Genome-wide analysis of TOPLESS/TOPLESS-RELATED co-repressors and functional characterization of BnaA9.TPL regulating the embryogenesis and leaf morphology in rapeseed.

TOPLESS/TOPLESS-RELATED (TPL/TPR) proteins belong to the Groucho (Gro)/Tup1 family co-repressors and act as broad co-repressors that modulate multiple phytohormone signalling pathways and various developmental processes in plant. However, TPL/TPR co-repressors so far are poorly understood in the rapeseed, one of the world-wide important oilseed crops. In this study, we comprehensively characterized eighteen TPL/TPR genes into five groups in the rapeseed genome. Members of TPL/TPR1/TPR4 and TPR2/TPR3 had close evolutionary relationship, respectively. All TPL/TPRs had similar expression patterns and encode conserved protein domain. In addition, we demonstrated that BnaA9.TPL interacted with all known plant repression domain (RD) sequences, which were distributed in non-redundant 24,238 (22.6 %) genes and significantly enriched in transcription factors in the rapeseed genome. These transcription factors were largely co-expressed with the TPL/TPR genes and involved in diverse pathway, including phytohormone signal transduction, protein kinases and circadian rhythm. Furthermore, BnaA9.TPL was revealed to regulate apical embryonic fate by interaction with Bna.IAA12 and suppression of PLETHORA1/2. BnaA9.TPL was also identified to regulate leaf morphology by interaction with Bna.AS1 (Asymmetric leaves 1) and suppression of KNOTTED-like homeobox genes and YABBY5. These data not only suggest the rapeseed TPL/TPRs play broad roles in different processes, but also provide useful information to uncover more TPL/TPR-mediated control of plant development in rapeseed.

Identification of Novel Regulators of Leaf Senescence Using a Deep Learning Model.

Deep learning has emerged as a powerful tool for investigating intricate biological processes in plants by harnessing the potential of large-scale data. Gene regulation is a complex process that transcription factors (TFs), cooperating with their target genes, participate in through various aspects of biological processes. Despite its significance, the study of gene regulation has primarily focused on a limited number of notable instances, leaving numerous aspects and interactions yet to be explored comprehensively. Here, we developed DEGRN (Deep learning on Expression for Gene Regulatory Network), an innovative deep learning model designed to decipher gene interactions by leveraging high-dimensional expression data obtained from bulk RNA-Seq and scRNA-Seq data in the model plant Arabidopsis. DEGRN exhibited a compared level of predictive power when applied to various datasets. Through the utilization of DEGRN, we successfully identified an extensive set of 3,053,363 high-quality interactions, encompassing 1430 TFs and 13,739 non-TF genes. Notably, DEGRN's predictive capabilities allowed us to uncover novel regulators involved in a range of complex biological processes, including development, metabolism, and stress responses. Using leaf senescence as an example, we revealed a complex network underpinning this process composed of diverse TF families, including bHLH, ERF, and MYB. We also identified a novel TF, named MAF5, whose expression showed a strong linear regression relation during the progression of senescence. The mutant maf5 showed early leaf decay compared to the wild type, indicating a potential role in the regulation of leaf senescence. This hypothesis was further supported by the expression patterns observed across four stages of leaf development, as well as transcriptomics analysis. Overall, the comprehensive coverage provided by DEGRN expands our understanding of gene regulatory networks and paves the way for further investigations into their functional implications.

Natural variation in Fatty Acid 9 is a determinant of fatty acid and protein content.

Soybean is one of the most economically important crops worldwide and an important source of unsaturated fatty acids and protein for the human diet. Consumer demand for healthy fats and oils is increasing, and the global demand for vegetable oil is expected to double by 2050. Identification of key genes that regulate seed fatty acid content can facilitate molecular breeding of high-quality soybean varieties with enhanced fatty acid profiles. Here, we analysed the genetic architecture underlying variations in soybean seed fatty acid content using 547 accessions, including mainly landraces and cultivars from northeastern China. Through fatty acid profiling, genome re-sequencing, population genomics analyses, and GWAS, we identified a SEIPIN homologue at the FA9 locus as an important contributor to seed fatty acid content. Transgenic and multiomics analyses confirmed that FA9 was a key regulator of seed fatty acid content with pleiotropic effects on seed protein and seed size. We identified two major FA9 haplotypes in 1295 resequenced soybean accessions and assessed their phenotypic effects in a field planting of 424 accessions. Soybean accessions carrying FA9H2 had significantly higher total fatty acid contents and lower protein contents than those carrying FA9H1 . FA9H2 was absent in wild soybeans but present in 13% of landraces and 26% of cultivars, suggesting that it may have been selected during soybean post-domestication improvement. FA9 therefore represents a useful genetic resource for molecular breeding of high-quality soybean varieties with specific seed storage profiles.

A cross-species co-functional gene network underlying leaf senescence.

The complex leaf senescence process is governed by various levels of transcriptional and translational regulation. Several features of the leaf senescence process are similar across species, yet the extent to which the molecular mechanisms underlying the process of leaf senescence are conserved remains unclear. Currently used experimental approaches permit the identification of individual pathways that regulate various physiological and biochemical processes; however, the large-scale regulatory network underpinning intricate processes like leaf senescence cannot be built using these methods. Here, we discovered a series of conserved genes involved in leaf senescence in a common horticultural crop (Solanum lycopersicum), a monocot plant (Oryza sativa), and a eudicot plant (Arabidopsis thaliana) through analyses of the evolutionary relationships and expression patterns among genes. Our analyses revealed that the genetic basis of leaf senescence is largely conserved across species. We also created a multi-omics workflow using data from more than 10 000 samples from 85 projects and constructed a leaf senescence-associated co-functional gene network with 2769 conserved, high-confidence functions. Furthermore, we found that the mitochondrial unfolded protein response (UPRmt) is the central biological process underlying leaf senescence. Specifically, UPRmt responds to leaf senescence by maintaining mitostasis through a few cross-species conserved transcription factors (e.g. NAC13) and metabolites (e.g. ornithine). The co-functional network built in our study indicates that UPRmt figures prominently in cross-species conserved mechanisms. Generally, the results of our study provide new insights that will aid future studies of leaf senescence.

Machine learning assisted dynamic phenotypes and genomic variants help understand the ecotype divergence in rapeseed.

Three ecotypes of rapeseed, winter, spring, and semi-winter, have been formed to enable the plant to adapt to different geographic areas. Although several major loci had been found to contribute to the flowering divergence, the genomic footprints and associated dynamic plant architecture in the vegetative growth stage underlying the ecotype divergence remain largely unknown in rapeseed. Here, a set of 41 dynamic i-traits and 30 growth-related traits were obtained by high-throughput phenotyping of 171 diverse rapeseed accessions. Large phenotypic variation and high broad-sense heritability were observed for these i-traits across all developmental stages. Of these, 19 i-traits were identified to contribute to the divergence of three ecotypes using random forest model of machine learning approach, and could serve as biomarkers to predict the ecotype. Furthermore, we analyzed genomic variations of the population, QTL information of all dynamic i-traits, and genomic basis of the ecotype differentiation. It was found that 213, 237, and 184 QTLs responsible for the differentiated i-traits overlapped with the signals of ecotype divergence between winter and spring, winter and semi-winter, and spring and semi-winter, respectively. Of which, there were four common divergent regions between winter and spring/semi-winter and the strongest divergent regions between spring and semi-winter were found to overlap with the dynamic QTLs responsible for the differentiated i-traits at multiple growth stages. Our study provides important insights into the divergence of plant architecture in the vegetative growth stage among the three ecotypes, which was contributed to by the genetic differentiation, and might contribute to environmental adaption and yield improvement.

Functional Teas from Penthorum chinense Pursh Alleviates Ethanol-Induced Hepatic Oxidative Stress and Autophagy Impairment in Zebrafish via Modulating the AMPK/p62/Nrf2/mTOR Signaling Axis.

Penthorum chinense Pursh (PCP), a medicinal and edible plant, is widely used in many clinical liver diseases. Oxidative stress and autophagy impairment play crucial roles in the pathophysiology of alcoholic liver disease (ALD). Therefore, the aim of this study was to elucidate the mechanism of PCP in attenuating ethanol-induced liver injury. The liver-specific transgenic zebrafish larvae (lfabp: EGFP) at three days post-fertilization (3 dpf) were treated with different concentrations of PCP (100, 50 and 25 µg/mL) for 48 h, after soaked in a 350 mM ethanol for 32 h. Whole-mount oil red O, H&E staining and biochemical kits were used to detect fatty liver function and fat accumulation, western blot (WB) and immunofluorescence were used to determine proteins expression, and RT-qPCR was used to further verify the related gene expression. PCP restored zebrafish liver function. Additionally, PCP (as dose-dependent) blocked the expression of cytochrome P450 2E1 (CYP2E1), the production of intracellular reactive oxygen species (ROS) and alleviated liver fat accumulation and oxidative damage. PCP exerted its hepatoprotective function by downregulating the expression of kelch-like ECH-associated protein 1 (Keap1), up-regulating the expression of nucleus factor-E2-related factor 2 (Nrf2) (transferring to the nucleus), and attenuating systemic oxidative stress. Furthermore, PCP reduced the expression of sequestosome 1 (p62/SQSTM1, p62), Atg13, and Beclin 1, up-regulating autophagy signaling pathway. Taken together, the molecular evidence that PCP protected the ethanol-induced hepatic oxidative stress and autophagy impairment through activating AMPK/p62/Nrf2/mTOR signaling axis.

Transposon insertions within alleles of BnaFT.A2 are associated with seasonal crop type in rapeseed.

KEY MESSAGE: We identified two new transposon insertions within the promoter of BnaFT.A2 in addition to an existing 288 bp MITE within the second intron. Each insertion event corresponds to a distinct BnaFT.A2 haplotype and is closely associated with established crop seasonal ecotypes. Florigen, encoded by FLOWERING LOCUS T (FT), plays key roles not only as a flowering hormone, but also a universal growth factor affecting several aspects of plant architecture. In rapeseed, BnaFT.A2 has been revealed as one of the major loci associated with flowering time and different ecotypes. However, it is unclear how allelic variations of BnaFT.A2 affect its function in flowering time regulation and beyond. In this study, we confirmed an existing 288 bp miniature inverted-repeat transposable element (MITE) insertion within the second intron and identified two new insertions within the promoter of BnaFT.A2-a 3971 bp CACTA and a 1079 bp Helitron. Each insertion event corresponds to a distinct BnaFT.A2 haplotype and is closely associated with established crop seasonal ecotypes. These alleles have similar tissue-specific expression patterns but discrete transcriptional patterns tightly associated with rapeseed flowering time and ecotype. RNAi lines and mutants of BnaFT.A2 flowered significantly later than controls. Differentially expressed genes (DEGs), identified in transcriptomic profiling of seedling leaves from two loss-of-function mutants (Bnaft.a2-L1 and Bnaft.a2-L2) compared with controls, indicated significant enrichment for hormone metabolic genes and roles related to plant cell wall synthesis and photosynthesis. Plants with loss-of-function BnaFT.A2 had smaller leaves and lower net photosynthetic rate compared to controls. These findings not only further clarify the genetic basis of flowering time variation and ecotype formation in B. napus, but also provide an additional toolbox for genetic improvement of seasonal adaptation and production.

Integrated network analyses identify MYB4R1 neofunctionalization in the UV-B adaptation of Tartary buckwheat.

A hallmark of adaptive evolution is innovation in gene function, which is associated with the development of distinct roles for genes during plant evolution; however, assessing functional innovation over long periods of time is not trivial. Tartary buckwheat (Fagopyrum tataricum) originated in the Himalayan region and has been exposed to intense UV-B radiation for a long time, making it an ideal species for studying novel UV-B response mechanisms in plants. Here, we developed a workflow to obtain a co-functional network of UV-B responses using data from more than 10,000 samples in more than 80 projects with multi-species and multi-omics data. Dissecting the entire network revealed that flavonoid biosynthesis was most significantly related to the UV-B response. Importantly, we found that the regulatory factor MYB4R1, which resides at the core of the network, has undergone neofunctionalization. In vitro and in vivo experiments demonstrated that MYB4R1 regulates flavonoid and anthocyanin accumulation in response to UV-B in buckwheat by binding to L-box motifs in the FtCHS, FtFLS, and FtUFGT promoters. We used deep learning to develop a visual discrimination model of buckwheat flavonoid content based on natural populations exposed to global UV-B radiation. Our study highlights the critical role of gene neofunctionalization in UV-B adaptation.

Tetramethylpyrazine Protects Endothelial Injury and Antithrombosis via Antioxidant and Antiapoptosis in HUVECs and Zebrafish.

Chuanxiong Rhizoma, the dried rhizome of Ligusticum chuanxiong Hort., is a commonly used drug for promoting blood circulation and dissipating congestion. Tetramethylpyrazine (TMP), the main active ingredient of Ligusticum chuanxiong, has significant antioxidant, anti-inflammatory, and vascular protective effects. However, the protective properties and underlying mechanisms of TMP against endothelial injury-induced insufficient angiogenesis and thrombosis have not been elucidated. Therefore, we aimed to explore the protective effects of TMP on endothelial injury and its antithrombotic effects and study the mechanism. In vitro experiments showed that TMP could alleviate hydrogen peroxide- (H2O2-) induced endothelial injury of human umbilical vein endothelial cells (HUVECs) and the protective mechanism might be related to the regulation of MAPK signaling pathway, and its antioxidative and antiapoptotic effects. In vivo experiments showed that TMP restored PTK787-induced damage to intersegmental vessels (ISVs) in Tg(fli-1: EGFP)y1 transgenic (Flik) zebrafish larvae. Similarly, adrenalin hydrochloride- (AH-) induced reactive oxygen species (ROS) production and thrombosis in AB strain zebrafish were inhibited by TMP. RT-qPCR assay proved that TMP could inhibit the expression of fga, fgb, fgg, f7, and von Willebrand factor (vWF) mRNA to exert an antithrombotic effect. Our findings suggest that TMP can contribute to endothelial injury protection and antithrombosis by modulating MAPK signaling and attenuating oxidative stress and antiapoptosis.

Research progress on the pharmacy of tetramethylpyrazine and its pharmacological activity in cardiovascular and cerebrovascular diseases.

OBJECTIVES: The role and mechanism of tetramethylpyrazine (TMP) in cardio-cerebrovascular diseases (CCVDs), as well as the research of its new formulations are reviewed, which provides a new strategy for the clinical application of TMP. METHODS: We searched the databases including PubMed, Web of Science, Google Scholar and CNKI for relevant literature from 1991 to 2021 by searching for the keywords "TMP", "ligustrazine", "cardiovascular disease" and "nanoformulation". The inclusion criteria are as follows: (1) the literature is an experimental article, (2) the article studies cardiovascular and cerebrovascular-related diseases and (3) the article also includes the pharmacy research of TMP. A total of 160 articles were screened. KEY FINDINGS: TMP has various pharmacological effects in the treatment of many CCVDs, such as atherosclerosis, myocardium, cerebral ischemia, reperfusion injury and hypertension. Its protective effects are mainly related to its anti-platelet activity, protection of endothelial cells, and anti-inflammation, anti-oxidant and anti-apoptotic effects. In addition to pharmacological activity studies, the information of the new formulations is also significant for the further development and utilization of TMP. CONCLUSIONS: Above all, TMP can protect cardio-cerebro vessels, and preparing new formulations can improve its bioavailability, indicating that TMP has broad prospects in the treatment of CCVDs.

Aconiti Lateralis Radix Praeparata lipid-soluble alkaloids alleviates IL-1ß-induced inflammation of human fibroblast-like synoviocytes in rheumatoid arthritis by inhibiting NF-κB and MAPKs signaling pathways and inducing apoptosis.

BACKGROUND: Fuzi lipid-soluble alkaloids (FLA) is the main bioactive components extracted from the traditional Chinese medicine Aconiti Lateralis Radix Praeparata ("Fuzi" in Chinese), which has promising analgesic and anti-inflammatory effects. However, the effects and the underlying mechanisms of FLA on rheumatoid arthritis (RA) have not been studied. The present study aimed to explore the anti-arthritic effects of FLA and its underlying mechanisms. METHODS: To standardize the FLA, UPLC-HR-MS was used for quantitative and qualitative analysis of the representative alkaloids. Cell viability was measured by MTT. The anti-inflammatory activity of FLA was examined by analyzing the expression levels of inflammatory mediators such as TNF-α, IL-6, MMP-1, MMP-3, PGE2, and COX-2 using ELISA and RT-PCR analysis. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of HFLS-RA and analyzed by flow cytometry. Western blot analysis was used to analyze the expression of NF-κB, MAPKs and mitochondrial apoptosis pathway related proteins. RESULTS: FLA had a significant inhibitory effect on the proliferation of HFLS-RA induced by IL-1ß, which was accompanied by decreased expression levels of TNF-α, IL-6, MMP-1, MMP-3, COX-2 and PGE2. Remarkably, FLA inhibited the activation of NF-κB and MAPKs signaling pathways in IL-1ß-induced HFLS-RA, as well as inducing HFLS-RA apoptosis through the mitochondrial apoptosis pathway. CONCLUSIONS: FLA inhibited the expression and synthesis of inflammatory mediators by inhibiting the activation of NF-κB and MAPKs signaling pathways in HFLS-RA, and induced apoptosis of HFLS-RA via the mitochondrial apoptosis pathway.

Effect of Emodin on Hyperlipidemia and Hepatic Lipid Metabolism in Zebrafish Larvae Fed a High-Cholesterol Diet.

Hyperlipidemia (HLP) is a complex pathological condition results from lipid metabolism disorder, which is closely related to obesity, atherosclerosis and steatohepatitis. Emodin (EM), a natural anthraquinone, exhibits prominent hypolipidemic effects. However, its exact mechanism is still unclear. In this study, we successfully established hyperlipidemic zebrafish model induced by 4 % high-cholesterol diet (HCD) for 10 days and explored the anti-hyperlipidemic roles and underlying mechanisms of EM. The results indicated that EM attenuated the mortality and body mass index (BMI) of zebrafish with HLP, and ameliorated abnormal lipid levels involved in TC, TG, LDL-C and HDL-C levels. Besides, EM effectively reduced lipid accumulation in blood vessels and liver, alleviated hepatic histological damage, and inhibited vascular neutrophil inflammation. Finally, the mRNA expression of molecules related to lipid metabolism were studied by using real-time quantitative polymerase chain reaction (RT-qPCR) to investigated the underlying mechanism. Further results found that treatment with EM up-regulated AMPKα, LDLR, ABCA1 and ABCG1, and down-regulated SREBP-2, PCSK9 and HMGCR expression. In conclusion, EM showed a prominent mitigative effect on lipid metabolism disorder in zebrafish larvae with HCD-stimulated HLP, which was associated with the enhancement of LDL-C uptake and reverse cholesterol transport, and inhibition of cholesterol synthesis.

Polygoni Multiflori Radix Praeparata Ethanol Extract Exerts a Protective Effect Against High-Fat Diet Induced Non-Alcoholic Fatty Liver Disease in Mice by Remodeling Intestinal Microbial Structure and Maintaining Metabolic Homeostasis of Bile Acids.

In the prescription of Traditional Chinese Medicine for lipid metabolism, Polygoni Multiflori Radix Preparata (ZhiHeShouWu, RPMP) was widely used. In recent years, RPMP ethanol extract has been reported for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the role of RPMP ethanol extract in the treatment of NAFLD has not been fully elucidated. Therefore, we examined the optimal therapeutic dose of RPMP ethanol extracts. Afterward, a mouse model of non-alcoholic fatty liver induced by a high-fat diet (HFD) was treated with RPMP ethanol extract to further evaluate the mechanism of action of RPMP ethanol extract treatment. And the serum lipid metabolism indexes and liver function indexes showed that the RPMP ethanol extract in the 1.35 g/kg dose group exhibited better therapeutic effects than the 2.70 g/kg dose group. Meanwhile, RPMP ethanol extract can regulate the biochemical indicators of serum and liver to normal levels, and effectively reduce liver steatosis and lipid deposition. RPMP ethanol extract treatment restored HFD-induced disruption of the compositional structure of the intestinal microbial (IM) and bile acids (BAs) pools. And restore the reduced expression of intestinal barrier-related genes caused by HFD administration, which also effectively regulates the expression of genes related to the metabolism of BAs in mice. Thus, RPMP ethanol extract can effectively improve the abnormal lipid metabolism and hepatic lipid accumulation caused by HFD, which may be related to the regulation of IM composition, maintenance of intestinal barrier function, and normal cholesterol metabolism in the body.

Advances of natural activators for Nrf2 signaling pathway on cholestatic liver injury protection: a review.

Cholestasis is a common manifestation of obstruction of bile flow in various liver diseases. If the bile acid accumulation is not treated in time, it will further lead to hepatocyte damage, liver fibrosis and ultimately to cirrhosis, which seriously affects human life. The pathogenesis of cholestatic liver injury is very complicated, mainly including oxidative stress and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor responsible for upregulating expression of various genes with cytoprotective functions. Nrf2 activation has been proved to inhibit oxidative stress and inflammatory reaction, modulate bile acid homeostasis, and alleviate fibrosis during cholestasis. Therefore, Nrf2 emerges as a potential therapeutic target for cholestatic liver injury. In recent years, natural products with various biological activities including anti-inflammatory, anti-oxidant, anti-tumor and anti-fibrotic effects have received growing attention for being hepatoprotective agents. Natural products like asiatic acid, diosmin, rutin, and so forth have shown significant potential in activating Nrf2 pathway which can lead to attenuate cholestatic liver injury. Therefore, this paper emphasizes the effect of Nrf2 signaling pathway on alleviating cholestasis, and summarizes recent evidence about natural Nrf2 activators with hepatoprotective effect in various models of cholestatic liver injury, thus providing theoretical reference for the development of anti-cholestatic drug.

Hepatoprotective effect of forsythiaside a against acetaminophen-induced liver injury in zebrafish: Coupling network pharmacology with biochemical pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Forsythiae Fructus, the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a commonly used traditional Chinese medicine and possesses various pharmacological activities, including anti-inflammation, anti-oxidant and liver protection. AIM OF THE STUDY: Although acetaminophen (APAP) has been frequently used for its antipyretic and analgesic effects, it leads to liver injury at an overdose or long-term medication. Forsythiaside A (FA), the principal active component of Forsythiae Fructus, exerts prominent antioxidant, anti-inflammatory and hepatoprotective effects. However, the protective property and underlying mechanism of FA against APAP challenge have not yet been elucidated. Therefore, we aimed to explore the hepatoprotective effect and action mechanism of FA against APAP-induced liver injury in zebrafish. MATERIALS AND METHODS: In this study, liver-specific transgenic zebrafish larvae (lfabp: EGFP) were used to investigate the protective effect of FA against overdose APAP exposure. The liver phenotype, morphological and biochemical assessments were carried out to evaluate the hepatoprotective effect of FA. Network pharmacology and molecular docking study were conducted to analyze the potential targets of FA in the treatment of APAP-induced liver injury. Finally, the mechanism of action was verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: The liver phenotype, morphological and biochemical assessments indicated that FA could mitigate APAP-triggered liver injury. Network pharmacology and molecular docking analysis indicated that the protective effect of FA might be related to the regulation of targets tumor necrosis factor (TNF), matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 2 (MMP2), and phosphatidylinositol 3-kinase (PI3K). PCR results confirmed that FA could reverse the progressive alterations of genes involving in extracellular matrix remolding and PI3K/AKT-mediated apoptosis signaling pathway. CONCLUSIONS: Our results indicated that FA could mitigate APAP-induced liver injury through modulating the remolding of extracellular matrix and PI3K/AKT-mediated apoptosis.

The pharmacological activity of berberine, a review for liver protection.

Liver plays an important role in bile synthesis, metabolic function, degradation of toxins, new substances synthesis in body. However, hepatopathy morbidity and mortality are increasing year by year around the world, which become a major public health problem. Traditional Chinese medicine (TCM) has a prominent role in the treatment of liver diseases due to its definite curative effect and small side effects. The hepatoprotective effect of berberine has been extensively studied, so we comprehensively summarize the pharmacological activities of lipid metabolism regulation, bile acid adjustment, anti-inflammation, oxidation resistance, anti-fibrosis and anti-cancer and so on. Besides, the metabolism and toxicity of berberine and its new formulations to improve its effectiveness are expounded, providing a reference for the safe and effective clinical use of berberine.

An Overview of the Mechanism of Penthorum chinense Pursh on Alcoholic Fatty Liver.

Alcohol liver disease (ALD) caused by excessive alcohol consumption is a progressive disease, and alcohol fatty liver disease is the primary stage. Currently, there is no approved drug for its treatment. Abstinence is the best way to heal, but patients' compliance is poor. Unlike other chronic diseases, alcohol fatty liver disease is not caused by nutritional deficiencies; it is caused by the molecular action of ingested alcohol and its metabolites. More and more studies have shown the potential of Penthorum chinense Pursh (PCP) in the clinical use of alcohol fatty liver treatment. The purpose of this paper is to reveal from the essence of PCP treatment of alcohol liver mechanism mainly by the ethanol dehydrogenase (ADH) and microsomal ethanol oxidation system-dependent cytochrome P4502E1 (CYP2E1) to exert antilipogenesis, antioxidant, anti-inflammatory, antiapoptotic, and autophagy effects, with special emphasis on its mechanisms related to SIRT1/AMPK, KEAP-1/Nrf2, and TLR4/NF-κB. Overall, data from the literature shows that PCP appears to be a promising hepatoprotective traditional Chinese medicine (TCM).

Forsythiae Fructuse water extract attenuates liver fibrosis via TLR4/MyD88/NF-κB and TGF-ß/smads signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Forsythiae Fructuse water extract (FSE) is a water-soluble component extracted from the traditional Chinese medicine Forsythiae Fructuse (The fruit of Forsythia suspensa (Thunb.) Vahl) usually used to treat inflammatory diseases. However, little is known about the therapeutic effect of FSE on liver fibrosis. AIM OF THE STUDY: The purpose of our study was to investigate the therapeutic effect of FSE on liver fibrosis and reveal the underlying mechanism. MATERIALS AND METHODS: Liver fibrosis model was established by subcutaneous injection of olive oil containing 40% CCl4. Rat liver tissue morphologic pathology was investigated by using HE staining, Masson staining and Sirius red staining. Several biochemical markers including liver (ALT, AST, AKP, γ-GT), fibrosis (HA, LN, PC III, Col IV) and inflammation (IL-6, IL-1ß, TNF-α) were determined by using Elisa kits. Immunohistochemistry was used to observe the distribution of α-SMA and COL1 in liver tissue. Effects of FSE on inflammatory pathway (TLR4/MyD88/NF-κB) and fibrotic pathway (TGF-ß/smads) were detected by western blot and qPCR. RESULTS: The results showed that hepatic histopathological injury, abnormal liver function, fibrosis and inflammation induced by CCl4 were improved by FSE (2.5, 5 g/kg). Immunohistochemistry and western blot results indicated that the expression of α-SMA and COL1 in liver tissue was inhibited by FSE (2.5, 5 g/kg). Western blot and qPCR results further proved that FSE (2.5, 5 g/kg) inhibited the transduction of TLR4/MyD88/NF-κB and TGF-ß/smads signaling pathways. CONCLUSION: FSE can inhibit the expression of inflammatory factors and fibrotic cytokines, reduce liver injury, and inhibit the development of liver fibrosis through TLR4/MyD88/NF-κB and TGF-ß/smads signaling pathways.

A Candidate Drug for Nonalcoholic Fatty Liver Disease: A Review of Pharmacological Activities of Polygoni Multiflori Radix.

Nonalcoholic fatty liver disease, a type of metabolic syndrome, continues to rise globally. Currently, there is no approved drug for its treatment. Improving lifestyle and exercise can alleviate symptoms, but patients' compliance is poor. More and more studies have shown the potential of Polygoni Multiflori Radix (PMR) in the treatment of NAFLD and metabolic syndrome. Therefore, this paper reviews the pharmacological effects of PMR and its main chemical components (tetrahydroxystilbene glucoside, emodin, and resveratrol) on NAFLD. PMR can inhibit the production of fatty acids and promote the decomposition of triglycerides, reduce inflammation, and inhibit the occurrence of liver fibrosis. At the same time, it maintains an oxidation equilibrium status in the body, to achieve the therapeutic purpose of NAFLD and metabolic syndrome. Although more standardized studies and clinical trials are needed to confirm its efficacy, PMR may be a potential drug for the treatment of NAFLD and its complications. However, the occurrence of adverse reactions of PMR has affected its extensive clinical application. Therefore, it is necessary to further study its toxicity mechanism, enhance efficacy and control toxicity, and even reduce toxicity, which will contribute to the safe clinical use of PMR.

Transposon insertions within alleles of BnaFLC.A10 and BnaFLC.A2 are associated with seasonal crop type in rapeseed.

In Brassicaceae, the requirement for vernalization is conferred by high expression of FLOWERING LOCUS C (FLC). The expression of FLC is known to be repressed by prolonged exposure to cold. Rapeseed (Brassica napus L.) cultivars can be classified into spring, winter, and semi-winter crop types, depending on their respective vernalization requirements. In addition to two known distinct transposon insertion events, here we identified a 4.422 kb hAT and a 5.625 kb long interspersed nuclear element transposon insertion within BnaFLC.A10, and a 810 bp miniature inverted-repeat transposable element (MITE) in BnaFLC.A2. Quantitative PCR demonstrated that these insertions lead to distinct gene expression patterns and contribute differentially to the vernalization response. Transgenic and haplotype analysis indicated that the known 621 bp MITE in the promoter region of BnaFLC.A10 is a transcriptional enhancer that appears to be the main determinant of rapeseed vernalization, and has contributed to the adaptation of rapeseed in winter cultivation environments. In the absence of this transposon insertion, the functional allele of BnaFLC.A2 is a major determinant of vernalization demand. Thus, the combination of BnaFLC.A10 carrying the 621 bp MITE insertion and a functional BnaFLC.A2 appears necessary to establish the winter rapeseed crop phenotype.