Recent Technological Advances in Phenolic Compounds Recovery and Applications: Source of Nutraceuticals for the Management of Diabetes
Abstract
:Featured Application
Abstract
1. Introduction
2. Phenolic Compounds Extraction from Renewable Resources within a Biorefinery Scheme
2.1. Techniques for Phenolic Compounds Extraction from Agri-Food By-Products
2.1.1. Natural Deep Eutectic Solvents
2.1.2. Surfactant Extraction and Colloidal Gas Aphrons
2.1.3. Enzyme Assisted Extraction (EAE)
2.2. Co-Production of Phenolic Compounds within a Biorefinery Scheme
3. Encapsulation Techniques for Improving Phenolic Compounds Functionality
Encapsulated Phenolic Compounds as Antidiabetic Agents
4. The Antidiabetic Effects of Dietary Phenolic Compounds: Preclinical and Clinical Evidence
Molecular Mechanisms Underlying the Benefits of Phenolic Compounds in Glucose Homeostasis
5. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Method | Advantages | Limitations | By-Products | Compounds | Refs |
---|---|---|---|---|---|
Ultrasonic assisted extraction | Lower temperature | Certain phenolic compounds are unstable | Acerola pomace | Phenolic compounds | [32] |
Less use of solvents | Formation of OH radicals | Anthocyanins | |||
Favours solubilisation | Unavoidable use of organic solvents | Pomegranate peel | Phenolic compounds | [33] | |
Challenging to scale | Punicalagin | ||||
Mango peel | Phenolic compounds | [34] | |||
Grape pomace | Phenolic compounds | [35,36,37] | |||
Anthocyanins | |||||
Strawberry by-product | Phenolic compounds | [38] | |||
Orange peel | Phenolic compounds | [39] | |||
Citrus pomace | Phenolic compounds | [40] | |||
Hesperidin | |||||
Olive pomace | Phenolic compounds | [41] | |||
Microwave-assisted extraction | Quick process | Affinity of the solvent to polyphenol-radiation | Grape and blueberry pomace | Phenolic compounds | [42] |
It can be done in absence of light | Risk due to flammable solvent | Grape pomace | Phenolic compounds | [43,44] | |
Low energy input | Damage to the analyte since radiation causes a rapid increase in temperature | Olive pomace | Phenolic compounds | [41] | |
It can be coupled with other methods such as UAE | Different plants and their parts can have different levels of interaction with microwaves | Kiwiberry leaves | Phenolic compounds | [45] | |
Açaí pomace | Phenolic compounds | [46] | |||
Spent coffee grounds | Caffeic acid | [47] | |||
Sunflower cake | Chlorogenic acid | [48] | |||
Supercritical fluid Extraction | Easy penetration to the matrix | Limited to compound with low or medium polarity | Cacao pod husk | Phenolic compounds | [49] |
Selective extraction of bioactives | High initial investment | Grape marc pomace and skins | Phenolic compounds | [43,70] | |
Rapid and simple | Particle size of the raw material to assure penetration but not clogging the filter (0.04–0.08 mm optimum) | ||||
No need for organic solvent, or in very low quantities | Apple pomace | Phenolic compounds | [50,51] | ||
CO2 is the most common solvent with is a Generally Recognised As Safe (GRAS) and inexpensive solvent | Orange pomace | Phenolic compounds | [52] | ||
Use of low temperatures, which is ideal for heat sensible bioactives | Coffee husk | Caffeine, chlorogenic acid | [53] |
Compound | Encapsulating Material/Technique | Type of Study/ Dose | Biological Parameters/Activities | Positive Effects | Refs |
---|---|---|---|---|---|
Curcumin | Poly (gammabenzyl l-glutamate)-poly (ethylene glycol)-poly (gammabenzyl l-glutamate)/Self-emulsification under digestive conditions | In vivo/20 mg/kg administered to diet-induced diabetic rats for over 8 weeks of either free or encapsulated curcumin | H2S and [Ca2+]i Calcium-sensing receptor (CaSR) H2S generating enzymes (CSE) Calmodulin (CaM) | Enhanced drug solubility Improve pharmacokinetics Alleviated pathological morphological damage of myocardium | [97] |
Polyalkylcyanoacrylate microspheres /Oil-in-water solvent evaporation | In vivo/4 mg/kg administered (sublingual vein injection) to diabetic rats in the 7th and 8th week | Blood glucose, weight Pro-inflammatory cytokines G protein-coupled receptor (P2Y12) | Decreased blood glucose levels Decreased mechanical and thermal hyperalgesia in diabetic rats | [98] | |
Gelatin microspheres into enzyme matrix metalloproteinase 9-responsive and thermoresponsive hydrogel/ Emulsification | In vitro using human normal skin fibroblast and immortalized human epidermal cells/0.01, 0.1, or 1 μg/mL for 24 h In vivo using diabetic-induced (streptozotocin) mice/200 μL hydrogel patches | Antioxidative activity after induced oxidation (H2O2) Cellular uptakeGlutathione peroxidase (GPx) α-smooth muscle actin (α-SMA) Neovascularization and cell proliferation | Decreased ROS and increased GSH levels Increased cellular uptake (48–60%) compared to free curcumin (29%) Enhanced wound healing by reducing antioxidative stress and increasing cell migration | [99] | |
Nanigerin | Chitosan alginate core-shell nanoparticles/ Ionotropic gelation | In vivo using streptozotocin-induced diabetic rats/50 mg/kg of either encapsulated or free naringenin for 19 days | Blood glucose Serum cholesterol and triglyceride Haemoglobin and free iron therein | Significant hypoglycemic effect Biocompatible according to serum and histological studies (liver and intestine) Normalises pancreatic abnormalities caused by diabetes Prevention of glycation-induced iron-mediated oxidative stress | [100] |
Berberin | Poly(lactic-co-glycolic acid)-poly (ethylene glycol)-Poly(lactic-co-glycolic acid) block copolymer nanoparticles/Nanoprecipitation | In vitro using Hep-G2 cells | PCSK-9, SREBP-1, LDL-r, HNF-1 alpha mRNAs and PCSK-9 protein expression | PCSK-9 modulation by improving Berberin pharmacokinetics compared to the free drug | [101] |
Proantocyanidin-rich extract | Gum Arabic, maltodextrin, gelatin microcapsules/Freeze-drying | In vitro assays/ 1–4 mg/mL | α-Amilase and α-glucosidase inhibitory activity Bioavailability | Inhibitory activity above 80% and 60% for α-amylase and α-glucosidase, respectively | [82,102] |
Quercitin | Alginate and succinyl chitosan core-shell-corona structured nanoparticles/Ionic cross-linking | In vivo using streptozotocin-induced diabetic rats/100 mg/kg of either encapsulated or free quercitin for 28 days | Fasting blood glucose and glucose tolerance test | Hypoglycaemic effect and efficient maintenance of glucose homeostasis compared to free oral quercitin | [103] |
Poly(lactic-co-glycolic acid) nanoparticles/ Emulsion-diffusion-evaporation method | In vivo using streptozotocin-induced diabetic rats/ 150 mg/kg of either free (daily) or encapsulated (every fifth day) quercitin | Blood glucose Catalase and SOD levels in pancreas and kidneys | Enhanced quercitin oral bioavailability (523% relative increase) sustained release compared to the free compound Significant lower glucose levels than free quercetin on days 7, 10, and 15 (but higher than normal) Increased activity of SOD and catalase due to reduced action of ROS | [104] | |
Quercitin nanorods/ Thermomagnetic treatment | In vivo alloxan-induced diabetic mice/20 mg/kg for four weeks | Blood glucose Glucose metabolic enzymes Antioxidant enzymes (SOD, CAT, GSH) Cellular reductants (SH, MDA) Kidney and liver function markers (Urea, GOT, GPT, ALPT) | Reduction in fasting blood glucose, oxidative stress, lipid peroxidation, and protein carbonylation in the quercetin nanoparticle supplemented group compared to the free drug | [105] | |
Resveratrol | Multilayered resveratrol nanoliposomes/ Dry film hydration method | In vitro using β-TC cells/30 μg/mL to glucose and streptozotocin diabetic-induced cells for 24 h | Biocompatibility and cellular uptake Insulin and glucose levels Antioxidant activity | Improved decreased insulin levels Reduced glucose levels Prolonged antioxidant compared to free resveratrol | [106] |
Polysorbate 80/poly-caprolactone -capric triglycerides-sorbitan monostearate nanocapsules/ Interfacial deposition method | In vivo using metabolic syndrome-induced mice | Blood glucose, weight, insulin, and lipid profile Insulin resistance (QUICKI index) Systolic and diastolic blood pressure | Regulation of insulin and glucose levels Controlled QUICKI index to the normal range | [43] |
Clinical Evidence | ||||
---|---|---|---|---|
Compound | Clinical Trial | Administration, Concentration, and Duration of the Treatment | Evidence of Antidiabetic Effects | Refs |
Phenolic compounds from red grape pomace | NCT02865278 Healthy individuals | One oral dose after overnight fasting 1.562 g gallic acid equivalents | Reduced postprandial insulin levels and improved insulin sensitivity | [128] |
Flavonoids and phenolic acids | NCT01154478 Individuals with metabolic syndrome | Dietary intervention 2.903 mg/day 8 weeks | Improved oral glucose tolerance and post-glucose insulin secretion and insulin sensitivity | [129] |
Grape phenolic compounds | NCT01478841 Obese and overweight individuals | Dietary intervention 2 g/day 9 weeks | Increased hepatic insulin sensitivity index and glucose infusion rate, and decreased systemic and muscle oxidative stress | [130] |
Resveratrol | IRCT201710108129N11 T1D patients | Oral: capsules 1 g/day 2 months | Reduced fasting glycemia, HbA1c, and oxidative stress | [131] |
Preclinical Evidence | ||||
Compound | Animal Model | Administraion, Concentration, and Duration of the Treatment | Evidence of Antidiabetic Effects | Refs |
Resveratrol | NOD mice: a non-obese model for T1D (NOD (H-2g7), NOD.BDC2.5 and NOD/SCID) | Daily oral gavage 250 mg/kg 23 weeks | Preventive effect: 30% of the mice without T1D 31% of insulitis-free pancreatic islets | [120] |
Every other day, subcutaneous injection 25 mg/kg 23 weeks | Preventive effect: 80% of the mice without T1D 69% of insulitis-free pancreatic islets | |||
db/db mice: T2D and obesity model (C57BL/KsJ-db/db mice) | Oral Supplementation of AIN-76 semisynthetic diet with 0.005% (w/w) resveratrol 6 weeks | Protective effect: Improved glycemic control and dyslipidemia | [125] | |
Streptozotocin-induced diabetic mice (C57BL/6) | Oral: drinking water 2.5 mg/kg/day 2 weeks from the onset of diabetes | Protective effect: Restoration of the insulin sensitivity and hepatic insulin signaling | [121] | |
Goto-Kakizaki rat: Non-obese diabetic rats (Wistar substrain) | Daily oral gavage 20 mg/kg 10 weeks | Protective effect: Improved glucose tolerance and structure of pancreatic islets Partial normalization of leptin and adiponectin | [126] | |
Cranberry extract (phenolic acids, flavonols, anthocyanins, and proanthocyanidins) | Diet-induced obese mice (C57Bl/6J) | Daily oral gavage 200 mg/kg 8 weeks | Protective effect: Restoration of hepatic steatosis Improved oral glucose tolerance Normalized insulin sensitivity | [124] |
Aspalathin | ob/ob mice: hyperphagic and overweight leptin-deficient type 2 diabetic mice (C57BL/6J) | Oral Supplementation of 20% casein diet with 0.1% aspalathin 5 weeks | Protective effect: Reduced fasting glycemia Improved glucose tolerance | [124] |
Green tea phenolic compounds | High-fat diet fed Zucker fatty (ZF) rats | Daily oral gavage 200 mg/kg 8 weeks | Protective effect: Reduced weight gain, visceral fat accumulation, fasting serum glucose and insulin, and amelioration of the insulin resistance | [127] |
Proanthocyanidins polymers | Diet-induced obese mice (C57BL/6J) | Daily oral gavage 37 mg/kg 8 weeks | Improved oral glucose tolerance | [133] |
In Vivo Approaches | ||||
---|---|---|---|---|
Compound | Animal Model | Administration, Concentration, and Duration of the Treatment | Molecular Mechanism | Refs |
Proanthocyanidins polymers | Diet-induced obese mice (C57BL/6J) | Daily oral gavage 37 mg/kg 8 weeks | Protection of the gut barrier integrity: Increased number of mucin-secreting globet cells | [133] |
Curcumin | Rats fed standard chow (Sprague-Dawley) | One oral dose by gavage 1.5 mg curcumin/kg | Enhanced glucose-induced secretion of GLP-1 through a GPR40/120-dependent mechanism | [134] |
Coffee polyphenol extract | Mice fed standard chow (C57BL/6J mice) | One oral dose by gavage 0.6 g/kg | Enhanced postprandial GLP-1 secretion coupled with a reduced postprandial glycemia | [135] |
Resveratrol | Diet-induced obese mice and GLP-1R KO mice (C57Bl/6J) | Oral Diet supplementation with 60 mg/kg | Improved oral glucose tolerance through a GLP-1 receptor-dependent mechanism | [19] |
Polyphenol-rich fruit extracts: Myrciaria dubia | Diet-induced obese mice (C57Bl/6J) | Daily oral gavage 200 mg/kg 8 weeks | Resistance to developing obesity due to changes in gut microbiota composition, especially an increase in the abundance of Akkermansia muciniphila | [136] |
In Vitro Approaches | ||||
Compound | Cell Line | Concentration and Time of Incubation | Molecular Mechanism | Refs |
Resveratrol | Primary cultures of splemocytes from resveratrol-treated-NOD mice | Every other day subcutaneous injection of 25 mg/kg for 23 weeks | Reduced migration of splenocytes from resveratrol-treated NOD mice into the compartment containing CCL20, a CCR6 ligand. This indicates an inhibition of the inflammatory cell trafficking from peripheral lymphoid organs to the pancreas by suppressing CCR6 production | [120] |
C2C12 myotubes (mouse myoblast cell line) | 20 μM (12 h) | Enhanced glycogen depots and reduced intracellular triglyceride content | [137] | |
HepG2 cells (human hepatoma) | 20 μM (48 h) | Downregulation of the methylation of Nrf2 promoter which attenuates the glucose-induced ROS production | [138] | |
Curcumin | C2C12 myotubes (mouse myoblast cell line) | 40 μM (16 h) | Suppression of the phosphorylation of IKKα-IKKβ, and JNK which protects against fatty acid-inflammation and ROS production | [139] |
Coculture model of Caco-2 (human colonic cells) and differentiated THP-1 (human monocytes) cells | 10 μM (48 h) | Upregulation of ZO-1 and claudin-1 Attenuation of oxidative stress markers and endoplasmic reticulum stress-induced apoptosis-related molecules | [140] | |
Curcumin and carnosol | Primary human dendritic cells | 10 μM (6 h) | Regulation of the dendritic cell metabolism through AMPK | [141] |
Aspalthin carnosol Green tea phenolic compounds | L6 myoblast cell line (rat) Rat ex vivo culture of isolated soleus muscle | 50–100 μM (4 h) 10, 25, 50, 75 μM (15 min–6 h) ZF rats treated with 200 mg/kg | Increased glucose uptake by enhancing GLUT4 translocation to the cell surface | [124,127,142] |
Epicatechin phenolic cocoa extract | HepG2 cells (human hepatoma) | 1, 5, 10 μM 1, 5, 10 μg/mL (24 h) | Activation of the AKT-mediated insulin signaling to inhibit gluconeogenesis | [143] |
Gallic acid | Co-culture of lipid-laden Hepa 1–6 hepatocytes and RAW264 macrophages | 50, 100, 200 μM (24 h) | Prevention of secretion of proinflammatory cytokines | [70] |
Quercetin, apigenin, luteolin genistein, and sulfuretin | RINm5F (RIN) cells (rat insulinoma cells) | 25, 50 μM (quercetin, apigenin, luteolin) 5, 10, 20, 40 μM (genistein) 40, 80, 100 μM (sulfuretin) (3–48 h) | Prevention of cytokine-induced cytotoxicity in β-cells | [144,145,146] |
Delphinidin 3-rutinoside | murine GLUTag L cell line | 10, 25, 50, 100 μM (2 h) | GLP-1 secretion by activating GPR40/120 coupled with the Ca2+-CaMKII pathway | [147] |
Coffee polyphenol extract | Human NCI-H716 cells (L cells) | 0.05%, 0.1% (2 h) | GLP-1 secretion through a cAMP-dependent mechanism | [135] |
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Dias, M.; Romaní-Pérez, M.; Romaní, A.; de la Cruz, A.; Pastrana, L.; Fuciños, P.; Amado, I.R. Recent Technological Advances in Phenolic Compounds Recovery and Applications: Source of Nutraceuticals for the Management of Diabetes. Appl. Sci. 2022, 12, 9271. https://doi.org/10.3390/app12189271
Dias M, Romaní-Pérez M, Romaní A, de la Cruz A, Pastrana L, Fuciños P, Amado IR. Recent Technological Advances in Phenolic Compounds Recovery and Applications: Source of Nutraceuticals for the Management of Diabetes. Applied Sciences. 2022; 12(18):9271. https://doi.org/10.3390/app12189271
Chicago/Turabian StyleDias, Marisol, Marina Romaní-Pérez, Aloia Romaní, Aimara de la Cruz, Lorenzo Pastrana, Pablo Fuciños, and Isabel R. Amado. 2022. "Recent Technological Advances in Phenolic Compounds Recovery and Applications: Source of Nutraceuticals for the Management of Diabetes" Applied Sciences 12, no. 18: 9271. https://doi.org/10.3390/app12189271
APA StyleDias, M., Romaní-Pérez, M., Romaní, A., de la Cruz, A., Pastrana, L., Fuciños, P., & Amado, I. R. (2022). Recent Technological Advances in Phenolic Compounds Recovery and Applications: Source of Nutraceuticals for the Management of Diabetes. Applied Sciences, 12(18), 9271. https://doi.org/10.3390/app12189271