Explore the active ingredients and potential mechanism of action on Actinidia arguta leaves against T2DM by integration of serum pharmacochemistry and network pharmacology.

BACKGROUND: Actinidia arguta leaves (AAL) are traditionally consumed as a vegetable and as tea in folk China and Korea. Previous studies have reported the anti-diabetic effect of AAL, but its bioactive components and mechanism of action are still unclear. AIM OF THE STUDY: This study aims to identify the hypoglycemic active components of AAL by combining serum pharmacochemistry and network pharmacology and to elucidate its possible mechanism of action. METHODS: Firstly, the effective components in mice serum samples were characterized by UPLC-Q/TOF-MSE. Furthermore, based on these active ingredients, network pharmacology analysis was performed to establish an "H-C-T-P-D" interaction network and reveal possible biological mechanisms. Finally, the affinity between serum AAL components and the main proteins in the important pathways above was investigated through molecular docking analysis. RESULTS: Serum pharmacochemistry analysis showed that 69 compounds in the serum samples were identified, including 23 prototypes and 46 metabolites. The metabolic reactions mainly included deglycosylation, dehydration, hydrogenation, methylation, acetylation, glucuronidation, and sulfation. Network pharmacology analysis showed that the key components quercetin, pinoresinol diglucoside, and 5-O-trans-p-coumaroyl quinic acid butyl ester mainly acted on the core targets PTGS2, HRAS, RELA, PRKCA, and BCL2 targets and through the PI3K-Akt signaling pathway, endocrine resistance, and MAPK signaling pathway to exert a hypoglycemic effect. Likewise, molecular docking results showed that the three potential active ingredients had good binding effects on the five key targets. CONCLUSION: This study provides a basis for elucidating the pharmacodynamic substance basis of AA against T2DM and further exploring the mechanism of action.

Chemical characterization, multivariate analysis and comparison of biological activities of different parts of Fraxinus mandshurica.

Fraxinus mandshurica (Oleaceae) is used as a traditional medicinal plant for the treatment of red eyes, menstrual disorders, excessive leucorrhea, chronic bronchitis and psoriasis. To perform chemical characterization of the secondary metabolites of F. mandshurica roots, bark, stems and leaves, 32 samples were collected from eight provinces in this study. A total of 64 chemical components were detected from four different parts of F. mandshurica by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Meanwhile, a total of nine secoiridoids were obtained by natural product chemical extraction, isolation and identification methods. Quantitative analysis by high-performance liquid chromatography-diode array detection-mass spectrometry showed the highest total content of secoiridoids in the bark, which is also consistent with the traditional medicinal parts. The results of methodological validation showed that the correlation coefficient (R2) values were all >0.9993, indicating a good linear range of the standard curve, while the relative standard deviations of precision, reproducibility and stability were <3%, and the spiked recoveries ranged from 98.22 to 102.27%, indicating that the experimental method was reliable and stable. In addition, fingerprinting and a heatmap were established to demonstrate the content trends of F. mandshurica more visually from different origins. Multivariate analysis, including principal component analysis and partial least squares discriminant analysis, was performed to determine the chemical characteristics of different parts of F. mandshurica, and six characteristic secoiridoids that could be used to distinguish different origins were screened. Finally, the inhibition of tyrosinase, α-glucosidase, acetylcholinesterase and pancreatic lipase activities by the nine characteristic compounds and extracts from different parts were investigated, and the results showed that they all exhibited different degrees of enzyme activity inhibition and thus have potential applications in whitening and blemish removal, hypoglycemia, anti-Alzheimer's disease and anti-obesity as a new source of natural enzyme activity inhibitors. This study establishes an identification and evaluation method applicable to phytochemistry of different origins, which is a guideline for quality control, origin evaluation and clinical application of traditional medicinal plants. This is also an unprecedented study on the identification of the chemical composition of different parts of F. mandshurica, characteristic compounds and the inhibition of enzyme activity of extracts from different parts.

Characterization, multivariate analysis and bioactivity evaluation of coumarins in the bark of Fraxinus mandshurica.

The bark of Fraxinus mandshurica is a traditional folk herb used to clear heat and dry dampness. To investigate the differences in coumarins content in the bark of F. mandshurica, 24 batches of samples from four origins were collected and analyzed. Eight coumarins were obtained by traditional natural product extraction, isolation and identification techniques and quantified by high performance liquid chromatography-photodiode array (HPLC-DAD). The quantitative results showed that the overall content of compound 30 (Fraxinol) was higher at 100.23 mg/g, while the overall content of compound 23 (Cichoriin) was lower, which may be related to environmental factors in different regions. The method validation showed that the linear range of the eight standards was between 10 and 2500 µg/mL with correlation coefficient (R2) values >0.9991; the relative standard deviation (RSD, %) values of intra-day precision were between 0.35 and 1.38, while the RSD values of inter-day precision were between 0. 29-1.78; the RSD (%) values for the reproducibility experiments ranged from 0.29 to 1.87, while the RSD (%) values for the stability experiments ranged from 0.22 to 2.33; the spiked recovery of the samples ranged from 98.65 to 101.34%, and the RSD (%) values ranged from 0.22 to 1.96. The method validation results showed that the instrument used for the analysis had good precision, the reproducibility and stability of the samples were good, and the accuracy of the experimental method was high. In addition, a total of 54 chemical components were identified from F. mandshurica bark by ultra performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS). Based on this, fingerprinting, heatmap and multivariate analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were established for 24 batches of samples, and four marker compounds that could be used to distinguish different origins of F. mandshurica were screened. To further investigate the bioactivities of the eight coumarins, in vitro enzyme activity inhibition studies were performed, and the results showed that they all exhibited different degrees of inhibition of acetylcholinesterase, tyrosinase and α-glucosidase, thus having potential applications in the treatment of Alzheimer's disease, blemish whitening and anti-diabetes, and becoming a new source of natural enzyme activity inhibitors. This study established an identification and evaluation method applicable to plants of different origins, which provides a strong reference for quality control, origin evaluation and clinical application of traditional medicinal plants.

Gut Microbiota Combined with Serum Metabolomics to Investigate the Hypoglycemic Effect of Actinidia arguta Leaves.

Actinidia arguta leaves (AAL) are an excellent source of bioactive components for the food industry and possess many functional properties. However, the hypoglycemic effect and mechanism of AAL remain unclear. The aim of this work was to investigate the potential hypoglycemic effect of AAL and explore its possible mechanism using 16S rRNA sequencing and serum metabolomics in diabetic mice induced by high-fat feeding in combination with streptozotocin injection. A total of 25 flavonoids from AAL were isolated and characterized, and the contents of the extract from the AAL ranged from 0.14 mg/g DW to 8.97 mg/g DW. The compound quercetin (2) had the highest content of 8.97 ± 0.09 mg/g DW, and the compound kaempferol-3-O-(2'-O-D-glucopyl)-ß-D-rutinoside (12) had the lowest content of 0.14 ± 0.01 mg/g DW. In vivo experimental studies showed that AAL reduced blood glucose and cholesterol levels, improved insulin sensitivity, and ameliorated oxidative stress and liver and kidney pathological damage. In addition, gut microbiota analysis found that AAL significantly reduced the F/B ratio, enriched the beneficial bacteria Bacteroides and Bifidobacterium, and inhibited the harmful bacteria Lactobacillus and Desulfovibrio, thereby playing an active role in intestinal imbalance. In addition, metabolomics analysis showed that AAL could improve amino acid metabolism and arachidonic acid metabolism, thereby exerting a hypoglycemic effect. This study confirmed that AAL can alleviate type 2 diabetes mellitus (T2DM) by regulating intestinal flora and interfering with related metabolic pathways, providing a scientific basis for its use as a dietary supplement and for further exploration of the mechanism of AAL against T2DM.

A comprehensive analysis of the chemical composition of Fraxinus mandshurica roots based on HPLC-DAD-MS, GC-MS and UPLC-ESI-Q-TOF-MS.

Fraxinus mandshurica is widely distributed around the world, which has significant economic value and pharmacological effects. However, its roots are often overlooked during processing and use. In this study, the preliminary identification of chemical components in F. mandshurica roots was carried out using ultra-performance liquid chromatography coupled with electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS), and a total of 37 characteristic components were identified, including 13 secoiridoids, 7 lignans, 6 coumarins, 4 flavonoids, 4 phenylethanols, 1 terpenoid and 2 other compounds. Meanwhile, to evaluate the 6 lignans content of F. mandshurica roots, the identification, quantitation analysis and methodological validation were performed by high-performance liquid chromatography with diode array detection mass spectrometry (HPLC-DAD-MS), which showed that the concentration range of standard compounds was 0.5-1000 µg/mL. The standard curve correlation coefficients (R2) were all greater than 0.9991, indicating that the linearity of the fitted curves was good. The highest lignan content in F. mandshurica roots was olivil (461.11 µg/g) and the lowest in buddlenol E (11.14 µg/g), and the total lignan content was 764.63 µg/g. The relative standard deviations (RSD, %) of both intra-day and inter-day precision were less than 1.95%. The RSD (%) of the reproducibility and stability experiments was less than 2.91%. The spiked recoveries of the samples were in the range of 98.29-102.62%, and the RSD (%) was in the range of 0.43-1.73, indicating that the method has high accuracy. In addition, a total of 20 volatile components in F. mandshurica roots were identified and quantified by gas chromatography-mass spectrometer (GC-MS) in this study, which laid a solid foundation for the comprehensive development and utilization of F. mandshurica resources.

The impact of phyto- and endo-cannabinoids on central nervous system diseases：A review.

Background and aim: Cannabis sativa L. is a medicinal plant with a long history. Phyto-cannabinoids are a class of compounds from C. sativa L. with varieties of structures. Endocannabinoids exist in the human body. This article provides an overview of natural cannabinoids (phyto-cannabinoids and endocannabinoids) with an emphasis on their pharmacology activities. Experimental procedure: The keywords "Cannabis sativa L″, "cannabinoids", and "central nervous system (CNS) diseases" were used for searching and collecting pieces of literature from PubMed, ScienceDirect, Web of Science, and Google Scholar. The data were extracted and analyzed to explore the effects of cannabinoids on CNS diseases. Result and conclusion: In this paper, schematic diagrams are used to intuitively show the phyto-cannabinoids skeletons' mutual conversion and pharmacological activities, with special emphasis on their relevant pharmacological activities on central nervous system (CNS) diseases. It was found that the endocannabinoid system and microglia play a crucial role in the treatment of CNS diseases. In the past few years, pharmacological studies focused on Δ9-THC, CBD, and the endocannabinoids system. It is expected to encourage new studies on a more deep exploration of other types of cannabinoids and the mechanism of their pharmacological activities in the future.

Nontargeted metabolomic analysis of four different parts of Actinidia arguta by UPLC-Q-TOF-MSE.

Actinidia arguta, an edible berry plant with high nutritional values, has been widely used in Asian countries as a food and traditional medicinal herb. The well-recognized health-promoting properties of A. arguta were associated with its bioactive components in its different botanical parts. To rapidly screen and identify chemical components and simultaneously determine the potential metabolites from different parts of A. arguta, UPLC-Q-TOF-MSE coupled with UNIFI platform and multivariate statistical analysis approach was established in this study. As a result, a total of 107 components were identified from the four different parts of A. arguta, in which 31 characteristic chemical markers were discovered among them, including 12, 8, 6, and 5 compounds from the fruits, leaves, roots, and stems, respectively. These results suggested that the combination of UPLC-Q-TOF-MSE and metabolomic analysis is a powerful method to rapidly screen characteristic markers for the quality control of A. arguta.

Exploring Active Ingredients, Beneficial Effects, and Potential Mechanism of Allium tenuissimum L. Flower for Treating T2DM Mice Based on Network Pharmacology and Gut Microbiota.

Forty compounds were isolated and characterized from A. tenuissimum flower. Among them, twelve flavonoids showed higher α-glucosidase inhibition activities in vitro than acarbose, especially kaempferol. The molecular docking results showed that the binding of kaempferol to α-glucosidase (GAA) could reduce the hydrolysis of substrates by GAA and reduce the glucose produced by hydrolysis, thus exhibiting α-glucosidase inhibition activities. The in vivo experiment results showed that flavonoids-rich A. tenuissimum flower could decrease blood glucose and reduce lipid accumulation. The protein expression levels of RAC-alpha serine/threonine-protein kinase (AKT1), peroxisome proliferator activated receptor gamma (PPARG), and prostaglandin G/H synthase 2 (PTGS2) in liver tissue were increased. In addition, the Firmicutes/Bacteroidetes (F/B) ratio was increased, the level of gut probiotics Bifidobacterium was increased, and the levels of Enterobacteriaceae and Staphylococcus were decreased. The carbohydrate metabolism, lipid metabolism, and other pathways related to type 2 diabetes mellitus were activated. This study indicating flavonoids-rich A. tenuissimum flower could improve glycolipid metabolic disorders and inflammation in diabetic mice by modulating the protein expression and gut microbiota.

Protective Mechanism of Fagopyrum esculentum Moench. Bee Pollen EtOH Extract Against Type II Diabetes in a High-Fat Diet/Streptozocin-Induced C57BL/6J Mice.

Bee pollen is known as a natural nutrient storehouse and plays a key role in many biological processes. Based on the preliminary separation, identification, and characterization of the main active components of Fagopyrum esculentum Moench. bee pollen (FBP), the protective effects of F. esculentum bee pollen extract (FBPE) on high-fat-diet (HFD) and streptozocin (STZ) induced type II diabetes mellitus (T2DM) was evaluated in this study. The results revealed that FBPE contains 10 active compounds mainly including luteolin (9.46 g/kg), resveratrol (5.25 g/kg), kaemferol (3.67 g/kg), etc. The animal experiment results showed that FBPE could improve HFD-STZ induced T2DM mice. Moreover, the underlying mechanism of the above results could be: (i) FBPE could reduce the inflammation related to phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, and (ii) the gut microbiota remodeling. The results of correlation analysis showed Candidatus Arthromitus and SMB53 indicated positive correlations to tumor necrosis factor-α (TNF-α); Coprococcus, Ruminocossus, and Odoribacteraceae reported negative correlations to transforming growth factor-ß (TGF-ß). That FBPE has an outstanding ability to improve T2DM and could be used as a kind of potential functional food for the prevention of T2DM.

Mitigation of DSS-Induced Colitis Potentially via Th1/Th2 Cytokine and Immunological Function Balance Induced by Phenolic-Enriched Buckwheat (Fagopyrum esculentum Moench) Bee Pollen Extract.

Colitis is an inflammatory disease that results from the overactivation of effector immune cells, producing a high quantity of pro-inflammatory cytokines. Our study aimed to explore whether buckwheat (F. esculentum) bee pollen extract (FBPE) could inhibit the progression of dextran sulfate sodium (DSS)-induced colitis via regulating immune function. We isolated and identified six main phenolic compounds of FBPE such as luteolin (9.46 mg/g) by column chromatography, HPLC-DAD, ESI-MS and NMR spectroscopy, then assessed their effects on colonic mucosal injury by clinical symptoms, histomorphology and immunohistochemistry examinations. The results showed that FBPE at 25.2 g/kg body weight (g/kg BW) changed the clinical symptoms of colitis, the ICAM-1 expression in colon, the activity of related inflammatory mediators in colon tissue and helped restore the immune system. Compared with the model group (40.28%), the CD4 positivity was significantly reduced in the HD (High-dose group: 25.2 g FBPE/kg BW/day) group (20.45%). Administration of 25.2 g/kg BW of FBPE decreased the IFN-γ, TNF-α and IL-4 levels, while enhancing the IL-10 level, and significantly inhibited the abnormally decreased IgG (Model: 13.25 mg/mL, HD: 14.06 mg/mL), showing a reversal effect on the Th1/Th2 levels in colitis. These findings suggested that FBPE at 25.2 g/kg BW had the effects of alleviating colitis and immunomodulation, which can help in the development of safe and effective immune therapy.

Ziziphi Spinosae Semen: An updated review on pharmacological activity, quality control, and application.

Ziziphi Spinosae Semen (the dried seeds of Ziziphus jujuba Mill. var. spinosa, Rhamnaceae) is a well-known traditional Chinese medicine (TCM) with high edible and pharmaceutical value. It contains abundant phytochemicals and possesses multiple biological activities. Phytochemicals include saponins, flavonoids, alkaloids, fatty acids, and others. Among them, saponins and flavonoids are considered to be the characteristic components of Ziziphi Spinosae Semen. Both crude extracts and isolated compounds exhibit excellent bioactivities, including sedative-hypnosis, anti-anxiety, antidepressant, anticancer, anti-inflammatory, anti-Alzheimer's disease (AD), and others. Its potential therapeutic effect on AD has received increasing attention in recent years. Updated reviews to summarize the current research progress and deficiencies are urgently needed. This review summarized its pharmacological activity, quality control, and application. In addition, the existing problems and future development directions are also discussed. PRACTICAL APPLICATIONS: Ziziphi Spinosae Semen is a vital traditional Chinese medicine that has a varied therapeutic effects. It is also added to food products due to its nontoxic properties. Reliable pharmacological studies have confirmed that it has multiple pharmacological activities. Particularly, its potential therapeutic effect on Alzheimer's disease (AD) has received significant attention, which makes Ziziphi Spinosae Semen an important potential candidate in the research of new drugs and health foods for the prevention of AD. This paper reviews the recent studies on Ziziphi Spinosae Semen in the treatment of AD. In addition, the quality control methods and practical applications are systematically summarized. It may provide essential guidance for the further utilization of Ziziphi Spinosae Semen in food and pharmaceutical industry.

Review on chemical compositions and biological activities of peanut (Arachis hypogeae L.).

Peanut (Arachis hypogeae L.) is a food resource with great nutritional and health functions. The present review summarized the nutrients (proteins, lipids, carbohydrates, vitamins, and minerals), chemical components (stilbenoids, flavonoids, phenolic acids, phytosterols, triterpenes, and alkaloids), and biological activities of edible parts of peanut, and research value of bioactive factor resveratrol. In vivo and in vitro studies, the biological activities of peanut were anticancer, cardiovascular protection, anti-inflammatory, antibacterial, and regulating intestinal flora, among which resveratrol had the most significant biological activity. The extraction methods of resveratrol are solvent extraction, ultrasonic-assisted extraction, supercritical fluid extraction, enzymatic hydrolysis. Improved extraction and detection methods of resveratrol can better develop high resveratrol peanut varieties. Multiple biological activities of peanuts indicate its potential in disease prevention and treatment. PRACTICAL APPLICATIONS: This review introduces the research progress of nutrients, chemical components, and biological activities of edible portions of peanuts, which will promote the development of peanuts in the food industry and its application as a pharmaceutical preparation. Some bioactive compounds in peanuts, including resveratrol, ß-sitosterol, procyanidins, oleic acid, and arachidins, have been found to have the potential to tackle diseases such as cancer, cardiovascular disease, diabetes, and oxidative stress, suggesting that peanuts can be used as nutritional foods to prevent and control these diseases.

Glycosides and flavonoids from the extract of Pueraria thomsonii Benth leaf alleviate type 2 diabetes in high-fat diet plus streptozotocin-induced mice by modulating the gut microbiota.

Twenty glycoside derivatives and nine flavonoids from the leaves of Pueraria (P. thomsonii) were isolated by column chromatography and characterized by nuclear magnetic resonance spectroscopy (NMR) and high performance liquid chromatography (HPLC). The contents of twenty glycosides and nine flavonoids from the extract of P. thomsonii leaf (PL) were 173.3 mg g-1 and 134.7 mg g-1, respectively. Two flavonoids with the highest content were robinin (49.28 mg g-1) and puerarin (42.87 mg g-1). Six flavonoids, i.e. puerarin, robinin, rutin, quercetin, quercitrin, and kaempferol showed more inhibitory effects against α-glucosidase than acarbose. PL could effectively increase the level of insulin, decrease the content of fasting blood glucose, reduce lipid accumulation in plasma, ameliorate oxidative injury and inflammation, and relieve liver and kidney damage in diabetic mice. Moreover, PL could increase intestinal probiotics to improve metabolic disorders caused by diabetes and decrease the level of Clostridium celatum to relieve inflammation. This study suggested that PL or its glycoside derivatives and flavonoids regulating glycolipid metabolism and inflammation levels might have the potential to be used to control type 2 diabetes.

Anti-Obesity and Gut Microbiota Modulation Effect of Secoiridoid-Enriched Extract from Fraxinus mandshurica Seeds on High-Fat Diet-Fed Mice.

Previously we conducted a phytochemical study on the seeds of Fraxinus excelsior and isolated nine secoiridoid compounds with adipocyte differentiation inhibitory activity and peroxisome proliferator activated receptor alpha (PPARα) activation effects. However, the bioactive constituents and functions of Fraxinus mandshurica seeds have not been studied. In the present study, we investigated the secoiridoid compounds in F. mandshurica seed extract (FM) using column chromatography, 1H-NMR, 13C-NMR and HPLC-DAD methods. The pancreatic lipase inhibitory activities of isolated compounds were evaluated in vitro. Additionally, the anti-obesity and gut microbiota modulation effect of FM on high-fat diet-induced obesity in C57BL/6 mice were also studied in vivo. The results showed that 19 secoiridoids were isolated from FM and identified. The total content of secoiridoids in FM reached 181.35 mg/g and the highest content was nuzhenide (88.21 mg/g). All these secoiridoid compounds exhibited good pancreatic lipase inhibitory activity with inhibition rate ranged from 33.77% to 70.25% at the concentration of 100 µM. After obese mice were administrated with FM at 400 mg/kg.bw for 8 weeks, body weight was decreased by 15.81%. Moreover, FM could attenuate the lipid accumulation in serum and liver, relieve the damage in liver and kidney, and extenuate oxidative stress injury and inflammation caused by obesity in mice. FM could also modulate the structural alteration of gut microbiota in obese mice, increasing the proportion of anti-obesity gut microbiota (Bacteroidetes, Bacteroidia, S24-7 and Allobaculum), and reducing the proportion of obesogenic gut microbiota (Firmicutes and Dorea). This study suggests that F. mandshurica seeds or their secoiridoids may have potential for use as a dietary supplement for obesity management.

Simultaneous characterization and quantification of flavonoids in Morus australis root as potential hepatoprotective nutraceutical.

Morus australis distributed widely in China has high value in food and agriculture. Twelve phenolic compounds were isolated and identified as major constituents of M. australis root from Shaanxi province, China, while the protective effect of M. australis root on liver injury has never been determined in detail. In this study, the hepatoprotective ability of M. australis root was investigated in vivo and in vitro. The ethanol-water extract prepared from M. australis root showed protection on alcohol-induced liver damage in mice by decreasing the levels of serum alanine aminotransferase, aspartate transaminase, triacylglycerol and malondialdehyde, and by increasing glutathione contents. Furthermore, among 12 major constituents of M. australis root, 10 flavonoids (especially 1) showed protection against carbon tetrachloride (CCl4 )-intoxicated HepG2 cell lines by decreased lactic dehydrogenase levels. In addition a validated HPLC-DAD method was established for the quantitative analysis of 10 flavonoids in the bioactive extract. PRACTICAL APPLICATIONS: Our results showed that M. australis root extract significantly alleviated the liver damage in mice. Ten flavonoids from the root of this plant exhibited protection on CCl4 -intoxicated HepG2 cell lines. This study suggests that Morus australis root has hepatoprotective potential as a promising supplement for the prevention and treatment of liver diseases.

The anti-diabetic effect of eight Lagerstroemia speciosa leaf extracts based on the contents of ellagitannins and ellagic acid derivatives.

Previously, we have reported the opposite effects of compounds isolated from Lagerstroemia speciosa leaves on a glucose transport (GLUT4) assay. Ellagitannins from L. speciosa activated GLUT4, while ellagic acid derivatives showed an inhibitory effect. As part of our continuing research on anti-diabetic nutritional supplements, we herein compared the anti-diabetic effects of several extracts (LE1-8) from leaves of L. speciosa using different manufacturing processes based on the contents of ellagitannins and ellagic acid derivatives. Their anti-diabetic effects were evaluated through glucose uptake and adipocyte differentiation in 3T3-L1 cells in vitro as well as alloxan induced diabetic mice in vivo. These extracts were given to mice by gavage at doses of 0.25, 1.0, and 4.0 g per kg body weight once a day for 21 consecutive days. Results showed that LE1 (1.0 g kg-1), LE3 (1.0 or 4.0 g kg-1), LE4 (1.0 or 4.0 g kg-1), LE5 (0.25 or 1.0 or 4.0 g kg-1) and LE7 (1.0 or 4.0 g kg-1) showed significant anti-diabetic effects in alloxan-induced diabetic mice as indicated by the decreased levels of fasting blood glucose, body weight, serum biomarkers, tissue weight and body fat, and increased final insulin levels. LE8 (1.0 g kg-1) showed a moderate anti-diabetic effect as illustrated by the reduced fasting blood glucose level while LE2 and LE6 showed slight effects in alloxan-induced diabetic mice. The potential correlation of the content of ellagitannins, ellagic acid derivatives, and corosolic acid with the anti-diabetic activity was discussed.

Chemical characterization of main bioactive constituents in Paeonia ostii seed meal and GC-MS analysis of seed oil.

The seeds of tree peony (Paeonia ostii) are promulgated as emerging edible oil crops. However, biological properties of principal constituents of peony seeds were not well studied. Fifteen main constituents including suffruticosols A and B, trans-ε-viniferin, ampelopsin E, resveratrol, trans-resveratrol-4'-O-ß-d-glucopyranoside, paeoniflorin, luteolin, luteolin-4'-O-ß-d-glucopyranoside, apigenin, kaempferol, oleanic acid, betulinic acid, hederagenin, and caffeic acid were isolated and identified. Their cytotoxicity against human tumor cell lines (COLO205, HT-29, HepG2, AGS, and HL-60) were evaluated. Among them, trans-ε-viniferin showed the most potent cytotoxicity against HL-60 cells (IC50 5.6 µM); ampelopsin E exhibited the most obvious antiproliferative properties on COLO205 (IC50 78.1 µM) and HT-29 (IC50 4.2 µM) cells, and betulinic acid showed the strongest growth inhibitory effects on HepG2 (IC50 6.6 µM) and AGS (IC50 5.4 µM) cells. Three enzymes (tyronsinase, α-glucosidase, and acetylcholinesterase) inhibitory activities of 12 compounds were also screened. Stilbene compounds, especially suffruticosols A and B, showed a significant inhibitory activity on all three enzymes. PRACTICAL APPLICATIONS: The cytotoxicity of 15 main constituents from peony seeds against COLO205, HT-29, HepG2, AGS, and HL-60 cells were evaluated. Among them, trans-ε-viniferin showed the most potent cytotoxicity against HL-60 cells (IC50 5.6 µM); ampelopsin E exhibited the most obvious antiproliferative properties on COLO205 (IC50 78.1 µM) and HT-29 (IC50 4.2 µM) cells, and betulinic acid showed the strongest growth inhibitory effects on HepG2 (IC50 6.6 µM) and AGS (IC50 5.4 µM) cells. Collectively, these results suggested that Paeonia ostii seed (POS) extracts are potential candidates for anticancer agents.

Chemical characterization of the main bioactive polyphenols from the roots of Morus australis (mulberry).

Morus species, commonly known as mulberry, is widely distributed in China. The mulberry tree is a high-value plant in agriculture. Morus australis is one of the major Morus species growing in Northern China. However, the biological properties of the main constituents of M. australis roots were not well studied. In the present study, through extensive chromatographic and spectral analysis, 12 phenolic compounds were isolated and identified from the M. australis roots. Compounds 1, 2, 8, 9 and 12 were isolated from M. australis roots for the first time. Antitumor activities of these polyphenols were studied on the A549 cell line. Compounds 1, 5 and 6 exhibited cytotoxicity on A549 cells and induced apoptosis in A549 cells via the intrinsic mitochondrial pathway. They also mediated inhibition of autophagic flux contributed cell death via the PI3k/Akt/mTOR pathway. In order to explore more potential bioactivities of these isolates, α-glucosidase, acetylcholinesterase and tyrosinase inhibitory activities were studied, and the results demonstrated that the inhibitory activity of these polyphenols on enzymes was not defined by their basic structural skeletons, but by the substituted position.

Bioactive Constituents of F. esculentum Bee Pollen and Quantitative Analysis of Samples Collected from Seven Areas by HPLC.

Bee pollen contains all the essential amino acids needed by humans. China is the largest producer of bee pollen in the world. In the present study, we identified 11 fatty acids in F. esculentum bee pollen oil by GC-MS analysis, and 16 compounds were isolated from F. esculentum bee pollen by column chromatography and identified. A high-performance liquid chromatography-diode array detector (HPLC-DAD) method was established for the quality control of F. esculentum bee pollen. A validated HPLC-DAD method was successfully applied to the simultaneous characterization and quantification of nine main constituents in seven samples collected from seven different areas in China. The results showed that all standard calibration curves exhibited good linearity (R2 > 0.999) in HPLC-DAD analysis with excellent precision, repeatability and stability. The total amount in the samples from the seven regions ranged from 23.50 to 46.05 mg/g. In addition, seven compounds were studied for their bioactivity using enzymic methods, whereby kaempferol (3) showed high α-glucosidase inhibitory activity (IC50: 80.35 µg/mL), ergosterol peroxide (8) showed high tyrosinase inhibitory activity (IC50: 202.37 µg/mL), and luteolin (1) had strong acetylcholinesterase inhibitory activity (IC50: 476.25 µg/mL). All results indicated that F. esculentum bee pollen could be a nutritious health food.

Stilbenoids and cannabinoids from the leaves of Cannabis sativa f. sativa with potential reverse cholesterol transport activity.

Three new stilbenoids (1-3) and 16 known stilbenoids (4-6) and cannabinoids (7-19) were isolated from the leaves of hemp (Cannabis sativa L.). The structures of the three new compounds were identified as α,α'-dihydro-3',4,5'-trihydroxy-4'-methoxy-3-isopentenylstilbene (HM1), α,α'-dihydro-3,4',5-trihydroxy-4-methoxy-2,6-diisopentenylstilbene (HM2), and α,α'-dihydro-3',4,5'-trihydroxy-4'-methoxy-2',3-diisopentenylstilbene (HM3) by 1D and 2D NMR spectroscopy, LC-MS, and HRESIMS. The known α,α'-dihydro-3,4',5-trihydroxy-4,5'-diisopentenylstilbene (5) and combretastatin B-2 (6) were isolated for the first time from C. sativa f. sativa. These isolated compounds exhibited cytotoxic effects on human cancer cells via inhibiting the proliferation of cancer cells and inducing cell death. Among them, compounds 4, 5, 10, 12, 13, 15, and 19 displayed broad-spectrum cytotoxicity, and 1, 7, and 11 displayed selectivity in inhibition efficiency on MCF-7 and A549 cells, which suppressed the proliferation of cancer cells significantly by inducing cell death. The effects of compounds 1-3 on improving reverse cholesterol transport (RCT) were evaluated by isotope-tracing and western blotting. Results showed that the three stilbenoids showed a cytotoxicity above 1.0 mg L-1, especially that of HM3. They could improve [3H]-cholesterol efflux from Raw 264.7 macrophages to high density lipoproteins by enhancing the protein expression of ABCG1 and SR-B1, and HM1 and HM2 showed a significant difference compared with fenofibrate at 1.0 mg L-1. The three stilbenoids could also significantly improve the protein expression of ABCA1. Further study on HepG2 cells indicated that they improve the protein expression of LDLR, SR-B1 and CYP7A1, especially that of HM1 and HM3. However, they showed no significant effect on PCSK9. The above results indicated that these stilbenoids may elevate the transfer of cholesterol to hepatocytes by improving the protein expression of SR-B1 and LDLR, and the synthesis of bile acid by increasing the protein expression of CYP7A1. In conclusion, HM1 showed lower cytotoxicity and higher activity in improving the RCT-related protein expression. Our study suggests that it may be explored as a novel lipid-lowering drug and as a beneficial ingredient in health functional foods and pharmaceuticals.