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1.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36077502

RESUMO

Cottonseed meal (CSM) is a good source of dietary proteins but is unsuitable for human consumption due to its gossypol content. To unlock its potential, we developed a protein extraction process with a gossypol removal treatment to generate CSM protein isolate (CSMPI) with ultra-low gossypol content. This process successfully reduced the free and total gossypol content to 4.8 ppm and 147.2 ppm, respectively, far below the US FDA limit. In addition, the functional characterisation of CSMPI revealed a better oil absorption capacity and water solubility than pea protein isolate. Proteome profiling showed that the treatment improved protein identification, while SDS-PAGE analysis indicated that the treatment did not induce protein degradation. Amino acid analysis revealed that post-treated CSMPI was rich in branched-chain amino acids (BCAAs). Mass spectrometry analysis of various protein fractions obtained from an in vitro digestibility assay helped to establish the digestibility profile of CSM proteins. Several potential allergens in CSMPI were also found using allergenic prediction software, but further evaluation based on their digestibility profiles and literature reviews suggests that the likelihood of CSMPI allergenicity remains low. Overall, our results help to navigate and direct the application of CSMPIs as alternative proteins toward nutritive human food application.


Assuntos
Óleo de Sementes de Algodão , Gossipol , Aminoácidos/análise , Ração Animal/análise , Óleo de Sementes de Algodão/análise , Óleo de Sementes de Algodão/química , Proteínas na Dieta , Humanos , Proteômica
2.
BMC Vet Res ; 18(1): 347, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109808

RESUMO

BACKGROUND: Cottonseed meal (CSM), a relatively rich source of protein and amino acids, is used as an inexpensive alternative to soybean meal (SBM) in poultry diets. However, the toxicity of free gossypol in CSM has been a primary concern. The present study was conducted to investigate the effects of CSM on growth performance, serum biochemical parameters, and liver redox status in goslings at 1 to 28 days of age. Three hundred 1-day-old male goslings were randomly divided into 5 groups (10 goslings/pen, 6 replicate pens/group) and subjected to a 28-day experiment. Five isonitrogenous and isoenergetic diets were formulated such that 0% (control), 25% (CSM25), 50% (CSM50), 75% (CSM75), and 100% (CSM100) of protein from SBM was replaced by protein from CSM. The free gossypol contents in the five diets were 0, 56, 109, 166, and 222 mg/kg, respectively. RESULTS: The results showed that dietary CSM was associated with linear decreases in body weight, average daily feed intake and average daily gain and linear increases in the feed-to-gain ratio from 1 to 28 days of age (P < 0.001). As the dietary CSM concentration increased, a numerical increase was found in the mortality of goslings. According to a single-slope broken-line model, the breakpoints for the average daily gain of dietary free gossypol concentration on days 1 to 14, 15 to 28, and 1 to 28 occurred at 23.63, 14.78, and 18.53 mg/kg, respectively. As the dietary CSM concentration increased, serum albumin (P < 0.001) concentrations decreased linearly and serum uric acid (P = 0.011) increased linearly. The hydroxyl radical scavenging ability (P = 0.002) and catalase (P < 0.001) and glutathione peroxidase (P = 0.001) activities of the liver decreased linearly with increasing dietary CSM. However, dietary CSM did not affect the concentrations of reactive oxygen metabolites, malondialdehyde, or protein carbonyl in the liver. CONCLUSIONS: The increasing dietary CSM increased the concentration of free gossypol and altered the composition of some amino acids in the diet. A high concentration of CSM reduced the growth performance of goslings aged 1 to 28 days by decreasing feed intake, liver metabolism, and antioxidant capacity. From the primary concern of free gossypol in CSM, the tolerance of goslings to free gossypol from CSM is low, and the toxicity of free gossypol has a cumulative effect over time.


Assuntos
Óleo de Sementes de Algodão , Gossipol , Aminoácidos/metabolismo , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Catalase , Óleo de Sementes de Algodão/análise , Óleo de Sementes de Algodão/metabolismo , Óleo de Sementes de Algodão/farmacologia , Gansos/metabolismo , Glutationa Peroxidase , Gossipol/análise , Gossipol/metabolismo , Gossipol/farmacologia , Radical Hidroxila/análise , Radical Hidroxila/metabolismo , Radical Hidroxila/farmacologia , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Oxirredução , Oxigênio/metabolismo , Albumina Sérica/análise , Soja/metabolismo , Ácido Úrico/análise
3.
Phytomedicine ; 106: 154398, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36049429

RESUMO

BACKGROUND: Male factor infertility often results from testicular disorders leading to inadequate sperm quantity and quality. Both beneficial and detrimental effects of botanical products, especially herbal medicines, on testicular functions and male fertility have been reported in the literature. PURPOSE: This scoping review aims to map the main clinical evidence on different impacts of botanical entities on the testis and to critically appraise relevant randomized controlled trials (RCTs) published in the recent 5 years, so as to inform the future. METHODS: Systematic reviews, meta-analyses and RCT reports on botanical impacts on testicular functions and male fertility were retrieved and synthesized from Pubmed, Web of Science, Scopus, Embase, ProQuest, Cochrane Library and Google Scholar up to 10th May 2022. RCTs published since 2018 were critically appraised against good practice guidelines for RCT and for reporting herbal studies. RESULTS: We identified 24 systematic reviews and meta-analyses published since 2005, by authors from Iran (25%), China (21%), USA (12.5%) and 9 other countries. All but two were published in English. Only 3 systematic review protocols were identified, all published in English from China in the recent 3 years. We identified 125 RCTs published in six languages, mainly English (55%) and Chinese (42%). They were published since 1994 from 23 countries on all the six inhabitable continents, with China (46%), Australia (8%), USA (8%), India (7%) and Iran (5%) being the leading contributors. 72% and 28% RCTs published in English were on efficacy (botanicals vs placebo) and comparative effectiveness (a botanical vs other treatments), respectively. In contrast, 98% RCT reports in Chinese were on comparative effectiveness, with merely 2% on efficacy. Among all the 125 RCTs, 57% were studies in patients with semen abnormality and/or male infertility, 22% investigated herbal effects in healthy men, 14% were on patients with male sexual dysfunction and hypogonadism, and 7% were conducted in men with non-sexual disorders. Since 2018, 32 RCTs have been published, in English (69%) or Chinese (31%). Nineteen RCT reports from China, India, Japan and Korea all studied herbal formulae while the 13 RCT reports from Australia, Brazil, Czech and Italy, Iran, Malaysia, Spain, the UK and the USA all exclusively studied extracts of a single species. Putting geo-cultural differences aside, gossypol and extracts of Tripterygium wilfordii Hook. f. were found to be detrimental to the testis and male fertility, while the extracts of Withania somnifera (L.) Dunal and traditional Chinese medicine Qilin Pill, etc., might improve testosterone levels and semen parameters, thus could be therapeutic for male sexual dysfunction and infertility. However, all still require further evaluation in view of recurring weaknesses in quality control of herbal materials, RCT design and reporting. For example, only 9%-23% of the RCTs published since 2018 provided information on voucher samples, chemical profiling, herbal authentication and herbal extraction. CONCLUSION: Research on botanicals and the testis has been reported worldwide, demonstrating clear geo-cultural differences in studied plant species, botanical types, study objectives and quality of research design, implementation and reporting. Due to a few recurring weaknesses in the literature, this study is unable to recommend the use of any specific botanicals, however, current evidence does indicate that botanicals can be double-edged swords to the testis and male fertility. To secure better clinical evidence, future studies must faithfully implement existing and emerging good practice guidelines.


Assuntos
Gossipol , Infertilidade Masculina , Fertilidade , Gossipol/uso terapêutico , Humanos , Infertilidade Masculina/tratamento farmacológico , Masculino , Testículo , Testosterona
4.
Planta ; 256(3): 63, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35995890

RESUMO

MAIN CONCLUSION: GhMYC2 regulates the gossypol biosynthesis pathway in cotton through activation of the expression of gossypol synthesis gene CYP71BE79, CDNC, CYP706B1, DH1, and CYP82D113. Cotton is one of the main cash crops globally. Cottonseed contains fiber, fat, protein, and starch, and has important economic value. However, gossypol in cottonseed seriously affects the development and utilization of cottonseed. Nonetheless, gossypol has great application potential in agriculture, medicine, and industry. Therefore, it is very important to study gossypol biosynthesis and its upstream regulatory pathways. It has been reported that the content of gossypol in hairy roots of cotton is regulated through jasmonic acid signaling; however, the specific molecular mechanism has not been revealed yet. We found that the expression of basic helix-loop-helix family transcription factor GhMYC2 was significantly upregulated after exogenous administration of methyl jasmonate to cotton seedlings, and the content of gossypol changed significantly with the variation of GhMYC2 expression. Further studies revealed that GhMYC2 could specifically bind to the G-Box in the promoter region of CDNC, CYP706B1, DH1, CYP82D113, CYP71BE79 to activate its expression and regulate gossypol synthesis, and its activation of CYP71BE79 promoter was inhibited by GhJAZ2. Not only that GhMYC2 could also interact with GoPGF. In this work, the molecular mechanisms of gossypol biosynthesis regulated by GhMYC2 were analyzed. The results provide a theoretical basis for cultivating new varieties of low-gossypol or high-gossypol cotton and creating excellent germplasm resources.


Assuntos
Gossipol , Vias Biossintéticas/genética , Óleo de Sementes de Algodão , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Gossypium/genética , Gossypium/metabolismo , Gossipol/metabolismo , Metabolismo Secundário
5.
Genes (Basel) ; 13(8)2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-36011363

RESUMO

Gossypium hirsutum is an important source of natural textile fibers. Gossypol, which is a sesquiterpenoid compound mainly existing in the cotton pigment glands, can facilitate resistance to the stress from diseases and pests. The level of gossypol in the cotton is positively correlated to the quantity of pigment glands. However, the underlying regulatory mechanisms of gossypol synthesis and gland morphogenesis are still poorly understood, especially from a transcriptional perspective. The transcripts of young leaves and ovules at 30 DPA of the glanded plants and glandless plants were studied by RNA-Seq and 865 million clean reads were obtained. A total of 34,426 differentially expressed genes (DEGs) were identified through comparative transcriptome analysis. Genes related to gossypol synthesis or gland morphogenesis displayed significant differential expression between the two cultivars. Functional annotation revealed that the candidate genes related to catalytic activity, the biosynthesis of secondary metabolites, and biomolecular decomposition processes. Our work herein unveiled several potential candidate genes related to gossypol synthesis or gland morphogenesis and may provide useful clues for a breeding program of cotton cultivars with low cottonseed gossypol contents.


Assuntos
Gossypium , Gossipol , Perfilação da Expressão Gênica , Gossypium/genética , Gossypium/metabolismo , Gossipol/metabolismo , Morfogênese/genética , Melhoramento Vegetal
6.
J Sci Food Agric ; 102(13): 6169-6174, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35808803

RESUMO

BACKGROUND: Cottonseed oil is one of the most widely consumed cooking oils because of its high nutritional benefits and relatively low price. The present study evaluated the effects of tetramethoxy gossypol (TMG), a rarely reported degradation product of free gossypol produced in crudely extracted cottonseed oil, on the metabolic responses of liver, heart, spleen, kidney and lung tissues in rats using proton nuclear magnetic resonance (1 H NMR) spectroscopy combined with chemometric and bioinformatics techniques. RESULTS: Endogenous low-molecular-weight metabolites in rat liver, heart, spleen, kidney and lung tissues were profiled by 1 H NMR spectroscopy. The unsupervised principal components analysis and the supervised orthogonal partial least squares discriminant analysis revealed that the metabolic profiles in liver samples were greatly changed after TMG administration. Twenty significantly changed liver metabolites were screened out and further evaluated by receiver operating characteristic curve analysis, which were closely related to amino acid, glutathione, energy and lipid metabolism. CONCLUSION: Concerning the potential chronic exposure to TMG in cottonseed oil and other cottonseed products, the cumulative effects of dietary TMG on tissues, especially the liver, should be noted when improving the quality control standard of cottonseed oil. © 2022 Society of Chemical Industry.


Assuntos
Óleo de Sementes de Algodão , Gossipol , Animais , Óleo de Sementes de Algodão/análise , Óleo de Sementes de Algodão/química , Óleo de Sementes de Algodão/farmacologia , Dieta , Gossipol/análise , Gossipol/química , Gossipol/farmacologia , Fígado , Espectroscopia de Ressonância Magnética , Ratos
7.
Chem Biol Interact ; 364: 110060, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35872041

RESUMO

Epirubicin (EPI)-based transarterial chemoembolization is an effective therapy for advanced hepatocellular carcinoma (HCC). However, EPI-induced survivin expression limits its tumor-killing potential in HCC. Interestingly, (-)-gossypol ((-)-Gsp), a male contraceptive, suppresses various malignancies. More importantly, (-)-Gsp also holds promise for enhancing the antitumor effects of chemotherapy in numerous cancer types. In the present study, we demonstrated for the first time that (-)-Gsp-sensitized EPI inhibited cell growth and induced apoptosis of HCC cells in vitro. Furthermore, (-)-Gsp sensitized EPI by attenuating the EPI-elevated survivin protein levels. Mechanistic studies showed that EPI stimulated survivin protein synthesis by promoting translation initiation, which was alleviated by (-)-Gsp mainly through suppressing the AKT-4EBP1/p70S6K-survivin and ERK-4EBP1-survivin pathways. HCC xenograft experiments in nude mice also showed that (-)-Gsp treatment acted synergistically with EPI to repress xenograft tumor growth. Overall, our proof-of-concept results may pave the way for novel strategies for the treatment of HCC based on the combination of EPI and (-)-Gsp.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Gossipol , Neoplasias Hepáticas , Animais , Apoptose , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Survivina , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Oral Oncol ; 132: 105979, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35816876

RESUMO

The purpose of this review was to summarise available literature concerning the anticancer effects of both putative and validated BH3-mimetics in head and neck squamous cell carcinomas. A literature search was performed and studies assessing malignant cell lines, xenograft models, and/or humans were considered eligible. A total of 501 studies were identified, of which 40 were included. One phase-II clinical trial assessing gossypol (combined with docetaxel) was found. The remaining 39 preclinical studies investigated cell lines and/or xenograft models involving the use of six validated BH3-mimetics (A-1210477, A-1331852, ABT-737, navitoclax, S63845, venetoclax) and six putative BH3-mimetics (ApoG2, gossypol, obatoclax, sabutoclax, TW-37, and YC137). In preclinical settings, most validated BH3-mimetics were capable of inducing apoptosis (in-vitro) and tumour growth inhibition (in-vivo). The majority of putative BH3-mimetics were also capable of inducing cell death, although important off-target effects, such as autophagy induction, were also described. Combinations with conventional anticancer drugs, ionising radiation, or multiple BH3-mimetics generally resulted in enhanced anticancer effects, such as increased sensitivity to apoptotic stimuli, especially considering some cell lines that showed resistance to either treatment alone. In conclusion, although clinical data are still insufficient to evaluate the anticancer effects of BH3-mimetics in head and neck squamous cell carcinomas, promising results in preclinical settings were observed concerning induction of cell death and inhibition of tumour growth. Therefore, further clinical trials are highly encouraged.


Assuntos
Antineoplásicos , Gossipol , Neoplasias de Cabeça e Pescoço , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Gossipol/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
9.
BMC Biol ; 20(1): 143, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35706035

RESUMO

BACKGROUND: Zika virus (ZIKV) and dengue virus (DENV) cause microcephaly and dengue hemorrhagic fever, respectively, leading to severe problems. No effective antiviral agents are approved against infections of these flaviviruses, calling for the need to develop potent therapeutics. We previously identified gossypol as an effective inhibitor against ZIKV and DENV infections, but this compound is toxic and not suitable for in vivo treatment. RESULTS: In this study, we showed that gossypol derivative ST087010 exhibited potent and broad-spectrum in vitro inhibitory activity against infections of at least ten ZIKV strains isolated from different hosts, time periods, and countries, as well as DENV-1-4 serotypes, and significantly reduced cytotoxicity compared to gossypol. It presented broad-spectrum in vivo protective efficacy, protecting ZIKV-infected Ifnar1-/- mice from lethal challenge, with increased survival and reduced weight loss. Ifnar1-/- mice treated with this gossypol derivative decreased viral titers in various tissues, including the brain and testis, after infection with ZIKV at different human isolates. Moreover, ST087010 potently blocked ZIKV vertical transmission in pregnant Ifnar1-/- mice, preventing ZIKV-caused fetal death, and it was safe for pregnant mice and their pups. It also protected DENV-2-challenged Ifnar1-/- mice against viral replication by reducing the viral titers in the brain, kidney, heart, and sera. CONCLUSIONS: Overall, our data indicate the potential for further development of this gossypol derivative as an effective and safe broad-spectrum therapeutic agent to treat ZIKV and DENV diseases.


Assuntos
Vírus da Dengue , Dengue , Gossipol , Infecção por Zika virus , Zika virus , Animais , Reações Cruzadas , Dengue/tratamento farmacológico , Dengue/prevenção & controle , Feminino , Gossipol/farmacologia , Gossipol/uso terapêutico , Masculino , Camundongos , Gravidez , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/prevenção & controle
10.
Front Cell Infect Microbiol ; 12: 870852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35521220

RESUMO

Babesia bigemina is a tick-borne apicomplexan hemoprotozoan responsible for bovine babesiosis. The current drugs used for bovine babesiosis treatment have several drawbacks, including toxicity, the lack of effectiveness to clear the parasite, and potential to develop resistance. Identifying compounds that target essential and unique parasite metabolic pathways is a rational approach toward finding alternative drug treatments. Based on the genome sequence and transcriptomics analysis, it can be inferred that anaerobic glycolysis is the dominant adenosine triphosphate (ATP) supply for Babesia, and lactate dehydrogenase (LDH) is one of the essential enzymes in this pathway. Furthermore, the Babesia LDH sequence is distinct from its bovine homologue and thus a potential chemotherapeutic target that would result in decreasing the ATP supply to the parasite but not to the host. Gossypol is a known efficient specific inhibitor of LDH in the sensu stricto B. bovis and the sensu lato B. microti, among other related parasites, but no such data are currently available in the sensu stricto B. bigemina parasites. Hereby, we show that the LDH amino acid sequence is highly conserved among sensu stricto but not in sensu lato Babesia spp. A predictive structural analysis of B. bigemina LDH showed the conservation of the key amino acids involved in the binding to gossypol compared to B. bovis. Gossypol has a significant (P < 0.0001) inhibitory effect on the in vitro growth of B. bigemina, with IC50 of 43.97 mM after 72 h of treatment. The maximum IC (IC98) was observed at 60 mM gossypol. However, a significant effect on the viability of cattle PBMC was observed when the cells were cultured with 60 mM (IC98) gossypol compared with DMSO-exposed control cells. Interestingly, B. bigemina cultured at 3% oxygen expresses significantly higher levels of LDH and is more resistant to gossypol than the parasites maintained at ambient conditions containing ~20% oxygen. Altogether, the results suggest the potential of gossypol as an effective drug against B. bigemina infection, but the risk of host toxicity at therapeutic doses should be further evaluated in in vivo studies.


Assuntos
Babesia bovis , Babesia , Babesiose , Doenças dos Bovinos , Gossipol , Trifosfato de Adenosina , Animais , Babesia bovis/genética , Babesiose/tratamento farmacológico , Babesiose/parasitologia , Bovinos , Doenças dos Bovinos/parasitologia , Gossipol/farmacologia , L-Lactato Desidrogenase/farmacologia , Leucócitos Mononucleares , Oxigênio
11.
Nat Prod Rep ; 39(6): 1282-1304, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35587693

RESUMO

Covering up to 2022Gossypol is a polyphenolic compound isolated from cottonseed. There are two optical enantiomers of gossypol, (-)-gossypol and (+)-gossypol. Gossypol exists as three different tautomers, aldehyde, ketone and lactol. Gossypol is toxic and provides a protective mechanism for cotton plants against pests. Gossypol was used as a male contraceptive in China in the 1970s. It was eventually abandoned due to noticeable side effects, disruption of potassium uptake and incomplete reversibility. Gossypol has gained considerable research interest due to its attractive biological activities, especially antitumor and antivirus. Gossypol derivatives are prepared by a structural modification to reduce toxicity and improve their therapeutic effect. This review depicts the bioactivity and regulation mechanisms of gossypol and its derivatives as drug lead compounds, with emphasis on its antitumor mechanism. The design and synthesis of pharmacologically active derivatives based on the structure of gossypol, such as gossypol Schiff bases, apogossypol, gossypolone, are thoroughly discussed. This review aims to serve as a reference for gossypol-based drug discovery and drug design.


Assuntos
Gossipol , Desenho de Fármacos , Descoberta de Drogas , Gossipol/química , Gossipol/farmacologia , Humanos , Masculino , Bases de Schiff/química , Estereoisomerismo
12.
Int J Mol Sci ; 23(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35563290

RESUMO

Cotton refers to species in the genus Gossypium that bear spinnable seed coat fibers. A total of 50 species in the genus Gossypium have been described to date. Of these, only four species, viz. Gossypium, hirsutum, G. barbadense, G. arboretum, and G. herbaceum are cultivated; the rest are wild. The black dot-like structures on the surfaces of cotton organs or tissues, such as the leaves, stem, calyx, bracts, and boll surface, are called gossypol glands or pigment glands, which store terpenoid aldehydes, including gossypol. The cotton (Gossypium hirsutum) pigment gland is a distinctive structure that stores gossypol and its derivatives. It provides an ideal system for studying cell differentiation and organogenesis. However, only a few genes involved in the process of gland formation have been identified to date, and the molecular mechanisms underlying gland initiation remain unclear. The terpenoid aldehydes in the lysigenous glands of Gossypium species are important secondary phytoalexins (with gossypol being the most important) and one of the main defenses of plants against pests and diseases. Here, we review recent research on the development of gossypol glands in Gossypium species, the regulation of the terpenoid aldehyde biosynthesis pathway, discoveries from genetic engineering studies, and future research directions.


Assuntos
Gossypium , Gossipol , Aldeídos/metabolismo , Fibra de Algodão , Regulação da Expressão Gênica de Plantas , Gossypium/metabolismo , Gossipol/metabolismo , Gossipol/farmacologia , Organogênese , Terpenos/metabolismo
13.
Fish Physiol Biochem ; 48(3): 785-804, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35553294

RESUMO

In a feeding experiment, cottonseed meal (CSM) was used to replace fishmeal (FM) in the diet of snubnose pompano, Trachinotus blochii, supplemented with lysine and methionine to assess the growth, nutritive profile, hematological, histological, and stress biomarker response. Experimental fishes were randomly stocked in five treatments each with triplicates. Five isonitrogenous and isolipidic diets with graded level of CSM (0, 8.7, 17.4, 26.0, and 34.7%) as replacement for FM protein (0, 25, 50, 75, and 100%) were formulated and fed to respective treatments. Comparison between various parameters among the treatments was made using orthogonal polynomial contrasts to indicate the statistical significance. Higher alkaline phosphatase, acid phosphatase, lactate dehydrogenase, malate dehydrogenase, aspartate, and alanine aminotransferase activities were observed in 0CSM group and followed by 100CSM group as higher inclusion level of CSM with higher free gossypol content did not affect the metabolic enzyme activities. The maximum muscular free gossypol accretion of 1.28 mg kg-1 (on wet basis) was recorded in 100CSM group which was very well below the critical limit set by FDA. As a conclusion, fishmeal can be completely replaced using cottonseed meal in the diet of pompano without adverse effect on growth, metabolism, and general health.


Assuntos
Óleo de Sementes de Algodão , Gossipol , Ração Animal/análise , Animais , Biomarcadores , Óleo de Sementes de Algodão/metabolismo , Dieta/veterinária , Peixes/metabolismo , Gossipol/metabolismo , Lisina , Metionina
14.
J Agric Food Chem ; 70(22): 6688-6697, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35635005

RESUMO

Gossypol, the main antinutritional factor in cottonseed protein concentrate (CPC), could affect the growth conditions of fish, but the underlying mechanism remains unclear. In this study, an 8-week feeding trial was carried out to investigate the effects of gossypol on Nile tilapia (Oreochromis niloticus). Three experimental diets were designed, including control diet (CON), control diet supplemented with 150 mg/kg gossypol (ML), and 300 mg/kg gossypol (MH). 16S rRNA gene sequencing showed that gossypol significantly reduced the richness and diversity of the gut microbiota. Untargeted metabolite analysis revealed that most metabolites were down-regulated by gossypol, and riboflavin was the key metabolite with significant difference between CON-treated and gossypol-treated groups. Gossypol caused intestinal inflammation, oxidative stress, and apoptosis. Through fecal bacteria transplantation experiments, we demonstrated that intestinal microbiota mediated gossypol-induced negative effects, suggesting that intestinal microbiota and its metabolite may account for the harmful effects of gossypol.


Assuntos
Ciclídeos , Microbioma Gastrointestinal , Gossipol , Ração Animal/análise , Animais , Apoptose , Ciclídeos/genética , Dieta/veterinária , Suplementos Nutricionais , Gossipol/toxicidade , Inflamação/induzido quimicamente , Estresse Oxidativo , RNA Ribossômico 16S/genética
15.
Gene ; 828: 146462, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35413394

RESUMO

Terpenoids are widely distributed in plants and play important roles in the regulation of plant growth and development and in the interactions between plants and both the environment and other organisms. However, terpene synthase (TPS) genes have not been systematically investigated in the tetraploid Gossypium hirsutum. In this study, whole genome identification and characterization of the TPS family from G. hirsutum were carried out. Eighty-five TPS genes, including 47 previously unidentified genes, were identified in the G. hirsutum genome and classified into 5 subfamilies according to protein sequence similarities, as follows: 43 GhTPS-a, 29 GhTPS-b, 4 GhTPS-c, 7 GhTPS-e/f, and 2 GhTPS-g members. These 85 TPS genes were mapped onto 19 chromosomes of the G. hirsutum genome. Segmental duplications and tandem duplications contributed greatly to the expansion of TPS genes in G. hirsutum and were followed by intense purifying selection during evolution. Indentification of cis-acting regulatory elements suggest that the expression of TPS genes is regulated by a variety of hormones. RNA sequencing (RNA-seq) expression profile analysis revealed that the TPS genes had distinct spatiotemporal expression patterns, and several genes were highly and preferentially expressed in the leaves of cotton with gossypol glands (glanded cotton) versus a glandless strain. Virus-induced gene silencing (VIGS) of three TPS genes yielded plants characterized by fewer, smaller, and lighter gossypol glands, which indicated that these three genes were responsible for gland activity. Taken together, our results provide a solid basis for further elucidation of the biological functions of TPS genes in relation to gland activity and gossypol biosynthesis to develop cotton cultivars with low cottonseed gossypol contents.


Assuntos
Alquil e Aril Transferases , Gossipol , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Regulação da Expressão Gênica de Plantas , Gossypium , Gossipol/metabolismo , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
16.
Mol Biol Rep ; 49(6): 4727-4735, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35290558

RESUMO

BACKGROUND: Gossypium hirsutum seeds are rich in gossypol. In addition to its diverse beneficial properties, it is a known anti-fertility inducing agent in humans. Oxycarenus laetus feeds on the cottonseeds and yet its courtship, mating and reproduction is unaffected. METHODS AND RESULTS: In this study, we performed a transcriptome profiling of O. laetus fed on Abutilon indicum (AB-no gossypol), G. hirsutum (GH-natural gossypol) and 1400 ppm commercial gossypol-soaked GH seeds (GHGO). Illumina NextSeq-500 paired-end 75 bp reads were generated and de novo assembled (48,214 genes) to identify the differentially expressed transcripts (DET) between the samples. Gene enrichment, KEGG pathway and cluster profiling of the DETs resulted in the identification of vital genes involved in the detoxification, pheromone biosynthesis, cuticle protein in the GHGO sample. Cyp4C1, Cyp6a13, Cyp6a14, Cyp4g15, Cyp4em8, Cyp303a1 were the detoxification related genes identified. Similarly, SDR dehydrogenase family 11 and fatty acid synthase in pheromone biosynthesis and cuticle proteins (RR1 and RR2) coding transcripts were found to be differentially expressed. CONCLUSION: This is the first study to report the expression of genes induced by gossypol in O. laetus. Based on the findings from the DET analysis, we conclude that the detoxification related genes of gossypol treated samples were affected.


Assuntos
Gossipol , Hemípteros , Animais , DEET/metabolismo , Perfilação da Expressão Gênica , Gossypium/genética , Gossypium/metabolismo , Gossipol/análise , Gossipol/metabolismo , Gossipol/farmacologia , Hemípteros/genética , Hemípteros/metabolismo , Humanos , Feromônios/metabolismo
17.
Mol Biol Rep ; 49(6): 4919-4928, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35338438

RESUMO

BACKGROUND: In cotton the identification and characterization of natural defense is a cost-effective, sustainable, and environment-friendly strategy to combat cotton pests. The secondary metabolites traits in cotton plant i.e., toxic gossypol glands play significant role for development and self-defense mechanism. To utilize gossypol in breeding implements, the understanding of gossypol initiation biosynthesis genes has vital importance at reproductive organ development stages. METHODS: Cotton germplasm of 100 genotypes screened visually based on gossypol glandedness and a core set of ten genotypes was developed. Further three genotypes FH-330 (high glanding), F-280 (low glanding) and IRMA-197 (glandless) were used for determining the transcript abundance of twelve gossypol biosynthesis genes. RESULTS: Out of 100, germplasm categorized as (76) high glanding, (22) medium glanding), one genotype for each (low glanding) and (glandless) category. Real-time qPCR analysis revealed varied expression patterns among selected three genotypes. Out of twelve, three genes CYP706B1, CDNC and 2ODD-1 had strong expression levels in all tested tissues in high glanded genotype, while, slight or no expression of these genes was recorded in low glanding and glandless genotype, respectively. The shell of developing boll (10, 20, 30 DPA), and developing embryo (20, 30 DPA) showed substantially medium to maximum expression, respectively while high to medium expression was recorded in sepals and leaf tissue. CONCLUSIONS: Our study demonstrated that CYP706B1, CDNC and 2ODD-1 are the most promising genes involved in gossypol biosynthesis. Developing boll shell, developing embryo, leaf and sepal also have significant ability to synthesize gossypol. This will provide scientists a way to manipulate gossypol contents in economically important organs of cotton plant for targeted breeding.


Assuntos
Gossipol , Gossypium/genética , Gossypium/metabolismo , Gossipol/metabolismo , Melhoramento Vegetal , Folhas de Planta/genética , Folhas de Planta/metabolismo
18.
Pest Manag Sci ; 78(6): 2357-2369, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35254729

RESUMO

BACKGROUND: Helicoverpa armigera and Aphis gossypii are two important insect species that feed on cotton plants. These insects have distinct abilities to induce plant resistance and tolerate plant toxins, which results in interspecific competition imbalance that may be fatal to the low-tolerance A. gossypii and force these insects to develop avoidance behaviors and subsequently separate from their niche. We implemented ecological experiments to test the effects of H. armigera-induced plant resistance and behavioral avoidance in A. gossypii, and employed transcriptomics and metabolomics analyses to reveal changes in resistance genes and metabolites in plants. RESULTS: Our results demonstrate that cotton plants induced by H. armigera cause significant inhibitory and avoidance effects on A. gossypii insect populations. Electrical penetration graph (EPG) analysis showed changes in plant resistance induced by H. armigera leading to a decreased feeding efficiency of A. gossypii. In addition, genes associated with jasmonic acid and ethylene signaling pathways were significantly up-regulated in cotton plants after H. armigera induction, which led to a significant up-regulation of metabolites inducing plant resistance. These observations were corroborated by bioactivity analysis on metabolites, which showed that jasmonic acid, gossypol and tannins have significant inhibitory effects on A. gossypii populations. In contrast, methylparaben is associated with avoidance behaviors on A. gossypii populations. CONCLUSION: Our study suggests that the differences in the ability to induce plant resistance and tolerance between two non-predatory insects were lethal to low-tolerance A. gossypii insects, which might be a major factor determining their niche differentiation. This was further demonstrated by screening anti-insect and bio-hormonal metabolites. Our study provides a reference for investigating the evolutionary relationship between non-predatory insects and insights to implement effective insect biocontrol. © 2022 Society of Chemical Industry.


Assuntos
Afídeos , Gossipol , Mariposas , Animais , Afídeos/metabolismo , Gossipol/metabolismo , Herbivoria , Insetos/metabolismo , Mariposas/genética , Plantas/metabolismo
19.
J Microbiol Biotechnol ; 32(5): 645-656, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35283426

RESUMO

Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol.


Assuntos
Gossipol , Neoplasias Pancreáticas , Apoptose , Estresse do Retículo Endoplasmático , Gossipol/farmacologia , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Transdução de Sinais , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Fator de Transcrição CHOP/farmacologia
20.
Environ Microbiol ; 24(8): 3764-3776, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35129273

RESUMO

Transmission rate and role in hosts contribute to the prevalence of an endosymbiont. However, factors affecting transmission and role of facultative endosymbionts are still not well understood. Here, we illustrated that host plants and environmental temperatures affected the transmission, relative abundance and role of Arsenophonus in the cotton aphid Aphis gossypii. The transmission rate of this endosymbiont from mother aphids to offspring was relatively lower. High temperatures impeded the transmission, and infection rates declined as aphids were exposed to 30°C. Contents of amino acids and secondary metabolites were remarkably different among host plants. Aphids feeding on zucchini leaves containing a higher titre of amino acids and lower secondary metabolites harboured a relatively lower abundance of Arsenophonus. Concentrations of an amino acid and a plant secondary metabolite, cucurbitacin B, in aphid diet were not associated with Arsenophonus abundance. However, gossypol, another plant secondary metabolite, was strongly related with the abundance. Arsenophonus imparted a fitness benefit to aphids, and the benefit was dependent on host plants and gossypol concentration. In sum, plant secondary metabolite and environmental temperature affect transmission, relative abundance and role of Arsenophonus, which determine the endosymbiont prevalence in aphid populations.


Assuntos
Afídeos , Gammaproteobacteria , Gossipol , Aminoácidos , Animais , Plantas , Prevalência , Simbiose , Temperatura
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