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1.
Ying Yong Sheng Tai Xue Bao ; 35(7): 1753-1761, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39233403

RESUMEN

Warming drives material cycling in terrestrial ecosystems by affecting litter decomposition, as it can alter litter yield, quality and decomposer composition and activity. The effect of warming on the decomposition of mixed litter in arid and semi-arid zones remains unknown. We investigated the mass loss and nutrient release dynamics during 450 days of decomposition of Artemisia ordosica, Leymus secalinus, and their mixture in Mu Us Desert by open-top chambers and litter bags. The results showed interspecific differences in the responses to warming, in that warming promoted mass loss and N and P release from L. secalinus and inhibited mass loss and P but promoting N release from A. ordosica. Mixing of A. ordosica and L. secalinus litter inhibited decomposition. Warming enhanced the antagonistic effects of mixed decomposition. The total mass loss of mixed litter was decreased by 9%, and the release of N and P was decreased by 4.9% and 12.6%, respectively. The antagonistic effects of mixed litter mass loss and P release under the warming treatment gradually strengthened with time, with N release changing from a synergistic to an antagonistic effect at 150 d. The non-additive effects produced by the mixed decomposition of A. ordosica and L. secalinus litter were jointly regulated by temperature and time. Future research on mixed litter decomposition should consider the interaction between temperature and time.


Asunto(s)
Artemisia , Clima Desértico , Artemisia/crecimiento & desarrollo , Artemisia/química , China , Poaceae/crecimiento & desarrollo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Nitrógeno/análisis , Nitrógeno/química , Ecosistema , Fósforo/química , Fósforo/análisis , Factores de Tiempo , Calor , Calentamiento Global
2.
Org Biomol Chem ; 22(34): 7006-7016, 2024 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-39135436

RESUMEN

The COVID-19 pandemic has spread throughout the whole globe, so it is imperative that all available resources be used to treat this scourge. In reality, the development of new pharmaceuticals has mostly benefited from natural products. The widespread medicinal usage of species in the Asteraceae family is extensively researched. In this study, compounds isolated from methanolic extract of Artemisia monosperma Delile, a wild plant whose grows in Egypt's Sinai Peninsula. Three compounds, stigmasterol 3-O-ß-D-glucopyranoside 1, rhamnetin 3, and padmatin 6, were first isolated from this species. In addition, five previously reported compounds, arcapillin 2, jaceosidin 4, hispidulin 5, 7-O-methyleriodictyol 7, and eupatilin 8, were isolated. Applying molecular modelling simulations revealed two compounds, arcapillin 2 and rhamnetin 3 with the best docking interactions and energies within SARS-CoV-2 Mpro-binding site (-6.16, and -6.70 kcal mol-1, respectively). The top-docked compounds (2-3) were further evaluated for inhibitory concentrations (IC50), and half-maximal cytotoxicity (CC50) of both SARS-CoV-2 and MERS-CoV. Interestingly, arcapillin showed high antiviral activity towards SARS-CoV-2 and MERS-CoV, with IC50 values of 190.8 µg mL-1 and 16.58 µg mL-1, respectively. These findings may hold promise for further preclinical and clinical research, particularly on arcapillin itself or in collaboration with other drugs for COVID-19 treatment.


Asunto(s)
Antivirales , Artemisia , Coronavirus del Síndrome Respiratorio de Oriente Medio , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Artemisia/química , Antivirales/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , SARS-CoV-2/efectos de los fármacos , Coronavirus del Síndrome Respiratorio de Oriente Medio/efectos de los fármacos , Humanos , Chlorocebus aethiops , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Proteasas 3C de Coronavirus/química , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Células Vero , Modelos Moleculares
3.
Phytomedicine ; 133: 155927, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39096543

RESUMEN

BACKGROUND: Moxibustion, a traditional Chinese medicine practice, employs Moxa Wool, derived from Artemisia argyi. Flavonoids, the key pharmacological constituents in Moxa Wool, are known for their anti-inflammatory and analgesic properties. The purity of Moxa Wool, particularly its flavonoid content, directly influences the efficacy of moxibustion treatments. However, quantifying these bioactive flavonoids accurately and non-destructively has been a challenge. PURPOSE: This study introduces terahertz spectroscopy as a non-destructive optical detection method for qualitative detection and quantitative analysis of flavonoids in Moxa Wool. By establishing a mathematical model between spectral signals and clinical efficacy, a reliable correlation between flavonoid concentration and the therapeutic effect of moxibustion can be established, providing a potential predictive model for the treatment outcomes of rheumatoid arthritis. STUDY DESIGN: We adopted terahertz spectroscopy technology and combined it with terahertz metamaterial biosensors to achieve rapid, efficient, and non-destructive testing of the quality of Moxa Wool. This method reduces the detection time from hours to minutes while lowering the sample detection limit, overcoming the limitations of traditional detection methods in pharmacological research. METHODS: Through terahertz metamaterial biosensors, rapid detection of the purity of Moxa Wool has been achieved. A combination of molecular simulation and terahertz spectroscopy was used to quantitatively analyze the flavonoid content in different purities of Moxa Wool. To ensure accuracy, the quantitative results of flavonoids obtained by terahertz spectroscopy were validated using high-performance liquid chromatography (HPLC). In addition, moxibustion treatment was performed on rats with rheumatoid arthritis using Moxa Wool, and medical indicator information was recorded. A mathematical analysis model was established to evaluate the correlation between flavonoid content and analgesic and anti-inflammatory effects. RESULTS: Terahertz spectroscopy analysis shows that there is a direct correlation between the flavonoid content in moxibustion and the absorption peak intensity. The maximum R2 in the model analysis is 0.98, indicating a high accuracy in predicting the purity of Moxa Wool. These results were also validated by HPLC. In a rat model, the purity of 30:1 Moxa Wool samples showed a 50 % decrease in TNF-α, IL-1ß, and IL-6 levels during treatment compared to low-purity samples, significantly reducing inflammation markers and pain symptoms. Meanwhile, The PLS prediction model established a correlation between terahertz-detected flavonoid levels and treatment outcomes (PWL and IL-1ß). The maximum R2 in the model is 0.91, indicating a high correlation between flavonoid levels and the anti-inflammatory and analgesic effects of moxibustion treatment. CONCLUSION: This study not only demonstrates the effectiveness of terahertz spectroscopy in the pharmacological quantification of bioactive compounds but also establishes a novel predictive model for the efficacy of moxibustion in rheumatoid arthritis treatment. It underscores the potential of integrating traditional medicine insights with advanced technology to enhance therapeutic strategies in pharmacology.


Asunto(s)
Artritis Reumatoide , Flavonoides , Moxibustión , Espectroscopía de Terahertz , Flavonoides/análisis , Animales , Moxibustión/métodos , Artritis Reumatoide/terapia , Artritis Reumatoide/tratamiento farmacológico , Espectroscopía de Terahertz/métodos , Ratas , Artemisia/química , Ratas Sprague-Dawley , Resultado del Tratamiento , Masculino , Artritis Experimental/terapia , Antiinflamatorios/química , Medicina Tradicional China , Lana/química
4.
J Ethnopharmacol ; 334: 118519, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38971340

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Vietnamese people use mugwort (Artemisia vulgaris L.) to treat arthritis and gout. Our previous research shows that mugwort contains flavonoids, and its extract possesses antibacterial and anti-inflammatory activities. However, no publications have been on the xanthine oxidase inhibitory activity of mugwort and acute anti-inflammatory activity in vivo. AIM OF THE STUDY: The study aimed to verify the antioxidant, xanthine oxidase inhibitory, and anti-inflammatory capabilities of mugwort extract in vitro and in vivo, isolate phyto-compounds from potential bioactive fractions, and then evaluate their potential in inhibiting xanthine oxidase. METHODS: According to established methods, the extract and the active flavonoids were obtained using different chromatographic techniques. DPPH, ABTS, reducing power, and H2O2 elimination were used to evaluate antioxidant activity. The model of LPS-induced RAW264.7 cells was used to measure the inhibition of NO production. The carrageenan-induced paw oedema model was used to assess acute inflammation in mice. In vitro, xanthine oxidase inhibition assay was applied to investigate the effects of extract/compounds on uric acid production. Chemical structures were identified by spectral analysis. RESULTS: The assessment of the acute inflammatory model in mice revealed that both the 96% ethanol and the 50% ethanol extracts significantly decreased oedema in the mice's feet following carrageenan-induced inflammation. 96% ethanol extract exhibited a better reduction in oedema at the low dose. The analysis revealed that the ethyl acetate fraction had the highest levels of total polyphenols and flavonoids. Additionally, this fraction demonstrated significant antioxidant activity in various assays, such as DPPH, ABTS, reducing power, and H2O2 removal. Furthermore, it displayed the most potent inhibition of xanthine oxidase, an anti-inflammatory activity. Five phytochemicals were isolated and determined from the active fraction such as luteolin (1), rutin (2), apigenin (3), myricetin (4), and quercetin (5). Except for rutin, the other compounds demonstrated the ability to inhibit effective xanthine oxidase compared to standard (allopurinol). Moreover, quercetin (5) inhibited NO production (IC50 21.87 µM). CONCLUSION: The results indicate that extracts from A. vulgaris effectively suppressed the activity of xanthine oxidase and exhibited antioxidant and anti-inflammatory properties, potentially leading to a reduction in the production of uric acid in the body and eliminating ROS. The study identified mugwort extract and bioactive compounds derived from Artemisia vulgaris, specifically luteolin, apigenin, and quercetin, as promising xanthine oxidase inhibitors. These findings suggest that further development of these compounds is warranted. At the same time, the above results also strengthen the use of mugwort to treat gout disease in Vietnam.


Asunto(s)
Antiinflamatorios , Antioxidantes , Artemisia , Edema , Extractos Vegetales , Xantina Oxidasa , Animales , Xantina Oxidasa/antagonistas & inhibidores , Xantina Oxidasa/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Ratones , Células RAW 264.7 , Edema/tratamiento farmacológico , Edema/inducido químicamente , Artemisia/química , Masculino , Ácido Úrico , Flavonoides/farmacología , Óxido Nítrico/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Carragenina
5.
J Ethnopharmacol ; 334: 118580, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39019419

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Artemisia argyi Levl.et Vant. have a long history of being used to treat skin diseases such as pruritus and dermatitis in China, but the therapeutic effect on allergic contact dermatitis (ACD) is still unclear. AIM OF THE STUDY: To investigate the effect and molecular mechanisms of the volatile oil of A. argyi leaves (abbreviated as 'AO') in the treatment of ACD. MATERIALS AND METHODS: The main components in AO were analyzed using GC-MS. The effect of AO on channel currents in hTRPA1-transfected HEK293T cells was studied by whole-cell patch clamp. Subsequently, chloroquine-evoked acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch model was established to evaluate the antipruritic effect through counting scratching behavior, and the anti-inflammatory effects on ACD mice were measured using histological analysis. Meanwhile, the changes of CGRP, the infiltration of nerve fibers and the recruitment of dendritic cells, the expression of Il-23 and Il-17 mRNA in skin lesions, the phosphorylation of ERK and p38 in dorsal root ganglion (DRG), were evaluated by molecular biological methods. Then the inhibitory effect of AO on AITC- or SADBE-activated TRPA1 channels in primary DRG neurons of C57BL/6, Trpa1-/- or Trpv1-/- mice was elucidated by Ca2+ imaging and immunofluorescence. RESULTS: AO treatment inhibited the activation of TRPA1 in HEK293T cells and alleviated acute itch caused by chloroquine, but this effect was lacking in Trpa1-/- mice. Furthermore, administration of AO attenuated scratching behavior in SADBE-induced ACD mice. AO also inhibited the increase of nerve fibers and recruitment of dendritic cells, and down-regulated the expression of CGRP and the levels of Il-23 and Il-17 mRNA. Meanwhile, AO reduced the expression of p-p38 and p-ERK in the lesioned skin and DRG of SADBE-induced ACD mice. Additionally, AO blocked the activation of TRPA1 channels and decreased the levels of CGRP, p-p38, and p-ERK in DRG neurons. CONCLUSION: AO could inhibit TRPA1 channels in sensory neurons, thereby reducing the release of CGRP and exerting anti-pruritic and anti-inflammatory effect. These findings also provide a new strategy for exploring the role of A. argyi in treating ACD.


Asunto(s)
Artemisia , Péptido Relacionado con Gen de Calcitonina , Dermatitis Alérgica por Contacto , Ratones Endogámicos C57BL , Aceites Volátiles , Transducción de Señal , Canal Catiónico TRPA1 , Animales , Canal Catiónico TRPA1/metabolismo , Humanos , Péptido Relacionado con Gen de Calcitonina/metabolismo , Péptido Relacionado con Gen de Calcitonina/genética , Artemisia/química , Células HEK293 , Transducción de Señal/efectos de los fármacos , Ratones , Masculino , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/metabolismo , Aceites Volátiles/farmacología , Prurito/tratamiento farmacológico , Prurito/inducido químicamente , Ratones Noqueados , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Hojas de la Planta/química , Modelos Animales de Enfermedad , Antipruriginosos/farmacología , Antipruriginosos/uso terapéutico
6.
J Ethnopharmacol ; 334: 118590, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39029542

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia stechmanniana Besser, one of the most prevalent botanical medicines in Chinese, has been traditionally used for hepatitis treatment. However, the bioactive components and pharmacological mechanism on alcohol-induced liver injury remains unclear. AIM OF THE STUDY: To investigate the effect of A. stechmanniana on alcohol-induced liver damage, and further explore its mechanism. MATERIALS AND METHODS: Phytochemical isolation and structural identification were used to determine the chemical constituents of A. stechmanniana. Then, the alcohol-induced liver damage animal and cell model were established to evaluate its hepato-protective potential. Network pharmacology, molecular docking and bioinformatics were integrated to explore the mechanism and then the prediction was further supported by experiments. Moreover, both compounds were subjected to ADMET prediction through relevant databases. RESULTS: 28 compounds were isolated from the most bioactive fraction, ethyl acetate extract A. stechmanniana, in which five compounds (abietic acid, oplopanone, oplodiol, hydroxydavanone, linoleic acid) could attenuate mice livers damage caused by alcohol intragastration, reduce the degree of oxidative stress, and serum AST and ALT, respectively. Furthermore, abietic acid and hydroxydavanone exhibited best protective effect against alcohol-stimulated L-O2 cells injury among five bioactive compounds. Network pharmacology and bioinformatics analysis suggested that abietic acid and hydroxydavanone exhibiting drug likeliness characteristics, were the principal active compounds acting on liver injury treatment, primarily impacting to cell proliferation, oxidative stress and inflammation-related PI3K-AKT signaling pathways. Both of them displayed strong binding energies with five target proteins (HRAS, HSP90AA1, AKT1, CDK2, NF-κB p65) via molecular docking. Western blotting results further supported the predication with up-regulation of protein expressions of CDK2, and down-regulation of HRAS, HSP90AA1, AKT1, NF-κB p65 by abietic acid and hydroxydavanone. CONCLUSION: Alcohol-induced liver injury protection by A. stechmanniana was verified in vivo and in vitro expanded its traditional use, and its two major bioactive compounds, abietic acid and hydroxydavanone exerted hepatoprotective effect through the regulation of PI3K-AKT signaling pathway.


Asunto(s)
Artemisia , Simulación del Acoplamiento Molecular , Extractos Vegetales , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Artemisia/química , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Masculino , Transducción de Señal/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fosfatidilinositol 3-Quinasas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Etanol/química , Línea Celular , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Sustancias Protectoras/farmacología , Hepatopatías Alcohólicas/prevención & control , Hepatopatías Alcohólicas/tratamiento farmacológico , Humanos
7.
Int Immunopharmacol ; 139: 112733, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39043105

RESUMEN

Psoriasis is an inflammatory immune-mediated skin disease that affects nearly 2-3 % of the global population. The current study aimed to develop safe and efficient anti-psoriatic nanoformulations from Artemisia monosperma essential oil (EO). EO was extracted using hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and head-space solid-phase microextraction (HS-SPME), as well as GC/ MS was used for its analysis. EO nanoemulsion (NE) was prepared using the phase inversion method, while the biodegradable polymeric film (BF) was prepared using the solvent casting technique. A.monosperma EO contains a high percentage of non-oxygenated compounds, being 90.45 (HD), 82.62 (MADH), and 95.17 (HS-SPME). Acenaphthene represents the major aromatic hydrocarbon in HD (39.14 %) and MADH (48.60 %), while sabinene as monoterpene hydrocarbon (44.2 %) is the primary compound in the case of HS-SPME. The anti-psoriatic Effect of NE and BF on the successful delivery of A.monosperma EO was studied using the imiquimod (IMQ)-induced psoriatic model in mice. Five groups (n = 6 mice) were classified into control group, IMQ group, IMQ+standard group, IMQ+NE group, and IMQ+BF group. NE and BF significantly alleviated the psoriatic skin lesions and decreased the psoriasis area severity index, Baker's score, and spleen index. Also, they reduced the expression of Ki67 and attenuated the levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 17. Additionally, NE and NF were able to downregulate the NF-κB and GSK-3ß signaling pathways. Despite the healing properties of BF, NE showed a more prominent effect on treating the psoriatic model, which could be referred to as its high skin penetration ability and absorption. These results potentially contribute to documenting experimental and theoretical evidence for the clinical uses of A.monosperma EO nanoformulations for treating psoriasis.


Asunto(s)
Artemisia , Imiquimod , Aceites Volátiles , Psoriasis , Animales , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Artemisia/química , Aceites Volátiles/uso terapéutico , Aceites Volátiles/química , Ratones , Humanos , Piel/efectos de los fármacos , Piel/patología , Modelos Animales de Enfermedad , Citocinas/metabolismo , Nanopartículas/química , Ratones Endogámicos BALB C , Femenino , Masculino , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Emulsiones
8.
Int Immunopharmacol ; 139: 112720, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39047450

RESUMEN

Periodontitis is a widely prevalent oral disease around the world characterized by the disruption of the periodontal ligament and the subsequent development of periodontal pockets, as well as the loss of alveolar bone, and may eventually lead to tooth loss. This research aims to assess the suppressive impact of Eupatilin, a flavone obtained from Artemisia argyi, on osteoclastogenesis in vitro and periodontitis in vivo. We found that Eupatilin can efficiently obstruct the differentiation of Raw264.7 and bone marrow-derived macrophages (BMDMs) induced by RANKL, leading to the formation of mature osteoclasts. Consistently, bone slice resorption assay showed that Eupatilin significantly inhibited osteoclast-mediated bone resorption in a dose-dependent manner. Eupatilin also downregulated the expression of osteoclast-specific genes and proteins in Raw264.7 and BMDMs. RNA sequencing showed that Eupatilin notably downregulated the expression of Siglec-15. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified significantly enriched pathways in DEGs, including MAPK signaling pathway. And further mechanistic investigations confirmed that Eupatilin repressed MAPKs/NF-κBsignaling pathways. It was found that Siglec-15 overexpression reversed the inhibitory impact of Eupatilin on the differentiation of osteoclasts. Furthermore, activating MAPK signaling pathway reversed the downregulation of Siglec-15 and the inhibition of osteoclastogenesis by Eupatilin. To sum up, Eupatilin reduced the expression of Siglec-15 by suppressing MAPK signaling pathway, ultimately leading to the inhibition of osteoclastogenesis. Meanwhile, Eupatilin suppressed the alveolar bone resorption caused by experimentalperiodontitis in vivo. Eupatilin exhibits potential therapeutic effects in the treatment of periodontitis, rendering it a promising pharmaceutical agent.


Asunto(s)
Pérdida de Hueso Alveolar , Flavonoides , Osteoclastos , Osteogénesis , Periodontitis , Animales , Ratones , Osteogénesis/efectos de los fármacos , Células RAW 264.7 , Flavonoides/farmacología , Flavonoides/uso terapéutico , Pérdida de Hueso Alveolar/tratamiento farmacológico , Osteoclastos/efectos de los fármacos , Periodontitis/tratamiento farmacológico , Ratones Endogámicos C57BL , Diferenciación Celular/efectos de los fármacos , Masculino , Macrófagos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Artemisia/química , Ligando RANK/metabolismo
9.
J Toxicol Environ Health A ; 87(20): 836-854, 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39028276

RESUMEN

Inflammatory Bowel Disease-Associated Arthritis (IBD-associated arthritis) poses a significant challenge, intertwining the complexities of both inflammatory bowel disease (IBD) and arthritis, significantly compromising patient quality of life. While existing medications offer relief, these drugs often initiate adverse effects, necessitating the requirement for safer therapeutic alternatives. Artemisia herba-alba, a traditional medicinal plant known for its anti-inflammatory properties, emerges as a potential candidate. Our computational study focused on examining 20 bioactive compounds derived from A. herba-alba for potential treatment of IBD-associated arthritis. These compounds detected in A. herba-alba include camphor, alpha-thujone, eucalyptol, cis-chrysanthenyl acetate, vicenin-2, 4,5-di-O-caffeoylquinic acid, chlorogenic acid, hispidulin, isoschaftoside, isovitexin, patuletin-3-glucoside, vanillic acid, rutin, schaftoside, lopinavir, nelfinavir, quercetin, artemisinin, gallic acid, and cinnamic acid. Following rigorous analysis encompassing pharmacokinetics, toxicity profiles, and therapeutic targets, compounds with favorable, beneficial characteristics were identified. In addition, comparative analysis with disease-gene associations demonstrated the interconnectedness of inflammatory pathways across diseases. Molecular docking studies provided mechanistic insights indicating this natural plant components potential to modulate critical inflammatory pathways. Overall, our findings indicate that A. herba-alba-derived compounds may be considered as therapeutic agents for IBD-associated arthritis, warranting further experimental validation and clinical exploration.


Asunto(s)
Artemisia , Enfermedades Inflamatorias del Intestino , Simulación del Acoplamiento Molecular , Extractos Vegetales , Artemisia/química , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Artritis/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/química
10.
Phytomedicine ; 132: 155897, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032279

RESUMEN

BACKGROUND: Intestinal health is affected by heredity, lifestyle, and structure of gut microbiota. The imbalance of symbiotic and harmful bacteria in gut microbiota may increase the occurrence of colonic inflammation. Supplementary A. muciniphila can improve the survival rate of colitis mice, reduce colon tissue injury, and the expression of anti-inflammatory factors was upregulated. Artemisia argyi has been reported to have anti-inflammatory, antioxidant, bactericidal, and immunomodulatory effects. However, its anti-inflammatory effect and mechanism, and its influence on gut microbiota and metabolites are still unclear yet. PURPOSE: To explore whether Artemisia argyi Polyphenols(AAPs) can alleviate ulcerative colitis (UC) by changing gut microbiota. METHODS: The therapeutic effect of AAPs on colitis was investigated by inducing ulcerative colitis in mice using dextran sodium sulfate (DSS) and administering different doses of AAPs orally to mice. Exploring the levels of inflammatory proteins, oxidative stress proteins, and barrier proteins using western blotting and immunofluorescence, and explored the structural changes of gut microbiota and its metabolites. Meanwhile, in order to explore whether the role of AAPs in alleviating colitis is based on the regulation of gut microbiota structure, we conducted fecal microbiota transplantation (FMT). RESULTS: It showed that AAPs and FMT trial alleviated DSS-induced colonic injury, including clinical parameters and pathological injury of colon tissue, reduction in the expression of inflammatory proteins: IL-6, TNF-α, p-p65, p-IκBα, and increase in the expression of antioxidant proteins: Nrf2, NQO-1 and HO-1 and barrier proteins: Claudin-1, Occludin, ZO-1 and MUC2. AAPs and FMT promoted the content of beneficial bacteria, such as Butyricimonas and Lactobacillus, and the content of beneficial metabolites for instance acetic acid, butyric acid, and valeric acid has also increased. CONCLUSION: These results suggested that AAPs might improve DSS-induced colonic injury by changing the structural of gut microbiota while promoting the synthesis of fatty acids in the intestine, thereby providing a theoretical basis for using AAPs to treat ulcerative colitis.


Asunto(s)
Artemisia , Colitis Ulcerosa , Sulfato de Dextran , Microbioma Gastrointestinal , Polifenoles , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Polifenoles/farmacología , Artemisia/química , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Masculino , Ratones Endogámicos C57BL , Colon/efectos de los fármacos , Colon/microbiología , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química
11.
J Photochem Photobiol B ; 258: 112989, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032373

RESUMEN

Exposure to ultraviolet B (UVB) radiation represents a significant environmental threat to human skin. This study investigates the protective mechanism of Artemisia Capillaris Thunb. (AC) extract against UVB-induced apoptosis and inflammation in HaCaT keratinocytes. AC extract demonstrated a significant protective effect, as evidenced by reduced early apoptosis, late apoptosis, and necrosis, as well as decreased apoptotic cell status upon UVB exposure. Additionally, AC extract effectively inhibited UVB-induced DNA damage, as indicated by diminished γ-H2AX foci formation. Restoration of mitochondrial damage and normalization of mitochondrial membrane potential, along with the reduction of intracellular and mitochondrial reactive oxygen species (ROS) levels, were observed with AC extract pre-treatment. The extract also exhibited anti-inflammatory properties, evidenced by the decreased release of IL-1α, IL-6, and PGE2 from keratinocytes. Additional research on the molecular mechanisms uncovered that the AC extract alters the cGAS/STING pathway, suppressing the mRNA (cGAS, STING, IRF3, IRF7 and TBK1) and protein levels (cGAS, STING, IRF3, IRF7 and NF-κB) linked to this particular pathway. The HPLC analysis identified chlorogenic acid and its derivatives as the major components in AC, constituting up to 16.44% of the total chlorogenic acid content. The cGAS/STING signaling pathway was found to be suppressed by chlorogenic acid and its derivatives, as indicated by molecular docking studies and RT-qPCR analysis. This suppression contributes to the protective effects against cell apoptosis and inflammation induced by UVB. To summarize, AC extract, which is abundant in chlorogenic acid and its derivatives, shows potential in protecting keratinocytes from damage caused by UVB by regulating the cGAS/STING signaling pathway.


Asunto(s)
Apoptosis , Artemisia , Queratinocitos , Proteínas de la Membrana , Nucleotidiltransferasas , Extractos Vegetales , Transducción de Señal , Rayos Ultravioleta , Humanos , Rayos Ultravioleta/efectos adversos , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Extractos Vegetales/farmacología , Extractos Vegetales/química , Artemisia/química , Nucleotidiltransferasas/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Proteínas de la Membrana/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Queratinocitos/citología , Especies Reactivas de Oxígeno/metabolismo , Inflamación/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de la radiación , Daño del ADN/efectos de los fármacos , Daño del ADN/efectos de la radiación , Ácido Clorogénico/farmacología , Ácido Clorogénico/química , Dinoprostona/metabolismo , Células HaCaT , Línea Celular
12.
Artículo en Inglés | MEDLINE | ID: mdl-39067315

RESUMEN

Artemisia capillaris Thunb. (A. capillaris) is a well-known traditional Chinese herbal medicine with a wide range of pharmacological effects, such as soothing the liver and gallbladder, heat clearance, and detoxifying. Hence, its extract is commonly added to various traditional Chinese medicine formulas. Traditional Chinese medicine injection (TCMI) is a mature pharmaceutical dosage form developed using TCM theory combined with modern science and technology. Notably, allergic reactions, especially pseudo­allergic reactions (PARs), greatly limited the use of these injections. Therefore, screening pseudo­allergic components in A. capillaris extract is clinically significant. In the present study, we proposed a two-dimensional screening and identification system based on mas-related G protein-coupled receptor X2-HALO-tag/cell membrane chromatography (MrgX2-HALO-tag/CMC) high performance liquid chromatography mass spectrometry (HPLC-MS); seven potential active components were screened from 75 % ethanol extract of A. capillaris: NCA, CA, CCA, 1,3-diCQA, ICA-B, ICA-A, and ICA-C. The receptor-ligand interactions between these seven compounds and MrgX2 protein were analyzed using frontal analysis and molecular docking technology. Furthermore, a mast cell degranulation-related assay was used to assess the pseudo­allergic activity of these compounds. The screened compounds can serve as ligands of MrgX2, and this study provides a research basis for pseudo­allergic reactions caused by TCMIs containing A. capillaris.


Asunto(s)
Artemisia , Receptores Acoplados a Proteínas G , Artemisia/química , Cromatografía Líquida de Alta Presión/métodos , Humanos , Ligandos , Receptores Acoplados a Proteínas G/metabolismo , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Medicamentos Herbarios Chinos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Animales , Simulación del Acoplamiento Molecular , Espectrometría de Masas/métodos , Proteínas del Tejido Nervioso , Receptores de Neuropéptido
13.
Med Oncol ; 41(8): 206, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037595

RESUMEN

Cure rates for acute myeloid leukemia (AML) remain suboptimal; thus, new treatment strategies are needed for this deadly disease. Artemisia campestris leaves hold significant value in traditional medicine. Despite extensive research conducted on this plant globally, the specific anti-AML properties of the leaves have received limited investigation. This study aims to explore the potential anti-leukemic activities of the ethyl acetate extract derived from Artemisia campestris (EAEAC), using mononuclear cells from bone marrow of thirteen AML patients. To this end, cytotoxic effects were evaluated using the MTT assay, and the mechanisms of cell death were investigated through various methods, including propidium iodide staining, annexin V/propidium iodide double staining, mitochondrial depolarization, and caspase-3/7 activation assays. Results demonstrated that EAEAC induced cell apoptosis by increasing DNA fragmentation, causing mitochondrial depolarization, and activating caspases 3/7. On the other hand, we assessed EAEAC's effect on two leukemia stem cell subpopulations, with results suggesting a potential decrease in their frequencies (three/five patients).


Asunto(s)
Apoptosis , Artemisia , Leucemia Mieloide Aguda , Extractos Vegetales , Humanos , Artemisia/química , Extractos Vegetales/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Apoptosis/efectos de los fármacos , Femenino , Adulto , Masculino , Persona de Mediana Edad , Caspasa 3/metabolismo , Antineoplásicos Fitogénicos/farmacología , Hojas de la Planta/química
14.
BMC Complement Med Ther ; 24(1): 264, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992644

RESUMEN

BACKGROUND: Artemisia argyi is a traditional herbal medicine belonging to the genus Artemisia that plays an important role in suppressing inflammation. However, the chemical constituents and underlying mechanisms of its therapeutic potential in neuroinflammation are still incompletely understood, and warrant further investigation. METHODS: Several column chromatography were employed to isolate and purify chemical constituents from Artemisia argyi, and modern spectroscopy techniques were used to elucidate their chemical structures. The screening of monomeric compounds with nitric oxide inhibition led to the identification of the most effective bioactive compound, which was subsequently confirmed for its anti-inflammatory capability through qRT‒PCR. Predictions of compound-target interactions were made using the PharmMapper webserver and the TargetNet database, and an integrative protein-protein interaction network was constructed by intersecting the predicted targets with neuroinflammation-related targets. Topological analysis was performed to identify core targets, and molecular docking and molecular dynamics simulations were utilized to validate the findings. The result of the molecular simulations was experimentally validated through drug affinity responsive target stability (DARTS) and Western blot experiments. RESULTS: Seventeen sesquiterpenoids, including fifteen known sesquiterpenoids and two newly discovered guaiane-type sesquiterpenoids (argyinolide S and argyinolide T) were isolated from Artemisia argyi. Bioactivity screening revealed that argyinolide S (AS) possessed the most potent anti-inflammatory activity. However, argyinolide T (AT) showed weak anti-inflammatory activity, so AS was the target compound for further study. AS may regulate neuroinflammation through its modulation of eleven core targets: protein kinase B 1 (AKT1), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein Kinase (FYN), Janus Kinase (JAK) 1, mitogen-activated protein (MAP) Kinase 1,8 and 14, matrix metalloproteinase 9 (MMP9), ras-related C3 botulinum toxin substrate 1 (RAC1), nuclear factor kappa-B p65 (RELA), and retinoid X receptor alpha (RXRA). Molecular dynamics simulations and DARTS experiments confirmed the stable binding of AS to JAK1, and Western blot experiments demonstrated the ability of AS to inhibit the phosphorylation of downstream Signal transducer and activator of transcription 3 (STAT3) mediated by JAK1. CONCLUSIONS: The sesquiterpenoid compounds isolated from Artemisia argyi, exhibit significant inhibitory effects on inflammation in C57BL/6 murine microglia cells (BV-2). Among these compounds, AS, a newly discovered guaiane-type sesquiterpenoid in Artemisia argyi, has been demonstrated to effectively inhibit the occurrence of neuroinflammation by targeting JAK1.


Asunto(s)
Antiinflamatorios , Artemisia , Simulación del Acoplamiento Molecular , Sesquiterpenos , Artemisia/química , Animales , Sesquiterpenos/farmacología , Sesquiterpenos/química , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Células RAW 264.7 , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Simulación de Dinámica Molecular
15.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3566-3573, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39041128

RESUMEN

This study established an ultra-performance liquid chromatography(UPLC) fingerprint of abandoned stems and leaves of Artemisia selengensis and quantitative analysis of multi-components by single marker(QAMS) for five phenolic acid components. Waters Acquity UPLC BEH C_(18) chromatography column(2.1 mm×100 mm, 1.7 µm) was used. The gradient elution was carried out with the mobile phase composed of 0.1% phosphoric acid water and acetonitrile at a flow rate of 0.3 mL·min~(-1) and a column temperature at 30 ℃. The detection wavelength was 330 nm, and the injection volume was 2 µL. Similarity evaluation and cluster analysis were conducted on the fingerprint data, and 15 common components in 13 batches of abandoned stems and leaves of A. selengensis were identified. The relative correction factors of ferulic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C were calculated using chlorogenic acid as the internal reference. The QAMS for determining five components in the abandoned stems and leaves of A. selengensis was established. At the same time, the content of these five components was determined using the external standard method(ESM), and the results showed that there were no significant differences in their content determined by the QAMS and the ESM. The results indicated that the content of phenolic acid components in the abandoned stems and leaves of A. selengensis from different varieties and different origins had obvious differences. In addition, the content of phenolic acid components in the abandoned stems and leaves of lignified A. selengensis was significantly higher than that of non-lignified A. selengensis. In summary, QAMS established in this study can be quickly, accurately, and economically used to determine the content of five phenolic acid components in abandoned stems and leaves of A. selengensis, laying a foundation for the resource development and utilization of abandoned stems and leaves of A. selengensis.


Asunto(s)
Artemisia , Hidroxibenzoatos , Hojas de la Planta , Tallos de la Planta , Control de Calidad , Hojas de la Planta/química , Tallos de la Planta/química , Artemisia/química , Cromatografía Líquida de Alta Presión/métodos , Hidroxibenzoatos/análisis , Hidroxibenzoatos/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis
16.
Fitoterapia ; 177: 106093, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38917891

RESUMEN

Four undescribed sesquiterpene compounds (1-4) and six known compounds (5-10) were isolated from A. mongolica. Furthermore, compound 5 was a new natural product previously synthesized. The LPS-stimulated BV2 cells were used as a model to evaluate the anti-inflammatory activity of the isolated compounds, among them, compounds 2, 3 and 4 showed significant inhibition of NO levels with IC50 values of 27.48, 27.39 and 24.96 µM, respectively.


Asunto(s)
Antiinflamatorios , Artemisia , Fitoquímicos , Sesquiterpenos , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Artemisia/química , Estructura Molecular , Ratones , Animales , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Línea Celular , Óxido Nítrico/metabolismo , China
17.
PLoS One ; 19(6): e0305155, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38865346

RESUMEN

Haemonchus contortus is a blood-feeding gastrointestinal parasite that impacts grazing sheep, causing economic losses in animal production. Due to its anthelmintic resistance, alternative antiparasitic treatments like plant-based anthelmintics are necessary to explore. Artemisia cina (Asteraceae) is a plant whose n-hexane extract and ethyl acetate extract exhibit anthelmintic activity against H. contortus, the n-hexane more active. To discover additional bioactive metabolites, a chemical analysis was performed on ethyl acetate extract, which presented an LC90 of 3.30 mg/mL and allowed the isolation of 11-[(1R,5S,7R,8R,10S,)-1,8-dihydroxy-5,10-dimethyl-4-oxodecahydroazulen-7-yl] acrylic acid. This new sesquiterpene was identified through one and two-dimensional NMR. The compound was named cinic acid and displayed an LC50 of 0.13 (0.11-0.14) mg/mL and LC90 of 0.40 (0.37-0.44) mg/mL, which, compared with ethyl acetate extract larvicidal activity, was 256-fold more active at LC50 and 15.71-fold at LC90. In this study, a new sesquiterpene with larvicidal activity against H. contortus L3 infective larvae was isolated from the ethyl acetate extract of Artemisia cina.


Asunto(s)
Antihelmínticos , Artemisia , Haemonchus , Larva , Extractos Vegetales , Sesquiterpenos , Artemisia/química , Haemonchus/efectos de los fármacos , Animales , Antihelmínticos/farmacología , Antihelmínticos/aislamiento & purificación , Antihelmínticos/química , Larva/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Ovinos , Espectroscopía de Resonancia Magnética
18.
Molecules ; 29(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38930948

RESUMEN

Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analyses were conducted on essential oil extracted from Saudi Arabian Artemisia judaica L. (A. judaica) aerial parts, resulting in the identification of 58 constituents, representing 93.0% of the total oil composition. The oil primarily consisted of monoterpenes (38.6%), sesquiterpenes (14.1%), and other compounds such as ethyl esters and cyclic ketones (40.3%). The main components identified were piperitone (16.5%), ethyl cinnamate (12.9%), and camphor (9.7%). Multivariate statistical analyses (MVAs), including principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) analysis, were employed to compare the chemical makeup of this oil with 20 other A. judaica oils from various regions. The study revealed distinct clusters, highlighting unique chemotypes and geographic variations. Particularly, the oil from the current study demonstrated a specialized chemical profile with significant concentrations of specific compounds, contributing significantly to its distinctiveness. Further cytotoxicity testing on RAW264.7 macrophages suggested that concentrations below 20 µg/mL of A. judaica oil are suitable for future pharmacological investigations. This study provides valuable insights into the chemical diversity, geographic variations, and potential biomedical applications of these essential oils.


Asunto(s)
Artemisia , Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles , Aceites Volátiles/química , Aceites Volátiles/farmacología , Artemisia/química , Arabia Saudita , Ratones , Animales , Células RAW 264.7 , Análisis de Componente Principal , Aceites de Plantas/química , Aceites de Plantas/farmacología
19.
Ultrason Sonochem ; 107: 106932, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38824698

RESUMEN

Artemisia argyi leaf polysaccharide (AALPs) were prepared through ultrasound-assisted extraction (UAE), and their antifatigue activities were evaluated. Extraction was optimized using response surface methodology (RSM), which yielded the following optimal UAE conditions: ultrasonication power of 300 W, extraction temperature of 51 °C, liquid:solid ratio of 20 mL/g, and ultrasonication time of 47 mins. The above optimal conditions resulted in the maximum extraction rate of 10.49 %. Compared with hot water extraction (HWE), UAE supported higher yields and total sugar, uronic acid, and sulfate contents of AALPs. Meanwhile, AALP prepared through UAE (AALP-U) exhibited higher stability due to its smaller particle size and higher absolute value of zeta potential than AALP prepared through HWE (AALP-H). In addition, AALP-U demonstrated stronger antioxidant activity than AALP-H. In forced swimming tests on mice, AALP-U could significantly prolong swimming time with a dose-dependent effect, increase liver and muscle glycogen levels, and improve other biochemical indices, thus showing great potential for application in functional food.


Asunto(s)
Artemisia , Hojas de la Planta , Polisacáridos , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Polisacáridos/química , Artemisia/química , Hojas de la Planta/química , Animales , Ratones , Ondas Ultrasónicas , Fraccionamiento Químico/métodos , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/química , Tecnología Química Verde/métodos , Masculino , Glucógeno/metabolismo , Natación , Hígado/efectos de los fármacos
20.
J Ethnopharmacol ; 333: 118458, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-38871010

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi essential oil (AAEO) is a traditional herbal remedy for asthma. However, the potential effect of AAEO on asthma has not been elucidated. AIM OF THE STUDY: To investigate the protective properties of AAEO upon asthma and elucidate its mechanism. MATERIALS AND METHODS: The effects of AAEO in asthma were assessed by histology and biochemical analysis. Then, we integrated real-time reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry and metabolomics analysis to reveal its mechanism. RESULTS: In vivo, AAEO reduced the counts of white blood cells (WBCs) and cytokines in bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations in lung tissues, and inhibited secretion of OVA-sIgE and muc5ac. Metabolomics results showed that AAEO can exert therapeutic effects on asthmatic mice by regulating disordered arachidonic acid metabolism and tryptophan metabolism. Further studies shown that AAEO inhibited the expression of 5-LOX and reduced the accumulation of CysLTs in mice. Meanwhile, AAEO promoted the activity of IDO-1, facilitated the conversion of tryptophan to kynurenine, and regulated the imbalance of Treg/Th17 immunity. Immunohistochemical results showed that AAEO promoted the expression of IDO-1. RT-qPCR results showed that AAEO promoted the expression of IL-10 and Foxp3 mRNA, and inhibited the expression of IL-17A and RORγt mRNA, thus regulated the imbalance of Treg/Th17 immunity and exerted its therapeutic effects. CONCLUSION: AAEO treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating lung tissue metabolism. The anti-asthmatic activity of AAEO may be achieved by reprogramming 5-LOX-CysLTs and IDO-1-KYN pathways.


Asunto(s)
Antiasmáticos , Artemisia , Asma , Aceites Volátiles , Transducción de Señal , Animales , Femenino , Masculino , Ratones , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Araquidonato 5-Lipooxigenasa/metabolismo , Araquidonato 5-Lipooxigenasa/genética , Artemisia/química , Asma/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Quinurenina/metabolismo , Leucotrienos/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Metabolómica , Ratones Endogámicos BALB C , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Transducción de Señal/efectos de los fármacos
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