Cynomorium Research Articles

Cynomorium songaricum: UHPLC/ESI-LTQ-Orbitrap-MS analysis and mechanistic study on insulin sensitivity of a flavonoid-enriched fraction

BackgroundType 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, posing a significant global health concern due to its increasing prevalence. Insulin resistance (IR) plays a major role in the development of T2DM and is often linked to factors such as obesity, physical inactivity, and a sedentary lifestyle. Recently, there has been growing interest in exploring the potential of natural products for improving insulin sensitivity and glucose metabolism. Among these, Cynomorium songaricum Rupr., an edible parasitic plant, has shown promising antidiabetic effects. However, research on its beneficial effects on IR is still nascent. Therefore, this study aims to investigate the application of a Cynomorium songaricum flavonoid-enriched fraction (CSF) in the treatment of IR in T2DM, along with elucidating the chemical and biochemical mechanisms involved. MethodFirst, UHPLC/ESI-LTQ-Orbitrap-MS was utilized to perform a chemical profiling of CSF. Subsequently, glycogen synthesis, gluconeogenesis and glucose consumption assays were conducted on HepG2 cells with a high glucose high insulin-induced IR model to illustrate the favorable impacts of CSF on IR. Then, an innovative network pharmacology analysis was executed to predict the potential chemical components and hub genes contributing to CSF's protective effect against IR. To further elucidate molecular interactions, molecular docking studies were performed, focusing on the binding interactions between active constituents of CSF and crucial targets. Additionally, an RNA-sequencing assay was employed to uncover the underlying biochemical signaling pathway responsible for CSF's beneficial effects. To validate these findings, western blot and qPCR assays were employed to verify the pathways related to IR and the potential signaling cascades leading to the amelioration of IR. ResultsThe UHPLC/ESI-LTQ-Orbitrap-MS analysis successfully identified a total of thirty-six flavonoids derived from CSF. Moreover, CSF was shown to significantly improve glycogen synthesis and glucose consumption as well as inhibit gluconeogenesis in HepG2 cells of IR. An innovative network pharmacology analysis unveiled key hub genes—AKT1 and PI3K—integral to metabolic syndrome-related signaling pathways, which contributed to the favorable impact of CSF against IR. Noteworthy active ingredients including quercetin, ellagic acid and naringenin were identified as potential contributors to these effects. The results of western blot and qPCR assays provided compelling evidence that CSF improved insulin sensitivity by modulating the PI3K-Akt signaling pathway. Subsequent RNA-sequencing analysis, in tandem with western blot assays, delved deeper into the potential mechanisms underlying CSF's advantageous effects against IR, potentially associated with the enhancement of endoplasmic reticulum (ER) proteostasis. ConclusionCSF exhibited a remarkable ability to enhance insulin sensitivity in the IR model of HepG2 cells. This was evident through enhancements in glycogen synthesis and glucose consumption, along with its inhibitory impact on gluconeogenesis. Furthermore, CSF demonstrated an improvement in the insulin-mediated PI3K-Akt signaling pathway. The potential active constituents were identified as quercetin, ellagic acid and naringenin. The underlying biochemical mechanisms responsible for CSF's beneficial effects against IR were closely linked to its capacity to mitigate ER stress, thereby offering a comprehensive understanding of its protective action.

Biotransformation of Cynomorium flavan-3-ols in dairy sheep and their effects on inflammation and liver growth retardation.

The stems of Cynomorium songaricum are used in traditional Chinese medicine as a tonic and also used locally as a food material and livestock feed. It is known that some of the falvan-3-ol monomers and dimers that entered the milk of dairy sheep fed with C. songaricum stems are biotransformation products of the original flavan-3-ol polymers in C. songaricum stems. This study was performed to investigate the biotransformation process of the flavan-3-ols in dairy sheep and to evaluate the bioactivities. The results showed that procyanidin A2 and epicatechin could be released from the polymeric flavan-3-ols of C. songaricum through rumen microbial metabolism. On traumatic and lipopolysaccharide (LPS)-induced inflammation models of Tg (mpx: EGFP) zebrafish larvae and LPS-induced liver injury models of Tg (fabp10a: DsRed) zebrafish larvae, the milk from sheep fed with C. songaricum stems showed stronger anti-inflammatory and hepatoprotective activities compared to blank milk. The absorbed chemical constituents of C. songaricum stems and the metabolites also exhibited anti-inflammatory and hepatoprotective activities, with the dimeric flavan-3-ols being more effective than the monomers. The milk, the absorbed chemical constituents of C. songaricum stems, and the metabolites alleviated the increased level of reactive oxygen species induced by LPS in zebrafish larvae. PRACTICAL APPLICATION: This study found that C. songaricum stems as livestock feed could produce milk that has a beneficial impact on consumer and livestock health in terms of anti-inflammation and hepatoprotection.

Distinguishing the intrinsic differences of Cynomorium songaricum from different origins using chemical fingerprinting combined with chemometric methods

Cynomorium songaricum is a commonly used medicinal and culinary plant renowned for its effects in tonifying kidney yang, as well as nourishing essence and blood. Consequently, it has garnered considerable attention within the fields of pharmacology and chemistry. However, given the distinct geographical distribution of C. songaricum resources, establishing an accurate analytical method to differentiate its origin becomes indispensable in ensuring its quality and efficacy. In this study, high-performance liquid chromatography (HPLC) was utilized to obtain comprehensive information on the chemical composition of C. songaricum samples from various regions and establish HPLC fingerprints. Through chemometrics analysis, essential chemical markers for classifying them were successfully identified. Additionally, the Kruskal–Wallis rank sum test was employed to evaluate differences in the content of intrinsic constituents of C. songaricum from different origins. The results demonstrated that C. songaricum samples from Neimenggu, Gansu, and Xinjiang could be accurately classified, highlighting the significance of chemical markers in assessing the quality of C. songaricum. This study provides a scientific basis for systematic quality control of Chinese herbal medicines, thereby contributing to advancements in the Chinese medicine industry.

Research Progress in Traditional Applications, Phytochemistry, Pharmacology, and Safety Evaluation of Cynomorium songaricum.

Cynomorium songaricum Rupr. (CSR) belongs to the family Cynomoriaceae. It is a perennial succulent parasitic herb with a reddish-brown coloration, predominantly submerged in sand and lacking chlorophyll. Traditionally, it has been used in ethnic medicine to treat various diseases, such as gastric ulcers, indigestion, bowel movements, and improving sexual function. To comprehensively collect CSR data, extensive literature searches were conducted using medical, ecological, and scientific databases such as Google Scholar, PubMed, Science Direct, Web of Science, and China National Knowledge Infrastructure (CNKI). This article summarizes and categorizes research on the uses, phytochemical characteristics, pharmacological activities, and toxicity of ethnic medicine, with the aim of establishing a solid foundation and proposing new avenues for exploring and developing potential applications of CSR. So far, a total of 98 compounds have been isolated and identified from CSR, including flavonoids, terpenes, steroids, and other compounds. It is worth noting that flavonoids and polysaccharides have significant antioxidant and anti-inflammatory properties. In addition, these compounds also show good application prospects in anti-tumor, antioxidant, anti-aging, anti-fatigue, anti-diabetes, and other aspects. Although extensive progress has been made in the basic research of CSR, further research is still needed to enhance the understanding of its mechanism of action and explore more unknown compounds. Our review indicates that CSR has broad prospects and deserves further research.

Identification, Antimicrobial and Plant Growth Promoting Activities of Endophytic Fungi Associated with Cynomorium songaricum Rupr., a Traditional Medicinal Plant in Mongolia

Endophytic fungi colonize the inner tissues and provide direct and indirect benefits to plants. Although Mongolia is rich in medicinal plants, due to climatic and anthropogenic reasons, the resources are being depleted, and many species are under threat of gradual extinction, while the endophytic fungi of Mongolian plants are largely unknown. In this study, a total of 24 culturable endophytic fungal strains were isolated from Cynomorium songaricum (Rupr.), a medicinal and vulnerable plant species of Mongolia. Based on the morphological characteristics and the sequences of the rDNA internal transcribed spacer (ITS) region, the isolates were identified into six genera: Fusarium (8), Clonostachys (7), Penicillium (6), Alternaria (1), Aspergillus (1), and Madurella (1). The antimicrobial activity was assessed by the agar-diffusion method, revealing that 15 strains were able to inhibit the growth of at least one of the test organisms. Among them, 1 strain showed inhibitory activity against Escherichia coli, 12 against Bacillus subtilis, 13 against Staphylococcus aureus, and 8 against Aspergillus niger, respectively. The ability to solubilize complex phosphorus and zinc minerals was observed in 3 and 21 strains, respectively, and the production of indole-3-acetic acid (IAA) was detected in nine strains in the presence of tryptophan. Our study provides the first insight into the cultivable endophytic fungal composition of C. songaricum, parasitizing the roots of Nitraria sibirica growing in the Gobi Desert of Mongolia. The resulting fungi, which have antimicrobial and plant growth-promoting properties, were preserved in the national culture collection and can be used to further exploit their biotechnological potential, as well as for the propagation of endangered and vulnerable medicinal plants.

Quality variation and salt-alkali-tolerance mechanism of Cynomorium songaricum: Interacting from microbiome-transcriptome-metabolome

Addressing soil salinization and implementing sustainable practices for cultivating cash crops on saline-alkali land is a prominent global challenge. Cynomorium songaricum is an important salt-alkali tolerant medicinal plant capable of adapting to saline-alkali environments. In this study, two typical ecotypes of C. songaricum from the desert-steppe (DS) and saline-alkali land (SAL) habitats were selected. Through the integration of multi-omics with machine learning, the rhizosphere microbial communities, genetic maps, and metabolic profiles of two ecotypes were created and the crucial factors for the adaptation of C. songaricum to saline-alkali stress were identified, including 7 keystone OTUs (i.e. Novosphingobium sp., Sinorhizobium meliloti, and Glycomyces sp.), 5 core genes (cell wall-related genes), and 10 most important metabolites (i.e. cucurbitacin D and 3-Hydroxybutyrate) were identified. Our results indicated that under saline-alkali environments, the microbial competition might become more intense, and the microbial community network had the simple but stable structure, accompanied by the changes in the gene expression related to cell wall for adaptation. However, this regulation led to the reduction in active ingredients, such as the accumulation of flavonoids and organic acid, and enhanced the synthesis of bitter substances (cucurbitacin D), resulting in the decrease in the quality of C. songaricum. Therefore, compared to the SAL ecotype, the DS was more suitable for the subsequent development of medicinal and edible products of C. songaricum. Furthermore, to explore the reasons for this quality variation, we constructed a comprehensive microbial-genetic-metabolic regulatory network, revealing that the metabolism of C. songaricum was primarily influenced by genetic factors. These findings not only offer new insights for future research into plant salt-alkali tolerance strategies but also provide a crucial understanding for cultivating high-quality medicinal plants.

Cynomorium songaricum Rupr. flavonoids improve cyclophosphamide-induced reproductive function damage by regulating the testosterone synthesis pathway.

The prevalence of male infertility has been increasing globally, necessitating the search for safe and nontoxic active compounds to alleviate reproductive dysfunction. Although the precise mechanism remains unknown, Cynomorium songaricum Rupr. (CS) extract has protective effects on the reproductive system. The effect of C. songaricum Rupr. flavonoids (CSF) on reproductive injury and testicular mesenchymal stem cell viability in male mice and TM3 cells was investigated. We explored the possible association between these effects and the testosterone (T) synthesis pathway. Mice were administered cyclophosphamide to induce reproductive damage, followed by CSF administration. Body mass and organ index were recorded. Pathological changes in T and the epididymis were observed using hematoxylin-eosin staining. ELISA measured the serum levels of T, luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and estradiol (E2) in mice. Fructose and zinc ion levels in the seminal plasma were measured. TM3 cells were treated with Bisphenol A (BPA) and different concentrations of CSF, followed by proliferative evaluations using the CCK-8 assay and T and LH level assessments using ELISA. Furthermore, the expression of steroidogenic enzyme genes and proteins was investigated using western blotting and RT-PCR. CSF exhibited a notable reduction in reproductive damage and improved pathological changes in testicular and epididymal tissues. CSF group demonstrated substantially higher levels of seminal plasma fructose and zinc ions; markedly elevated serum levels of T, LH, GnRH, and FSH; and lower levels of E2 than those of the model group. Intracellular T content and secretion of T and LH increase with CSF while effectively mitigating BPA-induced damage to TM3 cells. CSF group exhibited substantially higher gene and protein expression of steroidogenic enzymes than those of the model group, both in vivo and in vitro. CSF ameliorates reproductive impairment by enhancing the expression of pivotal enzymes involved in synthesizing T. CSF ameliorates cyclophosphamide-induced reproductive impairment and bisphenol A-induced TM3 cell damage in mice by regulating sex hormone levels in the Hypothalamic-Pituitary-Gonadal Axis (HPG axis) and upregulating the expression of steroidogenic enzymes. Therefore, CS is a potential treatment for male reproductive impairment.

Studies of the Immunomodulatory Activity of Polysaccharides from the Stem of Cynomorium songaricum Based on Intestinal Microbial Analysis.

Polysaccharides are the main effective components of Cynomorium songaricum's stem that perform biological activities and have positive impacts on immune enhancement. In this study, the polysaccharide CSP-III of Cynomorium songaricum's stem was isolated using a DEAE-52 cellulose column through Sephadex G-100 gel column chromatography. Upon analysis, the monosaccharide composition of CSP-III included Mannose (Man), Glucuronic acid (GlcA), Galacturonic acid (GalA), Rhamnose (Rha), Glucose (Glc), Galactose (Gal), and Arabinose (Ara), at a molar ratio of 0.01:0.11:0.03:0.57:0.02:0.32:1. The molecular weight of CSP-III was 4018234 Da. Meanwhile, the capacity of CSP-III, at various concentrations, to stimulate the proliferation of mouse spleen lymphocytes in vitro was compared, and the influence of CSP-III on cell proliferation was examined using RAW264.7 mouse mononuclear macrophages as a model. The influence of CSP-III on the expression of important phosphorylating proteins in the MAPK signaling pathway was initially analyzed by Western blotting. In RAW264.7 cells, CSP-III promoted the phosphorylation of JNK proteins, which thus activated the MAPK signaling cascade and exerted immunomodulatory effects. Moreover, according to in vivo studies using cyclophosphamide (CTX)-induced immunosuppression mouse models, CSP-III improved the CTX-induced histopathological damage, promoted T and B lymphocyte proliferation, upregulated CD4+ and CD8+ T-lymphocyte counts in the spleen, increased the serum levels of IgG and IgM, and activated three essential proteins of the MAPK signaling pathway. As revealed by analysis of intestinal flora, CSP-III improved the immune function by maintaining the homeostasis of the bacterial flora by boosting the relative abundances of some beneficial bacterial groups, such as Bacteroidetes, Desmodium, and Actinomyces, and reducing the relative abundance of Aspergillus phylum. Through in vitro and in vivo experiments, our present study demonstrates that polysaccharides from the stem of Cynomorium songaricum possess strong immunoregulatory effects. Findings in this work provide theoretical support for the potential application of Cynomorium songaricum in the field of health food.

Investigation of anti-depression effects and potential mechanisms of the ethyl acetate extract of Cynomorium songaricum Rupr. through the integration of in vivo experiments, LC-MS/MS chemical analysis, and a systems biology approach

Background:Cynomorium songaricum Rupr. has long been used as an anti-inflammatory, antidepressant, and anti-aging agent in traditional Chinese medicine in Asia. Its ethyl acetate extract (ECS) has been identified as the main antioxidant component with neuroprotective and estrogen-like effects. However, the potential of ECS in treating depression has not been explored yet.Methods: We identified the primary metabolites in ECS in this study using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). Network analysis was used to find the potential targets and pathways associated with the anti-neuroinflammatory depression action of the ECS. In addition, we established a corticosterone (CORT)-induced depression mouse model to assess ECS’s antidepressant effects by monitoring various behavioral changes (e.g., sucrose preference, forced swimming, tail suspension, and open field tests) and biochemical indices of the hippocampus, and validating the network analysis results. Significant pathways underwent verification through western blotting based on network analysis prediction.Results: Our study demonstrates that ECS possesses significant antidepressant activity. The LC-MS/MS analysis of ECS identified 30 main metabolites, including phloridzin, phlorizin, ursolic acid, and naringenin, as well as other flavonoids, terpenoids, and phenolic acids. These metabolites were found to be associated with 64 candidate target proteins related to neuroinflammatory depression from the database, and ten hub proteins were identified through filtration: CXCL8, ICAM1, NOS2, SELP, TNF, IL6, APP, ACHE, MAOA and ADA. Functional enrichment analyses of the candidate targets revealed their primary roles in regulating cytokine production, inflammatory response, cytokine activity, and tumor necrosis factor receptor binding. In vivo, ECS improved hippocampal neuroinflammation in the mouse model. Specifically, ECS reduced the expression of inflammatory factors in the hippocampus, inhibited M1 microglial cell polarization, and alleviated depression through the regulation of the NF-κB-NLRP3 inflammation pathway.Conclusion: Based on experimental and network analysis, this study revealed for the first time that ECS exerted antidepression effect via anti-neuroinflammation. Our research provides valuable information on the use of ECS as an alternative therapeutic approach for depression.

Total flavonoids of Cynomorium songaricum attenuates cognitive defects in an Aβ 1-42 -induced Alzheimer's disease rat model by activating BDNF/TrkB signaling transduction.

Alzheimer's disease (AD) is a degenerative disorder characterized by cognitive dysfunction and BDNF/TrkB is a well-conceived anti-AD signaling. Cynomorium songaricum Rupr. ( C. songaricum ) is a herb with promising neuroprotective effects and the function is majorly attributed to flavonoids. The current study attempted to explore the effects of total flavonoids of C. songaricum (CS) on AD model by focusing on changes in BDNF/TrkB axis. AD model was induced in rats via transcranial injection of Aβ 1-42 and AD symptoms treated with CS of three doses. Donepezil was used as the positive control. Changes in rat memory and learning abilities, brain histological, apoptosis, production of neurotransmitters, BDNF/TrkB axis, and apoptosis-related markers were measured. The injection of Aβ 1-42 induced cognitive dysfunction in AD rats. The integrity of brain tissue structure was destructed and apoptosis was induced in AD rats, in which was found the increased production of AChE and Aβ 1-42 , and decreased production of ChAT, ACH. At the molecular level, the expression of BDNF, TrkB, and Bcl-2 was suppressed, while the expression of Bax, caspase-3, and caspase-9 was induced. After the administration of CS, the memory and learning abilities of rats were improved, the production of neurotransmitter was restored, ordered arrangement of pyramidal cells was retained, and neuron apoptosis was inhibited. The attenuation of Aβ 1-42 -indcued impairments was associated with the activation of BDNF/TrkB axis and blockade of apoptosis-related pathways. Collectively, CS can improve learning and memory abilities in Aβ 1-42 -induced AD model rats. which may depend on the activation of the hippocampal BDNF/TrkB signaling pathway.

Effects of different drying methods on physico-chemical properties, bioactive and taste substances of Cynomorium songaricum

Cynomorium songaricum is a typical edible and medicinal plant, also called Suoyang (Chinese name). The effect of different drying methods on Suoyang quality has not yet been performed. Here, four drying methods were tested, including sun drying (SD), microwave drying (MD), hot air drying (HAD), and vacuum freeze drying (VFD), to evaluate the influences of various drying methods on the physico-chemical properties, bioactive and taste substances of dried Suoyang. Results showed that VFD treated samples maintained the original cellular structure and color, and had higher textural properties, antioxidant activities, and rich flavor. In addition, a total of 980 metabolites in four kinds of dried Suoyang were detected and clustered into 9 co-response modules based on utilizing widely targeting metabolomics method and weighted metabolite co-response network analysis (WMCNA). Among the important modules, 3 key metabolites were identified as potential quality markers of overall antioxidant capacity and 30 key metabolites were identified as the main taste substances, which also might be relate to the nutritional value of dried Suoyang. This finding will provide reference for choosing proper drying method that can maintain the quality of dried Suoyang and adapt to industrial production.

Content analysis and quality evaluation of main active components and mineral elements of Cynomorium songaricum in different habitats

To clarify the content characteristics of the main active components and mineral elements of Cynomorium songaricum under different habitat conditions, and further explore the relationship between the quality of C. songaricum and habitats, this study took C. songaricum from 25 different habitats in China as the research object, and measured the contents of 8 main active components and 12 mineral elements separately. Diversity analysis, correlation analysis, principal component analysis and cluster analysis were carried out. The results showed that the genetic diversity of total flavonoids, ursolic acid, ether extract, potassium(K), phosphorus(P) and zinc(Zn) in C. songaricum was high. The coefficient of variation of crude polysaccharide, ether extract, gallic acid, protocatechuic aldehyde, catechin, epicatechin, calcium(Ca), sodium(Na), magnesium(Mg), sulfur(S), iron(Fe), manganese(Mn), selenium(Se) and nickel(Ni) were all over 36%, indicating that the quality of C. songaricum was significantly affected by habitats. There were strong synergistic and weak antagonistic effects among the contents of the 8 active components, and complex antagonistic and synergistic effects among the contents of the 12 mineral elements. Principal component analysis revealed that crude polysaccharide, ursolic acid, catechin, epicatechin and total flavonoids could be used as the characteristic components to evaluate the quality of C. songaricum, and Na, copper(Cu), Mn and Ni were the characteristic elements to evaluate the quality of C. songaricum. In cluster ana-lysis, the second group with the main active components as cluster center had better quality in terms of the content of active substances, and the second group with the mineral elements as cluster center had higher utilization potential in the exploitation of mineral elements. This study could provide a basis for resource evaluation and breeding of excellent varieties of C. songaricum in different habitats, and provide a reference for cultivation and identification of C. songaricum.

Anti-oxidant, Anti-inflammatory, Astringent Activities and Skin Barrier Enhancement Effects of Cynomorium songaricum Extract

The present study investigates the effects of two extracts from <i>Cynomorium songaricum</i> (CS) on the skin barrier enhancement and astringent activity. Although the effects of CS have been reported in various diseases including cancer, diabetes and inflammatory diseases, the skin protective effects of CS are poorly understood. To test the skin protection abilities, anti-oxidant and anti-inflammatory activities including radical scavenging activity, polyphenol contents measurement, nitric oxide (NO) production, iNOS protein level and IL-6 cytokine were tested. The <i>C. songaricum</i> methanol extract (CSM) showed potent anti-oxidant and anti-inflammatory activities. The CSM also enhanced the astringent activity in a dose-dependent manner. In addition, the anti-wrinkle activities were tested using elastase inhibition rate, MMP-1, and AQP-3 protein expressions. Furthermore, the mRNA level of filaggrin, loricrin, and involucrin was significantly increased in the CSM treated cells, as compared with the TNF-α treated cells. Therefore, <i>C. songaricum</i> may be a potent source for cosmetics or treating inflammatory skin diseases.

Anticancer, Cardio-Protective and Anti-Inflammatory Potential of Natural-Sources-Derived Phenolic Acids.

Phenolic acids (PAs) are one of the utmost prevalent classes of plant-derived bioactive chemicals. They have a specific taste and odor, and are found in numerous medicinal and food plants, such as Cynomorium coccineum L., Prunus domestica (L.), and Vitis vinifera L. Their biosynthesis, physical and chemical characteristics and structure-activity relationship are well understood. These phytochemicals and their derivatives exert several bioactivities including but not limited to anticancer, cardioprotective, anti-inflammatory, immune-regulatory and anti-obesity properties. They are strong antioxidants because of hydroxyl groups which play pivotal role in their anticancer, anti-inflammatory and cardioprotective potential. They may play significant role in improving human health owing to anticarcinogenic, anti-arthritis, antihypertensive, anti-stroke, and anti-atherosclerosis activities, as several PAs have demonstrated biological activities against these disease during in vitro and in vivo studies. These PAs exhibited anticancer action by promoting apoptosis, targeting angiogenesis, and reducing abnormal cell growth, while anti-inflammatory activity was attributed to reducing proinflammatory cytokines. Pas exhibited anti-atherosclerotic activity via inhibition of platelets. Moreover, they also reduced cardiovascular complications such as myocardial infarction and stroke by activating Paraoxonase 1. The present review focuses on the plant sources, structure activity relationship, anticancer, anti-inflammatory and cardioprotective actions of PAs that is attributed to modulation of oxidative stress and signal transduction pathways, along with highlighting their mechanism of actions in disease conditions. Further, preclinical and clinical studies must be carried out to evaluate the mechanism of action and drug targets of PAs to understand their therapeutic actions and disease therapy in humans, respectively.

Combined Chemo-Immuno-Photothermal Therapy for Effective Cancer Treatment via an All-in-One and One-for-All Nanoplatform.

Tumor metastasis and recurrence are recognized to be the main causes of failure in cancer treatment. To address these issues, an "all in one" and "one for all" nanoplatform was established for combined "chemo-immuno-photothermal" therapy with the expectation to improve the antitumor efficacy. Herein, Docetaxel (DTX, a chemo-agent) and cynomorium songaricum polysaccharide (CSP, an immunomodulator) were loaded into zein nanoparticles coated by a green tea polyphenols/iron coordination complex (GTP/FeIII, a photothermal agent). From the result, the obtained nanoplatform denoted as DTX-loaded Zein/CSP-GTP/FeIII NPs was spherical in morphology with an average particle size of 274 nm, and achieved pH-responsive drug release. Moreover, the nanoplatform exhibited excellent photothermal effect both in vitro and in vivo. It was also observed that the nanoparticles could be effectively up take by tumor cells and inhibited their migration. From the results of the in vivo experiment, this nanoplatform could completely eliminate the primary tumors, prevent tumor relapses on LLC (Lewis lung cancer) tumor models, and significantly inhibit metastasis on 4T1 (murine breast cancer) tumor models. The underlying mechanism was also explored. It was discovered that this nanoplatform could induce a strong ICD effect and promote the release of damage-associated molecular patterns (DAMPs) including CRT, ATP, and HMGB1 by the dying tumor cells. And the CSP could assist the DAMPs in inducing the maturation of dendritic cells (DCs) and facilitate the intratumoral infiltration of T lymphocytes to clear up the residual or disseminated tumor cells. In summary, this study demonstrated that the DTX-loaded Zein/CSP-GTP/FeIII is a promising nanoplatform to completely inhibit tumor metastasis and recurrence.

Integrated Metabolites and Transcriptomics at Different Growth Stages Reveal Polysaccharide and Flavonoid Biosynthesis in Cynomorium songaricum.

Cynomorium songaricum is a perennial parasitic herb, and its stem is widely used as a traditional Chinese medicine, which largely relies on bioactive compounds (e.g., polysaccharides, flavonoids, and triterpenes). To date, although the optimum harvest time of stems has been demonstrated at the unearthed stage (namely the early flowering stage, EFS), the accumulation mechanism of polysaccharides and flavonoids during growth stages is still limited. In this study, the physiological characteristics (stem fresh weight, contents of soluble sugar and flavonoids, and antioxidant capacity) at four different growth stages (germination stage (GS), vegetative growth stage (VGS), EFS, and flowering stage (FS)) were determined, transcriptomics were analyzed by illumina sequencing, and expression levels of key genes were validated by qRT-PCR at the GS, VGS, and EFS. The results show that the stem biomass, soluble sugar and total flavonoids contents, and antioxidant capacity peaked at EFS compared with GS, VGS, and FS. A total of 6098 and 13,023 differentially expressed genes (DEGs) were observed at VGS and EFS vs. GS, respectively, with 367 genes co-expressed. Based on their biological functions, 109 genes were directly involved in polysaccharide and flavonoid biosynthesis as well as growth and development. The expression levels of key genes involved in polysaccharides (e.g., GLCs, XTHs and PMEs), flavonoids (e.g., 4CLLs, CYPs and UGTs), growth and development (e.g., AC58, TCPs and AP1), hormones biosynthesis and signaling (e.g., YUC8, AIPT and ACO1), and transcription factors (e.g., MYBs, bHLHs and WRKYs) were in accordance with changes of physiological characteristics. The combinational analysis of metabolites with transcriptomics provides insight into the mechanism of polysaccharide and flavonoid biosynthesis in C. songaricum during growth stages.

Predicting the potential distribution of four endangered holoparasites and their primary hosts in China under climate change.

Climate change affects parasitic plants and their hosts on distributions. However, little is known about how parasites and their hosts shift in distribution, and niche overlap in response to global change remains unclear to date. Here, the potential distribution and habitat suitability of four endangered holoparasites and their primary hosts in northern China were predicted using MaxEnt based on occurrence records and bioclimatic variables. The results indicated that (1) Temperature annual range (Bio7) and Precipitation of driest quarter (Bio17) were identified as the common key climatic factors influencing distribution (percentage contribution > 10%) for Cynomorium songaricum vs. Nitraria sibirica (i.e., parasite vs. host); Temperature seasonality (Bio4) and Precipitation of driest month (Bio14) for Boschniakia rossica vs. Alnus mandshurica; Bio4 for Cistanche deserticola vs. Haloxylon ammodendron; Precipitation of warmest quarter (Bio18) for Cistanche mongolica vs. Tamarix ramosissima. Accordingly, different parasite-host pairs share to varying degree the common climatic factors. (2) Currently, these holoparasites had small suitable habitats (i.e., moderately and highly) (0.97–3.77%), with few highly suitable habitats (0.19–0.81%). Under future scenarios, their suitable habitats would change to some extent; their distribution shifts fell into two categories: growing type (Boschniakia rossica and Cistanche mongolica) and fluctuating type (Cynomorium songaricum and Cistanche deserticola). In contrast, the hosts’ current suitable habitats (1.42–13.43%) varied greatly, with highly restricted suitable habitats (0.18–1.00%). Under future scenarios, their suitable habitats presented different trends: growing type (Nitraria sibirica), declining type (Haloxylon ammodendron) and fluctuating type (the other hosts). (3) The niche overlaps between parasites and hosts differed significantly in the future, which can be grouped into two categories: growing type (Boschniakia rossica vs. Alnus mandshurica, Cistanche mongolica vs. Tamarix ramosissima), and fluctuating type (the others). Such niche overlap asynchronies may result in severe spatial limitations of parasites under future climate conditions. Our findings indicate that climate factors restricting parasites and hosts’ distributions, niche overlaps between them, together with parasitic species identity, may jointly influence the suitable habitats of parasitic plants. Therefore, it is necessary to take into account the threatened holoparasites themselves in conjunction with their suitable habitats and the parasite-host association when developing conservation planning in the future.

Ecotype Division and Chemical Diversity of Cynomorium songaricum from Different Geographical Regions.

Cynomorium songaricum is an important endangered plant with significant medicinal and edible values. However, the lack of resources and quality variation have limited the comprehensive developments and sustainable utilization of C. songaricum. Here, we evaluated the chemical and genetic traits of C. songaricum from the highly suitable habitat regions simulated with species distribution models. The PCA and NJ tree analyses displayed intraspecific variation in C. songaricum, which could be divided into two ecotypes: ecotype I and ecotype II. Furthermore, the LC-MS/MS-based metabolomic was used to identify and analyze the metabolites of two ecotypes. The results indicated that a total of 589 compounds were detected, 236 of which were significantly different between the two ecotypes. Specifically, the relative content and the kind of flavonoids were more abundant in ecotype I, which were closely associated with the medicinal activities. In contrast, amino acids and organic acids were more enriched in ecotype II, which may provide better nutritional quality and unique flavor. In summary, our findings demonstrate the ecotype division and chemical diversity of C. songaricum in China from different geographical regions and provide a reference for the development of germplasm and directed plant breeding of endangered medicinal plants.

Identification and bioactivity evaluation of flavan-3-ols in the milk of dairy sheep fed Cynomorium songaricum

Cynomorium songaricum is a traditional medicine and also a food material that is eaten raw or processed as tea or beverages. As a featured plant in semi-desert grasslands, C. songaricum is also eaten by the cattle and sheep in the area. This research study fed dairy sheep C. songaricum to determine the flavan-3-ols in sheep milk. Catechin (Cat), epicatechin (Epi), procyanidin A1 (A1), procyanidin A2 (A2), and procyanidin B1 (B1) were detected in sheep milk with the concentration being Epi > A2 > Cat > B1 > A1 at 24 h after the administration of C. songaricum. Neither A1 nor A2 were detected in the methanol extract of C. songaricum. Cysteine degradation of the plant revealed that in addition to Epi, A2 was the extending unit of the polymeric flavan-3-ols in C. songaricum, indicating that A2 is released digestively from the polymers and enters the milk. Procyanidin B-1 was converted to A1 on incubation in raw but not heated milk, indicating that the A1 in milk is the enzymatically transformed product of B1. Accelerated oxidation showed that the flavan-3-ols, B1, Cat, and Epi significantly protects the unsaturated triacyglycerols in the milk from oxidation. The flavan-3-ol could slow down the oxidation of glutathione and the latter may play an important role in preventing the milk triglycerides from oxidation. Flavan-3-ols are polyphenols with many health benefits. The present research revealed the antioxidant activities of flavan-3-ols that could be absorbed to sheep milk, adding new evidences for the values of these flavan-3-ols and for the milk.

Structures and neuroprotective activities of triterpenoids from Cynomorium coccineum subsp. songaricum (Rupr.) J. Leonard

Cynomorium coccineum subsp. songaricum (Rupr.) J. Leonard has been widely used as a Chinese herbal remedy or a functional food for treating symptoms of aging or neurodegenerative diseases. A further investigation on the finding of active constituents led to the isolation and identification of four previously undescribed triterpenoids, together with 20 known compounds. Their structures were elucidated by extensive spectroscopic analysis (IR, NMR, HRMS, and CD). Sixteen compounds showed significant neuroprotective effects against glutamate-induced or oxygen-glucose deprivation-induced SK-N-SH cell death. Our findings revealed the active constituents of C. coccineum subsp. songaricum and indicated that both oleanane-type and ursane-type triterpenes could be valuable platforms for neurodegenerative agents based on primary structure-activity relationship analysis.