Discovery of a Potent Antiosteoporotic Drug Molecular Scaffold Derived from Angelica sinensis and Its Bioinspired Total Synthesis.

Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4). Falcarinphthalides A and B (1 and 2) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated. The structures of 1 and 2, including their absolute configurations, were established using extensive analysis of NMR spectra, chemical derivatization, and ECD/VCD calculations. Based on LC-HR-ESI-MS analysis and DFT calculations, a production mechanism for 1 and 2 involving enzyme-catalyzed Diels-Alder/retro-Diels-Alder reactions was proposed. Falcarinphthalide A (1), the most promising lead compound, exhibits potent in vitro antiosteoporotic activity by inhibiting NF-κB and c-Fos signaling-mediated osteoclastogenesis. Moreover, the bioinspired gram-scale total synthesis of 1, guided by intensive DFT study, has paved the way for further biological investigation. The discovery and gram-scale total synthesis of falcarinphthalide A (1) provide a compelling lead compound and a novel molecular scaffold for treating osteoporosis and other metabolic bone diseases.

Forsythoside A protects against Zearalenone-induced cell damage in chicken embryonic fibroblasts via mitigation of endoplasmic reticulum stress.

Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin that exerts its toxic effects through various damage mechanisms such as oxidative stress, endoplasmic reticulum stress (ERS), mitochondrial damage, cell cycle arrest, and apoptosis. At present, there are few studies on drugs that can rescue ZEA-induced chicken embryonic fibroblasts damage. Forsythoside A (FA) is one of effective ingredients of traditional Chinese medicine that plays a role in various biological functions, but its antitoxin research has not been investigated so far. In this study, in vitro experiments were carried out. Chicken embryo fibroblast (DF-1) cells was used as the research object to select the appropriate treatment concentration of ZEA and examined reactive oxygen species (ROS), mitochondrial membrane potential, ERS and apoptosis to investigate the effects and mechanisms of FA in alleviating ZEA-induced cytotoxicity in DF-1 cells. Our results showed that ZEA induced ERS and activated the unfolded protein response (UPR) leading to apoptosis, an apoptotic pathway characterized by overproduction of Lactate dehydrogenase (LDH), Caspase-3, and ROS and loss of mitochondrial membrane potential. We also demonstrated that FA help to prevent ERS and attenuated ZEA-induced apoptosis in DF-1 cells by reducing the level of ROS, downregulating GRP78, PERK, ATF4, ATF6, JNK, IRE1, ASK1, CHOP, BAX expression, and up-regulating Bcl-2 expression. Our results provide a basis for an in-depth study of the mechanism of toxic effects of ZEA on chicken cells and the means of detoxification, which has implications for the treatment of relevant avian diseases.

Herbal Products-Powered Thermosensitive Hydrogel with Phototherapy and Microenvironment Reconstruction for Accelerating Multidrug-Resistant Bacteria-Infected Wound Healing.

Wound healing and infection remain significant challenges due to the ineffectiveness against multidrug-resistant (MDR) bacteria and the complex oxidative wound microenvironments. To address these issues, thymoquinone-reinforced injectable and thermosensitive TQ@PEG-PAF-Cur hydrogels with dual functions of microenvironment reshaping and photodynamic therapy are developed. The hydrogel comprises natural compound thymoquinone (TQ) and poly (ethylene glycol)-block-poly (alanine-co-phenyl alanine) copolymers (PEG-PAF) conjugated with natural photosensitizer curcumin (Cur). The incorporation of TQ and Cur reduces the sol-to-gel transition temperature of TQ@PEG-PAF-Cur to 30°C, compared to PEG-PAF hydrogel (37°C), due to the formation of strong hydrogen bonding, matching the wound microenvironment temperature. Under blue light excitation, TQ@PEG-PAF-Cur generates significant amounts of reactive oxygen species such as H2O2, 1O2, and ·OH, exhibiting rapid and efficient bactericidal capacities against methicillin-resistant Staphylococcus aureus and broad spectrum ß-lactamases Escherichia coli via photodynamic therapy (PDT). Additionally, Cur effectively inhibits the expressions of proinflammatory cytokines in skin tissue-forming cells. As a result, the composite hydrogel can rapidly transform into a gel to cover the wound, reshape the wound microenvironment, and accelerate wound healing in vivo. This collaborative antibacterial strategy provides valuable insights to guide the development of multifunctional materials for efficient wound healing.

A TME-activated nano-catalyst for triple synergistic therapy of colorectal cancer.

Colorectal cancer cells are highly heterogeneous and exhibit various drug resistances, making personalized treatment necessary. This typically involves a combination of different treatment modalities such as surgery, radiation, and chemotherapy to increase patient survival. Inspired by this, synergistic therapy, which combines multiple modalities into a single nanotherapeutic drug, shows promise in treating cancer. In this study, a nano-catalyst based on calcium peroxide (CaO2) and the chemotherapeutic drug doxorubicin hydrochloride (DOX) co-loaded into HPB nanoparticles (HPB@CaO2/DOX-PAA) was developed to achieve synergistic cancer treatment through chemodynamic/chemo/photothermal (CDT/CT/PTT) mechanisms. After being endocytosed by cancer cells, the nano-catalyst decomposes, releasing cargo. During near-infrared light irradiation, HPB induces a photothermal effect, DOX exhibits significant RNA and DNA destruction capabilities, meanwhile CaO2 produces a large amount of H2O2 in the moderately acidic TME, which combines with Fe2+ ions derived from HPB to form the highly toxic •OH in a Fenton-like reaction, enhancing the chemodynamic treatment. Assays conducted ex vivo and in vivo have exhibited the efficacy of this triple synergistic therapeutic regimen, indicating its potential clinical application.

Anthocyanins-natural pigment of colored rice bran: Composition and biological activities.

Rice by-products are a potential source of various bioactive substances with great processing potential, which are receiving increasing attention. Among them, rice bran is a by-product of rice milling, with high nutritional value and health benefits. Colored rice bran contains a large amount of anthocyanins responsible for color and bioactivities. And anthocyanins are often added to foods as a natural pigment, serving to enhance both the visual appeal and nutritional value. Recent advances in the composition and bioactivities of four common colored rice bran anthocyanins (black, purple, red, and purple red rice) are reviewed in this paper. Rice bran anthocyanins have been confirmed to exhibit biological potential for human health, with their main biological activities being antioxidant, anti-atherosclerosis, anti-cancer, neuroprotective, retinoprotective, immunomodulatory, anti-aging and anti-obesity effects. The structure of anthocyanins determines their biological activities. The anthocyanins composition of rice bran with different colors varied greatly, while that of rice bran with the same color is also slightly different, which is attributed to the rice varieties, growing environment and cropping conditions. However, it remains necessary to conduct further clinical studies to support the health activities of anthocyanins. The present review provides information value for the further development and comprehensive utilization of rice bran anthocyanins.

Exploring acupuncture treatment strategies for snoring based on meridian theory. / 基于经络学说探析鼾症的针刺治疗思路.

Starting from the perspective of meridian theory, this article briefly analyzes the meridian pathophysiology of snoring and the relationship between snoring and meridian theory. It proposes that acupuncture treatment for snoring should focus on regulating qi from the shaoyang meridians, harmonizing the spirit by the governor vessel, resolving phlegm through the three yang meridians, and harmonizing qi and blood from the yangming meridians. Additionally, attention is placed on both the root cause and the symptoms, the theory of "four seas". The ultimate goal is to promote the flow of meridian and qi-blood, improve symptoms such as nighttime snoring, poor sleep quality, and daytime sleepiness, and achieve the desired outcome of stopping snoring and ensuring restful sleep.

Release characteristic of bound polyphenols from tea residues insoluble dietary fiber by mixed solid-state fermentation with cellulose degrading strains CZ-6 and CZ-7.

The purpose of this work was to investigate the release characteristic of bound polyphenols (BP) from tea residues insoluble dietary fiber (IDF) by mixed solid-state fermentation (SSF) with cellulose degrading strains CZ-6 and CZ-7. The results implied that cellulase, ß-glucosidase and filter paper lyase activities were strongly correlated with the BP content. The scanning electron microscop and fourier transform infrared spectroscopy manifested that the cellulose network of the IDF was decomposed and dissolve, forming more loose fibrous structure. Additionally, 28 polyphenols components were detected and their biotransformation pathways were preliminary speculated. Moreover, the BP obtained by mixed SSF produced prominent inhibitory activities against α-glucosidase and α-amylase, as well as exhibited significant scavenging effects on DPPH•, ABTS+• free radicals and ferric reducing antioxidant power. These findings could further promote the utilization of BP from agricultural by-products in a more natural and economical method, CZ-6 and CZ-7 strains provide a new approach to expound the release and conversion of BP.

[Application of single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical trials].

Due to various constraints, such as clinical implementation conditions and unique characteristics of acupuncture-moxibustion, some randomized controlled trials (RCTs) of acupuncture-moxibustion still suffer from relatively low quality and limited applicability. The single-arm objective performance criteria/performance goal can be considered as an ideal supplementary and alternative research approach to RCTs. In this paper, the feasibility of applying the single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical research is explored from the limitations of conducting acupuncture-moxibustion RCTs, the principles, the essential design considerations and key statistical steps. In addition, illustrative examples are provided. The objective is to offer insights into resolving practical difficulties in acupuncture-moxibustion clinical research.

[Clinical thinking of acupuncture for snoring based on "disharmony qi leads to restlessness"].

This study summarizes the clinical thinking of acupuncture for snoring based on "disharmony qi leads to restlessness". According to the pathological characteristics of qi stagnation and blood stasis, phlegm dampness and internal obstruction in snoring patients, combined with the etiology, pathogenesis and location of the disease, the innovative viewpoint of "disharmony qi leads to restlessness" is proposed. It is believed that the key to snoring treatment lies in "regulating qi ". In clinical practice, acupuncture can directly regulate the qi of the disease's location, regulate the qi of the organs and viscera, and regulate the qi of the meridians to achieve overall regulation of the body's internal and external qi, smooth circulation of qi and blood, and ultimately achieve the therapeutic goal of harmonizing qi, stopping snoring, and improving sleep quality.

Phyllanthus emblica fruits: a polyphenol-rich fruit with potential benefits for oral management.

The fruit of Phyllanthus emblica Linn., which mainly grows in tropical and subtropical regions, is well-known for its medicine and food homology properties. It has a distinctive flavor, great nutritional content, and potent antioxidant, anti-inflammatory, anti-cancer and immunoregulatory effects. According to an increasing amount of scientific and clinical evidence, this fruit shows significant potential for application and development in the field of oral health management. Through the supplementation of vitamins, superoxide dismutase (SOD) and other nutrients reduce virulence expression of various oral pathogens, prevent tissue and mucosal damage caused by oxidative stress, etc. Phyllanthus emblica fruit can promote saliva secretion, regulate the balance of the oral microecology, prevent and treat oral cancer early, promote alveolar bone remodeling and aid mucosal wound healing. Thus, it plays a specific role in the prevention and treatment of common oral disorders, producing surprising results. For instance, enhancing the effectiveness of scaling and root planing in the treatment of periodontitis, relieving mucosal inflammation caused by radiotherapy for oral cancer, and regulating the blood glucose metabolism to alleviate oral discomfort. Herein, we systematically review the latest research on the use of Phyllanthus emblica fruit in the management of oral health and examine the challenges and future research directions based on its chemical composition and characteristics.

Exploring the efficacy of herbal medicinal products as oral therapy for inflammatory bowel disease.

Inflammatory bowel disease (IBD) encompasses a collection of idiopathic diseases characterized by chronic inflammation in the gastrointestinal (GI) tract. Patients diagnosed with IBD often experience necessitate long-term pharmacological interventions. Among the multitude of administration routes available for treating IBD, oral administration has gained significant popularity owing to its convenience and widespread utilization. In recent years, there has been extensive evaluation of the efficacy of orally administered herbal medicinal products and their extracts as a means of treating IBD. Consequently, substantial evidence has emerged, supporting their effectiveness in IBD treatment. This review aimed to provide a comprehensive summary of recent studies evaluating the effects of herbal medicinal products in the treatment of IBD. We delved into the regulatory role of these products in modulating immunity and maintaining the integrity of the intestinal epithelial barrier. Additionally, we examined their impact on antioxidant activity, anti-inflammatory properties, and the modulation of intestinal flora. By exploring these aspects, we aimed to emphasize the significant advantages associated with the use of oral herbal medicinal products in the treatment of IBD. Of particular note, this review introduced the concept of herbal plant-derived exosome-like nanoparticles (PDENs) as the active ingredient in herbal medicinal products for the treatment of IBD. The inclusion of PDENs offers distinct advantages, including enhanced tissue penetration and improved physical and chemical stability. These unique attributes not only demonstrate the potential of PDENs but also pave the way for the modernization of herbal medicinal products in IBD treatment.

Extraction optimization of tea saponins from Camellia oleifera seed meal with deep eutectic solvents: Composition identification and properties evaluation.

Traditional organic solvent extractions of tea saponins have many drawbacks. This study aimed to establish an environment-friendly and efficient technology based on deep eutectic solvents (DESs) to extract tea saponins from Camellia oleifera seed meal. The solvent consisting of choline chloride and methylurea was screened as optimal DES. Under the optimal extraction conditions obtained by response surface methodology, the extraction yield of tea saponins reached 94.36 mg/g, which increased by 27% compared with ethanol extraction, while the extraction time was reduced by 50%. Analysis of UV, FT-IR, and UPLC-Q/TOF-MS indicated tea saponins did not alter during DES extraction. Surface activity and emulsification evaluation showed that extracted tea saponins could reduce interfacial tension at the oil-water interface with excellent foamability and foam stability, and they could form nanoemulsions (d32 < 200 nm) with excellent stability. This study provides a suitable approach for the efficient extraction of tea saponins.

[Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope].

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

Rheology, Texture and Swallowing Characteristics of a Texture-Modified Dysphagia Food Prepared Using Common Supplementary Materials.

A dysphagia diet is a special eating plan. The development and design of dysphagia foods should consider both swallowing safety and food nutritional qualities. In this study, the effects of four food supplements, namely vitamins, minerals, salt and sugar, on swallowing characteristics, rheological and textural properties were investigated, and a sensory evaluation of dysphagia foods made with rice starch, perilla seed oil and whey isolate protein was carried out. The results showed that all the samples belonged to foods at level 4 (pureed) in The International Dysphagia Diet Standardization Initiative (IDDSI) framework, and exhibited shear thinning behavior, which is favorable for dysphagia patients. Rheological tests showed that the viscosity of a food bolus was increased with salt and sugar (SS), while it decreased with vitamins and minerals (VM) at shear rates of 50 s-1. Both SS and VM strengthened the elastic gel system, and SS enhanced the storage modulus and loss modulus. VM increased the hardness, gumminess, chewiness and color richness, but left small residues on the spoon. SS provided better water-holding, chewiness and resilience by influencing the way molecules were connected, promoting swallowing safety. SS brought a better taste to the food bolus. Dysphagia foods with both VM and 0.5% SS had the best sensory evaluation score. This study may provide a theoretical foundation for the creation and design of new dysphagia nutritional food products.

[Overview on the modern development of fire needling device: from tradition to innovation].

The appropriate needle device is crucial for obtaining the curative effect of fire needling therapy. The article introduces the material specification, clinical operation, indications, characteristics and advantages of the contemporary traditional fire needling devices (e.g. He's fire needle and Shi 's fire needle) and the contemporary new-type ones (e.g. fire needling with filiform needle and micro-needle); and determines the innovations of modern fire needling. It is anticipated that the needle specifications, production process and operation standard of fire needling devices should be further unified so as to provide the references for the selection of fire needling devices in treatment based on clinical syndrome differentiation and expand the clinical application of fire needling therapy.

Bioactive compounds from Polygonatum genus as anti-diabetic agents with future perspectives.

Diabetes mellitus (DM) is one of the most serious health problems worldwide. Species in the genus Polygonatum are traditional food and medicinal plants, which play an important role in controlling blood glucose. In this reveiw, we systematically summarized the traditional and modern applications of the genus Polygonatum in DM, focused on the material bases of polysaccharides, flavonoids and saponins. We highlighted their mechanisms of action in preventing obese diabetes, improving insulin resistance, promoting insulin secretion, regulating intestinal microecology, inhibiting advanced glycation end products (AGEs) accumulation, suppressing carbohydrate digestion and obsorption and modulating gluconeogenesis. Based on the safety and efficacy of this 'medicinal food' and its utility in the prevention and treatment of diabetes, we proposed a research and development program that includs diet design (supplementary food), medical nutrition therapy and new drugs, which could provide new pathways for the use of natural plants in prevention and treatment of DM.

Overview on the modern development of fire needling device: from tradition to innovation / 中国针灸

The appropriate needle device is crucial for obtaining the curative effect of fire needling therapy. The article introduces the material specification, clinical operation, indications, characteristics and advantages of the contemporary traditional fire needling devices (e.g. He's fire needle and Shi 's fire needle) and the contemporary new-type ones (e.g. fire needling with filiform needle and micro-needle); and determines the innovations of modern fire needling. It is anticipated that the needle specifications, production process and operation standard of fire needling devices should be further unified so as to provide the references for the selection of fire needling devices in treatment based on clinical syndrome differentiation and expand the clinical application of fire needling therapy.

[PK/PD model of Chuanxiong gel plaster in treatment of rheumatoid arthritis].

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1ß, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1ß was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.

Purification, composition and activity of bound polyphenols from mung bean coat dietary fiber.

In this study, the static adsorption-desorption performance of seven macroporous resins for bound polyphenols from mung bean coat dietary fiber (MBDF-BP) was compared, and NKA-9 macroporous resin was preferably screened for subsequent separation and purification. The composition of the purified products was identified and quantified, 44 major compounds were detected, with the main phenolic acid being p-hydroxybenzoic acid, which contained up to 8881.90 µg/g DW. The purification enriched flavonoids, with high contents of catechin (1419.03 µg/g DW) and vitexin (615.88 µg/g DW). The MBDF-BP purified products (pMBDF-BP) produced significant reversible inhibitory activity against α-glucosidase in a mixed-type inhibition manner, which was superior to the reported crude extracts. The antioxidant activity assays showed that pMBDF-BP exhibited distinct scavenging effects on DPPH•, ABTS+•, •OH free radicals, as well as reactive oxygen species (ROS) in Caenorhabditis elegans (C. elegans). These results demonstrated that NKA-9 macroporous resin could effectively enrich MBDF-BP extracts and enhance its antioxidant activity, which was promising to explore new sights into the applications of bound polyphenols from mung bean coat dietary fiber in functional foods or dietary supplements, thus contributing to the scientific utilization of mung bean coat resources and increasing the added value of related products.

Exploration of the role of bound polyphenols on tea residues dietary fiber improving diabetic hepatorenal injury and metabolic disorders.

Consumption of tea residues dietary fiber (TRDF) contributed to the relief of hyperglycemia symptoms in type 2 diabetes (T2D). Given the properties of TRDF abundant in bound polyphenols, the research intended to evaluate the effect of the presence or absence of bound polyphenols in TRDF on the improvement of diabetic complications (liver and kidney injury, metabolic disorders) in T2D rats induced by high-fat diet and streptozocin injection. Our results revealed that the presence of bound polyphenols in TRDF was remarkably beneficial for the amelioration of liver and kidney damage caused by T2D, which was supported by significant differences in activities of serum glutamic oxaloacetic transaminase (AST) and glutamic-pyruvic transaminase (ALT), contents of inflammatory factors in liver and kidney, the levels of kidney oxidative stress, as well as histopathological status between TRDF and bound polyphenols removed-TRDF (TRDF-DF) groups. In addition, metabolomic analysis revealed that TRDF interventions could increase the levels of metabolites such as S-Adenosylmethionine, L-Homophenylalanine and Riboflavin, as well as differ in the regulation of the metabolic pathways including arachidonic acid metabolism and cysteine and methionine metabolism as compared to TRDF-DF without bound polyphenols. These results suggested that bound polyphenols ensured the health-promoting effects for T2D complications of TRDF.