Natural products as a source of Coronavirus entry inhibitors.

The COVID-19 pandemic has had a significant and lasting impact on the world. Four years on, despite the existence of effective vaccines, the continuous emergence of new SARS-CoV-2 variants remains a challenge for long-term immunity. Additionally, there remain few purpose-built antivirals to protect individuals at risk of severe disease in the event of future coronavirus outbreaks. A promising mechanism of action for novel coronavirus antivirals is the inhibition of viral entry. To facilitate entry, the coronavirus spike glycoprotein interacts with angiotensin converting enzyme 2 (ACE2) on respiratory epithelial cells. Blocking this interaction and consequently viral replication may be an effective strategy for treating infection, however further research is needed to better characterize candidate molecules with antiviral activity before progressing to animal studies and clinical trials. In general, antiviral drugs are developed from purely synthetic compounds or synthetic derivatives of natural products such as plant secondary metabolites. While the former is often favored due to the higher specificity afforded by rational drug design, natural products offer several unique advantages that make them worthy of further study including diverse bioactivity and the ability to work synergistically with other drugs. Accordingly, there has recently been a renewed interest in natural product-derived antivirals in the wake of the COVID-19 pandemic. This review provides a summary of recent research into coronavirus entry inhibitors, with a focus on natural compounds derived from plants, honey, and marine sponges.

Structurally Orientated Rheological and Gut Microbiota Fermentation Property of Mannans Polysaccharides and Oligosaccharides.

Three mannan polysaccharides and their oligosaccharides were investigated in terms of physicochemical characteristics and effects on gut microbiota. Oligosaccharides from guar gum had the fastest fermentation kinetics for SCFAs generation at the initial stage, while the locust bean of both polymers and oligosaccharides demonstrated the lowest SCFAs through the whole fermentation process. In contrast, konjac gum steadily increased SCFAs and reached its maximum level at 24 h fermentation, indicating its fermentation character may be associated with its rheological properties. Compared to their corresponding polysaccharides, all the oligosaccharides demonstrated a faster fermentation kinetics, followed by an enriched abundance of propionate-producing bacterial Prevotella and a decreased abundance of Megamonas and Collinsella. Meanwhile, oligosaccharides reduced the Firmicutes/Bacteroidota ratio as well as the abundance of Bacteroidetes and Escherichia-Shigella. The fermentation of konjac substrate significantly promoted the abundance of butyrate-producing bacterial Faecalibacterium. In contrast, although the fermentation of locust bean and guar gum substrates benefited Bifidobacterium abundance due to their similar structure and monosaccharides composition, the fermentation of locust bean gum led to greater Bifidobacterium than the others, which may be associated with its higher mannose composition in the molecules. Interestingly, the partial hydrolysis of the three polysaccharides slightly reduced their prebiotic function.

Mapping the metabolic characteristics of probiotic-fermented Ganoderma lucidum and its protective mechanism against Cd-induced nephrotoxicity.

An animal model of Cd-induced kidney damage was designed to investigate the nephroprotective potential of the probiotic-fermented Ganoderma lucidum (FGL) via metabonomic analysis. The results showed that FGL enhanced sugar and amino acid metabolism. The interaction of Ganoderma lucidum (GL) and probiotics efficiently elevated short-chain fatty acid production following gut microbiota fermentation. The current data revealed that the FGL intervention alleviated Cd-induced nephrotoxicity via elevating the activity of antioxidant enzymes and decreasing the levels of pro-inflammatory and apoptotic factors. Based on transcriptome analysis, FGL intervention mediated renal dysfunction via decreasing the expressions of Nos2, Tnfsf14, S100a9, Map3k6 and Hk3, which were involved in oxidative stress, inflammatory response and the apoptosis process. The current study highlights a new approach for achieving positive nephroprotection via natural product intervention.

Impact of de-branched starch molecules and fatty acid complexes on the attenuation of ageing-induced cognitive impairment.

BACKGROUND: Ageing and associated cognitive impairments are becoming serious issues around the world. In this study, the physiological properties of three kinds of complexes of fatty acid (capric, stearic and oleic acid, respectively) and de-branched starch molecules were investigated via a d-galactose-induced ageing model. This study revealed differences in the regulation of cognitive impairment and brain damage following intervention of different complexes, which might highlight a potent approach for the prevention of this chronic disease. RESULTS: Data indicated that three complexes improved response time and cognitive function and the bio-parameter markers associated with oxidative stress in ageing rats. Among them, the complexes prepared from de-branched starch-oleic acid showed a greater improvement compared to others. In addition, de-branched starch-capric acid complex showed a higher improvement in the morphology of colon cells and hippocampal neuronal cells. The consumption of de-branched starch-capric acid and -oleic acid complexes generated more short-chain fatty acids in the gut. More importantly, the complexation of de-branched starch with either caprate or stearate enhanced gut Akkermansia. Therefore, it was proposed that the richness in Akkermansia and gut metabolites might be associated with reduced damage of the hippocampal neuronal cells induced by the ageing progress. Moreover, the AMPK (AMP-activated protein kinase) pathway was activated in liver in de-branched starch-capric acid complex diet. In summary, de-branched starch-capric acid complex exhibited a greater effect on the attenuation of ageing-induced cognitive impairment. CONCLUSION: This study might highlight a new approach for intervening in the cognitive impairment during the ageing progress via a food supply. © 2023 Society of Chemical Industry.

Characterization of Pickering emulsion by SCFAs-modified debranched starch and a potent for delivering encapsulated bioactive compound.

The Pickering emulsion was prepared by short-chain fatty acids (SCFAs) esterified debranched starch. The microstructure, particle size distribution, rheological properties and stability of the emulsions showed that the introduction of acyl groups improved the ability of starch to stabilize the emulsions, in which the butyrylated starch with longer acyl side chains exhibited higher emulsifying ability compared to acetylated and propionylated starches. Pickering emulsions stabilized with butyrylated starch as stabilizer have better stability after 30 days of storage. The particle size distribution of SCFAs-esterified starch emulsions with enzymatic debranching pretreatment was more concentrated and the droplet size was further reduced, which improved the instability factors such as flocculation, agglomeration or Ostwald ripening of emulsions induced by conventional SCFAs-esterified emulsions and further improved the stability of SCFAs-esterified emulsions. More importantly, butyrylated starch (with or without debranched pretreatment) emulsions exhibited smaller and more uniform droplet shapes and higher curcumin encapsulation efficiency (EE%) in SCFAs-esterified starch emulsions, and the EE% of curcumin in debranched butyrylated starch emulsion increasing from 10.04 % in native starch emulsions to 50.70 %.

Gut microbiota derived structural changes of phenolic compounds from colored rice and its corresponding fermentation property.

The influence of phenolic compound extracts from three colored rice cultivars on the gut microbiota was investigated. The results revealed that protocatechuic acid, chlorogenic acid, caffeic acid and p-coumaric acid were the major metabolites after gut microbiota fermentation. The presence of phenolic compounds led to a significantly decreased ratio of Firmicutes and Bacteroidetes, while the abundance of Proteobacteria decreased. At the genus level, phenolic compounds promoted an increase of Prevotella, Megamonas and Bifidobacterium, while the abundance of Bacteroides and Escherichia-Shigella was inhibited. The concentration of ferulic acid and syringic acid was positively correlated with Bifidobacterium, while Megamonas was positively correlated with catechin and caffeic acid. The abundance of Escherichia-Shigella and Citrobacter was found to be significantly negatively correlated with chlorogenic acid. More importantly, this study revealed that the presence of phenolic compounds generated more propionate, followed by acetate, but not butyrate after gut microbiota fermentation.

Starch propionylation acts as novel encapsulant for probiotic bacteria: A structural and functional analysis.

Propionylated potato starch (PPS) with different degrees of substitution (DS) was prepared from native potato starch (NPS) and their potential to encapsulate Lactobacillus rhamnosus GG (LGG) was analyzed. Fourier transform infrared spectroscopy (FTIR) showed a characteristic peak of propionyl groups, which appeared at 1746 cm-1, demonstrating that propionylation occurred. X-ray diffraction (XRD) results revealed that the characteristic diffraction peak intensity of PPS gradually disappeared with the increasing of the DS, which was related to the loss of the ordered crystalline structure of starch granules. Propionylation resulted in the starch to be more thermally stable than its native starch. Furthermore, the propionylated starch had a higher resistance to digestion and hydrophobicity. More importantly, the micro-capsulated LGG derived from propionylated starch could achieve a maximum embedding efficiency of 87.77% at starch DS = 1.54, and also demonstrated a higher resistance to a strong acidic condition and a greater storage stability at 4 °C. This study may highlight a novel approach for probiotic encapsulation using propionylated potato starch as an encapsulant.

Starch acylation of different short-chain fatty acids and its corresponding influence on gut microbiome and diabetic indexes.

This study investigated correlations between gut microbiota and type 2 diabetic (T2D) indexes using either native resistant starch (RS, from high amylose maize starch, HAMS) or acylated starch via short-chain fatty acids (SCFAs) acylation. Compared to HAMS, consumption of acylated starch achieved a greater impact on the improvement of T2D indexes in term of body weight loss, fasting blood glucose, serum insulin level and amino acid metabolism. Intervention with acylated starches alleviated metabolism disorders and modified the gut microbiota. This study found all the acylated starch significantly enhanced the growth of SCFAs-producing bacteria compared to its native HAMS, and this change was highly consistent with their corresponding SCFAs concentration both in serum and fecal samples. This is the first reported to reveal that propionylated HAMS promoted the abundance of Bifidobacterium, while acetylated and butylated HAMS benefited the enrichment of Coprococcus, Butyricimonas and Blautia, which may indicate their different intervention pathway.

Association of gut microbiota characteristics and metabolites reveals the regulation mechanisms under cadmium consumption circumstance.

BACKGROUND: Cadmium is a non-biodegradable heavy metal with a long biological half-life. Although its negative impact on human health has been previously reported, the association of cadmium consumption overdose with changes in the gut microbiota and its corresponding metabolites has not been fully elucidated so far. RESULTS: Cadmium consumption overdose led to a reduced body weight gain accompanied by an enhanced level of the proinflammatory cytokine tumor necrosis factor-α, interleukin-6, and histamine in the serum of the rats in comparison with normal rats. Furthermore, hepatotoxicity was also observed to be induced by cadmium, which was consistent with abnormal hepatic activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and oxidative stress. In contrast, Lactobacillus rhamnosus-fermented Ganoderma lucidum (FGL) slice supplementation improved the aforementioned physiological properties. More importantly, microbiome and metabolites analysis indicated cadmium exposure significantly reduced the generation of short-chain fatty acids in the gut, particularly butyrate. However, rats in the FGL group had the highest level of butyrate in the feces, characterized with significantly enriched probiotics (Lactobacillus, Bifidobacterium) and butyrate-producing bacteria (Roseburia). CONCLUSION: The targeted regulation of the gut microbial community and its metabolites might be the essential association for attenuating body dysfunction induced by cadmium. The supplementation of FGL, as evidenced in this study, might highlight a novel approach to this field. © 2022 Society of Chemical Industry.

Physicochemical and volatile characteristics present in different grain layers of various rice cultivars.

Five rice cultivars were applied for investigating effect of milling degree on rice physicochemical properties. The first layer had the lowest peak viscosity, followed by the second and third layers, indicating the effect of non-starchy components on starch gelatinization behaviors. Consistently, more content of non-starch components in the first layer led to an enhanced gelatinization temperature. Rheological study demonstrated the G' and G" were successively increased as the layer moved inward, indicating a stronger gel network due to the increased amylose content and crystallinity in the corresponding layer. This is the first study to reveal the second layer has the highest digestibility, suggesting both non-starch components and starch structure control starch digestion. Furthermore, analysis of volatile compounds found alcohols and ketones concentrated in the first layer, whilst compounds including (E,E)-2,4-decadienal, 3-octanone and 3-nonen-2-one only existed in the second layer, serving as an indicator for managing the rice quality during milling.

A review on rice yellowing: Physicochemical properties, affecting factors, and mechanism.

Yellowing is a critical issue that reduces quality and commodity value of rice. This article presents an overview on rice yellowing and the mechanism of rice yellowing was addressed as the emphasis. The change of physicochemical and nutritive properties in yellowed rice depends on the exposure temperature and time, as well as rice cultivar. The temperature and moisture on rice yellowing were dominant. There is no consensus on the relationship between microorganisms and rice yellowing. The occurrence of yellowing is mainly associated with heat stress induced by heaping heat or respiration of grain, and the yellowing is the collective result of primary and secondary metabolism. The upregulation of flavonoids is the direct cause of rice yellowing, which can be used as metabolic markers of rice yellowing. The Maillard reaction also contributes to yellowing during storage. Aeration and cooling are recommended to lessen the occurring of rice yellowing during commercial storage.

Ultrasonication enhanced the multi-scale structural characteristics of rice starch following short-chain fatty acids acylation.

Considering the variation of the diffusion character of the three anhydrides, ultrasonication was applied for investigating its impact on the reaction efficiency of the rice starch acylation from three short-chain fatty acids (SCFAs). The current data indicated that the signal peak of the FTIR spectrum at 1720 cm-1 and additional resonances in the NMR confirmed the occurrence of the acylation reaction onto the starch molecules. More interestingly, this is the first study to reveal that a lower power density ultrasonication improved the reaction efficiencies of acetylation (19%), while a higher power density could lead to a reduced acylation reactivity of propionylation compared to the control one. On the contrary, the reaction efficiency of butyrylation (64%) was significantly enhanced by the ultrasound-assisted treatment with a greater association between reaction efficiency and ultrasonic power density, indicating the importance of the diffusion character for impacting the acylation reactivity among these three anhydrides. The ultrasonic-assisted SCFAs-modified rice starch has a lower peak viscosity and setback value, indicating that the replacement of the acyl groups for OH groups in the starch avoids starch molecules rearrangement. Meanwhile, the rheological properties exhibited that the starch achieved from ultrasonic-assistance significantly reduced the area of the hysteresis curve, suggesting a destroyed gel textural property. Thus, an appropriate ultrasonication but not all could effectively enhance the acylation efficiency and improve starch rheological property.

Manipulation of the internal structure of starch by propionyl treatment and its diverse influence on digestion and in vitro fermentation characteristics.

High amylose maize starch (HAMS) and waxy maize starch (WMS) were modified by propionylation and their corresponding physicochemical characteristics, digestion and fermentation properties were studied. The results indicated that two new peaks related to methylene (2.20 ppm) and methyl (0.97 ppm) in the NMR spectrum were formed, indicating the occurrence of propionylation, and this was further confirmed by the formation of a characteristic absorption at 1747 cm-1 in the FTIR spectrum. The propionylation led the modified starch having a lower electron density contrast between the crystalline and amorphous flakes, resulting in the formation of a more compact structure following the increased degrees of substitution (DS). The propionylated starch also had a higher thermal stability and hydrophobicity. These structural changes increased the content of resistant starch (RS) and reduced the predicted glycemic index. More importantly, the gut microbiota fermentation properties indicated that the propionylation of the starch can not only increase the yield of propionate, but also increase the concentration of total short-chain fatty acids (SCFAs). This study highlights a new approach to significantly enhance the RS content in starch, together with an increased SCFA generation capacity.

Microbiota fermentation characteristics of acylated starches and the regulation mechanism of short-chain fatty acids on hepatic steatosis.

Starches acylated with specific short-chain fatty acids (SCFAs) have the potential to provide specificity in SCFA delivery. It is well documented that SCFAs are involved in lipid metabolism, but the underlying mechanism is still unclear. For characterizing the fermentation properties of acylated starches with various SCFAs in terms of SCFA production, three different acylated starches were prepared following the esterification of high amylose maize starch (HAMS) using acetic anhydride, propionic anhydride and butyric anhydride, respectively. Compared with HAMS, the gut microbiota fermentation of acetylated, propionylated and butylated starches specifically increased the production of acetic acid, propionic acid, and butyric acid, respectively, indicating that the introduced acyl group can be effectively released during the fermentation process. Furthermore, the utilization of these starches generated more total SCFAs, suggesting that they can be effectively fermented by the microbiota as a carbohydrate substrate. Study on an in vitro model of cultured rat hepatocytes indicated that either mixed SCFAs or butyrate play an important role in regulating lipid metabolism via activating AMPK and PPAR signaling pathways, implying the importance of butyrate in the improvement of lipid metabolism and accumulation. This study may provide further understanding of the individual function of the corresponding SCFA.

Manipulations of glucose/lipid metabolism and gut microbiota of resistant starch encapsulated Ganoderma lucidum spores in T2DM rats.

Our team previously demonstrated that Ganoderma lucidum spores (GLS) and resistant starch (RS) had hypoglycemic effects separately on type 2 diabetic mellitus (T2DM) rats. This work was to explore the effects of administering encapsulated GLS within RS (referred to as EGLS) in the T2DM rats, which were induced by streptozotocin (STZ). The EGLS was orally administered to rats for 28 days. The parameters of glycometabolism and lipometabolism were evaluated, and fecal microbiota composition was investigated. The results showed that EGLS significantly enhanced glycometabolism and lipometabolism parameters in T2DM rats, which might be associate with the enhancement of the glucose and lipid metabolism, insulin secretion, and glycogen synthesis and reduced lipogenesis. Furthermore, the intervention of EGLS also reduced the Proteobacteria community and improved dysfunctional gut microbiota. This study indicated EGLS may be a potential candidate for dietary intervention to modulate diabetes.

Preparation, structural characteristics and physiological property of resistant starch.

Starch is of the most important carbohydrates in human diets for maintaining normal body's energy metabolisms. However, due to the increased number of chronic diseases worldwide, the further study of the starch property in the dietary formula becomes essential for revealing its association with preventing or intervening the occurrence of such diseases as diabetes, obesity, intestinal diseases and even cardiovascular diseases. Considering that different starches demonstrate different digestion property based on their individual structural characteristics, in particular, the existence of resistant starch (RS) attracts much more interests recently because of its being a major producer of short-chain fatty acids followed by gut microbial fermentation. Furthermore, the understanding of the interaction between RS and microbiota in the gut and its substantial influence on the regulation of diabetes, kidney, disease hypertension and others is still being under investigated. Therefore, this chapter summarized the fine structure of starch, resistant starch structural characteristics, formation and preparation of resistant starches and their corresponding physiological property.

Hitting the sweet spot: A systematic review of the bioactivity and health benefits of phenolic glycosides from medicinally used plants.

Phenolic acid and flavonoid glycosides form a varied class of naturally occurring compounds, characterised by high polarity-resulting from the glycone moiety-and the presence of multiple phenol functionalities, which often leads to strong antioxidant activity. Phenolic glycosides, and in particular flavonoid glycosides, may possess strong bioactive properties with broad spectrum activity. This systematic literature review provides a detailed overview of 28 studies examining the biological activity of phenolic and flavonoid glycosides from plant sources, highlighting the potential of these compounds as therapeutic agents. The activity of glycosides depends upon the biological activity type, identity of the aglycone and the identity and specific location of the glycone moiety. From studies reporting the activity of both glycosides and their respective aglycones, phenolic glycosides appear to generally be a storage/reserve pool of precursors of more bioactive compounds. The glycosylated compounds are likely to be more bioavailable compared to their aglycone forms, due to the presence of the sugar moieties. Hydrolysis of the glycoside in the in vivo environment would release the free aglycone, potentiating their biological activity. However, further high-quality studies are needed to firmly establish the clinical efficacy of glycosides from many of the plant species studied.

Association of enriched metabolites profile with the corresponding volatile characteristics induced by rice yellowing process.

Change in metabolites and volatiles during yellowing process in six rice cultivars was analyzed. Based on the yellowness, the study indicated Japonica was more prone to yellowing than Indica rice. Metabonomics analysis showed most differential metabolites were up-regulated, in which pathways of flavone and flavonol biosynthesis were significantly enriched following the yellowing process. Meanwhile, 54 differential metabolites were overlapped in six comparative groups, which is characterized by commonly-shared metabolic regulation pathway in each rice. Phenylalanine content was increased, followed by the enhanced phenylpropanoids formation, showing transformation between primary and secondary metabolites during yellowing process. Furthermore, 43 volatile compounds were identified, and the yellowed rice had more volatiles, including ketones, alcohols, esters and hydrocarbons, suggesting a positive correlation with the yellowing. Compounds 6-methyl-5-hepten-2-one and 6,10,14-trimethyl-2-pentadecanone were increased steadily during yellowing process, which may be applied for monitoring rice yellowing progress. This investigation provides further insight for revealing rice yellowing mechanism.

Analysis of secondary metabolites induced by yellowing process for understanding rice yellowing mechanism.

The current study applied wide-targeted metabolomics based approach using LC-ESI-MS/MS to characterize the secondary metabolic difference between yellowed and normal rice. The results indicated that the biosynthesis of secondary metabolites including flavonoids, flavonols and phenolic acids was significantly enhanced during the rice yellowing process, which appears to be highly managed by phenylpropanoid metabolism and flavonoid biosynthetic pathways. Furthermore, rice yellowing led to an increased color parameter b* value, and a number of increased secondary metabolites in the yellowed rice such as homoeriodictyol, naringenin chalcone, 4,2',4',6'-tetrahydroxychalcone contributed to the yellow color. These may have application as potential biomarkers for characterizing rice yellowing.

Analysis of the physiochemical properties of rice induced by postharvest yellowing during storage.

Pasting properties indicated that the yellowing process led to a reduced peak viscosity and breakdown value of the postharvest yellowing (PHY) rice compared to corresponding normal one. More importantly, the current study revealed that both moduli of G' and G″ of the gel formed from the PHY rice was lower than that of its corresponding rice and the yellowing significantly reduced the area of the hysteresis curve. Thus, it is proposed that PHY may inhibit the formation of a continuous network structure. Studies of moisture absorption dynamics and low-field NMR suggested that the yellowing process led to a faster moisture absorption and de-absorption, indicating a faster moisture fluidity in rice kernels induced by yellowing process. Potent of the "capillary channels" might be formed during rice yellowing, and these structural characteristics may be associated with its higher digestibility due to the accelerated diffusion of the digestive enzymes in rice kernels.