The genus Dioscorea L. (Dioscoreaceae), a review of traditional uses, phytochemistry, pharmacology, and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Dioscorea, a member of the Dioscoreaceae family, comprises approximately 600 species and is widely distributed across temperate and tropical regions such as Asia, South Africa, and North America. The traditional medicinal uses of Dioscorea have been documented in Asian and African pharmacological systems. In Asia, this genus is traditionally used to treat respiratory illnesses, rheumatism, diabetes, diarrhea, dysentery, and other conditions. In Africa, this genus has been used to treat human immunodeficiency virus and ring worms. However, the traditional medicinal practices in North America rarely mention the use of this genus. AIM OF THE STUDY: The aim of this review is to comprehensively review the genus Dioscorea, focusing on its traditional uses, phytochemical constituents, pharmacological activities, and potential toxicities. The research also aims to highlight the valuable bioactive compounds within Dioscorea and emphasize the need for further investigations into acute and chronic toxicity, activity mechanisms, molecular markers, and other relevant factors to contribute to the discovery of novel pharmaceuticals. MATERIALS AND METHODS: A search for available information on Dioscorea was conducted using scientific databases, including PubMed, ISI-WOS, Scopus, and Google Scholar, as well as recent academic publications from reputable publishers and other literature sources. The search was not limited by language and spanned the literature published between 1950 and 2022. RESULTS: This article provides a comprehensive review of the Dioscorea genus, focusing on its traditional uses, phytochemical constituents, pharmacological activities, and potential toxicities. Extensive research has been conducted on this genus, resulting in the isolation and examination of over 1000 compounds, including steroids, terpenoids, and flavonoids, to determine their biological activities. These activities include anti-tumor, anti-inflammatory, immunomodulatory, neuroprotective, hypoglycemic, and hypolipidemic effects. However, some studies have indicated the potential toxicity of high doses of Dioscorea, highlighting the need for further investigations to assess the safety of this genus. Additionally, this review explores potential avenues for future research and discusses the challenges associated with a comprehensive understanding of the Dioscorea genus. CONCLUSIONS: Based on the existing literature, it can be concluded that Dioscorea is a valuable source of bioactive compounds that have the potential to treat various disorders. Future research should prioritize the investigation of acute and chronic toxicity, activity mechanisms, molecular markers, and other relevant factors. This review provides a comprehensive analysis of the Dioscorea genus, emphasizing its potential to enable a deeper exploration of the biological activity mechanisms of these plants and contribute to the discovery of novel pharmaceuticals.

Super-enhancer mediated upregulation of MYEOV suppresses ferroptosis in lung adenocarcinoma.

Super-enhancers (SEs) exerted a crucial role in regulating the transcription of oncogenes across various malignancies while the roles of SEs driven genes and the core regulatory elements remain elusive in LUAD. In this study, cancer-specific-SE-genes of lung adenocarcinoma (LUAD) were profiled through H3K27ac ChIP-seq data of cancer cell lines and normal lung tissues, which enriched in in biological processes and pathways integral to the pathophysiology of LUAD. Based on this study, LUAD cells were susceptible to SEs inhibitors, with a reduction of cell proliferation as well as an elevation of apoptosis upon JQ1 or THZ1 intervention. Moreover, the integration of SEs landscapes, CRISPRi, ChIP-PCR, Hi-C data analysis and dual-luciferase reporter assays revealed that myeloma overexpressed gene (MYEOV) was aberrantly overexpressed in LUAD via transcriptional activation by the core SE elements. Functionally, the knockdown of MYEOV undermined cell proliferation in vitro and tumor growth in vivo. In addition, the knockdown of MYEOV generated a prominent ferroptotic phenotype, characterized by elevation of intracellular ferrous iron, reactive oxygen species and lipid peroxidation, together with alteration in marker proteins (SLC7A11, GPX4, FTH1, and ACSL4). Instead, the overexpression of MYEOV accelerated cell proliferation and abrogated ferroptosis. Clinically, the overexpression of MYEOV was observed in LUAD tissues indicating a poor prognosis in patients with LUAD. Mechanistically, SMPD1-induced autophagic degradation of GPX4 assumed a crucial role in the process of ferroptosis triggered by MYEOV knockdown. Serving as an oncogene repressing ferroptosis, promoting proliferation as well as shortening survival in LUAD, SEs-mediated activation of MYEOV might distinguish as a promising therapeutic target.

A Non-Bonding Interaction-Based Fluorescent Probe for Detection of Halogenated Carbonyl Compounds.

The fluorescent detection of neutral and volatile carbonyl halogenated compounds had not been studied before. We describe here a simple and sensitive turn-on rhodamin fluorescent probe for the selective detection of fluorinated/brominated/chlorinated/iodinated carbonyl compounds. A wide range of linear or cyclic volatile organic halides was detected with a limit of detection as low as 45.6 nM within 1 min. Mechanistic experiments and DFT calculations indicate the reversible formation of a 1:1 complex of sensor and analyst through non-bonding interaction.

Sex Differences in Depressive Symptoms in 1308 Patients Post-Stroke at Entry to Cardiac Rehabilitation.

PURPOSE: The objective of this study was to determine whether a sex difference exists in the prevalence of post-stroke depressive symptoms (PSDS) at entry to cardiac rehabilitation (CR) and to determine the correlates of PSDS in all patients, and in women and men separately. METHODS: People post-stroke at entry to CR from database records (2006-2017) were included. Bivariate analyses identified PSDS correlates (≥16 on the Center for Epidemiologic Studies Depression Scale) in all patients and women and men separately. RESULTS: Patients (n = 1308, 28.9% women), mean age of 63.9 ± 12.9 yr, were 24.2 ± 49.9 mo post-stroke at CR entry. Among all patients, 30.0% had PSDS. A greater proportion of women than men had PSDS (38.6 vs 26.6%; P < .001). Correlates of PSDS in all patients were sex (women) (OR = 1.6: 95% CI, 1.14-2.12), being unemployed, ≤60 yr old, prescribed antidepressant medication, having lower cardiorespiratory fitness (peak oxygen uptake [V˙ O2peak ]), chronic obstructive pulmonary disease (COPD), higher body mass index (BMI), no transient ischemic attack, and longer time from stroke to CR entry (>12 mo). Correlates in women were being obese (BMI ≥ 30), 51-70 yr old, prescribed antidepressant medication, and not married. Correlates in men were being ≤60 yr old, unemployed, prescribed antidepressant medication, having lower V˙ O2peak , sleep apnea, COPD, and no hypertension. CONCLUSION: Women were disproportionately affected by PSDS at entry to CR in bivariate and multivariable analyses. Women and men had mostly unique correlates of PSDS, indicating tailored strategies to address PSDS are required. Post-stroke depressive symptoms disproportionately affected patients with longer delay to CR entry, suggesting efforts should target timely referral to facilitate earlier and repeated assessments and management.

Confinement of ionomer for electrocatalytic CO2 reduction reaction via efficient mass transfer pathways.

Gas diffusion electrodes (GDEs) mediate the transport of reactants, products and electrons for the electrocatalytic CO2 reduction reaction (CO2RR) in membrane electrode assemblies. The random distribution of ionomer, added by the traditional physical mixing method, in the catalyst layer of GDEs affects the transport of ions and CO2. Such a phenomenon results in elevated cell voltage and decaying selectivity at high current densities. This paper describes a pre-confinement method to construct GDEs with homogeneously distributed ionomer, which enhances mass transfer locally at the active centers. The optimized GDE exhibited comparatively low cell voltages and high CO Faradaic efficiencies (FE > 90%) at a wide range of current densities. It can also operate stably for over 220 h with the cell voltage staying almost unchanged. This good performance can be preserved even with diluted CO2 feeds, which is essential for pursuing a high single-pass conversion rate. This study provides a new approach to building efficient mass transfer pathways for ions and reactants in GDEs to promote the electrocatalytic CO2RR for practical applications.

Review of the Chemical Composition and Biological Activities of Essential Oils from Artemisia Argyi, Artemisia Princeps, and Artemisia Montana.

BACKGROUND: Artemisia argyi Lévl. et Van., Artemisia princeps Pamp., and Artemisia montana Pamp., which are the sources of mugwort, have been popular across East Asian countries for nearly 2000 years now. Essential oils are the major chemical component obtained from them, exhibiting a variety of biological activities. OBJECTIVE: This review mainly focuses on the chemical composition and biological activities of A. argyi essential oil (AAEO), A. princeps essential oil (APEO), and A. montana essential oil (AMEO), with a special focus on their common and specific characteristics. The traditional use, distribution, and botany of A. argyi, A. princeps, and A. montana have also been summarized. In addition, the pharmacokinetics of AAEO was involved. METHODS: We collected literature from online and offline databases by entering the following keywords: mugwort, wormwood, A. argyi, A. princeps, A. montana, essential oil, and volatile oil. No language limitation was present in our search. RESULTS: A. argyi, A. princeps, and A. montana were used as traditional medicine, food, and health care products for a long time in Asia. They are widely distributed in most parts of China, Korea, and Japan. AAEO, APEO, and AMEO composed of monoterpenes, sesquiterpenes and their derivatives, alkanes, olefins, etc. Most of the specific compounds of AAEO were monoterpenoids, nearly half of the specific compounds of APEO were aliphatic hydrocarbons, and the sesquiterpenes were the typical specific compounds of AMEO. The mugwort essential oil showed multiple biological activities, such as anti-microbial, anti-inflammatory, antioxidant, antitumor, anticoagulation, sedative, and insecticide. CONCLUSION: The present review provided insight into the chemical composition and biological activity of AAEO, APEO, and AMEO. The comprehensive literature showed that they possessed wide application prospects in various fields. However, they should be studied in more depth. The underlying bioactive mechanisms should be elucidated and their toxicity and quality control should be determined.

Effects of surface properties of GaN semiconductors on cell behavior.

In recent years, semiconductors have aroused great interest in connecting, observing and influencing the behavior of biological elements, and it is possible to use semiconductor-cell compound interfaces to discover new signal transduction in the biological field. Among them, III-V nitride semiconductors, represented by gallium nitride (GaN), are used as substrates to form semiconductor-biology interfaces with cells, providing a platform for studying the effects of semiconductors on cell behavior. The interfaces between GaN substrate and cells play an important role in detecting and manipulating cell behaviors and provide a new opportunity for studying cell behavior and developing diagnostic systems. Hence, it is necessary to understand how the properties of the GaN substrate directly influence the behavior of biological tissues, and to create editable biological interfaces according to the needs. This paper reviews the synergism between GaN semiconductors and biological cells. The electrical properties, persistent photoconductivity (PPC), nanostructures, and chemical functionalization of GaN on the promotion of cell behaviors, such as growth, adhesion, differentiation, and signal transduction, are emphatically introduced. The purpose of this study is to provide guidance to explore the detection and regulation methods of cell behavior based on semiconductors and promote the application of them in the field of bioelectronics, such as biochips, biosensors, and implantable systems.

[Correlations between appearance traits and internal quality of Bupleurum scorzonerifolium roots based on theory of "quality evaluation through morphological identification"].

It is generally believed that high-quality Bupleurum scorzonerifolium roots possess specific morphological characteristics, being red, robust, and long with strong odor. However, the scientific connotation of these characteristics has not been elucidated. According to the theory of "quality evaluation through morphological identification", we studied the correlations between appearance traits(the RGB value of root surface, root length, root diameter, dry weight, and ratio of phloem to xylem) and content of main chemical components(volatile oils, total saponins, total flavonoids, total polysaccharides, and seven saikosaponins) of B. scorzonerifolium roots. Epson Scanner and ImageJ were used to scan the root samples and measure the appearance traits. Ultraviolet spectrophotometry and HPLC were employed to determine the content of chemical components. The correlation, regression, and cluster analyses were performed to study the correlations between the appearance traits and the content of chemical components. The results showed that the content of volatile oils and saikosaponins were significantly correlated with RGB value, root length, and root diameter, indicating that within a certain range, the roots being redder, longer, and thicker had higher content of volatile oils and saikosaponins. According to the appearance traits and chemical component content, the 14 samples from different producing areas were classified into four grades, and the differences in morphological traits and chemical component content were consistent among different grades. The findings in this study demonstrate that appearance traits(RGB value, root length, and root diameter) can be used to evaluate the quality of B. scorzonerifolium roots. Meanwhile, this study lays a foundation for establishing an objective quality evaluation method for B. scorzonerifolium roots.

Profiling and integrated analysis of transcriptional addiction gene expression and prognostic value in hepatocellular carcinoma.

Transcriptional dysregulation caused by genomic and epigenetic alterations in cancer is called "transcriptional addiction". Transcriptional addiction is an important pathogenic factor of tumor malignancy. Hepatocellular carcinoma (HCC) genomes are highly heterogeneous, with many dysregulated genes. Our study analyzed the possibility that transcriptional addiction-related genes play a significant role in HCC. All data sources for conducting this study were public cancer databases and tissue microarrays. We identified 38 transcriptional addiction genes, and most were differentially expressed genes. Among patients of different groups, there were significant differences in overall survival rates. Both nomogram and risk score were independent predictors of HCC outcomes. Transcriptional addiction gene expression characteristics determine the sensitivity of patients to immunotherapy, cisplatin, and sorafenib. Besides, HDAC2 was identified as an oncogene, and its expression was correlated with patient survival time. Our study conclusively demonstrated that transcriptional addiction is crucial in HCC. We provided biomarkers for predicting the prognosis of HCC patients, which can more precisely guide the patient's treatment.

Study on molecular mechanism of volatiles variation during Bupleurum scorzonerifolium root development based on metabolome and transcriptome analysis.

Bupleurum scorzonerifolium Willd. is a medicinal herb. Its root has a high content of volatile oil (BSVO), which shows a variety of biological activities. Currently, BSVO in the injectable form is used for treating fever in humans and livestock. The yield and quality of volatile oils depends on the developmental stages of plants. However, the changes in BSVO yield and quality during root development in Bupleurum scorzonerifolium and the underlying molecular regulatory mechanisms remain unclear. This knowledge gap is limiting the improvement in the quality of BSVO. In the present study, B. scorzonerifolium root was collected at germinative, vegetative, florescence, fruiting and defoliating stages. The yield of BSVO, metabolic profile of volatile components and transcriptome of root samples at various developmental stages were comprehensively determined and compared. BSVO continuously accumulated from the germinative to fruiting stages, and its level slightly decreased from the fruiting to defoliating stages. A total of 82 volatile components were detected from B. scorzonerifolium root, of which 22 volatiles were identified as differentially accumulated metabolites (DAMs) during the root development. Of these volatiles, fatty acids and their derivatives accounted for the largest proportion. The contents of most major volatiles were highest at the fruiting stage. A large number of differentially expressed genes (DEGs) were detected during B. scorzonerifolium root development, of which 65 DEGs encoded various enzymes and transcription factors regulating the biosynthesis of fatty acids and their derivatives. In further analysis, 42 DEGs were identified to be significantly correlated with DAMs, and these DEGs may be the key genes for the biosynthesis of volatiles. To the best of our knowledge, this is the first study to comprehensively report the changes in the composition and content of volatiles and underlying mechanism during B. scorzonerifolium root development. This study provided important reference for future studies to determine the harvest time of B. scorzonerifolium roots and improve the quality of BSVO.

Single molecule localizations of voltage-gated sodium channel NaV1.5 on the surfaces of normal and cancer breast cells.

Voltage-gated sodium channels (VGSCs) are widely expressed in various types of tumor and cancer cells, and NaV1.5 is overexpressed in highly metastatic breast cancer cells. There may be positive relations between the expression levels of NaV1.5 and breast cancer recurrence and metastasis. Herein, NaV1.5 was detected and localized on the surfaces of normal and cancer breast cells by the single molecule recognition imaging (SMRI) mode of atomic force microscopy (AFM). The results reveal that NaV1.5 was irregularly distributed on the surfaces of normal and cancer breast cells. The NaV1.5 has an area percentage of 0.6% and 7.2% on normal and cancer breast cells, respectively, which indicates that there is more NaV1.5 on cancer cells than on normal cells. The specific interaction forces and binding kinetics in the NaV1.5-antibody complex system were investigated with the single molecule force spectroscopy (SMFS) mode of AFM, indicating that the stability of the NaV1.5-antibody on normal breast cells is higher than that on cancer breast cells. All these results will be useful to study the interactions of other ion channel-antibody systems, and will also be useful to understand the role of sodium channels in tumor metastasis and invasion.

New insights into immunomodulatory properties of lactic acid bacteria fermented herbal medicines.

The COVID-19 pandemic has brought more attention to the immune system, the body's defense against infectious diseases. The immunomodulatory ability of traditional herbal medicine has been confirmed through clinical trial research, and has obvious advantages over prescription drugs due to its high number of potential targets and low toxicity. The active compounds of herbal drugs primarily include polysaccharides, saponins, flavonoids, and phenolics and can be modified to produce new active compounds after lactic acid bacteria (LAB) fermentation. LAB, primary source of probiotics, can produce additional immunomodulatory metabolites such as exopolysaccharides, short-chain fatty acids, and bacteriocins. Moreover, several compounds from herbal medicines can promote the growth and production of LAB-based immune active metabolites. Thus, LAB-mediated fermentation of herbal medicines has become a novel strategy for regulating human immune responses. The current review discusses the immunomodulatory properties and active compounds of LAB fermented herbal drugs, the interaction between LAB and herbal medicines, and changes in immunoregulatory components that occur during fermentation. This study also discusses the mechanisms by which LAB-fermented herbal medicines regulate the immune response, including activation of the innate or adaptive immune system and the maintenance of intestinal immune homeostasis.

Linguistic features and psychological states: A machine-learning based approach.

Previous research mostly used simplistic measures and limited linguistic features (e.g., personal pronouns, absolutist words, and sentiment words) in a text to identify its author's psychological states. In this study, we proposed using additional linguistic features, that is, sentiments polarities and emotions, to classify texts of various psychological states. A large dataset of forum posts including texts of anxiety, depression, suicide ideation, and normal states were experimented with machine-learning algorithms. The results showed that the proposed linguistic features with machine-learning algorithms, namely Support Vector Machine and Deep Learning achieved a high level of performance in the detection of psychological state. The study represents one of the first attempts that uses sentiment polarities and emotions to detect texts of psychological states, and the findings may contribute to our understanding of how accuracy may be enhanced in the detection of various psychological states. Significance and suggestions of the study are also offered.

Study of Saponin Components after Biotransformation of Dioscorea nipponica by Endophytic Fungi C39.

This study conducted the solid fermentation process of Dioscorea nipponica using endophytic fungi C39 to determine the changes in the diosgenin concentration. The results revealed that endophytic fungi C39 could effectively biotransform the saponin components in D. nipponica. Moreover, the maximum increase in the diosgenin concentration reached 62.67% in 15 days of solid fermentation. MTT assay results demonstrated that the inhibitory effects of the fermentation drugs on four types of cancer cells (liver cancer cells (HepG2), stomach cancer cells (BGC823), cervical cancer cells (HeLa), and lung cancer cells (A549)) were better than those of the crude drugs obtained from D. nipponica. The chemical composition of the samples obtained before and after the biotransformation of D. nipponica was analyzed by UPLC-Q-TOF-MS. A total of 32 compounds were identified, 21 of which have been reported in Dioscorea saponins and the ChemSpider database and 11 compounds were identified for the first time in D. nipponica. The biotransformation process was inferred based on the variation trend of saponins, which included transformation pathways pertaining to glycolytic metabolism, ring closure reaction, dehydrogenation, and carbonylation. The cumulative findings provide the basis for the rapid qualitative analysis of the saponin components of D. nipponica before and after biotransformation. The 11 metabolites obtained from biotransformation are potential active ingredients obtained from D. nipponica, which can be used to further identify pharmacodynamically active substances.

Analysis of the mechanism of saponin biotransformation in Dioscoreae nipponicae rhizoma by the endophytic fungus Fusarium sp. C39 using whole-genome sequencing.

Fusarium sp. C39 is an endophytic fungus of Dioscorea nipponica Makino. Symbiosis of Fusarium sp. C39 with Rhizoma Dioscoreae Nipponicae (RDN) can significantly increase the content of saponin, which provides a new approach for saponin production and reduces the pressure on natural sources of saponins. However, the underlying mechanism is not clear, limiting its application. In this study, the genome of Fusarium sp. C39 was sequenced, the gene functions were predicted via gene annotation, and the genome was compared to the genomes of four related species. Fusarium sp. C39 is predicted to encode many key enzyme genes involved in saponin synthesis, which could transform the mevalonate, isopentenyl pyrophosphate, and various intermediate compounds present in the RDN extract into saponins. The Fusarium sp. C39 genome contains specific genes that are conducive to its endophytic lifestyle and can provide abundant raw materials for saponin synthesis. Based on the genomic analysis, we proposed the mechanism by which Fusarium sp. C39 generates saponins and provides a theoretical basis for rapid, efficient, low-cost production of saponins.

Direct investigations of the electrical conductivity of normal and cancer breast cells by conductive atomic force microscopy.

Breast cancer is one of the most commonly diagnosed malignant cancers that threatens the health of women severely. The pathogenesis has not been revealed exhaustively due to the complex mechanisms. Evidences suggest that electrical conductivity properties play critical roles in cellular functions and activities. But the roles of electrical conductivity in pathogenesis of breast cancer cells have not been studied clearly at the nanometer level yet. In the present work, the electrical conductivity and electron transport of two normal and one cancer breast cell lines were investigated and compared at nanometer spatial level and picoampere current level by Conductive Atomic Force Microscopy (CAFM). The cell bodies of normal and cancer breast cells show the typical capacitor behaviors with little conductivity capability for electricity. The capacitance of cell bodies of the cancer breast cells is less than the normal breast cells. The conductivity of the processes of normal and cancer breast cells has also been investigated. The processes of the normal breast cells also exhibit the capacitor behavior. While the processes of the breast cells are electrically conductive along micrometer length scales, and show the semiconductor like conductive characteristics with Schottky barrier of 0.8391 V. All these demonstrate that the electrical conductivity of the cancer breast cells is better than the normal breast cells. This work will be helpful in the further investigations of electrical conductivity of normal and cancer cells at nanometer level, and will also pave new way in the distinguishing the cancer cells and tissues from the normal cells and tissues.

Linguistic Features and Psychological States: The Case of Virginia Woolf.

This study investigated the relation between psychological states and linguistic features with the case of Virginia Woolf. We analyzed the data from The Diary of Virginia Woolf and Virginia Woolf: Biography by automatic text analysis and statistical analysis, including stepwise multiple regression and Deep Learning algorithm. The results suggested that the significant linguistic features can jointly predict the psychological states of Virginia Woolf, including the emotional value of anger, the absolutist word "everything," and the total of first-person plural pronouns. In addition, we found that the total use of first-person plural pronouns and the emotional value of anger were negatively related to mental health of Virginia Woolf. While the use of the absolutist word "everything" was positively related to mental health of Virginia Woolf. Meanwhile, we developed a model that can predict the psychological states of Virginia Woolf, with 86.9% accuracy. We discussed the findings and enumerated the limitations of this study at the end of the paper. The results not only complemented previous studies in the understanding of the relation between language and psychological health, but also facilitated timely identification, intervention, and prevention of mental disorders.

Disulfiram/copper induces antitumor activity against gastric cancer cells in vitro and in vivo by inhibiting S6K1 and c-Myc.

PURPOSE: Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence. Accumulating evidence indicates that DSF, alone or in combination with copper (Cu), possesses strong antitumor activity in various malignancies. This study investigated the effects of DSF on gastric cancer (GC) and the potential mechanisms involved. METHODS: GC cell proliferation and apoptosis upon treatment with DSF with or without copper were analyzed using CCK-8 assay, colony formation assay, and flow cytometry. Glucose metabolism was investigated using glucose consumption and lactate production assays. The expression of caspase-3, Bcl-2, LC-3, P62, S6K1, c-Myc, GLUT1, PKM2, and LDHA was analyzed using western blot assay. In vivo nude mice studies were performed to verify the findings from in vitro analyses. RESULTS: Our study showed that DSF was highly toxic to GC cells in a Cu-dependent manner. Nontoxic concentrations of Cu enhanced the inhibitory effects of DSF on cell viability and colony formation. DSF also induced apoptotic and autophagic cell death in the presence of Cu. In addition, DSF/Cu inhibited glycolysis and xenograft growth of GC cells by suppressing the expression of S6K1, c-Myc, and their downstream molecules, including GLUT1, PKM2, and LDHA. CONCLUSION: Our study demonstrated that DSF/Cu exerted antitumor activity against GC cells both in vitro and in vivo. DSF/Cu may represent a promising therapeutic strategy for the treatment of GC.

Studies on biotransformation mechanism of Fusarium sp. C39 to enhance saponin content of Paridis Rhizoma.

Paridis Rhizoma is a natural medicine with strong anti-tumor and anti-inflammatory activities. Our previous research have found that Fusarium sp. C39, an endophytic fungus isolated from Dioscorea nipponica which contains the similar chemical components, significantly increased the steroidal saponins content of Paridis Rhizoma by fermentation. In this study, the inhibitory effects of fermentated Paridis Rhizoma extract (PRE) on liver cancer cells (Hepal-6), cervical cancer cells (Hela), and lung cancer cells (A549) were determined to be stronger than that of the unfermented extract. For discovering the fermentation mechanism of PRE with Fusarium sp. C39, 36 components with obviously quantitative variations were screened out by UPLC-Q/TOF-MS and 53 key genes involved in the metabolic pathways of steroidal saponins were identified by transcriptome. On the basis of comprehensively analyzing information from the metabonomics and transcriptome, it can be speculated that the increase of spirostanol saponins and nuatigenin-type saponins enhanced the inhibitory effect of fermented PRE on cancer cell proliferation. Under the action of glycosidase, glycosyltransferase, oxidoreductases, and genes involved in sterol synthesis, strain C39 achieved the synthesis of diosgenin and the alteration of configurations, sugar chain and substituent of steroidal saponins. The research suggested a microbial transformation approach to increase the resource utilization and activity of Paris polyphylla.

Advances in steroidal saponins biosynthesis.

MAIN CONCLUSION: This work reviews recent advances in the pathways and key enzymes of steroidal saponins biosynthesis and sets the foundation for the biotechnological production of these useful compounds through transformation of microorganisms. Steroidal saponins, due to their specific chemical structures and active effects, have long been important natural products and that are irreplaceable in hormone production and other pharmaceutical industries. This article comprehensively reviewed the previous and current research progress and summarized the biosynthesis pathways and key biosynthetic enzymes of steroidal saponins that have been discovered in plants and microoganisms. On the basis of the general biosynthetic pathway in plants, it was found that the starting components, intermediates and catalysing enzymes were diverse between plants and microorganisms; however, the functions of their related enzymes tended to be similar. The biosynthesis pathways of steroidal saponins in microorganisms and marine organisms have not been revealed as clearly as those in plants and need further investigation. The elucidation of biosynthetic pathways and key enzymes is essential for understanding the synthetic mechanisms of these compounds and provides researchers with important information to further develop and implement the massive production of steroidal saponins by biotechnological approaches and methodologies.