Digestive characteristics of Gastrodia elata Blume polysaccharide and related impacts on human gut microbiota in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume is a traditional Chinese medicine with the effects of improving the deficiency of the body and maintaining health, and polysaccharide (GEP) is one of the effective ingredients to play these activities of G. elata. Traditionally, G. elata is orally administered, so the activities of GEP are associated with digestive and intestinal metabolism. However, the digestive behavior of GEP and its effects on the human gut microbiota are unclear and need to be fully studied. AIM OF THE STUDY: This study aimed to investigate the changes in structural characteristics of GEP during digestion and the related impacts of its digestive product on gut microbiota in human fecal fermentation, and to explain the beneficial mechanism of GEP on human health from the perspective of digestive characteristics and "gut" axis. MATERIALS AND METHODS: The changes of reducing sugars, free monosaccharides and physicochemical properties of GEP during digestion were investigated by GPC, HPLC, FT-IR, CD, NMR, SEM, and TGA. Moreover, polysaccharide consumption, pH value changes, SCFAs production, and changes in gut microbiota during fermentation were also discussed. RESULTS: During digestion of GEP, glucose was partially released causing a decrease in molecular weight, and a change in monosaccharide composition. In addition, the characteristics of GEP before and after digestion, including configuration, morphology, and stability, were different. The digestive product of GEP was polysaccharide (GEP-I), which actively participated in the fecal fermentation process. As the fermentation time increased, the utilization of GEP-I by the microbiota gradually increased. The abundance of probiotics such as Bifidobacterium, Collinsella, Prevotella, and Faecalibacterium was significantly increased, and the abundance of pathogenic Shigella, Dorea, Desulfovibrio, and Blautia was significantly inhibited, thereby suggesting that GEP has the potential to maintain human health through the "gut" axis. In addition, the beneficial health effects of GEP-I have also been observed in the influence of microbial metabolites. During the fermentation of GEP-I, the pH value gradually decreased, and the contents of beneficial metabolites such as acetic acid, propionic acid, and caproic acid significantly increased. CONCLUSION: The structure of GEP changed significantly during digestion, and its digestive product had the potential to maintain human health by regulating gut microbiota, which may be one of the active mechanisms of GEP.

Gastrodia elata polysaccharide alleviates Parkinson's disease via inhibiting apoptotic and inflammatory signaling pathways and modulating the gut microbiota.

Parkinson's disease (PD) is a common, chronic, and progressive degenerative disease of the central nervous system for which there is no effective treatment. Gastrodia elata is a well-known food and medicine homologous resource with neuroprotective potential. Gastrodia elata polysaccharide (GEP), which is a highly active and safe component in Gastrodia elata, is an important ingredient in the development of functional products. In this study, GEP was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice over 3 weeks to investigate its neuroprotective effects. The results showed that GEP significantly alleviated the motor dysfunction of PD mice, inhibited the accumulation of α-synuclein, and reduced the loss of dopaminergic neurons in the brain. Moreover, GEP increased the Bcl-2/Bax ratio and decreased the cleaved-caspase-3 level, suggesting that GEP may ameliorate PD by preventing MPTP-induced mitochondrial apoptosis. GEP also significantly inhibited the increase of GFAP and decreased the levels of TNF-α, IL-1ß, and IL-6 in the brain of PD mice, which may be the result of the inhibition of neuroinflammation by the inactivation of the TLR4/NF-κB pathway. Furthermore, the neuroprotective effects of GEP involve the gut-brain axis, as it has been shown that GEP regulated the dysbiosis of PD-related gut microbiota such as Akkermansia, Lactobacillus, Bacteroides, Prevotella, and Faecalibacterium, increased the content of microbial metabolites SCFAs in the colon and increased the level of occludin that repairs the intestinal barrier of PD mice. In conclusion, this study is expected to provide a theoretical basis for the development and application of functional products with GEP from the perspective of neuroprotective effects.

The Integration of the Metabolome and Transcriptome for Dendrobium nobile Lindl. in Response to Methyl Jasmonate.

Dendrobium nobile Lindl., as an endangered medicinal plant within the genus Dendrobium, is widely distributed in southwestern China and has important ecological and economic value. There are a variety of metabolites with pharmacological activity in D. nobile. The alkaloids and polysaccharides contained within D. nobile are very important active components, which mainly have antiviral, anti-tumor, and immunity improvement effects. However, the changes in the compounds and functional genes of D. nobile induced by methyl jasmonate (MeJA) are not clearly understood. In this study, the metabolome and transcriptome of D. nobile were analyzed after exposure to MeJA. A total of 377 differential metabolites were obtained through data analysis, of which 15 were related to polysaccharide pathways and 35 were related to terpenoids and alkaloids pathways. Additionally, the transcriptome sequencing results identified 3256 differentially expressed genes that were discovered in 11 groups. Compared with the control group, 1346 unigenes were differentially expressed in the samples treated with MeJA for 14 days (TF14). Moreover, the expression levels of differentially expressed genes were also significant at different growth and development stages. According to GO and KEGG annotations, 189 and 99 candidate genes were identified as being involved in terpenoid biosynthesis and polysaccharide biosynthesis, respectively. In addition, the co-expression analysis indicated that 238 and 313 transcription factors (TFs) may contribute to the regulation of terpenoid and polysaccharide biosynthesis, respectively. Through a heat map analysis, fourteen terpenoid synthetase genes, twenty-three cytochrome P450 oxidase genes, eight methyltransferase genes, and six aminotransferase genes were identified that may be related to dendrobine biosynthesis. Among them, one sesquiterpene synthase gene was found to be highly expressed after the treatment with MeJA and was positively correlated with the content of dendrobine. This study provides important and valuable metabolomics and transcriptomic information for the further understanding of D. nobile at the metabolic and molecular levels and provides candidate genes and possible intermediate compounds for the dendrobine biosynthesis pathway, which lays a certain foundation for further research on and application of Dendrobium.

Highly specific colon-targeted transformable capsules containing indomethacin immediate-release pellets for colon cancers therapy.

Generally, definite intestine targeting and immediate drug releasing are both important for the treatment of colon cancer via oral administration of anti-cancer drugs. We developed a highly specific oral colon-targeted pulsatile capsule, based on the effective enzyme-responsive 'pulse plug', which can be degraded under mannanase abundant in colon. Indomethacin (IN) solid dispersion immediate-release pellets were filled in an insoluble capsule body, a guar gum-lactose-hydroxypropyl methylcellulose (HPMC) composed tablet was embedded on the top of capsule as the 'pulse plug', and then covered by enteric soluble cap. In this study, the influence of the proportion of guar gum/lactose/HPMC, the viscosity of HPMC, and the tablet weight on the degradation behaviour of the plug tablet was investigated. The drug-releasing profiles of those pulsatile capsules in different simulated colon medium verified the 'pulse plug' could realise the colon-targeted pulsatile drug-releasing. Furthermore, the rabbit pharmacokinetic experiments showed that the in vivo time lag of drug loaded pulsatile capsules was significantly extended to 5.61 ± 0.08 h (p<.01), compared with that (0.33 ± 0.47 h) of the marketed tablets (YUNPENG®). These results indicated that colon-targeted pulsatile capsules would be effective oral delivering system for colon cancers therapy.