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Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.
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Acetilcolinesterase , Queratinócitos , MicroRNAs , Pele , Raios Ultravioleta , Urticária , Acetilcolinesterase/metabolismo , Acetilcolinesterase/genética , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Pele/efeitos da radiação , Pele/metabolismo , Urticária/metabolismo , Urticária/etiologia , Camundongos , Acetilcolina/metabolismo , MasculinoRESUMO
This study investigated the reproductive traits of the hermaphroditic four-finger threadfin, Eleutheronema tetradactylum, along the coasts of Thailand during January to December 2021. Fish samples were collected from Pattani Bay, Thailand to assess the sex ratio, gonadosomatic index (GSI), maturity stage and fecundity. Additional fish samples were also collected from other areas to evaluate the length and weight at first sex change (Ls50 and Ws50) and length at first maturity (Lm50). The overall sex ratio for male and female was 1:0.69 with male being predominant throughout the year. Threadfin fish spawn the whole year round with peaks during moderate rainy and heavy rainy seasons. Histological examination confirmed its protandrous hermaphrodite posing multiple spawning habits. The average fecundity was 1.85 × 105 ± 1.05 × 105 eggs and positively related with standard length, body weight, gonad weight, and egg diameter (p < 0.05). The Ls50 and Ws50 were 27.58 cm and 419.39 g, and 29.71 cm and 457.28 g, for fish from Pattani Bay and Samut Prakan province, respectively. The Lm50 of male from Pattani Bay and Samut Prakan province were 25.78 cm and 25.56 cm, respectively, which were larger than those from Satun and Nakhon Sri Thammarat provinces. The Lm50 of females from Pattani Bay was smaller than that from Samut Prakan province. This study provided fundamental information on the reproductive characteristics of E. tetradactylum, which can be implemented to support management of natural fish stock and aquaculture development.
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Flavonoids are the most common phytochemicals in vegetables and herbal products. The beneficial functions of flavonoids in the brain and erythropoietic system have been proposed. Erythropoietin (EPO) is a potent protective agent in the brain; but which has difficulty to cross the blood brain barrier (BBB). Here, about 60 flavonoids were screened for their potential activation on the transcription of EPO mRNA in the neuronal embryonic stem cell lines, NT2/D1 and PC12. Amongst the screened flavonoids, formononetin, calycosin, ononin, chrysin, baicalein and apigenin showed robust up regulation of EPO production via enhancement of hypoxia response element (HRE) activity in cultured embryonic stem cells. In addition, the flavonoids showed activation of HRE activity by having increased accumulation of HIF-1α, but not on level of HIF-1ß, in the cultures. The accumulation of HIF-1α was attributed to up regulation of HIF-1α mRNA and blockade of HIF-1α degradation upon treatment of the flavonoids. These results suggested a promising trend of developing commercial products of flavonoids as food supplements tailored for brain health.
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Eritropoetina , Subunidade alfa do Fator 1 Induzível por Hipóxia , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Eritropoetina/genética , Eritropoetina/farmacologia , Linhagem Celular , Hipóxia/metabolismo , Flavonoides/farmacologiaRESUMO
Understanding the adaptive ecological divergence provides important information for revealing biodiversity generation and maintenance. Adaptive ecology divergence in populations occurs in various environments and locations, but its genetic underpinnings remain elusive. We generated a chromosome-level genome of Eleutheronema tetradactylum (~582 Mb) and re-sequenced 50 allopatric E. tetradactylum in two independent environmental axes in China and Thailand Coastal waters as well as 11 cultured relatives. A low level of whole genome-wide diversity explained their decreased adaptive potential in the wild environment. Demographic analysis showed evidence of historically high abundance followed by a continuous distinct decline, plus signs of recent inbreeding and accumulation of deleterious mutations. Extensive signals of selective sweeps with signs of local adaptation to environmental differentiation between China and Thailand at genes related to thermal and salinity adaptation were discovered, which might be the driving factors of the geographical divergence of E. tetradactylum. Many genes and pathways subjected to strong selection under artificial breeding were associated with fatty acids and immunity (ELOVL6L, MAPK, p53/NF-kB), likely contributing to the eventual adaptation of artificial selective breeding. Our comprehensive study provided crucial genetic information for E. tetradactylum, with implications for the further conservation efforts of this threatened and ecologically valuable fish.
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Genoma , Metagenômica , Animais , Genoma/genética , Peixes , Sequência de Bases , CromossomosRESUMO
Zinc ion (Zn) is an essential nutrition element and it is important to understand its regulation and distribution among different cellular organelles. Here, subcellular trafficking of Zn in rabbitfish fin cells was investigated through bioimaging, and the results showed that the toxicity and bioaccumulation of Zn were both dose- and time-dependent. Cytotoxicity of Zn only occurred when the Zn concentration reached 200-250 µM after 3 h of exposure when the cellular quota of Zn:P reached a threshold level around 0.7. Remarkably, the cells were able to maintain homeostasis at a low Zn exposure concentration or within the first 4-h exposure. Zn homeostasis was mainly regulated by the lysosomes which stored Zn within the short exposure period, during which the number and size of lysosomes as well as the lysozyme activity increased in response to incoming Zn. However, with increasing Zn concentration beyond a threshold concentration (> 200 µM) and an exposure time > 3 h, homeostasis was disrupted, leading to an Zn spillover to cytoplasm and other cellular organelles. At the same time, cell viability decreased due to the Zn damage on mitochondria which caused morphological changes (smaller and rounder dots) and over production of reactive oxygen species, indicating the dysfunction of mitochondria. By further purifying the cellular organelles, cell viability was found to be consistent with the mitochondrial Zn amount. This study suggested that the amount of mitochondrial Zn was an excellent predictor of Zn toxicity on fish cells.
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Mitocôndrias , Zinco , Animais , Zinco/toxicidade , Zinco/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lisossomos , Sobrevivência CelularRESUMO
This study assessed the feeding habits of four-finger threadfin fish, Eleutheronema tetradactylum, and its diet relationship with other fish species in the tropics. Fish samples were collected from four locations along the coastal regions of Thailand. A whole year field sampling event was conducted to investigate the diet relationship of threadfin fish with other ten co-existing fish species in Pattani Bay during January 2021 and January 2022. E. tetradactylum was an active and specific predator with significant diet shift during ontogeny. Specifically, the juvenile fish fed largely on zooplankton especially Acetes/shrimp postlarvae, and small sized-fish fed on penaeid shrimps, while medium and large-sized fish shifted their diets to a combination of penaeid shrimp, fish and squid. Size and sex of fish as well as site of collection significantly affected gut fullness index and average number of food type (p < 0.05). Transitional sex fish predated almost entirely on other fishes (87.2%), whereas male and female fish fed mainly on penaeid shrimp (66.5%) and other fish (51.3%), respectively. Fish size and mouth opening controlled the size of prey, with the larger fish with larger mouth-opening fed primarily on the larger size of prey. Moreover, E. tetradactylum shared its diets inclusively with Epinephelus coioides, Johnius belangerii, Scomberomorus commerson, Scomberoides lysan, Otolithes ruber and Lutjanus russelli. Penaeid shrimp and teleost fish were the main food types shared by these fishes. This study provided important information on the feeding habits of E. tetradactylum and its diet relationship with other co-existing fish species living in the same habitat of a tropical coastal region.
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Bass , Penaeidae , Perciformes , Animais , Feminino , Masculino , Tailândia/epidemiologia , Dieta/veterinária , HábitosRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the acute respiratory disease coronavirus disease 2019 (COVID-19), which has resulted in millions of deaths globally. Here, we explored the mechanism of host cell entry of a luciferase-ZsGreen spike (SARS-CoV-2)-pseudotyped lentivirus using zebrafish embryos/larvae as an in vivo model. Successful pseudovirus entry was demonstrated via the expression of the luciferase (luc) gene, which was validated by reverse transcription-PCR (RT-PCR). Treatment of larvae with chloroquine (a broad-spectrum viral inhibitor that blocks membrane fusion) or bafilomycin A1 (a specific inhibitor of vacuolar proton ATPases, which blocks endolysosomal trafficking) significantly reduced luc expression, indicating the possible involvement of the endolysosomal system in the viral entry mechanism. The pharmacological inhibition of two-pore channel (TPC) activity or use of the tpcn2dhkz1a mutant zebrafish line also led to diminished luc expression. The localized expression of ACE2 and TPC2 in the anterior neuromasts and the forming olfactory organs was demonstrated, and the occurrence of endocytosis in both locations was confirmed. Together, our data indicate that zebrafish embryos/larvae are a viable and tractable model to explore the mechanism of SARS-CoV-2 host cell entry, that the peripheral sense organs are a likely site for viral host cell entry, and that TPC2 plays a key role in the translocation of the virus through the endolysosomal system. IMPORTANCE Despite the development of effective vaccines to combat the COVID-19 pandemic, which help prevent the most life-threatening symptoms, full protection cannot be guaranteed, especially with the emergence of new viral variants. Moreover, some resistance to vaccination remains in certain age groups and cultures. As such, there is an urgent need for the development of new strategies and therapies to help combat this deadly disease. Here, we provide compelling evidence that the peripheral sensory organs of zebrafish possess several key components required for SARS-CoV-2 host cell entry. The nearly transparent larvae provide a most amenable complementary platform to investigate the key steps of viral entry into host cells, as well as its spread through the tissues and organs. This will help in the identification of key viral entry steps for therapeutic intervention, provide an inexpensive model for screening novel antiviral compounds, and assist in the development of new and more effective vaccines.
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COVID-19 , SARS-CoV-2 , Animais , Humanos , COVID-19/transmissão , Ligação Proteica , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus , Peixe-Zebra , Modelos Animais de Doenças , Virologia/métodos , LarvaRESUMO
OBJECTIVES: This study aimed to further explore the efficacy and safety of Danggui Buxue Tang (DBT), a simple herbal formula, for improving the quality of life of women suffering from menopausal symptoms. METHODS: A third clinical trial to determine the clinical efficacy of high-dose DBT for a period of 12 weeks was carried out. The standard Menopause-Specific Quality of Life (MENQOL) assessment chart was used for the evaluation. Safety was defined as an absence of direct estrogenic effects, serum inflammatory cytokines. Notably, interleukin IL-6, IL-8 and tumor necrosis factor TNF-α, known to be directly related to estrogenic reactions in menopause studies, were monitored. RESULTS: The third clinical trial indicated an overall improvement in the four domains of MENQOL, offering further proof of the efficacy of DBT demonstrated in the two previous trials. The serial checks of the three cytokines related to estrogen activities did not show either upward or downward trends. The haphazard behavior reactions of the three cytokines offered indirect indications that DBT improved the MENQOL independently from estrogen activities. CONCLUSIONS: The three clinical trials using DBT to relieve menopausal syndrome have offered solid evidence for its efficacy. The uncertainty regarding whether the "phytoestrogen" contained in DBT had bioactivities similar to estrogen was alleviated through the confirmation that no strict estrogenic bioactivities were observed. The issue of safety was further clarified via laboratory platform studies on DBT, which not only showed the lack of similarity with estrogen actions but also confirmed the value of combining the two herbs in the classic formula.
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Capsaicin, a major ingredient in chili pepper, has broad pharmaceutical applications, including relieving pain, anti-inflammation, and treating psoriasis. In dermatological biology, capsaicin has been shown to prevent the ultraviolet (UV)-induced melanogenesis via TRPV1 receptor. To strengthen the roles of capsaicin in skin function, the damaged skin, triggered by exposure to UV, was reversed by capsaicin in both in vitro and in vivo models. In cultured dermal fibroblasts, the exposure to UV induced a decrease of collagen synthesis and increases expression of matrix metalloproteinases (MMPs), generation of reactive oxygen species (ROS), and phosphorylation of Erk and c-Jun, and these events subsequently led to skin damage. However, the UV-mediated damages could be reversed by pre-treatment with capsaicin in a dose-dependent manner. The effect of capsaicin in blocking the UV-mediated collagen synthesis was mediated by reducing generation of ROS in dermal fibroblasts, instead of the receptor for capsaicin. Hence, capsaicin has high potential value in applying as an agent for anti-skin aging in dermatology.
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The threadfin Eleutheronema are the important fishery resources in Indo-Pacific regions and classified as the endangered species with considerable conservation values. Their genetic diversity and population structure remain essentially unknown but are critical for the proper management and sustainable harvests of such important fisheries. Here, the mitochondrial DNA sequences of CO1 and 16s rRNA were determined from 75 individuals of Eleutheronema tetradactylum and 89 individuals of Eleutheronema rhadinum collected from different locations of South China Sea and Thailand coastal waters. Genetic diversity analysis revealed that both E. tetradactylum (Haplotype diversity, H = 0.105-0.211; Nucleotide diversity, π = 0.00017-0.00043) and E. rhadinum (H = 0.074-0.663, π = 0.00013-0.01088) had low diversity. Population structure analysis demonstrated the shallow genetic differentiation among the South China Sea populations. The limited communication between China and Thailand populations caused the high genetic differentiation in all groups due to the low dispersal ability. Reconstruction of CO1 phylogenetic relationships and demographic studies across Indo-West-Pacific regions provided strong evidence for a shared common origin or ancestor of E. tetradactylum and E. rhadinum. Eleutheronema rhadinum were further subdivided into two distinct genetic lineages, with Clade A dominantly distributing in Thailand and Malaysia and Clade B distributing in China coastal waters. Phenotypic divergence, characterized mainly by the depth of caudal peduncle and length of caudal peduncle, was also observed for all populations, which was possibly associated with specific local adaptations to environmental changes. Our study suggested a strong need for the development of proper fishery management strategies and conservation actions for the imperiled Eleutheronema species.
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Pesqueiros , Peixes , Animais , DNA Mitocondrial/genética , Demografia , Peixes/genética , Variação Genética , Filogenia , RNA Ribossômico 16SRESUMO
The non-classical function of acetylcholine (ACh) has been reported in neuroinflammation that represents the modulating factor in immune responses via activation of α7 nicotinic acetylcholine receptor (α7 nAChR), i.e., a cholinergic anti-inflammatory pathway (CAP). Acetylcholinesterase (AChE), an enzyme for ACh hydrolysis, has been proposed to have a non-classical function in immune cells. However, the involvement of AChE in neuroinflammation is unclear. Here, cultured BV2 cell, a microglial cell line, and primary microglia from rats were treated with lipopolysaccharide (LPS) to induce inflammation and to explore the regulation of AChE during this process. The expression profiles of AChE, α7 nAChR, and choline acetyltransferase (ChAT) were revealed in BV2 cells. The expression of AChE (G4 form) was induced significantly in LPS-treated BV2 cells: the induction was triggered by NF-κB and cAMP signaling. Moreover, ACh or α7 nAChR agonist suppressed the LPS-induced production of pro-inflammatory cytokines, as well as the phagocytosis of microglia, by activating α7 nAChR and followed by the regulation of NF-κB and CREB signaling. The ACh-induced suppression of inflammation was abolished in AChE overexpressed cells, but did not show a significant change in AChE mutant (enzymatic activity knockout) transfected cells. These results indicate that the neuroinflammation-regulated function of AChE may be mediated by controlling the ACh level in the brain system.
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Acetilcolinesterase/metabolismo , Lipopolissacarídeos/toxicidade , Microglia/metabolismo , Acetilcolinesterase/genética , Animais , Linhagem Celular , Células Cultivadas , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Camundongos , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Fagocitose , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Acetylcholinesterase inhibitors (AChEIs), the most developed treatment strategies for Alzheimer's disease (AD), will be used in clinic for, at least, the next decades. Their side effects are in highly variable from drug to drug with mechanisms remaining to be fully established. The withdrawal of tacrine (Cognex) in the market makes it as an interesting case study. Here, we found tacrine could disrupt the proper trafficking of proline-rich membrane anchor-linked tetrameric acetylcholinesterase (AChE) in the endoplasmic reticulum (ER). The exposure of tacrine in cells expressing AChE, e.g., neurons, caused an accumulation of the misfolded AChE in the ER. This misfolded enzyme was not able to transport to the Golgi/plasma membrane, which subsequently induced ER stress and its downstream signaling cascade of unfolded protein response. Once the stress was overwhelming, the cooperation of ER with mitochondria increased the loss of mitochondrial membrane potential. Eventually, the tacrine-exposed cells lost homeostasis and underwent apoptosis. The ER stress and apoptosis, induced by tacrine, were proportional to the amount of AChE. Other AChEIs (rivastigmine, bis(3)-cognitin, daurisoline, and dauricine) could cause the same problem as tacrine by inducing ER stress in neuronal cells. The results provide guidance for the drug design and discovery of AChEIs for AD treatment. SIGNIFICANCE STATEMENT: Acetylcholinesterase inhibitors (AChEIs) are the most developed treatment strategies for Alzheimer's disease (AD) and will be used in clinic for at least the next decades. This study reports that tacrine and other AChEIs disrupt the proper trafficking of acetylcholinesterase in the endoplasmic reticulum. Eventually, the apoptosis of neurons and other cells are induced. The results provide guidance for drug design and discovery of AChEIs for AD treatment.
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Acetilcolinesterase/metabolismo , Apoptose/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Tacrina/farmacologia , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Células Cultivadas , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/fisiologia , Células HEK293 , Humanos , Camundongos , Simulação de Acoplamento Molecular/métodos , Neurônios/enzimologia , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Tacrina/químicaRESUMO
Systems biology unravels the black box of signaling pathway of cells; but which has not been extensively applied to reveal the mechanistic synergy of a herbal formula. The therapeutic efficacies of a herbal formula having multi-target, multi-function and multi-pathway are the niches of traditional Chinese medicine (TCM). Here, we reported an integrated omics approach, coupled with the knockout of an active compound, to measure the regulation of cellular signaling, as to reveal the landscape in cultured rat osteoblasts having synergistic pharmacological efficacy of Danggui Buxue Tang (DBT), a Chinese herbal formula containing Angelicae Sinensis Radix and Astragali Radix. The changes in signaling pathways responsible for energy metabolism, RNA metabolism and protein metabolism showed distinct features between DBT and calycosin-depleted DBT. Here, our results show that calycosin within DBT can orchestrate the osteoblastic functions and signaling pathways of the entire herbal formula. This finding reveals the harmony of herbal medicine in pharmacological functions, as well as the design of drug/herbal medicine formulation. The integration of systems biology can provide novel and essential insights into the synergistic property of a herbal formula, which is a key in modernizing TCM.
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BACKGROUND: Cisplatin (DDP) is the first-in-class drug for advanced and non-targetable non-small-cell lung cancer (NSCLC). A recent study indicated that DDP could slightly induce non-apoptotic cell death ferroptosis, and the cytotoxicity was promoted by ferroptosis inducer. The agents enhancing the ferroptosis may therefore increase the anticancer effect of DDP. Several lines of evidence supporting the use of phytochemicals in NSCLC therapy. Ginkgetin, a bioflavonoid derived from Ginkgo biloba leaves, showed anticancer effects on NSCLC by triggering autophagy. Ferroptosis can be triggered by autophagy, which regulates redox homeostasis. Thus, we aimed to elucidate the possible role of ferroptosis involved in the synergistic effect of ginkgetin and DDP in cancer therapy. METHODS: The promotion of DDP-induced anticancer effects by ginkgetin was examined via a cytotoxicity assay and western blot. Ferroptosis triggered by ginkgetin in DDP-treated NSCLC was observed via a lipid peroxidation assay, a labile iron pool assay, western blot, and qPCR. With ferroptosis blocking, the contribution of ferroptosis to ginkgetin + DDP-induced cytotoxicity, the Nrf2/HO-1 axis, and apoptosis were determined via a luciferase assay, immunostaining, chromatin immunoprecipitation (CHIP), and flow cytometry. The role of ferroptosis in ginkgetin + DDP-treated NSCLC cells was illustrated by the application of ferroptosis inhibitors, which was further demonstrated in a xenograft nude mouse model. RESULTS: Ginkgetin synergized with DDP to increase cytotoxicity in NSCLC cells, which was concomitant with increased labile iron pool and lipid peroxidation. Both these processes were key characteristics of ferroptosis. The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured NSCLC cells. Furthermore, blocking ferroptosis reversed the ginkgetin-induced inactivation of Nrf2/HO-1 as well as the elevation of ROS formation, MMP loss, and apoptosis in DDP-treated NSCLC cells. CONCLUSION: This study is the first to report that ginkgetin derived from Ginkgo biloba leaves promotes DDP-induced anticancer effects, which can be due to the induction of ferroptosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biflavonoides/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Células A549 , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Biflavonoides/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Receptores ErbB/genética , Ferroptose/efeitos dos fármacos , Ginkgo biloba/química , Heme Oxigenase-1/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Nus , Folhas de Planta/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The fruits of Ziziphus jujuba, commonly known as jujube, red date or Chinese date, are taken as fresh or dried food, and as traditional medicine worldwide due to high nutritional and health values. Traditionally in China, jujube is considered as a medicinal fruit that is being used in treating blood deficiency. In this review, the beneficial effects of jujubes on the hematopoietic functions are summarized and discussed. As illustrated in cell and animal models, the application of jujube extract possessed beneficial effects, including regulation of erythropoiesis via activation of hypoxia inducible factor-induced erythropoietin, potential capacity in recycling heme iron during erythrophagocytosis and bi-directional regulation of immune response. Thus, the blood-nourishing function of jujube is being proposed here. Flavonoid, polysaccharide and triterpenoid within jujube could serve as the potential active ingredients accounting for the aforementioned health benefits. Taken together, these findings provide several lines of evidence for further development of jujube as supplementary products for prevention and/or treatment of anemia.
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Corydalis Rhizoma (CR) is a commonly used traditional Chinese medicine for its potency in activating blood circulation and analgesia. In clinic, CR extracts or components are commonly used in the treatment of myocardial ischemia, rheumatism, and dysmenorrhea with different types of inflammation. However, due to different mechanism of pain and inflammation, the anti-inflammatory property of CR has not been fully revealed. Here, the major chromatographic peaks of CR extracts in different extracting solvents were identified, and the anti-inflammatory activities of CR extracts and its major alkaloids were evaluated in LPS-treated macrophages by determining expressions of proinflammatory cytokines, IκBα and NF-κB. The most abundant alkaloid in CR extract was dehydrocorydaline, having >50% of total alkaloids. Besides, the anti-inflammatory activities of dehydrocorydaline and its related analogues were demonstrated. The anti-inflammatory roles were revealed in LPS-treated cultured macrophages, including (i) inhibiting proinflammatory cytokines release, for example, TNF-α, IL-6; (ii) suppressing mRNA expressions of proinflammatory cytokines; (iii) promoting IκBα expression and suppressing activation of NF-κB transcriptional element; and (iv) reducing the nuclear translocation of NF-κB. The results supported that dehydrocorydaline was the major alkaloid in CR extract, which, together with its analogous, accounted the anti-inflammatory property of CR.
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Stephaniae tetrandrae radix (STR) is a commonly used traditional Chinese medicine in alleviating edema by inducing diuresis. In the clinic, STR extracts or its components are widely used in the treatment of edema, dysuria, and rheumatism for the regulation of water metabolism. Furthermore, STR has been used in treating emotional problems for years by combining with other Chinese herbs. However, the material basis and mechanism of STR on the nervous system have not been revealed. Here, the main components of STR extracts with different extracting solvents were identified, including three major alkaloids, i.e., cyclanoline, fangchinoline, and tetrandrine. The cholinesterase inhibitory activity of STR extracts and its alkaloids was determined using the Ellman assay. Both cyclanoline and fangchinoline showed acetylcholinesterase (AChE) inhibitory activity, demonstrating noncompetitive enzyme inhibition. In contrast, tetrandrine did not show enzymatic inhibition. The synergism of STR alkaloids with huperzine A or donepezil was calculated by the median-effect principle. The drug combination of fangchinoline-huperzine A or donepezil synergistically inhibited AChE, having a combination index (CI) < 1 at Fa = 0.5. Furthermore, the molecular docking results showed that fangchinoline bound with AChE residues in the peripheral anionic site, and cyclanoline bound with AChE residues in the peripheral anionic site, anionic site, and catalytic site. In parallel, cyclanoline bound with butyrylcholinesterase (BChE) residues in the anionic site, catalytic site, and aromatic site. The results support that fangchinoline and cyclanoline, alkaloids derived from STR, could account for the anti-AChE function of STR. Thus, STR extract or its alkaloids may potentially be developed as a therapeutic strategy for Alzheimer's patients.