Acute Anti-Hyperglycaemic Activity of Five Traditional Medicinal Plants in High Fat Diet Induced Obese Rats.

BACKGROUND: Diabetes mellitus (DM), a prevalent non-communicable disease, is a metabolic condition involving defective pancreatic ß-cells and/or insulin resistance. Researchers are presently exploring traditional medicinal plants to identify alternatives for treating diabetes due to the various disadvantage of current anti-diabetic medicines. OBJECTIVE: The present study evaluated the anti-hyperglycaemic effects of ethanol extracts of five medicinal plants (EEMPs) (Gynura nepalensis, Glochidion thomsonii, Clerodendrum splendens, Clerodendrum infortunatum and Xanthium strumarium) which are traditionally used as an ethnomedicine to treat diabetes and numerous other health problems. METHODS: High-fat fed (HFF) obese rats were used to perform acute in vivo tests, including oral glucose tolerance, feeding test, metabolic studies, and gastrointestinal motility using BaSO4 milk solution. Priliminary phytochemical screening were performed to discover the presence or absence of alkaloids, tannins, saponins, steroids, glycosides, flavonoids, and reducing sugars in extracts. RESULTS: Oral administration of ethanol extracts (250 mg/kg, body weight), along with glucose (18 mmoL/kg body weight), ameliorated glucose tolerance (p < 0.05-0.01). In addition, the extracts improved gut motility (250 mg/kg; p < 0.05-0.001), as well as reduced food intake during the feeding test (250 mg/kg; p < 0.05-0.001). Phytochemical screening of these medicinal plants depicted the presence of flavonoids, alkaloids, tannins, saponins, steroids and reducing sugars. CONCLUSIONS: Phytochemicals such as flavonoids, tannins and saponins may be responsible for the glucose-lowering properties for these plants. Additional research is warranted to fully identify the bioactive phytomolecules and mechanistic pathways that might lead to the development of a viable, cost-effective type 2 diabetes therapy.

Antioxidant and chemotherapeutic efficacies of seaweed-derived phlorotannins in cancer treatment: A review regarding novel anticancer drugs.

The ineffectiveness of traditional cancer therapies due to drug resistance, nontargeted delivery, and chemotherapy-associated adverse side effects has shifted attention to bioactive phytochemicals. Consequently, research efforts toward screening and identification of natural compounds with anticancer properties have increased in recent years. Marine seaweed-derived bioactive compounds, such as polyphenolic compounds, have exhibited anticancer properties. Phlorotannins (PTs), a major group of seaweed-derived polyphenolic compounds, have emerged as powerful chemopreventive and chemoprotective compounds, regulating apoptotic cell death pathways both in vitro and in vivo. In this context, this review focuses on the anticancer activity of polyphenols isolated from brown algae, with a special reference to PTs. Furthermore, we highlight the antioxidant effects of PTs and discuss how they can impact cell survival and tumor development and progression. Moreover, we discussed the potential therapeutic application of PTs as anticancer agents, having molecular mechanisms involving oxidative stress reduction. We have also discussed patents or patent applications that apply PTs as major components of antioxidant and antitumor products. With this review, researcher may gain new insights into the potential novel role of PTs, as well as uncover a novel cancer-prevention mechanism and improve human health.

Anti-Inflammatory, analgesic and anti-pyretic activity of Fagonia bruguieri DC in rats.

Traditional medicine has employed the plant Fagonia bruguieri DC. to alleviate inflammation, fever and pain. The goal of this study was to test the anti-inflammatory, analgesic and antipyretic properties of the methanol extract of whole plant of Fagonia bruguieri (F. bruguieri). The writhing test and Eddy's hot plate test were used to assess the analgesic potential of F. bruguieri at three different doses. Carrageenan-induced rat paw edema was applied to investigate anti-inflammatory activity, whereas antipyretic activity was estimated in Brewer's yeast induced pyrexia model. Flavonoids, alkaloids, saponins, tannins and glycosides were found in F. bruguieri's phytochemical analysis. F. bruguieri at 750 mg/kg reduced writhing count by 62.23 percent, while F. bruguieri enhanced latency in Eddy's hot plate test. In carrageenan-induced edema, F. bruguieri at 750 mg/kg exhibited considerable anti-inflammatory effect (41.11 percent) after 2 nd, 3 rd and 4 th hours of therapy. F. bruguieri was also found to show antipyretic properties. The anti-inflammatory, analgesic and antipyretic properties of F. bruguieri were confirmed in this study, which might be attributable to the presence of several phyto-constituents.

Alkaloidal Phytoconstituents for Diabetes Management: Exploring the Unrevealed Potential.

The main characteristic feature of diabetes mellitus is the disturbance of carbohydrate, lipid, and protein metabolism, which results in insulin insufficiency and can also lead to insulin resistance. Both the acute and chronic diabetic cases are increasing at an exponential rate, which is also flagged by the World Health Organization (WHO) and the International Diabetes Federation (IDF). Treatment of diabetes mellitus with synthetic drugs often fails to provide desired results and limits its use to symptomatic treatment only. This has resulted in the exploration of alternative medicine, of which herbal treatment is gaining popularity these days. Owing to their safety benefits, treatment compliance, and ability to exhibit effects without disturbing internal homeostasis, research in the field of herbal and ayurvedic treatments has gained importance. Medicinal phytoconstituents include micronutrients, amino acids, proteins, mucilage, critical oils, triterpenoids, saponins, carotenoids, alkaloids, flavonoids, phenolic acids, tannins, and coumarins, which play a dynamic function in the prevention and treatment of diabetes mellitus. Alkaloids found in medicinal plants represent an intriguing potential for the inception of novel approaches to diabetes mellitus therapies. Thus, this review article highlights detailed information on alkaloidal phytoconstituents, which includes sources and structures of alkaloids along with the associated mechanism involved in the management of diabetes mellitus. From the available literature and data presented, it can be concluded that these compounds hold tremendous potential for use as monotherapies or in combination with current treatments, which can result in the development of better efficacy and safety profiles.

Tumor Microenvironment Stimuli-Responsive Single-NIR-Laser Activated Synergistic Phototherapy for Hypoxic Cancer by Perylene Functionalized Dual-Targeted Upconversion Nanoparticles.

Although synergistic therapy has shown great promise for effective treatment of cancer, the unsatisfactory therapeutic efficacy of photothermal therapy/photodynamic therapy is resulted from the absorption wavelength mismatch, tumor hypoxia, photosensitizer leakage, and inability in intelligent on-demand activation. Herein, based on the characteristics of tumor microenvironment (TME), such as the slight acidity, hypoxia, and overexpression of H2 O2 , a TME stimuli-responsive and dual-targeted composite nanoplatform (UCTTD-PC4) is strategically explored by coating a tannic acid (TA)/Fe3+ nanofilm with good biocompatibility onto the upconversion nanoparticles in an ultrafast, green and simple way. The pH-responsive feature of UCTTD-PC4 remains stable during the blood circulation, while rapidly releases Fe3+ in the slightly acidic tumor cells, which results in catalyzing H2 O2 to produce O2 and overcoming the tumor hypoxia. Notably, the emission spectrum of the UCTTD perfectly matches the absorption spectrum of the photosensitizer (perylene probe (PC4)) to achieve the enhanced therapeutic effect triggered by a single laser. This study provides a new strategy for the rational design and development of the safe and efficient single near-infrared laser-triggered synergistic treatment platform for hypoxic cancer under the guidance of multimodal imaging.

Long-term Outcomes of Aluminum Potassium Sulfate and Tannic Acid Sclerotherapy for Prolapsed Hemorrhoids: A Single-Center, Observational Study.

BACKGROUND: Aluminum potassium sulfate and tannic acid sclerotherapy for hemorrhoids produced almost the same effects as excisional hemorrhoidectomy. However, its long-term effectiveness remains unknown. OBJECTIVE: The purpose of this study was to investigate the long-term results of sclerotherapy using aluminum potassium sulfate and tannic acid for treating prolapsed hemorrhoids. DESIGN: This was a retrospective review of a single-institution experience. SETTINGS: This study was conducted within a coloproctology unit at a community-based hospital. PATIENTS: In total, 1180 patients with grade II to IV hemorrhoids treated with injection sclerotherapy were enrolled. MAIN OUTCOME MEASURES: Efficacy measures included cumulative recurrence rates and postoperative complications. RESULTS: Recurrence rates at 3, 6, and 9 years were 7.4%, 27.2%, and 47.5%. Postoperative complications included fever ≥38°C in 16 (1.4%) patients, rectal ulcer in 10 (0.9%) patients, rectal stricture in 5 (0.4%) patients, and perianal abscess in 4 (0.3%) patients. LIMITATIONS: This was a retrospective, nonrandomized, single-center study. In addition, office visits after 3 years were optional and the number of follow-ups steadily decreased. CONCLUSIONS: Sclerotherapy using aluminum potassium sulfate and tannic acid offers reasonable long-term results and is associated with low complication rates. Therefore, it seems to be an attractive alternative for patients with prolapsed hemorrhoids. See Video Abstract at http://links.lww.com/DCR/B733.RESULTADOS A LARGO PLAZO DE LA ESCLEROTERAPIA CON SULFATO DE ALUMINIO Y POTASIO, Y ÁCIDO TÁNICO PARA LAS HEMORROIDES PROLAPSADAS: ESTUDIO OBSERVACIONAL DE UN SOLO CENTRO. ANTECEDENTES: La escleroterapia con sulfato de aluminio y potasio, y ácido tánico para las hemorroides produjo casi los mismos efectos que la hemorroidectomía por escisión. Sin embargo, se desconoce su eficacia a largo plazo. OBJETIVO: El propósito de este estudio fue investigar los resultados a largo plazo de la escleroterapia con sulfato de aluminio y potasio, y ácido tánico para tratar las hemorroides prolapsadas. DISEO: Revisión retrospectiva de la experiencia de una sola institución. ENTORNO CLINICO: Este estudio se realizó dentro de una unidad de coloproctología en un hospital comunitario. PACIENTES: En total, 1.180 pacientes fueron inscritos con hemorroides grado II a IV tratados con inyecciones esclerosantes. PRINCIPALES MEDIDAS DE VALORACION: Las medidas de eficacia incluyeron tasas acumulativas de recurrencia y complicaciones posoperatorias. RESULTADOS: La tasa de recurrencia a los 3, 6 y 9 años fue del 7,4%, 27,2% y 47,5%, respectivamente. Las complicaciones posoperatorias incluyeron fiebre ≥ 38 grados Celsius en 16 pacientes (1,4%), úlcera rectal en 10 (0,9%), estenosis rectal en 5 (0,4%) y absceso perianal en 4 (0,3%) pacientes. LIMITACIONES: Este fue un estudio retrospectivo, no aleatorio, de un solo centro. Adicionalmente, las visitas al consultorio después de 3 años eran opcionales y el número de seguimientos disminuyó constantemente. CONCLUSIONES: La escleroterapia con sulfato de aluminio y potasio, y ácido tánico ofrece resultados razonables a largo plazo y está asociada con bajas tasas de complicaciones. Por tanto, parece ser una alternativa atractiva para pacientes con hemorroides prolapsadas. Consulte Video Resumen en http://links.lww.com/DCR/B733. (Traducción- Dr. Francisco M. Abarca-Rendon).

Biomedical applications of tannic acid.

Tannic Acid (TA) is a naturally occurring antioxidant polyphenol that has gained popularity over the past decade in the field of biomedical research for its unique biochemical properties. Tannic acid, typically extracted from oak tree galls, has been used in many important historical applications. TA is a key component in vegetable tanning of leather, iron gall ink, red wines, and as a traditional medicine to treat a variety of maladies. The basis of TA utility is derived from its many hydroxyl groups and its affinity for forming hydrogen bonds with proteins and other biomolecules. Today, the study of TA has led to the development of many new pharmaceutical and biomedical applications. TA has been shown to reduce inflammation as an antioxidant, act as an antibiotic in common pathogenic bacterium, and induce apoptosis in several cancer types. TA has also displayed antiviral and antifungal activity. At certain concentrations, TA can be used to treat gastrointestinal disorders such as hemorrhoids and diarrhea, severe burns, and protect against neurodegenerative diseases. TA has also been utilized in biomaterials research as a natural crosslinking agent to improve mechanical properties of natural and synthetic hydrogels and polymers, while also imparting anti-inflammatory, antibacterial, and anticancer activity to the materials. TA has also been used to develop thin film coatings and nanoparticles for drug delivery. In all, TA is fascinating molecule with a wide variety of potential uses in pharmaceuticals, biomaterials applications, and drug delivery strategies.

Laxative Effects of Phlorotannins Derived from Ecklonia cava on Loperamide-Induced Constipation in SD Rats.

This study investigated the laxative effects of phlorotannins (Pt) derived from Ecklonia cava (E. cave) on chronic constipation by evaluating alterations in stool parameters, gastrointestinal motility, histopathological structure, mucin secretion, gastrointestinal hormones, muscarinic cholinergic regulation, and fecal microbiota in SD rats with loperamide (Lop)-induced constipation subjected to Pt treatment. Stool-related parameters (including stool number, weight, and water contents), gastrointestinal motility, and length of intestine were significantly enhanced in the Lop+Pt-treated group as compared to the Lop+Vehicle-treated group. A similar recovery was detected in the histopathological and cytological structure of the mid-colon of Lop+Pt-treated rats, although the level of mucin secretion remained constant. Moreover, rats with Lop-induced constipation subjected to Pt treatment showed significant improvements in water channel expression, gastrointestinal hormone secretions, and expression of muscarinic acetylcholine receptors M2/M3 (mAChRs M2/M3) and their mediators of muscarinic cholinergic regulation. Furthermore, the Lop+Pt-treated group showed a significant recovery of Bifidobacteriaceae, Muribaculaceae, Clostridiaceae, and Eubacteriaceae families in fecal microbiota. Taken together, these results provide the first evidence that exposure of SD rats with Lop-induced constipation to Pt improves the constipation phenotype through the regulation of membrane water channel expression, GI hormones, the mAChR signaling pathway, and fecal microbiota.

Universal Antifouling and Photothermal Antibacterial Surfaces Based on Multifunctional Metal-Phenolic Networks for Prevention of Biofilm Formation.

Biofilms formed from the pathogenic bacteria that attach to the surfaces of biomedical devices and implantable materials result in various persistent and chronic bacterial infections, posing serious threats to human health. Compared to the elimination of matured biofilms, prevention of the formation of biofilms is expected to be a more effective way for the treatment of biofilm-associated infections. Herein, we develop a facile method for endowing diverse substrates with long-term antibiofilm property by deposition of a hybrid film composed of tannic acid/Cu ion (TA/Cu) complex and poly(ethylene glycol) (PEG). In this system, the TA/Cu complex acts as a multifunctional building block with three different roles: (i) as a versatile "glue" with universal adherent property for substrate modification, (ii) as a photothermal biocidal agent for bacterial elimination under irradiation of near-infrared (NIR) laser, and (iii) as a potent linker for immobilization of PEG with inherent antifouling property to inhibit adhesion and accumulation of bacteria. The resulted hybrid film shows negligible cytotoxicity and good histocompatibility and could prevent biofilm formation for at least 15 days in vitro and suppress bacterial infection in vivo, showing great potential for practical applications to solve the biofilm-associated problems of biomedical materials and devices.

Chitosan/gelatin-tannic acid decorated porous tape suture with multifunctionality for tendon healing.

The inferior tendon healing after surgery is inextricably linked to the surgical suture. Poor load transfer along the suture often results in a high tendon re-tear rate. Besides, the severe inflammation and infection induced by sutures even cause a second surgery. Herein, to alleviate the above-mentioned issues, a multifunctional suture was fabricated by decorating chitosan/gelatin-tannic acid (CS/GE-TA) on the porous tape suture. The porous tape suture ensured the required mechanical properties and sufficient space for tissue integration. Compared to the pristine suture, the CS/GE-TA decorated suture (TA100) presented a 332% increase in pull-out force from the tendon, indicating potentially decreased re-tear rates. Meanwhile, TA100 showed superior anti-inflammatory and antibacterial performances. In vivo experiments further proved that TA100 could not only reduce inflammatory action but also facilitate collagen deposition and blood vessel formation. These results indicate that the multifunctional sutures are promising candidates for accelerating tendon healing.

Therapeutic potential of plant-derived tannins in non-malignant respiratory diseases.

Respiratory diseases are the major cause of human illness and death around the world. Despite advances in detection and treatment, very few classes of safe and effective therapy have been introduced to date. At present, phytochemicals are getting more attention because of their diverse beneficial activities and minimal toxicity. Tannins are polyphenolic secondary metabolites with high molecular weights, which are naturally present in a wide variety of fruits, vegetables, cereals, and leguminous seeds. Many tannins are endowed with well-recognized protective properties, such as anti-cancer, anti-microbial, anti-oxidant, anti-hyperglycemic, and many others. This review summarizes a large body of experimental evidence implicating that tannins are helpful in tackling a wide range of non-malignant respiratory diseases including acute lung injury (ALI), pulmonary fibrosis, asthma, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). Mechanistic pathways by which various classes of tannins execute their beneficial effects are discussed. In addition, clinical trials and our perspective on future research with tannins are also reviewed.

Tannins in Terminalia bellirica inhibit hepatocellular carcinoma growth by regulating EGFR-signaling and tumor immunity.

The fruits of Terminalia bellirica (Gaertn.) Roxb. (TB) are used as a multi-use therapeutic herbal product in the Tibetan medicinal system and are prescribed as a general health tonic in the traditional Ayurvedic medicinal system. It has been demonstrated that these fruits have a variety of pharmacological activities, including anti-tumor, anti-oxidative, anti-inflammatory, hepatoprotective and immunoregulatory effects, etc. However, the therapeutic effects of tannins in TB on HCC and the underlying mechanisms remain uncharacterized. In the current study, we aimed to identify the anti-tumor effect of tannins in TB by employing a H22 xenograft mouse model and by performing cell-based in vitro studies with the assistance of the network pharmacology analysis. The crude extract of TB was purified to yield total tannin fraction (TB-TF), and our results found that TB-TF significantly inhibited the tumor growth of H22 xenografts in mice by inducing apoptosis and reducing angiogenesis. A total of 90 compounds were then identified in TB-TF by UPLC-MS/MS, and 27 were found in serum after oral administration of TB-TF in mice. The network pharmacology analysis based on these absorbed components was performed and, along with experimental evidence, it revealed that the ERBB, PI3K-Akt, and MAPK signaling pathways may be involved in the anti-tumor effect of TB-TF on HCC. Furthermore, we suggested that TB-TF effectively modulated the immunosuppressive tumor microenvironment in H22 xenograft mice. In summary, our study demonstrated that TB-TF could be developed as a functional food, which is not only a promising anti-cancer reagent but also a potential candidate with bright prospects for the emerging trends of immunotherapy for HCC.

Persimmon-derived tannin ameliorates the pathogenesis of ulcerative colitis in a murine model through inhibition of the inflammatory response and alteration of microbiota.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) induced by dysregulation of the immune response in the intestinal mucosa. Although the underlying mechanisms of UC development are not fully understood, disruption of gut microbiota, "dysbiosis", is thought to lead to the development of IBD. Persimmon (Ebenaceae Diospyros kaki Thunb.)-derived tannin, which is a condensed polymeric tannin consisting of catechin groups, has antioxidant, anti-inflammatory, and antimicrobial activities. In this study, we assessed the effect of persimmon-derived tannin on a murine model of UC established by dextran sulfate sodium-induced colitis in female mice. Dietary supplementation of tannin significantly decreased disease activity and colon inflammation. A hydrolysate of tannin directly suppressed expression of inflammatory genes in macrophages in vitro. In faecal microbiota, the relative abundance of Bacteroides was increased significantly by tannin supplementation. Alpha-diversity indices in colitis-induced mice were significantly higher in the tannin diet group compared with the control diet group. Additionally, expansion of Enterobacteriaceae and Enterococcus, which is associated with disease progression of IBD, was remarkably suppressed in the tannin diet group. These results suggest that persimmon-derived tannin ameliorates colon inflammation in UC through alteration of the microbiota composition and immune response, which may be a promising candidate for IBD therapy.

Tannic Acid-Stabilized Silver Nanoparticles Used in Biomedical Application as an Effective Antimelioidosis and Prolonged Efflux Pump Inhibitor against Melioidosis Causative Pathogen.

Burkholderia pseudomallei is the causative pathogen of melioidosis and this bacterium is resistant to several antibiotics. Silver nanoparticles (AgNPs) are an interesting agent to develop to solve this bacterial resistance. Here, we characterize and assess the antimelioidosis activity of AgNPs against these pathogenic bacteria. AgNPs were characterized and displayed a maximum absorption band at 420 nm with a spherical shape, being well-monodispersed and having high stability in solution. The average size of AgNPs is 7.99 ± 1.46 nm. The antibacterial efficacy of AgNPs was evaluated by broth microdilution. The bactericidal effect of AgNPs was further assessed by time-kill kinetics assay. Moreover, the effect of AgNPs on the inhibition of the established biofilm was investigated by the crystal violet method. In parallel, a study of the resistance induction development of B. pseudomallei towards AgNPs with efflux pump inhibiting effect was performed. We first found that AgNPs had strong antibacterial activity against both susceptible and ceftazidime-resistant (CAZ-resistant) strains, as well as being efficiently active against B. pseudomallei CAZ-resistant strains with a fast-killing mode via a bactericidal effect within 30 min. These AgNPs did not only kill planktonic bacteria in broth conditions, but also in established biofilm. Our findings first documented that the resistance development was not induced in B. pseudomallei toward AgNPs in the 30th passage. We found that AgNPs still showed an effective efflux pump inhibiting effect against these bacteria after prolonged exposure to AgNPs at sublethal concentrations. Thus, AgNPs have valuable properties for being a potent antimicrobial agent to solve the antibiotic resistance problem in pathogens.

An All-in-One Tannic Acid-Containing Hydrogel Adhesive with High Toughness, Notch Insensitivity, Self-Healability, Tailorable Topography, and Strong, Instant, and On-Demand Underwater Adhesion.

Hydrogels that are mechanically tough and capable of strong underwater adhesion can lead to a paradigm shift in the design of adhesives for a variety of biomedical applications. We hereby innovatively develop a facile but efficient strategy to prepare hydrogel adhesives with strong and instant underwater adhesion, on-demand detachment, high toughness, notch-insensitivity, self-healability, low swelling index, and tailorable surface topography. Specifically, a polymerization lyophilization conjugation fabrication method was proposed to introduce tannic acid (TA) into the covalent network consisting of polyethylene glycol diacrylate (PEGDA) of substantially high molecular weight. The presence of TA facilitated wet adhesion to various substrates by forming collectively strong noncovalent bonds and offering hydrophobicity to allow water repellence and also provided a reversible cross-link within the binary network to improve the mechanical performance of the gels. The long-chain PEGDA enhanced the efficacy and stability of TA conjugation and contributed to gel mechanics and adhesion by allowing chain diffusion and entanglement formation. Moreover, PEGDA/TA hydrogels were demonstrated to be biocompatible and capable of accelerating wound healing in a skin wound animal model as compared to commercial tissue adhesives and can be applied for the treatment of both epidermal and intracorporeal wounds. Our study provides new, critical insight into the design principle of all-in-one hydrogels with outstanding mechanical and adhesive properties and can potentially enhance the efficacy of hydrogel adhesives for wound healing.

Pyrogallol-Phloroglucinol-6 6-Bieckol on Attenuates High-Fat Diet-Induced Hypertension by Modulating Endothelial-to-Mesenchymal Transition in the Aorta of Mice.

Endothelial-to-mesenchymal transition (EndMT), which is involved in the development of various cardiovascular diseases, is induced by dyslipidemia or obesity. In dyslipidemia, the increased levels of oxidized low-density lipoproteins (oxLDL) upregulated the lectin-type oxidized LDL receptor 1 (Lox-1), which then upregulated the down signaling pathways of PKC-α/MMPs/TGF-ß/SMAD2 or 3 and increased the EndMT. In this study, we investigated the effect of pyrogallol-phloroglucinol-6,6-bieckol (PPB), which is a compound of Ecklonia cava (E. cava), on decreased blood pressure (BP) by attenuating the EndMT in a high-fat diet- (HFD-) fed animal model. We also investigated PPB's attenuation effect on EndMT in oxLDL-treated mouse endothelial cells as an in vitro model. The results indicated that, in the aorta or endothelial cells of mice, the HFD or oxLDL treatment significantly increased the expression of Lox-1/PKC-α/MMP9/TGF-ß/SMAD2/SMAD3. The PPB treatment significantly decreased its expression. In contrast, the HFD or oxLDL treatment significantly decreased the expression of the EC markers (PECAM-1 and vWF) while the PPB treatment significantly increased them. Moreover, the HFD or oxLDL treatment significantly increased the expression of the mesenchymal cell markers (α-SMA and vimentin) while PPB treatment significantly decreased them. PPB decreased the intima-media thickness and extracellular matrix amount of the aorta and attenuated the BP, which was increased by the HFD. In conclusion, PPB attenuated the upregulation of Lox-1/PKC-α/MMP9/TGF-ß/SMAD2 and 3 and restored the EndMT in HFD-fed animals. Moreover, PPB showed a restoring effect on HFD-induced hypertension.

Apple polyphenol extract alleviates lipid accumulation in free-fatty-acid-exposed HepG2 cells via activating autophagy mediated by SIRT1/AMPK signaling.

Defective degradation of intracellular lipids induced by autophagy is causally linked to the development of non-alcoholic fatty liver disease (NAFLD). Natural agents that can restore autophagy could therefore have the potentials for clinical applications for this public health issue. Herein, we investigated the effects of apple polyphenol extract (APE) on fatty acid-induced lipids depositions in HepG2 cells. APE treatment alleviated palmitic acid and oleic acid-induced intracellular lipid accumulation, concomitant with the increased autophagy, restored lysosomal acidification, inhibited lipid synthesis and slight promotion of fatty acid oxidation. Mechanistically, APE up-regulated the expression of SIRT1, activated LKB1/AMPK pathway and inhibited mTOR signaling. Over-expressed or knock-down SIRT1 positively regulated AMPK and ATG7 expressions. SIRT1 and ATG7 knock-down impaired APE induction of improved lipid accumulation, increased intracellular TG content. Thus, APE induction of autophagy to ameliorate fatty acid-induced lipid deposition is SIRT1 dependent, APE conserved preventive potentials for clinical hepatosteatosis.

Apple polyphenols extract alleviated dextran sulfate sodium-induced ulcerative colitis in C57BL/6 male mice by restoring bile acid metabolism disorder and gut microbiota dysbiosis.

To investigate and compare the preventive effects of apple polyphenols extract (APE) with phloretin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC), 60 male mice were treated with 125 or 500 mg/(kg bw d) APE or 100 mg/(kg bw d) phloretin, the single-ingredient of APE, for continuous 3 weeks by intragastric administration, meanwhile, mice were provided with 3% DSS dissolved in drinking water to induce UC during the third week. Both APE and phloretin significantly ameliorated DSS-induced UC by inhibiting body weight loss, preventing colon shortening and mucosa damage. Except the same mechanisms of the inhibited activation of NF-κB signaling, decreased hyodeoxycholic acid level and increased abundance of Verrucomicrobia at phylum and Bacteroides and Akkermansia at genus, APE increased ß-muricholic acid level and decreased Bacterodetes abundance, while phloretin decreased Firmicutes abundance. Furthermore, APE treatment showed much lower disease activity index score, less body weight loss and lighter spleen than phloretin. Thus, our study supported the potentiality of APE as a promising dietary intervention for the prevention of experimental UC.

Bioresponsive supramolecular hydrogels for hemostasis, infection control and accelerated dermal wound healing.

Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including hemostasis and anti-bacterial activity are essential for successful wound healing; however, designing ideal materials is still challenging. Herein, we demonstrate the fabrication of a biodegradable, temperature-pH dual responsive supramolecular hydrogel (SHG) scaffold based on sodium alginate/poly(N-vinyl caprolactam) (AG/PVCL) through free radical polymerization and the subsequent chemical and ionic cross-linking. A natural therapeutic molecule, tannic acid (TA)-incorporated SHG (AG/PVCL-TA), was also fabricated and its hemostatic and wound healing efficiency were studied. In the AG/PVCL-TA system, TA acts as a therapeutic molecule and also substitutes as an effective gelation binder. Notably, the polyphenol-arm structure and diverse bonding abilities of TA can hold polymer chains through multiple bonding and co-ordinate cross-linking, which were vital in the formation of the mechanically robust AG/PVCL-TA. The SHG formation was successfully balanced by varying the composition of SA, VCL, TA and cross-linkers. The AG/PVCL-TA scaffold was capable of releasing a therapeutic dose of TA in a sustained manner under physiological temperature-pH conditions. AG/PVCL-TA displayed excellent free radical scavenging, anti-inflammatory, anti-bacterial, and cell proliferation activity towards the 3T3 fibroblast cell line. The wound healing performance of AG/PVCL-TA was further confirmed in skin excision wound models, which demonstrated the potential application of AG/PVCL-TA for skin regeneration and rapid wound healing.

Pomegranate juice as a functional food: a comprehensive review of its polyphenols, therapeutic merits, and recent patents.

Pomegranate (Punica granatum) is an ancient perennial plant species of the Punicaceae family and is regarded as the 'miracle fruit' for its seeds being consumed as food, juice and as a functional food. Significant modern pharmacological and clinical evidence has highlighted the wide medicinal applications of pomegranate fruit parts and its juice. Pomegranate juice (PJ) that is superior to other fruit juices is a fortified source of dietary polyphenols with potential antioxidant capacity. Polyphenols of PJ include tannins, anthocyanins, and flavonoids. The presence of these beneficial phytochemicals is directly linked to its favourable health benefits viz., obesity and diabetes management and anti-inflammatory effects. This comprehensive review capitalizes on PJ with emphasis on the interrelationship between its holistic chemical composition, metabolism and biological effects. Moreover, the review recapitulates on the diverse health benefits of PJ and related patents in the field of PJ production to ensure the best produced juice quality.