Determination of leaf nitrogen content in apple and jujube by near-infrared spectroscopy.

The nitrogen content of apple leaves and jujube leaves is an important index to judge the growth and development of apple trees and jujube trees to a certain extent. The prediction performance of the two samples was compared between different models for leaf nitrogen content, respectively. The near-infrared absorption spectra of 287 apple leaf samples and 192 jujube leaf samples were collected. After eliminating the outliers by Mahalanobis distance method, the remaining spectral data were processed by six different preprocessing methods. BP neural network (BP), random forest regression (RF), least partial squares (PLS), K-Nearest Neighbor (KNN), and support vector regression (SVR) were compared to establish prediction models of nitrogen content in apple leaves and jujube leaves. The results showed that the determination coefficient (R2), root mean square error (RMSE) and residual prediction deviation (RPD) of the models established by different combined pretreatment methods were compared among the five methods. Compared with the performance of the other four models, the modeling method of SG + SD + CARS + RF was suitable for the prediction of nitrogen content in apple leaves, and its modeling set R2 was 0.85408, RMSE was 0.082188, and RPD was 2.5864. The validation set R2 is 0.75527, RMSE is 0.099028, RPD is 2.1956. The modeling method of FD + CARS + PLS was suitable for the prediction of nitrogen content in jujube leaves. The modeling set R2 was 0.7954, RMSE was 0.14558, and RPD was 2.4264; the validation set R2 is 0.81348, RMSE is 0.089217, and RPD is 2.4552.In the prediction modeling of apple leaf nitrogen content in the characteristic band, the model quality of RF was better than the other four prediction models. The model quality of PLS in predictive modeling of nitrogen content of jujube leaves in characteristic bands is superior to the other four predictive models, These results provide a reference for the use of near-infrared spectroscopy to determine whether apple trees and jujube trees are deficient in nutrients.

Green synthesis of trimetallic CuO/Ag/ZnO nanocomposite using Ziziphus spina-christi plant extract: characterization, statistically experimental designs, and antimicrobial assessment.

In this study, Ziziphus spina christi leaves was used to synthesize a trimetallic CuO/Ag/ZnO nanocomposite by a simple and green method. Many characterizations e.g. FTIR, UV-vis DRS, SEM-EDX, TEM, XRD, zeta-size analysis, and DLS, were used to confirm green-synthesized trimetallic CuO/Ag/ZnO nanocomposite. The green, synthesized trimetallic CuO/Ag/ZnO nanocomposite exhibited a spherical dot-like structure, with an average particle size of around 7.11 ± 0.67 nm and a zeta potential of 21.5 mV. An extremely homogeneous distribution of signals, including O (79.25%), Cu (13.78%), Zn (4.42%), and Ag (2.55%), is evident on the surface of green-synthetic nanocomposite, according to EDX data. To the best of our knowledge, this is the first study to effectively use an industrially produced green trimetallic CuO/Ag/ZnO nanocomposite as a potent antimicrobial agent by employing different statistically experimental designs. The highest yield of green synthetic trimetallic CuO/Ag/ZnO nanocomposite was (1.65 mg/mL), which was enhanced by 1.85 and 5.7 times; respectively, by using the Taguchi approach in comparison to the Plackett-Burman strategy and basal condition. A variety of assays techniques were utilized to evaluate the antimicrobial capabilities of the green-synthesized trimetallic CuO/Ag/ZnO nanocomposite at a 200 µg/mL concentration against multidrug-resistant human pathogens. After a 36-h period, the tested 200 µg/mL of the green-synthetic trimetallic CuO/Ag/ZnO nanocomposite effectively reduced the planktonic viable counts of the studied bacteria, Escherichia coli and Staphylococcus aureus, which showed the highest percentage of biofilm reduction (98.06 ± 0.93 and 97.47 ± 0.65%; respectively).

Ameliorating effect of Chinese jujube polyphenol on blood glucose oxidative stress in type 2 diabetic rats.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common metabolic disease characterized by insulin resistance and insufficient relative insulin secretion, leading to elevated blood sugar and the development of diabetic complications. T2DM not only seriously affects people's health and quality of life, but also brings a heavy burden to society and economy. At present, the treatment of T2DM mainly relies on drug therapy, but these drugs often have problems such as side effects, resistance and high cost, and can not fully meet the needs and expectations of patients. Therefore, it is of great significance and value to find safe and effective natural medicines or functional foods to assist the treatment and prevention of T2DM. OBJECTIVE: Chinese jujube are a common fruit that contain abundant polyphenolic compounds, which exhibit multiple physiological activities, such as antioxidation, anti-inflammation, and blood glucose lowering. The objective of this study was to explore the impact of red date polyphenols on glycemic control and oxidative stress status in patients with type 2 diabetes mellitus (T2DM).

Effect of different extraction methods on the lipid composition and antioxidant activity of Ziziphi spinosae semens oil.

Chinese sour jujube is an important fruit for both medicine and food and effects various biological activities. Although the Chinese sour jujube seed (Ziziphi spinosae semen) is rich in oil, its lipid profiles is significantly affected by the extraction process. However, no studies to date have comprehensively analysed the lipid composition and bioactivity of Ziziphi spinosae semen oil processed using different methods. In this study, we compared the effects of commonly-used pressed, ultrasonic-assisted, and Soxhlet extraction methods on the lipid composition, characteristics, and antioxidant properties of Ziziphi spinosae semen oil. Nineteen subclasses and 390 lipid molecular species were identified, of which 24 lipid molecular species could potentially be used as biomarkers for different processing methods. Correlation analysis revealed that 57 lipids were significantly correlated with the antioxidant capacity (r > 0.9 and P < 0.05). These results indicate that Ziziphi spinosae semen oil is rich in bioactive lipids. These data greatly expand our understanding of the bioactive lipids of Ziziphi spinosae semen oil. Additionally, it could provide useful information for Ziziphi spinosae semen oil applications in functional products or the food industry and new insights into the effects of active vegetable oil processing.

Effect of jujube orchard abandonment time on soil properties and enzyme activities at soil profile in the Loess Plateau.

In the Loess Plateau, the impact of abandoned farmland on soil properties and enzyme activity, along with its temporal variations and potential driving factors, remains a mystery. This study was designed to systematically and comprehensively examine the variations in soil enzyme activities, particle size distribution, and stability of soil aggregates at different stages of ecological recovery in the Loess Plateau. Our findings reveal a nuanced temporal pattern: with the progression of cropland abandonment, there is a notable decrease in soil bulk density. Concurrently, a dynamic trend in enzyme activities is observed-initially exhibiting a decline, followed by an increase over extended periods of recovery. Notably, prolonged abandonment leads to marked enhancements in soil structure. Parameters such as the mean weight diameter (MWD) and geometric mean diameter (GMD) of soil aggregates show an overall increasing trend. In terms of the Relative Dissipation Index (RSI), our data indicate a sequence of control > 2 years of abandonment > 4 years > 6 years > 14 years. From this, it can be seen that fallowing may be an effective natural restoration strategy for improving the physical structure of soils in the Loess Plateau and restoring soil nutrients. However, positive changes may take a long time to become evident.

Functional Nutrients and Jujube-Based Processed Products in Ziziphus jujuba.

Jujube (Ziziphus jujuba Mill.) is the first tree species in China, with a long history and abundant yield. However, fresh jujubes have a short shelf-life and are not resistant to storage. Therefore, more and more processed jujube products are being studied. These processed products can extend the shelf-life of jujubes and attract widespread attention for their rich functional nutrients. This review summarized changes in nutrients of fresh jujube and processed products and the research progress of different preparation methods of jujubes. Meanwhile, the pharmacological effects of bioactive components in jujube-based products were concluded. Jujube and its processed products contain rich polysaccharides, vitamin C, and other functional nutrients, which are beneficial to humans. As the initial processing method for jujubes, vacuum freezing or microwave drying have become the most commonly used and efficient drying methods. Additionally, processed jujube products cannot be separated from the maximum retention of nutrients and innovation of flavor. Fermentation is the main deep-processing method with broad development potential. In the future, chemical components and toxicological evaluation need to be combined with research to bring consumers higher quality functional jujube products and ensure the sustainable development of the jujube industry.

Spatial distribution of metabolites in processing Ziziphi Spinosae Semen as revealed by matrix-assisted laser desorption/ionization mass spectrometry imaging.

Ziziphi Spinosae Semen (ZSS) is the first choice for the treatment of insomnia. This research aimed to reveal the spatial distribution of identifying quality markers of ZSS and to illustrate the metabolite quality characteristics of this herbal medicine. Here, we performed a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in situ to detect and image 33 metabolites in ZSS, including three saponins, six flavonoids, four alkaloids, eight fatty acids, and 12 amino acids. The MALDI images of the metabolites clearly showed the heterogeneous spatial distribution in different regions of ZSS tissues, such as the cotyledon, endosperm, and radicle. The distribution area of two saponins, six flavonoids, and three alkaloids increased significantly after the fried processing of ZSS. Based on the ion images, samples with different processing technologies were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 23 major influencing components exerting higher ion intensities were identified as the potential quality markers of ZSS. Results obtained in the current research demonstrate that the processing of ZSS changes its content and distribution of the medicinal components. The analysis of MALDI-MSI provides a novel MS-based molecular imaging approach to investigate and monitor traditional medicinal plants.

Fructus Jujubae cooperated with water-expelling members in Shizao decoction alleviated intestinal injury and malignant ascites by modulating gut microbiota and metabolic homeostasis.

BACKGROUND: Shizao decoction (SZD) consisted of Euphorbia kansui (EK), Euphorbia pekinensis (EP), Daphne genkwa (DG), and Fructus Jujubae (FJ) is a classic Chinese herbal medicine formula for treating malignant ascites, which is closely related to the modulation of gut microbiota by our previous study. For water-expelling members (WEM) including EK, EP, and DG may have side effects on the intestine, FJ is employed for detoxification and effectivity enhancement of WEM. However, the underlying mechanism for the compatibility of WEM and FJ is still unknown. PURPOSE: To investigate the effect of the compatibility of WEM with FJ in SZD on malignant ascites and elucidate the potential mechanism from the perspective of the modulation of gut microbiota and related metabolic function. METHODS: Qualitative and quantitative evaluation of main components was conducted for comprehensive characterization of SZD and WEM. The effect of WEM and SZD was compared on malignant ascites effusion (MAE) rats. The intestinal injury was evaluated by HE staining and oxidative damage. Ascites weight, urine amount, fecal water content, the expression of aquaporins, and cytokines in ascites (IL-6, VEGF, and TNF-α) were measured to estimate the water-expelling activity. The intestinal flora was detected by 16S rDNA sequencing and the content of fecal short-chain fatty acids (SCFAs) was analyzed using gas chromatography-mass spectrometry. Pseudo-germ-free (PGF) and fecal bacteria transplantation animal experiments were subsequently employed to validate this finding. The fecal metabolomics and correlation analysis were finally conducted to explore the related metabolic changes. RESULTS: 51 and 33 components were identified in SZD and WEM, respectively. Compared to WEM alone, the compatibility with FJ remarkably reduced intestinal oxidative damage in MAE rats. Ascites was also relieved by downregulating the expression of AQP3 in the colon and decreasing the levels of IL-6, TNF-α and VEGF in ascites. The diversity of gut microbiota was reversed with an increase in Lactobacillus and Clostridia_UCG-014 while a decrease in Colidextribacter. Under the PGF condition, compatibility of WEM with FJ failed to reduce intestinal injury and alleviate MA significantly, but this effect was further enhanced after FMT. 23 potential fecal metabolites were finally identified. Correlation analysis further showed that Lactobacillus and Clostridia_UCG-014 were positively correlated with SCFAs and l-tryptophan. Colidextribacter was negatively correlated with thymidine but positively correlated with ursodeoxycholic acid and deoxycholic acid. CONCLUSION: FJ cooperated with WEM reduced intestinal injury and alleviated malignant ascites by modulating gut microbiota, short-chain fatty and tryptophan metabolism. These findings provide a scientific basis for the clinical application of FJ from SZD and the safe usage of SZD.

Variations in the biochemical characteristics of Lavandula sublepidota Rech.f. in response to the foliar enrichment of green-synthesized copper nano complexes from extract of neem and jujube.

Copper (Cu) is an essential micronutrient in plant physiology and biochemistry. This article synthesized copper nano complexes (Cu-NCs) based on aqueous extracts of jujube and neem leaves. The effects of foliar application of Cu-jujube and Cu-neem Cu-NCs at concentrations of 0, 10, 25, and 50 mg L-1 on the bioactive compounds, antioxidant capacity, and essential oil of the Iranian native medicinal herb Lavandula sublepidota Rech. f. was investigated. The highest levels of flavonoids and polyphenols were observed in the plants treated with Cu-NCs at 25 mg L-1. However, no superiority was observed between the two types of Cu-NCs. Furthermore, 25 mg L-1 nCu-Z and nCu-N foliar application boosted essential oil yield (48 and 52%, respectively) over control. This suggests an ideal threshold beyond which toxicity was found. Similarly, the amount of commercially significant secondary metabolites increased at 25 mg L-1 CuNCs compared to 10 and 50 mg L-1 concentrations. The maximum antioxidant activity was found in extracts of lavender that had been treated with 25 mg L-1 CuNCs. When CuNCs were applied exogenously, the extracts' antibacterial activity (MIC µg mL-1) was substantially increased against the three pathogen strains. The results suggest that CuNCs demonstrate notably greater effectiveness, particularly at an ideal concentration of 25 mg L-1, in enhancing the production of essential oil and bioactive compounds in Lavandula sublepidota Rech. f. Therefore, these findings indicate the importance of the biosynthesis of NCs using plants and measuring the phytochemical changes of lavender plants.

Ziziphus spina-christi L. extract attenuates bleomycin-induced lung fibrosis in mice via regulating TGF-ß1/SMAD pathway: LC-MS/MS Metabolic profiling, chemical composition, and histology studies.

Ancient Egyptians (including Bedouins and Nubians) have long utilized Ziziphus spina-christi (L.), a traditional Arabian medicinal herb, to alleviate swellings and inflammatory disorders. It is also mentioned in Christian and Muslim traditions. Ziziphus spina-christi L. (Family: Rhamnaceae) is a plentiful source of polyphenols, revealing free radical scavenging, antioxidant, metal chelating, cytotoxic, and anti-inflammatory activities. Herein, different classes of the existing bioactive metabolites in Z. spina-christi L. were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the first time. The study also aimed to assess the anti-inflammatory and antifibrotic properties of Z. spina-christi L. extract against bleomycin-induced lung fibrosis in an experimental mouse model. 32 male Swiss Albino mice were assigned into 4 groups; the first and second were the normal control group and the bleomycin positive control (single 2.5 U/kg bleomycin intratracheal dose). The third and fourth groups received 100 and 200 mg/kg/day Z. spina-christi L. extract orally for 3 weeks, 2 weeks before bleomycin, and 1 week after. The bioactive metabolites in Z. spina-christi L. extract were identified as phenolic acids, catechins, flavonoids, chalcones, stilbenes, triterpenoid acids, saponins, and sterols. The contents of total phenolic compounds and flavonoids were found to be 196.62 mg GAE/gm and 33.29 mg QE/gm, respectively. In the experimental study, histopathological examination revealed that lung fibrosis was attenuated in both Z. spina-christi L.- treated groups. Z. spina-christi L. extract downregulated the expression of nuclear factor kappa B (NF-κB) p65 and decreased levels of the inflammatory markers tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and c-Jun N-terminal kinase (JNK) in lung tissue. Z. spina-christi L. also downregulated the expression of the fibrotic parameters collagen-1, alpha-smooth muscle actin (α-SMA), transforming growth factor-beta 1 (TGF-ß1), matrix metalloproteinase-9 (MMP-9) and SMAD3, with upregulation of the antifibrotic SMAD7 in lung tissue. Overall, the present study suggests a potential protective effect of Z. spina-christi L. extract against bleomycin-induced lung fibrosis through regulation of the TGF-ß1/SMAD pathway.

Jujubae Fructus extract prolongs lifespan and improves stress tolerance in Caenorhabditis elegans dependent on DAF-16/SOD-3.

Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

[Determination of nine components of fried Ziziphi Spinosae Semen extract in beagle dog plasma by UPLC-MS/MS and its application in pharmacokinetic research].

This study established a convenient, rapid, and sensitive ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, swertisin, N-nornuciferine, 6-feruloylspinosin, and jujuboside B in beagle dog plasma after oral administration of fried Ziziphi Spinosae Semen(FZSS) extract. The Waters HSS-T3 C_(18) column(2.1 mm×100 mm, 1.8 µm) was used. The methanol-aqueous solution(containing 0.01% formic acid) was adopted as the mobile phase for gradient elution. The nine components and two internal standards were completely separated within 8 min. The mass spectrometry detection was performed in multiple reaction monitoring(MRM) mode by positive and negative ion switching of electrospray ionization. The analytical method was validated in terms of specificity, selectivity, linear range, accuracy, precision, recovery, matrix effect, and stability. It could meet the requirement of pharmacokinetic research after oral administration of FZSS extract to beagle dogs. The results showed that the time to reach the peak concentration(T_(max)) of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, 6-feruloylspinosin, and jujuboside B was 2.40-3.20 h, and the elimination halflife(t_(1/2)) was 2.08-6.79 h after a single-dose oral administration of FZSS to beagle dogs. The exposure of magnoflorine and spinosin was high, with a peak concentration(C_(max)) of 76.7 and 31.5 ng·mL~(-1) and an area under the curve(AUC_(0-∞)) of 581 and 315 ng·h·mL~(-1), respectively. The exposure of the remaining five compounds was lower, with a C_(max) of 0.81-13.0 ng·mL~(-1) and an AUC_(0-∞) of 6.00-106 ng·h·mL~(-1). This study provides a reference for the follow-up research of FZSS.

The adsorption-desorption behavior of chlorothalonil in the cuticles of apple and red jujube.

The distribution fate of chlorothalonil (CHT) in the environment (soil and water) and fruits is controlled by the capacity of cuticles to adsorb and desorb CHT, which directly affects the safety of both the environment and fruits. Batch experiments were conducted to reveal the adsorption-desorption behaviors of CHT in the cuticles of apple and red jujube. The adsorption kinetics showed that both physisorption and chemisorption occurred during the adsorption process. Furthermore, the isothermal adsorption of CHT in the fruit cuticles followed the Freundlich model. The thermodynamic parameters (ΔG ≤ -26.16 kJ/mol, ΔH ≥ 31.05 kJ/mol, ΔS ≥ 0.20 kJ/(mol K) showed that the whole CHT adsorption process was spontaneous, and the hydrophobic interaction was predominant. The CHT adsorption capacity of the apple cuticle was higher than that of the red jujube cuticle, potentially due to the significantly higher alkanes content of apples than that of red jujubes. An appropriate ionic strength (0.01 moL/L) could induce a higher adsorption capacity. In addition, the desorption kinetics were shown to conform to a Quasi-first-order model, meaning that not all the adsorbed CHT could be easily desorbed. The desorption ratios in apple and red jujube cuticles were 41.38% and 35.64%, respectively. The results of Fourier-transformed infrared spectroscopy and X-ray photoelectron spectroscopy further confirmed that CHT could be adsorbed and retained in the fruit cuticles. Investigating the adsorption-desorption behavior of CHT in the apple and red jujube cuticles allowed to determine the ratio of its final distribution in the fruits and environment, providing a theoretical basis to evaluate the risk of residue pesticide.

Ethanol extract of Ziziphus nummularia ameliorates formaldehyde-induced arthritis in rats by regulating oxidative stress biomarkers and haematological profile.

BACKGROUND: Rheumatoid arthritis is an autoimmune inflammatory disorder that mainly affects bone and cartilage architecture. The continuous use of NSAIDs and DMARDs is associated with severe toxic effects. Therefore, the current study was designed to scrutinize herb-based therapy for the treatment of RA. AIM: To evaluate the anti-arthritic activity of ethanol extract of Ziziphus nummularia using formaldehyde-induced arthritic model in rats and elucidate the possible mechanism for anti-arthritic activity. MATERIALS AND METHODS: Anti-arthritic activity of ETZN was studied at three oral doses, i.e., 200, 400, and 600 mg/kg. Selected doses were studied using various clinical parameters viz. paw volume, inflammatory index, motility test, stair test, anti-nociceptive efficacy, walking track analysis, and motor activity) from day 1 to day 10. On the last day, the animals were killed for the evaluation of hematological parameters, oxidative stress biomarkers, and histological and radiographic studies of the hind paw. RESULTS: Treatment with ETZN 400 mg/kg and 600 mg/kg markedly elicited a significant reduction in paw volume, inflammatory index, and nociceptive action compared to diseased animals. Furthermore, the anti-inflammatory activity was confirmed by increased latency of pain threshold in thermal and mechanical algesia models. The anti-arthritic activity is mainly attributed to a reduction in oxidative stress biomarkers as well as restoration of haematological profile in treated animals when compared to diseased animals. Lastly, the anti-arthritic potential was confirmed by histological and radiological analysis which revealed a marked reduction in inflammatory cells and bone destruction as compared to diseased animals. CONCLUSION: The study revealed that ETZN exhibits significant anti-arthritic activity via modulation of oxidative stress biomarkers, restoration of hematological profile, and reduction in bone erosion.

UHPLC-PDA-Q-TOF-MS-α-amylase-FLD activity detection system and molecular docking.

INTRODUCTION: Traditional and some scientific literature document the antidiabetic effects of the Ziziphi Spinosae Semen (ZSS). However, the bioactive compounds of ZSS responsible for the antidiabetic effects are not well known. OBJECTIVES: This study aimed to investigate the material basis of the antidiabetic effects of ZSS by inhibiting α-amylase. METHODOLOGY: An online analysis platform was established and optimized using an ultra-performance liquid chromatography-photo-diode array-quadrupole-time-of-flight-mass spectrometry-α-amylase-fluorescence detector (UHPLC-PDA-Q-TOF-MS-α-amylase-FLD) system to screen α-amylase inhibitors in ZSS rapidly. The inhibitory effect of these compounds was confirmed by molecular docking screening. and the molecular interactions between α-amylase and active compounds were evaluated, which strongly supported the experimental results. RESULTS: Seventy-eight compounds were identified in the ZSS extract, eleven of which were screened to have significant α-amylase binding activity. CONCLUSION: This study demonstrated the feasibility of using an established platform to screen for effective components in ZSS, providing a practical method for the rapid screening of potential antidiabetic active ingredients in traditional Chinese medicine.

Phytochemical evaluation of Ziziphus mucronata and Xysmalobium undulutum towards the discovery and development of anti-malarial drugs.

BACKGROUND: The development of resistance by Plasmodium falciparum is a burdening hazard that continues to undermine the strides made to alleviate malaria. As such, there is an increasing need to find new alternative strategies. This study evaluated and validated 2 medicinal plants used in traditional medicine to treat malaria. METHODS: Inspired by their ethnobotanical reputation of being effective against malaria, Ziziphus mucronata and Xysmalobium undulutum were collected and sequentially extracted using hexane (HEX), ethyl acetate (ETA), Dichloromethane (DCM) and methanol (MTL). The resulting crude extracts were screened for their anti-malarial and cytotoxic potential using the parasite lactate dehydrogenase (pLDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, respectively. This was followed by isolating the active compounds from the DCM extract of Z. mucronata using silica gel chromatography and structural elucidation using spectroscopic techniques (NMR: 1H, 12C, and DEPT). The active compounds were then targeted against P. falciparum heat shock protein 70-1 (PfHsp70-1) using Autodock Vina, followed by in vitro validation assays using ultraviolet-visible (UV-VIS) spectroscopy and the malate dehydrogenase (MDH) chaperone activity assay. RESULTS: The extracts except those of methanol displayed anti-malarial potential with varying IC50 values, Z. mucronata HEX (11.69 ± 3.84 µg/mL), ETA (7.25 ± 1.41 µg/mL), DCM (5.49 ± 0.03 µg/mL), and X. undulutum HEX (4.9 ± 0.037 µg/mL), ETA (17.46 ± 0.024 µg/mL) and DCM (19.27 ± 0.492 µg/mL). The extracts exhibited minimal cytotoxicity except for the ETA and DCM of Z. mucronata with CC50 values of 10.96 and 10.01 µg/mL, respectively. Isolation and structural characterization of the active compounds from the DCM extracts revealed that betulinic acid (19.95 ± 1.53 µg/mL) and lupeol (7.56 ± 2.03 µg/mL) were responsible for the anti-malarial activity and had no considerable cytotoxicity (CC50 > µg/mL). Molecular docking suggested strong binding between PfHsp70-1, betulinic acid (- 6.8 kcal/mol), and lupeol (- 6.9 kcal/mol). Meanwhile, the in vitro validation assays revealed the disruption of the protein structural elements and chaperone function. CONCLUSION: This study proves that X undulutum and Z. mucronata have anti-malarial potential and that betulinic acid and lupeol are responsible for the activity seen on Z. mucronata. They also make a case for guided purification of new phytochemicals in the other extracts and support the notion of considering medicinal plants to discover new anti-malarials.

The therapeutic potential of Ziziphi Spinosae Semen and Polygalae Radix in insomnia management: Insights from gut microbiota and serum metabolomics techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphi Spinosae Semen and Polygalae Radix (ZSS-PR) constitute a traditional Chinese herbal combination with notable applications in clinical and experimental settings due to their evident sedative and calming effects. Aligned with traditional Chinese medicine principles, Ziziphi Spinosae Semen supports cardiovascular health, nourishes the liver, and induces mental tranquillity. Simultaneously, Polygalae Radix elicits calming effects, fosters clear thinking, and reinstates proper coordination between the heart and kidneys. ZSS-PR is commonly employed as a therapeutic intervention for various insomnia types, demonstrating distinct clinical efficacy. Our previous study findings provide evidence that ZSS-PR administration significantly reduces sleep onset latency, increases overall sleep duration, and improves abnormal neurotransmitter levels in a murine insomnia model. AIM OF STUDY: This investigation aimed to scrutinize the intrinsic regulatory mechanism of ZSS-PR in managing insomnia using gut microbiota and serum metabolomics techniques. MATERIALS AND METHODS: Mice were given DL-4-Chlorophenylalanine to induce insomnia and then treated with ZSS-PR. The open-field test assessed the animals' spontaneous activity. Concentrations of neurotransmitters, endocrine hormones, and cytokines in the duodenum were measured using enzyme linked immunosorbent assay, and brain histopathology was evaluated with H&E staining. The impact of ZSS-PR on the metabolic profile was examined by liquid chromatography couped to high resolution mass spectrometry, and 16S rDNA sequencing was used to study the influence of ZSS-PR on the gut microbiota. Additionally, the content of short-chain fatty acids (SCFAs) was analyzed by GC-MS. Finally, correlation analysis investigated relationships between biochemical markers, metabolites, SCFAs, and gut microbiota. RESULTS: ZSS-PR treatment significantly increased movement time and distance in mice with insomnia and improved pathological impairments in the cerebral cortex and hippocampus. It also restored abnormal levels of biochemical markers in the gut of insomnia-afflicted mice, including 5-hydroxytryptamine, dopamine, gastrin, melatonin, tumour necrosis factor-α, and interleukin-1ß. Metabolomics findings showed that ZSS-PR had a significant restorative effect on 15 endogenous metabolites in mice with insomnia. Furthermore, ZSS-PR primarily influenced five metabolic pathways, such as phenylalanine, tyrosine, and tryptophan biosynthesis, glutamine, and glutamate metabolism. Additionally, gut microbiota analysis revealed notable alterations in both diversity and microbial composition after ZSS-PR treatment. These changes were primarily attributed to the relative abundances of microbiota, including Firmicutes, Bacteroidota, Fusobacteriota, Muribaculaceae_unclassified, and Ligilactobacillus. The results of SCFAs analysis demonstrated that ZSS-PR effectively restored abnormal levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid in insomniac mice. Subsequent correlation analysis revealed that microbiota show obvious correlations with both biochemical markers and metabolites. CONCLUSIONS: The results provide compelling evidence that ZSS-PR effectively mitigates abnormal activity, reduces cerebral pathological changes, and restores abnormal levels of neurotransmitters, endocrine hormones, and cytokines in mice with insomnia. The underlying mechanism is intricately linked to the modulation of gut microbiota and endogenous metabolic pathways.

Study on the antidepressive effects and mechanism of raw and fried Ziziphi Spinosae Semen via metabolomics and gut microbiota analysis.

Ziziphi Spinosae Semen (ZSS) and fried ZSS (FZSS) have been used for treating insomnia and depression in China. However, the potential influence of chemical variations on their efficacy remains unclear. This study demonstrated that compared with ZSS, FZSS exhibited an increase in the content of seven compounds, while the fatty oil content decreased. Both ZSS and FZSS exhibited antidepressive effects in a chronic unpredictable mild stress rat model, indicating a synergistic regulation of deficiencies in 5-hydroxytryptamine in the brain and the hyperactivation of severe peripheral inflammation. ZSS demonstrated a superior modulatory effect compared with FZSS, as indicated by integrated pharmacodynamic index, metabolic profile, and relative distance value. The potential mechanism underlying their antidepressive effects involved the modulation of gut microbiota structure to alleviate excessive inflammatory responses and imbalanced tryptophan metabolism. Correlation analysis indicated that the higher fatty oil contents should be comprehensively considered as the main reason for ZSS's superior antidepressive effects, achieved through the regulation of pyroglutamic acid levels.

Polyphenol Extracts from Ziziphus jujuba Mill. "Junzao" Attenuates Ulcerative Colitis by Inhibiting the NLRP3 and MAPKs Signaling Pathways and Regulating Gut Microbiota Homeostasis in Mice.

SCOPE: Polyphenols are the major active substances in red jujube fruit, and their anti-inflammatory and antioxidant activities suggest their potential utility in the prevention of ulcerative colitis (UC). METHODS AND RESULTS: In this study, the effect of polyphenol extracts from red jujube (Ziziphus jujuba Mill. "Junzao") (PERJ) on the dextron sulfate sodium (DSS)-induced UC mice is investigated. The result shows that PERJ effectively improves clinical symptoms, including food and water intake, the disease activity insex (DAI) and spleen index, and routine blood levels, and alleviates the shortening of the colon, in mice with DSS-induced UC. Meanwhile, PERJ remarkably decreases the expression of proinflammatory factors. Moreover, PERJ repairs intestinal barrier damage by increasing the expression level of mucin 2 and mucin 3, and the result is also confirmed in the histological assessment. Besides, the expression levels of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and mitogen-activated protein kinase cascade (MAPKs) signaling pathway-related proteins are inhibited by the PERJ administration. Finally, 16S rRNA sequencing analyses reveal that PERJ reverses intestinal microbiota dysbiosis by enhancing the abundance of Firmicutes and decreasing that of Proteobacteria and Bacteroidetes. CONCLUSION: PERJ probably inhibits the development of UC by suppressing the NLRP3 and MAPKs signaling pathways and regulating gut microbiota homeostasis, and can be considered as a potential resource for preventing UC.

Preparation of a ß-cyclodextrin grafted magnetic biochar for efficient extraction of four antiepileptic drugs in plasma samples.

Simultaneous monitoring of plasma concentration levels of multiple antiepileptic drugs (AEDs) is essential for dose adjustment in comprehensive epilepsy treatment, necessitating a sensitive technique for accurate extraction and determination of AEDs. Herein, a magnetic solid-phase extraction (MSPE) technique on the basis of modified biochar (BC) is investigated to extract four AEDs from plasma, in conjunction with high performance liquid chromatography. BC derived from Zizyphus jujuba seed shells was activated by phosphoric acid (PBC) and magnetized via coprecipitation to produce MPBC. The MPBCCD obtained after modification with ß-cyclodextrin (CD) was characterized and evaluated for adsorption. It exhibited fast adsorption kinetics based on second-order kinetics and satisfactory adsorption capacity for AEDs. Then it was employed as the MSPE adsorbent and the influencing parameters were optimized. The enrichment factor was 18.75. The validation analysis revealed a favorable linearity that ranged from 0.04 to 20 µg·mL-1 along with a low limit of detection of 6.85 to 10.19 ng·mL-1. The recovery of the AEDs ranged from 78.7 to 109.2 %, with relative standard deviations below 6.7 %. Using quantum chemistry theory calculations and experimental results analysis, the adsorption mechanism was investigated. It disclosed that the suggested strategy built upon MPBCCD was appropriate for the assessment of AEDs in plasma and expanded the usage of BC as the environmentally favorable matrix for the analysis of biological samples.