Exploring Phytochemical Mechanisms in the Prevention of Cholesterol Dysregulation: A Review.

Although cholesterol plays a key role in many physiological processes, its dysregulation can lead to several metabolic diseases. Statins are a group of drugs widely used to lower cholesterol levels and cardiovascular risk but may lead to several side effects in some patients. Therefore, the development of a plant-based therapeutic adjuvant with cholesterol-lowering activity is desirable. The maintenance of cholesterol homeostasis encompasses multiple steps, including biosynthesis and metabolism, uptake and transport, and bile acid metabolism; issues arising in any of these processes could contribute to the etiology of cholesterol-related diseases. An increasing body of evidence strongly indicates the benefits of phytochemicals for cholesterol regulation; traditional Chinese medicines prove beneficial in some disease models, although more scientific investigations are needed to confirm their effectiveness. One of the main functions of cholesterol is bile acid biosynthesis, where most bile acids are recycled back to the liver. The composition of bile acid is partly modulated by gut microbes and could be harmful to the liver. In this regard, the reshaping effect of phytochemicals on gut microbiota has been widely reported in the literature for its significance. Therefore, we reviewed studies conducted over the past 5 years elucidating the regulatory effects of phytochemicals or herbal medicines on cholesterol metabolism. In addition, their effects on the recomposition of gut microbiota and bile acid metabolism due to modulation are discussed. This review aims to provide novel insights into the treatment of cholesterol dysregulation and the anticipated development of natural-based compounds in the near and far future.

Efficacy and Mechanism of the Action of Live and Heat-Killed Bacillus coagulans BC198 as Potential Probiotic in Ameliorating Dextran Sulfate Sodium-Induced Colitis in Mice.

Inflammatory bowel disease alters the gut microbiota, causes defects in mucosal barrier function, and leads to dysregulation of the immune response to microbial stimulation. This study investigated and compared the efficacy of a candidate probiotic strain, Bacillus coagulans BC198, and its heat-killed form in treating dextran sulfate sodium-induced colitis. Both live and heat-killed B. coagulans BC198 increased gut barrier-associated protein expression, reduced neutrophil and M1 macrophage infiltration of colon tissue, and corrected gut microbial dysbiosis induced by colitis. However, only live B. coagulans BC198 could alleviate the general symptoms of colitis, prevent colon shortening, and suppress inflammation and tissue damage. At the molecular level, live B. coagulans BC198 was able to inhibit Th17 cells while promoting Treg cells in mice with colitis, reduce pro-inflammatory MCP-1 production, and increase anti-inflammatory IL-10 expression in the colonic mucosa. The live form of B. coagulans BC198 functioned more effectively than the heat-killed form in ameliorating colitis by enhancing the anti-inflammatory response and promoting Treg cell accumulation in the colon.

3'-Hydroxypterostilbene Potently Suppresses Tumor Growth via Inhibiting the Activation of the JAK2/STAT3 Pathway in Ovarian Clear Cell Carcinoma.

SCOPE: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin-6 (IL-6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti-cancer effect of pterostilbene (PSB) and 2'- and 3'-hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway. METHODS AND RESULTS: In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti-proliferative and pro-apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation. CONCLUSION: This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.

Purple Napiergrass (Pennisetum purpureum Schumach) Hot Water Extracts Ameliorate High-Fat Diet-Induced Obesity and Metabolic Disorders in Mice.

Purple Pennisetum (Pennisetum purpureum Schumach), a hybrid between Taihucao No. 2 and the local wild species of purple Pennisetum, has dark red stems and leaves due to its anthocyanin content. This study explores the potential of purple napiergrass extracts (PNE) in alleviating obesity and metabolic disorders induced by a high-fat diet in mice, where 50% of the caloric content is derived from fat. Mice were orally administered low-dose or high-dose PNE alongside a high-fat diet. Experimental findings indicate that PNE attenuated weight gain, reduced liver, and adipose tissue weight, and lowered blood cholesterol, triglyceride, low-density lipoprotein, and blood sugar levels. Stained sections showed that PNE inhibited lipid accumulation and fat hypertrophy in the liver. Immunoblotting analysis suggested that PNE improved the inflammatory response associated with obesity, dyslipidemia, and hyperglycemia induced by a high-fat diet. Furthermore, PNE potentially functions as a PPAR-γ agonist, increasing the adiponectin (ADIPOQ) concentration and suppressing inflammatory factors, while elevating the anti-inflammatory factor interleukin-10 (IL-10) in the liver. PNE-treated mice showed enhanced activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and AMP-activated protein kinase (AMPK) pathways and increased fatty acid oxidation and liver lipolysis. In conclusion, this study elucidated the mechanisms underlying the anti-inflammatory, PI3K/Akt, and AMPK pathways in a high-fat diet-induced obesity model. These findings highlight the potential of PNE in reducing weight, inhibiting inflammation, and improving blood sugar and lipid levels, showing the potential for addressing obesity-related metabolic disorders in humans.

Identification of Indicative Gut Microbial Guilds in a Natural Aging Mouse Model.

Gut microbial dysbiosis during later life may contribute to health conditions, possibly due to an increase in intestinal permeability, immune changes, and systemic inflammation. Mouse models have been employed to determine the influence of gut microbes on aging; however, suitable gut microbial indicators are currently lacking. Therefore, this study aimed to determine the gut microbial indicators and their potential guilds in a natural aging mouse model. In agreement with previous studies, alpha diversity indices-including observed OTUs, ACE, Chao1, and Simpson-were significantly lower in aged mice than in younger mice. The results of beta diversity analysis revealed the compositional differences between young and aged mice, and the MRPP, ANOSIM, and Adonis tests indicated that the results were representative. By employing ANCOM and LEfSe analyses, Bacteroides thetaiotaomicron (Bacteroides) and Anaeroplasma were identified as the indicators of young and aged mice, respectively. Notably, these indicators were still present after 3 months. The result of network analysis confirmed the negative correlation of these genera in mice, and the potential guild members were identified based on the increased abundance of Anaeroplasma in aged mice. The gut microbes of aged mice tend to correspond to those involved in human diseases, selenocompound metabolism, and glycolysis/gluconeogenesis in functional predictions. In this study, the gut microbial indicators in aged mice have been identified, and it is envisaged that these findings could provide a new approach for future studies of antiaging.

High Gamma-Aminobutyric Acid (GABA) Oolong Tea Alleviates High-Fat Diet-Induced Metabolic Disorders in Mice.

Obesity and overweight are associated with an increasing risk of developing health conditions and chronic non-communicable diseases, including cardiovascular diseases, cancer, musculoskeletal problems, respiratory problems, and mental health, and its prevalence is rising. Diet is one of three primary lifestyle interventions. Many bioactive components in tea especially oolong tea, including flavonoids, gamma-aminobutyric acid (GABA), and caffeine were reported to show related effects in reducing the risk of obesity. However, the effects of GABA oolong tea extracts (OTEs) on high-fat diet (HFD)-induced obesity are still unclear. Therefore, this study aims to explore whether the intervention of GABA OTEs can prevent HFD-induced obesity and decipher its underlying mechanisms using male C57BL/6 J mice. The result indicated that GABA OTEs reduced leptin expression in epididymal adipose tissue and showed a protective effect on nonalcoholic fatty liver disease. It promoted thermogenesis-related protein of uncoupling protein-1 and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), boosted lipid metabolism, and promoted fatty acid oxidation. It also reduced lipogenesis-related protein levels of sterol regulatory element binding protein, acetyl-CoA carboxylase, and fatty acid synthase and inhibited hepatic triglyceride (TG) levels. These data suggest that regular drinking of GABA oolong tea has the potential to reduce the risk of being overweight, preventing obesity development through thermogenesis, lipogenesis, and lipolysis.

Effects of Debranching Conditions and Annealing Treatment on the Formation of Starch Nanoparticles and Their Physicochemical Characteristics.

Starch nanoparticles (SNPs) have unique attributes that make them suitable for specific applications. In this study, we assessed the optimum conditions for the fabrication of SNPs from the rice starches of low- (TCSG2) and medium-amylose rice lines (TK11) using pullulanase debranching combined with annealing treatment and evaluated their physicochemical and digestion properties. The highest crystalline SNP percent recoveries of 15.1 and 11.7% were obtained from TK11 and TCSG2, respectively, under the following debranching conditions: 540-630 NPUN/g, pH 5.0, 60 °C, and 12 h. The percent recovery of the crystalline SNPs by the combined modification of the debranching and the annealing treatment with an extended annealing incubation prepared from TK11 and TCSG2 was significantly increased to 25.7 and 23.8%, respectively. The modified starches from TK11 had better percent recovery of the crystalline SNPs than those from TCSG2. They exhibited a higher weight-average molecular weight (Mw) and a broader/bimodal molecular weight distribution with a higher polydispersity (PDI) (Mw = 92.76-92.69 kDa; PDI = 4.4) than those from TCSG2 (Mw = 7.13-7.15 kDa; PDI = 1.7). Compared to the native counterparts, the color analyses showed that the modified starches from TK11 and TCSG2 exhibited decreased brightness (L*)/whiteness index (WI) values with marked color difference values (∆E) ranging between 6.32 and 9.39 and 10.67 and 11.32, respectively, presumably due to the protein corona formed on the surface of SNPs which induced the browning reaction during the treatments. The pasting properties revealed that the modified starches displayed restricted swelling power with extremely low pasting viscosities, reflecting that they were highly thermally stable. The modified starches, especially those treated with an extended annealing incubation, exhibited marked decreases in the rate and extent of digestion and estimated glycemic index due to the honeycomb-like agglomerates comprising an assembly of densely packed SNPs. The results could provide helpful information for the preparation and characterization of the crystalline SNPs for potential applications such as emulsion stabilizers for Pickering emulsion and health-promoting ingredients.

Pterostilbene Enhances Thermogenesis and Mitochondrial Biogenesis by Activating the SIRT1/PGC-1α/SIRT3 Pathway to Prevent Western Diet-Induced Obesity.

SCOPE: Sirtuin 1/peroxisome proliferator-activated receptor gamma co-activator 1 alpha (SIRT1/PGC-1α) pathway activation is known to promote thermogenesis and mitochondrial biogenesis. Pterostilbene (PSB) and pinostilbene (PIN), the methylated analogs of resveratrol, are potential candidates to enhance thermogenesis and mitochondrial biogenesis. METHOD AND RESULTS: A model of Western diet-induced obesity in mice is designed. Either PSB or PIN is supplemented in the diet for 16 weeks. Both samples can significantly reduce body weight gain but only PSB can decrease inguinal adipose tissue weight. Besides, both samples can promote lipolysis but only PSB supplementation activates the SIRT1/PGC-1α/SIRT3 pathway to enhance mitochondrial biogenesis and thermogenesis in the inguinal adipose tissue. In addition, although both samples exert a modulatory effect on gut microbiota but significant increments in fecal isobutyric acid, valeric acid, and isovaleric acid are only observed in the PSB group, functioning as gut microbial metabolites. CONCLUSION: Overall, these findings suggest PSB and PIN as potential candidates for the improvement of obesity and gut microbiota dysbiosis. With its higher stability, PSB exerts a greater effect than PIN by promoting thermogenesis and mitochondrial biogenesis via SIRT1 activation.

Cross-Sectional Study: New Approach for Diagnostic Identification of Non-Robust Older Adult.

SCOPE: The aging biomarkers are alternatives and none of them can act as a strong predictor of frailty during the progression of aging. Several studies reveal the relationship between metabolites and frailty or gut microbiota and frailty. However, the connection between metabolites and gut microbiota in non-robust older adults has not been discussed yet. The study aims to combine the findings of serum metabolites and gut microbiota in non-robust subjects as a possible diagnostic biomarker. METHODS AND RESULTS: Frailty-related assessments are conducted to ensure the discrimination of non-robustness. The serum and fecal are collected for serum metabolomics and gut microbiota analysis. Robust and non-robust subjects show very different gut microbial compositions. Among the gut microbial differences, Escherichia/Shigella and its higher taxonomic ranks are found to have the most discriminative abundance among compared groups. More importantly, the abundance of Escherichia/Shigella is found to be positively correlated (p < 0.05) with the level of discriminant metabolites, such as serum oxoglutarate, glutamic acid, and 1-methyladenosine. CONCLUSION: These results indicate the obvious interrelation between gut microbiota and serum metabolites in non-robust older adults. Besides, the findings suggest that Escherichia/Shigella can be a potential biomarker candidate for robustness sub-phenotypic identification.

Prevention of Glutamate-Induced Neurodegeneration by Piceatannol via Mitochondrial Rescue In Vitro and In Vivo.

SCOPE: Parkinson's disease is one of the neurodegenerative diseases that have no cure. Excitotoxicity induced by excess glutamate is known to be a hallmark of these diseases. Therefore, this study aims to evaluate the preventive effect of piceatannol on glutamate-induced neurodegeneration via mitochondrial rescue. METHODS AND RESULTS: The PC12 cell line and three Caenorhabditis elegans (C. elegans) strains are employed to achieve the aim. In the in vitro study, the results show that piceatannol can prevent glutamate-induced apoptosis. Piceatannol also reduces mitochondrial reactive oxygen species (ROS) accumulation by activating the antioxidant system. Moreover, piceatannol can also promote mitochondrial biogenesis and induced mitochondrial fusion-related genes to preserve mitochondrial functionality. In the C. elegans model, piceatannol can prevent mitochondrial fragmentation induced by glutamate. More importantly, piceatannol effectively protects dopaminergic neurons from degradation and preserves the responses controlled by these neurons. CONCLUSION: The findings suggest that piceatannol can be a more effective and potent candidate for the treatment of neurodegenerative diseases, such as Parkinson's disease, compared to resveratrol. It is capable of preventing neurodegeneration induced by excess glutamate, possibly via mitochondrial rescue. It is recommended that piceatannol be developed into a neuroprotective agent.

The Role of Mitochondria in Phytochemically Mediated Disease Amelioration.

Mitochondrial dysfunction may cause cell death, which has recently emerged as a cancer prevention and treatment strategy mediated by chemotherapy drugs or phytochemicals. However, most existing drugs cannot target cancerous cells and may adversely affect normal cells via side effects. Mounting studies have revealed that phytochemicals such as resveratrol could ameliorate various diseases with dysfunctional or damaged mitochondria. For instance, resveratrol can regulate mitophagy, inhibit oxidative stress and preserve membrane potential, induce mitochondrial biogenesis, balance mitochondrial fusion and fission, and enhance the functionality of the electron transport chain. However, there are only a few studies suggesting that phytochemicals could potentially protect against the cytotoxicity of some current cancer drugs, especially those that damage mitochondria. Besides, COVID-19 and long COVID have also been reported to be correlated to mitochondrial dysfunction. Curcumin has been reported bringing a positive impact on COVID-19 and long COVID. Therefore, in this study, the benefits of resveratrol and curcumin to be applied for cancer treatment/prevention and disease amelioration were reviewed. Besides, this review also provides some perspectives on phytochemicals to be considered as a treatment adjuvant for COVID-19 and long COVID by targeting mitochondrial rescue. Hopefully, this review can provide new insight into disease treatment with phytochemicals targeting mitochondria.

Modulatory Effect of Fermented Black Soybean and Adlay on Gut Microbiota Contributes to Healthy Aging.

SCOPE: Aging is a natural process characterized by a multifactorial, physical decline, and functional disability. Nevertheless, healthy aging can be achieved by following a multidirectional strategy. The current study aims to investigate the anti-aging potential of fermented black soybean and adlay (FBA). METHODS AND RESULTS: FBA supplements are incorporated into a natural aging mouse model that is designed to evaluate anti-aging effects. Results show that FBA supplementation prevents muscle loss and visceral adipose tissue accumulation. FBA can also reduce aging biomarkers (including the expression of hepatic p16INK4A and galactosidase beta-1 (GLB1). Hepatic 8-hydoxy-2'-deoxyguanosine (8-oxodG) and pro-inflammatory cytokines have been significantly reduced. Lastly, FBA supplementation improves aging-related gut microbial dysbiosis by reshaping gut microbial composition and promoting the growth of beneficial microbes such as Alistipes, Anaeroplasma, Coriobacteriaceae UCG002, and Parvibacter members in both genders of aged mice. In the functional prediction of gut microbiota, correlations to metabolic, neurodegenerative, infectious, and immune system diseases have been reduced in supplemented mice compared to aged mice. Moreover, FBA supplementation can reverse the reduced ability of microbiota in aged mice for lipid metabolism and xenobiotics biodegradation. CONCLUSIONS: The results suggest that FBA exhibits noteworthy anti-aging effects and that it can potentially be developed into a functional food for healthy aging.

Amination Potentially Augments the Ameliorative Effect of Curcumin on Inhibition of the IL-6/Stat3/c-Myc Pathway and Gut Microbial Modulation in Colitis-Associated Tumorigenesis.

Epigallocatechin gallate and tetrahydrocurcumin are aminated as colonic metabolites, preserving their bioactivities and improving their capabilities. We compared the bioactivities of unaminated (CUR) and aminated (AC) curcumin in inflammatory colitis-associated tumorigenesis. The anti-inflammatory and anticancer capabilities of CUR and AC were evaluated using RAW264.7 and HT29 cell lines, respectively. An azoxymethane/dextran sodium sulfate-induced colitis-associated carcinogenesis mouse model was used with CUR and two-dose AC interventions. AC had a greater anti-inflammatory effect but a similar anticancer effect as CUR in vitro. CUR and low-dose AC (LAC) significantly preserved colon length and reduced tumor number in vivo. Both CUR and LAC inhibited activation of the protein kinase B (AKT)/nuclear factor kappa B (NF-κB) signaling pathway, its downstream cytokines, and the interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3)/c-myelocytomatosis oncogene (c-MYC) pathway. However, only LAC significantly preserved E-cadherin, reduced N-cadherin, and facilitated beneficial gut microbial growth, including Akkermansia and Bacteroides, potentially explaining AC's better ameliorative effect at low than high doses.

The Anti-Obesity and Anti-Inflammatory Capabilities of Pterostilbene and its Colonic Metabolite Pinostilbene Protect against Tight Junction Disruption from Western Diet Feeding.

SCOPE: Tight junctions (TJs) are a member of the intestinal epithelium barrier that provides the first line of protection against external factors. Anti-obesity and protective effects of pterostilbene (PSB) on TJs have previously been reported, but the effect of its colonic metabolite, pinostilbene (PIN), is less understood. METHODS AND RESULTS: A 16-week animal model feed with western-diet to induce colonic TJs disruption is designed, supplemented with PSB and PIN to evaluate their potent in colonic TJ protection. The results show that both PSB and PIN exert suppressive effects on obesity, hepatic steatosis, and chronic inflammation in western-diet-fed mice. Western-diet feeding significantly reduces expression of TJ proteins, including ZO-1, occludin, and claudin-1, while PSB and PIN supplementation effectively protects TJ proteins against disruption. Increment in serum, hepatic, and mesenteric pro-inflammatory cytokines suggests their probable involvement in TJ disruption supported with the findings in macrophage polarization. The adverse are revered by PSB and PIN. The protective effect of PSB and PIN on TJ proteins may stem from their anti-inflammation capabilities. CONCLUSION: This is the first study suggesting that PIN, the metabolite of PSB, demonstrates a similar protective effect on colonic TJ proteins via its anti-obesity, hepatic protection, and anti-inflammatory capabilities.

Dietary Pterostilbene and Resveratrol Modulate the Gut Microbiota Influenced by Circadian Rhythm Dysregulation.

SCOPE: A causal relationship between circadian misalignment and microbiota dysbiosis has been discussed recently, due to their association to pathogenesis. Herein, the possible impact of pterostilbene (PSB) and resveratrol (RES) on the gut microbiota brought by chronic jet-lag in mice is investigated. METHODS AND RESULTS: Dietary supplement of RES and PSB (0.25%) are given to 16 week-jetlagged mice to examine the effects on microbiota and physiological functions. Jetlag significantly induces weight gained that could be effectively prevented by PSB. Both supplements also retain oscillation patterns that found to be lost in jetlag induced (JLG) group, including serum biochemical parameters and gut microbiota. The results of beta diversity suggest the supplementations efficiently lead to distinct gut microbial composition as compared to JLG group. Besides, the supplementation forestalls some microbial elevation, such as Eubacterium ventriosum and Acetitomaculum. Growth of health beneficial bacteria like Blautia and Lachnospiraceae UCG-001 is facilitated and abundance of these bacteria could be correlated to oscillation of biochemical parameters. Result of KEGG indicates distinct effect brought by microbial re-shaping. CONCLUSION: The result suggests that supplementation of RES and PSB could potentially dampen some adverse effects of gut microbiota dysbiosis, and at the same time, re-composite and facilitate the growth of health beneficial microbiota.

Recent Advances in Health Benefits of Stilbenoids.

Biological targeting or molecular targeting is the main strategy in drug development and disease prevention. However, the problem of "off-targets" cannot be neglected. Naturally derived drugs are preferred over synthetic compounds in pharmaceutical markets, and the main goals are high effectiveness, lower cost, and fewer side effects. Single-target drug binding may be the major cause of failure, as the pathogenesis of diseases is predominantly multifactorial. Naturally derived drugs are advantageous because they are expected to have multitarget effects, but not off-targets, in disease prevention or therapeutic actions. The capability of phytochemicals to modulate molecular signals in numerous diseases has been widely discussed. Among them, stilbenoids, especially resveratrol, have been well-studied, along with their potential molecular targets, including AMPK, Sirt1, NF-κB, PKC, Nrf2, and PPARs. The analogues of resveratrol, pterostilbene, and hydroxylated-pterostilbene may have similar, if not more, potential biological targeting effects compared with their original counterpart. Furthermore, new targets that have been discussed in recent studies are reviewed in this paper.

A Natural Degradant of Curcumin, Feruloylacetone Inhibits Cell Proliferation via Inducing Cell Cycle Arrest and a Mitochondrial Apoptotic Pathway in HCT116 Colon Cancer Cells.

Feruloylacetone (FER) is a natural degradant of curcumin after heating, which structurally reserves some functional groups of curcumin. It is not as widely discussed as its original counterpart has been previously; and in this study, its anticancer efficacy is investigated. This study focuses on the suppressive effect of FER on colon cancer, as the efficacious effect of curcumin on this typical cancer type has been well evidenced. In addition, demethoxy-feruloylacetone (DFER) was applied to compare the effect that might be brought on by the structural differences of the methoxy group. It was revealed that both FER and DFER inhibited the proliferation of HCT116 cells, possibly via suppression of the phosphorylated mTOR/STAT3 pathway. Notably, FER could significantly repress both the STAT3 phosphorylation and protein levels. Furthermore, both samples showed capability of arresting HCT116 cells at the G2/M phase via the activation of p53/p21 and the upregulation of cyclin-B. In addition, ROS elevation and changes in mitochondrial membrane potential were revealed, as indicated by p-atm elevation. The apoptotic rate rose to 36.9 and 32.2% after being treated by FER and DFER, respectively. In summary, both compounds exhibited an anticancer effect, and FER showed a greater proapoptotic effect, possibly due to the presence of the methoxy group on the aromatic ring.

A multi-targeting strategy to ameliorate high-fat-diet- and fructose-induced (western diet-induced) non-alcoholic fatty liver disease (NAFLD) with supplementation of a mixture of legume ethanol extracts.

NAFLD (non-alcoholic fatty liver disease) is a multifactorial liver disease related to multiple causes or unhealthy conditions, including obesity and chronic inflammation. The accumulation of excess triglycerides, called steatosis, is known as a hallmark of an imbalance between the rates of hepatic fatty acid uptake/synthesis and oxidation/export. Furthermore, occurrence of NAFLD may lead to a cocktail of disease consequences caused by the altered metabolism of glucose, lipids, and lipoproteins, for instance, insulin resistance, type II diabetes, nonalcoholic steatohepatitis (NASH), liver fibrosis, and even hepatocarcinogenesis. Due to the complexity of the occurrence of NAFLD, a multi-targeting strategy is highly recommended to effectively address the issue and combat the causal loop. Ethanol extracts of legumes are popular supplements due to their richness and diversity in phytochemicals, especially isoflavones and anthocyanins. Although many of them have been reported to have efficacy in the treatment of different metabolic syndromes and obesity, there have not been many studies on them as a supplemental mixture. In this study, the alleviative effects of selected legume ethanol extracts (CrE) on high-fat-diet- and fructose-induced obesity, liver steatosis, and hyperglycemia are discussed. As revealed by the findings, CrE not only ameliorated obesity in terms of weight gained and enlargement of adipose tissue, but also significantly reduced the incidence of steatosis via phosphorylation of AMPK, resulting in inhibition of the downstream SREBP-1c/FAS pathway and an increase in an indicator of ß-oxidation (carnitine palmitoyl transferase 1a, CPT1A). Furthermore, CrE dramatically alleviated inflammatory responses, including both plasma and hepatic TNF-α, IL-6, and MCP-1 levels. CrE also had attenuating effects on hyperglycemia and insulin resistance and significantly reduced the fasting glucose level, fasting insulin level, and plasma leptin, and it exhibited positive effects in the Oral glucose tolerance test (OGTT) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). At the molecular level, CrE could activate the PI3K/Akt/Glut2 pathway, which indicated an increase in insulin sensitivity and glucose uptake. Taken together, these results suggest that ethanol extracts of legumes could be potential supplements for metabolic syndromes, and their efficacy and effectiveness might facilitate the multi-targeting strategy required to mitigate NAFLD.

Recent advances in cancer chemoprevention with phytochemicals.

Over the past few decades, phytochemicals widely present in edible plants have exhibited compelling positive biological impact on human health, including treating some cancers. In some cases, metabolites and artificially modified products of these natural compounds have shown better chemopreventive effects than their natural counterparts. Along with direct chemopreventive strategies using phytochemicals to treat cancer by leading to cell cycle arrest, autophagy and apoptosis, natural compounds have been shown to reverse adverse epigenetic regulation, including altering DNA methylation and histone modification, modulating miRNA expression, promoting expression of phase II enzyme for detoxification, balancing inflammation responses, recovering circadian rhythm from misalignment, and modifying gut microbiota. These have all become part of indirect but effective and novel strategies in cancer prevention using phytochemicals. Therefore, in this review, we are going to summarize some findings of phytochemicals in cancer chemoprevention via several distinct strategies, both to highlight promising treatments and to encourage new ideas for future studies.

Resveratrol and Oxyresveratrol Activate Thermogenesis via Different Transcriptional Coactivators in High-Fat Diet-Induced Obese Mice.

Obesity is a global public health issue. Thermogenesis is a novel way to promote anti-obesity by consuming energy as heat rather than storing it as triacylglycerols. The browning program allows mitochondrial biosynthesis and thermogenesis-related gene expression to occur in subcutaneous white adipose tissue, which results in the formation of beige adipose tissue. Some phytochemicals have exerted the capability to activate the fat browning process. Resveratrol and oxyresveratrol are both natural stilbenoids that have been reported for their anti-obesity efficacy. However, the comparison between the two as they relate to thermogenesis as well as the differences in their underlying mechanisms are still not widely discussed. Our result reveals that both resveratrol and oxyresveratrol could elevate the expression of thermogenesis-related protein expression including UCP1 (uncoupling protein-1) and PRDM (PR domain containing 16) via Sirt1/PGC-1α (sirtuin 1/peroxisome proliferation gamma coactivator-1 α) activation. However, it is suggested that the transcriptional factor PPARα (peroxisome proliferator-activator receptor α) was activated by resveratrol (1.38 ± 0.07 fold) but not oxyresveratrol. Conversely, C/EBPß (CCAAT/enhancer-binding protein ß) was upregulated by oxyresveratrol (1.58 ± 0.05 fold) but not by resveratrol. On the other hand, CPT1 (carnitine palmitoyltransferase) was found to be significantly activated at lower concentrations of oxyresveratrol up to 1.89 ± 0.04 fold as compared to high-fat diet, and it could be a leading reason for UCP1 activation. Lastly, adiponectin expression was promoted in all experimental groups (1.53 ± 0.08 and 1.49 ± 0.11-fold in resveratrol (RES) and high oxyresveratrol (HOXY), respectively), which could be an activator for mitochondrial biosynthesis and UCP1 expression.