Gynostemma Pentaphyllum Ameliorates Lipid Metabolic Abnormalities in Diabetic Kidney Disease

Background: Patients with diabetic kidney disease (DKD) were often accompanied with dislipidemia. Gynostemma pentaphyllum can ameliorate insulin resistance and reduce the synthesis of triglycerides and cholesterol, but the underlying mechanism is still unclear. Therefore, we used the network pharmacologic strategies to evaluate potential therapeutic effects and protective mechanisms of gynostemma pentaphyllum on diabetic kidney disease. Methods: Gynostemma pentaphyllum's potential targets were predicted using the TCMSP databases. The pathogenic factors involved in DKD and dislipidemia were screened by the OMIM and Gene Cards databases. The common targets of gynostemma pentaphyllum, DKD and dislipidemia were used to establish a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the potential molecular pathways. Results: The key targets for the therapeutic effects of gynostemma pentaphyllum included IL-6, AKT1, VEGFA, PTGS2, CCL2 and CASP3. Enrichment analysis showed that the underlying mechanism were mainly the involved in inhibition of inflammatory response, negative regulation of apoptotic process and angiogenesis. TNF, PI3K-Akt, and HIF-1 signaling pathways were considered as the key pathways. Conclusion: Gynostemma pentaphyllum played a therapeutic role in DKD complicated with dislipidemia, mainly through influencing inflammation response, apoptosis and angiogenesis.

Genome-Wide Identification of R2R3-MYB Transcription Factors: Discovery of a “Dual-Function” Regulator of Gypenoside and Flavonol Biosynthesis in Gynostemma pentaphyllum

The R2R3-MYB gene family participates in several plant physiological processes, especially the regulation of the biosynthesis of secondary metabolites. However, little is known about the functions of R2R3-MYB genes in Gynostemma pentaphyllum (G. pentaphyllum), a traditional Chinese medicinal herb that is an excellent source of gypenosides (a class of triterpenoid saponins) and flavonoids. In this study, a systematic genome-wide analysis of the R2R3-MYB gene family was performed using the recently sequenced G. pentaphyllum genome. In total, 87 R2R3-GpMYB genes were identified and subsequently divided into 32 subgroups based on phylogenetic analysis. The analysis was based on conserved exon–intron structures and motif compositions within the same subgroup. Collinearity analysis demonstrated that segmental duplication events were majorly responsible for the expansion of the R2R3-GpMYB gene family, and Ka/Ks analysis indicated that the majority of the duplicated R2R3-GpMYB genes underwent purifying selection. A combination of transcriptome analysis and quantitative reverse transcriptase-PCR (qRT-PCR) confirmed that Gynostemma pentaphyllum myeloblastosis 81 (GpMYB81) along with genes encoding gypenoside and flavonol biosynthetic enzymes exhibited similar expression patterns in different tissues and responses to methyl jasmonate (MeJA). Moreover, GpMYB81 could bind to the promoters of Gynostemma pentaphyllum farnesyl pyrophosphate synthase 1 (GpFPS1) and Gynostemma pentaphyllum chalcone synthase (GpCHS), the key structural genes of gypenoside and flavonol biosynthesis, respectively, and activate their expression. Altogether, this study highlights a novel transcriptional regulatory mechanism that suggests that GpMYB81 acts as a “dual-function” regulator of gypenoside and flavonol biosynthesis in G. pentaphyllum.

Gynostemma Pentaphyllum Ameliorates Lipid Metabolic Abnormalities in Diabetic Kidney Disease

Background: Patients with diabetic kidney disease (DKD) were often accompanied with dislipidemia. Gynostemma pentaphyllum can ameliorate insulin resistance and reduce the synthesis of triglycerides and cholesterol, but the underlying mechanism is still unclear. Therefore, we used the network pharmacologic strategies to evaluate potential therapeutic effects and protective mechanisms of gynostemma pentaphyllum on diabetic kidney disease. Methods: Gynostemma pentaphyllum's potential targets were predicted using the TCMSP databases. The pathogenic factors involved in DKD and dislipidemia were screened by the OMIM and Gene Cards databases. The common targets of gynostemma pentaphyllum, DKD and dislipidemia were used to establish a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the potential molecular pathways. Results: The key targets for the therapeutic effects of gynostemma pentaphyllum included IL-6, AKT1, VEGFA, PTGS2, CCL2 and CASP3. Enrichment analysis showed that the underlying mechanism were mainly the involved in inhibition of inflammatory response, negative regulation of apoptotic process and angiogenesis. TNF, PI3K-Akt, and HIF-1 signaling pathways were considered as the key pathways. Conclusion: Gynostemma pentaphyllum played a therapeutic role in DKD complicated with dislipidemia, mainly through influencing inflammation response, apoptosis and angiogenesis.

Gene excavation and expression analysis of CYP and UGT related to the post modifying stage of gypenoside biosynthesis in Gynostemma pentaphyllum (Thunb.) Makino by comprehensive analysis of RNA and proteome sequencing

Previous studies have revealed that gypenosides produced from Gynostemma pentaphyllum (Thunb.) Makino are mainly dammarane-type triterpenoid saponins with diverse structures and important biological activities, but the mechanism of diversity for gypenoside biosynthesis is still unclear. In this study, a combination of isobaric tags for relative and absolute quantification (iTRAQ) proteome analysis and RNA sequencing transcriptome analysis was performed to identify the proteins and genes related to gypenoside biosynthesis. A total of 3925 proteins were identified by proteomic sequencing, of which 2537 were quantified. Seventeen cytochrome P450 (CYP) and 11 uridine 5’-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) candidate genes involved in the side chain synthesis and modification of gypenosides were found. Seven putative CYPs (CYP71B19, CYP77A3, CYP86A7, CYP86A8, CYP89A2, CYP90A1, CYP94A1) and five putative UGTs (UGT73B4, UGT76B1, UGT74F2, UGT91C1 and UGT91A1) were selected as candidate structural modifiers of triterpenoid saponins, which were cloned for gene expression analysis. Comprehensive analysis of RNA sequencing and proteome sequencing showed that some CYPs and UGTs were found at both the transcription and translation levels. In this study, an expression analysis of 7 CYPs and 5 UGTs that contributed to gypenoside biosynthesis and distribution in G. pentaphyllum was performed, providing consistent results that will inspire more future research on vital genes/proteins involved in gypenoside biosynthesis.

Analysis of Serum Biochemical Indexes, Egg Quality, and Liver Transcriptome in Laying Hens Fed Diets Supplemented with Gynostemma pentaphyllum Powder

Gynostemma pentaphyllum (GP), known as “southern ginseng”, can reduce the blood pressure and blood lipid levels. In this study, 300 layer chicks of one day old were divided randomly into three groups (control group (base diet), high addition group (base diet with 1% GP), and low addition group (base diet with 0.5% GP)). After 29 weeks, the growth performance, egg quality, and serum index were determined. Additionally, liver mRNA was identified using RNA-seq to investigate the molecular mechanisms. The results indicated that the serum total cholesterol and triglycerides decreased significantly in the GP addition group. The addition of GP increased the egg weight, Haugh unit and redness (a*) of the egg yolk color, and reduced the yolk cholesterol concentration. Moreover, 95 differentially expressed genes (DEGs) were screened between the control and GP addition group. GO and the KEGG analysis showed that the PPAR pathway was significantly enriched. Five fatty acid metabolism-related genes (FABP3, CYP7A1, ANKRD22, SCD1, and PCK1) were validated by qRT-PCR analysis, which confirmed the tendency of the expression. These DEGs in the PPAR pathway may be the key factors of GP affecting fatty acid metabolism. These results may provide a theoretical basis for further research and new insights into GP as a feed additive.