Comparative analysis and evaluation of wild and cultivated Radix Fici Simplicissimae using an UHPLC-Q-Orbitrap mass spectrometry-based metabolomics approach.

Radix Fici Simplicissimae (RFS) is widely studied, and is in demand for its value in medicines and food products, with increased scientific focus on its cultivation and breeding. We used ultra-high-performance liquid chromatography quadrupole-orbitrap mass spectrometry-based metabolomics to elucidate the similarities and differences in phytochemical compositions of wild Radix Fici Simplicissimae (WRFS) and cultivated Radix Fici Simplicissimae (CRFS). Untargeted metabolomic analysis was performed with multivariate statistical analysis and heat maps to identify the differences. Eighty one compounds were identified from WRFS and CRFS samples. Principal component analysis and orthogonal partial least squares discrimination analysis indicated that mass spectrometry could effectively distinguish WRFS from CRFS. Among these, 17 potential biomarkers with high metabolic contents could distinguish between the two varieties, including seven phenylpropanoids, three flavonoids, one flavonol, one alkaloid, one glycoside, and four organic acids. Notably, psoralen, apigenin, and bergapten, essential metabolites that play a substantial pharmacological role in RFS, are upregulated in WRFS. WRFS and CRFS are rich in phytochemicals and are similar in terms of the compounds they contain. These findings highlight the effects of different growth environments and drug varieties on secondary metabolite compositions and provide support for targeted breeding for improved CRFS varieties.

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.

AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.

A general copper-catalysed enantioconvergent C(sp3)-S cross-coupling via biomimetic radical homolytic substitution.

Although α-chiral C(sp3)-S bonds are of enormous importance in organic synthesis and related areas, the transition-metal-catalysed enantioselective C(sp3)-S bond construction still represents an underdeveloped domain probably due to the difficult heterolytic metal-sulfur bond cleavage and notorious catalyst-poisoning capability of sulfur nucleophiles. Here we demonstrate the use of chiral tridentate anionic ligands in combination with Cu(I) catalysts to enable a biomimetic enantioconvergent radical C(sp3)-S cross-coupling reaction of both racemic secondary and tertiary alkyl halides with highly transformable sulfur nucleophiles. This protocol not only exhibits a broad substrate scope with high enantioselectivity but also provides universal access to a range of useful α-chiral alkyl organosulfur compounds with different sulfur oxidation states, thus providing a complementary approach to known asymmetric C(sp3)-S bond formation methods. Mechanistic results support a biomimetic radical homolytic substitution pathway for the critical C(sp3)-S bond formation step.

Combining lipidomics and efficacy-oriented compatibility revealed that Qi Ge decoction compatibility improved lipid metabolism in hyperlipidemic rats.

The mechanism underlying traditional Chinese medicine (TCM) compatibility is difficult to understand. This study combined lipidomics and efficacy-oriented compatibility to explore underlying compatibility mechanisms of Qi Ge decoction (QG) for improving lipid metabolism in hyperlipidemic rats. The QG was divided into three groups according to the efficacy group strategy: the Huangqi-Gegen (HG), Chenpi (CP), and QG groups. Hyperlipidemic rats were treated with QG, HG, CP, or atorvastatin for 3 weeks. The mass spectral data of widely targeted lipidomics were used to evaluate lipid changes. Principal component analysis and orthogonal partial least squares discriminant analysis were used to assess the lipidomic differences between the groups. MetaboAnalyst 5.0 was used to explore metabolic pathways. Compared with the model group, serum cholesterol, triglyceride, and hepatic steatosis were significantly reduced by QG, whereas HG and CP had no significant effects on these indexes. Lipidomics showed that QG, HG, and CP back-regulated 60, 11, and 14 lipids, respectively. Compared with HG and CP, QG had more metabolic targets in diglycerides, triglycerides, ceramides, and phosphatidylethanolamines. Pathway analysis indicated that QG mainly regulated glycerophospholipid and glycerolipid metabolism. This study provided a new method of combining lipidomics and efficacy-oriented compatibility for exploring the scientific connotation of TCM compatibility.

Enzymatic preparation of Crassostrea oyster peptides and their promoting effect on male hormone production.

ETHNOPHARMACOLOGICAL RELEVANCE: Crassostrea gigas Thunberg and other oysters have been traditionally used in China as folk remedies to invigorate the kidney and as natural aphrodisiacs to combat male impotence. AIM OF THE STUDY: Erectile dysfunction (ED) has become a major health problem for the global ageing population. The aim of this study is therefore to evaluate the effect of peptide-rich preparations from C. gigas oysters on ED and related conditions as increasing evidence suggests that peptides are important bioactive components of marine remedies and seafood. MATERIALS AND METHODS: Crassostrea oyster peptide (COP) preparations COP1, COP2 and COP3 were obtained from C. gigas oysters by trypsin, papain or sequential trypsin-papain digestion, respectively. The contents of testosterone, cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in mice and/or cells were measured by enzyme-linked immunosorbent assays. Real-time PCR was used to assess the expression of genes associated with sex hormone secretion pathways. The model animal Caenorhabditis elegans was also used to analyze the gene expression of a conserved steroidogenic enzyme. In silico analysis of constituent peptides was performed using bioinformatic tools based on public databases. RESULTS: The peptide-rich preparation COP3, in which >95% peptides were <3000 Da, was found to increase the contents of male mouse serum testosterone and cAMP, both of which are known to play important roles in erectile function, and to increase the activity of mouse penile NOS, which is closely associated with ED. Further investigation using mouse Leydig-derived TM3 cells demonstrates that COP3 was able to stimulate the production of testosterone as well as NO, a pivotal mediator of penile erection. Real-time PCR analysis reveals that COP3 up-regulated the expression of Areg and Acvr2b, the genes known to promote sex hormone secretion, but not Fst, a gene involved in suppressing follicle-stimulating hormone release. Furthermore, COP3 was also shown to up-regulate the expression of let-767, a well-conserved C. elegans gene encoding a protein homologous to human 17-ß-hydroxysteroid dehydrogenases. Preliminary bioinformatic analysis using the peptide sequences in COP3 cryptome identified 19 prospective motifs, each of which occurred in more than 10 peptides. CONCLUSIONS: In this paper, Crassostrea oyster peptides were prepared by enzymatic hydrolysis and were found for the first time to increase ED-associated biochemical as well as molecular biology parameters. These results may help to explain the ethnopharmacological use of oysters and provide an important insight into the potentials of oyster peptides in overcoming ED-related health issues.

Antioxidant and anti-aging effects of a sea cucumber protein hydrolyzate and bioinformatic characterization of its composing peptides.

Sea cucumbers have been used as food delicacies and traditional medicine for centuries, and their health benefits are partly attributed to their repertoire of proteins. Peptides prepared from the sea cucumber Apostichopus japonicus are reported to have in vitro antioxidant activities. Here, we investigated the in vivo antioxidant capacity of AjPH, a peptide-rich A. japonicus protein hydrolyzate, and found that AjPH is capable of increasing the survival rate and reducing the reactive oxygen species (ROS) level in the animal model Caenorhabditis elegans under increased oxidative stress induced by paraquat. AjPH is also shown to enhance the antioxidant defense system in paraquat-exposed nematodes, including upregulation of superoxide dismutase and catalase activities and reduction of malondialdehyde contents. To explore underpinning antioxidant mechanisms, cellular and chemical assays were used to demonstrate that AjPH not only reduces ROS accumulation in cells but also directly scavenges DPPH free radicals. Further studies indicate that AjPH can decrease age pigments and extend lifespan but does not reduce food intake, body length and brood size of the nematodes, demonstrating its capacity to delay physiological aging. Using activity-guided fractionation by ultrafiltration and gel filtration, we then isolated antioxidant fractions from AjPH and identified the sequences of their composing peptides, which were subjected to in silico analysis for prospective motifs, physicochemical properties and antioxidant potential. Taken together, our results provide an insight into the nutraceutical potential of the sea cucumber protein hydrolyzate for aging and related conditions and also a basis for future mechanistic studies of individual antioxidant peptides.