Gardenia jasminoides extract mitigates acetaminophen-induced liver damage in mice.

BACKGROUND: Acetaminophen (APAP)-induced hepatotoxicity is a potentially life-threatening condition. Gardenia jasminoides fruit extract (GJE), which contains geniposide (Gen) as its major active constituent, possesses anti-inflammatory and antioxidant properties and may help address the underlying pathogenesis of APAP-induced hepatotoxicity. This study aimed to evaluate the effects of GJE in a mouse model of APAP-induced hepatotoxicity. METHODS: Twenty-four male ICR mice were divided into 4 groups (n = 6/group): [1] Control group, mice were given distilled water; [2] APAP group, mice received a single dose of 600 mg/kg APAP; [3] APAP + low-dose GJE group, mice received APAP followed 30 min later by 2 doses of low-dose GJE (0.44 g/kg/dose, containing Gen 100 mg/kg/dose) 8 h apart; [4] APAP + high-dose GJE group, mice received APAP followed by 2 doses of high-dose GJE (0.88 g/kg/dose, containing Gen 200 mg/kg/dose). All mice were euthanized 24 h after APAP administration. Liver tissue was used for histological examination and to measure glutathione (GSH) and malondialdehyde (MDA) levels. Serum was used to determine levels of ALT and inflammatory cytokines (tumor necrosis factor- α (TNF-α) and interleukin-6 (IL-6)). RESULTS: Liver histopathology showed moderate to severe hepatic necroinflammation in the APAP group, whereas only mild necroinflammation was observed in both treatment groups. Serum ALT levels were significantly elevated in the APAP group compared to the control group but were significantly reduced after low- and high-dose GJE treatment. Serum TNF- α levels were significantly higher in the APAP group than in the control group and were significantly lower after high-dose GJE treatment (135.5 ± 477.2 vs. 35.5 ± 25.8 vs. 74.7 ± 47.2 vs. 41.4 ± 50.8 pg/mL, respectively). Serum IL-6 followed a similar pattern. Hepatic GSH levels were significantly lower in the APAP group compared to the control group but significantly increased after both low- and high-dose GJE treatment (19.9 ± 4.5 vs. 81.5 ± 12.4 vs. 71.4 ± 7.8 vs. 82.6 ± 6.6 nmol/mg protein, respectively). Conversely, hepatic MDA levels were significantly elevated in the APAP group compared with the control group but significantly decreased after high-dose GJE treatment (108.6 ± 201.5 vs. 40.5 ± 18.0 vs. 40.5 ± 16.8 nmol/mg protein, respectively). CONCLUSIONS: Treatment with G. jasminoides fruit extract can alleviate APAP-induced hepatotoxicity, likely through its anti-inflammatory and antioxidant properties.

A Comparison Analysis of Four Different Drying Treatments on the Volatile Organic Compounds of Gardenia Flowers.

The gardenia flower not only has extremely high ornamental value but also is an important source of natural food and spices, with a wide range of uses. To support the development of gardenia flower products, this study used headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) technology to compare and analyze the volatile organic compounds (VOCs) of fresh gardenia flower and those after using four different drying methods (vacuum freeze-drying (VFD), microwave drying (MD), hot-air drying (HAD), and vacuum drying (VD)). The results show that, in terms of shape, the VFD sample is almost identical to fresh gardenia flower, while the HAD, MD, and VD samples show significant changes in appearance with clear wrinkling; a total of 59 volatile organic compounds were detected in the gardenia flower, including 13 terpenes, 18 aldehydes, 4 esters, 8 ketones, 15 alcohols, and 1 sulfide. Principal component analysis (PCA), cluster analysis (CA), and partial least-squares regression analysis (PLS-DA) were performed on the obtained data, and the research found that different drying methods impact the VOCs of the gardenia flower. VFD or MD may be the most effective alternative to traditional sun-drying methods. Considering its drying efficiency and production cost, MD has the widest market prospects.

Quantification and comparison of major secondary metabolites and antioxidant efficacy in Gardenia jasminoides mother plant, callus and suspension culture: An exploratory study to enhance bioactive compounds.

Gardenia jasminoides suspension culture has gained recognition as a functional approach for bioactive component development in the pharmaceutical industries but exhibits limited biomass accumulation and secondary metabolite production. This study presents the first record of maximum biomass production and demonstrates the cumulative levels of phenols, flavonoids and terpenoids observed through the growth trajectory of G. jasminoides suspension culture. Successful callus induction was obtained from leaf explants cultured on Murashige and Skoog (MS) medium augmented with a standardized conjunction of 1 mg/L of 2,4-Dichlorophenoxyacetic acid (2,4-D) and 0.5 mg/L kinetin (KT). The experimental outcomes revealed that on the 35th day, the in vitro suspension culture exhibited the highest biomass accumulation which was 5.43 times greater than the initial inoculation level. The study quantified total phenols, flavonoids, and terpenoids present in leaf explants, callus cultures, and suspension cultures and determined antioxidant efficacy. Findings suggest that an optimized growth regulator in G. jasminoides suspension culture significantly increases biomass accumulation. Quantification of secondary metabolites offers a promising path for future enhancement of their yield through elicitation and holds the potential to achieve extensive yield of cost-effective bioactive components.

A refined formula derived from Jiawei-Xiaoyao pill exerts rapid antidepressant-like effects in LPS-induced depression by reducing neuroinflammation and restoring neuroplasticity signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet. AIM OF THE STUDY: Here we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula. MATERIALS AND METHODS: Individual herbs (MC; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested in a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using Western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) was used as a positive control for induction of rapid antidepressant effects. RESULTS: A combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA. CONCLUSION: GMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In the LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity.

A metabolomics study on the mechanisms of Gardeniae fructus against α-naphthylisothiocyanate-induced cholestatic liver injury.

Gardeniae fructus (GF) is known for its various beneficial effects on cholestatic liver injury (CLI). However, the biological mechanisms through which GF regulates CLI have not been fully elucidated. This study aimed to explore the potential mechanisms of GF against α-naphthylisothiocyanate (ANIT)-induced CLI. First, HPLC technology was used to analyze the chemical profile of the GF extract. Second, the effects of GF on serum biochemical indicators and liver histopathology were examined. Lastly, metabolomics was utilized to study the changes in liver metabolites and clarify the associated metabolic pathways. In chemical analysis, 10 components were identified in the GF extract. GF treatment regulated serum biochemical indicators in ANIT-induced CLI model rats and alleviated liver histological damage. Metabolomics identified 26 endogenous metabolites as biomarkers of ANIT-induced CLI, with 23 biomarkers returning to normal levels, particularly involving primary bile acid biosynthesis, glycerophospholipid metabolism, tryptophan metabolism, and arachidonic acid metabolism. GF shows promise in alleviating ANIT-induced CLI by modulating multiple pathways.

Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking.

OBJECTIVE: To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG). METHODS: The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies. RESULTS: FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking. CONCLUSION: FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.

Neuroprotective effect of GJ-4 against cognitive impairments in vascular dementia by improving white matter damage.

BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.

Geniposide dosage and administration time: Balancing therapeutic benefits and adverse reactions in liver disease treatment.

Gardenia jasminoides Ellis, a staple in herbal medicine, has long been esteemed for its purported hepatoprotective properties. Its primary bioactive constituent, geniposide, has attracted considerable scientific interest owing to its multifaceted therapeutic benefits across various health conditions. However, recent investigations have unveiled potential adverse effects associated with its metabolite, genipin, particularly at higher doses and prolonged durations of administration, leading to hepatic injury. Determining the optimal dosage and duration of geniposide administration while elucidating its pharmacological and toxicological mechanisms is imperative for safe and effective clinical application. This study aimed to evaluate the safe dosage and administration duration of geniposide in mice and investigate its toxicological mechanisms within a comprehensive dosage-duration-efficacy/toxicity model. Four distinct mouse models were employed, including wild-type mice, cholestasis-induced mice, globally farnesoid X-activated receptor (FXR) knock out mice, and high-fat diet-induced (HFD) NAFLD mice. Various administration protocols, spanning one or four weeks and comprising two or three oral doses, were tailored to each model's requirements. Geniposide has positive effects on bile acid and lipid metabolism at doses below 220 mg/kg/day without causing liver injury in normal mice. However, in mice with NAFLD, this dosage is less effective in improving liver function, lipid profiles, and bile acid metabolism compared to lower doses. In cholestasis-induced mice, prolonged use of geniposide at 220 mg/kg/day worsened liver damage. Additionally, in NAFLD mice, this dosage of geniposide for four weeks led to intestinal pyroptosis and liver inflammation. These results highlight the lipid-lowering and bile acid regulatory effects of geniposide, but also warn of potential negative impacts on intestinal epithelial cells, particularly with higher doses and longer treatment durations. Therefore, achieving optimal therapeutic results requires a decrease in treatment duration as the dosage increases, in order to maintain a balanced approach to the use of geniposide in clinical settings.

Advances in the mechanisms of Gardenia jasminoides Ellis in improving diabetes and its complications.

Gardenia jasminoides Ellis (Zhi-zi), which belongs to the Rubiaceae family, has been used mainly with its fry fruit for thousands of years, and it is an herb with the homology of medicine and food. In traditional Chinese medicine (TCM) theory, Zhi-zi can be used for "Quench Xiaoke", meaning for therapying diabetes in modern medicine. Based on numerous pharmacological studies, Gardenia jasminoides Ellis (Zhi-zi), and its ingredients, mainly including iridoid glycosides and carotenoids (crocins), possess potent antioxidant and anti-inflammatory properties, and can promote insulin secretion and sensitization, stimulate GLP-1 pathway activity, and protect islet ß cells and the macro- and microvascular systems. These properties are the primary reasons why Zhi-zi and its ingredients are effective in reducing glucose levels, treating diabetes, and preventing its complications. This review aims to summarize the current situation and the advances of the studies on the mechanisms of Zhi-zi in improving diabetes and its complications, and it is expected to provide useful and systematic references for future research and clinical application of Zhi-zi and its active ingredients in the therapy of diabetes and complications.

Detection of sulphur(II) of carbon dots synthesized from Gardenia residue.

The detection of anions using carbon dots (CDs) has received less attention compared to cations. Therefore, the present study aimed to develop a fluorescence sensor based on carbon dots (CDs) capable of detecting S2- in real water samples. The CDs were successfully prepared from the residues of a traditional Chinese herb, Gardenia, which emitted green photoluminescence (PL) under ultraviolet light irradiation. The as-prepared CDs were quasi-spherical in shape and ranged in size from 10 to 30 nm. Different detailed analyses proved that the CDs had good morphology, various functional groups, high water solubility, great optical features, and excellent stability under diverse environmental conditions. The ion detection showed that only Ag+ had the strongest fluorescence quenching effect on the CDs, however, the addition of S2- could recover their fluorescence. Based on these results, an "off-on" fluorescence sensor was achieved to selectively detect the concentration of S2- in real water samples with a limit of detection (LOD) of 39 µM, which further expanded the application of residues from traditional Chinese herbal medicine.

Geniposide ameliorates atherosclerosis by restoring lipophagy via suppressing PARP1/PI3K/AKT signaling pathway.

BACKGROUND: Atherosclerosis (AS) is the leading cause of global death, which manifests as arterial lipid stack and plaque formation. Geniposide is an iridoid glycoside extract from Gardenia jasminoides J.Ellis that ameliorates AS by mediating autophagy. However, how Geniposide regulates autophagy and treats AS remains unclear. PURPOSE: To evaluate the efficacy and mechanism of Geniposide in treating AS. STUDY DESIGN AND METHODS: Geniposide was administered to high-fat diet-fed ApoE-/- mice and oxidized low-density lipoprotein-incubated primary vascular smooth muscle cells (VSMCs). AS was evaluated with arterial lipid stack, plaque progression, and collagen loss in the artery. Foam cell formation was detected by lipid accumulation, inflammation, apoptosis, and the expression of foam cell markers. The mechanism of Geniposide in treating AS was assessed using network pharmacology. Lipophagy was measured by lysosomal activity, expression of lipophagy markers, and the co-localization of lipids and lipophagy markers. The effects of lipophagy were blocked using Chloroquine. The role of PARP1 was assessed by Olaparib (a PARP1 inhibitor) intervention and PARP1 overexpression. RESULTS: In vivo, Geniposide reversed high-fat diet-induced hyperlipidemia, plaque progression, and inflammation. In vitro, Geniposide inhibited VSMC-derived foam cell formation by suppressing lipid stack, apoptosis, and the expressions of foam cell markers. Network pharmacological analysis and in vitro validation suggested that Geniposide treated AS by enhancing lipophagy via suppressing the PI3K/AKT signaling pathway. The benefits of Geniposide in alleviating AS were offset by Chloroquine in vivo and in vitro. Inhibiting PARP1 using Olaparib promoted lipophagy and alleviated AS progression, while PARP1 overexpression exacerbated foam cell formation and lipophagy blockage. The above effects of PARP1 were weakened by PI3K inhibitor LY294002. PARP1 also inhibited the combination of the ABCG1 and PLIN1. CONCLUSION: Geniposide alleviated AS by restoring PARP1/PI3K/AKT signaling pathway-suppressed lipophagy. This study is the first to present the lipophagy-inducing effect of Geniposide and the binding of ABCG1 and PLIN1 inhibited by PARP1.

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.

Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota-gut-brain axis in corticosterone combined with chronic restraint stress-induced mice.

BACKGROUND: The microbiota-gut-brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota-gut-brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive. MATERIALS AND METHODS: In this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme-linked immunosorbent assay (ELISA), 16S rRNA technology, high-throughput sequencing, quantitative RT-PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder. RESULTS: We found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune-related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi-target therapeutic effects of ZZCD against anxiety and depression. CONCLUSIONS: These findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota-gut-brain.

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.

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.

A countercurrent chromatography solvent system based on deep eutectic solvents for separation of cis- and trans-crocetin from Gardenia jasminoides Ellis.

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.

Preparative separation of iridoid glucosides and crocins from Gardeniae Fructus using sequential macroporous resin column chromatography and evaluation of their anti-inflammatory and antioxidant activities.

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.

Transcriptome and metabolome analysis revealed the changes of Geniposide and Crocin content in Gardenia jasminoides fruit.

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.

An intelligent extraction approach of feature information from three-dimensional DAD chromatogram for integrated quality control of traditional Chinese medicines: Gardenia jasminoides root as an example.

Traditional Chinese medicine (TCM) fingerprinting, which has the characteristics of holism and ambiguity, is a conventional strategy for the holistic quality control of TCMs. However, the fingerprinting of TCMs at the current stage generally adopts a single wavelength or few wavelengths, lacking the effective utilization of diode-array detector (DAD) chromatogram data. This study proposes an intelligent extraction approach of feature information from a three-dimensional DAD chromatogram to establish a novel bar-form-diagram (BFD) for integrated quality control of TCMs. The BFD was automatically established by the chromatographic and spectral information of a complex hybrid system in a DAD chromatogram. This covered the peak areas of target compositions at the optimal absorption wavelength. Taking 27 batches of Gardenia jasminoides root as samples, the BFD combined with chemometrics was applied for assessing the quality of samples completely, which improved the accuracy of origin classification using hierarchical cluster analysis, principal component analysis, soft independent modeling of class analogy and orthogonal partial least squares discriminant analysis. Single-wavelength fingerprinting and BFD used 23 and 38 common peaks as variables respectively, and the adjusted rand index results of the single wavelength and BFD were 0.559 and 0.819, respectively. Compared with the ergodic methods of each single wavelength, the peak recognition method in this study improved the operation speed from 180 s to 4 s and the computational complexity. The established BFD approach performed more abundant characteristic information of chemical components of TCMs and more accurate origin classification ability, and it had great advantages in the overall quality control of TCMs.

Elucidation of Natural Components of Gardenia thunbergia Thunb. Leaves: Effect of Methanol Extract and Rutin on Non-Alcoholic Fatty Liver Disease.

The rising prevalence of non-alcoholic fatty liver disease NAFLD has strained the healthcare system. Natural products could solve this problem, so the current study focused on the impact of G. thunbergia Thunb. against this ailment. LC-ESI-MS/MS revealed the phytochemical profile of the methanol extract from Gardenia thunbergia leaves (GME). Forty-eight compounds were tentatively identified, and stigmasterol, fucosterol, ursolic acid, and rutin were isolated. The separation of the last three compounds from this plant had not before been achieved. The anti-NAFLD effect of the methanol extract of the leaves of G. thunbergia, and its major metabolite, rutin, was assessed in mice against high-fructose diet (HFD)-induced obesity. Male mice were allocated into nine groups: (1) saline (control), (2) 30% fructose (diseased group), (3) HFD, and 10 mg/kg of simvastatin. Groups 4-6 were administered HFD and rutin 50, 75, and 100 mg/kg. Groups (7-9) were administered HFD and methanol extract of leaves 100, 200, and 300 mg/kg. Methanol extract of G. thunbergia leaves at 200 mg/kg, and rutin at 75 mg/kg significantly reduced HFD-induced increments in mice weight and hepatic damage indicators (AST and ALT), steatosis, and hypertrophy. The levels of total cholesterol, LDL-C, and triglycerides in the blood decreased. In addition, the expressions of CYP2E1, JNK1, and iNOS in the diseased mice were downregulated. This study found that GME and rutin could ameliorate NAFLD in HFD-fed mice, with results comparable to simvastatin, validating G. thunbergia's hepatoprotective effects.