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1.
Phytomedicine ; 125: 155374, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301302

RESUMO

BACKGROUND: In China, Gardenia jasminoides Ellis (GJE) has a longstanding history of application. The Ministry of Health has listed it as one of the first pharmaceutical or food resources. In ethnic, traditional, and folk medicine, GJE has been used to treat fever and cold and relieve nervous anxiety. Recent studies have confirmed the significant efficacy of GJE for treating central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder; however, GJE has not been systematically evaluated. PURPOSE: This research systematically summarizes global studies on the use of GJE for treating CNS disorders and explores the potential applications and underlying mechanisms via intestinal flora analysis and network pharmacology, aiming to establish a scientific basis for innovative CNS disorder treatment with GJE. METHODS: The PRISMA guidelines were used, and electronic databases such as the Web of Science, PubMed, and China National Knowledge Infrastructure were searched using the following search terms: "Gardenia jasminoides Ellis" with "central nervous system disease," "neuroprotection," "Alzheimer's disease," "Parkinson's disease," "ischemic stroke," "Epilepsy," and "major depressive disorder." The published literature up to September 2023 was searched to obtain relevant information on the application of GJE for treating CNS disorders. RESULTS: There has been an increase in research on the material formulation and mechanisms of action of GJE for treating CNS disorders, with marked effects on CNS disorder treatment in different countries and regions. We summarized the research results related to the role of GJE in vitro and in vivo via multitargeted interventions in response to the complex mechanisms of action of CNS disorders. CONCLUSION: We systematically reviewed the research progress on traditional treatment for GJE and preclinical mechanisms of CNS disorders and explored the potential of optimizing network pharmacology strategies and intestinal flora analysis to elucidate the mechanisms of action of GJE. The remarkable therapeutic efficacy of GJE, an important resource in traditional medicine, has been well documented in the literature, highlighting its significant medicinal potential.


Assuntos
Doença de Alzheimer , Transtorno Depressivo Maior , Gardenia , Doença de Parkinson , Humanos , Gardenia/química , Doença de Alzheimer/tratamento farmacológico , Neuroproteção
2.
Food Res Int ; 179: 113981, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342530

RESUMO

Food coloring plays a vital role in influencing consumers' food choices, imparting vibrant and appealing colors to various food and beverage products. Synthetic food colorants have been the most commonly used coloring agents in the food industry. However, concerns about potential health issues related to synthetic colorants, coupled with increasing consumer demands for food safety and health, have led food manufacturers to explore natural alternatives. Natural pigments not only offer a wide range of colors to food products but also exhibit beneficial bioactive properties. Gardenia yellow pigment is a water-soluble natural pigment with various biological activities, widely present in gardenia fruits. Therefore, this paper aims to delve into Gardenia Yellow Pigment, highlighting its significance as a food colorant. Firstly, a thorough understanding and exploration of various methods for obtaining gardenia yellow pigment. Subsequently, the potential functionality of gardenia yellow pigment was elaborated, especially its excellent antioxidant and neuroprotective properties. Finally, the widespread application trend of gardenia yellow pigment in the food industry was explored, as well as the challenges faced by the future development of gardenia yellow pigment in the field of food and health. Some feasible solutions were proposed, providing valuable references and insights for researchers, food industry professionals, and policy makers.


Assuntos
Corantes de Alimentos , Gardenia , Extratos Vegetais , Corantes
3.
Planta ; 259(3): 62, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319463

RESUMO

MAIN CONCLUSION: The operation of 8HGO-ISY fusion enzymes can increase nepetalactol flux to iridoid biosynthesis, and the Gj8HGO-CrISY expression in Gardenia jasminoides indicates that seco-iridoids and closed-ring iridoids share a nepetalactol pool. Nepetalactol is a common precursor of (seco)iridoids and their derivatives, which are a group of noncanonical monoterpenes. Functional characterization of an 8HGO (8-hydroxygeraniol oxidoreductase) from Catharanthus roseus, a seco-iridoids producing plant, has been reported; however, the 8HGO from G. jasminoides with plenty of closed-ring iridoids remains uninvestigated. In this work, a Gj8HGO was cloned and biochemically characterized. In addition, the relatively low production of nepetalactol in plants and engineered microbial host is likely to be attributed to the fact that Cr8HGO and CrISY (iridoid synthase) are substrate-promiscuous enzymes catalyzing unexpected substrates to the undesired products. Herein, a bifunctional enzyme consisting of an 8HGO fused to an ISY was designed for the proximity to the substrate and recycling of NADP+ and NADPH cofactor to reduce the undesired intermediate in the synthesis of nepetalactol. Of four fusion enzymes (i.e., Gj8HGO-GjISY, Gj8HGO-GjISY2, Gj8HGO-GjISY4, and Gj8HGO-CrISY), interestingly, only the last one can enable cascade reaction to form cis-trans-nepetalactol. Furthermore, we establish a reliable Agrobacterium-mediated transformation system. The expression of Gj8HGO-CrISY in G. jasminoides led to a significant enhancement of nepetalactol production, about 19-fold higher than that in wild-type plants, which further resulted in the twofold to fivefold increase of total iridoids and representative iridoid such as geniposide, indicating that seco-iridoids in C. roseus and closed-ring iridoids in G. jasminoides share a nepetalactol pool. All results suggest that 8HGO and ISY can be manipulated to maximize metabolic flux for nepetalactol and iridoid production.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Catharanthus , Gardenia , Terpenos , Oxirredutases , Catharanthus/genética , Iridoides
4.
J Ethnopharmacol ; 326: 117934, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38387681

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.


Assuntos
Antipiréticos , Gardenia , Ratos , Animais , NF-kappa B/metabolismo , Antipiréticos/farmacologia , Antipiréticos/uso terapêutico , Receptor 4 Toll-Like , Frutas/metabolismo , Saccharomyces cerevisiae , Iridoides/farmacologia , Iridoides/uso terapêutico , Transdução de Sinais , Glicosídeos Iridoides/farmacologia
5.
Fitoterapia ; 174: 105829, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38278422

RESUMO

Gardenia jasminoides Ellis, a plant widely used in traditional medicine, is known for its array of biological activities. A key bioactive compound, geniposide (GE), an iridoid glycoside, significantly contributes to the medicinal properties of the plant, with potential side effects. Thus, a reliable and efficient method for GE detection is required to ensure the quality of medicinal-grade G. jasminoides Ellis. This study developed such a method by first synthesizing GE-bovine serum albumin conjugates to function as immunizing agents in mice. This led to the production of a monoclonal antibody (mAb 3A6) against GE from the fusion of splenocytes from immunized mice with myeloma cells (P3U1), resulting in a hybridoma that produces mAb 3A6. Thereafter, we developed a mAb 3A6-based indirect competitive enzyme-linked immunosorbent assay (icELISA). The icELISA exhibited satisfactory sensitivity (0.391-12.5 µg/ml) and repeatability (coefficients of variation <10%). The accuracy of this method was validated through a spike-recovery assay (recovery of 101-112%). Furthermore, the icELISA was employed to determine the GE content in plant and Kampo medicine samples. The GE content positively correlated with those determined by high-performance liquid chromatography-ultraviolet. The proposed icELISA is rapid, cost-effective, and reliable for high-throughput GE detection in G. jasminoides Ellis, thereby contributing to the improved quality control and standardization of this valuable medicinal plant.


Assuntos
Gardenia , Medicina Kampo , Camundongos , Animais , Anticorpos Monoclonais , Estrutura Molecular , Iridoides
6.
Brain Res ; 1824: 148687, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38000495

RESUMO

Alzheimer's disease (AD) is characterized by degeneration of the central nervous system. Recently, many studies have emphasized the beneficial role of Gardenia jasminoides J. Ellis extract (GJ-4) in neuroprotection, which is considered a potential drug for treating AD. However, the mechanism underlying its neuroprotective effects is obscure. This research intended to analyze the effectiveness of GJ-4 to induce neuronal protective role on a rat model of neurotoxicity and probe the potential mechanism. An AD model was established by intraperitoneal injection of aluminum chloride (AlCl3). Then, AlCl3-induced rats were administered 25 mg/kg and 50 mg/kg of GJ-4 orally. This study indicated that GJ-4 (25 and 50 mg/kg) mitigated AD-like behaviors, as evidenced by enhanced ambulation frequency, rearing frequency, and time spent in the target quadrant and decreased grooming frequency, defecation frequency, and escape latency in AlCl3-challenged rats. Also, GJ-4 at 25 and 50 mg/kg exerted an anti-apoptosis effect in the hippocampus of AlCl3-treated rats. Furthermore, GJ-4 (25 and 50 mg/kg) exhibited an anti-inflammatory effect in the hippocampus by repressing the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, further inhibiting the activation of Caspase 1, ASC, IL-1ß, and IL-18 in AD hippocampus. Altogether, GJ-4 mitigated AlCl3-triggered impairment of learning and memory in AD rats via repressing NLRP3 inflammasome.


Assuntos
Doença de Alzheimer , Gardenia , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doença de Alzheimer/tratamento farmacológico , Gardenia/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Transtornos da Memória/tratamento farmacológico
7.
Bioorg Chem ; 143: 107036, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141330

RESUMO

This study reports a thermostable glucose-stimulated ß-glucosidase, BglY442, from hot-spring metagenomic data that was cloned and expressed in Escherichia coli BL21 (DE3). The molecular mass of recombinant BglY442 was 69.9 kDa and was used in the production of gardenia blue. The recombinant BglY442 showed its maximum activity at pH 6.0 and 75 °C, maintained 50 % activity at 70 °C for 36 h, presented over 90 % activity in a broad pH range and a wide range of pH stability. Moreover, BglY442 exhibited excellent tolerance toward methanol and ethanol. The specific activity of BglY442 was 235 U/mg at pH 6.0 and 75 °C with 10 mM pNPG as substrate. BglY442 activity increased by over fourfold with 2 M glucose or xylose. Specifically, the enzyme kinetics of BglY442 seem to be non-Michaelis-Menten kinetics or atypical kinetics because the Michaelis-Menten saturation kinetics were not observed with pNPG, oNPG or geniposide as substrates. Under optimum conditions, geniposide was dehydrated by BglY442 and reacted with nine amino acids respectively by the one-pot method. Only the Arg or Met derived pigments showed bright blue, and these two pigments had similar ultraviolet absorption spectra. The OD590 nm of GB was detected to be 1.06 after 24 h with the addition of Arg and 1.61 after 36 h with the addition of Met. The intermediate was elucidated and identified as ginipin. Molecular docking analysis indicated that the enzyme had a similar catalytic mechanism to the reported GH1 Bgls. BglY442 exhibited potential for gardenia blue production by the one-pot method. With outstanding thermostability and glucose tolerance, BglY442 should be considered a potential ß-glucosidase in biotechnology applications.


Assuntos
Gardenia , Glucose , Iridoides , Glucose/farmacologia , Proteínas Recombinantes/metabolismo , beta-Glucosidase/metabolismo , Metagenoma , Simulação de Acoplamento Molecular , Concentração de Íons de Hidrogênio , Estabilidade Enzimática , Especificidade por Substrato , Temperatura , Cinética
8.
Ultrason Sonochem ; 101: 106658, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913593

RESUMO

The simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) was performed by integrating natural deep eutectic solvents (NADES) and ultrasound-assisted extraction (UAE). Among the eight kinds of NADES screened, choline chloride-1,2-propylene glycol was the most suitable extractant. The probe-type ultrasound-assisted NADES extraction system (pr-UAE-NADES) demonstrated higher extraction efficiency compared with plate-type ultrasound-assisted NADES extraction system (pl-UAE-NADES). Orthogonal experimental design and a modified multi-index synthetic weighted scoring method were adopted to optimize pr-UAE-NADES extraction process. The optimal extraction conditions that had a maximum synthetic weighted score of 29.46 were determined to be 25 °C for extraction temperature, 600 W for ultrasonic power, 20 min for extraction time, and 25% (w/w) for water content in NADES, leading to the maximum yields (7.39 ± 0.20 mg/g and 57.99 ± 0.91 mg/g, respectively) of crocin and geniposide. Thirty-three compounds including iridoids, carotenoids, phenolic acids, flavonoids, and triterpenes in the NADES extract were identified by LC-Q-TOF-MS2 coupled with a feature-based molecular networking workflow. The kinetics evaluation of the conjugated dienes generation on Cu2+-induced low density lipoprotein (LDL) oxidation via the four-parameter logistic regression model showed that crocin increased the lag time of LDL oxidation in a concentration-dependent manner (15 µg/mL, 30 µg/mL, 45 µg/mL) by 12.66%, 35.44%, and 73.42%, respectively. The quantitative determination for fluorescence properties alteration of the apolipoprotein B-100 exhibited that crocin effectively inhibited the fluorescence quenching of tryptophan residues and the modification of lysine residues caused by reactive aldehydes and malondialdehydes. The pr-UAE-NADES showed significant efficiency toward the simultaneous extraction of crocin and geniposide from gardenia fruits. And this study demonstrates the potential utility of gardenia fruits in developing anti-atherogenic functional food.


Assuntos
Solventes Eutéticos Profundos , Gardenia , Gardenia/química , Frutas/química , Iridoides/farmacologia , Iridoides/análise , Carotenoides/farmacologia , Carotenoides/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Solventes
9.
Molecules ; 28(21)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37959800

RESUMO

Traditional Chinese medicine (TCM) possesses unique advantages in the management of blood glucose and lipids. However, there is still a significant gap in the exploration of its pharmacologically active components. Integrated strategies encompassing deep-learning prediction models and active validation based on absorbable ingredients can greatly improve the identification rate and screening efficiency in TCM. In this study, the affinity prediction of 11,549 compounds from the traditional Chinese medicine system's pharmacology database (TCMSP) with dipeptidyl peptidase-IV (DPP-IV) based on a deep-learning model was firstly conducted. With the results, Gardenia jasminoides Ellis (GJE), a food medicine with homologous properties, was selected as a model drug. The absorbed components of GJE were subsequently identified through in vivo intestinal perfusion and oral administration. As a result, a total of 38 prototypical absorbed components of GJE were identified. These components were analyzed to determine their absorption patterns after intestinal, hepatic, and systemic metabolism. Virtual docking and DPP-IV enzyme activity experiments were further conducted to validate the inhibitory effects and potential binding sites of the common constituents of deep learning and sequential metabolism. The results showed a significant DPP-IV inhibitory activity (IC50 53 ± 0.63 µg/mL) of the iridoid glycosides' potent fractions, which is a novel finding. Genipin 1-gentiobioside was screened as a promising new DPP-IV inhibitor in GJE. These findings highlight the potential of this innovative approach for the rapid screening of active ingredients in TCM and provide insights into the molecular mechanisms underlying the anti-diabetic activity of GJE.


Assuntos
Aprendizado Profundo , Inibidores da Dipeptidil Peptidase IV , Gardenia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Gardenia/química , Glicosídeos Iridoides/química , Dipeptidil Peptidases e Tripeptidil Peptidases , Dipeptidil Peptidase 4 , Simulação de Acoplamento Molecular
10.
BMC Genomics ; 24(1): 588, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794356

RESUMO

BACKGROUND: The fruits of Gardenia are rich in flavonoids and geniposides, which have various pharmacological effects such as antioxidant, anti-inflammatory and anticancer. In this study, we analyzed the transcriptome and metabolome of gardenia peel and kernel at different growth stages, revealed the regulatory network related to flavonoid synthesis, and identified the key regulatory genes. RESULTS: The results showed that in terms of flavonoid metabolic pathways, gardenia fruits mainly synthesized cinnamic acid through the phenylpropanoid pathway, and then synthesized flavonoids through the action of catalytic enzymes such as 4-coumaroyl-CoA ligase, chalcone synthase, chalcone isomerase and flavanol synthase, respectively. In addition, we found that the metabolomics data showed a certain spatial and temporal pattern in the expression of genes related to the flavonoid metabolism pathway and the relative content of metabolites, which was related to the development and ripening process of the fruit. CONCLUSIONS: In summary, this study successfully screened out the key genes related to the biosynthesis metabolism of flavonoids in gardenia through the joint analysis of transcriptome and metabolome. This is of certain significance to the in-depth study of the formation mechanism of gardenia efficacy components and the improvement of quality.


Assuntos
Gardenia , Iridoides , Gardenia/genética , Frutas/genética , Flavonoides , Multiômica
11.
Artigo em Inglês | MEDLINE | ID: mdl-37714051

RESUMO

Iridoid glycosides (geniposide (GP), genipin-1-gentiobioside (GB), etc.) and crocins (crocin Ⅰ (CR1), crocin Ⅱ(CR2), etc.) are two main bioactive components in Gardeniae Fructus (GF), which is a famous traditional Chinese medicine. Iridoid glycosides exhibit many activities and are used to manufacture gardenia blue pigment for the food industry. Crocins are rare natural water-soluble carotenoids that are often used as food colorants. A sequential macroporous resin column chromatography technology composed of HC-500B and HC-900B resins was developed to selectively separate iridoid glucosides and crocins from GF. The adsorption of GP on HC-900B resin was an exothermic process. The adsorption of CR1 on HC-500B resin was an endothermic process. The two kinds of components were completely separated by a sequential resin column. GB and GP were mainly found in product 1 (P1) with purities of 11.38% and 46.83%, respectively, while CR1 and CR2 were mainly found in product 2 (P2) with purities of 12.32% and 1.40%, respectively. The recovery yields of all the compounds were more than 80%. The above results showed that sequential resin column chromatography technology achieved high selectivity and recovery yields. GF extract, P1 and P2 could significantly inhibit the secretion of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells, indicating that iridoid glycosides and crocins provide a greater contribution to the anti-inflammatory activity of GF. At the same time, compared to the GF extract and P1, P2 exhibited stronger scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, indicating that crocins may provide a significant contribution to the antioxidant activity of GF.


Assuntos
Medicamentos de Ervas Chinesas , Gardenia , Glucosídeos Iridoides/análise , Antioxidantes/farmacologia , Gardenia/química , Cromatografia Líquida de Alta Pressão/métodos , Carotenoides/farmacologia , Glicosídeos Iridoides/análise , Medicamentos de Ervas Chinesas/análise , Anti-Inflamatórios/farmacologia
12.
J Sep Sci ; 46(21): e2300469, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37691120

RESUMO

Due to the structural similarity and large difference in concentration, the separation of trans- and cis-crocetin has been challenging, and the cis-crocetin is usually neglected. In this work, a countercurrent chromatography method was developed for the quick separation of trans-crocetin and cis-crocetin from the hydrolytic extract of Gardenia jasminoides Ellis. High purity of trans-crocetin (>95%) and cis-crocetin (>91%) were prepared simultaneously for the first time through a novel biphasic system based on deep eutectic solvents, n-heptane/n-butyl alcohol/13 mmol/L Na2 CO3 in water/acetamide-benzyltrimethylammonium chloride (4:1, mol/mol) (4:7:9:1, v/v). The addition of deep eutectic solvent significantly improved the separation efficiency. The two targets can be easily recovered from the separation system through simple acidification and precipitation. It has potential for preparative separations on a large scale.


Assuntos
Distribuição Contracorrente , Gardenia , Distribuição Contracorrente/métodos , Solventes/química , Gardenia/química , Solventes Eutéticos Profundos
13.
PeerJ ; 11: e16056, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744244

RESUMO

Background: Gardenia jasminoides is a species of Chinese medicinal plant, which has high medicinal and economic value and rich genetic diversity, but the study on its genetic diversity is far not enough. Methods: In this study, one wild and one cultivated gardenia materials were resequenced using IlluminaHiSeq sequencing platform and the data were evaluated to understand the genomic characteristics of G. jasminoides. Results: After data analysis, the results showed that clean data of 11.77G, Q30 reached 90.96%. The average comparison rate between the sample and reference genome was 96.08%, the average coverage depth was 15X, and the genome coverage was 85.93%. The SNPs of FD and YP1 were identified, and 3,087,176 and 3,241,416 SNPs were developed, respectively. In addition, SNP non-synonymous mutation, InDel mutation, SV mutation and CNV mutation were also detected between the sample and the reference genome, and KEGG, GO and COG database annotations were made for genes with DNA level variation. The structural gene variation in the biosynthetic pathway of crocin and gardenia, the main medicinal substance of G. jasminoides was further explored, which provided basic data for molecular breeding and genetic diversity of G. jasminoides in the future.


Assuntos
Carotenoides , Gardenia , Plantas Medicinais , Análise de Sequência de DNA , Gardenia/genética , Gardenia/metabolismo , Genômica , Plantas Medicinais/genética , Plantas Medicinais/metabolismo , China , Carotenoides/metabolismo , Variação Genética/genética
14.
Chem Res Toxicol ; 36(9): 1483-1494, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37622730

RESUMO

Genipin (GP) is the reactive aglycone of geniposide, the main component of traditional Chinese medicine Gardeniae Fructus (GF). The covalent binding of GP to cellular proteins is suspected to be responsible for GF-induced hepatotoxicity and inhibits drug-metabolizing enzyme activity, although the mechanisms remain to be clarified. In this study, the mechanisms of GP-induced human hepatic P450 inactivation were systemically investigated. Results showed that GP inhibited all tested P450 isoforms via distinct mechanisms. CYP2C19 was directly and irreversibly inactivated without time dependency. CYP1A2, CYP2C9, CYP2D6, and CYP3A4 T (testosterone as substrate) showed time-dependent and mixed-type inactivation, while CYP2B6, CYP2C8, and CYP3A4 M (midazolam as substrate) showed time-dependent and irreversible inactivation. For CYP3A4 inactivation, the kinact/KI values in the presence or absence of NADPH were 0.26 or 0.16 min-1 mM-1 for the M site and 0.62 or 0.27 min-1 mM-1 for the T site. Ketoconazole and glutathione (GSH) both attenuated CYP3A4 inactivation, suggesting an active site occupation- and reactive metabolite-mediated inactivation mechanism. Moreover, the in vitro and in vivo formation of a P450-dependent GP-S-GSH conjugate indicated the involvement of metabolic activation and thiol residues binding in GP-induced enzyme inactivation. Lastly, molecular docking analysis simulated potential binding sites and modes of GP association with CYP2C19 and CYP3A4. We propose that direct covalent binding and metabolic activation mediate GP-induced P450 inactivation and alert readers to potential risk factors for GP-related clinical drug-drug interactions.


Assuntos
Citocromo P-450 CYP3A , Gardenia , Humanos , Citocromo P-450 CYP2C19 , Simulação de Acoplamento Molecular , Sistema Enzimático do Citocromo P-450
15.
Mol Biol Rep ; 50(8): 6851-6861, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37392282

RESUMO

BACKGROUND: Gardenia jasminoides Ellis is a perennial evergreen shrub of G. jasminoides of Rubiaceae. Geniposide and Crocin are important components in the fruit of G. jasminoides. In addition to being used as medicinal materials, they are also widely used in food, medicine, cosmetics, and other fields. They have high medicinal value, economic value, and ornamental value. However, at present, the utilization rate of G. jasminoides resources is low, mainly focused on germplasm cultivation, primary processing, and clinical pharmacology, and there are few studies on the quality of Gardenia fruit. METHODS AND RESULTS: Based on transcriptome sequencing and metabolic group analysis, the morphological and structural changes of Gardenia fruit with young fruit, middle fruit, and ripe fruit were analyzed, and the formation mechanism and content changes of Geniposide and Crocin in Gardenia fruit were studied. The content of Geniposide decreased with the development of fruit, so did the expression of the main structural gene GES, G10H, and IS in its synthesis pathway, while the content of Crocin increased with the development of fruit, and the expression of the main structural gene CCD, ALDH, and UGT in its synthesis pathway also increased. The relationship between the morphological structure of G. jasminoides and the accumulation of Geniposide and Crocin was summarized. CONCLUSIONS: This study not only provides a theoretical basis for the mining and utilization of Geniposide and Crocin, but also provides a theoretical basis for genetic background for the identification and cloning of bioactive substances in gardenia fruit in future. At the same time, it provides support for increasing the dual-use value of G. jasminoides and breeding excellent germplasm resources.


Assuntos
Gardenia , Gardenia/química , Frutas/genética , Frutas/química , Transcriptoma/genética , Melhoramento Vegetal , Iridoides/farmacologia , Iridoides/química , Metaboloma
16.
J Sep Sci ; 46(17): e2300163, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37496306

RESUMO

The utilization of deep eutectic solvent as an alternative and environmentally friendly option has gained significant attention. This study first proposed a series of benzylammonium chloride based-deep eutectic systems for the extraction of bioactive compounds from Gardenia jasminoides Ellis. Through the implementation of response surface methodology, the optimal solvent was determined to be dodecyldimethylbenzylammonium chloride-levulinic acid (1:3, mol/mol) with 35% (v/v) water, specifically tailored to extract geniposide, genipin-1-ß-d-gentiobioside, crocin-1, and crocin-2 from gardenia fruits with the ratio of solid to liquid of 1:20 at 86°C for 16 min. Their total extraction yields could reach 70.6 mg/g, outperforming those obtained by other solvents and corresponding techniques. Furthermore, the eutectic system was retrieved after first-cycle extraction, and then applied in the subsequent extraction progress, yielding a consistent extraction efficiency of 97.1%. As compared to previous traditional methods, a quick, high-yielding, and green extraction procedure was achieved through simple heating settings that did not constrain the instrument. Therefore, dodecyldimethylbenzylammonium chloride-levulinic acid could serve as a sustainable and reusable solvent for efficient extraction of natural bioactive compounds from plant-based raw materials. The application of deep eutectic solvents has demonstrated their potential as designable solvents with stronger extraction capabilities than traditional organic solvents.


Assuntos
Gardenia , Solventes Eutéticos Profundos , Frutas , Extratos Vegetais , Solventes
17.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3602-3611, 2023 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-37474993

RESUMO

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1ß, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.


Assuntos
Artrite Reumatoide , Gardenia , Microbioma Gastrointestinal , Ratos , Animais , Cromatografia Líquida , Espectrometria de Massas em Tandem , Ácido alfa-Linolênico , Metabolômica/métodos , Artrite Reumatoide/tratamento farmacológico , Inflamação , Glicerofosfolipídeos
18.
Int J Biol Macromol ; 248: 125895, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37481185

RESUMO

This study identified two homogeneous acidic polysaccharides from Gardeniae fructus, GJP50-3 and GJP50-4, which exhibited potential immunomodulatory activities in macrophage activation assays, via liquid-chip technology, and in a zebrafish model. Monosaccharide composition analysis and gel permeation chromatography revealed that GJP50-3 and GJP50-4 were composed of Rha, GalA, Glc, Gal, and Ara in specific ratios and had molecular weights of 91.5 kDa and 140.3 kDa, respectively. Based on FT-IR, GC-MS, and NMR analyses, these polysaccharides were identified as typical pectin polysaccharides with methylation degrees of 24.7 % and 21.4 %, respectively. The primary structures of GJP50-3 and GJP50-4 included linear HG domains and branched RG-I domains with arabinans and AG side chains. In vitro, GJP50-3 and GJP50-4 could stimulate NO release and increase the secretion of TNF-α in a RAW 264.7 macrophage model. Luminex liquid suspension chip detection revealed that GJP50-3 significantly promoted the secretion of multiple interleukins [IL-6, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13], TNF-α, and chemokines (G-CSF, GM-CSF, MCP-1 and RANTES). In vivo, these polysaccharides could also increase NO release and neutrophil count in a zebrafish model. These findings suggested that GJP50-3 and GJP50-4 might have the potential to be used as immunomodulators in the food and pharmaceutical industries.


Assuntos
Gardenia , Animais , Peixe-Zebra , Fator de Necrose Tumoral alfa , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/farmacologia , Polissacarídeos/química , Interleucina-12
19.
Front Cell Infect Microbiol ; 13: 1167312, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37377643

RESUMO

Fructus gardeniae (FG) is a traditional Chinese medicine and health food for thousands of years of application throughout Chinese history and is still widely used in clinical Chinese medicine. FG has a beneficial impact on anxiety, depression, insomnia, and psychiatric disorders; however, its mechanism of action requires further investigation. This study aimed to investigate the effects and mechanisms of FG on sleep deprivation (SD)-induced anxiety-like behavior in rats. A model of SD-induced anxiety-like behavior in rats was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). This was accompanied by neuroinflammation and metabolic abnormalities in the hippocampus and disturbance of intestinal microbiota. However reduced SD-induced anxiety-like behavior and decreased levels of pro-inflammatory cytokines including TNF-α and IL-1ß were observed in the hippocampus of rats after 7 days of FG intervention. In addition, metabolomic analysis demonstrated that FG was able to modulate levels of phosphatidylserine 18, Phosphatidylinositol 18, sn-glycero-3-phosphocholine, deoxyguanylic acid, xylose, betaine and other metabolites in the hippocampus. The main metabolic pathways of hippocampal metabolites after FG intervention involve carbon metabolism, glycolysis/gluconeogenesis, pentose phosphate, and glycerophospholipid metabolism. 16S rRNA sequencing illustrated that FG ameliorated the dysbiosis of gut microbiota in anxious rats, mainly increased the abundance of Muribaculaceae and Lactobacillus, and decreased the abundance of Lachnospiraceae_NK4A136_group. In addition, the correlation analysis demonstrated that there was a close relationship between hippocampal metabolites and intestinal microbiota. In conclusion, FG improved the anxiety behavior and inhibited of neuroinflammation in sleep-deprived rats, and the mechanism may be related to the FG regulation of hippocampal metabolites and intestinal microflora composition.


Assuntos
Gardenia , Microbioma Gastrointestinal , Ratos , Animais , Gardenia/genética , Privação do Sono , Doenças Neuroinflamatórias , RNA Ribossômico 16S/genética , Metabolômica , Hipocampo , Ansiedade/tratamento farmacológico
20.
Dig Endosc ; 35(4): 481-482, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37167029

Assuntos
Gardenia , Humanos , Flores
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