Prebiotic stachyose inhibits PRDX5 activity and castration-resistant prostate cancer development.

Stachyose (STA) is a prebiotic with poor oral bioavailability. In this study, we developed stachyose caproate (C6-STA), as a novel STA derivative, to demonstrate its high adsorption rate via oral administration. Pharmacokinetic analysis reveals that after absorption, the STA derived from C6-STA reaches its highest peak in the blood, liver, and kidney at 20 min, 30 min, and 12-24 h, with approximate levels of 1200 µg/mL, 0.14 µg/mL, and 0.2-0.3 µg/mL, respectively. In addition, the accumulation of STA in prostate tissues of mice with castration-resistant prostate cancer (CRPC) (1.75 µg/mg) is 10-fold higher than that in normal prostate tissues (0.14 µg/mg). The analysis also reveals that C6-STA has t1/2 of 12.8 h and Tmax of 0.25 h, indicating that it has the potential to be used as a promising drug in clinical practice. The toxicological evaluation shows no obvious side effects of C6-STA in mice administered with a 0.2 g/kg intragastric dose. Pharmacodynamic analysis and mechanism investigation of C6-STA show its ability to inhibit peroxiredoxin 5 (PRDX5) enzyme activity, disrupt PRDX5-nuclear factor erythroid 2-related factor 2 (NRF2) interaction, and decrease NAD(P)H quinone dehydrogenase 1 (NQO1) levels. NQO1 decrease further causes the accumulation of quinone radicals, which ultimately leads to the apoptosis of LNCaP cell-derived drug-tolerant persister (DTP) cells and slows CRPC progression. Our study discovered the anti-tumor activity of stachyose and shows that prebiotics have biological functions in vivo besides in the gut. Further investigation of C6-STA, especially in CRPC patients, is warranted.

Identification of PRDX5 as A Target for The Treatment of Castration-Resistant Prostate Cancer.

Treatment of castration-resistant prostate cancer (CRPC) is a long-standing clinical challenge. Traditionally, CRPC drugs work by either reducing dihydrotestosterone biosynthesis or blocking androgen receptor (AR) signaling. Here it is demonstrated that AR inhibitor treatment gives rise to a drug-tolerant persister (DTP) state. The thioredoxin/peroxiredoxin pathway is up-regulated in DTP cells. Peroxiredoxin 5 (PRDX5) promotes AR inhibitor resistance and CRPC development. Inhibition of PRDX5 suppresses DTP cell proliferation in culture, dampens CRPC development in animal models, and stabilizes PSA progression and metastatic lesions in patients. Therefore, the study provides a novel mechanism and potential target for the management of castration-resistant prostate cancer.

Insights into Sucrose Metabolism and Its Ethylene-Dependent Regulation in Cucumis melo L.

The melon (Cucumis melo L.), a fruit crop of significant economic importance, is prized for its sweet and succulent fruits. Among variations of soluble sugars, sucrose, a disaccharide composed of glucose and fructose, is a key carbohydrate present in melon fruits. The sucrose content also determines the quality and value of melon fruits. However, the accumulation of sucrose is a complex process involving the coordinated actions of multiple enzymes and pathways. In melon species, there are two types of fruit ripening modes including climacteric and non-climacteric. Due to this biological characteristic, melon is emerging as a good model for studying the ripening process. Ethylene is a well-known phytohormone regulating the ripening of climacteric fruits. Recently, a few studies have elucidated a primary ethylene-dependent signaling pathway of sucrose accumulation in melon fruits. This review aims to provide a careful overview of the sucrose biosynthesis pathways in melon. It is essential to understand the molecular mechanisms of sucrose metabolism as well as its regulation mode. The information will be useful for developing molecular marker-assisted breeding as well as genetic engineering strategies aiming to improve the sucrose content and quality of melon fruits. In addition, even though limited, the impacts of genetic background and environmental factors on sucrose accumulation in melon fruits are also discussed. These are useful for practical applications in melon cultivation and quality management.

Study on the anti-inflammatory effect of stachyose by inhibiting TLR4/NF-κB signalling pathway in vitro and in vivo.

This study aimed to explore the anti-inflammatory effect of stachyose, a tetrasaccharide extracted from Stachys sieboldii Miq. A lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages model and a dextran sodium sulfate (DSS)-induced ulcerative colitis BALB/C mice model was used to assess the anti-inflammatory effect of stachyose both in vitro and in vivo. The levels of nitric oxide (NO) and cytokines (interleukin-1ß, interleukin-6 and tumour necrosis factor-α) were detected using enzyme-linked immunosorbent assay methods; moreover, haematoxylin-eosin staining was used to observe changes in intestinal morphology of mice. In addition, the possible mechanisms were explored by reverse transcription-polymerase chain reaction and western blot. Results showed that stachyose and four other oligosaccharides (galacto-oligosaccharides, xylo-oligosaccharides, inulin and resistant dextrin) inhibited NO secretion and the production of pro-inflammatory cytokines in LPS-stimulated RAW264.7 macrophages in a dose-dependent manner, whereas stachyose was most effective in vitro. In mice, different doses of stachyose significantly alleviated the symptoms of DSS-induced ulcerative colitis and stachyose also significantly inhibited the production of inflammatory cytokines and myeloperoxidase in vivo. In addition, our findings illustrated that stachyose inhibited expression of toll-like receptor 4 (TLR4) and suppressed the phosphorylation of nuclear factor (NF)-κB p65 both in vitro and in vivo. Taken together, results demonstrated that stachyose exerted anti-inflammatory effect through inhibition of the TLR4/NF-κB signalling pathway.

Stachyose Alleviates Corticosterone-Induced Long-Term Potentiation Impairment via the Gut-Brain Axis.

Stress can induce learning and memory impairment; corticosterone is often used to study the effects and mechanisms of stress in animal models. Long-term potentiation (LTP) has been widely used for tackling the mechanisms of memory. Liuwei Dihuang decoction-active fraction combination (LW-AFC) can improve stress-induced LTP and cognition impairment; stachyose is an oligosaccharide in LW-AFC. The effects and mechanisms of stachyose on stress are unknown. In this study, stachyose showed protective effects against LTP impairment by corticosterone in vivo only via intragastric administration for 7 consecutive days, but there was little effect even after direct intracerebroventricular injection; the protective effect of stachyose could be canceled by non-absorbable antibiotics (ATB) which disturbed gut flora. 16S rRNA sequencing, alpha diversity, and principal coordinate analysis (PCoA) revealed that the gut flora in corticosterone-treated mice was disturbed and stachyose could improve corticosterone-induced gut flora disturbance. Bacteroidetes were decreased and Deferribacteres were increased significantly in corticosterone-treated mice, and stachyose restored Bacteroidetes and Deferribacteres to the normal level. D-serine, a coactivator of NMDA receptors, plays an important role in synaptic plasticity and cognition. Here, corticosterone had little effect on the content of D-serine and L-serine (the precursor of D-serine), but it reduced the D-serine release-related proteins, Na+-independent alanine-serine-cysteine transporter-1 (ASC-1), and vesicle-associated membrane protein 2 (VAMP2) significantly in hippocampus; stachyose significantly increased ASC-1 and VAMP2 in corticosterone-treated mice, and ATB blocked stachyose's effects on ASC-1 and VAMP2. NMDA receptors co-agonists L-serine, D-serine, and glycine significantly improved LTP impairment by corticosterone. These results indicated that stachyose might indirectly increase D-serine release through the gut-brain axis to improve LTP impairment by corticosterone in the hippocampus in vivo.

Chemical Composition and Antioxidant Activity of Monguba (Pachira aquatica) Seeds.

Monguba fruit has a seed with a chestnut-like flavor that can be consumed boiled, fried, and roasted. These nutritious seeds also have been used in popular medicine to treat several diseases. Nevertheless, the nutritional and functional potential of monguba seed is still underexploited. In this sense, we investigated the nutritional and functional components of monguba seeds. These seeds showed high total content of sugars, mainly sucrose, whereas the content of the raffinose family oligosaccharides was low. The mineral assay showed high amount of minerals, namely potassium, calcium, magnesium and zinc, which indicate that monguba seeds can be a new source of these minerals. UHPLC-ESI-MS/MS analysis showed caffeic, ferulic and 4-hydroxybenzoic acids as the main phenolic compounds, mainly in the esterified form, in these seeds. Monguba seed showed high lipid content, in which the main compounds were palmitic acid and γ-tocopherol. The soluble and insoluble phenolic fractions from monguba seeds showed high antioxidant activity measured by the oxygen radical absorption capacity (ORAC) and the trolox equivalent antioxidant capacity (TEAC) assays. Therefore, the monguba seeds have great potential to be explored by food, pharmaceutical and cosmetic industries due to their chemical composition.

Assessment of flatulence causing agents in Chickpea (Cicer arietinum L.) and their possible removal

Abstract Flatulence and fullness of stomach is one of the most common problem associated with chickpea primary due to presence of some oligosaccharides and phenols. In this investigation Desi and Kabuli varieties were compared for these oligosaccharides and phenolic compounds. Furthermore, the effect of different processing and cooking methods such as soaking, cooking and germination in the reduction of these antiphysiological factors were are also studies. Maximum tannic acid (0.90 ± 0.20%) was observed in Parbat and C-44 while minimum (0.60 ± 0.04%) in Karak-2. Stachyose contents ranged between 1.10 ± 0.05 (Karak-3) to 1.42 ± 0.02% (Parbat) while raffinose was 0.63 ± 0.05(Karak-3) to 0.81 ± 0.02% (Dasht). The highest tannic acid content was reduced up to 50% in C-44 by cooking of 72 hours germinated seeds. Stachyose and raffinose contents were completely removed after 72 hours germination. Present studies revealed that cooking after germination is the most effective method to reduce the anti-nutritional factors of chickpea. Individually, soaking and cooking also contributed to the loss of the same factors but to a lesser extent.

Stachyose Improves Inflammation through Modulating Gut Microbiota of High-Fat Diet/Streptozotocin-Induced Type 2 Diabetes in Rats.

SCOPE: The present study is undertaken to assess the effects of stachyose (STS) on type 2 diabetes in rats and changes in the gut microbiota compared to metformin (MET). METHODS AND RESULTS: The type 2 diabetic model is successfully established via a high-fat diet /streptozotocin in Wistar rats, and STS or MET is administered for 4 weeks. Blood is collected to analyze biochemical parameters, pancreas for mRNA expression of related gene, and contents of colon for gut microbiota. STS or MET decreases serum LPS, mRNA expression of IL-6, and tumor necrosis factor-α (TNF-α). In addition, STS and MET show a similar shifting of the structure of the gut microbiota and a selective enrichment of key species. At the genus level, STS shows selective enrichment of Phascolarctobacterium, Bilophila, Oscillospira, Turicibacter, and SMB5, but MET demonstrates a selective effect on Sutterella, Prevotella, 02d06, and rc4. The correlation analysis indicates that STS and MET decrease IL-6 and TNF-α and increase Akt/PI3K expression, which are relative to key species of gut microbiota. CONCLUSION: STS decreases pancreatic mRNA expression of IL-6 and TNF-α via key species of gut microbiota. The mechanism of this effect is similar to that of MET.

Bioaccessibility and antioxidant activity of free phenolic compounds and oligosaccharides from corn (Zea mays L.) and common bean (Phaseolus vulgaris L.) chips during in vitro gastrointestinal digestion and simulated colonic fermentation.

Corn (Zea mays L.) and common beans (Phaseolus vulgaris L.) are alternative suitable ingredients for snacks, because of their content of bioactive compounds such as phenolic compounds (PC) and oligosaccharides (OS). However, there is no information about the transformation of these compounds associated with food matrix during gastrointestinal digestion. Therefore, the objective of this work was to simulate the whole digestion process (mouth to colon) to estimate bioaccessibility and small intestine permeability of free PC and OS, and the antioxidant capacity of free PC. Digested nixtamalized corn-cooked common bean chips exhibited significant different quantities of free PC and OS, and higher antioxidant activity compared to methanolic extract. The free PC showed high values of apparent permeability coefficients (0.023-0.729×10-3), related with their absorption in the small intestine. Both free PC and OS were retained in the non-digestible fraction of chips (10.24-64.4%) and were able to reach the colon. Our results suggest the digestion potential to increase chip bioactive compounds and antioxidant activity. Additional studies are required to evaluate their in vivo effects.

Stachyose increases absorption and hepatoprotective effect of tea polyphenols in high fructose-fed mice.

SCOPE: The consumption of tea polyphenols (TP) and stachyose contributes to preventive effects on hepatic injury. This study examined the effects of stachyose on absorption and hepatoprotective effects of TP in mice. METHODS AND RESULTS: GC-MS measurement showed that stachyose significantly increased serum total phenolic, ECG and EGCG contents in mice. The mice fed with high fructose (HF)-diet for 56 days exhibited oxidative stress observed by an increase in hepatic MDA levels and decreases in GSH-Px and SOD activities. Serum TC, TG, LDL-C and CRP levels, and ALT and AST activities were increased, while HDL-C concentrations were decreased following HF diet. Co-supplementation of stachyose and TP more effectively improved all parameters mentioned above when compared to administration of stachyose or TP alone. Histological observations of hepatic tissues also confirmed the beneficial effects of co-administration of stachyose and TP. CONCLUSION: Our results suggest that stachyose enhances absorption and hepatoprotective effects of TP, and combined ingestion of stachyose and TP is a novel strategy for alleviating HF diet-induced hepatic injury.