Rumen fermentation and microbiota in Shami goats fed on condensed tannins or herbal mixture.

BACKGROUND: Phytochemical compounds can modify the rumen microbiome and improve rumen fermentation. This study evaluated the impact of supplementation with tannin and an herbal mixture containing ginger (Zingiber officinale), garlic (Allium sativum), Artemisia (Artemisia vulgaris), and turmeric (Curcuma longa) on the rumen fermentation and microbiota, and histology of rumen tissue of goats. Eighteen Shami male goats were divided into three groups (n = 6): non-supplemented animals fed the basal diet (C, control); animals fed basal diet and supplemented with condensed tannin (T); and animals fed basal diet and supplemented with herbal mixture (HM). Each animal received a basal diet composed of Alfalfa hay and a concentrate feed mixture. RESULTS: Group HM revealed higher (P < 0.05) rumen pH, total volatile fatty acids (VFA), acetic, propionic, isobutyric, butyric, isovaleric, and valeric. Principal Co-ordinate analysis (PCoA) showed that rumen microbial communities in the control group and supplemented groups were distinct. The supplementation increased (P < 0.05) the relative abundances of phylum Bacteroidota and Proteobacteria and declined (P < 0.05) Firmicutes and Fibrobacterota. Additionally, the dominant genus Prevotella and Rikenellaceae RC9 gut group were increased (P < 0.05) and the family Ruminococcaceae was declined (P < 0.05) due to the supplementation. The supplementation decreased (P < 0.05) the archaeal genus Methanobrevibacter and increased (P < 0.05) Candidatus Methanomethylophilus. Tannin supplementation in T group shortened the rumen papillae. CONCLUSIONS: The results revealed that the herbal mixture might be used to alter the rumen microbiota to improve rumen fermentation.

Abrupt Photoperiod Changes Differentially Modulate Hepatic Antioxidant Response in Healthy and Obese Rats: Effects of Grape Seed Proanthocyanidin Extract (GSPE).

Disruptions of the light/dark cycle and unhealthy diets can promote misalignment of biological rhythms and metabolic alterations, ultimately leading to an oxidative stress condition. Grape seed proanthocyanidin extract (GSPE), which possesses antioxidant properties, has demonstrated its beneficial effects in metabolic-associated diseases and its potential role in modulating circadian disruptions. Therefore, this study aimed to assess the impact of GSPE administration on the liver oxidant system of healthy and diet-induced obese rats undergoing a sudden photoperiod shift. To this end, forty-eight photoperiod-sensitive Fischer 344/IcoCrl rats were fed either a standard (STD) or a cafeteria diet (CAF) for 6 weeks. A week before euthanizing, rats were abruptly transferred from a standard photoperiod of 12 h of light/day (L12) to either a short (6 h light/day, L6) or a long photoperiod (18 h light/day, L18) while receiving a daily oral dose of vehicle (VH) or GSPE (25 mg/kg). Alterations in body weight gain, serum and liver biochemical parameters, antioxidant gene and protein expression, and antioxidant metabolites were observed. Interestingly, GSPE partially ameliorated these effects by reducing the oxidative stress status in L6 through an increase in GPx1 expression and in hepatic antioxidant metabolites and in L18 by increasing the NRF2/KEAP1/ARE pathway, thereby showing potential in the treatment of circadian-related disorders by increasing the hepatic antioxidant response in a photoperiod-dependent manner.

Tartary Buckwheat (Fagopyrum tataricum) FtTT8 Inhibits Anthocyanin Biosynthesis and Promotes Proanthocyanidin Biosynthesis.

Tartary buckwheat (Fagopyrum tataricum) is an important plant, utilized for both medicine and food. It has become a current research hotspot due to its rich content of flavonoids, which are beneficial for human health. Anthocyanins (ATs) and proanthocyanidins (PAs) are the two main kinds of flavonoid compounds in Tartary buckwheat, which participate in the pigmentation of some tissue as well as rendering resistance to many biotic and abiotic stresses. Additionally, Tartary buckwheat anthocyanins and PAs have many health benefits for humans and the plant itself. However, little is known about the regulation mechanism of the biosynthesis of anthocyanin and PA in Tartary buckwheat. In the present study, a bHLH transcription factor (TF) FtTT8 was characterized to be homologous with AtTT8 and phylogenetically close to bHLH proteins from other plant species. Subcellular location and yeast two-hybrid assays suggested that FtTT8 locates in the nucleus and plays a role as a transcription factor. Complementation analysis in Arabidopsis tt8 mutant showed that FtTT8 could not recover anthocyanin deficiency but could promote PAs accumulation. Overexpression of FtTT8 in red-flowering tobacco showed that FtTT8 inhibits anthocyanin biosynthesis and accelerates proanthocyanidin biosynthesis. QRT-PCR and yeast one-hybrid assay revealed that FtTT8 might bind to the promoter of NtUFGT and suppress its expression, while binding to the promoter of NtLAR and upregulating its expression in K326 tobacco. This displayed the bidirectional regulating function of FtTT8 that negatively regulates anthocyanin biosynthesis and positively regulates proanthocyanidin biosynthesis. The results provide new insights on TT8 in Tartary buckwheat, which is inconsistent with TT8 from other plant species, and FtTT8 might be a high-quality gene resource for Tartary buckwheat breeding.

Effects of Hydrogen Peroxide on In Vitro Cultures of Tea (Camellia sinensis L.) Grown in the Dark and in the Light: Morphology, Content of Malondialdehyde, and Accumulation of Various Polyphenols.

Tea plants (Camellia sinensis L.) are phenol-accumulating crops that are widely used for public health. The healing effect of tea leaf products is due to the biosynthesis of such phenolic compounds (PCs) as flavans, which have P-vitamin capillary-strengthening activity. Due to their limited habitat and the value of their specialized metabolites of a phenolic nature, a promising approach is to establish in vitro cultures from them that retain the ability to form PCs, which is characteristic of ex vivo tea plants. The aim of this study was to investigate the effect of exogenic H2O2 (0.01 mM; 0.1 mM; 1 mM) on the growth, morphology, degree of stress response, and accumulation of various phenolic compounds in tea plant callus cultures of different ages (24 or 36 days) grown under different cultivation conditions (darkness or light). According to the results obtained, the H2O2 effect on tea callus cultures of different ages did not cause changes in their morphophysiological characteristics, both after 2 h of exposure (rapid response of callus culture, RRCC) and after 48 h (delayed response of callus culture, DRCC). The determination of the malondialdehyde (MDA) content, which serves as an indicator of changes in the level of lipid peroxidation (LPO) and the presence of stress responses in plant cells, indicated either its maintenance at the control level, a decrease, or an increase. All these effects depended on the growth conditions of the tea callus cultures (darkness or light), their age, the duration of exposure (rapid or delayed response), and the H2O2 concentration. Similar trends were noted for the total content of PCs as well as the amount of flavans, proanthocyanidins (soluble and insoluble forms), and lignin. The plant cell responses reflected changes in its adaptation programs, when specialized metabolites act as a target for the action of H2O2, thereby contributing to an increase in their resistance.

Grape Seed Proanthocyanidins Modulate the Hepatic Molecular Clock via MicroRNAs.

SCOPE: Circadian rhythm is an endogenous and self-sustained timing system, responsible for the coordination of daily processes in 24-h timescale. It is regulated by an endogenous molecular clock, which is sensitive to external cues as light and food. This study has previously shown that grape seed proanthocyanidins extract (GSPE) regulates the hepatic molecular clock. Moreover, GSPE is known to interact with some microRNAs (miRNAs). Therefore, the aim of this study is to evaluate if the activity of GSPE as modulator of hepatic clock genes can be mediated by miRNAs. METHODS AND RESULTS: 250 mg kg-1 of GSPE is administered to Wistar rats before a 6-h jet lag and sacrificed at different time points. GSPE modulated both expression of Bmal1 and miR-27b-3p in the liver. Cosinor-based analysis reveals that both Bmal1 and miR-27b-3p expression follow a circadian rhythm, a negative interaction between them, and the role of GSPE adjusting the hepatic peripheral clock via miRNA. Additionally, in vitro studies show that Bmal1 is sensitive to GSPE (25 mg L-1 ). However, this effect is independent of miR-27b-3p. CONCLUSION: miRNA regulation of peripheral clocks via GSPE may be part of a complex mechanism that involves the crosstalk with the central system rather than a direct effect.

Further slowing down of hydrolysis of amylose heated with black soybean extract by treating with nitrite under gastric conditions.

Black soybean (BSB), which contains cyanidin-3-O-glucoside (C3G) and procyanidins, is cooked with rice in Japan. The color of the cooked rice is purplish red due to the binding of C3G and reddish oxidation products of procyanidins. These components can slowdown pancreatin-induced hydrolysis of amylose more significantly than the hydrolysis of amylopectin, and can react with nitrous acid in the stomach. This manuscript deals with the effects of nitrous acid on pancreatin-induced hydrolysis of amylose heated with BSB extract. The hydrolysis of amylose heated with BSB extract was slow, and the slowdown was due to the binding of C3G/its degradation products and degradation products of procyanidins. The amylose hydrolysis was slowed down further by treating with nitrite under gastric conditions. The further slowdown was discussed to be due to the binding of the products, which were formed by the reaction of procyanidins with nitrous acid, to amylose. In the products, dinitroprocyanidins were included. In this way, the digestibility of amylose heated with BSB extract can be slowed down further by reacting with nitrous acid in the stomach.

An Emerging Role of Proanthocyanidins on Psoriasis: Evidence from a Psoriasis-Like Mouse Model.

Background: Psoriasis is an immune-mediated, chronic inflammatory disease, and genetic, immune, oxidative stress (OS), and environmental factors are all thought to contribute to its occurrence. Proanthocyanidins (PCs) are natural flavonoids consisting of catechins and epicatechins which have anti-inflammatory and anti-OS activities. PCs have been widely used to treat various diseases, but reports regarding psoriasis are rare. Objective: To investigate the therapeutic effect and potential mechanisms of action of PCs in a psoriasis-like mouse model. Methods: Thirty male BALB/c hairless mice were assigned to six groups (n = 5): normal, model, low-dose PCs, medium-dose PCs, high-dose PCs, and control groups. The final five groups were dorsally exposed to 5% imiquimod (IMQ) cream once a day for 6 consecutive days, while the normal group received no intervention. Following the first day of IMQ application, mice in the PC-treated group were dosed with different amounts of PCs daily by oral gavage for six days, whereas mice in the control group received normal saline in the same way. One week later, skin lesions were evaluated by the severity of scoring system based on psoriasis area and severity index (PASI), and pathological alterations were assessed by hematoxylin-eosin (HE) staining. Indicators of inflammation or OS, such as interleukin- (IL-) 17, IL-23, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), and heme oxygenase-1 (HO-1), were determined by ELISA, RT-PCR, western blot, and immunohistochemistry (IHC) analysis. Results: IMQ administration induced the formation of large dark red plaques with thickly layered scales on the dorsal skin of mice; nevertheless, the lesions were substantially alleviated by PC administration. Histopathological alterations were observed in both model and control groups with epidermal hyperkeratosis, granulosa layer thinning, acanthosis, downward extension of rete ridges, dermal papillae expansion, capillary hyperplasia, and infiltration by inflammatory cells around blood vessels. These pathological changes, however, were restored by a range of doses of PCs, high-dose PCs in particular. Different doses of PCs significantly lowered the spleen index, levels of inflammatory or oxidative proteins (IL-17, IL-23, MDA, ROS, p-PI3K, and p-STAT3), and the mRNA expression of Il-17, Il-23, Vegf, and iNos. Protein and mRNA levels of anti-OS and anti-inflammatory biomarkers, including SOD, CAT, GSH, and HO-1, greatly increased after PC treatment, especially at the highest dose. Conclusions: Our findings reveal that PCs ameliorate psoriasis-like symptoms, suppressing the inflammatory response and mitigating OS damage in an IMQ-induced psoriasis-like mouse model. These effects are probably related to the inactivation of STAT3 and PI3K and activation of HO-1 signaling.

Grape Seed Proanthocyanidins Mitigate the Disturbances Caused by an Abrupt Photoperiod Change in Healthy and Obese Rats.

Variations in the light/dark cycle and obesogenic diets trigger physiological and behavioral disorders. Proanthocyanidins, in addition to their healthy properties, have recently demonstrated a modulating effect on biological rhythms. Therefore, the aim of this study was to evaluate the administration of a grape seed proanthocyanidin-rich extract (GSPE) to mitigate the disruption caused by a sudden photoperiod change in healthy and cafeteria (CAF)-diet obese rats. For this, 48 photoperiod-sensitive Fischer 344 rats were fed standard or CAF diets for 6 weeks under a standard (12 h light/day, L12) conditions. Then, rats were switched to a long (18 h light/day, L18) or short (6 h light/day, L6) photoperiod and administered vehicle or GSPE (25 mg/kg) for 1 week. Body weight (BW) and food intake (FI) were recorded weekly. Animal activity and serum hormone concentrations were studied before and after the photoperiod change. Hormone levels were measured both at 3 h (ZT3) and 15 h (ZT15) after the onset of light. Results showed the impact of the CAF diet and photoperiod on the BW, FI, activity, and hormonal status of the animals. GSPE administration resulted in an attenuation of the changes produced by the photoperiod disruption. Specifically, GSPE in L6 CAF-fed rats reduced serum corticosterone concentration, restoring its circadian rhythm, increased the T3-to-T4 ratio, and increased light phase activity, while under L18, it decreased BW and testosterone concentration and increased the animal activity. These results suggest that GSPE may contribute to the adaptation to the new photoperiods. However, further studies are needed to elucidate the metabolic pathways and processes involved in these events.

Procyanidin C1 from Viola odorata L. inhibits Na+,K+-ATPase.

Members of the Viola genus play important roles in traditional Asian herbal medicine. This study investigates the ability of Viola odorata L. extracts to inhibit Na+,K+-ATPase, an essential animal enzyme responsible for membrane potential maintenance. The root extract of V. odorata strongly inhibited Na+,K+-ATPase, while leaf and seeds extracts were basically inactive. A UHPLC-QTOF-MS/MS metabolomic approach was used to identify the chemical principle of the root extract's activity, resulting in the detection of 35,292 features. Candidate active compounds were selected by correlating feature area with inhibitory activity in 14 isolated fractions. This yielded a set of 15 candidate compounds, of which 14 were preliminarily identified as procyanidins. Commercially available procyanidins (B1, B2, B3 and C1) were therefore purchased and their ability to inhibit Na+,K+-ATPase was investigated. Dimeric procyanidins B1, B2 and B3 were found to be inactive, but the trimeric procyanidin C1 strongly inhibited Na+,K+-ATPase with an IC50 of 4.5 µM. This newly discovered inhibitor was docked into crystal structures mimicking the Na3E1∼P·ADP and K2E2·Pi states to identify potential interaction sites within Na+,K+-ATPase. Possible binding mechanisms and the principle responsible for the observed root extract activity are discussed.

Time-of-Day Circadian Modulation of Grape-Seed Procyanidin Extract (GSPE) in Hepatic Mitochondrial Dynamics in Cafeteria-Diet-Induced Obese Rats.

Major susceptibility to alterations in liver function (e.g., hepatic steatosis) in a prone environment due to circadian misalignments represents a common consequence of recent sociobiological behavior (i.e., food excess and sleep deprivation). Natural compounds and, more concisely, polyphenols have been shown as an interesting tool for fighting against metabolic syndrome and related consequences. Furthermore, mitochondria have been identified as an important target for mediation of the health effects of these compounds. Additionally, mitochondrial function and dynamics are strongly regulated in a circadian way. Thus, we wondered whether some of the beneficial effects of grape-seed procyanidin extract (GSPE) on metabolic syndrome could be mediated by a circadian modulation of mitochondrial homeostasis. For this purpose, rats were subjected to "standard", "cafeteria" and "cafeteria diet + GSPE" treatments (n = 4/group) for 9 weeks (the last 4 weeks, GSPE/vehicle) of treatment, administering the extract/vehicle at diurnal or nocturnal times (ZT0 or ZT12). For circadian assessment, one hour after turning the light on (ZT1), animals were sacrificed every 6 h (ZT1, ZT7, ZT13 and ZT19). Interestingly, GSPE was able to restore the rhythm on clock hepatic genes (Bmal1, Per2, Cry1, Rorα), as this correction was more evident in nocturnal treatment. Additionally, during nocturnal treatment, an increase in hepatic fusion genes and a decrease in fission genes were observed. Regarding mitochondrial complex activity, there was a strong effect of cafeteria diet at nearly all ZTs, and GSPE was able to restore activity at discrete ZTs, mainly in the diurnal treatment (ZT0). Furthermore, a differential behavior was observed in tricarboxylic acid (TCA) metabolites between GSPE diurnal and nocturnal administration times. Therefore, GSPE may serve as a nutritional preventive strategy in the recovery of hepatic-related metabolic disease by modulating mitochondrial dynamics, which is concomitant to the restoration of the hepatic circadian machinery.

Combination of tea polyphenols and proanthocyanidins prevents menopause-related memory decline in rats via increased hippocampal synaptic plasticity by inhibiting p38 MAPK and TNF-α pathway.

OBJECTIVE: Many studies have examined the beneficial effects of tea polyphenols (TP) and proanthocyanidins (PC) on the memory impairment in different animal models. However, the combined effects of them on synaptic, memory dysfunction and molecular mechanisms have been poorly studied, especially in the menopause-related memory decline in rats. METHODS: In this rat study, TP and PC were used to investigate their protective effects on memory decline caused by inflammation. We characterized the learning and memory abilities, synaptic plasticity, AMPAR, phosphorylation of the p38 protein, TNF-ɑ, structural synaptic plasticity-related indicators in the hippocampus. RESULTS: The results showed that deficits of learning and memory in OVX + D-gal rats, which was accompanied by dendrites and synaptic morphology damage, and increased expression of Aß1-42 and inflammation. The beneficial effects of TP and PC treatment were found to prevent memory loss and significantly improve synaptic structure and functional plasticity. TP+PC combination shows more obvious advantages than intervention alone. TP and PC treatment improved behavioral performance, the hippocampal LTP damage and the shape and number of dendrites, dendritic spines and synapses, reduced the burden of Aß and decreased the inflammation in hippocampus. In addition, TP and PC treatment decreased the expressions of Iba-1, TNF-α, TNFR1, and TRAF2. CONCLUSIONS: These results provided a novel evidence TP combined with PC inhibits p38 MAPK pathway, suppresses the inflammation in hippocampus, and increase the externalization of AMPAR, which may be one of the mechanisms to improve synaptic plasticity and memory in the menopause-related memory decline rats.

Administration Time Significantly Affects Plasma Bioavailability of Grape Seed Proanthocyanidins Extract in Healthy and Obese Fischer 344 Rats.

SCOPE: Phenolic compounds are bioactive molecules that are associated with several health benefits. Metabolization and absorption are the main determinants of their bioavailability and bioactivity. Thus, the study of the factors that modulate these processes, such as sex or diet is essential. Recently, it has been shown that biological rhythms may also play a key role. Hence, the aim of this study is to evaluate if the bioavailability of a grape proanthocyanidin extract (GSPE) is affected by the administration time in an animal model of metabolic syndrome (MetS). METHODS AND RESULTS: Female and male Fischer 344 rats are fed either a standard or a cafeteria diet (CAF) for 9 weeks, and an oral dose of GSPE (25 mg kg-1 ) is daily administered either at 8:00 am (zeitgeber time (ZT)-0) or at 8:00 pm (ZT-12) during the last 4 weeks. Plasma phenolic compounds are then quantified by liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Phase-II and gut microbiota-derived phenolic metabolites are affected by ZT in all conditions or only in obese rats, respectively. CAF feeding affected the bioavailability of phenolic acids and free flavan-3-ols. Differences due to sex are also observed. CONCLUSION: These findings demonstrate that ZT, diet, and sex are key factors influencing phenolic compounds bioavailability.

Comprehensive feature-based molecular networking and metabolomics approaches to reveal the differences components in Cinnamomum cassia and Cinnamomum verum.

Cinnamon was been a widely used plant in medicinal and spices for a long time and has spread all over the world. However, the differences in the components of the bark from Cinnamomum cassia and Cinnamomum verum, the two most common types of cinnamon, have not been thoroughly investigated. In the present experiment, ultra-high-performance liquid chromatography LTQ-Orbitrap Velos Pro hybrid mass spectrometer-based metabolomics coupled with chemometrics and feature-based molecular networking were employed to dramatically distinguish and annotate Cinnamomum cassia Bark and Cinnamomum verum bark. As a consequence, principal component analysis, orthogonal projection to latent structures discriminates analysis, and heat map analysis demonstrated clear discrimination between the profiles of metabolites in cinnamon. Besides, as the known compounds, proanthocyanidins (cinnamtannin B1 and procyanidin B2) and alkaloids (norboldine, norisoboldine) with variable importance in the projection scores >6, and an unknown alkaloid (formula C24 H33 NO6 ) were selected as the best markers to discriminate cinnamon. Furthermore, large numbers of proanthocyanidins and alkaloids components were identified through feature-based molecular networking for the first time. Our investigation provides new ideas for the discovery of quality markers and identification of unknown components in natural products.

Chemical Identification of Specialized Metabolites from Sulla (Hedysarum coronarium L.) Collected in Southern Italy.

Sulla (Hedysarum coronarium L.) is a biennal forage legume originated from the Mediterranean basin and used for animal feeding due to its high forage quality and palatability. Several species of Hedysarum have been considered for their nutritional, pharmaceutical, and biological properties, and different applications have been reported, both for human consumption and animal nutrition. Although a systematic investigation of the chemical constituents of Hedysarum spp. has been performed in order to provide chemotaxonomic evidences for the genus and to support the pharmacological application of several species within the genus, few data are available on the chemical constituents of H. coronarium, and only the content of condensed tannins and flavonoids in leaves has been previously reported. In the present paper, results from a detailed chemical analysis of the extracts from the leaves and flowers of H. coronarium grown wild in southern Italy are presented. Identification of the main specialized metabolites within the chemical classes of flavonoids, proanthocyanidins and saponins, is described, including considerations on their content in the two plant organs. Information acquired from this study expands the knowledge on H. coronarium as a source of valuable phytochemicals for different applications in human and animal health and nutrition.

A Prospective of Multiple Biopharmaceutical Activities of Procyanidins-Rich Uapaca togoensis Pax Extracts: HPLC-ESI-TOF-MS Coupled with Bioinformatics Analysis.

The article reports the chemical composition, antioxidant, six key enzymes inhibitory and antimicrobial activities of two solvent extracts (water and methanol) of leaves and stem bark of Uapaca togoensis. For chemical composition, methanol extract of stem bark exhibited significant higher total phenolic (129.86 mg GAE/g) and flavanol (10.44 mg CE/g) contents. Methanol extract of leaves and water extract of stem bark showed high flavonoids (20.94 mg RE/g) and phenolic acid (90.40 mg CAE/g) content, respectively. In addition, HPLC-ESI-TOF-MS analysis revealed that U. togoensis was rich in procyanidins. The methanol and water extracts of stem bark had overall superior antioxidant activity; however, only methanol extract of stem bark showed higher inhibition of cholinesterase (AChE: 2.57 mg GALAE/g; BChE: 4.69 mg GALAE/g), tyrosinase (69.53 mg KAE/g) and elastase (2.73 mmol CE/g). Potent metal chelating ability was showed by water extract of leaves (18.94 mg EDTAE/g), higher inhibition of amylase was detected for water extracts of leaves (0.94 mmol ACAE/g) and stem bark (0.92 mmol ACAE/g). The tested extracts have shown wide-spectrum antibacterial properties and these effects have shown to be more effective against Aspergillus ochraceus, Penicillium funiculosum, Trichoderma viride, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The results revealed that the antioxidant, enzyme inhibitory and antimicrobial activities depended on the extraction solvents and the parts of plant. Bioinformatics analysis on the 17 major compounds showed modulation of pathway associated with cancer. In brief, U. togoensis might be valuable as potential source of natural agents for therapeutic application.

Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer.

The high degree of morbidity and mortality in colorectal cancer (CRC) patients is largely due to the development of chemoresistance against conventional chemotherapeutic drugs. In view of the accumulating evidence that various dietary botanicals offer a safe, inexpensive and multi-targeted treatment option, herein, we hypothesized that a combination of Andrographis paniculata and Oligomeric Proanthocyanidins (OPCs) might interact together with regard to anti-tumorigenic activity in CRC. As a result, we demonstrated the enhanced anti-cancer activity between these two botanical extracts in terms of their ability to inhibit cancer cell growth, suppress colony formation and induce apoptosis. Furthermore, we validated these findings in subcutaneous xenograft model and in patient derived primary epithelial 3D organoids. Transcriptomic profiling identified involvement of metabolic pathways and ferroptosis-associated genes, including HMOX1, GCLC and GCLM, that may be responsible for the increased anti-tumorigenic activity by the two compounds. Collectively, our study provides novel evidence in support of the combinatorial use of andrographis and OPCs as a potential therapeutic option, perhaps as an adjunctive treatment to classical drugs, in patients with colorectal cancer.

Root Secondary Metabolites in Populus tremuloides: Effects of Simulated Climate Warming, Defoliation, and Genotype.

Climate warming can influence interactions between plants and associated organisms by altering levels of plant secondary metabolites. In contrast to studies of elevated temperature on aboveground phytochemistry, the consequences of warming on root chemistry have received little attention. Herein, we investigated the effects of elevated temperature, defoliation, and genotype on root biomass and phenolic compounds in trembling aspen (Populus tremuloides). We grew saplings of three aspen genotypes under ambient or elevated temperatures (+4-6 °C), and defoliated (by 75%) half of the trees in each treatment. After 4 months, we harvested roots and determined their condensed tannin and salicinoid (phenolic glycoside) concentrations. Defoliation reduced root biomass, with a slightly larger impact under elevated, relative to ambient, temperature. Elevated temperature decreased condensed tannin concentrations by 21-43% across the various treatment combinations. Warming alone did not alter salicinoid concentrations but eliminated a small negative impact of defoliation on those compounds. Graphical vector analysis suggests that effects of warming and defoliation on condensed tannins and salicinoids were predominantly due to reduced biosynthesis of these metabolites in roots, rather than to changes in root biomass. In general, genotypes did not differ in their responses to temperature or temperature by defoliation interactions. Collectively, our results suggest that future climate warming will alter root phytochemistry, and that effects will vary among different classes of secondary metabolites and be influenced by concurrent ecological interactions such as herbivory. Temperature- and herbivory-mediated changes in root chemistry have the potential to influence belowground trophic interactions and soil nutrient dynamics.

Pancreatic lipase and α-amylase inhibitory activity of extracts from selected plant materials after gastrointestinal digestion in vitro.

A screening of inhibitory activity of α-amylase, as well as pancreatic lipase (PL), under the influence of aqueous and ethanolic preparations from 12 plant materials was performed. The most active aqueous extracts from the fruits of Chaenomeles japonica (CJ) and Hippophaë rhamnoides (HR) were selected for artificial gastrointestinal digestion (GID). The aim of this study was to evaluate the inhibitory effect of the fractions obtained after GID on PL and α-amylase activities using a fluorescence assay. The changes in the composition of crude extracts in GID aliquots were followed by analysis with HPLC-DAD-MSn method in order to indicate active constituents. The main constituents of CJ and HR extracts were procyanidins and isorhamnetin derivatives, respectively. The most abundant compounds of extracts were found in all compartments of the digestion model correlated with relevant lipase/α-amylase inhibitory activity. What is more, the gastric and intestinal fractions inhibited enzymatic activity by at least 40%.

Three flavanols delay starch digestion by inhibiting α-amylase and binding with starch.

The study aimed to reveal the different mechanisms of delaying starch digestion by ECG, EGCG and Procyanidin based on the perspective of α-amylase-flavanol interaction and starch-flavanol interaction. The interaction characteristics of flavanols with α-amylase were studied from five aspects: enzyme inhibition, kinetics, fluorescence quenching, circular dichroism (CD) and computer simulation. The IC50 of flavanols (ECG, EGCG and Procyanidin) against α-amylase were 172.21 ± 0.22, 732.15 ± 0.13 and 504.45 ± 0.19 µg/mL according to the results of α-amylase inhibition experiment, respectively. ECG and Procyanidin showed mixed inhibition against α-amylase, while EGCG showed non-competition against α-amylase. However, thermodynamic parameters，computer-based docking and dynamic simulation proved that ECG and EGCG-α-amylase complexs were mainly driven by van der Waals and hydrogen bonds, while Procyanidin-α-amylase complexs was driven by hydrophobic interaction. In addition, it was indicated, by means of starch­iodine complex spectroscopy, that flavanols inhibited the digestion of starch not only through bind with α-amylase but also through bind with starch. Thus, flavanols as a starch-based food additive have the potential to be employed as adjuvant therapy for diabetes.

Effects of dietary grapeseed extract on performance, energy and nitrogen balance as well as methane and nitrogen losses of lambs and goat kids.

The influence of phenol-rich dietary grapeseed extract on performance, energy and N balance and methane production was determined in sixteen lambs and thirteen goat kids (body weight 20·5 and 19·0 kg, 2 months of age, day 1 of study). Half of the animals received a concentrate containing grapeseed extract, and the others received concentrate without grapeseed extract (total extractable phenols analysed 27 v. 9 g/kg dietary DM; concentrate and hay 1:1). Diets were fed for 7 weeks with 1 week for determining intake, excretion and gaseous exchange in metabolism crates and respiration chambers. Overall, there was an adverse effect of the phenolic diet on apparent N digestibility and body N retention. Faecal N loss as proportion of N intake increased while urinary N loss declined. Relative to N intake, total N excretion was higher and body N retention lower in goat kids than lambs. Diets and animal species had no effect on methane emissions. The saliva of the goat kids had a higher binding capacity for condensed tannins (CT). Goat kids on the phenolic diet had higher CT concentrations in faeces and excreted more CT compared with the lambs (interaction species × diet P < 0·001). The lambs had overall higher (P < 0·001) urinary phenol concentrations than the goat kids (2·19 v. 1·48 g/l). The negative effect on body N retention and lack of effect on methane emissions make the use of the extract in the dosage applied not appealing. Species differences need to be considered in future studies.