Unveiling molecular mechanisms of pigment synthesis in gardenia (Gardenia jasminoides) fruits through integrative transcriptomics and metabolomics analysis.

This study conducted a combined transcriptomics and metabolomics analysis in premature and mature developmental stages of Gardenia jasminoides Ellis fruits to identify the molecular mechanisms of pigment synthesis. The transcriptomics data produced high-quality clean data amounting to 46.98 gigabytes, exhibiting a mapping ratio of 86.36% to 91.43%. Transcriptomics analysis successfully identified about 3,914 differentially expressed genes which are associated with pivotal biological processes, including photosynthesis, chlorophyll, biosynthetic processes, and protein-chromophore linkage pathways. Functional diversity was clarified by the Clusters of Orthologous Groups (COG) classification, which focused mainly on pigment synthesis functions. Pathways analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) revealed critical pathways affecting pigment development. Metabolomics studies were carried out utilizing Ultra Performance Liquid Chromatography and mass spectrometry (UPLC-MS). About 480 metabolites were detected via metabolomics investigation, the majority of that were significantly involved in pigment synthesis. Cluster and pathway analyses revealed the importance of pathways such as plant secondary metabolite biosynthesis, biosynthesis of phenylpropanoids and plant hormone signal transduction in pigment synthesis. Current research advances our comprehension of the underlying mechanisms at the molecular level governing pigment synthesis in gardenia fruits, furnishing valuable insights for subsequent investigations.

Construction of an explanatory model for predicting hepatotoxicity: a case study of the potentially hepatotoxic components of Gardenia jasminoides.

It is well-known that the hepatotoxicity of drugs can significantly influence their clinical use. Despite their effective therapeutic efficacy, many drugs are severely limited in clinical applications due to significant hepatotoxicity. In response, researchers have created several machine learning-based hepatotoxicity prediction models for use in drug discovery and development. Researchers aim to predict the potential hepatotoxicity of drugs to enhance their utility. However, current hepatotoxicity prediction models often suffer from being unverified, and they fail to capture the detailed toxicological structures of predicted hepatotoxic compounds. Using the 56 chemical constituents of Gardenia jasminoides as examples, we validated the trained hepatotoxicity prediction model through literature reviews, principal component analysis (PCA), and structural comparison methods. Ultimately, we successfully developed a model with strong predictive performance and conducted visual validation. Interestingly, we discovered that the predicted hepatotoxic chemical constituents of Gardenia possess both toxic and therapeutic effects, which are likely dose-dependent. This discovery greatly contributes to our understanding of the dual nature of drug-induced hepatotoxicity.

Transcriptional profiling of geniposide bioconversion into genipin during gardenia fructus extract fermentation by Lactobacillus (Lactiplantibacillus) plantarum SN13T.

Lactiplantibacillus plantarum SN13T is a probiotic plant-derived lactic acid bacterium that can grow in various medicinal plant extracts. In this study, we fermented an aqueous extract of gardenia fructus, the fruit of a medicinal plant, with SN13T, such that the bioactivity of the extract was potentiated after fermentation to suppress the release of inflammatory mediators, such as nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), as well as downregulate inflammatory genes in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. This increased antioxidant and anti-inflammatory activity was mediated through bioconversion of the iridoid glycoside geniposide to its aglycone genipin via the supposed hydrolytic action of ß-glucosidases harbored by SN13T. In the complete genome of SN13T, ten putative genes encoding ß-glucosidases of glycosyl hydrolase (GH) family 1 organized among eight gene operons were identified. Transcriptional profiling revealed that two 6-phospho-ß-glucosidase genes, pbg9 and SN13T_1925, located adjacently in the gene operon SN13T_1923, were transcribed significantly more than the remaining genes during fermentation of the gardenia extract. This suggests the role of these ß-glucosidases in bioconversion of geniposide to genipin and the subsequent enhanced bioactivity of the gardenia fructus extract after fermentation with SN13T.

Extract of Gardenia jasminoides Ellis Attenuates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats by Targeting Gut Microbiota and TLR4/Myd88/NF-κB Pathway.

Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

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.

Molecular Characterization of an Isolate of Bean Common Mosaic Virus First Identified in Gardenia Using Metatranscriptome and Small RNA Sequencing.

Gardenia (Gardenia jasminoides) is a popular and economically vital plant known for its ornamental and medicinal properties. Despite its widespread cultivation, there has been no documentation of plant viruses on gardenia yet. In the present study, gardenia leaves exhibiting symptoms of plant viral diseases were sampled and sequenced by both metatranscriptome and small RNA sequencing. As a consequence, bean common mosaic virus (BCMV) was identified in gardenia for the first time and named BCMV-gardenia. The full genome sequence of BCMV-gardenia is 10,054 nucleotides (nt) in length (excluding the poly (A) at the 3' termini), encoding a large polyprotein of 3,222 amino acids. Sequence analysis showed that the N-termini of the polyprotein encoded by BCMV-gardenia is less conserved when compared to other BCMV isolates, whereas the C-termini is the most conserved. Maximum likelihood phylogenetic analysis showed that BCMV-gardenia was clustered closely with other BCMV isolates identified outside the leguminous plants. Our results indicated that the majority of BCMV-gardenia virus-derived small interfering RNAs (vsiRNAs) were 21 nt and 22 nt, with 21 nt being more abundant. The first nucleotide at the 5' termini of vsiRNAs derived from BCMV-gardenia preferred U and A. The ratio of vsiRNAs derived from sense (51.1%) and antisense (48.9%) strands is approaching, and the distribution of vsiRNAs along the viral genome is generally even, with some hot spots forming in local regions. Our findings could provide new insights into the diversity, evolution, and host expansion of BCMV and contribute to the prevention and treatment of this virus.

Neuropharmacological insights into Gardenia jasminoides Ellis: Harnessing therapeutic potential for central nervous system disorders.

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.

Convective drying of Gardenia erubescens fruits: Effect of pretreatment, slice thickness and drying air temperature on drying kinetics and product quality.

Gardenia erubescens fruits are regarded as nutrient-dense, capable of promoting nutritional and metabolic human health. However, they are seasonal and highly perishable which limits their consumption and wider utilization. In this study, the effect of slice thickness (3 mm and 5 mm), pretreatments (steam blanching and dipping in ascorbic acid solution) and drying air temperature (40 °C, 50 °C, 60 °C and 70 °C) on drying kinetics, color, ß-carotene and vitamin C content of Gardenia erubescens fruits were investigated. The results showed that the drying time increased as slice thickness increased, and decreased as drying air temperature increased but did not follow any trend for pretreatment. The Page model (R2 values of 0.9998-0.9999) exhibited the best fit to the drying kinetics data. The diffusivity values (5.31 × 10-11 to 4.14 × 10-10 m2s-1) increased as the slice thickness and drying air temperature increased but had no linear trends with pretreatment. The activation energy ranged from 14.35 to 44.78 kJmol-1, with the highest being recorded by 5 mm untreated samples and the lowest by the 3 mm blanched samples. The total color change (ΔE*) of the samples generally decreased as the drying air temperature increased but increased as the slice thickness increased. The ascorbic acid pretreated samples had the least color change, followed by the untreated samples while the blanched samples had the highest change. Overall, the 5 mm ascorbic acid pretreated samples dried at 70 °C had the least color change (13.33 ± 0.52). The blanching and dipping in ascorbic acid solution generally yielded lower ß-carotene and vitamin C values as compared to the untreated samples. The 3 mm ascorbic acid pretreated samples dried at 50 °C recorded the lowest ß-carotene (42.70 ± 3.21 µg/100 g) while the 5 mm ascorbic acid pretreated samples had the lowest vitamin C (37.50 ± 2.65 mg/100 g) at 70 °C. Pretreatments and drying air temperatures showed mixed effects on the drying characteristics, color, ß-carotene and vitamin C contents of fruit slices. The findings, therefore, indicate that a compromise may have to be made on the aforementioned processing conditions in order to meet the desired attributes of one's interest.

Gardenia yellow pigment: Extraction methods, biological activities, current trends, and future prospects.

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.

A fused hybrid enzyme of 8-hydroxygeraniol oxidoreductase (8HGO) from Gardenia jasminoides and iridoid synthase (ISY) from Catharanthus roseus significantly enhances nepetalactol and iridoid production.

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.

Advanced quality assessment of Sanshishi (Gardenia jasminoides Ellis) and Kampo medicines using a monoclonal antibody against geniposide.

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.

Protective effects of leaf aqueous extracts from Gardenia ternifolia Schumach. on alcoholic liver disease in Wistar rats.

BACKGROUND: Gardenia ternifolia (GT) is a plant of the Rubiaceae family, with a wide range of ethnopharmacological properties. However, its hepatoprotective effects were poorly investigated. This work aimed at assessing the hepatoprotective activity of GT leaf aqueous extracts against chronic ethanol-induced damage in vivo. MATERIALS AND METHODS: Male Wistar albino rats were given orally 10 % ethanol (10 mL/kg) and different doses of GT extracts (50, 100, and 200 mg/kg) or distilled water (negative control) simultaneously and daily for 28 days. Normal controls were fed with a normal diet while positive controls received, in addition to ethanol, silymarin (50 mg/kg). After treatment, animals were sacrificed, blood and liver samples were collected, various biochemical parameters were quantified and the histological sections were performed. Moreover, a qualitative phytochemical analysis of this extract was carried out. RESULTS: GT administration significantly reduced alanine aminotransferase (10.35 ± 2.13 U/L and 9.07 ± 2.13 U/L vs 24.43 ± 4.28 UI/L) and aspartate aminotransferase (14.25 ± 3.02 and 18.32 ± 2.13 UI/L vs 34.61 ± 3.23 UI/L) activities at doses of 50 and 100 mg/kg respectively in comparison with the negative control. Likewise, serum triglyceride and total cholesterol levels were significantly reduced by GT extract, especially at the dose of 200 mg/kg compared to the ethanol-treated group. Histological examination showed that the extract protected the liver by reducing hepatic cytolysis, and leukocyte infiltration. Different secondary metabolites including condensed tannins, phenolic acids, and saponins were found in the GT extract but none of these compounds corresponded to epicatechin, coumarin and naringenin. CONCLUSION: These results show that GT extract may be a potential therapeutic agent against alcoholic liver disease.

Gardenia jasminoides J. Ellis extract attenuates memory impairment in rats with Alzheimer's disease by suppressing NLRP3 inflammasome.

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.

Expression of a thermostable glucose-stimulated ß-glucosidase from a hot-spring metagenome and its promising application to produce gardenia blue.

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.

Gardenia Iridoid Glucosides Protect Against α-Naphthalene Isothiocya-Nate-Induced Cholestatic Rats Through Activation of the FXR-SHP Signaling Pathway.

Introduction: Cholestasis is a common liver disorder that currently has limited treatment options. Gardenia Iridoid Glucosides (GIG) have been found to possess various physiological activities, such as cholagogic, hypoglycemic, antibacterial, and anti-inflammatory effects. The objective of this study was to investigate the effects of GIG on bile acid enterohepatic circulation and explore the underlying mechanism in cholestatic rats. Methods: In order to identify key pathways associated with cholestasis, we conducted Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. In vivo experiments were then performed on alpha-naphthylisothiocyanate (ANIT)-treated rats to assess the impact of GIG. We measured bile flow and various biomarkers including total bilirubin (TB), total bile acids (TBA), total cholesterol (TC), malondialdehyde (MDA), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and total superoxide dismutase (T-SOD) in the serum. We also examined the expression levels of bile salt export pump (BSEP), ATP-binding cassette subfamily B member 4 (ABCB4), far-nesoid X receptor (FXR), small heterodimer partner (SHP), cholesterol 7α-hydroxylase (CYP7A1), and sodium taurocholate cotransporting polypeptide (NTCP) in liver tissue. In vitro experiments were conducted on primary hepatocytes to further investigate the mechanism of action of GIG on the expression of SHP, CYP7A1, NTCP, and FXR. Results: Our in vivo experiments demonstrated that GIG significantly increased bile flow and reduced the levels of TB, TBA, TC, MDA, GPT, and GOT, while increasing T-SOD levels in ANIT-treated rats. Addi-tionally, GIG ameliorated liver tissue damage induced by ANIT, upregulated the expression of BSEP and ABCB4, and modulated the protein expression of FXR, SHP, CYP7A1, and NTCP in model rats. In vitro experiments further revealed that GIG inhibited the expression of SHP, CYP7A1, and NTCP by suppressing the expression of FXR. Conclusion: This study provides new insights into the therapeutic potential of GIG for the treatment of cholestasis. GIG demonstrated beneficial effects on bile acid enterohepatic circulation and liver biomarkers in cholestatic rats. The modulation of FXR and its downstream targets may contribute to the mechanism of action of GIG. These findings highlight the potential of GIG as a therapeutic intervention for cholangitis.

Integration of Deep Learning and Sequential Metabolism to Rapidly Screen Dipeptidyl Peptidase (DPP)-IV Inhibitors from Gardenia jasminoides Ellis.

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.

Ternifoliasaponin, a new triterpenoid saponin from the roots of Gardenia ternifolia Schumach & Thonn (Rubiaceae).

A new triterpenoid saponin, Ternifoliasaponin (1), together with four known compounds (2-5) chikusetsusaponin IVa (2), chikusetsusaponin IVa methyl ester (3), bonushenricoside B (4) and Dianoside C (5) were isolated from roots of Gardenia ternifolia Schumach. & Thonn (Rubiaceae). The structures of isolated compounds were elucidated on the basis of spectroscopic analysis and chemical methods. The antibacterial activities of compounds (3), and (4) were performed by the Muller-Hinton agar diffusion method. The antimicrobial activities of the compounds were studied on Salmonella typhi (Enterobacteriaceae), Staphylococcus aureus and Pseudomonas aeruginosa microorganisms. Compound (3) at 25 mg/mL, showed moderately sensitive effect (8.0 ˂ DIZ ˂14.0 mm) on S. typhi, S. aureus and P. aeruginosa. Compound (4) at 25 mg/mL and compound (3) at 12.5 mg/mL exhibited moderately sensitive effect on S. typhi and S. aureus. Compound (4) inhibited moderately sensitive the S. typhi and P. aeruginosa colonies at 12.5 mg/mL.

Simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) by probe-type ultrasound-assisted natural deep eutectic solvents and their inhibition effects on low density lipoprotein oxidation.

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.

Health oil preparation from gardenia seeds by aqueous enzymatic extraction combined with puffing pre-treatment and its properties analysis.

Gardenia jasminoides Ellis, a representative for "homology of medicine and food", can be used to produce pigment and edible oil. Here, aqueous enzymatic extraction (AEE) combined with puffing pre-treatment was explored to prepare oil from gardenia seeds. Both wet-heating puffing (WP) at 90 °C and dry-heating puffing (DP) at 1.0 MPa facilitated the release of free oil by AEE, resulting in the highest free oil yields (FOY) of 21.8% and 23.2% within 3 h, much higher than that of un-puffed group. Additionally, active crocin and geniposide were also completely released. The FOY obtained was much higher than mechanical pressing method (10.44%), and close to solvent extraction (25.45%). Microstructure analysis indicated that gardenia seeds expanded by dry-heating puffing (1.0 MPa) had a larger, rougher surface and porous structure than other groups. Overall, AEE coupled with puffing pre-treatment developed is an eco-friendly extraction technology with high efficiency that can be employed to oil preparation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01319-9.