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Solid-State Fermentation With Aspergillus cristatus Enhances the Protopanaxadiol- and Protopanaxatriol-Associated Skin Anti-aging Activity of Panax notoginseng.

ABSTRACT: A metabolomics approach was used to profile metabolites of Panax notoginseng fermented with Aspergillus cristatus in two ways, liquid-state fermentation (LF-P) and solid-state fermentation (SSF-P) and examine metabolite markers representing antioxidant activity and skin anti-aging. Protopanaxadiol (PPD) and protopanaxatriol (PPT) contents were higher in SSF-P than in LF-P and showed a multiplicative increase over the fermentation period of four days. PPD and PPT levels also correlated with antioxidant and anti-aging effects in skin, based on the mRNA expression of dermal extracellular matrix components. In the bioactivity validation assays, PPD and PPT significantly improved the expression of type-I collagen, fibrillin-1, and elastin in human dermal fibroblasts from both young and old subjects; these were comparable with the effects of the SSF-P extracts. Overall, our results suggest that changes in the metabolites of P. notoginseng fermented with A. cristatus enhance the quality and availability of bioactive compounds associated with skin anti-aging.

SUBMITTER: Lee S

PROVIDER: S-EPMC8718098 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Integrated Chemical and Transcriptomic Analysis Reveals the Distribution of Protopanaxadiol- and Protopanaxatriol-Type Saponins in Panax notoginseng.

Project description:Panax notoginseng is famous for its important therapeutic effects and commonly used worldwide. The active ingredients saponins have distinct contents in different tissues of P. notoginseng, and they may be related to the expression of key genes in the synthesis pathway. In our study, high-performance liquid chromatography results indicated that the contents of protopanaxadiol-(Rb1, Rc, Rb2, and Rd) and protopanaxatriol-type (R1, Rg1, and Re) saponins in below ground tissues were higher than those in above ground tissues. Clustering dendrogram and PCA analysis suggested that the below and above ground tissues were clustered into two separate groups. A total of 482 and 882 unigenes were shared in the below and above ground tissues, respectively. A total of 75 distinct expressions of CYPs transcripts (RPKM ? 10) were detected. Of these transcripts, 38 and 37 were highly expressed in the below ground and above ground tissues, respectively. RT-qPCR analysis showed that CYP716A47 gene was abundantly expressed in the above ground tissues, especially in the flower, whose expression was 31.5-fold higher than that in the root. CYP716A53v2 gene was predominantly expressed in the below ground tissues, especially in the rhizome, whose expression was 20.1-fold higher than that in the flower. Pearson's analysis revealed that the CYP716A47 expression was significantly correlated with the contents of ginsenoside Rc and Rb2. The CYP716A53v2 expression was associated with the saponin contents of protopanaxadiol-type (Rb1 and Rd) and protopanaxatriol-type (R1, Rg1, and Re). Results indicated that the expression patterns of CYP716A47 and CYP716A53v2 were correlated with the distribution of protopanaxadiol-type and protopanaxatriol-type saponins in P. notoginseng. This study identified the pivotal genes regulating saponin distribution and provided valuable information for further research on the mechanisms of saponin synthesis, transportation, and accumulation.

| S-EPMC6099965 | biostudies-literature

Highly Regioselective Biotransformation of Protopanaxadiol-type and Protopanaxatriol-type Ginsenosides in the Underground Parts of <i>Panax notoginseng</i> to 18 Minor Ginsenosides by <i>Talaromyces flavus</i>.

Project description:The transformation of major ginsenosides to minor ginsenosides by microorganisms was considered to be an environmentally friendly method. Compared with GRAS (generally recognized as safe) strains, non-food-grade microorganisms could transform polar ginsenosides to various minor ginsenosides. In this study, Talaromyces flavus screened from the P. notoginseng rhizosphere was capable of transforming PPD-type and PPT-type ginsenosides in the underground parts of P. notoginseng to 18 minor ginsenosides. The transformation reactions invovled deglycosylation, epimerization, and dehydration. To the best of our knowledge, this transformation characteristic of T. flavus was first reported in fungi. Its crude enzyme can efficiently hydrolyze the outer glucose linked to C-20 and C-3 in major ginsenosides Rb1, Rb2, Rb3, Rc, Rd, and 20(S)-Rg3 within 48 h. The transformation of major ginsenosides to minor ginsenosides by T. flavus will help raise the functional and economic value of P. notoginseng.

| S-EPMC9089366 | biostudies-literature

Potential Dissociative Glucocorticoid Receptor Activity for Protopanaxadiol and Protopanaxatriol.

Project description:Glucocorticoids are steroid hormones that regulate inflammation, growth, metabolism, and apoptosis via their cognate receptor, the glucocorticoid receptor (GR). GR, acting mainly as a transcription factor, activates or represses the expression of a large number of target genes, among them, many genes of anti-inflammatory and pro-inflammatory molecules, respectively. Transrepression activity of glucocorticoids also accounts for their anti-inflammatory activity, rendering them the most widely prescribed drug in medicine. However, chronic and high-dose use of glucocorticoids is accompanied with many undesirable side effects, attributed predominantly to GR transactivation activity. Thus, there is a high need for selective GR agonist, capable of dissociating transrepression from transactivation activity. Protopanaxadiol and protopanaxatriol are triterpenoids that share structural and functional similarities with glucocorticoids. The molecular mechanism of their actions is unclear. In this study applying induced-fit docking analysis, luciferase assay, immunofluorescence, and Western blot analysis, we showed that protopanaxadiol and more effectively protopanaxatriol are capable of binding to GR to activate its nuclear translocation, and to suppress the nuclear factor-kappa beta activity in GR-positive HeLa and HEK293 cells, but not in GR-low level COS-7 cells. Interestingly, no transactivation activity was observed, whereas suppression of the dexamethasone-induced transactivation of GR and induction of apoptosis in HeLa and HepG2 cells were observed. Thus, our results indicate that protopanaxadiol and protopanaxatriol could be considered as potent and selective GR agonist.

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20(S)-Protopanaxadiol Saponins Mainly Contribute to the Anti-Atherogenic Effects of Panax notoginseng in ApoE Deficient Mice.

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| S-EPMC6832312 | biostudies-literature

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Project description:Panax notoginseng saponins (PNS) are the main active components of Panax notoginseng. But after oral administration, they need to be converted into rare ginsenosides by human gut microbiota and gastric juice before they can be readily absorbed into the bloodstream and exert their effects. The sources of rare ginsenosides are extremely limited in P. notoginseng and other medical plants, which hinders their application in functional foods and drugs. Therefore, the production of rare ginsenosides by the transformation of PNS using Aspergillus fumigatus was studied in this research. During 50 days at 25 ℃ and 150 rpm, A. fumigatus transformed PNS to 14 products (1-14). They were isolated by varied chromatographic methods, such as silica gel column chromatography, Rp-C18 reversed phase column chromatography, semi-preparative HPLC, Sephadex LH-20 gel column chromatography, and elucidated on the basis of their 1H-NMR, 13C-NMR and ESIMS spectroscopic data. Then, the transformed products (1-14) were isolated and identified as Rk3, Rh4, 20 (R)-Rh1, 20 (S)-Protopanaxatriol, C-K, 20 (R)-Rg3, 20 (S)-Rg3, 20 (S)-Rg2, 20 (R)-R2, Rk1, Rg5, 20 (S)-R2, 20 (R)-Rg2, and 20 (S)-I, respectively. In addition, all transformed products (1-14) were tested for their antimicrobial activity. Among them, compounds 5 (C-K) and 7 [20 (S)-Rg3] showed moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 6.25, 1.25 μg/mL and 1.25, 25 μg/mL, respectively. This study lays the foundation for production of rare ginsenosides.

| S-EPMC11319572 | biostudies-literature

Comparative genomic and transcriptomic analyses of the Fuzhuan brick tea-fermentation fungus Aspergillus cristatus.

Project description:Aspergillus cristatus is the dominant fungus involved in the fermentation of Chinese Fuzhuan brick tea. Aspergillus cristatus is a homothallic fungus that undergoes a sexual stage without asexual conidiation when cultured in hypotonic medium. The asexual stage is induced by a high salt concentration, which completely inhibits sexual development. The taxon is therefore appropriate for investigating the mechanisms of asexual and sexual reproduction in fungi. In this study, de novo genome sequencing and analysis of transcriptomes during culture under high- and low-osmolarity conditions were performed. These analyses facilitated investigation of the evolution of mating-type genes, which determine the mode of sexual reproduction, in A. cristatus, the response of the high-osmolarity glycerol (HOG) pathway to osmotic stimulation, and the detection of mycotoxins and evaluation of the relationship with the location of the encoding genes.The A. cristatus genome comprised 27.9 Mb and included 68 scaffolds, from which 10,136 protein-coding gene models were predicted. A phylogenetic analysis suggested a considerable phylogenetic distance between A. cristatus and A. nidulans. Comparison of the mating-type gene loci among Aspergillus species indicated that the mode in A. cristatus differs from those in other Aspergillus species. The components of the HOG pathway were conserved in the genome of A. cristatus. Differential gene expression analysis in A. cristatus using RNA-Seq demonstrated that the expression of most genes in the HOG pathway was unaffected by osmotic pressure. No gene clusters associated with the production of carcinogens were detected.A model of the mating-type locus in A. cristatus is reported for the first time. Aspergillus cristatus has evolved various mechanisms to cope with high osmotic stress. As a fungus associated with Fuzhuan tea, it is considered to be safe under low- and high-osmolarity conditions.

| S-EPMC4895823 | biostudies-literature

Comparative genomic and transcriptomic analyses of the Fuzhuan brick tea-fermentation fungus Aspergillus cristatus

Project description:The purpose of this study is to find the differently expressed genes in Aspergillus cristatus at different osmotic pressure.

2016-09-01 | GSE65662 | GEO

Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells.

Project description:BACKGROUND AND PURPOSE: Ginsenosides are used widely for medicinal purposes, but the mechanisms of their action are still unclear, although there is some evidence that these effects are mediated by nuclear receptors. Here we examined whether two metabolites of ginsenoside, protopanaxadiol (g-PPD) and protopanaxatriol (g-PPT), could modulate endothelial cell functions through the glucocorticoid receptor (GR) and oestrogen receptor (ER). EXPERIMENT APPROACHES: The effects of g-PPD and g-PPT on intracellular calcium ion concentration ([Ca(2+)](i)) and nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) were measured using Fura-2-acetoxymethyl ester, 4-amino-5-methylamino-2',7'-difluorofluorescein and Griess reagent. Effects on expression of GR and ER isoforms in HUVECs were determined using reverse transcriptase-/real-time PCR and immunocytochemistry. Phosphorylation of endothelial NO synthase (eNOS) was assessed by Western blotting. RESULTS: Ginsenoside protopanaxadiol and g-PPT increased [Ca(2+)](i), eNOS phosphorylation and NO production in HUVECs, which were inhibited by the GR antagonist, RU486, the ER antagonist, ICI 182,780 and siRNA targeting GR or ERbeta. The NO production was Ca(2+)-dependent and the [Ca(2+)](i) elevation in HUVECs resulted from both intracellular Ca(2+) release and extracellular Ca(2+) influx. CONCLUSIONS AND IMPLICATIONS: Ginsenoside protopanaxadiol and g-PPT were functional ligands for both GR and ERbeta, through which these ginsenoside metabolites exerted rapid, non-genomic effects on endothelial cells.

| S-EPMC2697710 | biostudies-literature

Phased secondary small interfering RNAs in Panax notoginseng

Project description:Recent results demonstrated that either non-coding or coding genes generate phased secondary small interfering RNAs (phasiRNAs) guided by specific miRNAs. Till now, there is no studies for phasiRNAs in Panax notoginseng (Burk.) F.H. Chen (P. notoginseng), an important traditional Chinese herbal medicinal plant species. Here we performed a genome-wide discovery of phasiRNAs and its host PHAS loci in P. notoginseng by analyzing small RNA sequencing profiles. Degradome sequencing profile was used to identify the trigger miRNAs of these phasiRNAs and potential targets of phasiRNAs. We also used RLM 5'-RACE to validate some of the identified phasiRNA targets. After analyzing 24 small RNA sequencing profiles of P. notoginseng, 204 and 90 PHAS loci that encoded 21 and 24 nucleotide (nt) phasiRNAs were identified. Furthermore, we found that phasiRNAs produced from some pentatricopeptide repeat-contain (PPR) genes target another layer of PPR genes as validated by both the degradome sequencing profile and RLM 5'-RACE analysis. We also find that miR171 with 21 nt triggers the 21 nt phasiRNAs from its conserved targets. We validated that some phasiRNAs generated from PPRs are functional by targeting other PPRs in trans. These results provide the first set of PHAS loci and phasiRNAs in P. notoginseng, and enhance our understanding of PHAS in plants.

2018-02-14 | GSE98118 | GEO

Study on the hypnotic effect of rare protopanaxadiol-type and protopanaxatriol-type ginsenosides.

Project description:Ginsenosides, as major active components of ginseng, possess various pharmacological activities, including anti-tumor, anti-diabetic and hypotensive effects. However, the sedative and hypnotic effect of ginsenosides and the involved mechanism remain unclear. In the present study, the hypnotic effect of rare protopanaxadiol-type (PD) ginsenosides, consisting of Rg3, Rk1, Rg5, and protopanaxatriol-type (PT) ginsenosides, consisting of Rh1, Rk3, Rh4, was investigated and compared in rodent models through behavioral pharmacology methods. Both rare PD and PT ginsenosides decreased spontaneous locomotion activity in normal mice and reduced sleep latency, and extended sleep duration in pentobarbital-treated mice. Moreover, PD and PT ginsenosides attenuated the insomnia induced by caffeine in mice. These hypnotic effects of PD and PT ginsenosides were potentiated by 5-hydroxytryptophan (5-HTP), a precursor of serotonin, and inhibited by p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. Flumazenil (FLU, a specific gamma aminobutyric acid (GABA) antagonist) also impaired the hypnotic effect of both PD and PT ginsenosides. The aforementioned results indicated that PD and PT ginsenosides exhibit sedative and hypnotic activity, and PT ginsenosides show higher activity than PD ginsenosides at high doses (96 mg kg-1). Furthermore, the bioactivity of these two types of ginsenosides might be mediated via the serotonergic and GABAergic systems.

| S-EPMC9065700 | biostudies-literature

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