Antidiabetic Activity Research Articles

Effects of Drying Methods on the Phytochemical Contents, Antioxidant Properties, and Anti-Diabetic Activity of Nasturtium officinale R.Br. (Betong Watercress) from Southern Thailand.

Nasturtium officinale R.Br. (Betong watercress) contains high levels of secondary metabolites that offer health benefits. However, fresh-cut watercress has a short shelf life. This study aimed to assess the effect of drying methods on the phytochemical contents, antioxidant activity, and anti-diabetic activity of Betong watercress. The watercress was dried using three methods: roasting (R, 50 °C, 40 min); roasting and drying (RD, 40 min roasting at 50 °C and 1 h drying at 80 °C); and blanching, roasting, and drying (BRD, 30 s blanching at 80 °C, 20 min roasting at 50 °C, and 1 h drying at 80 °C). Aqueous extracts from each drying method were analyzed for total phenolic content, total flavonoid content, total glucosinolate content, antioxidant activities (FRAP, DPPH, and ABTS assays), and α-amylase enzyme inhibition. From the results, the R method provided the highest level of total phenolic, total flavonoid, and total glucosionolate content compared to the RD and BRD methods. Similarly, antioxidant activities and α-amylase enzyme inhibition were highest in the R method, followed by the RD and BRD methods. Our results demonstrate that roasting of Betong watercress without the addition of blanching or drying effectively preserves the phytochemical contents, antioxidant activities, and anti-diabetic activity.

El extracto metanólico de <i>Tillandsia recurvata</i> reduce los niveles de glucosa, triglicéridos y colesterol en sangre

Background: Tillandsia recurvata collected in San Luis Potosí does not have studies focused on its use as an adjuvant in treating diabetes mellitus. Questions and / or Hypotheses: Will Tillandsia recurvata L. (Bromeliaceae) have antidiabetic activity in vitro and in vivo? Studied species: Tillandsia recurvata L. (Bromeliaceae) Study site and dates: T. recurvata was collected in Guadalcázar municipality, San Luis Potosí, México, in December 2021. Methods: The antidiabetic potential of Tillandsia recurvata methanol extract (TRM) was evaluated using in vitro and in vivo models, and its secondary metabolite content was analyzed using Gas chromatography-mass spectrometry. Results: Results demonstrate that extract reduces blood glucose, triglyceride, and cholesterol levels in vivo. In addition, in vitro tests showed that extract diminished the formation of advanced glycation end products, methylglyoxal concentrations, and glycosylated hemoglobin levels. Gas chromatography-mass spectrometry analysis identified several compounds in the extract, including 2-methylbenzaldehyde, 4-hydroxy-2-methylacetophenone, 3',5' dimethoxyacetophenone, pentanoic acid, palmitic acid, linoleic acid, phytol, margaric acid, oleamide, cis-11-eicosenamide, stearic acid, 13-docosenamide, (Z), campesterol, and β-sitosterol. Conclusions: These results highlight the potential of T. recurvata collected in San Luis Potosi as an adjuvant in treatment of diabetes mellitus.

Preparation and biological evaluation of a glucose-responsive block copolymer nanoparticle with the ability to ameliorate diabetic kidney damage

In this study, a p(AAPBA-b-Daidzein) block copolymer was designed and synthesised using glucose-responsive 3-acrylamidophenylboronic acid (AAPBA) and esterified daidzein as structural units; this copolymer possessed anti-diabetic pharmacological activity. After confirming the chemical structure of the copolymer, nanoparticles of the copolymer were prepared using the water-in-oil method. The results of the in vitro experiments showed that nanoparticles swelled when the pH was >7 or when the glucose concentration exceeded 1.0 mg/mL. Particle size measurements showed that the size of the nanoparticles was kept in the range of 100–300 nm before and after the glucose response, which helped avoid their clearance by the liver and kidneys. As the nanoparticles swelled, insulin and esterified daidzein were continuously released. The nanoparticles subcutaneously injected into mice with streptozotocin-induced diabetes were able to quickly and continuously reduce the blood sugar levels; significantly improve renal pathological damage and reduce renal function damage, inflammatory factors and oxidative stress indicators. In summary, the p(AAPBA-b-Daidzein) glucose-responsive nanoparticles prepared in the current study possess good pH value and glucose sensitivity, can achieve a precise and controlled release of insulin and exert the pharmacological activity of esterified daidzein. Therefore, it shows potential clinical application value in the treatment of diabetes and its complications.

A Compressive Review on Source, Toxicity and Biological Activity of Flavonoid.

Flavonoids are biologically active chemicals in various fruits, plants, vegetables, and leaves, which have promising uses in medicinal science. The health properties of these natural chemicals are widely accepted, and efforts are underway to extract the specific components referred to as flavonoids. Flavonoids demonstrate a diverse range of bio-activities, anticancer, antioxidant activity, anti-cholinesterase activity, antiinflammatory activity, antimalarial activity, antidiabetic activity, neurodegenerative disease, cardiovascular effect, hepatoprotective effects, and antiviral and antimicrobial activity. This study aims to examine the prevailing trends in flavonoid investigation studies, elucidate the activity of flavonoids, examine their various functions and uses, assess the potential of flavonoids as preventive medications for chronic diseases, and outline future research opportunities in this field. This review explores the diverse functions of flavonoids in preventing and managing various diseases.

Antidiabetic and Antihyperlipidemic Activities and Molecular Mechanisms of Phyllanthus emblica L. Extract in Mice on a High-Fat Diet.

We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by EPE, fenofibrate (Feno), or metformin (Metf) treatment daily for another 4-week HFD in HFD-fed mice. Finally, we harvested blood to analyze some tests on circulating glycemia and blood lipid levels. Western blotting analysis was performed on target gene expressions in peripheral tissues. The present findings indicated that EPE treatment reversed the HFD-induced increases in blood glucose, glycosylated HbA1C, and insulin levels. Our findings proved that treatment with EPE in HFD mice effectively controls hyperglycemia and hyperinsulinemia. Our results showed that EPE reduced blood lipid levels, including a reduction in blood triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA); moreover, EPE reduced blood leptin levels and enhanced adiponectin concentrations. EPE treatment in HFD mice reduced BUN and creatinine in both blood and urine and lowered albumin levels in urine; moreover, EPE decreased circulating concentrations of inflammatory NLR family pyrin domain containing 3 (NLRP3) and kidney injury molecule-1 (KIM-1). These results indicated that EPE displayed antihyperglycemic and antihyperlipidemic activities but alleviated renal dysfunction in HFD mice. The histology examinations indicated that EPE treatment decreased adipose hypertrophy and hepatic ballooning, thus contributing to amelioration of lipid accumulation. EPE treatment decreased visceral fat amounts and led to improved systemic insulin resistance. For target gene expression levels, EPE enhanced AMP-activated protein kinase (AMPK) phosphorylation expressions both in livers and skeletal muscles and elevated the muscular membrane glucose transporter 4 (GLUT4) expressions. Treatment with EPE reduced hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) expressions to suppress glucose production in the livers and decreased phosphorylation of glycogen synthase kinase 3β (GSK3β) expressions to affect hepatic glycogen synthesis, thus convergently contributing to an antidiabetic effect and improving insulin resistance. The mechanism of the antihyperlipidemic activity of EPE involved a decrease in the hepatic phosphorylation of mammalian target of rapamycin complex C1 (mTORC1) and p70 S6 kinase 1 (S6K1) expressions to improve insulin resistance but also a reduction in hepatic sterol regulatory element binding protein (SREBP)-1c expressions, and suppression of ACC activity, thus resulting in the decreased fatty acid synthesis but elevated hepatic peroxisome proliferator-activated receptor (PPAR) α and SREBP-2 expressions, resulting in lowering TG and TC concentrations. Our results demonstrated that EPE improves insulin resistance and ameliorates hyperlipidemia in HFD mice.

Carnosic Acid and its Pharmacological Activities: An Updated Review

Carnosic acid (CA), a polyphenolic diterpene naturally found in Rosmarinus officinalis, has demonstrated a wide range of pharmacological activities according to scientific research, making it a key candidate for new therapeutic product development. The aim of this manuscript is to present an updated review of the literature on the latest research findings about carnosic acid, emphasizing its most relevant biological functions. Accordingly, this work highlights the main reported pharmacological activities, such as antioxidant, antidiabetic, anti-inflammatory, antimicrobial, antiobesity, anticancer, and neuroprotective properties. We conducted a systematic search of bibliographic databases for peer-reviewed literature based on a specific review question, utilizing scientific databases including PubMed, Scopus, Science Direct, and Google Scholar published since 1990. Numerous studies have highlighted the extensive therapeutic applications of carnosic acid. Among others, carnosic acid was found to have antioxidant, antidiabetic, anti-inflammatory, antimicrobial, antiobesity, anticancer, and neuroprotective activities. Further, carnosic acid displayed low toxicity levels and few side effects. CA shows great promise as a therapeutic agent in the prevention and treatment of many diseases, such as numerous cancers, infectious diseases, and newly emerging illnesses like Alzheimer’s and Parkinson’s diseases. In recent times, there has been a significant push to improve PBMs, proposing their application as natural drugs for several pathological conditions, with a focus on their anti-inflammatory and antioxidant capabilities. Carnosic acid exhibits antidiabetic, antimicrobial, antiobesity, and neuroprotective effects, as well as antitumor, anti-infectious, CNS, and endocrine system activities. However, further research on its precise pharmacological mechanisms is required before it can be reliably used to treat human diseases.

A Captivating Potential of Schiff Bases Derivatives for Antidiabetic Activity.

A double bond between the nitrogen and carbon atoms characterizes a wide class of compounds known as Schiff bases. The flexibility of Schiff bases is formed from several methods and may be combined with alkyl or aryl substituents. The group is a part of organic compounds, either synthetic or natural, and it serves as a precursor and an intermediate in drugs that have therapeutic action. The review focuses on molecular docking and structure-activity relationship (SAR) analysisfor antidiabetic effects of the different non-metal Schiff bases. Many studies have found that Schiff bases are used as linkers in an extensive range of synthesized compounds and other activities. Thus, this current study aims to give the scientific community a thoughtful look at the principal ideas put forward by investigators regarding antidiabetic actions exhibited by certain Schiff-based derivatives, as this review covered many aspects, including docking and SAR analysis. For individuals who intend to create novel antidiabetic compounds with Schiff bases as pharmacophores or physiologically active moieties, it will be an invaluable informational resource.

Hemocompatibility and hemorheological activity of aqueous extracts from Phyllanthus sellowianus: effects on in vitro glycated erythrocytes

IntroductionPhyllanthus sellowianus (Klotzsch) Müll Arg. is an Argentinian and Brazilian native plant used to treat diabetes. In vascular diseases like diabetes, erythrocytes form anomalous aggregates resistant to dissociation, associated with high glucose levels. This work aims to evaluate the hemocompatibility and hemorheological activity of aqueous extracts from P. sellowianus and its anti-diabetic activity using in vitro glycated erythrocytes as occur by hyperglycemia. MethodsFor this work, P. sellowianus specimens were collected on the Nogoyá River coast, Argentina, and morphoanatomical identified. Infusion, maceration, digestion, and cooking extracts were prepared with collected leaves and bark using saline as solvent. The osmolality and pH of the extracts were adjusted to an adequate interaction with human cells. Red blood cells (RBCs) from healthy donors (n=3) were used and incubated with glucose solution for in vitro simulation of the hyperglycemia effects. RBCs were incubated with the aqueous extracts to assess their hemocompatibility. Also, glycated RBCs were incubated with the extracts to analyze their anti-diabetic properties. Erythrocyte Rheometer and Optical Chip Aggregameter were used for the hemorheological evaluation. ResultsAssays with the different P. sellowianus extracts modified the viscoelasticity and aggregation of RBCs. Moreover, in some cases, P. sellowianus extracts reversed the in vitro glycation effect and hemorheological parameters got nearer control values. ConclusionThese results would be helpful for the development of pharmaceutical formulations using this species or its phytocomponents. They also give relevant information to understand the action mechanisms through which these extracts or their components can be used as anti-diabetics in Phytomedicine.

Pyrazole-based N-phenyl pyrazolines: Synthesis, docking, and pharmacological evaluation

A series of methoxy substituted pyrazole based pyrazoline derivatives (4a-j) were synthesized in good to excellent yield from corresponding pyrazole-chalcones (3a-j). All synthesized derivatives were characterized and screened for their in vitro anti-inflammatory, antioxidant, antidiabetic, and antibacterial activities. Among the series, compounds 4f, 4j, 4a, and 4i showed better anti-inflammatory activity as compared to diclofenac sodium. In DPPH free radical scavenging assay, all the compounds were shown excellent activity and moderate to good activity in SO and NO free radical scavenging assay as compared to standard ascorbic acid. Antibacterial screening of synthesized pyrazolines showed that compounds 4f and 4j have significant antibacterial activity. The compounds 4j, 4f, 4h, 4a, and 4c have shown comparable inhibition of alpha-amylase enzyme leading to good antidiabetic activity as compared to standard acarbose. Molecular docking studies suggest that these compounds have strong binding with COX-2 and alpha-amylase enzyme due to significant capability of aromatic and hydrophobic interaction. The outstanding results of reported compounds in all biological screening will pave the way for the design of new drug candidate bearing pyrazole moiety.

Synthesis, characterization, in vitro and in silico studies of N, N-dimethyl phenyl chalcone-Schiff’s base hybrid

Three dissimilar N, N-dimethylphenyl chalcone Schiff's base hybrids (CSBHs) were synthesized and characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared (FT-IR) and ultraviolet-visible spectroscopic techniques by the theoretical as well as investigational methods. The molecular weights of the CSBHs were also confirmed by the Electrospray ionization Mass technique. The in vitro antidiabetic, anti-inflammatory and cytotoxicity were tested for the CSBHs using α-amylase inhibitory and protein anti-denaturation methods. The CSBHs showed good antidiabetic and anti-inflammatory activities and the percentage of inhibitions is nearer to standard drugs acarbose and diclofenac sodium. The molecular docking studies for CSBHs were investigated and their docking results are superior and also density functional theory method are performed for CSBHs to support biological and molecular docking results. The CSBHs showed very good hydrogen bonding interactions with amino acid residues of the enzymes and the CSBHs showed lower band gap and higher electrophilicity index values. In addition, (ADMET) Absorption, Distribution, Metabolism, Excretion and Toxicity study and Protox-II toxicity predictions were performed to check the pharmacological properties of CSBHs.

Predicting Antidiabetic Peptide Activity: A Machine Learning Perspective on Type 1 and Type 2 Diabetes.

Diabetes mellitus (DM) presents a critical global health challenge, characterized by persistent hyperglycemia and associated with substantial economic and health-related burdens. This study employs advanced machine-learning techniques to improve the prediction and classification of antidiabetic peptides, with a particular focus on differentiating those effective against T1DM from those targeting T2DM. We integrate feature selection with analysis methods, including logistic regression, support vector machines (SVM), and adaptive boosting (AdaBoost), to classify antidiabetic peptides based on key features. Feature selection through the Lasso-penalized method identifies critical peptide characteristics that significantly influence antidiabetic activity, thereby establishing a robust foundation for future peptide design. A comprehensive evaluation of logistic regression, SVM, and AdaBoost shows that AdaBoost consistently outperforms the other methods, making it the most effective approach for classifying antidiabetic peptides. This research underscores the potential of machine learning in the systematic evaluation of bioactive peptides, contributing to the advancement of peptide-based therapies for diabetes management.

Development, Validation, and Greenness Assessment of HPLC and ATR-FTIR for Mangiferin Quantitative Analysis in Raw Material

Due to the benefits of mangiferin, including antidiabetic, antibacterial, antiviral, antioxidant, and anti-inflammatory activities, it is a natural raw material used in botanical health and cosmetic products. This research aims to develop and validate analytical methods for the quantification of mangiferin in raw material, isolated from Mangifera indica L. leaves, using high performance liquid chromatography (HPLC) and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The greenness assessment of both analytical methods was performed. The results indicated that both methods were validated in terms of specificity, linearity, range, detection limit, quantitation limit, accuracy, and precision. The ranges of mangiferin used in HPLC and ATR-FTIR were 30 to 360 µg/mL and 5.00 to 27.27% w/w, respectively. The mangiferin content in five batches, analyzed by using the validated HPLC and ATR-FTIR, ranged from 88.35 to 109.4% w/w and 90.7 to 111.8% w/w, respectively. Statistical analysis using a paired t-test revealed no significant difference in the mangiferin quantity between the two techniques at a 95% confidence level. The greenness scores of the HPLC and ATR-FTIR determined according to AGREE metric were 0.49 and 0.81, respectively. Both methods can be applied to quantify mangiferin content and control the quality of mangiferin raw material. Additionally, the validated ATR-FTIR, which proposed excellent environmental friendliness, was suggested as an alternative analytical method for routine assay of mangiferin raw material.

Investigation of Phytochemical Composition, Radical Scavenging Potential, Anti-obesogenic Effects, and Anti-diabetic Activities of Kaempferia parviflora Rhizomes.

Kaempferia parviflora or commonly known as "Kunyit hitam" by locals, is an edible plant, native to tropical regions, has been extensively utilized for culinary and medicinal applications. The present study aimed to investigate the phytochemical composition and biological activities of the rhizomes of K. parviflora. The ethanol crude and fractionated extracts (hexane and chloroform) of the rhizomes were evaluated for their total phenolic content, total steroidal content, as well as antioxidant, anti-obesogenic, and anti-diabetic activities. The chloroform extract demonstrated the highest concentration of plant sterols (432 ± 0.23 mg BSE/g extract) and a substantial amount of phenolic compounds (1.19 × 103 ± 0.41 mg GAE/g extract). Gas chromatography-mass spectrometry (GC/MS) analysis revealed that the chloroform extract of the rhizomes is predominantly composed of bioactive flavonoids including tectochrysin (1), 5,7-dimethoxyflavone (2), 3,5,7-trimethoxyflavone (3), 3,4',5,7-tetramethoxyflavone (4), and 4',5,7-trimethoxyflavone (5). Furthermore, the chloroform extract exhibited the highest overall radical scavenging and α-glucosidase inhibitory activities, which can be attributed to the presence of compounds 1-5 in the extract. Collectively, these findings suggest that the chloroform extract of the rhizomes of K. parviflora is a potentially valuable source of bioactive compounds with antioxidant, anti-obesogenic, and anti-diabetic properties, with potential application in therapeutics and functional foods.

Phytochemical profiling and bioactivity analysis of Citrus japonica leaves volatile oil from Palestine

BackgroundExploring the therapeutic potential of unutilized plant parts from agricultural crops represents a promising strategy for discovering novel medications with high positive economic value. This study aimed to characterize the composition, antidiabetic, anti-obesity, antioxidant, and cytotoxic effects of volatile oil (VO) extracted from the leaves of Citrus japonica trees. This is the first research to assess the C. japonica VO’s anti-obesity, anti-lipase, and cytotoxic properties. Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays and gas chromatography–mass spectrometry (GC–MS) analysis, the components of VO and its capacity to suppress the growth of cancer and other abnormal cells were ascertained, respectively. Stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, p-nitrophenyl butyrate (PNPB), and dinitrosalicylic acid (DNSA) assays were employed to determine antioxidant, anti-obesity, and antidiabetic activities, respectively.ResultsThe C. japonica leaf showed significant diversity in type and percentage of VO molecules. Overall, 45 compounds were identified in the VO, constituting 99.69% of the total oil composition. γ-Muurolene (28.12%), β-eudesmol (10.93%), γ-eudesmol (8.44%), germacrene B (7.39%), and elemol (7.27%) are the major characterized molecules. According to the inhibition percentage results of DPPH free radicals, porcine pancreatic lipase, and α-amylase, the VO exhibits strong antioxidant properties and weak inhibitory effects on lipase and α-amylase enzymes. The C. japonica VO showed a moderate cytotoxic effect against Hep3B and considerable activity on B16F1, CaCo-2, HeLa, MCF-7, and HepG2, with IC50 doses in the range of 69.7–171.96 µg/mL. The VO cytotoxic effect IC50 against the normal cell line LX-2 was 224.95 µg/mL.ConclusionThe current study collectively presented the chemical constituents of C. japonica leaf VO from Palestine for the first time and demonstrated its inhibitory effects against DPPH free radicals, porcine pancreatic lipase, and α-amylase. The results suggest that C. japonica leaf VO has the potential to be used as a natural supplement to prevent or treat cancer, as well as in the food industry as a natural antioxidant.Graphical

Targeting FAK, VEGF, and MTA1 proteins with Terminalia elliptica: a computational approach for anticancer activity.

Cancer remains a significant global health challenge, prompting exploration into alternative treatments such as those derived from natural compounds found in traditional medicine. Recent research has underscored the role of proteins like Focal Adhesion Kinase (FAK), Vascular Endothelial Growth Factor (VEGF), and Metastasis-Associated Protein 1 (MTA1) in driving cancer cell proliferation and survival. Here, we investigated the potential of a single molecule to modulate these key proteins involved in metastasis, offering a promising avenue for cancer therapy. Terminalia elliptica, commonly known as Asna, possesses a diverse range of medicinal properties, including antimicrobial, anti-inflammatory, anticancer, antidiabetic, antiaging, hepatoprotective, antioxidant, and neuroprotective activities. Our study aimed to explore the anticancer potential of Terminalia elliptica by identifying bioactive compounds capable of targeting FAK, VEGF, and MTA1 to impede cancer metastasis. Through in silico analysis, we conducted network analysis using Cytoscape to assess the significance of these bioactive compounds in the inhibition of signaling pathways driving metastasis. The utilization of these bioactives as potential candidates for targeted therapy of VEGF, FAK, and MTA1 regulated pathways was preliminarily assessed by Molecular Docking and MD Simulation. Our findings revealed that phytobioactives namely, Chebulinic Acid of Terminalia elliptica, exhibited notable binding affinity and interaction with FAK, and Chebulagic Acid with VEGF, and MTA1. This discovery holds promise as a novel therapeutic approach for combating cancer, offering potential benefits in cancer treatment and management.

Inoculation with Jeotgalicoccus sp. improves nutritional quality and biological value of Eruca sativa by enhancing amino acid and phenolic metabolism and increasing mineral uptake, unsaturated fatty acids, vitamins, and antioxidants.

Plant growth-promoting bacteria (PGPB) are considered a promising tool for triggering the synthesis of bioactive compounds in plants and to produce healthy foods. This study aimed to demonstrate the impact of PGPB on the growth, accumulation of primary and secondary metabolites, biological activities, and nutritional qualities of Eruca sativa (arugula), a key leafy vegetable worldwide. To this end, Jeotgalicoccus sp. (JW0823), was isolated and identified by using partial 16S rDNA-based identification and phylogenetic analysis. The findings revealed that JW0823 significantly boosted plant biomass production by about 45% (P<0.05) and enhanced pigment contents by 47.5% to 83.8%. JW0823-treated plants showed remarkable improvements in their proximate composition and vitamin contents, with vitamin E levels increasing by 161.5%. JW0823 induced the accumulation of bioactive metabolites including antioxidants, vitamins, unsaturated fatty acids, and essential amino acids, thereby improving the nutritional qualities of treated plants. An increase in the amounts of amino acids was recorded, with isoleucine showing the highest increase of 270.2%. This was accompanied by increased activity of the key enzymes involved in amino acid biosynthesis, including glutamine synthase, dihydrodipicolinate synthase, cystathionine γ-synthase, and phenylalanine ammonia-lyase enzymes. Consequently, the total antioxidant and antidiabetic activities of the inoculated plants were enhanced. Additionally, JW0823 improved antimicrobial activity against several pathogenic microorganisms. Overall, the JW0823 treatment is a highly promising method for enhancing the health-promoting properties and biological characteristics of E. sativa, making it a valuable tool for improving the quality of this important leafy vegetable.

Investigation of the mechanism underlying the antidiabetic actions of extracts of Ocimim basilicum

Investigation of the mechanism underlying the antidiabetic actions of extracts of <i>Ocimim basilicum</i>

Corilagin alleviates podocyte injury in diabetic nephropathy by regulating autophagy via the SIRT1-AMPK pathway.

Diabetic nephropathy (DN) is the most frequent chronic microvascular consequence of diabetes, and podocyte injury and malfunction are closely related to the development of DN. Studies have shown that corilagin (Cor) has hepatoprotective, anti-inflammatory, antibacterial, antioxidant, anti-hypertensive, anti-diabetic, and anti-tumor activities. To explore the protective effect of Cor against podocyte injury in DN mice and the underlying mechanisms. Streptozotocin and a high-fat diet were combined to generate DN mice models, which were then divided into either a Cor group or a DN group (n = 8 in each group). Mice in the Cor group were intraperitoneally injected with Cor (30 mg/kg/d) for 12 wk, and mice in the DN group were treated with saline. Biochemical analysis was used to measure the blood lipid profiles. Hematoxylin and eosin staining was used to detect pathological changes in kidney tissue. Immunohistochemistry and Western blotting were used to assess the protein expression of nephrin and podocin. Mouse podocyte cells (MPC5) were cultured and treated with glucose (5 mmol/L), Cor (50 μM), high glucose (HG) (30 mmol/L), and HG (30 mmol/L) plus Cor (50 μM). Real-time quantitative PCR and Western blotting were performed to examine the effects of Cor on podocyte autophagy. Compared with the control group, the DN mice models had increased fasting blood glucose, glycosylated hemoglobin, triglycerides, and total cholesterol, decreased nephrin and podocin expression, increased apoptosis rate, elevated inflammatory cytokines, and enhanced oxidative stress. All of the conditions mentioned above were alleviated after intervention with Cor. In addition, Cor therapy improved SIRT1 and AMPK expression (P < 0.001), inhibited reactive oxygen species and oxidative stress, and elevated autophagy in HG-induced podocytes (P < 0.01). Cor alleviates podocyte injury by regulating autophagy via the SIRT1-AMPK pathway, thereby exerting its protective impact on renal function in DN mice.

Antioxidant and anti-diabetic effects in vitro of extract from the above-ground parts of Acanthus ilicifolius

The in vitro antioxidant and anti-diabetic activity of the extract from the above-ground parts of Acanthus ilicifolius was evaluated to assess the potential of this plant as a probable natural medicinal source for diseasetreatment. The aqueous extract from the above-ground parts of this plant demonstrated the existence of alkaloids, polyphenols, flavonoids, steroids, triterenes, tannins, saponins, and glycosides, providing promising results in all the tests performed. The antioxidant activity of A. ilicifolius's above-ground parts extract was graded by five methods, including total antioxidant capacity (TAC), reducing power (RP), ferric reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS•+), and the results showed that the extract has strong antioxidant effects. The inhibitory activity of two enzymes, α-amylase and α-glucosidase enzymes was assessed and compared with the standard acarbose. Extract from A. ilicifolius's above-ground parts could inhibit the enzyme α-amylase with an EC50 value of 136.35 ± 2.11 µg/mL and α-glucosidase with an EC50 value of 49.81 ± 0.37 µg/mL. The results confirmed that A. ilicifolius can be an important natural medicinal source with antioxidant, α-amylase, and αglucosidase inhibitory properties. Keywords: Acanthus ilicifolius; antioxidant; anti-diabetic; α-amylase; α-glucosidase; medicinal.

Fibroblast growth factor 21 improves insulin sensitivity by modulating the bile acid-gut microbiota axis in type Ⅱ diabetic mice

BackgroundFibroblast growth factor 21 (FGF21) is an important regulator of glycolipid metabolism. However, whether the gut microbiota is related to the anti-diabetic and obesity effects of FGF21 remains unclear. MethodsOur research used KO/KO db/db male mice and streptozotocin (STZ)-induced to simulate the construction of two type II diabetic mellitus (T2DM) models, and detected impaired glucose tolerance in the model by using the ipGTT and ITT assays, and collected feces from the model mice for sequencing of the intestinal flora and the content of short-chain fatty acids. H＆E staining was used to detect changes in intestinal tissue, the serum levels of LPS and GLP-1 were detected by ELISA. ResultsIn this study, we found that FGF21 significantly improved insulin sensitivity, attenuated intestinal lesions, and decreased serum lipopolysaccharide (LPS) concentrations in T2DM mice. Moreover, FGF21 reshaped the gut microbiota and altered their metabolic pathways in T2DM mice, promoting the production of short-chain fatty acids (SCFAs) and the secretion of glucagon-like peptide 1 (GLP-1). Fecal transplantation experiments further confirmed that feces from FGF21-treated diabetic mice demonstrated similar effects as FGF21 in terms of anti-diabetic activity and regulation of gut microbiota dysbiosis. Additionally, the antibiotic depletion of gut microbiota abolished the beneficial effects of FGF21, including increased GLP-1 secretion and fecal SCFA concentration. Additionally, the FGF21 effects of ameliorating intestinal damage and suppressing plasma LPS secretion were suppressed. All these findings suggest that FGF21 prevents intestinal lesions by modifying the gut microbiota composition. Furthermore, FGF21 affected bile acid synthesis by inhibiting CYP7A1, the key enzyme of bile acid synthesis. ConclussionTherefore, FGF21 enriched beneficial bacteria by preventing bile acid synthesis and stimulating the secretion of the intestinal hormone GLP-1 via the increased production of gut microbiota metabolites, thereby exerting its anti-diabetic effects.