Gardenia Fruit Research Articles

Microeukaryotic Communities on the Fruit of Gardenia thunbergia Thunb. with a Focus on Pathogenic Fungi.

Woody fruit which stay on ornamental plants for a long time may present a risk of infection to other organisms due to the presence of pathogens on their surface. We compared the microbe communities on the fruit surfaces of garden ornamental Gardenia thunbergia Thunb. with those on other surfaces in the study region. As Gardenia fruit contain antifungal substances, the focus of this study was on the fungal communities that exist thereon. We used Illumina sequencing to identify Amplicon Sequence Variants (ASV) of the internal transcribed spacer 2 (ITS2) of the ribosomal RNA. The microbial communities of the Gardenia fruit are distinct from the communities from the surrounding environments, indicating a specialized microhabitat. We employed clustering methods to position unidentified ASVs relative to known ASVs. We identified a total of 56 ASVs representing high risk fungal species as putative plant pathogens exclusively found on the fruit of Gardenia. Additionally, we found several ASVs representing putative animal or human pathogens. Those pathogens were distributed over distinct fungi clades. The infection risk of the high diversity of putative pathogens represented on the Gardenia fruit needs to be elucidated in further investigations.

525 Genipin contained in gardenia fruit induced skin pigmentation

525 Genipin contained in gardenia fruit induced skin pigmentation

薬用植物栽培における使用農薬の実態調査（第3報）中国産サンシシの使用農薬

薬用植物栽培における使用農薬の実態調査（第3報）中国産サンシシの使用農薬

Adverse Effects of Kampo Medicines.

This review summarizes the adverse effects of Kampo medicines. These adverse effects in terms of immunoallergic reactions include interstitial pneumonia, liver injury, allergic cystitis, and drug eruption. Many cases of interstitial pneumonia, liver injury, and allergic cystitis associated with Kampo formulas have been reported to be caused by formulas containing Scutellariae Radix (Scutellaria root, ogon). The known adverse effects linked to overdose of Kampo formulas include pseudoaldosteronism [caused by Glycyrrhizae Radix (licorice, kanzo)], sympathomimetic symptoms [caused by Ephedrae Herba (ephedra, mao)], aconite poisoning [caused by Aconiti Tuber (processed aconite root, bushi and uzu)], and diarrhea [caused by Rhei Rhizoma (rhubarb, daio)]. In recent years, mesenteric phlebosclerosis caused by the long-term administration of Gardeniae Fructus (gardenia fruit, sanshishi) has also been reported. It is necessary to consider these potential adverse effects when prescribing Kampo medicines in clinical practice.

Genipin and insulin combined treatment improves implant osseointegration in type 2 diabetic rats

BackgroundType 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and antidiabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms.MethodsStreptozotocin-induced diabetic rats received implant surgery in their femurs and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at 3 months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment.ResultsThe results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group.ConclusionOur study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.

Evaluation of inhibitory effects of geniposide on a tumor model of human breast cancer based on 3D printed Cs/Gel hybrid scaffold

Traditional Chinese medicine therapy, which can serve as adjuvant therapy for cancer treatment, has no obvious side effects on the human body. Geniposide (GEN), one of the main iridoid glycosides in gardenia fruit, has been widely reported to have anti-cancer effects. In this study, we aimed to inspect whether GEN could inhibit proliferation and promote the apoptosis of human breast cancer cells (MCF-7). In order to better predict the efficacy of GEN, we have prepared the Cs/Gel composite scaffolds by 3D printing technology to mimic the MCF-7 cell growth microenvironment. The prepared Cs/Gel scaffold has good mechanical properties and biocompatibility, which can provide a more accurate platform for drug screening. The semi-inhibitory concentration (IC50) evaluated by CCK-8 assay was 16.06 mg/mL (24 h), 14.85 mg/mL (48 h), and 13.14 mg/mL (72 h). After exposed to GEN for 48 h, the cancer cell survival rate reduced from 69.15 ± 2.86% (13 mg/mL) to 20.97 ± 3.24% (16 mg/mL). Although the inhibitory effect was weaker in the 3D culture system, it also managed to inhibit cell proliferation and induce cell apoptosis. Besides, Live/Dead staining, Hematoxylin-Eosin (H&E) staining and SEM evaluation were also conducted to estimate the anti-cancer effect of GEN in 2D and 3D cultures. The results indicate that GEN has an anti-cancer effect based on a time- and dose-dependent manner.

Recovery of Crocins From Floral Tissue of Gardenia jasminoides Ellis.

In this research, a novel source of phytopigment crocins from fully open mature flowers of cape jasmine (Gardenia jasminoides) is introduced. Methanol and deionized water were appropriate solvents for pigment recovery with maximum yields of at least 17% from the floral tissue. Pigment separation by thin layer chromatography also confirmed the presence of the carotenoids, which dissolved well in these high-strength polar solvents, in fruit, flower, and leaf materials. The spectral patterns of the extracts from ultraviolet and nuclear magnetic resonance showed maximum absorption at ~420 nm and the chemical shift values were similar to those of crocetin aglycones (crocins) in the methanol extracts of a commercial source of yellow gardenia (fructus or fruit of Gardenia florida). Chemical compositions were then evaluated using aqueous-phase capillary electrophoresis of the methanol extracts. The methanolic extracts of the flowers and fruit had 11 principal ingredients in common. Among these, crocetin and crocin 2 belong to the crocin group and are known to be the major components of commercial yellow Gardenia. This research not only demonstrates a sustainable means of raw material utilization for natural product recovery, but also encourages a movement toward an edible landscape for the community.

Geniposide attenuates dextran sulfate sodium-induced colitis in mice via Nrf-2/HO-1/NF-κB pathway.

Geniposide (GE) is the main component in gardenia fruit. This study aimed to investigate the protective effects and potential mechanisms of GE on dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced RAW 264.7 cells. The in vivo acute colitis experimental model was established by administering drinking water containing 3% DSS to the mice for 7 days. GE was administered to the mice via oral gavage at 20 and 40 mg/kg for 7 days. Colon length, colon myeloperoxidase (MPO) level, serum and colon malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity were determined, and histological evaluation was performed. The levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) in the serum and colon were detected. The expression of proteins of the nuclear factor E2 related factor 2 (Nrf-2)/HO-1/ NF-κB pathway in the colon was detected. The in vitro model of LPS-induced RAW 264.7 cells to simulate enteritis model. Cell viability, IL-6, IL-1β, and TNF-α levels in the cell supernatant were measured. The MPO levels in RAW 264.7 cells and DSS-induced mice and MDA and SOD levels in the cell supernatant were measured. The expression of proteins of the Nrf-2/HO-1/NF-κB pathway in RAW 264.7 cells was determined. GE treatment resulted in significant histological changes and reduced the expression of inflammatory mediators IL-6, IL-1β, and TNF-α the in serum, colon, and cell supernatant effectively. Parenteral nutrition reduced MPO content in the colon and RAW 264.7 cells. GE treatment increased SOD levels in the serum, colon, and cell supernatant. GE restored the protein expression of the Nrf-2/HO-1/ NF-κB pathway in RAW 264.7 cells and nude mice, and these changes were blocked significantly by Nrf-2 siRNA. These findings demonstrated that GE ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf-2/HO-1/NF-κB pathway. Thus, GE could serve as a potential therapeutic agent for the treatment of ulcerative colitis (UC).

Solubility enhancement of berberine\u2013baicalin complex by the constituents of Gardenia Fruit

A Kampo prescription usually consists of several crude drugs and contains many kinds of compounds. Physicochemical interactions between the compounds may occur in the process of decoction, by which Kampo prescriptions are usually prepared for ingestion, and the interactions may change the extraction yields of the constituents. Berberine and baicalin have been reported to form precipitates. Orengedokuto, which consist of Coptis Rhizome, Gardenia Fruit, Phellodendron Bark and Scutellaria Root, has been a representative Kampo prescription used to treat inflammatory diseases. In our previous papers, we revealed that the precipitates formed in the decoction of orengedokuto without Gardenia Fruit mainly consists of berberine–baicalin complex and that Gardenia Fruit reduced the amount of the precipitates in orengedokuto decoction. In this report, through solubility-enhancement assay based on HPLC, we identified crocins as the constituents of Gardenia Fruits, which enhanced the solubility of berberine–baicalin complex. All-trans crocin-1 (1) and 13-cis crocin-1 (5) showed high activities among the isolated crocins, and the number of glucosyl groups in the molecule seemed correlated with the activity. As berberine and baicalin were reported as the anti-inflammatory constituents of Coptis Rhizome and Phellodendron Bark, and Scutellaria Root, respectively, Gardenia Fruit contributes anti-inflammatory activity of orengedokuto by increasing solubilities of anti-inflammatory constituents of the other component crude drugs in the prescription. Our result will add a scientific basis to the understanding of the effectiveness of orengedokuto as a whole.

The active ingredients in the anti‐obesity drug bofutsushosan in high‐fat‐diet‐fed obese mice

ABSTRACTAimCombined effects on the body weights and white adipose tissues in high‐fat‐diet‐fed obese mice due to bofutsushosan (BTS) were investigated.MethodsMale ICR mice (four weeks old) were fed a 60% kcal fat diet for five weeks and fed the same diet with administration of aqueous extracts (2.0 g/kg/day) of BTS, component‐removed BTS, and a mixture of the ingredients and the component‐removed BTS for 28 days.ResultsThe BTS extract reduced the body weight from 2 to 28 days after administration while also reducing the weight of the subcutaneous and visceral white adipose tissues after administration for 28 days. Extracts of BTS with Glycyrrhizae radix (Glycyrrhiza root; abbreviated as glycyrrhiza) removed, Rhei rhizoma (rhubarb rhizome; rhubarb) removed, Gardeniae fructus (Gardenia fruit; gardenia) removed, Ephedrae herba (Ephedra herb; ephedra) removed, or Sal mirabilis (sodium sulfate hydrate; mirabilite) removed reduced the anti‐obesity and fat‐loss activity compared to that of the BTS extract after administration for 28 days. Glycyrrhizic acid (0.89% [w/w]) and 0.046%(w/w) sennoside AB calcium salt ameliorated the anti‐obesity activity of BTS with glycyrrhiza removed and rhubarb removed eight days after administration, respectively. Geniposide (0.78% [w/w]) and 0.16% (w/w) ephedrine hydrochloride ameliorated the anti‐obesity and fat‐loss activity of BTS with gardenia removed and with ephedra removed respectively after administration for 28 days.ConclusionGlycyrrhiza, rhubarb, gardenia, ephedra and mirabilite were the active components responsible for the effect of BTS. Glycyrrhizic acid and sennoside AB induced the early phase while geniposide and ephedrine hydrochloride induced the later phase of the anti‐obesity activity of BTS.

Using orthogonal arrays to obtain efficient and reproducible extraction conditions of geniposide and genipin in gardenia fruit with liquid chromatography-mass spectrometry determinations

The conditions to efficiently and reproducibly extract geniposide and genipin in Gardenia fruit powders were established using Taguchi experimental design approaches to improve extraction recovery. Geniposide, the major iridoid glycoside component of Gardenia fruits, which has been recognized to have choleretic effects, is transformed to Genipin in animals. In this study, the extraction conditions of geniposide and genipin such as solvent types, solvent acidities and boiling times were investigated under the guidance of experimental designs to obtain the highest content in extracts determined with liquid chromatography-mass spectrometry (LC-MS) methods. Herbal powders ground from Gardenia fruits, Gardenia jasminoides Ellis and Gardenia jasminoides Ellis var. grandiflora Nakai, were used. This paper has successfully demonstrated the use of Taguchi orthogonal arrays to obtain proper extraction conditions of geniposide and genipin in the above fruits. These design methods are capable of obtaining the optimum extraction conditions in only nine trials in which three factors, namely solvent type, boiling time and solvent acidity are investigated. The results show that solvent acidity is the influencing factor in achieving adequate contents and the other factors only have minor influences. The highest content obtained is similar to the reported data. In addition, using Taguchi orthogonal arrays within four experimental trials has identified that the extraction of ground fine powders results in more reproducible recovery than that of coarse ones.

Hydrothermal synthesis of fluorescent carbon dots from gardenia fruit for sensitive on-off-on detection of Hg2+ and cysteine.

Nitrogen and sulfur co-doped carbon dots (N/S-CDs) were prepared by a simple hydrothermal method using gardenia fruit as precursor. The N/S-CDs are nearly spherical particles with a size of 2.1nm and possess excellent fluorescence stability in a wide pH range and high NaCl concentrations, as well as under UV light irradiation. The absolute quantum yield (QY) without any surface modification reaches up to 10.7%. Meanwhile, the N/S-CDs can be quenched by Hg2+ (turn-off), while the quenched fluorescence can be recovered (turn-on) by introducing cysteine (Cys), with linear ranges of 2-20μM for Hg2+and 0.1-2.0μM for Cys. On the basis of the on-off-on sensing mode, the N/S-CDs can be used to detect Hg2+ and Cys. Hence, the N/S-CDs would be a promising sensor in environmental and biological analysis.

A systematic metabolic pathway identification of Common Gardenia Fruit (Gardeniae Fructus) in mouse bile, plasma, urine and feces by HPLC-Q-TOF-MS/MS

Gardeniae Fructus was a traditional Chinese medicine (TCM) containing various biological ingredients including iridoids and crocetins, monocyclic monoterpenes, organic acids, and flavonoids. However, few systematic identification studies of the bioactive components in vivo have been reported. Herein, the ingredients and metabolites of Gardeniae Fructus were investigated using high-performance liquid chromatography coupled with high-sensitivity Q-TOF mass spectrometry. A total of 45 prototype compounds in Gardeniae Fructus extract were tentatively identified. After oral administration, 69 of prototypes and metabolites were identified from mice bile, plasma, urine, and feces, in which, 31 compounds were prototypes, and 38 chemicals were metabolites. The in vivo biotransformation pathways of these metabolites were also proposed including phase I (hydrolysis, hydrogenation, oxidation, loss of O, and ketone formation, decarboxylation) and phase II reactions (glycine, cysteine, glutathione, and glutamine, and sulfate conjugation, and glucuronidation). For the first time, our results had revealed systematic metabolic profiles of ingredients in Gardeniae Fructus extract in vivo of mice and replenished novel knowledge into the explanation of effective material and/or toxicological basis of Gardeniae Fructus which deserves further investigation.

Antidementia effects, metabolic profiles and pharmacokinetics of GJ-4, a crocin-rich botanical candidate from Gardeniae fructus.

Crocins, a series of hydrophilic carotenoids that are either mono- or di-glycosyl polyene esters of crocetin extracted from dried saffron stigma or fruits of gardenia, are attracting much attention due to their wide range of pharmacological effects. In our previous study, GJ-4, a mixture of crocin analogues, was obtained and derived from gardenia fruits. Mainly 18 crocin analogues were identified from GJ-4 and found to exhibit neuroprotective effects in in vitro and in vivo models. In this present study, we continue to investigate the therapeutic effects of GJ-4 on learning and memory impairments in a 2VO-induced VaD model, and the potential mechanism. In addition, the metabolic profiles and pharmacokinetic properties of GJ-4 were determined using liquid chromatography-electrospray ionization-mass spectrometry after single and multiple oral doses. All these findings presented here will serve as a solid basis to develop GJ-4 as a new therapeutic agent for dementia.

Genipin Inhibits Hypoxia-Induced Accumulation of HIF-1α and VEGF Expressions in Human Cervical Carcinoma Cells

Objectives Hypoxia—a characteristic of almost all types of solid tumors—has been associated with poor outcomes in several human malignancies. Genipin—an active constituent of Gardenia fruit— has been reported to exert an anti-tumor effect in several cancers. In this study, we investigated inhibition of angiogenesis using Genipin-mediated hypoxia-induced hypoxia inducible factor (HIF-1) and VEGF expression in human cervical cancer cells. Methods Under normoxic and hypoxic conditions, the expression of HIF-1α and VEGF in cervical cancer HeLa cells was detected by quantitative reverse transcription polymerase chain reaction and western blotting. Luciferase reporter assays were used to investigate the molecular mechanisms underlying the hypoxia-induced survivin activation. Results Surprisingly, we found that Genipin suppressed the HIF-1α accumulation during hypoxia in human liver cancer cell line (HepG2), human prostate cancer cell line (LNCaP), colon cancer cell line (HCT116), and breast cancer cell line (MDA231). Genipin treatment also significantly reduced hypoxia-induced secretion of VEGF. Conclusions Suppression of HIF-1α accumulation following treatment with Genipin under hypoxia was associated with PI3K and MAPK pathways. Taken together, these results suggested that Genipin inhibits HIF-1α expression through inhibition of PI3K and MAPK signaling pathways. These results provide new insights into a potential mechanism of the anticancer properties of Genipin.

Stability assessment of crocetin and crocetin derivatives in Gardenia yellow pigment and Gardenia fruit pomace in presence of different cooking methods

Gardenia fruit pomace (GFP) is a byproduct during the Gardenia oil production and rich in Gardenia yellow pigment (GY) in which the major functional components are crocetin and crocetin derivatives (CDs). The application of GFP was still limited. In this research, the stabilities of CDs during thermal and lighting treatment were studied, food systems with GY or GFP were simulated to evaluate the effects of cooking methods on CDs. Seven CDs were identified and determined in GY and GFP by UPLC-QToF-MS and HPLC. The stability results showed that CDs were sensitive to heat and light, the great loss of total CDs and detachment of aglycon were observed during thermal treatment. Light-driven degradation reactions of CDs fitted the first-order model. Different cooking methods (boiling, baking, steaming) had distinct impacts on the CDs contents in the simulated food system with GY and GFP, steaming should be an appropriate method for cooking.

Abstract A021: Genipin enhanced apoptosis of gastric cancer by mitochondrial dysfunction and downregulation of Stat3/JAK2/Mcl-1 signaling pathway

Abstract Genipin is known as a compound derived from gardenia fruit extract. Although Genipin is known to have an anti-tumor effects in various cancers, its effect and mechanism are unknown in gastric cancer. In our studies, Genipin induced apoptosis in gastric cancer cells including AGS and MKN45 cells. Genipin reduced Mcl-1 mRNA levels and confirmed with transfection of Mcl-1 siRNA. Furthermore, We found that phospho Stat3 is regulated by Genipin through proteome profiler phosphor-kinase array. In addition, protein level of phosphor JAK2 decreased in Genipin treatment. The results elucidate that Stat3/JAK2/Mcl-1 signaling pathway was suppressed with Genipin treatment in gastric cancer cells. Mcl-1 is known to be closely related to the function of mitochondria. Genipin has been shown to result in the collapse of mitochondrial function such as mitochondrial membrane potential. In conclusion, Genipin induced apoptosis by suppressing Stat3/JAK2/Mcl-1 pathway and led to mitochondrial dysfunction. Our finding implies that a novel mechanism of anti-cancer effect of Genipin in gastric cancer can be identified. Citation Format: Min Jee Jo, Soyeon Jeong, Hye Kyeong Yun, Dae Yeong Kim, Bo Ram Kim, Jung Lim Kim, Yoo Jin Na, Seong Hye Park, Yoon A Jeong, Bu Gyeom Kim, Hassan Ashktorab, Duane T Smoot, Jun Young Heo, Jeongsu Han, Dae-Hee Lee, Sang Cheul Oh. Genipin enhanced apoptosis of gastric cancer by mitochondrial dysfunction and downregulation of Stat3/JAK2/Mcl-1 signaling pathway [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A021. doi:10.1158/1535-7163.TARG-19-A021

Estimated incidence per population of adverse drug reactions to Kampo medicines from the Japanese adverse drug event report database (JADER)

ABSTRACTAimLittle information is available on the incidence per population of adverse drug reactions (ADR) to Kampo medicines. We estimated the incidence of ADRs for each Kampo medicine and examined the crude drug components of Kampo medicines that may cause ADRs.MethodsWe extracted information on ADRs caused by Kampo medicines from the Japanese Adverse Drug Event Report database (JADER) between fiscal years 2008 and 2014. The number of people who took Kampo medicines was estimated based on the production value of the Kampo formulation, the drug price, and the duration of administration.ResultsThe incidences of interstitial pneumonia and liver disorder were highest for formulations that contained Scutellaria root. However, 33% of interstitial pneumonia and 39% of liver disorder cases were reported for formulations that did not contain Scutellaria root. The majority of pseudoaldosteronism cases were caused by formulations that contained Glycyrrhiza. Mesenteric phlebosclerosis occurred most commonly in response to formulations that contained Gardenia fruit. The incidences of these ADRs varied among formulations containing these crude drugs. Odds ratio analysis indicated that additional crude drugs may have also been responsible for these ADRs. In addition, some crude drugs may prevent these ADRs.ConclusionEstimation of the incidence of ADRs caused by Kampo medicines could be a prelude to a new risk management plan, and may focus attention on formulations and crude drug components associated with previously unindicated risks.

Genipin induces mitochondrial dysfunction and apoptosis via downregulation of Stat3/mcl-1 pathway in gastric cancer

BackgroundGenipin is a compound derived from gardenia fruit extract. Although Genipin has anti-tumor effects in various cancers, its effect and mechanism in gastric cancer remain unclear. Here, we investigated the relationship between the anticancer effect of Genipin and signal transducer and activator of transcription (Stat3)/myeloid cell leukemia-1 (Mcl-1) in human gastric cancers.MethodsMTT assays were performed to determine the cell viability of gastric cancer and gastric epithelial cell lines (AGS, MKN45, SNU638, MKN74, HFE-145). A TUNEL assay and Western blotting were carried out to investigate apoptosis. Stat3 activity was measured by proteome profiler phospho kinase array, immunofluorescence and immunoblotting. Mitochondria function was monitored with an XF24 analyzer and by flow cytometry, confocal microscopy using fluorescent probes for general mitochondrial membrane potential (MMP).ResultsGenipin induced apoptosis in gastric cancer cells, including AGS and MKN45 cells. Genipin also reduced Mcl-1 mRNA and protein levels. Furthermore, we found that phosphorylation of Stat3 is regulated by Genipin. Additionally, the protein level of phospho Janus kinase 2 (JAK2) was decreased by Genipin treatment, indicating that the Stat3/JAK2/Mcl-1 pathway is suppressed by Genipin treatment in gastric cancer cells. Mcl-1 is closely related to mitochondrial function. These findings suggest that Genipin contributes to the collapse of mitochondrial functions like MMP.ConclusionsGenipin induced apoptosis by suppressing the Stat3/Mcl-1 pathway and led to mitochondrial dysfunction. Our results reveal a novel mechanism for the anti-cancer effect of Genipin in gastric cancer.

Characterization of Crocetin-Monoglucuronide as a Neuron-Protective Metabolite of Crocin-1.

Crocins are important apocarotenoids in the extract of saffron (Crocus sativus L.) and fruits of gardenia (Gardenia jasminoides E.). Crocins have shown versatile biological activities and thus they have been considered to be promising therapeutics for neurodegenerative and heart diseases. Metabolism studies report that crocetin-monoglucuronide (CM) is produced and detected in rat blood plasma after oral administration of crocins. However, due to the lack of standard compound of CM, its unambiguous identification, quantification, and bioactivity studies have been hindered. CM is synthetized and its existence in blood plasma in Sprague-Dawley (SD) rats is quantified. The pharmacokinetic studies show that CM is produced in blood and brain after oral administration of crocin-1. It is then discovered that CM possesses neuroprotective activity against beta-amyloid (Aβ) toxicity in PC-12 cells and drosophila models. The enzymatic assay shows that CM can effectively inhibit AChE and docking studies indicate that CM may bind in the gorge channel of AChE. The work discovered that CM is a neuron-protective metabolite of the orally administrated crocin-1. It is demonstrated that AChE can be one of the targets of CM in its neuron-protective activity.