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1.
J Anim Sci ; 1022024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38456567

RESUMEN

Angus-cross steers (n = 144; 359 kg ±â€…13.4) were used to assess the effect of dietary Mn and steroidal implants on performance, trace minerals (TM) status, hepatic enzyme activity, hepatic gene expression, and serum metabolites. Steers (n = 6/pen) were stratified by BW in a 3 × 2 factorial. GrowSafe bunks recorded individual feed intake (experimental unit = steer; n = 24/treatment). Dietary treatments included (MANG; 8 pens/treatment; Mn as MnSO4): (1) no supplemental Mn (analyzed 14 mg Mn/kg DM; Mn0); (2) 20 mg supplemental Mn/kg DM (Mn20); (3) 50 mg supplemental Mn/kg DM (Mn50). Within MANG, steers received a steroidal implant treatment (IMP) on day 0: (1) no implant; NO; or (2) combination implant (Revalor-200; REV). Liver biopsies for TM analysis and qPCR, and blood for serum glucose, insulin, non-esterified fatty acids, and urea-N (SUN) analysis were collected on days 0, 20, 40, and 77. Data were analyzed as a randomized complete block with a factorial arrangement of treatments including fixed effects of Mn treatment (MANG) and implant (IMP) using PROC MIXED of SAS 9.4 using initial BW as a covariate. Liver TM, serum metabolite, enzyme activity, and gene expression data were analyzed as repeated measures. No MANG × IMP effects were noted (P ≥ 0.12) for growth performance or carcass characteristic measures. Dietary Mn did not influence final body weight, overall ADG, or overall G:F (P ≥ 0.14). Liver Mn concentration increased with supplemental Mn concentration (MANG; P = 0.01). An IMP × DAY effect was noted for liver Mn (P = 0.01) where NO and REV were similar on day 0 but NO cattle increased liver Mn from days 0 to 20 while REV liver Mn decreased. Relative expression of MnSOD in the liver was greater in REV (P = 0.02) compared to NO and within a MANG × IMP effect (P = 0.01) REV increased liver MnSOD activity. These data indicate current NASEM Mn recommendations are adequate to meet the demands of finishing beef cattle given a steroidal implant. Despite the roles of Mn in metabolic pathways and antioxidant defense, a basal diet containing 14 mg Mn/kg DM was sufficient for the normal growth of finishing steers. This study also provided novel insight into how implants and supplemental Mn influence genes related to arginine metabolism, urea synthesis, antioxidant capacity, and TM homeostasis as well as arginase and MnSOD activity in hepatic tissue of beef steers.


Steroidal implants improve cattle growth and efficiency partially through increased net protein synthesis resulting in increased skeletal muscle hypertrophy. Necessary to support this increased growth are trace minerals (TM). Manganese (Mn) is essential, serving as a cofactor and activator of various enzymes. Manganese plays a crucial role in ruminant animals by supporting nitrogen recycling while also being essential for mitochondrial antioxidant defense. Consulting nutritionists routinely supplement Mn, amongst other TM, at concentrations greater than current recommendations. However, there is limited research on the impact of supplemental Mn in implanted finishing cattle. Our prior work suggests steroidal implants decrease liver Mn concentration. This is of interest as liver Mn concentration is tightly regulated. Therefore, this study evaluated the effects of steroidal implants and manganese sulfate supplementation on cattle growth performance, trace mineral status, expression of relevant hepatic genes, hepatic enzyme activity, and circulating metabolites in feedlot steers. In this study, supplementing Mn at the recommended concentration did not influence the growth of both implanted and non-implanted cattle.


Asunto(s)
Compuestos de Manganeso , Sulfatos , Oligoelementos , Bovinos , Animales , Oligoelementos/farmacología , Oligoelementos/metabolismo , Suplementos Dietéticos , Antioxidantes/metabolismo , Alimentación Animal/análisis , Dieta/veterinaria , Hígado/metabolismo , Esteroides/farmacología , Urea/metabolismo , Expresión Génica
2.
Phytomedicine ; 128: 155432, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38518645

RESUMEN

BACKGROUND: Cancer, the second leading cause of death worldwide following cardiovascular diseases, presents a formidable challenge in clinical settings due to the extensive toxic side effects associated with primary chemotherapy drugs employed for cancer treatment. Furthermore, the emergence of drug resistance against specific chemotherapeutic agents has further complicated the situation. Consequently, there exists an urgent imperative to investigate novel anticancer drugs. Steroidal saponins, a class of natural compounds, have demonstrated notable antitumor efficacy. Nonetheless, their translation into clinical applications has remained unrealized thus far. In light of this, we conducted a comprehensive systematic review elucidating the antitumor activity, underlying mechanisms, and inherent limitations of steroidal saponins. Additionally, we propose a series of strategic approaches and recommendations to augment the antitumor potential of steroidal saponin compounds, thereby offering prospective insights for their eventual clinical implementation. PURPOSE: This review summarizes steroidal saponins' antitumor activity, mechanisms, and limitations. METHODS: The data included in this review are sourced from authoritative databases such as PubMed, Web of Science, ScienceDirect, and others. RESULTS: A comprehensive summary of over 40 steroidal saponin compounds with proven antitumor activity, including their applicable tumor types and structural characteristics, has been compiled. These steroidal saponins can be primarily classified into five categories: spirostanol, isospirostanol, furostanol, steroidal alkaloids, and cholestanol. The isospirostanol and cholestanol saponins are found to have more potent antitumor activity. The primary antitumor mechanisms of these saponins include tumor cell apoptosis, autophagy induction, inhibition of tumor migration, overcoming drug resistance, and cell cycle arrest. However, steroidal saponins have limitations, such as higher cytotoxicity and lower bioavailability. Furthermore, strategies to address these drawbacks have been proposed. CONCLUSION: In summary, isospirostanol and cholestanol steroidal saponins demonstrate notable antitumor activity and different structural categories of steroidal saponins exhibit variations in their antitumor signaling pathways. However, the clinical application of steroidal saponins in cancer treatment still faces limitations, and further research and development are necessary to advance their potential in tumor therapy.


Asunto(s)
Antineoplásicos Fitogénicos , Saponinas , Esteroides , Saponinas/farmacología , Saponinas/química , Saponinas/uso terapéutico , Humanos , Esteroides/farmacología , Esteroides/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Neoplasias/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos
3.
Phytochemistry ; 221: 114039, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38417722

RESUMEN

Steroids are farnesyl diphosphate-derived triterpene derivatives widely distributed in Meliaceae plants that can have several health benefits due to their biological activities. This literature survey on chemical and pharmacological studies of steroids from the Meliaceae plants indicates that 157 distinct steroids classified into six subclasses including (in decreasing number): pregnane-, stigmastane-, ergostane-, cholestane-, androstane- and ecdysterone-type steroids have been reported from a total of 49 plant species. This review aims to provide a reference document compiling information about the occurrence, chemistry and biological activities of meliaceous steroids for the period from 1988 to July 2023. In particular, generalities about the chemistry of steroids with unusual skeletons and underlying biosynthetic pathways are highlighted. In addition, some structural relationships between different compound types and their biological activities are presented. The information used during the writing of this paper was collected from the online libraries PubMed, Google Scholar and Scifinder using the keywords steroids and Meliaceae with no language restriction. This review points out new avenues for further investigations of steroids from plants of the Meliaceae family.


Asunto(s)
Meliaceae , Meliaceae/química , Esteroides/farmacología , Esteroides/química , Pregnanos/química , Extractos Vegetales/química , Fitoquímicos/farmacología
4.
Phytochemistry ; 219: 113985, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38237845

RESUMEN

Ornithogalum thyrsoides Jacq belongs to the Asparagaceae family and is cultivated for ornamental purposes. The authors have previously reported several cholestane- and spirostan-type steroidal glycosides from O. thyrsoides. Conventional TLC analysis of the methanolic bulb extract of O. thyrsoides suggested the presence of unprecedented compounds; therefore, a detailed phytochemical investigation of the extract was performed and 35 steroidal glycosides (1-35), including 21 previously undescribed ones (1-21) were collected. The structures of 1-21 were determined mainly by analyses of their 1H and 13C NMR spectra with the aid of two-dimensional NMR spectroscopy. The isolated compounds were classified into three distinct groups: furostan-type (1, 2, 8-12, and 22), spirostan-type (3-7 and 23-26), and cholestane-type (13-21 and 27-35). Although the C/D-ring junction of the steroidal skeleton is typically trans-oriented, except for some cardiotonic and pregnane-type steroidal derivatives, 7 possess a cis C/D-ring junction. This is the first reported instance of such a configuration in spirostan-type steroidal derivatives, marking it as a finding of significant interest. Compounds 1-35 were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells and SBC-3 human small-cell lung cancer cells. Compounds 3-6, 9, 17-21, 23-25, and 30-35 demonstrated cytotoxicity in a dose-dependent manner with IC50 values ranging from 0.000086 to 18 µM and from 0.00014 to 37 µM toward HL-60 and SBC-3 cells, respectively. Compound 19, which is obtained in a good yield and shows relatively potent cytotoxicity among the undescribed compounds, induces apoptosis in HL-60 cells, accompanied by arresting the cell cycle of HL-60 cells at the G2/M phase. In contrast, 19 causes oxidative stress-associated necrosis in SBC-3 cells. The cytotoxic mechanism of 19 is different between HL-60 and SBC-3 cells.


Asunto(s)
Colestanos , Leucemia , Neoplasias Pulmonares , Ornithogalum , Espirostanos , Humanos , Células HL-60 , Ornithogalum/química , Glicósidos/química , Colestanos/química , Esteroides/farmacología , Esteroides/química , Extractos Vegetales/farmacología
5.
Chem Biodivers ; 20(12): e202301381, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37968243

RESUMEN

Four undescribed steroidal compounds along with twenty known compounds were isolated from n-butanol extracted fraction of the whole plants of Solanum lyratum Thunb (SLNF). Their structures were assigned based on analyses of the extensive spectroscopic data (including MS, 1D/2D NMR, and ECD) or comparisons of the NMR data with those reported. Among the knowns, three compounds were isolated from Solanum plants for the first time, while one compound was isolated from S. lyratum for the first time. In addition, the cytotoxicities of these isolates against human colon SW480 and hepatoma Hep3B cells were evaluated by a MTT assay. And, nine of them and SLNF exhibited significant activities against both SW480 and Hep3B cells, while twelve of them significantly inhibited the activities of SW480 cells. This study allows for the exploitation of chemical markers with potential significance in discrimination of Solanum plants, and uncovers the diverse steroidal constituents from S. lyratum dedicated for its future application in cancer treatment.


Asunto(s)
Saponinas , Solanum , Humanos , Solanum/química , Saponinas/farmacología , Esteroides/farmacología , Estructura Molecular
6.
Chin J Nat Med ; 21(10): 789-800, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37879796

RESUMEN

Five new saponins, including three steroid saponins, paristenoids A-C (1-3), and two triterpenoid saponins, paristenoids D-E (4-5), along with four known ones (6-9) were isolated from the rhizomes of Paris polyphylla var. stenophylla. The structures of the isolated compounds were identified mainly by detailed spectroscopic analysis, including extensive 1D and 2D NMR, MS, as well as chemical methods. Compound 3 is a new cyclocholestanol-type steroidal saponin with a rare 6/6/6/5/5 fused-rings cholestanol skeleton, and this skeleton has been first found from the genus Paris. The cytotoxicities of the isolated compounds against three human three glioma cell lines (U87MG, U251MG and SHG44) were evaluated, and compound 7 displayed certain inhibitory effect with IC50 values of 15.22 ± 1.73, 18.87 ± 1.81 and 17.64 ± 1.69 µmol·L-1, respectively.


Asunto(s)
Liliaceae , Saponinas , Triterpenos , Humanos , Rizoma/química , Esteroides/farmacología , Esteroides/química , Liliaceae/química , Saponinas/química , Triterpenos/farmacología , Triterpenos/análisis
7.
Molecules ; 28(14)2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37513375

RESUMEN

Cancer, as one of the leading causes of death worldwide, has challenged current chemotherapy drugs. Considering that treatments are expensive, alongside the resistance of tumor cells to anticancer drugs, the development of alternative medicines is necessary. Anemarrhena asphodeloides Bunge, a recognized and well-known medicinal plant for more than two thousand years, has demonstrated its effectiveness against cancer. Timosaponin-AIII (TSAIII), as a bioactive steroid saponin isolated from A. asphodeloides, has shown multiple pharmacological activities and has been developed as an anticancer agent. However, the molecular mechanisms of TSAIII in protecting against cancer development are still unclear. In this review article, we provide a comprehensive discussion on the anticancer effects of TSAIII, including proliferation inhibition, cell cycle arrest, apoptosis induction, autophagy mediation, migration and invasion suppression, anti-angiogenesis, anti-inflammation, and antioxidant effects. The pharmacokinetic profiles of TSAII are also discussed. TSAIII exhibits efficacy against cancer development. However, hydrophobicity and low bioavailability may limit the application of TSAIII. Effective delivery systems, particularly those with tissue/cell-targeted properties, can also significantly improve the anticancer effects of TSAIII.


Asunto(s)
Anemarrhena , Antineoplásicos , Neoplasias , Plantas Medicinales , Saponinas , Humanos , Esteroides/farmacología , Esteroides/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Saponinas/farmacología , Saponinas/uso terapéutico
8.
Fitoterapia ; 169: 105603, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37421992

RESUMEN

Three previously undescribed steroidal constituents including two sterols (1-2) and one pregnane-type steroidal glycoside (6), along with nineteen known ones (3-5, 7-22), were isolated from the 80% alcohol extraction of Solanum nigrum L. Their structures and the absolute configurations were established by analysis of the extensive spectroscopic data (1H/13 NMR, 1H1H COSY, HSQC, HMBC, and NOESY), and/or by comparisons of the experimental electronic circular dichroism (ECD) spectra with those calculated ones by TDDFT method. Further, a MTT assay was applied to demonstrate that compounds 1-4, 6-12, 18, and 22 exhibited significant cytotoxic activities against SW480 cells, and compounds 1-4, 6-14, and 16-22 showed significant cytotoxic activities against Hep3B cells.


Asunto(s)
Fitosteroles , Solanum nigrum , Solanum , Solanum nigrum/química , Estructura Molecular , Esteroides/farmacología , Esteroides/química , Espectroscopía de Resonancia Magnética , Fitosteroles/farmacología , Solanum/química
9.
Phytochemistry ; 213: 113782, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37451564

RESUMEN

A phytochemical investigation of the dichloromethane soluble fraction of the ethanolic extract obtained from the roots of Marsdenia tenacissima led to the discovery of the sixteen undescribed pregnane C21 steroids (1-16) and isolation of eleven known C21 steroidal analogues (17-27). Their chemical structures were elucidated by one- and two-dimensional nuclear magnetic resonance spectroscopy and, high resolution-electrospray ionization mass spectrometry and their absolute configurations were determined using electronic circular dichroism or single-crystal X-ray diffraction. The in vitro anti-proliferative effects of 1-16 were evaluated against HepG2 (human hepatocellular cancer), A549 (lung cancer), and MCF-7 (human breast cancer) cell lines. Even though some of them showed moderate cytotoxic activities, marsectohexol derivative 12 exhibited significant cytotoxicity against A549 cells with an IC50 value of 5.2 µM.


Asunto(s)
Antineoplásicos , Marsdenia , Humanos , Marsdenia/química , Esteroides/farmacología , Esteroides/química , Pregnanos/química , Extractos Vegetales/química
10.
Molecules ; 28(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37175205

RESUMEN

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCß), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated ß-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded ß-catenin expression. As ß-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with ß-catenin function through the activation of a PDE5/cGMP functional axis.


Asunto(s)
Glioblastoma , beta Catenina , Humanos , beta Catenina/metabolismo , Glioblastoma/tratamiento farmacológico , Esteroides/farmacología , Apoptosis , Transducción de Señal , GMP Cíclico/metabolismo
11.
Fitoterapia ; 168: 105551, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37247696

RESUMEN

Twenty compounds comprising four pregnane steroids (2-4 & 20) and 16 pregnane glycosides (1 & 5-19) have been obtained from the ethanol extract of the roots of a Dai ethnological herb, Marsdenia tenacissima. Their structures were characterized on the basis of comprehensive spectroscopic analyses with 17 ones (1-17) being reported for the first time, including the rare cases (2 & 3) of free C21 steroids with 17α-acetyl substitution, compounds 4-7 bearing an unusual 14α-OH, and the first examples with simultaneous 14α-OH/17α-acetyl substitution (7) and glycosylation at C-12 position (10 & 11). An empirical rule for the identification of C-17 configuration, in C21 steroids incorporating the marsdenin constitution structure, was also proposed. All the isolates, along with an array of previously reported analogues in our compound library, were screened for their chemo-reversal ability against P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in MCF-7/ADR cell line, and six compounds exhibited moderate MDR reversal activity with reversal folds ranging from 1.92 to 4.44.


Asunto(s)
Marsdenia , Marsdenia/química , Estructura Molecular , Esteroides/farmacología , Esteroides/química , Pregnanos/farmacología , Pregnanos/química , Glicósidos/farmacología , Glicósidos/química , Resistencia a Múltiples Medicamentos
12.
J Cell Mol Med ; 27(9): 1227-1238, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37016544

RESUMEN

Graft-versus-host disease (GVHD) is a complication of allogeneic haematopoietic cell transplantation. Endothelial injury is crucial as pathophysiological substrate for GVHD. GVHD first-line treatment is high-dose corticosteroids, although some patients are steroid-refractory. Through the present study, we compared the endothelial proteomic profiles in response to serum from steroid-refractory acute GVHD (SR-aGVHD) and steroid-sensitive acute GVHD (SS-aGVHD) patients. Blood samples from SR-aGVHD (n = 4) and SS-aGVHD (n = 8) patients were collected at aGVHD diagnosis. Endothelial cell cultures were exposed (48 h) to patients' serum. Protein extraction and proteomic analysis were performed. Differences were statistically evaluated by multivariate analysis. Forty-four proteins contributed to separate all samples into the two study groups, among which 15 participated significantly (p < 0.05), 10 exhibiting a fold change >1.2. Differentially expressed proteins were mainly associated with oxidative phosphorylation (Cytochrome C oxidase subunit 6B1, CX6B1), inflammation and angiogenesis (Apolipoprotein D, APOD), cell survival (Rapamycin-insensitive companion of mTOR, RICTR), and oxidative stress (Riboflavin kinase, RIFK). This pilot study used a novel approach to distinguish the aGVHD response to steroid treatment. The proteins differentially expressed could constitute potential biomarkers for steroid-treatment response. These findings signify a step forward to identify the mechanisms of response to steroids, of high clinical relevance considering the SR-aGVHD elevated mortality.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Células Endoteliales , Proyectos Piloto , Proteómica , Enfermedad Injerto contra Huésped/etiología , Esteroides/farmacología , Esteroides/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Aguda
13.
Chem Commun (Camb) ; 59(3): 326-329, 2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36511292

RESUMEN

Veratrazine A (1), a steroidal alkaloid with a unique 6/5/5 triheterocyclic scaffold as the side chain, was isolated from Veratrum stenophyllum, and its structure was established via spectroscopic analyses and X-ray diffraction. A plausible biosynthetic pathway for 1 is proposed. Bioassy exhibits moderate anti-inflammatory activities in vitro and in vivo.


Asunto(s)
Alcaloides , Antineoplásicos , Veratrum , Alcaloides/farmacología , Alcaloides/química , Extractos Vegetales/química , Veratrum/química , Esteroides/farmacología , Antiinflamatorios , Estructura Molecular
14.
Br J Neurosurg ; 37(5): 1117-1123, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35129010

RESUMEN

BACKGROUND: Lumbosacral Spinal Stenosis (LSS) is a degenerative spine disease and a major cause of pain and disability, especially in geriatrics. Primary symptom control in patients with LSS includes conservative treatment and non-surgical methods. In this study, we aimed to compare the effect of steroid injection via epidural and gluteal trigger point techniques. METHODS: Patients aged 40-75 years old who had pain and other clinical signs of spinal stenosis in the last 6 months were included in our study and divided into two groups of gluteal trigger point (TP) or epidural steroid injection (ESI). The patients were evaluated based on the visual analog scale (VAS), Roland-Morris Disability Questionnaire (RDQ), Oswestry Disability Index (ODI), and the Quebec back pain disability scales during their pre-injection period and 2 weeks after follow-ups till 8 weeks. A P value of less than 0.05 was considered significant. RESULTS: A total of 44 patients were included in our study. The TP group had a significant decrease in comparison with their follow-ups; however, in the epidural group, the significant decrease was only observed compared to the pre-injection period and the scores did not have any significant decreases after the second week regarding the ODI, RQM, and VAS scales. The TP group demonstrated significantly higher scores of decreases of ODI and Quebec score compared to the epidural group at weeks 4 and 8. Regarding RQM, the TP groups demonstrated significantly higher scores of decreases compared to the epidural group at weeks 2, 4 and 8. (p < 0.001 p = 0.008, and p < 0.001, respectively). CONCLUSION: Both epidural and TP steroid injection significantly reduced the patients' pain and improved their QoL and function; however, more satisfactory results were observed in the TP group during the patients' follow-ups, while the epidural group demonstrated only statistically significant improvement during the short-term follow-up.


Asunto(s)
Estenosis Espinal , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estenosis Espinal/complicaciones , Estenosis Espinal/tratamiento farmacológico , Estenosis Espinal/diagnóstico , Constricción Patológica , Calidad de Vida , Puntos Disparadores , Resultado del Tratamiento , Dolor de Espalda , Esteroides/uso terapéutico , Esteroides/farmacología , Inyecciones Epidurales/métodos , Vértebras Lumbares/cirugía
15.
Fitoterapia ; 163: 105339, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36272704

RESUMEN

Eight new steroids, designated mantuoluosides A-H (1-8), were obtained from the enrichment of steroids of the Datura stramonium L. using HPD-BJQH macroporous resin. Their respective structures were elucidated based on spectroscopic methods and comparison data with literature. The anti-inflammatory activities of these compounds were evaluated on (LPS)-induced RAW264.7 cells with inhibition ratio. It was found that most isolates showed potential anti-inflammatory activity with varying degrees of inhibition rate in a concentration-dependent manner at non-cytotoxic concentrations.


Asunto(s)
Datura stramonium , Datura stramonium/química , Estructura Molecular , Hojas de la Planta/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Esteroides/farmacología
16.
Biochem Biophys Res Commun ; 630: 101-111, 2022 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-36152347

RESUMEN

Postmenopausal women have an increased risk of obesity, but the underlying cause is not clear. We unexpectedly found that excess dietary zinc induced severe obesity and a Cushing's-like syndrome without increased food intake in ovariectomized (Ovx) but not in sham-operated mice. Zinc accumulated in the adrenal glands and inhibited adrenal 17,20-lyase activity and steroid synthesis. As adrenal steroids are the only source of estrogen in Ovx mice, estrogen deficiency induced adrenal hyperplasia, glucocorticoid overproduction, and consequent development of a Cushing's-like syndrome. Adrenal steroid supplementation prevented the effects of zinc. Plasma zinc was positively correlated with cortisol level and negatively correlated with the levels of adrenal steroids and estrogen in obese postmenopausal women. The finding of a link between dietary zinc, estrogen deficiency, and postmenopausal obesity, implies that postmenopausal obesity might be prevented by supplementation with a adrenal steroid and avoiding excess dietary zinc.


Asunto(s)
Síndrome de Cushing , Glándulas Suprarrenales , Animales , Síndrome de Cushing/etiología , Estrógenos/farmacología , Femenino , Glucocorticoides/farmacología , Hidrocortisona , Ratones , Obesidad/complicaciones , Posmenopausia , Esteroide 17-alfa-Hidroxilasa , Esteroides/farmacología , Zinc/farmacología
17.
Zhongguo Zhong Yao Za Zhi ; 47(18): 4966-4971, 2022 Sep.
Artículo en Chino | MEDLINE | ID: mdl-36164906

RESUMEN

Two previously undescribed steroidal alkaloids, compounds 1-2, along with two known ones(3-4), were isolated from the 80% ethanol extract of ripe berries of Solanum nigrum by chromatographic methods, including silica gel, ODS, and HPLC. Based on spectroscopic and chemical evidence, including IR, NMR, and HR-ESI-MS data, the structures of the isolated compounds were identified as 12ß,27-dihydroxy solasodine-3-O-ß-D-glucopyranoside(1), 27-hydroxy solasodine-3-O-ß-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranoside(2), solalyraine A(3), and 12ß,27-dihydroxy solasodine(4). Compounds 1-2 were tested for their potential effects against the proliferation of A549 cells, which revealed that compounds 1-2 had weak cytotoxic activity.


Asunto(s)
Alcaloides , Saponinas , Solanum nigrum , Solanum , Alcaloides/análisis , Etanol , Frutas/química , Estructura Molecular , Extractos Vegetales/química , Saponinas/análisis , Gel de Sílice/análisis , Solanum/química , Solanum nigrum/química , Esteroides/farmacología
18.
Int J Biol Macromol ; 219: 964-979, 2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-35940431

RESUMEN

Organic chromium is of great interest and has become an important chromium supplement resource in recent years because of its low toxicity and easy absorption. In our previous study, we synthesized a novel organic chromium [GLP-Cr] through the chelation of Ganoderma lucidum polysaccharide and chromium (III). The purpose of this study was to investigate the beneficial effects of GLP-Cr on the improvement of metabolic syndromes (MetS) in mice fed with a high-fat and high-fructose diet (HFHFD) and its mechanism of action. The results indicated that oral administration of GLP-Cr inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic total cholesterol (TC), triglyceride (TG) levels caused by HFHFD. Besides, 16S rRNA amplicon sequencing showed that GLP-Cr intervention evidently ameliorated intestinal microbiota dysbiosis by changing the proportions of some intestinal microbial phylotypes. In addition, correlation network-based analysis indicated that the key intestinal microbial phylotypes were closely related to biochemical parameters associated with MetS under GLP-Cr intervention. Liver metabolomics analysis suggested that GLP-Cr intervention significantly regulated the levels of some biomarkers involved in alpha-linolenic acid metabolism, fatty acid biosynthesis, steroid hormone biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, steroid hormone biosynthesis, primary bile acid biosynthesis, and so on. Moreover, GLP-Cr intervention regulated liver mRNA levels of key genes associated with glucose and lipid metabolism. The mRNA level of glucose transporter type 4 (Glut4) was markedly increased by GLP-Cr intervention, and the mRNA levels of phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6Pase) in the liver were significantly decreased. Meanwhile, GLP-Cr intervention significantly decreased hepatic mRNA levels of cluster of differentiation 36 (Cd36), acetyl-CoA carboxylase 1 (Acc1) and sterol regulatory element binding protein-1c (Srebp-1c), indicating that GLP-Cr intervention inhibited the excessive accumulation of free fatty acids in the liver. These findings suggest that the prevention of hyperglycemia and dyslipidemia by GLP-Cr may be closely related to the regulation of gut microbial composition and hepatic metabolic pathways, thus GLP-Cr can be serving as a functional component in the prevention of MetS.


Asunto(s)
Microbioma Gastrointestinal , Síndrome Metabólico , Reishi , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Acetil-CoA Carboxilasa/farmacología , Animales , Ácidos y Sales Biliares/farmacología , Biomarcadores , Glucemia/metabolismo , Colesterol , Cromo/química , Dieta , Dieta Alta en Grasa/efectos adversos , Disbiosis/tratamiento farmacológico , Ácidos Grasos no Esterificados , Fructosa/efectos adversos , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4 , Glucosa-6-Fosfatasa/metabolismo , Glucosa-6-Fosfatasa/farmacología , Glicerofosfolípidos , Hormonas , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/etiología , Ratones , Fosfoenolpiruvato/farmacología , Polisacáridos/farmacología , ARN Mensajero/metabolismo , ARN Ribosómico 16S , Reishi/genética , Esteroides/farmacología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Triglicéridos , Ácido alfa-Linolénico/farmacología
19.
Molecules ; 27(16)2022 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-36014585

RESUMEN

Plants of the Veratrum genus have been used throughout history for their emetic properties, rheumatism, and for the treatment of high blood pressure. However, inadvertent consumption of these plants, which resemble wild ramps, induces life-threatening side effects attributable to an abundance of steroidal alkaloids. Several of the steroidal alkaloids from Veratrum spp. have been investigated for their ability to antagonize the Hedgehog (Hh) signaling pathway, a key pathway for embryonic development and cell proliferation. Uncontrolled activation of this pathway is linked to the development of various cancers; most notably, basal cell carcinoma and acute myeloid leukemia. Additional investigation of Veratrum spp. may lead to the identification of novel alkaloids with the potential to serve as chemotherapeutics. V. parviflorum is a relatively uncommon species of Veratrum that resides in the southeastern regions of North America. The phytochemical profile of this plant remains largely unexplored; however, bioactive steroidal alkaloids, including cyclopamine, veratramine, veratridine, and verazine were identified in its extract. The structural elucidation and bioactivity assessment of steroidal alkaloids in lesser abundance within the extract of V. parviflorum may yield potent Hh pathway inhibitors. This review seeks to consolidate the botanical and phytochemical information regarding V. parviflorum.


Asunto(s)
Alcaloides , Veratrum , Alcaloides/farmacología , Proteínas Hedgehog/metabolismo , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Esteroides/farmacología , Veratrum/química
20.
Phytochemistry ; 202: 113317, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35820506

RESUMEN

Eight undescribed, along with five known steroidal alkaloids were isolated from Solanum nigrum L., a plant used in traditional Chinese medicine. Their structures were elucidated by NMR, HR-ESI-MS, and IR spectroscopy. Two compounds displayed an unusual structure in steroidal alkaloids with an open E-ring and without an F-ring present. To evaluate their bioactivities, nine compounds were selected to intervene five human cancer cell lines including H1299, HepG2, HeLa, HCT116, and MCF7 respectively. All compounds exhibited inhibitory effects for the five cell lines, revealing potential anti-tumor activities from Solanum nigrum.


Asunto(s)
Alcaloides , Antineoplásicos , Solanum nigrum , Solanum , Alcaloides/química , Alcaloides/farmacología , Humanos , Extractos Vegetales/química , Solanum nigrum/química , Esteroides/química , Esteroides/farmacología
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