embryo-larvae model from 4 to 96 h post-fertilization (hpf) did not exhibit any harmful repercussions. In addition, gene expression investigations confirmed artemisinin's potential mechanism in modulating hyperglycaemia and oxidative stress through the regulation of the PI3K/AKT pathway. Overall, our investigation suggests that artemisinin can be used as a therapeutic intervention for diabetes and oxidative stress, opening up opportunities for future investigation in clinical settings. [ABSTRACT FROM AUTHOR]

Artemisinin is a natural sesquiterpene lactone obtained from the traditional Chinese medicinal herb Artemisia annua L. (qinghao). Artemisinin and its derivatives share an unusual endoperoxide bridge and are extensively used for malaria treatment worldwide. In addition to antimalarial activities, artemisinin and its derivatives have been reported to exhibit promising anticancer effects in recent decades. In this review, we focused on the research progress of artemisinin and its derivatives with potential anticancer activities. The pharmacological effects, potential mechanisms, and clinical trials in cancer therapy of artemisinin and its derivatives were discussed. This review may facilitate the future exploration of artemisinin and its derivatives as effective anticancer agents. [ABSTRACT FROM AUTHOR]

Background: Transcription factors (TFs) of plant-specific SHORT INTERNODES (SHI) family play a significant role in regulating development and metabolism in plants. In Artemisia annua, various TFs from different families have been discovered to regulate the accumulation of artemisinin. However, specific members of the SHI family in A. annua (AaSHIs) have not been identified to regulate the biosynthesis of artemisinin. Results: We found five AaSHI genes (AaSHI1 to AaSHI5) in the A. annua genome. The expression levels of AaSHI1, AaSHI2, AaSHI3 and AaSHI4 genes were higher in trichomes and young leaves, also induced by light and decreased when the plants were subjected to dark treatment. The expression pattern of these four AaSHI genes was consistent with the expression pattern of four structural genes of artemisinin biosynthesis and their specific regulatory factors. Dual-luciferase reporter assays, yeast one-hybrid assays, and transient transformation in A. annua provided the evidence that AaSHI1 could directly bind to the promoters of structural genes AaADS and AaCYP71AV1, and positively regulate their expressions. This study has presented candidate genes, with AaSHI1 in particular, that can be considered for the metabolic engineering of artemisinin biosynthesis in A. annua. Conclusions: Overall, a genome-wide analysis of the AaSHI TF family of A. annua was conducted. Five AaSHIs were identified in A. annua genome. Among the identified AaSHIs, AaSHI1 was found to be localized to the nucleus and activate the expression of structural genes of artemisinin biosynthesis including AaADS and AaCYP71AV1. These results indicated that AaSHI1 had positive roles in modulating artemisinin biosynthesis, providing candidate genes for obtaining high-quality new A. annua germplasms. [ABSTRACT FROM AUTHOR]

As the most effective therapeutic drug for malaria, artemisinin can only be extracted from Artemisia annua L., which is sensitive to the surrounding growing habitat. Histone acetyltransferases (HATs) contain acetyl groups, which modulate mRNA transcription and thereby regulate plant environmental adaptation. Comprehensive analyses of HATs have been performed in many plants, but systematic identification of HATs in medicinal plants is lacking. In the present study, we identified 11 AaHATs and characterized these genes into four classes according to their conserved protein structures. According to the phylogenetic analysis results, potential functions of HAT genes from Arabidopsis thaliana, Oryza sativa, and A. annua were found. According to our results, AaHAT has a highly conserved evolutionary history and is rich in highly variable regions; thus, AaHAT has become a comparatively ideal object of medical plant identification and systematic study. Moreover, motifs commonly present in histone acetyltransferases in the A. annua genome may be associated with functional AaHATs. AaHATs appear to be related to gene-specific functions. AaHATs are regulated by cis-elements, and these genes may affect phytohormone responsiveness, adaptability to stress, and developmental growth. We performed expression analyses to determine the potential roles of AaHATs in response to three environmental stresses. Our results revealed a cluster of AaHATs that potentially plays a role in the response of plants to dynamic environments. [ABSTRACT FROM AUTHOR]

The sesquiterpene lactone artemisinin is an important anti‐malarial component produced by the glandular secretory trichomes of sweet wormwood (Artemisia annua L.). Light was previously shown to promote artemisinin production, but the underlying regulatory mechanism remains elusive. In this study, we demonstrate that ELONGATED HYPOCOTYL 5 (HY5), a central transcription factor in the light signaling pathway, cannot promote artemisinin biosynthesis on its own, as the binding of AaHY5 to the promoters of artemisinin biosynthetic genes failed to activate their transcription. Transcriptome analysis and yeast two‐hybrid screening revealed the B‐box transcription factor AaBBX21 as a potential interactor with AaHY5. AaBBX21 showed a trichome‐specific expression pattern. Additionally, the AaBBX21–AaHY5 complex cooperatively activated transcription from the promoters of the downstream genes AaGSW1, AaMYB108, and AaORA, encoding positive regulators of artemisinin biosynthesis. Moreover, AaHY5 and AaBBX21 physically interacted with the A. annua E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1). In the dark, AaCOP1 decreased the accumulation of AaHY5 and AaBBX21 and repressed the activation of genes downstream of the AaHY5–AaBBX21 complex, explaining the enhanced production of artemisinin upon light exposure. Our study provides insights into the central regulatory mechanism by which light governs terpenoid biosynthesis in the plant kingdom. [ABSTRACT FROM AUTHOR]

BackgroundSheep coccidiosis could disturb the balance of intestinal microbiota, causing diarrhea, and even death in lambs. Chemical drugs are the primary method of treating sheep coccidiosis, but their use will bring drug resistance, toxic side effects, drug residues, and other problems. Chinese herbal medicines are investigated as alternative methods for controlling coccidian infections.MethodsIn this study, the effect of fermented Artemisia annua (FA) on oocysts per gram (OPG), average daily gain (ADG), and expression of inflammatory factors were investigated in lambs that were naturally infected with coccidia.ResultsThe results showed that the FA had similar anti-coccidiosis effect to the original drug, while the FA demonstrated a more significant effect on weight gain, and a better ability to reduce the inflammatory response compared to the unfermented drug during the treatment period (P < 0.05). Furthermore, High-throughput sequencing technology was used to study the effects of FA on intestinal microbiota, and fecal metabolites of naturally infected lambs. The species richness of intestinal microbiota of lambs was significantly improved by FA. The abundance of bacteria unclassified_Muribaculaceae, and UCG_005 were increased by fermentation of A. annua. The abundance of bacteria Escherichia_Shigella, unclassified_Clostridia_UCG_014, and Alistipes was reduced. The prevention, and treatment of coccidiosis by fermentation of A. annua may also be related to a series of metabolites affected by intestinal microbiota, including artemisinin, Lysyl-Proline, and TRP-tyrosine.ConclusionFA was found to have superior anti-coccidiosis, anti-inflammatory, and weight gain effects compared to the original Artemisia annua. Intestinal microbes and metabolites such as unclassified_Muribaculaceae, UCG-005, and Artemisinin were identified, suggesting their potential significance. Alistipes was proposed as a biomarker for predicting intestinal coccidia outbreak risk in lambs, pending further validation. The correlation between microbiota, and metabolites may provide new insights into pathogenic changes associated with Eimeria spp.

The citrus nematode (Tylenchulus semipentrans) is one of the most important parasitic nematodes affecting citrus trees, causing gradual decline and reduced yield. Potential risks, high costs and environmental consequences of chemical compounds have led researchers to explore non-chemical methods such as using plant-based products for nematode management. The present study was conducted to control citrus nematodes using essential oil and water extract of Artemisia annua and methanolic extract of Melia azederach under laboratory and greenhouse conditions. In vitro bioassays were carried out, and the effects on toxicity, mortality, and egg hatching were assessed. The highest in vitro nematistatic activity was recorded for 250 ppm of A. annua essential oil and 500 ppm of M. azederach methanol extract by 100% paralysis of nematodes after 48 h. Furthermore, the highest nematicidal activity of A. annua essential oil, aqueous extract and methanolic extract of M. azederach was recorded to be about 60−100%, 40−87% and 38−100%, respectively. Among all concentrations of M. azederach methanolic extract and high concentrations of A. annua essential oil and aqueous extract, the repellents and motility inhibitors for nematodes were found. The results of egg hatching showed that essential oil of A. annua at a concentration of 250 ppm had the greatest reduction of egg hatching. In a greenhouse experiment, all the treatments were found to be significantly effective against the citrus nematode population in soil and roots compared to the control. Maximum reduction was observed in 500 ppm of methanolic extract of Melia azederach. Growth parameters (plant height, fresh and dry shoot and root weight) increased compared to the control when treatments were applied. Based on the results, plants such as A. annua and M. azedarach are considered to be promising control agents for citrus nematodes. The results indicate that products derived from these plants may be potential candidates for formulating new nematicides suitable for sustainable nematode management, although field trials are still needed to demonstrate their effectiveness for commercial use.

Background and Aim: Artemisia annua (AA), used as a growth promoter in poultry, lowers feed costs and enhances economic efficiency. This study aimed to assess the impact of varying AA concentrations on broiler chicken growth, gene expression, and profitability. Materials and Methods: Two hundred 1-day-old male Cobb chicks were randomly allocated into four treatment groups, each containing five replicates and 10 birds. The experimental groups consisted of G1 (basal diet), G2 (basal diet with 0.3% AA), G3 (basal diet with 0.6% AA), and G4 (basal diet with 0.9% AA). The birds had continuous access to feed and water throughout the study. The experiment lasted for 42 days. we measured the growth performance (Feed intake, Life weight), carcass traits (weight after slaughter, dressed carcass, heart, gizzard, spleen, giblet and thymus weight), liver and spleen antioxidants (CAT, GSH, SOD), and gene expression of anti-inflammatory and immune- related genes. Results: The primary findings revealed that the addition of 0.6% AA had a positive impact (p < 0.05) on all investigated variables compared with the control and other groups. Dietary supplementation with 0.6% AA led to increased breast, giblet, skeleton, and total yield, and net return compared with the control group. Supplementation with AA exhibited antioxidant, anti-inflammatory, and immunological effects through improved levels of antioxidant superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in tissue homogenates of the liver and spleen. It also upregulated the relative messenger RNA levels of anti-inflammatory interleukin (IL)-10, SOD, CAT, and GSH-Px, whereas IL-1β and tumor necrosis factor-alpha were downregulated. Conclusion: The study found that AA is a promising replacement for antibiotics in poultry farming as a growth promoter for chickens. 0.6% AA in the broiler diet yielded the best results, striking a balance between superior performance and robust economic benefits.

Abstract Background In November 2019, the world faced a pandemic called SARS-CoV-2, which became a major threat to humans and continues to be. To overcome this, many plants were explored to find a cure. Methods Therefore, this research was planned to screen out the active constituents from Artemisia annua that can work against the viral main protease Mpro as this non-structural protein is responsible for the cleavage of replicating enzymes of the virus. Twenty-five biocompounds belonging to different classes namely alpha-pinene, beta-pinene, carvone, myrtenol, quinic acid, caffeic acid, quercetin, rutin, apigenin, chrysoplenetin, arteannunin b, artemisinin, scopoletin, scoparone, artemisinic acid, deoxyartemisnin, artemetin, casticin, sitogluside, beta-sitosterol, dihydroartemisinin, scopolin, artemether, artemotil, artesunate were selected. Virtual screening of these ligands was carried out against drug target Mpro by CB dock. Results Quercetin, rutin, casticin, chrysoplenetin, apigenin, artemetin, artesunate, sopolin and sito-gluside were found as hit compounds. Further, ADMET screening was conducted which represented Chrysoplenetin as a lead compound. Azithromycin was used as a standard drug. The interactions were studied by PyMol and visualized in LigPlot. Furthermore, the RMSD graph shows fluctuations at various points at the start of simulation in Top1 (Azithromycin) complex system due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points resulting in increased RMSD with a time frame of 50 ns. But this change remains stable after the extension of simulation time intervals till 100 ns. On other side, the Top2 complex system remains highly stable throughout the time scale. No such structural dynamics were observed bu the ligand attached to the active site residues binds strongly. Conclusion This study facilitates researchers to develop and discover more effective and specific therapeutic agents against SARS-CoV-2 and other viral infections. Finally, chrysoplenetin was identified as a more potent drug candidate to act against the viral main protease, which in the future can be helpful.

Synucleinopathies, typified by Parkinson’s disease (PD), entail the accumulation of α-synuclein (αSyn) aggregates in nerve cells. Various αSyn mutants, including the αSyn A53T variant linked to early-onset PD, increase the propensity for αSyn aggregate formation. In addition to disrupting protein homeostasis and inducing proteostatic stress, the aggregation of αSyn in PD is associated with an imbalance in iron metabolism, which increases the generation of reactive oxygen species and causes oxidative stress. This study explored the impact of αSyn A53T expression in transgenic hairy roots of four medicinal plants (Lobelia cardinalis, Artemisia annua, Salvia miltiorrhiza, and Polygonum multiflorum). In all tested plants, αSyn A53T expression triggered proteotoxic stress and perturbed iron homeostasis, mirroring the molecular profile observed in human and animal nerve cells. In addition to the common eukaryotic defense mechanisms against proteostatic and oxidative stresses, a plant stress response generally includes the biosynthesis of a diverse set of protective secondary metabolites. Therefore, the hairy root cultures expressing αSyn A53T offer a platform for identifying secondary metabolites that can ameliorate the effects of αSyn, thereby aiding in the development of possible PD treatments and/or treatments of synucleinopathies.

Artesunate (ART), a natural product isolated from traditional Chinese plant Artemisia annua, has not been extensively explored for its anti-melanoma properties. In our study, we found that ART inhibited melanoma cell proliferation and induced melanoma cell ferroptosis. Mechanistic study revealed that ART directly targets Ido1, thereby suppressing Hic1-mediated transcription suppression of Hmox1, resulting in melanoma cell ferroptosis. In CD8+ T cells, ART does not cause cell ferroptosis due to the low expression of Hmox1. It also targets Ido1, elevating tryptophan levels, which inhibits NFATc1-mediated PD1 transcription, consequently activating CD8+ T cells. Our study uncovered a potent and synergistic anti-melanoma efficacy arising from ART-induced melanoma cell ferroptosis and concurrently enhancing CD8+ T cell-mediated immune response both in vivo and in vitro through directly targeting Ido1. Our study provides a novel mechanistic basis for the utilization of ART as an Ido1 inhibitor and application in clinical melanoma treatment. [ABSTRACT FROM AUTHOR]

Malaria, transmitted through the bite of a Plasmodium-infected Anopheles mosquito, remains a significant global health concern. This review examines the complex life cycle of Plasmodium, emphasizing the role of humans and mosquitoes in its transmission and proliferation. Malarial parasites are transmitted as sporozoites to the human body by biting an infected female Anopheles mosquito. These sporozoites then invade liver cells, multiply, and release merozoites, which infect red blood cells, perpetuating the cycle. As this cycle continues, the affected person starts experiencing the clinical symptoms of the disease. The current treatments for malaria, including chloroquine, artemisininbased combination therapy, and quinine, are discussed alongside the challenges of drug resistance and misdiagnosis. Although efforts have been made to develop a malarial vaccine, they have so far been unsuccessful. Additionally, the review explores the potential of medicinal plants as remedies for malaria, highlighting the efficacy of compounds derived from Artemisia annua, Cinchona species, and Helianthus annuus L., as well as exploration of plants and phytocompounds like cryptolepine, and isoliquiritigenin against drug-resistant Plasmodium species. Moreover, studies from Pakistan further highlight the diverse vegetal resources utilized in malaria treatment, emphasizing the need for further research into natural remedies. Despite the advantages of herbal medicines, including costeffectiveness, and fewer side effects; their limitations must be taken into account, including variations in potency and potential drug interactions. The review concludes by advocating for a balanced approach to malaria treatment and prevention, emphasizing the importance of early detection, accurate diagnosis, and integrated efforts to combat the disease in the endemic regions. [ABSTRACT FROM AUTHOR]

Trichomes are known to be important biofactories that contribute to the production of secondary metabolites, such as terpenoids. C2H2‐zinc finger proteins (C2H2‐ZFPs) are vital transcription factors of plants' trichome development. However, little is known about the function of Artemisia annua C2H2‐ZFPs in trichome development. To explore the roles of this gene family in trichome development, two C2H2‐ZFP transcription factors, named AaZFP8L and AaGIS3, were identified; both are hormonally regulated in A. annua. Overexpression of AaZFP8L in tobacco led to a significant increase in the density and length of glandular trichomes, and improved terpenoid content. In contrast, AaGIS3 was found to positively regulate non‐glandular trichome initiation and elongation, which reduces terpenoid accumulation. In addition, ABA contents significantly increased in AaZFP8L‐overexpressing tobacco lines and AaZFP8L also can directly bind the promoter of the ABA biosynthesis genes. This study lays the foundation for further investigating A. annua C2H2‐ZFPs in trichome development and terpenoid accumulation. [ABSTRACT FROM AUTHOR]

The expected progress in SARS-CoV-2 vaccinations, as anticipated in 2020 and 2021, has fallen short, exacerbating global disparities due to a lack of universally recognized "safe and effective" vaccines. This study focuses on extracts of South African medicinal plants, Artemisia annua and Artemisia afra, to identify metabolomic bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors. The extracts were monitored for cytotoxicity using a resazurin cell viability assay and xCELLigence real-time cell analyzer. Chemical profiling was performed using UPLC-MS/MS, orthogonal projection to latent structures (OPLS), and evaluated using principle component analysis (PCA) models. Identified bioactive compounds were subjected to in vitro SARS-CoV-2 enzyme inhibition assay using standard methods and docked into the spike (S) glycoprotein of SARS-CoV-2 using Schrodinger® suite followed by molecular dynamics simulation studies. Cell viability assays revealed non-toxic effects of extracts on HEK293T cells at lower concentrations. Chemical profiling identified 81 bioactive compounds, with compounds like 6″-O-acetylglycitin, 25-hydroxyvitamin D3-26,23-lactone, and sesaminol glucoside showing promising binding affinity. Molecular dynamics simulations suggested less stable binding, but in vitro studies demonstrated the ability of these compounds to interfere with SARS-CoV-2 spike protein's binding to the human ACE2 receptor. Sesaminol glucoside emerged as the most effective inhibitor against this interaction. This study emphasizes the importance of multiplatform metabolite profiling and chemometrics to understand plant extract composition. This finding is of immense significance in terms of unravelling metabolomics bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors and holds promise for phytotherapeutics against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Malaria is a mosquito-borne, life-threatening illness caused by the parasite, Plasmodium. Around 50% of the world’s population is endangered by this infectious disease. The antimalarial drug, artemisinin (ART), which is extracted from the plant Artemisia annua, has become a fundamental part of the treatment regime for malaria across the world. The use of ART-based combination therapies against uncomplicated malaria has been endorsed by the World Health Organization (WHO). As per the latest World Malaria Report in 2022, around 247 million malaria cases were reported in 2021 from 84 malariaendemic nations, including the territory of French Guiana, a considerable upsurge from the 245 million reported in 2020. One of the foremost reasons for this increase was linked with disturbances to services for prevention, diagnosis, and treatment measures during the recent COVID-19 pandemic. On October 6, 2021, the WHO suggested the RTS,S vaccine as the first malaria vaccine to be used against Plasmodium falciparum malaria in children residing in areas with moderate to high transmission. In July 2022, the WHO granted prequalification support for this vaccine. Over one million children living in African countries, mainly in Ghana, Kenya, and Malawi, have gotten at least one dose of this groundbreaking malaria vaccine through programs coordinated by the WHO, as well as international and country-level partners. RTS,S is a significant initial step in the path to the production of other highly protective and multi-stage vaccines that may become part of malaria eradication programs in the near future. Several malariologists are working on the early clinical development or trial phases of first-generation and next-generation malaria vaccines, such as R21/Matrix-M, using mRNA technology. [ABSTRACT FROM AUTHOR]