Exploring the potential of Ziziphus nummularia and luteolin-7-O-glucoside as tubulin inhibitors in cancer therapy and survival.

Cancer is responsible for approximately 10 million deaths worldwide, with 70% of the deaths occurring in low- and middle-income countries; as such safer and more effective anti-cancer drugs are required. Therefore, the potential benefits of Ziziphus nummularia and Ziziphus spina-christi as sources of anti-cancer agents were investigated. Z. nummularia and Z. spina-christi extracts were prepared using chloroform, ethanol, ethyl acetate, and water. The extracts' anti-cancer properties were determined using the MTT Cell Viability Assay in four cancer cell lines: breast (KAIMRC2 and MDA-MB-231), colorectal (HCT8), and liver (HepG2). The ApoTox-Glo Triplex Assay and high-content imaging (HCI)-Apoptosis Assay were used to assess KAIMRC2 and HCT8 cells further. In addition, KAIMRC2 cells were tested for microtubule staining, and AKT/mTOR protein expression was determined by western blot analysis. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the secondary metabolites in the ethanol and ethyl acetate extracts, followed by in silico techniques to predict molecular targets and interactions, safety, and pharmacokinetic profile for identified metabolites. Out of the eight extracts, the ethanolic extract of Z. nummularia, exhibited the most potent activity against KAIMRC2 cells with an IC50 value of 29.2 µg/ml. Cancer cell treatment with the ethanolic extract of Z. nummularia resulted in a dose-dependent decrease in cell viability with increased apoptosis and cytotoxic effects. Microtubule staining showed a disrupted microtubular network. The ethanolic extract treatment of KAIMRC2 cells led to upregulated expression of pAKT and pmTOR. In silico studies predicted luteolin-7-O-glucoside to be a ligand for tubulin with the highest docking score (- 7.686) and similar binding interactions relative to the native ligand. Further computational analysis of the metabolites showed acceptable pharmacokinetic and safety profiles, although ethanolic extract metabolites were predicted to have cardiotoxic effects. Ethanolic extraction is optimal for solubilizing active anticancer metabolites from Z. nummularia, which may act by causing M-phase arrest via inhibition of tubulin polymerization. Luteolin-7-O-glucoside is the lead candidate for further research and development as an anti-cancer agent. In addition, this study suggests that herbal treatment could switch on mechanisms of adaptation and survival in cancer cells.

[Qualitative and semiquantitative analyses of the chemical components of the seed coat and kernel of Ziziphi Spinosae Semen].

Ziziphi Spinosae Semen refers to the dried seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou. The seed is composed of a reddish brown coat and a yellow kernel. A comparative study was conducted to investigate differences in the chemical composition and their relative contents between the seed coat and kernel of Ziziphi Spinosae Semen. First, the chemical compounds found in the seed coat and kernel were characterized and identified using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The analytical results tentatively identified 57 chemical compounds based on reference-compound comparison, literature retrieval, and chemical-database (e. g., MassBank) searches; these compounds included 14 triterpenes, 23 flavonoids, 7 alkaloids, 6 carboxylic acids, and 7 other types of compounds. The mass error of the identified compounds was within the mass deviation range of 5×10-6 (5 ppm). Next, two methods of multivariate statistical analysis, namely, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), were used to compare the differential compounds between the two seed parts. A total of 17 differential compounds were screened out via OPLS-DA based on a variable importance in projection (VIP) value of >5. The results revealed that betulinic acid, betulonic acid, alphitolic acid, and jujuboside Ⅰ mainly existed in the seed coat whereas the 13 other compounds, such as spinosin, jujuboside A, and 6‴-feruloylspinosin, mainly existed in the seed kernel. Therefore, these 17 differential compounds can be used to distinguish between the two seed parts. Finally, a semiquantitative method was established using UPLC and a charged aerosol detector (CAD) with inverse gradient compensation in the mobile phase. Six representative compounds with different types were selected to examine the CAD response consistency: magnoflorine (alkaloid), spinosin (flavone), 6‴-feruloylspinosin (flavone), jujuboside A (triterpenoid saponin), jujuboside B (triterpenoid saponin), and betulinic acid (triterpenoid acid). The results showed that the relative standard deviation (RSD) of the average response factors at different levels of these six compounds was 7.04% and that their response intensities were similar. Moreover, each compound in the fingerprint demonstrated good response consistency, and the peak areas obtained directly reflected the contents of each compound. Based on the semiquantitative fingerprints obtained, betulinic acid and oleic acid were considered the main components of the seed coat. The betulinic acid content in the seed coat was approximately 7 times higher than that in the seed kernel. Spinosin, jujuboside A, linoleic acid, betulinic acid, and oleic acid were the main components of the seed kernel. The spinosin content in the seed kernel was 18 times higher than that in the seed coat. In addition, the jujuboside A content in the seed kernel was 24 times higher than that in the seed coat. The proposed method can accurately determine the main components and compare the relative contents of these components in different seed parts. In summary, this study identified the differences in chemical components between the seed coat and kernel of Ziziphi Spinosae Semen and clarified the main components and their relative contents in these parts. The findings can not only provide a basis for the identification of chemical compounds and quality research on different parts of Ziziphi Spinosae Semen but also promote the development and utilization of this traditional Chinese medicine.

Preparation of red jujube powder with high content of Amadori compounds and higher antioxidant activity by controlling the Maillard reaction.

Amadori compounds (ACs) are stable compounds produced in the early stage of the Maillard reaction (MR) with health benefits such as immunomodulatory, antithrombosis, and tumor-preventive effects. Jujube is a medicinal and edible fruit in China. It is rich in free amino acids and reducing sugar, but traditionally, little attention was paid to the formation of ACs when jujube was processed, neither the influence of ACs on health effects. In this paper, we aimed to increase ACs through controlling the MR during different heating processes of jujube powder with adjusted water content and find the most effective AC that contributed to the antioxidant effects of jujube powder. The optimal dry-heating conditions to produce ACs were as follows: The water activity was 0.294, the heating temperature was 90°C, and the time was 120 min. After processing, the ACs content of jujube powder was 18.55 ± 0.19 mg/g dry weight (DW), which was more than 100 times of those in the unheated jujube powder (0.153 ± 0.003 mg/g DW). Besides, the antioxidant activity of jujube powder after dry-heating process was higher than that of unheated one. As the most abundant AC in the dry-heated jujube powder (12.90 ± 0.75 mg/g DW), N-(1-deoxy-d-fructose-1-yl) proline (Fru-Pro) showed the highest antioxidant activity (62% of equivalent l-ascorbic acid) among 12 ACs in ferric reducing antioxidant power assay. This result provided a method to produce jujube product with high content of ACs and confirmed the positive contribution of Fru-Pro to the antioxidant activity of the jujube powder.

Nontargeted metabolomics and enzyme inhibitory and antioxidant activities for chemical and biological characterization of jujube (Ziziphus jujuba) extracts.

The chemical and biologically active characterization of jujube samples (fruits, cores, and leaves) were carried out by the integrated nontargeted metabolomics and bioassay. Firstly, collision cross-section values of active compounds in jujubes were determined by ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry. Then, a multidimensional statistical analysis that contained principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis was employed to effectively cluster different tissues and types of jujubes, making identification more scientific. Furthermore, angiotensin-converting enzyme (ACE) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the quality of jujubes from a double activity dimension. The analytical results obtained by using ACE and DPPH to evaluate the quality of jujube were different from multivariate statistics, providing a reference for the application of jujube. Therefore, integrating chemical and biological perspectives to evaluate the quality of jujube provided a more comprehensive evaluation and effective reference for clinical needs.

New cytotoxic dammarane type saponins from Ziziphus spina-christi.

Cancer is the world's second-leading cause of death. Drug development efforts frequently focus on medicinal plants since they are a valuable source of anticancer medications. A phytochemical investigation of the edible Ziziphus spina-christi (F. Rhamnaceae) leaf extract afforded two new dammarane type saponins identified as christinin E and F (1, 2), along with the known compound christinin A (3). Different cancer cell lines, such as lung cancer (A549), glioblastoma (U87), breast cancer (MDA-MB-231), and colorectal carcinoma (CT-26) cell lines, were used to investigate the extracted compounds' cytotoxic properties. Our findings showed significant effects on all the tested cell lines at varying concentrations (1, 5, 10, and 20 µg/mL). The three compounds exhibited potent activity at low concentrations (< 10 µg/mL), as evidenced by their low IC50 values. To further investigate the complex relationships between these identified cancer-relevant biological targets and to identify critical targets in the pathogenesis of the disease, we turned to network pharmacology and in silico-based investigations. Following this, in silico-based analysis (e.g., inverse docking, ΔG calculation, and molecular dynamics simulation) was performed on the structures of the isolated compounds to identify additional potential targets for these compounds and their likely interactions with various signalling pathways relevant to this disease. Based on our findings, Z. spina-christi's compounds showed promise as potential anti-cancer therapeutic leads in the future.

[Advances in pharmacological effects of jujuboside B].

Ziziphi Spinosae Semen(ZSS) is an edible TCM derived from the dried ripe seeds of Ziziphus jujube Mill. var. spinosa(Bunge)Hu ex H. F. Chou(Rhamnaceae), which has the effects of nourishing the heart, tonifying the liver, calming the heart, tranquilizing the mind, arresting sweating, and promoting fluid production, and is widely used in the treatment and health care of diseases related to cardiovascular, nervous, and immune systems. Jujuboside B(JuB), one of the main active ingredients of ZSS, possesses various pharmacological effects with application values. This paper reviewed the chemical structure and pharmacological effects of JuB. JuB has sedative, hypnotic, antitumor, anti-platelet, anti-inflammatory, and other biological activities, which shows the potential thera-peutic effects on insomnia, tumors, coronary artery disease, airway inflammation, and liver injury. However, there are some limitations to the results of current studies. More comprehensive studies, including basic research and clinical trials, need to be carried out to provide more reliable evidence.

Effect of poly(L-lactic acid)/poly(ethylene glycol)-poly(L-lactic acid) block copolymer blend film on preservation of Chinese winter jujube (Ziziphus Jujuba Mill. cv. Dongzao).

The effect of poly(L-lactic acid)/poly(ethylene glycol)-poly(L-lactic acid) block film on preservation of Chinese winter jujube (Ziziphus Jujuba Mill.cv.Dongzao) was investigated. Eight arm poly(ethylene glycol)-poly(L-lactic acid) block copolymer (8-PEG/PLLA) and net structure 8-PEG/PLLA (NET-PEL) were successfully synthetized by ring-opening polymerization, and different percentages (5, 10, and 20 %) of them were blended with PLLA to prepared blends films. Mechanical properties, modulated different scanning calorimetry (MDSC), gas and water vapor permeability results showed that 8-PEG/PLLA and NET-PEL block copolymer greatly increased the toughness of blend films, could be decrease PLLA segment glass transition temperature (Tg)from 59.5 °C to 41.6-46.7 °C and cold crystallization temperature(Tcc)from 89.4 °C to 73.5-77.7 °C, and increased the oxygen (O2), carbon dioxide (CO2), and water vapor transmission rate. The an appropriate gas concentration [O2 (2.56-3.51 %), CO2 (5.05-5.56 %)] was created inside the PLLA/NET-PEL20% (NEPEL20)group, which could restrain increase of total soluble solids (TSS), malonaldehyde content. The firmness, color luminosity (L*), total phenols, and ascorbic acid were maintained at higher level，and kept its commercial value after 40 days of storage. The present data indicated that treating post-harvest winter jujubes with NEPEL20 MAP packaging was an effective method for preservation of postharvest winter jujube.

HPLC-MS/MS-based and transcriptome analysis reveal the effects of ABA and MeJA on jujube (Ziziphus jujuba Mill.) cracking.

Fruit cracking is a physiological disease that occurs during the development of jujube, abscisic acid (ABA) and jasmonic acid (JA) mainly regulate the cell wall metabolic pathway and induce fruit cracking. Here, we used high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to detect phytohormone-related metabolites at different developmental stages in cracking-susceptible (CS-15) and cracking-resistant (CR-04) individuals of full-sibling hybrid offspring. The fruit of 'Pingshunbenzao' jujube was treated with ABA and MeJA at the white-ripening stage, and the 48-h fruit cracking index was significantly increased compared to that of CK (water). Furthermore, RNA-seq of semi-red stage fruits identified several differentially expressed genes, related to the cell wall, such as SBT1.7 (Contig21.0.484), EXPA (Contig12.0.7) and QRT3 (newGene_1935), and transcription factors (TFs). These results reveal the relationship between the levels of different hormones and fruit cracking, identify genes associated with fruit cracking, and provide new insights to solve the problem of fruit cracking through hormonal regulation.

Fingerprinting Evaluation and Gut Microbiota Regulation of Polysaccharides from Jujube (Ziziphus jujuba Mill.) Fruit.

Jujube fruit was well-loved and praised by the broad masses due to its delicious taste, abundant nutritional value, and medicinal properties. Few studies reported the quality evaluation and gut microbiota regulation effect of polysaccharides of jujube fruits from different producing areas. In the present study, multi-level fingerprint profiling, including polysaccharides, oligosaccharides, and monosaccharides, was established for the quality evaluation of polysaccharides from jujube fruits. For polysaccharides, the total content in jujube fruits ranged from 1.31% to 2.22%, and the molecular weight distribution (MWD) ranged from 1.14 × 105 to 1.73 × 106 Da. The MWD fingerprint profiling of polysaccharides from eight producing areas was similar, but the profile of infrared spectroscopy (IR) showed differentiation. The characteristic signals were screened and used to establish a discrimination model for the identification of jujube fruits from different areas, and the accuracy of identification reached 100.00%. For oligosaccharides, the main components were galacturonic acid polymers (DP, 2-4), and the profile of oligosaccharides exhibited high similarity. The monosaccharides, GalA, Glc, and Ara, were the primary monosaccharides. Although the fingerprint of monosaccharides was semblable, the composing proportion of monosaccharides revealed significant differences. In addition, the polysaccharides of jujube fruits could regulate the gut microbiota composition and possess potential therapeutic effects on dysentery and nervous system diseases.

Three acidic polysaccharides derived from sour jujube seeds protect intestinal epithelial barrier function in LPS induced Caco-2 cell inflammation model.

Normal intestinal epithelial barrier function plays a key role in the prevention of many diseases such as infectious enteritis, inflammatory bowel disease, obesity, etc. In this study, three novel acidic polysaccharides ZY-2, ZY-3 and ZY-4 were isolated from sour jujube (Ziziphus jujuba Mill. var. Spinosa) seeds and purified by DEAE Sephrose Fast Flow gel. The molecular weight of ZY-2, ZY-3 and ZY-4 was 7.76 kDa, 10.71 kDa and 8.31 kDa respectively, mainly composed of different proportions of mannose, rhamnose, glucose, glucuronic acid, galacturonic acid, galactose, xylose and arabinose. 1H NMR and Congo red experiment results showed that the three polysaccharides mainly contained both α-type and ß-type glycosidic bonds with obvious triple helix structural traits. The polysaccharides could up-regulate the expression levels of occludin and ZO-1 in LPS-induced inflammation Caco-2 cells, and reduce IL-6, IL-8, IL-1ß and TNF-α significantly. In conclusion, the acidic polysaccharides from sour jujube seeds exhibited great potential in protection intestinal epithelial barrier function through anti-inflammatory effects.

Ultrasound-assisted ascorbic acid solution pretreated hot-air drying improves drying characteristics and quality of jujube slices.

BACKGROUND: The effective hot-air drying of foods such as jujube requires an effective green pretreatment alternative to chemical pretreatments. Jujube slices were pretreated using 5 and 10 mg mL-1 ultrasound-assisted vitamin C (UVC) for 10, 20, and 30 min, followed by hot-air drying. RESULTS: Ultrasound-assisted vitamin C pretreatment for 10, 20, and 30 min modulated the characteristics of fresh jujube slices such as water loss (from -28.25% to -25.52% after 30 min of UVC pretreatment), solid gain (from -31.68% to -26.82% after 30 min of UVC pretreatment), loss of total and reducing sugars (from 200.25 mg and 34.88 mg to 287.14 mg and 4.71 mg, respectively, after 30 min of UVC pretreatment), total soluble solids (from 76.32 o Brix to 82.08 o Brix), and water diffusivity (from 9.01 × 10-10 m2 s-1 to 6.71 × 10-10 m2 s-1 ). These characteristics were associated with altered surface morphology and improved drying characteristics. The UVC pretreatment preserved an acceptable reddish-yellow or orange-like color during hot-air drying and reduced the browning index from 26.3 optical density (OD)/g DM to 23.25 OD/g dry mass basis (DM), which was connected with reduced 5-hydroxymethylfurfural (HMF) content. On the other hand, the proportions of bioactive components such as vitamin C increased from 1.05 mg g-1 DM to 9.02 mg g-1 DM, phenolics increased from 12.8 mg gallic acid equivalent (GAE)/g DM to 17.5 mg GAE/g DM, flavonoids increased from 4.0 mg rutin equivalent (RE)/g DM to 4.4 mg RE/g DM, and procyanidin content increased from 2.0 mg catechin equivalents (CE)/g DM to 2.9 mg CE/g DM in UVC pretreated jujube slices, which had a positive association with increased antioxidant activity - for example, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) increased from IC50 22.5 mg DM/mL to 8.0 mg DM/mL, 2,2-diphenyl-1-picrylhydrazyl (DPPH) changed from IC50 36.5 mg DM/mL to 9.5 mg DM/mL, and ferric reducing antioxidant power (FRAP) increased from 2.0 mg vitamin C equivalent (VCE)/g DM to 11.9 mg VCE/g DM). CONCLUSION: The data indicated that UVC can be used as a promising pretreatment method for improving the hot-air drying characteristics and the quality of jujube slices. © 2023 Society of Chemical Industry.

[Optimization of ethanol reflux extraction process of Ziziphi Spinosae Semen- Schisandrae Sphenantherae Fructus based on network pharmacology combined with response surface methodology].

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.

Phenolic characterization of fermented jujube puree by HPLC-MS/MS and their release during in vitro dynamic digestion.

Health benefits of fruit products fermented with probiotics are partially attributed to their increased contents of phenolic compounds. In this study, the effect of in vitro dynamic gastrointestinal digestion on the release of phenolic compounds and changes in the antioxidant activity of jujube puree fermented with Streptococcus thermophilus was investigated. Thirteen target phenolic compounds were characterized by high-performance liquid chromatography-tandem mass spectrometry. The recovery of this developed method ranged from 87.41% to 111.03%, and the limits of detection and quantification were low. Fermentation with Streptococcus thermophilus significantly increased the contents of most phenolic compounds in jujube puree. Fermentation reduced the decrease in the contents of most phenolic compounds in jujube puree during gastrointestinal digestion and, as a consequence improved the antioxidant capacity of digested fractions. These findings indicated that fermentation could increase the bioaccessibility of specific phenolics in jujube, as well as the antioxidant activity of this fruit.

Ziziphus spina-christi extract-stabilized novel silver nanoparticle synthesis for combating Fusarium oxysporum-causing pepper wilt disease: in vitro and in vivo studies.

The novelty of the present study is studying the ability of aqueous Ziziphus spina-christi leaves' extract (ZSCE) to produce eco-friendly and cost-effective silver nanoparticles (Ag NPs) against Fusarium wilt disease. Phytochemical screening of ZSCE by HPLC showed that they contain important antimicrobial substances such as Rutin, Naringin, Myricetin, Quercetin, Kaempferol, Hesperidin, Syringeic, Eugenol, Pyrogallol, Gallic and Ferulic. Characterization methods reveal a stable Ag NPs with a crystalline structure, spherical in shape with average particle size about 11.25 nm. ZSCE and Ag NPs showed antifungal potential against F. oxysporum at different concentrations with MIC of Ag NPs as 0.125 mM. Ag NPs treatment was the most effective, as it gave the least disease severity (20.8%) and the highest protection rate (75%). The application of ZSCE or Ag NPs showed a clear recovery, and its effectiveness was not limited for improving growth and metabolic characteristics only, but also inducing substances responsible for defense against pathogens and activating plant immunity (such as increasing phenols and strong expression of peroxidase and polyphenol oxidase as well as isozymes). Owing to beneficial properties such as antifungal activity, and the eco-friendly approach of cost and safety, they can be applied in agricultural field as novel therapeutic nutrients.

Systematic Comparison of Structural Characterization of Polysaccharides from Ziziphus Jujuba cv. Muzao.

To investigate the structural information differences of Ziziphus Jujuba cv. Muzao polysaccharides, ten samples were successfully extracted from aqueous and alkaline solutions, prepared via DEAE-Sepharose Fast Flow through different eluents and Sephacryl S-300 columns, and systematically analyzed. Their characteristics were studied and then compared using chemical testing, high-performance gel permeation chromatography (HPGPC), gas chromatography (GC), methylation analysis, and NMR spectroscopy. The data achieved demonstrated that different jujube polysaccharide fractions possessed different structural characteristics, and most of them belonged to pectic polysaccharides. Overall, the structural information difference of jujube polysaccharides was preliminarily illuminated, which could not only promote the potential application of Z. Jujuba cv. Muzao polysaccharides but also provide an effective way to analyze the structures of polysaccharides from other genera jujube fruit.

Novel insight into the evolution of volatile compounds during dynamic freeze-drying of Ziziphus jujuba cv. Huizao based on GC-MS combined with multivariate data analysis.

To understand the evolution of aroma in jujubes during dynamic freeze drying (FD), the relationship between aroma compounds, precursors, and related enzyme activities were analyzed. Fifty-three volatiles were identified during FD processing. After FD, the total aroma contents were increased from 11,004 to 14,603 µg/kg, ketones content was significantly decreased by 54.11 %, resulted in the loss of creamy note in freeze-dried jujube (FDJ). Through the network analysis, serine, glycine, proline, valine, cysteine, arginine, glutamic acid, lysine and leucine had the significant correlation with pyrazines, dominated the roasty note of FDJ. Linoleic acid, α-linolenic acid and oleic acid with lipoxygenase had important effects on the increase of esters (from 412 to 9,486 µg/kg), contributed fruity and sweet notes of FDJ. Besides, through the Mantel test, the influence degree of factors on the formation of FDJ aroma was ranked as temperature > enzyme activity > fatty acids > amino acids.

Two new 5(14)-membered type cyclopeptide alkaloids from root bark of Ziziphus spina-christi (L.) Desf.

Six 5(14)-membered ring type of cyclopeptide alkaloids (CPAs), including two undescribed members, 1-hydro,2ß-methoxy-mauritine-A (1) and 1-hydro,2α-methoxy-mauritine-A (2), together with four known compounds, mauritine-A (3), mauritine C (4), amphibine-A (5), and amphibine-E (6), were isolated from the root bark of Ziziphus spina-christi (L.) Desf., Their structures were determined by multiple spectral analyses, including UV, IR, 1D NMR, 2D NMR, EI-MS, HR-EI-MS, FAB-MS and ESI-MS, and by comparison with literature. All six CPAs were tested in vitro for cytotoxicity by three human cancer cell lines (MCF7, H460 and Hela) and a human normal cell line (BJ). None of the compounds showed cytotoxicity towards all tested cell lines.

Three new 8,4'-type oxyneolignans from the seeds of Ziziphus jujuba mill and their antitumor studies.

Ziziphus jujuba Mill. is a deciduous shrub, belonging to the Rhamnaceae family. Phytochemical investigation of Z. jujuba seeds showed the presence of three undescribed 8,4'-type oxyneolignans (1-3). Their structures were elucidated by comprehensive spectroscopic analyses. All isolated compounds were tested for antitumor activity against two human hepatoma cells (Hep3B and HepG2) and exhibited moderate cytotoxicity (IC50: 33.79-49.62 µM).

A strategy to explore the quality markers of Ziziphi Spinosae semen by combining metabolic in vivo study with network pharmacology.

Ziziphi Spinosae semen (ZSS), the dried and ripe seed of Ziziphus jujube Mill. var. spinosa (Bunge) Hu ex H. F. Chou, has been used as a sedative in China and other Asian countries for over a millennium. However, its quality markers (Q-markers) are not completely clear. In this study, Q-markers selected by a metabolic in vivo study combined with network pharmacology are proposed for ZSS quality control. An UHPLC (ultra-high-performance liquid chromatography)-Q-Orbitrap-MS method was developed to identify or tentatively assign 48 components including 21 flavonoid C-glycosides, 2 flavonoid O-glycosides, 11 dammarane triterpenoid saponins, 13 alkaloids, and 1 other, using a diagnostic product ion filtering strategy in ZSS. Subsequently, 147 metabolites detected from serum, urine, bile, and feces samples of para-chlorophenylalanine-induced insomnia rats treated with ZSS aqueous extracts could be linked to their respective parent compounds, including 27 prototypes. Meanwhile, three metabolic networks of flavonoids, saponins, and alkaloids are preliminarily established and potential metabolic pathways are investigated under the insomnia condition. Finally, 12 key bioactive components against insomnia including magnoflorine, caaverine, coclaurine, norisocorydine, genkwanin, juzinrine, apigenin, jujubogenin, kaempferol-3-O-rutinoside, jujuboside A, jujuboside B, and spinosin with the highest degree values in component-target-pathways network were selected as Q-markers for the quality control of ZSS.

Detection of Alternaria alternata infection in winter jujubes based on optical properties and their correlation with internal quality parameters during storage.

In this work, a single integrating sphere system was applied to characterize the optical absorption (µa) and reduced scattering (µs') properties (550 - 1050 nm) in winter jujube flesh infected by Alternaria alternata during storage at 4 and 20 °C, respectively. Meanwhile, physical (L*, a*, weight loss) and biochemical characteristics (soluble solids content, titratable acids, chlorophyll, total phenolic, and ascorbic acid) of winter jujubes were measured. Among them, chlorophyll, weight loss and ascorbic acid were highly correlated with µa at 680 nm, 690 nm, while chlorophyll and a* had the best correlations with µs' at 700 - 920 nm. These optimal optical properties were proved efficiently contributed to the disease detection of winter jujubes after 12 days at 4 °C and 3 days at 20 °C during storage, with satisfactory discrimination accuracies (acc > 93.75 %). Consequently, optical properties in Vis-NIR region were available to detect the postharvest disease in winter jujubes.