Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca2+ Signaling.

OBJECTIVE: To evaluate the chemical composition and effects of Artemisia vulgaris (AV) hydroalcoholic extract (HEAV) on breast cancer cells (MCF-7 and SKBR-3), chronic myeloid leukemia (K562) and NIH/3T3 fibroblasts. METHODS: Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass (HPLC) spectrometry. Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD, respectively. Ferrostatin-1 (Fer-1) and necrostatin-1 (Nec-1) were used to assess the mode of HEAV-induced cell death and acetoxymethylester (BAPTA-AM) was used to verify the involvement of cytosolic calcium in this event. Cytosolic calcium measurements were made using Fura-2-AM. RESULTS: HEAV decreased the viability of MCF-7, SKBR-3 and K562 cells (P<0.05). The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts (P<0.05). Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD (P<0.05). The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone (P<0.01). HEAV-induced Ca2+ release mainly from lysosomes in K562 cells (P<0.01). Furthermore, BAPTA-AM, an intracellular Ca2+ chelator, decreased the number of non-viable cells treated with HEAV (P<0.05). CONCLUSIONS: HEAV is cytotoxic and activates several modalities of cell death, which are partially dependent on lysosomal release of Ca2+. These effects may be related to artemisinin and caffeoylquinic acids, the main compounds identified in HEAV.

A phytotherapic blend immunity-6™ inhibits myeloid leukemic cells 2 activation involving purinergic signaling.

Leukemia is among the most common types of hematological cancers and the use of herbal medicines to prevent and treat leukemia are under quick development. Among several molecular pathways involved in leukemia pathogenesis and exacerbations, purinergic signaling is revealed as a key component. In the present study, the effects of two doses (5 ug/mL and 10 ug/mL) of Immunity-6™, a phytocomplex composed by beta-glucan, green tea (Camelia sinensis), chamomile (Matricaria chamomilla), and ascorbic acid (vitamin C) was tested in vitro, using chronic myelogenous leukemia cell line (K-562; 5 ×104/mL/well), which were challenged with lipopolysaccharide (LPS; 1 ug/mL) for 24 h. The results demonstrated that both doses of Immunity-6™ inhibited ATP release (p < 0.001) and P2×7 receptor at mRNA levels expression (p < 0.001). Purinergic inhibition by Immunity-6™ was followed by reduced release of proinflammatory cytokines IL-1beta (p < 0.001) and IL-6 (p < 0.001), while only 5 ug/mL of Immunity-6™ reduced the release of TNF-alpha (p < 0.001). Beyond to inhibit the release of pro-inflammatory cytokines, both doses of Immunity-6™ induced the release of anti-inflammatory cytokine IL-10 (p < 0.001), while only the higher dose (10 ug/mL) of Immunity-6™ induced the release of anti-inflammatory IL-1ra (p < 0.05) and klotho (p < 0.001). Thus, Immunity-6™ may be a promising adjuvant in the treatment of leukemia and further clinical trials are guaranteed.

Molecular Dereplication and In Vitro and In Silico Pharmacological Evaluation of Coriandrum sativum against Neuroblastoma Cells.

The aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the "Five Rules" of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value.

Antiviral activity of medicinal plant-derived products against SARS-CoV-2.

This review presents information from several studies that have demonstrated the antiviral activity of extracts (Andrographis paniculata, Artemisia annua, Artemisia afra, Cannabis sativa, Curcuma longa, Echinacea purpurea, Olea europaea, Piper nigrum, and Punica granatum) and phytocompounds derived from medicinal plants (artemisinins, glycyrrhizin, and phenolic compounds) against SARS-CoV-2. A brief background of the plant products studied, the methodology used to evaluate the antiviral activity, the main findings from the research, and the possible mechanisms of action are presented. These plant products have been shown to impede the adsorption of SARS-CoV-2 to the host cell, and prevent multiplication of the virus post its entry into the host cell. In addition to antiviral activity, the plant products have also been demonstrated to exert an immunomodulatory effect by controlling the excessive release of cytokines, which is commonly associated with SARS-CoV-2 infections.

Therapeutic use of intravenous selenium in respiratory and immunological diseases: evidence based on reviews focused on clinical trials.

The oxidative stress caused by systemic inflammatory response syndrome (SIRS), septic shock, and sepsis, is a risk factor triggering an increase in mortality in patients diagnosed with these pathologies. Selenium (Se) is an essential mineral that has antioxidant and cytoprotective functions, being strongly associated with the proper functioning of intracellular metabolic processes. In this context, the present study aims to investigate de therapeutic effects of intravenous selenium use considering pathologies such as SIRS, septic shock, sepsis, acute respiratory distress syndrome (ARDS), ventilator associated pneumonia (VAP), and coronavirus disease (COVID-19). This is an narrative literature review in which six main articles found in databases of SciELO, PubMed, and Google Scholar, were selected and analyzed. As a result, articles were found evidencing the benefit of Se in the inflammatory response, increasing the GPx-3 activity and decreasing the inflammatory cytokines, in addition to generating a lower risk of VAP, shortening the hospitalization time, and mortality. Thus, Se supplementation has beneficial evidence for acute respiratory diseases and should be considered as a viable option as adjuvant therapy.

Anti-Inflammatory Activity of Miodesin™: Modulation of Inflammatory Markers and Epigenetic Evidence.

PURPOSE: To investigate the effects of a combined herbal medicine Miodesin™ on the inflammatory response of key cells involved in the acute and chronic inflammatory processes as well as the possible epigenetic involvement. METHODS: After the establishment of the IC50 dose, the chondrocyte, keratinocyte, and macrophage cell lines were pretreated for 2 hours with Miodesin™ (200 µg/mL) and stimulated with LPS (1 µg/mL) for 24 hours. The supernatant was used to measure the levels of cytokines (IL-1ß, IL-6, IL-8, and TNF-α) and chemokines (CCL2, CCL3, and CCL5), and the cells were used to extract the mRNA for the transcription factor (NF-κß), inflammatory enzymes (COX-1, COX-2, PLA2, and iNOS), and chemokines (CCL2, CCL3, and CCL5). RESULTS: Miodesin™ inhibited the release of LPS-induced cytokines (IL-1ß, IL-6, IL-8, and TNF-α; p < 0.01) and chemokines (CCL2, CCL3, and CCL5; p < 0.01) and the expression of the transcription factor (NF-κß; p < 0.01), inflammatory enzymes (COX-1, COX-2, PLA2, iNOS; p < 0.01), and chemokines (CCL2, CCL3, and CCL5; p < 0.01). In addition, the evaluation of epigenetic mechanism revealed that Miodesin™ did not induce changes in DNA methylation, assuring the genetic safeness of the compound in terms of the inflammatory response. CONCLUSIONS: Miodesin™ presents anti-inflammatory properties, inhibiting hyperactivation of chondrocytes, keratinocytes, and macrophages, involving epigenetics in such effects.

In vitro study activity proliferative fibroblast human submitted to treatment Zincummetallicum and Calendula officianlis in homeopathic ultra dilutions

Cicatrization can be divided into three phases: inflammation, fibroblastic, maturation and remodeling [1]. The extracellular matrix may be replaced by a stronger and more elastic connective tissue. In a scar collagen is the major component of the mature connective tissue [2]. In homeopathic area, the greater is the investigated segment ultra dilutions [6]. However, little research has been done to explore the effect of dynamized drugs in in vitro cell culture [4]. Using the Zincum metallicum 6CH and Calendula officinalis 6CH applied independently in different concentrations in fibroblast cultures sought to determine the increase in proliferative activity using techniques such as IC50, MTT, flow cytometry and quantification of collagen. As expected from the literature, ie both homeopathic according to the literature are used for treatments that Require skin healing, both showed increased proliferative activity, having Calendula most cellular response, presenting as cell cycle stimulating checked via flow cytometry.

In vitro study activity proliferative fibroblast human submitted to treatment zincum metallicum and calendula officinalis in ultra dilutions homeopathic

Cicatrization can be divided into three phases: inflammation, fibroblastic, maturation and remodeling [1]. The extracellular matrix may be replaced by a stronger and more elastic connective tissue. In a scar collagen is the major component of the mature connective tissue [2]. In homeopathic area, the greater is the investigated segment ultra dilutions [6]. However, little research has been done to explore the effect of dynamized drugs in in vitro cell culture [4]. Using the Zincum metallicum 6CH and Calendula officinalis 6CH applied independently in different concentrations in fibroblast cultures sought to determine the increase in proliferative activity using techniques such as IC50, MTT, flow cytometry and quantification of collagen. As expected from the literature, ie both homeopathic according to the literature are used for treatments that Require skin healing, both showed increased proliferative activity, having Calendula most cellular response, presenting as cell cycle stimulating checked via flow cytometry.(AU)

Plantas com potencial adaptogénico utilizadas na medicina popular brasileira: Ptychapetalum olacaides, Pfaffia spp. E Trichilia catigua / Plantas con potencial adaptogénico utilizadas en la medicina popular brasileña: Ptychopetalum olacoides, Pfaflia spp. y Trichilia catigua / Potentially adaptogenic plants used in Brazilian folk medicine: Ptychopetalum olacoides, Pfaffia spp. A Trichilia catigua

O estresse já foi definido como uma reaçáo capaz de perturbar a homeostase do organismo. Nesse contexto es adaptógenos permitem equilibrar o organismo durante tais situaçoes. Pesquisas demonstram que a flora brasileira e rica em especies com potencial adaptógeno, dentre as quais destacam: Ptycopetalum olacoides (marapuama), descrita por seus efeitos anti-inflamatórios, antioxidante, antibacteriano e estimulante de sistema imunológico; o genero Pfaffia spp, entre eles o ginseng brasileiro, com usos na fadiga cronica, estresse, impotencia masculina e reduçáo nos niveis circulantes de colesterol; e a Trichilia catigua (catuaba) utilizada como tonico para tratamento do estresse, fadiga, impotencia e déficit de memoria (AU)

El estrés se define como una reacción capaz de alterar la homeostasis del organismo. En este contexto, los adaptógenes permiten equilibrar el organismo en tales situaciones. Las investigaciones han mostrado que la fiera brasileña es rica en especies con potencial adaptegénice, entre las que destacan: Ptycopetalum olacoides (marapuama), descrita por sus efectos estimulantes, antiinflamatories, antioxidantes, antibacterianes e inmuneestimulantes; Pfaffia spp, (ginseng brasileño), con usos en fatiga crónica, estrés, impotencia masculina y reducción de los niveles plasmáticos de colesterol; y Trichilia catigua (catuaba), utilizada en el tratamiento del estrés, la fatiga, la impotencia y el déficit de memoria (AU)

Stress has already been defined as a reaction able to disrupt the homeostasis of the organism. In this context adaptogens allow te balance the body in such situations. Research has shown that Brazilian flora is rich in species with adaptegenic potential, among which the following are outstanding: Ptycopetalum olacoides (marapuama), known for its anti-inflammatory, antiexidant, antibacterial and immunestimulant effects; the genus Pfaffia spp, including the Brasilian ginseng, used in chronic fatigue, stress, male impotence and reduction of blood cholesterol levels; and Trichilia catigua (catuaba) used for the treatment of stress, fatigue, impotence and memory deficit (AU)