Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

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Ethno-pharmacological relevance: The genus Aloe has a long history of usage in medicine. Aloe barbadensis Miller, commonly known as Aloe vera, is said to possess anti-diabetic, anti-inflammatory, anti-cancer, anti-microbial, immunomodulation, wound healing properties. Aim of the study: In diabetes mellitus, loss in intestinal permeability is observed with high levels of zonulin and low levels of glucagon-like peptide-1 (GLP-1) leading to hyperglycemia. The aim of the study was to understand the role of peptide/polypeptide fraction (PPF) of Aloe vera in the alleviation of diabetes through maintaining the intestinal permeability by regulating the zonulin and GLP-1 levels. Materials and methods: The PPF of Aloe vera was obtained through trichloroacetic acid precipitation. The anti-diabetic potential of the PPF was tested through DPP-IV inhibition, glucose diffusion assay, and by using Rin-m5F cells. The anti-diabetic potential of the PPF was tested at a dose of 0.450 mg/kg bw in vivo using streptozotocin-induced diabetic Wistar rats. The effect of PPF on fasting plasma glucose, insulin, glucagon, Zonulin, GLP-1, DPP-IV, levels were studied in diabetic rats. The histopathological studies of the pancreas, small intestine, and liver were carried out for organ-specific effects. Results: PPF has the ability to reduce fasting plasma glucose levels with concomitant increase in insulin levels in streptozotocin-induced diabetic rats. It was also observed that increase in GLP-1 levels with a decrease in DPP-IV and zonulin levels thereby mitigating the loss of intestinal permeability. These findings correlate with the small intestine's histopathological observation where the excessive proliferation of epithelium in the small intestine of diabetic rats was reduced after PPF treatment. Conclusion: These results suggest that the PPF of Aloe vera alleviates diabetes through islet cell rejuvenation via GLP-1/DPP-IV pathway and thereby suggesting the usage of PPF as an alternate medicine for diabetes mellitus with the possibility to reduce the intestinal permeability and zonulin levels. © 2021 Elsevier B.V.

World University root node

Centre for Bio-Separation and Technology

Vellore Campus

Journal of Ethnopharmacology

Role of zonulin and GLP-1/DPP-IV in alleviation of diabetes mellitus by peptide/polypeptide fraction of Aloe vera in streptozotocin- induced diabetic wistar rats

A series of spiro-[indoline-3,3′-pyrrolizin/pyrrolidin]-2-ones, 4, 5 and 6 were synthesized in a sequential manner from Cu-TEMPO catalyzed dehydrogenation of alkylated ketones, 1 followed by 1,3-dipolar cycloaddition of azomethine ylides via decarboxylative condensation of isatin, 2 and l-proline/sarcosine, 3 in high regioselectivities and yields. The detailed mechanistic studies were performed to identify the reaction intermediates, which revealed that the reaction proceeds via dehydrogenative cycloaddition. Additionally, the regio and stereochemistry of the synthesized derivatives were affirmed by 2D NMR spectroscopic studies. The synthesized derivatives were explored further with molecular docking, in vitro antioxidant, and anti-diabetic activities. © 2020 The Royal Society of Chemistry.

Department of Chemistry

School of Advanced Sciences

Fulltext

RSC Advances

Cu/TEMPO catalyzed dehydrogenative 1,3-dipolar cycloaddition in the synthesis of spirooxindoles as potential antidiabetic agents

The therapeutic and pharmacological properties of plant bioactive constituents still continue to be the subject of many researches. Species of the Aloe genus have a history in folklore medicine and they have gained more attention over the years due to their various medicinal properties. Phytochemical studies have revealed that the Aloe species contain a number of constituents, such as polyphenols, phytosterols, polysaccharides, proteins, amino acids, chromones, and mineral elements. A comprehensive evidence-based review on the different constituents of Aloe species is needed in order to understand the benefits imparted by them. This review presents an overview of the bioactive components of the Aloe genus with emphasis on their anti-diabetic potential and other pharmacological benefits. This information will be beneficial for the advancement of new strategies of Aloe formulations with therapeutic and economical value in the near future. Furthermore, the potential applications and constraints have also been discussed so as to provide a wider prospect for research in this field for the benefit of the society. © xxxx **

Journal of Applied Pharmaceutical Science

Bioactive constituents of the genus Aloe and their potential therapeutic and pharmacological applications: A review

Streptozocin (STZ) is a broad range antibiotic, highly genotoxic, antineoplastic and hyperglycemic. HSA is the most abundant protein in physiology and it binds to almost all exogenic and endogenic ligands, including drugs. STZ-induced <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/quenching-fluorescence">fluorescence quenching</a> of HSA has been done at pH 7.4, pH 3.5 and at pH 7.4 with 4.5 M urea at temperatures 286 K, 291 K, and 306 K. Ksv found to be 103 M−1, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/binding-affinity">binding constant</a> 1.5X103M−1 and binding sites ~1. But, Ksv for HSA and glucopyranose interaction was found lesser than that of HSA-STZ binding. Binding of STZ/glucopyranose on HSA seems to result in complex formation as calculated Kq &gt; 1010 M−1 s−1. The number of binding sites, binding constants, and binding energies were increased with temperature. The ΔG0, ΔH0, and ΔS0 for HSA-STZ interaction were found to be −17.7 × 103 J·mol−1; 2.34 × 105 J·mol−1 and 841 JK−1 mol−1 respectively at pH 7.4 and 291 K. The comparative bindings of N, F and I states of HSA with STZ and their <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/docking-molecular">molecular docking</a> analyses indicate that IIIA-B junction (i.e., inter-helix h6DOM3-h7DOM3) is the probable binding site, a locus close to fatty acid binding site-5. These results could be useful for therapeutic and analytical exploitation of STZ, as <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/albumin">albumin</a> used as the vehicle for drug delivery.

VIT Unitversity

Department of Biotechnology

School of Bio Sciences and Technology

International Journal of Biological Macromolecules

Streptozocin; a GLUT2 binding drug, interacts with human serum albumin at loci h6DOM3-h7DOM3

Aloe vera (Aloe barbadensis Miller) is a perennial succulent plant belonging to the Aloeaceae family and has been used for many centuries for its medicinal properties. Among the Aloe vera plant parts, gel is being widely studied for their biological properties. However, epidermis and flowers are neglected and are not probed for their importance. In this study, the methanolic extracts of Aloe vera gel, leaf and flower were evaluated for their anti-oxidant and anti-diabetic potential in vitro and other phytochemical constituents. We observed that the Aloe vera gel, leaf and flowers have shown significant anti-oxidant potential. When compared between leaf, gel and flower of Aloe vera, the leaf showed better antioxidant activity in ABTS, DPPH, H2O2 radical scavenging activities, Metal chelating activity and reducing power. However, the gel extract showed better anti-diabetic efficacy compared to the flower extract with respect to α-amylase, α-glucosidase, DPP-IV inhibition and anti-glycation activities. This study suggests that different parts of Aloe vera exhibit great potential for antioxidant and anti-diabetic activity and may be useful in new health-care food supplements or nutraceutical. © RJPT All right reserved.

Research Journal of Pharmacy and Technology

Evaluation of In vitro anti-diabetic and anti-oxidant activities and preliminary phytochemical screening of gel, epidermis and flower extract of Aloe vera

Objective: To evaluate the anti-inflammatory potential of peptide/polypeptide fraction of Aloe vera through in vitro and in vivo studies. Methods: The peptide/polypeptide fraction from Aloe vera was obtained through trichloroacetic acid precipitation. The anti-inflammatory property of the peptide/polypeptide fraction was tested by protein denaturation, membrane stabilization assays. The effect of the fraction on RAW 264.7 cell viability was examined by MTT assays. The nitric oxide level was determined through Griess reagent. TNF-α and IL-6 levels were estimated using ELISA kits. In vivo studies were carried out in male Wistar rats through injection of Freund's adjuvant in the hind paw. Paw edema was measured through the Vernier scale and levels of alanine aminotransferase, aspartate transaminase, TNF-α, IL-6, and secretory phospholipase A2 were estimated through their respective kits after fourteen days of treatment. GraphPad Prism6 was used for analyzing the results. Results: The peptide/polypeptide extract inhibited protein denaturation with an IC50 value of (218.9±15.6) μg/mL and stabilized the membrane of red blood cells with an IC50 value of (275.9±19.1) μg/mL. The extract showed no changes in cell morphology or cytotoxicity up to the concentration of 20 μg/mL in MTT assays. The peptide/polypeptide fraction markedly reduced the levels of proinflammatory markers and mediators in both in vitro and in vivo studies. Conclusions: The results indicate that the peptide/polypeptide fraction of Aloe vera has anti-inflammatory property through inhibition of inflammatory markers and mediators responsible for NF-κB and mitogen-activated protein kinase pathways. © 2019 Wolters Kluwer Medknow Publications. All rights reserved.

Asian Pacific Journal of Tropical Biomedicine

Aloe barbadensis Miller peptide/polypeptide fraction alleviates inflammation through inhibition of proinflammatory cytokines and mediators in vitro and in rats with Freund's adjuvant-induced hind paw edema

Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Plant extracts and their products are being used as an alternative system of medicine for the treatment of diabetes. Aloe vera has been traditionally used to treat several diseases and it exhibits antioxidant, anti-inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar diabetic rats were used in this study to understand the potential protective effect of A. vera extract on the pancreatic islets. Objective: The aim of the present study was to evaluate the A. vera extract on improvement of insulin secretion and pancreatic β-cell function by morphometric analysis of pancreatic islets in STZ-induced diabetic Wistar rats. Materials and Methods: After acclimatization, male Wistar rats, maintained as per the Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines, were randomly divided into four groups of six rats each. Fasting plasma glucose and insulin levels were assessed. The effect of A. vera extract in STZ-induced diabetic rats on the pancreatic islets by morphometric analysis was evaluated. Results: Oral administration of A. vera extract (300 mg/kg) daily to diabetic rats for 3 weeks showed restoration of blood glucose levels to normal levels with a concomitant increase in insulin levels upon feeding with A. vera extract in STZ-induced diabetic rats. Morphometric analysis of pancreatic sections revealed quantitative and qualitative gain in terms of number, diameter, volume, and area of the pancreatic islets of diabetic rats treated with A. vera extract when compared to the untreated diabetic rats. Conclusion: A. vera extract exerts antidiabetic effects by improving insulin secretion and pancreatic β-cell function by restoring pancreatic islet mass in STZ-induced diabetic Wistar rats. © 2017 Pharmacognosy Research | Published by Wolters Kluwer-Medknow.

Department of Integrative Biology

Pharmacognosy Research

Improvement of insulin secretion and pancreatic β-cell function in streptozotocin-induced diabetic rats treated with Aloe vera extract

Diabetes is a growing health concern worldwide and now emerging as an epidemic world over. The management of diabetes is still a major challenge. Thus there is great demand for research on natural products with anti-diabetic properties. Numerous studies have confirmed the benefits of medicinal plants with anti-hyperglycemic effects in the management of diabetes mellitus. In this review, we address the beneficial effects of selective medicinal plant species such as Allium cepa, Allium sativum, Aloe vera, Azadirachta indica, Gymnema sylvestre, Syzygium cumini and Pterocarpus marsupium, and emphasize on the role of active biomolecules which possess anti-diabetic activity.

Current Science

Current update on anti-diabetic biomolecules from key traditional indian medicinal plants

Black gram (Vigna mungo) is a legume which belongs to Fabaceae family. It is a rich source of protein. It has been known to have interesting small molecule antioxidant activity. However, its enzymatic antioxidant properties have not been explored much. In the present work we studied catalase, a principal antioxidant enzyme from black gram seeds. Day four sprouted black gram seeds were found to have a significant catalase content approximately of 15,240 U/g seeds. IMAC (Seph 4B-IDA-Zn(II)) was used for purifying this catalase, a purification fold of 106 and a high specific activity of 25,704 U/mg was obtained. The K(m) and V(max) of the purified catalase were found to be 16.2 mM and 2.5 μmol/min. The effect of inhibitors like Sodium azide (NaN(3)) and EDTA and different metal ions on catalase activity were studied. NaN(3), Fe(3+)and Cu(2+) were found to have profound inhibitory effects on the enzyme activity. Other metal ions like Ni(2+), Ca(2+), Mg(2+) and Mn(2+) had both enhancing and inhibitory effects. The enzyme showed optimal activity at a temperature of 40°C and pH 7.0. It was stable over a broad range of pH 6.0-10.0 and had a half life of 7h 30 min at 50°C.

Journal of Chromatography B

Purification and characterization of catalase from sprouted black gram (Vigna mungo) seeds

The context and purpose of the study: Plants that have been used for traditional medicines are very good sources of phyotochemicals. There are many plants like Casuarina equisetifolia, which are still unexplored for their medicinal properties. In the present study, we have elucidated the in vitro antioxidant and antiproliferative activity of different solvent extracts (both polar and non polar) of C. equisetifolia needles. Main findings: In vitro antioxidant activity of different solvent extracts of C. equisetifolia needles was studied by analyzing the total polyphenols, flavonoids, total antioxidant capacity and free radical scavenging activity. The polar solvent extracts showed significantly high amount total polyphenols, flavonoids, antioxidants and free radical scavenging activity compared to the non polar solvent extracts. The cytotoxic and apoptosis inducing activity of the different solvent extracts were analyzed on MCF-7 cells by MTT assay, acridine orange/ethidium bromide staining, DAPI staining and caspase-3 release. The polar solvent extracts did not show any growth inhibition in MCF-7 cancer cells. But the non polar solvent extracts are very good in inducing cell death by inducing apoptosis which involves DNA fragmentation and release of caspase 3. Using silica gel fractionation and RPHPLC analysis the active component present in non-polar solvent extracts was identified as ascorbic acid. Brief summary and potential implications: Our results indicated that the needles of C. equisetifolia are rich sources of antioxidants and also contain potential anticancer agents. Detailed study on the mechanism of action of purified compound on inhibition of cancer cell growth may provide some potential anticancer molecule from natural source.

International Journal of Phytomedicine

Antioxidant and anti-proliferative activity of different solvent extracts of Casuarina equisetifolia needles

In the present study, we have developed an encapsulation procedure which retains the antioxidant properties and polyphenol contents from two novel plants stable over a period of one year at room temperature at non-toxic level. Methanolic extracts containing polyphenols were prepared from Cordyline terminalis and Myristica fragrans under optimized conditions (C. terminalis polyphenol extracts - CTPE and M. fragrans polyphenol extracts - MFPE). These extracts contained 102.6 and 72.9 mg/g of gallic acid equivalent of polyphenols respectively, when measured using the Folin-Ciocalteu method. The antioxidant activity of CTPE and MFPE was 13.4 and 10 mg/g of ascorbic acid equivalent respectively, when measured using the 2,2-diphenyl-1-picryl-hydrazyl method. CTPE and MFPE were individually encapsulated in sodiumcaseinate beads in order to protect the polyphenol content from oxidation, and were stored separately in dark at room temperature. The stability of the encapsulated extracts was studied over a period of 12 months after dissolution of the beads in deionized water. We observed that the polyphenol content and antioxidant activity remained stable in the encapsulated beads compared to the unencapsulated extracts. Sodium-caseinate beads prove to be a promising technique for food supplementation with natural antioxidants.

Antioxidant properties of Cordyline terminalis (L.) Kunth and Myristica fragrans Houtt. encapsulated separately into casein beads

An attempt was made to study the beneficial effects of Aloe vera (L.) Burm. fil. in streptozotocin-induced diabetic rats. In diabetic induced rats fed with A. vera (300 mg/kg body wt), the fasting plasma glucose levels were reduced to normal and body weight was found to be increased. In the pancreatic sections of diabetic rats fed with A. vera, the islets were comparable to normal rats. In liver, the changes caused after induction of diabetes are granular cytoplasm, dilated sinusoids, shrunken nuclei and inflammation, which was re duced after feeding with A. vera. Excess proliferation of epithelium in the small intestine was observed in diabetic rats, which was reduced after A. vera feeding. In diabetic rats and diabetic rats fed with A. vera, no change was noticed in the kidney and stomach.