Spatial metabolome of biosynthesis and metabolism in Cyclocarya paliurus leaves.

A large number of plant metabolites were discovered, but their biosynthetic and metabolic pathways are still largely unknown. However, the spatial distribution of metabolites and their changes in metabolic pathways can be supplemented by mass spectrometry imaging (MSI) techniques. For this purpose, the combination of desorption electrospray ionization (DESI)-MSI and non-targeted metabolomics was used to obtain the spatial distribution information of metabolites in the leaves of Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus). The sample pretreatment method was optimized to have higher detection sensitivity in DESI. The changes of metabolites in C. paliurus were analyzed in depth with the integration of the spatial distribution information of metabolites. The main pathways for biosynthesis of flavonoid precursor and the effect of changes in compound structure on the spatial distribution were found. Spatial metabolomics can provide more metabolite information and a platform for the in-depth understanding of the biosynthesis and metabolism in plants.

The chromatographic fingerprinting study and genotoxicity evaluation of aqueous extract from Cyclocarya paliurus leaves.

Cyclocarya paliurus leaf is a medicinal and edible homologous plant, which possess various bioactive components with significant health benefits. However, the quality and safety of the aqueous extract from Cyclocarya paliurus leaves (CPLAE) vary greatly due to the raw materials and preparation technology. At present, chromatographic fingerprinting has been widely used for qualitative and quantitative analysis of traditional Chinese medicine (TCM). In this study, a method combining high performance liquid chromatography (HPLC) fingerprint with quantitative analysis was established and successfully applied to the characterization and quality evaluation of the CPLAE. In addition, the genetic safety of the CPLAE was evaluated by genotoxicity tests, including Ames test, chromosomal aberration test of Chinese hamster lung (CHL) cell in vitro, and bone marrow micronucleus test in mice. The results showed that 10 batches of CPLAE samples were analyzed by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS), and the similarity of chromatographic fingerprint of each batch was above 0.961, indicating good similarity. At the same time, the 6 compounds with high absorption strength in the chromatogram were quantitatively analyzed. The results showed that all 6 compounds had good regression (R2=1.000) in the test range, and the recoveries ranged from 96.25% to 102.46%. The results of the 3 genotoxicity tests showed that the highest dose of CPLAE had no genotoxicity. In conclusion, the newly established chromatographic fingerprint and multi-component quantitative analysis method is stable and accurate, and can be used for the identification and quality evaluation of the CPLAE. Moreover, the CPLAE has the characteristics of safety and high quality as functional materials in food.

Triterpenoid Compounds from Cyclocarya paliurus: A Review of Their Phytochemistry, Quality Control, Pharmacology, and Structure-Activity Relationship.

Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) is a single species of Cyclocarya paliurus in Juglandaceae. It is a unique rare medicinal plant resource in China that is mainly distributed in the south of China. The leaves of C. paliurus, as a new food ingredient, are processed into tea products in daily life. Triterpenoids are the main active ingredient in C. paliurus. So far, 164 triterpenoid compounds have been isolated and identified from C. paliurus, which are included 3,4-seco-dammaranes, dammaranes, oleanane, ursane, lupinanes, taraxeranes, and norceanothanes. Modern pharmacological studies manifested that these ingredients have a wide range of pharmacological activities both in vitro and in vivo, such as reducing blood sugar, lowering blood lipids, and anti-tumor, anti-inflammatory, anti-oxidant, and other activities. In addition, current results indicate that the pharmacological mechanisms of triterpenoids were closely related to their chemical structure, molecular signaling pathways, and the expression of related proteins. In order to further study C. paliurus based on the current research situation, this review summarizes the prospect and systematic summary of the triterpenes of C. paliurus from the aspects of structural characteristics, quality control, biological activity, and the structure-activity relationship, which provide a reference for further research and application of the triterpenoids from C. paliurus in the field of functional food and medicine.

Squalene epoxidase (SE) gene related to triterpenoid biosynthesis assists to select elite genotypes in medicinal plant: Cyclocarya paliurus (Batal.) Iljinskaja.

Triterpenoids, known for their anti-inflammatory, anticancer, and hypoglycemic properties, are the major bioactive components in Cyclocarya paliurus (Batal.) Iljinskaja. Selecting elite individuals with high triterpenoids content is the basis of C. paliurus industry for medicinal use. In this study, seasonal variation patterns of total triterpenoids and five triterpene monomers accumulation for three groups with different total triterpenoid contents (TTC; H: 59.74-64.03 mg g-1; M: 47.66-57.08 mg g-1, and L: 35.26-42.22 mg g-1) were surveyed. Seasonal expression dynamics of 6 key genes relevant to triterpenoids biosynthesis, including HMGR, DXR, SQS, SE, LUS, and ß-AS, were described by quantitative real-time PCR (qRT-PCR) for three groups. The expression levels of HMGR, SE, LUS, and ß-AS genes in group H were higher than in groups M and L. In addition, Pearson correlation analysis showed that they were significantly positively correlated with triterpene accumulation, and the expression level of SE gene not only was significantly correlated with downstream genes, but also exhibited a linear relationship with TTC, especially in September. These results suggest that SE gene could serve as an effective make for screening elite individuals with high TTC from the germplasm of C. paliurus for medicinal use. Further testing on randomly selected individuals in next September proved the feasibility and reliability of SE gene in assisted selection. Also, we successfully cloned the full-length cDNA of SE. Thus, our work provides an efficient way to attain superior genotypes to develop medicinal industry of C. paliurus in practice.

Inhibition of nitrogen assimilation promotes carbon-based secondary metabolism in callus of Cyclocarya paliurus.

The biosynthesis and accumulation of secondary metabolites are critical important to quality formation of medicinal plants, which are usually give way to primary processes and growth. Here, methionine sulfoximine (MSO) was used to inhibit the nitrogen assimilation in callus of Cyclocarya paliurus. The newly assimilated nitrogen characterized by 15N atom percentage excess, and the levels of amino acid and protein were reduced. The other primary processes such as carbohydrate metabolism and lipid metabolism were also repressed. In addition, the expression of the growth-related target of rapamycin (TOR) signaling was repressed, indicating nitrogen assimilation inhibition led to a systematic down-regulated primary metabolisms and resulted in a disruption of growth. In contrast, the biosynthesis of flavonoids and triterpenoids, antioxidase system, and the SnRK2-mediated abscisic acid (ABA) and jasmonic acid (JA) signaling were induced, which can improve plant stress resistance and defense. Nitrogen assimilation inhibition led to the carbon metabolic flux redirection from primary processes to secondary pathways, and facilitated the biosynthesis of flavonoids and triterpenoids in calluses of C. paliurus. Our results provide a comprehensive understanding of metabolic flux redirection between primary and secondary metabolic pathways and a potential means to improve the quality of medicinal plants.

The phytochemicals and health benefits of Cyclocarya paliurus (Batalin) Iljinskaja.

Cyclocarya paliurus (C. paliurus), a nutritional and nutraceutical resource for human and animal diets, has been constantly explored. The available biological components of C. paliurus were triterpenoids, polysaccharides, and flavonoids. Recent studies in phytochemical-phytochemistry; pharmacological-pharmacology has shown that C. paliurus performed medicinal value, such as antihypertensive, antioxidant, anticancer, antimicrobial, anti-inflammatory and immunological activities. Furthermore, C. paliurus and its extracts added to drinks would help to prevent and mitigate chronic diseases. This review provides an overview of the nutritional composition and functional applications of C. paliurus, summarizing the research progress on the extraction methods, structural characteristics, and biological activities. Therefore, it may be a promising candidate for developing functional ingredients in traditional Chinese medicine. However, a more profound understanding of its active compounds and active mechanisms through which they perform biological activities is required. As a result, the plant needs further investigation in vitro and in vivo.

Structurally diverse glycosides with α-glucosidase inhibitory properties from water extract of the leaves of Cyclocarya paliurus.

In this work we investigated the chemical constituents of water extract of the leaves of Cyclocarya paliurus. Two new megastigmane glycosides (3 and 8), three aliphatic alcohol glycosides (9-11), and two aromatic glycosides (12 and 13), along with fourteen known compounds were isolated, and their in vitro inhibitory activity against α-glucosidase was evaluated. Compounds 13 and 15-18 displayed inhibitory activity with IC50 values varying from 27.05 to 96.58 µM, and the structure-activity relationship among isolated compounds was discussed.

Whole-genome Duplication Reshaped Adaptive Evolution in A Relict Plant Species, Cyclocarya paliurus.

Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently. Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B. Here, we presented three C. paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly. Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage effects that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids. Resequencing analysis of 45 C. paliurus individuals uncovered two bottlenecks, consistent with the known events of environmental changes, and many selectively swept genes involved in critical biological functions, including plant defense and secondary metabolite biosynthesis. We also proposed the biosynthesis pathway of cyclocaric acid B based on multi-omics data and identified key genes, in particular gibberellin-related genes, associated with the heterodichogamy in C. paliurus species. Our study sheds light on evolutionary history of C. paliurus and provides genomic resources to study the medicinal herbs.

Two new dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus.

Two undescribed dammarane triterpenoid saponins, cypaliurusides O and P (1 and 2), were isolated from the ethanol extracts of the leaves of Cyclocarya paliurus. Bioactivity assay results showed that compound 1 has potential cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 14.55 ± 0.55 to 22.75 ± 1.54 µM. Compound 1 showed better antitumor activity against HepG2 cells with IC50 of 14.55 ± 0.55 µM. In addition, compound 2 showed no obvious antitumor activity.

Genome-wide identification and analysis of bZIP gene family reveal their roles during development and drought stress in Wheel Wingnut (Cyclocarya paliurus).

BACKGROUND: The bZIP gene family has important roles in various biological processes, including development and stress responses. However, little information about this gene family is available for Wheel Wingnut (Cyclocarya paliurus).  RESULTS: In this study, we identified 58 bZIP genes in the C. paliurus genome and analyzed phylogenetic relationships, chromosomal locations, gene structure, collinearity, and gene expression profiles. The 58 bZIP genes could be divided into 11 groups and were unevenly distributed among 16 C. paliurus chromosomes. An analysis of cis-regulatory elements indicated that bZIP promoters were associated with phytohormones and stress responses. The expression patterns of bZIP genes in leaves differed among developmental stages. In addition, several bZIP members were differentially expressed under drought stress. These expression patterns were verified by RT-qPCR. CONCLUSIONS: Our results provide insights into the evolutionary history of the bZIP gene family in C. paliurus and the function of these genes during leaf development and in the response to drought stress. In addition to basic genomic information, our results provide a theoretical basis for further studies aimed at improving growth and stress resistance in C. paliurus, an important medicinal plant.

New triterpenoids from the Cyclocarya paliurus (Batalin) Iljinskaja and their anti-fibrotic activity.

Cyclocarya paliurus, a Chinese herbal medicine and new food resource, contains a triterpenic-acid-rich extract that demonstrated ameliorative effect on diabetic nephropathy (DN). A more in-depth discovery of functional components led to the isolation of seven new triterpenoids including two pentacyclic triterpenes, 1α,2α,3ß,23-tetrahydroxyolean-12-en-28-oic acid and 2α,3ß,22α-tirhydroxyurs-12-en-28-oic acid 28-O-ß-D-glucopyranoside, and five tetracyclic triterpenoid glycosides (cypaliurusides N-R), together with twelve known compounds from the leaves of C. paliurus. Their structures were determined using a comprehensive analysis of chemical and spectroscopic data. Partial compounds were assessed for anti-fibrotic activities in high-glucose and TGF-ß1 induced HK-2 cells. Compound 16 remarkably decreased the level of fibronectin with an inhibition rate of 37.1%. Furthermore, 16 effectively alleviated the epithelial-mesenchymal transformation (EMT) process by upregulating E-cadherin expression and downregulating α-SMA expression, and it significantly decreased the level of the transcriptional inhibitors (Snail and Twist) of E-cadherin. The discovery of anti-fibrotic compounds from C. paliurus provides the potential utilization and functional candidates for the DN prevention.

Amino acids profiling and transcriptomic data integration demonstrates the dynamic regulation of amino acids synthesis in the leaves of Cyclocarya paliurus.

Background: Cyclocarya paliurus is a tree well known for its edible and medicinal leaves. Amino acids are essential nutritional components that are present in foods and closely related to the flavor and quality of tea. However, the abundance of amino acids and the regulation of amino acid biosynthesis in the leaves of C. paliurus have not been investigated across different developmental stages. Methods: A combined metabolomic and transcriptomic analysis was employed to investigate the changes in the amino acid profile over several developmental stages (S1, the smallest fully expanded leaf; S3, full leaf enlargement and full leaf thickness; and S2, an intermediate developmental stage between S1 and S3) and the molecular mechanism was elucidated. Results: The results showed that leaves at the S1 stage had the highest content, while those at the S3 stage had the lowest content of amino acids; fourteen differentially expressed genes were involved in the glycolysis pathway, the tricarboxylic acid cycle and the pentose phosphate pathway, which indicated that the reduced abundance of amino acids in the leaves of C. paliurus (mature leaves) may be attributable to reduced gene expression related to carbohydrate metabolism. Four basic leucine zipper transcription factors might play important roles in the regulation of the biosynthesis of amino acids in the leaves of C. paliurus. Conclusions: Leaves at the S1 stage are recommended for high quality tea production because of their high content of amino acids, while leaves at the S2 stage are recommended for generous tea production because of their high levels of sweet flavor amino acids (alanine) and essential amino acids (methionine, phenylalanine, threonine, and tryptophan).

Inhibition of α-glucosidase by Cyclocarya paliurus based on HPLC fingerprinting integrated with molecular docking and molecular dynamics.

Cyclocarya paliurus (CP) extracts have been shown to lower sugar and lipid levels in blood, but the material basis is not clear. We analyzed CP aqueous extracts using high-performance liquid chromatography "fingerprinting", checked their pharmacological parameters using virtual screening, and undertook molecular docking and molecular dynamics simulations. Also, the inhibitory effects of CP components upon α-glucosidase in vitro were evaluated. Fingerprinting and virtual screening showed that the aqueous extract of CP contained the active components protocatechuic acid, chlorogenic acid, caffeic acid and rutin, which were safe and had no side effects in vivo. Molecular docking and molecular dynamics simulations showed that chlorogenic acid and rutin might have a potent inhibitory effect on α-glucosidase. An enzyme-activity assay in vitro showed that the half-maximal inhibitory values of chlorogenic acid and rutin were 398.9 and 351.8 µg/ml, respectively. Chlorogenic acid and rutin had an inhibitory effect on α-glucosidase. Cyclocarya paliurus could be developed as a natural α-glucosidase inhibitor.

The Modulatory Effect of Cyclocarya paliurus Flavonoids on Intestinal Microbiota and Hypothalamus Clock Genes in a Circadian Rhythm Disorder Mouse Model.

Circadian rhythm disruption is detrimental and results in adverse health consequences. We used a multi-omics profiling approach to investigate the effects of Cyclocarya paliurus flavonoid (CPF)-enriched diets on gut microbiota, metabolites, and hypothalamus clock genes in mice with induced circadian rhythm disruption. It was observed that CPF supplementation altered the specific composition and function of gut microbiota and metabolites induced by circadian rhythm disruption. Analysis showed that the abundance of Akkermansia increased, while the abundance of Clostridiales and Ruminiclostridium displayed a significant downward trend after the CPF intervention. Correlation analysis also revealed that these gut microbes had certain correlations with the metabolites, suggesting that CPFs help the intestinal microbiota to repair the intestinal environment and modulate the release of some beneficial metabolites. Notably, single-cell RNA-seq revealed that CPF supplementation significantly regulated the expression of genes associated with circadian rhythm, myelination, and neurodegenerative diseases. Altogether, these findings highlight that CPFs may represent a promising dietary therapeutic strategy for treating circadian rhythm disruption.

The Leaves of Cyclocarya paliurus: A Functional Tea with Preventive and Therapeutic Potential of Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) has become a universal and chronic global public health concern and causes multiple complex complications. In order to meet the rapidly growing demand for T2DM treatment, increased research has been focused on hypoglycemic drugs. Cyclocarya paliurus (Batal.) Iljinsk is the only living species of the genus Cyclocarya Iljinskaja, whose leaves have been extensively used as a functional tea to treat obesity and diabetes in China. An enormous amount of very recent pharmacological research on the leaves of C. paliurus has demonstrated that they carry out numerous biological activities, such as hypoglycemic, anti-inflammatory, and intestinal microbiota regulation. Multiple in vitro and in vivo studies have also shown that the extracts of C. paliurus leaves are innocuous and safe. This study aims to provide an up-to-date review of the botany, traditional uses, phytochemistry, pharmacological effects against diabetes, toxicology, and clinical studies of C. paliurus leaves, in hopes of promoting a better understanding of their role in the prevention and treatment of T2DM.

Screening and identification of α-glucosidase inhibitors from Cyclocarya paliurus leaves by ultrafiltration coupled with liquid chromatography-mass spectrometry and molecular docking.

Cyclocarya paliurus, as an important edible and medicinal product, has shown a good prospect in the prevention of diabetes mellitus (DM). However, it is unclear which active compounds derived from C. paliurus play a significant role in inhibiting α-glucosidase activity. In present study, affinity-based screening assay was developed to screen and identify potential α-glucosidase inhibitors from C. paliurus leaves based on affinity ultrafiltration coupled with ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) and molecular docking. After being enriched by D-101 macroporous resin, five eluent fractions with different polarity were obtained and their inhibitory activities on α-glucosidase were evaluated by an enzyme inhibition assay in vitro. The result showed that 70% ethanol fraction of C. paliurus leaves exhibited remarkable α-glucosidase inhibitory activity with the IC50 value of 17.81 µg/mL. The 70% ethanol fraction was incubated with α-glucosidase and then active compounds would form enzyme-inhibitor complexes. The complexes could be separated from inactive components by the interception ability of ultrafiltration membrane under centrifugation. A total of 36 active compounds were screened from C. paliurus leaves and the chemical structures were further characterized by UPLC-QTOF-MS/MS. Furthermore, molecular docking was performed to investigate possible inhibitory mechanisms between active compounds and α-glucosidase. The docking result showed that cyclocarioside I, pterocaryoside B, arjunolic acid, cyclocarioside Z5, cypaliuruside D and cyclocarioside N could be embedded well into the active pocket of α-glucosidase, and had significant affinity interactions with critical amino acid residues by forming hydrogen bonds, hydrophobic interactions and van der Waals, and affinity energies ranged from -9.3 to -6.7 kJ/mol. The results indicated that the developed method is rapid and effective for high throughput screening of potential α-glucosidase inhibitors from complex mixtures. Moreover, C. paliurus exhibited a remarkable inhibitory activity on α-glucosidase, making it a promising candidate for the prevention of DM.

Cyclocarya paliurus triterpenoids suppress hepatic gluconeogenesis via AMPK-mediated cAMP/PKA/CREB pathway.

BACKGROUND: Abnormal enhancement of hepatic gluconeogenesis is a vital mechanism of the pathogenesis of Type 2 diabetes mellitus (T2DM); thus, its suppression may present an efficient therapeutic strategy for T2DM. Cyclocarya paliurus (CP), a plant species native to China, has been reported to have anti-hyperglycemia activity. Our previous studies have revealed that Cyclocarya paliurus triterpenic acids (CPT) exert the favorable glucose-lowering activity, but the regulatory effect of CPT on hepatic gluconeogenesis is still unclarified. PURPOSE: This study aimed to investigate the potential role and mechanism of CPT in gluconeogenesis. STUDY DESIGN: In this study, the ameliorative effect and underlying mechanism of CPT on gluconeogenesis were investigated: high-fat diet and streptozotocin-induced T2DM mice and glucagon-challenged mouse primary hepatocytes. METHODS: T2DM model mice with or without oral administration of CPT for 4 weeks were monitored for body weight, glucose and lipid metabolism. Hematoxylin and eosin staining was used to observe liver lipid deposition. Real-time PCR assays were performed to examine the mRNA expression of glucose-6-phosphate (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes involved in liver gluconeogenesis. Western blotting was used to determine AMP-dependent protein kinase (AMPK) expression and induction of the glucagon signaling pathway. The possible mechanism of CPT on liver gluconeogenesis was further explored in glucagon-induced mouse primary hepatocytes. RESULTS: In vivo and in vitro experiments revealed that CPT treatment significantly reduced fasting blood glucose, total cholesterol and triglyceride levels, and improved insulin resistance. Furthermore, CPT could obviously decreased the mRNA and protein expression of G6Pase and PEPCK, the cyclic AMP content, the phosphorylation level of protein kinase A and cyclic AMP response element-binding protein. But CPT promoted the phosphorylation of AMP-dependent protein kinase (AMPK) and activation of phosphodiesterase 4B. Mechanistically, intervention with Compound C (an AMPK inhibitor) partially blocked the suppressive effect of CPT on hepatic gluconeogenesis. CONCLUSION: These findings suggested that CPT may inhibit hepatic gluconeogenesis against T2DM by activating AMPK.

Cyclocarya paliurus triterpenoids attenuate glomerular endothelial injury in the diabetic rats via ROCK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (Batal.) Iljinskaja. (C. paliurus) is a distinctive traditional Chinese herb, with remarkable hypoglycemic capacity. Emerging evidence suggested that glomerular endothelial injury is a crucial pathological process of diabetic kidney disease (DKD). Our previous research found that C. paliurus triterpenoids fraction (CPT) has ameliorative effects on DKD. However, whether C. paliurus could counteract the glomerular endothelial injury of DKD is still undefined. AIM OF THE STUDY: We aimed to investigate the effects of CPT on glomerular endothelial function and explore its underlying mechanisms with in vivo and in vitro experiments. MATERIALS AND METHODS: The effects and possible mechanisms of CPT on glomerular endothelial injury in streptozotocin (STZ)-induced diabetic rats and H2O2-challenged primary rat glomerular endothelial cells were successively investigated. RESULTS: In vivo, we found that CPT treatment obviously decreased the levels of blood glucose, microalbumin, BUN and mesangial expansion. Additionally, CPT could ameliorate renal endothelium function by reducing the content of VCAM-1 and ICAM-1, and blocking the loss of glycocalyx. In vitro, CPT could also alleviate H2O2-induced endothelial injury. Mechanistically, CPT remarkably increased the phosphorylation levels of Akt and eNOS, decreased the expression of ROCK and Arg2in vivo and in vitro. Noticeably, the favorable effects mediated by CPT were abolished following ROCK overexpression with plasmid transfection. CONCLUSION: These findings suggested that CPT could be sufficient to protect against glomerular endothelial injury in DKD through regulating ROCK pathway.

α-Glucosidase inhibitors screening from Cyclocarya paliurus based on spectrum-effect relationship and UPLC-MS/MS.

Cyclocarya paliurus is an edible and medicinal plant exhibiting significant hypoglycemic effect. However, its active components are still unclear and need further elucidation. In this research, the active components of the leaves of C. paliurus responsible for the α-glucosidase inhibitory activity were screened and identified based on a spectrum-effect relationship study in combination with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The 70% ethanol eluate fraction of the leaves of C. paliurus with the strongest α-glucosidase inhibitory activity was obtained after extraction and purification with macroporous resin. Their chromatographic fingerprints (15 batches) were established by UPLC analysis and 32 common peaks were specified by similarity analysis. Their IC50 values for α-glucosidase inhibition were measured by an enzymatic reaction. Several multivariate statistical analysis methods including hierarchical cluster analysis, principal component analysis, partial least square analysis and gray relational analysis were applied to explore the spectrum-effect relationship between common peaks and IC50 values, and the chromatographic peaks making a large contribution to efficacy were screened out. To further elucidate the active components of leaves of C. paliurus, the 70% ethanol eluate fraction was characterized by UPLC-MS/MS analysis, and 10 compounds were identified. This study provides a valuable reference for further research and development of hypoglycemic active components of C. paliurus.

Cyclocarya paliurus (Batalin) Iljinskaja: Botany, Ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (Batalin) Iljinskaja (C. paliurus) also known as Sweet tea tree, Money tree, Money willow, green money plum, mountain willow and shanhua tree, is a native rare monocotyledonous plant in Southern China. It possesses numerous traditional benefits, including clearing heat, detoxification, producing saliva, slake thirst, anti-inflammatory, insecticidal, dispelling wind and relieving itching. It is also effective in preventing and treating diabetes, hypertension, hyperlipidemia, dizziness and swelling and pain, as well as reducing cholesterol, and modulating the functions of the immune system. The stem, leaves and bark of this plant are all medicinal parts, but the leaves have the highest research value. AIM OF THE STUDY: This article summarized the plant's botanical description, distribution, ethnopharmacology, phytochemical profiles and pharmacological for the first time, to provide possible directions for future development and research in brief. MATERIAL AND METHODS: The literature for this current manuscript was obtained from reports published from 1992 to May 2021 in diverse databases such as the China Knowledge Resource Integrated databases (CNKI), SciFinder, Google Scholar, Baidu Scholar, Elsevier and Pub-Med. The domestic and foreign references published about C. paliurus over recent years were collected, analyzed and summarized. RESULTS: The botanical characteristics of the fruits of C. paliurus are unique in having a central nutlet surrounded by a circular wing to distinguish the living genera of Juglandaceae. In traditional medicine, C. paliurus leaves are used by the local people of Southern China to make tea to prevent diabetes. More than 210 compounds have been isolated from C. paliurus. Among them, the characteristic 3,4-seco-dammaranes accounted for the most. Other compounds include dammarane tetracyclic triterpenoids, various pentacyclic triterpenoids, flavonoids, isosclerones, phenolic derivatives and polysaccharides. The plant extracts and compounds have been reported to exert various pharmacological activities, such as anti-hyperglycemic, anti-hyperlipidemic, anti-cancer, cytotoxic, anti-oxidative, anti-inflammatory, hepatoprotective, and anti-microbial activities. CONCLUSIONS: Comprehensive literature analysis shows that C. paliurus extract and its compounds have a variety of biological activities for the treatment of various diseases. The current modern pharmacology research is mostly related to the records of ethnic pharmacology, mainly in vitro research, relatively few in vivo research. Therefore, future studies should focus on this aspect. In addition, we also would like to recommend further research should concentrate on toxicity studies and quality control of C. paliurus to fill the study gap, as well as to provide theoretical support for the further development of the potential functions and clinical applications of the plant.