Ginsenosides are a series of glycosylated triterpenoids which belong to protopanaxadiol (PPD)-, protopanaxatriol (PPT)-, ocotillol (OCT)- and oleanane (OA)-type saponins known as active compounds of ...Panax genus. They are accumulated in plant roots, stems, leaves, and flowers. The content and composition of ginsenosides are varied in different ginseng species, and in different parts of a certain plant. In this review, we summarized the representative saponins structures, their distributions and the contents in nearly 20 Panax species, and updated the biosynthetic pathways of ginsenosides focusing on enzymes responsible for structural diversified ginsenoside biosynthesis. We also emphasized the transcription factors in ginsenoside biosynthesis and non-coding RNAs in the growth of Panax genus plants, and highlighted the current three major biotechnological applications for ginsenosides production. This review covered advances in the past four decades, providing more clues for chemical discrimination and assessment on certain ginseng plants, new perspectives for rational evaluation and utilization of ginseng resource, and potential strategies for production of specific ginsenosides.
Ginsenosides are produced mainly via MVA pathway. Functional genes are regulated by multiple elicitors through different transcriptional factors, which together play pivotal roles in ginsenoside structure diversities. Display omitted
Bile acids(BAs) are not only digestive surfactants but also important cell signaling molecules,which stimulate several signaling pathways to regulate some important biological processes. The ...bileacid-activated nuclear receptor, farnesoid X receptor(FXR), plays a pivotal role in regulating bile acid,lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles ofFXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases.
Viral DNA and RNA polymerases are two kinds of very important enzymes that synthesize the genetic materials of the virus itself, and they have become extremely favorable targets for the development ...of antiviral drugs because of their relatively conserved characteristics. There are many similarities in the structure and function of different viral polymerases, so inhibitors designed for a certain viral polymerase have acted as effective universal inhibitors on other types of viruses. The present review describes the development of classical antiviral drugs targeting polymerases, summarizes a variety of viral polymerase inhibitors from the perspective of chemically synthesized drugs and natural product drugs, describes novel approaches, and proposes promising development strategies for antiviral drugs.
The Gravity Recovery and Climate Experiment (GRACE) mission ended its operation in October 2017, and the GRACE Follow‐On mission was launched only in May 2018, leading to approximately 1 year of data ...gap. Given that GRACE‐type observations are exclusively providing direct estimates of total water storage change (TWSC), it would be very important to bridge the gap between these two missions. Furthermore, for many climate‐related applications, it is also desirable to reconstruct TWSC prior to the GRACE period. In this study, we aim at comparing different data‐driven methods and identifying the more robust alternatives for predicting GRACE‐like gridded TWSC during the gap and reconstructing them to 1992 using climate inputs. To this end, we first develop a methodological framework to compare different methods such as the multiple linear regression (MLR), artificial neural network (ANN), and autoregressive exogenous (ARX) approaches. Second, metrics are developed to measure the robustness of the predictions. Finally, gridded TWSC within 26 regions are predicted and reconstructed using the identified methods. Test computations suggest that the correlation of predicted TWSC maps with observed ones is more than 0.3 higher than TWSC simulated by hydrological models, at the grid scale of 1° resolution. Furthermore, the reconstructed TWSC correctly reproduce the El Nino‐Southern Oscillation (ENSO) signals. In general, while MLR does not perform best in the training process, it is more robust and could thus be a viable approach both for filling the GRACE gap and for reconstructing long‐period TWSC fields globally when combined with statistical decomposition techniques.
Key Points
We develop a unified methodological framework to compare viable approaches for reconstructing and predicting globally gridded GRACE fields
Predicted total water storage change fields fit better to the observations than those simulated by hydrological models
Reconstructed total water storage change correctly reproduces a strong abnormal signal in the tropical river basin during the El Niño period
Irinotecan (CPT11) and its active metabolite ethyl-10-hydroxy-camptothecin (SN38) are broad-spectrum cytotoxic anticancer agents. Both cause cell death in rapidly dividing cells (e.g., cancer cells, ...epithelial cells, hematopoietic cells) and commensal bacteria. Therefore, CPT11 can induce a series of toxic side-effects, of which the most conspicuous is gastrointestinal toxicity (nausea, vomiting, diarrhea). Studies have shown that the gut microbiota modulates the host response to chemotherapeutic drugs. Targeting the gut microbiota influences the efficacy and toxicity of CPT11 chemotherapy through three key mechanisms: microbial ecocline, catalysis of microbial enzymes, and immunoregulation. This review summarizes and explores how the gut microbiota participates in CPT11 metabolism and mediates host immune dynamics to affect the toxicity and efficacy of CPT11 chemotherapy, thus introducing a new concept that is called “microbiota-host-irinotecan axis”. Also, we emphasize the utilization of bacterial β-glucuronidase-specific inhibitor, dietary interventions, probiotics and strain-engineered interventions as emergent microbiota-targeting strategies for the purpose of improving CPT11 chemotherapy efficiency and alleviating toxicity.
Gentiana crassicaulis and G. straminea are alpine plants of Gentiana with important medicinal value and complex genetic backgrounds. In this study, the mitochondrial genomes (mtDNAs) of these two ...species were sequenced. The mtDNAs of G. crassicaulis and G. straminea are 368,808 and 410,086 bp long, respectively, 52 and 49 unique genes are annotated in the two species, and the gene arrangement varies widely. Compared to G. crassicaulis, G. straminea loses three effective genes, namely atp6, trnG-GCC and trnV-GAC. As a pseudogene, the atp6 gene of G. straminea is incomplete, which is rare in higher plants. We detected 1696 and 1858 pairs of long repeats and 213 SSRs and 250 SSs in the mtDNAs of G. crassicaulis and G. straminea, respectively. There are 392 SNPs and 18 InDels between the two genomes, and syntenic sequence and structural variation analysis show low collinearity between the two genomes. Chloroplast DNA transferring to mtDNA is observed in both species, and 46,511 and 55,043 bp transferred segments containing three tRNA genes are identified, respectively. Comparative analysis of mtDNAs of G. crassicaulis, G. straminea and four species of Gentianales determined 18 core genes, and there is no specific gene in G. crassicaulis and G. straminea. The phylogenetic tree based on mtDNAs places Gentianaceae in a branch of Gentianales. This study is the first to analyze the mtDNAs of Gentianaceae, which could provide information for analysis of the structure of mtDNAs of higher plants and phylogenetic research of Gentianaceae and Gentianales.
Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the ...pathogenesis of MS. In current study, astragaloside IV (ASI), a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE) in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS) as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.
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Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against ...APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, this baicalin-provided protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury. Baicalein and baicalin induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of its downstream antioxidant genes. Baicalein and baicalin-provided protection was diminished after the application of Nrf2 siRNA in hepatocytes and Nrf2 knock-out mice. Molecular docking results indicate the potential interaction of baicalein and baicalin with kelch-like ECH-associated protein-1 (Keap1). Baicalein and baicalin induced the sustained phosphorylation of extracellular regulated protein kinases (ERK)1/2 and protein kinase C (PKC). Moreover, ERK1/2 and PKC inhibitors both abrogated Nrf2 phosphorylation and its subsequent activation, and the protection against APAP-induced hepatotoxicity induced by baicalein and baicalin. In summary, baicalein and baicalin alleviate APAP-induced hepatotoxicity by activating Nrf2 via blocking the binding of Nrf2 with Keap1 and inducing Nrf2 phosphorylation. ERK1/2 and PKC are both critical for regulating the phosphorylation of Nrf2 induced by baicalein or baicalin.
Quantitative estimates of the groundwater depletion and droughts in the Tigris-Euphrates Basin (TEB) can be useful for sustainably managing its water resources. Here, data from the Gravity Recovery ...and Climate Experiment (GRACE) satellite mission are used to infer the monthly changes in the total water storage of the TEB from January 2003 to December 2015. Additionally, the data of altimetry and output from land surface models are used to remove the contributions from lake water changes and other hydrological factors to obtain the total groundwater depletion (TGWD), human-driven groundwater depletion (HGWD), and climate-driven groundwater depletion. We conclude that an alarming rate of decrease in the total water storage and the loss of TGWD have an "accelerating" trend, as the trend during 2007 to 2015 was 3.6 times that during 2003 to 2006. Moreover, the HGWD is 116.09 Gt, which accounts for 98% of the TGWD. Finally, the total storage deficit index (TSDI) is derived from the GRACE data to characterize the drought of the TEB. The results show that TSDI agrees well with the actual drought rather than the Palmer drought severity index (PDSI) and that the TEB has been undergoing a severe drought since September 2007 according to both the TSDI and PDSI. The research in this study provides an effective and unique method for understanding the hydrological processes and sustainable use of water resources in regions or countries with little data, which is essential for more efficient, sustainable, and cross-boundary cooperative water resource management.
Limonoids, as the vital bioactive chemical compounds in genus
plants, have attracted significant attention owing to their exclusive structural characteristics and remarkable biological activity. ...These compounds can be usually classified into two categories, including the ring-intact group and the ring-C-seco group. Benefiting from the development of separation and analysis technology, more than 200 limonoids have been isolated and identified from this genus. There is growing evidence that limonoids from genus
possess diverse pharmacological activities, especially anti-cancer effects, insecticidal activities, and anti-botulism effects. Toosendanin, one of the paramount limonoids, was considered as the pivotal bioactive marker in two medicinal herbs, including
Sieb. et Zucc and
L. In particular, limonoids are found to exhibit non-negligible toxic effects, a finding which needs further research. Besides this, the lack of clinical research data seriously hinders its further development and utilization, and necessary clinical trials should be taken into consideration. In this review, we systematically summarized the phytochemical compounds and their synthesis methods, pharmacological activities, and the structure-activity relationship, pharmacokinetics, and toxicology of genus
-derived limonoids. We believe that this up-to-date review could provide scientific evidence for the application of limonoids as agents beneficial to health in future clinical practice.
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