Antioxidant effects of some selected flavonoids: a structure-activity relationship based study

Objective: To investigate the antioxidant and radical scavenging activities of some selected flavonoids with respect to identify key positions responsible for antioxidant effects as well as the effect of derivatisation on the antioxidative effects. Design and method: Antioxidant potential was evaluated using different sets of assays viz., rapid test by dot blot, 1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging, ABTS+ radical cation scavenging, ferric reducing antioxidant powder (FRAP) and xanthine oxidase inhibitory (XOI) assays. Results: It was determined that the total number and the configuration of hydroxyl group play an important role in regulating bioactivity of flavonoids in scavenging DPPH radical, ABTS+ radical cation and FRAP assays. Presence of catechol and the absence of C-2-C-3 double bond as well as ketonic group at C-4 reduced the xanthine oxidase inhibitory activity. Methylation and acetylation of hydroxyl groups at particular positions were also found to decrease the in vitro bioactivity of flavonoids. Conclusions: The results of this study will further help to understand the role of flavonoids as natural antioxidants which might facilitate in the development of nutritional products and semi synthetic analogs that retain substantial antioxidant capacity with minimal adverse effects. Keywords: Flavonoids; antioxidant activity; derivatisation, structure activity relationshi

Potential bioactive coating system for high-performance absorbable magnesium bone implants

Magnesium alloys are considered the most suitable absorbable metals for bone fracture fixation implants. The main challenge in absorbable magnesium alloys is their high corrosion/degradation rate that needs to be controlled. Various coatings have been applied to magnesium alloys to slow down their corrosion rates to match their corrosion rate to the regeneration rate of the bone fracture. In this review, a bioactive coating is proposed to slow down the corrosion rate of magnesium alloys and accelerate the bone fracture healing process. The main aim of the bioactive coatings is to enhance the direct attachment of living tissues and thereby facilitate osteoconduction. Hydroxyapatite, collagen type I, recombinant human bone morphogenetic proteins 2, simvastatin, zoledronate, and strontium are six bioactive agents that show high potential for developing a bioactive coating system for high-performance absorbable magnesium bone implants. In addition to coating, the substrate itself can be made bioactive by alloying magnesium with calcium, zinc, copper, and manganese that were found to promote bone regeneration

Healing effect of Vicenin-2 (VCN-2) on Human Dermal Fibroblast (HDF) and development VCN-2 hydrocolloid film based on alginate as potential wound dressing

Chronic wounds represent serious globally health care and economic issues especially for patients with hyperglycemic condition. Wound dressings have a predominant function in wound treatment; however, the dressings for the long-lasting and non-healing wounds are still a significant challenge in the wound care management market. Astonishingly, advanced wound dressing which is embedded with a synthetic drug compound in a natural polymer compound that acts as drug release carrier has brought about promising treatment effect toward injured wound. In the current study, results have shown that Vicenin-2 (VCN-2) compound in low concentration significantly enhanced cell proliferation and migration of HDF. It also regulated the production of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α from HDF in wound repair. Treatment of VCN-2 also has facilitated the expression of TGF-1β and VEGF wound healing maker in a dose-dependent manner. A hydrocolloid film based on sodium alginate (SA) incorporated with VCN-2 synthetic compound which targets to promote wound healing particularly in diabetic condition was successfully developed and optimized for its physico-chemical properties. It was discovered that all the fabricated film formulations prepared were smooth, translucent, and good with flexibility. The thickness and weight of the formulations were also found to be uniform. The hydrophilic polymer comprised of VCN-2 were shown to possess desirable wound dressing properties and superior mechanical characteristics. The drug release profiles have revealed hydrocolloid film, which is able to control and sustain the VCN-2 released to wound area. In short, hydrocolloid films consisting of VCN-2 formulations are suitably used as a potential wound dressing to promote restoration of wound injury

Antidiabetic Activity of Wogonin Isolated from Tetracera indica Merr. Leaves Extract in Streptozotocin-Nicotinamide Induced Diabetic Rats

The leaves of Tetracera indica Merr. (Dilleniaceae) have been used to treat diabetes in Malaysia. However, the active principles responsible for the leaf’s antidiabetic effect are yet to be confirmed and evaluated through an in vivo investigation. Hence, a phenolic compound as a flavonoid (wogonin) was isolated as a major compound from the leaves methanol extract and subjected to antidiabetic evaluation. Initially, the powdered leaves were macerated with methanol for 72 h. The resultant methanol extract was subjected to column chromatography to isolate the pure wogonin. Its structure was elucidated through 1H- & C-13 NMR spectral analysis. Finally, the wogonin was orally given to streptozotocin-nicotinamide (STZ-NA) induced diabetic rats at three different doses (25, 40, 80 mg/kg b.w.). The histological alteration of vital organs, insulin release, biochemical assays, and blood glucose serum were evaluated and compared to standard hypoglycaemic drug i.e., metformin (0.5 mg/kg b.w.). Data of the blood glucose serum of rats treated with wogonin at 40 and 80 mg/kg b.w. revealed a significant decrease in blood glucose when compared to the diabetic control (p<0.05). Biochemical analyses for all doses displayed no significant difference when compared to the normal group and positive control (p>0.05) for triglyceride, total cholesterol, high-density, and low-density lipoprotein. However, the results were significantly different for triglyceride, total cholesterol, high-density, and low-density lipoprotein when compared to diabetic control (p<0.05). In addition, wogonin at 40 mg/kg b.w. was found to enhance insulin secretion by day 30. The histopathology data of the pancreas showed that wogonin at 40 and 80 mg/kg b.w. was observed to regenerate pancreatic β-cells in diabetic rats without demonstrating any liver and kidney toxicities. The results indicated that wogonin possesses an in vivo antidiabetic property and therefore might provide a lead for the synthesis of a safe natural product-based antidiabetic agent

Structure, degradation, drug release and mechanical properties relationships of iron-based drug eluting scaffolds : the effects of PLGA

The effects of poly(lactic‑co‑glycolic acid) (PLGA) on structure, degradation, drug release and mechanical properties relationships of iron-based drug eluting scaffolds have been studied comprehensively. The porous structure of the iron has been incorporated with the curcumin-loaded PLGA (CP) particles through dipping method to produce CP-coated porous Fe (CP-Fe). The CP-Fe degradation has been escalated with the increase of PLGA composition due to the hydrolysis of PLGA. The degradation of iron substrate triggered the kinetics of curcumin release as there was a direct correlation between the curcumin release rate and the degradation rate of the CP-Fe scaffold. The stiffness of the CP particles and the interfacial interactions developed between the CP coating and iron surface have enhanced scaffolds' mechanical strengths. The curcumin released from the scaffold significantly arrested osteosarcoma cells growth. It is demonstrated that the PLGA played an important role to control the scaffold degradation and curcumin release as well as enhancing the mechanical properties of the drug device as an integrated system for favorable scaffold-based drug design

Antioxidant and antidiabetic effects of flavonoids: a structure-activity relationship based study

The best described pharmacological property of flavonoids is their capacity to act as potent antioxidant that has been reported to play an important role in the alleviation of diabetes mellitus. Flavonoids biochemical properties are structure dependent; however, they are yet to be thoroughly understood. Hence, the main aim of this work was to investigate the antioxidant and antidiabetic properties of some structurally related flavonoids to identify key positions responsible, their correlation, and the effect of methylation and acetylation on the same properties. Antioxidant potential was evaluated through dot blot, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ABTS+ radical scavenging, ferric reducing antioxidant power (FRAP), and xanthine oxidase inhibitory (XOI) assays. Antidiabetic effect was investigated through α-glucosidase and dipeptidyl peptidase-4 (DPP-4) assays. Results showed that the total number and the configuration of hydroxyl groups played an important role in regulating antioxidant and antidiabetic properties in scavenging DPPH radical, ABTS+ radical, and FRAP assays and improved both α-glucosidase and DPP-4 activities. Presence of C-2-C-3 double bond and C-4 ketonic group are two essential structural features in the bioactivity of flavonoids especially for antidiabetic property. Methylation and acetylation of hydroxyl groups were found to diminish the in vitro antioxidant and antidiabetic properties of the flavonoids

Structure, degradation, drug release and mechanical properties relationships of iron-based drug eluting scaffolds: the effects of PLGA

The effects of poly(lactic‑co‑glycolic acid) (PLGA) on structure, degradation, drug release andmechanical properties relationships of iron-based drug eluting scaffolds have been studied comprehensively. The porous structure of the iron has been incorporated with the curcumin-loaded PLGA (CP) particles through dippingmethod to produce CP-coated porous Fe (CP-Fe). The CP-Fe degradation has been escalated with the increase of PLGA composition due to the hydrolysis of PLGA. The degradation of iron substrate triggered the kinetics of curcumin release as therewas a direct correlation between the curcumin release rate and the degradation rate of the CP-Fe scaffold. The stiffness of the CP particles and the interfacial interactions developed between the CP coating and iron surface have enhanced scaffolds'mechanical strengths. The curcumin released fromthe scaffold significantly arrested osteosarcoma cells growth. It is demonstrated that the PLGA played an important role to control the scaffold degradation and curcumin release aswell as enhancing the mechanical properties of the drug device as an integrated system for favorable scaffold-based drug design

Phytoconstituents from Vernonia glaberrima Welw. Ex O. Hoffm. leaves and their cytotoxic activities on a panel of human cancer cell lines

Vernonia glaberrima is a medicinal plant that is used in African traditional medicine for the treatment of skin cancer. The aim of this study was to investigate the anticancer activity of V. glaberrima leaves and isolate its bioactive constituents. Crude methanolic leaves extract of V. glaberrima showing significant cytotoxic activity against cancer cell lines was subjected to chromatographic separation, purification and hydrolysis to yield four compounds namely, nonacosanoic acid, lupeol, 5-methylcoumarin-4-β-glucoside and 4-hydroxy-5-methylcoumarin. Three of the isolated compounds showed significant cytotoxic activity against human malignant melanoma (A375) cell line (IC50: 59.18 ± 2.70 to 139.53 ± 10.79 μg/mL) and human caucasian colon adenocarcinoma (HT-29) cell line (IC50: 4.22 ± 0.13 to 20.0 ± 1.91 μg/mL) while only lupeol displayed significant activity against human breast adenocarcinoma (MCF7) (IC50: 34.15 ± 2.32 μg/mL) cell line. CDK2 receptor and CAIX were identified through molecular docking as potential targets for the bioactive compounds. The findings of this study have revealed the therapeutic potential of V. glaberrima against breast cancer, skin cancer and colorectal carcinoma, respectively and further support its traditional uses in the treatment of skin cancer. Keywords: Vernonia glaberrima; Anticancer activity; 5-Methylcoumarin-4-β-glucoside; Molecular docking; Carbonic anhydrase I

Flavonoids as antidiabetic and anti-inflammatory agents: a review on structural activity relationship-based studies and meta-analysis

Abstract: Flavonoids are a group of naturally occurring polyphenolic secondary metabolites which have been reported to demonstrate a wide range of pharmacological properties, most importantly, antidiabetic and anti-inflammatory effects. The relationship between hyperglycaemia and inflammation and vascular complications in diabetes is now well established. Flavonoids possessing antidiabetic properties may alleviate inflammation by reducing hyperglycaemia through different mechanisms of action. It has been suggested that the flavonoids’ biochemical properties are structure-dependent; however, they are yet to be thoroughly grasped. Hence, the main aim of this review is to understand the antidiabetic and anti-inflammatory properties of various structurally diverse flavonoids and to identify key positions responsible for the effects, their correlation, and the effect of different substitutions on both antidiabetic and anti-inflammatory properties. The general requirement of flavonoids for exerting both anti-inflammatory and antidiabetic effects is found to be the presence of a C2–C3 double bond (C-ring) and hydroxyl groups at the C3’, C4’, C5, and C7 positions of both rings A and B of a flavonoid skeleton. Furthermore, it has been demonstrated that substitution at the C3 position of a C-ring decreases the anti-inflammatory action of flavonoids while enhancing their antidiabetic activity. Correlation is discussed at length to support flavonoids possessing essential pharmacophores to demonstrate equipotent effects. The consideration of these structural features may play an important role in synthesizing better flavonoid-based drugs possessing dual antidiabetic and anti-inflammatory effects. A meta-analysis further established the role of flavonoids as antidiabetic and anti-inflammatory agents

Flavonoids as antidiabetic and anti-inflammatory agents: A review on structural activity relationship-based studies and meta-analysis

Flavonoids are a group of naturally occurring polyphenolic secondary metabolites which have been reported to demonstrate a wide range of pharmacological properties, most importantly, antidiabetic and anti-inflammatory effects. The relationship between hyperglycaemia and inflammation and vascular complications in diabetes is now well established. Flavonoids possessing antidiabetic properties may alleviate inflammation by reducing hyperglycaemia through different mechanisms of action. It has been suggested that the flavonoids’ biochemical properties are structure-dependent; however, they are yet to be thoroughly grasped. Hence, the main aim of this review is to understand the antidiabetic and anti-inflammatory properties of various structurally diverse flavonoids and to identify key positions responsible for the effects, their correlation, and the effect of different substitutions on both antidiabetic and anti-inflammatory properties. The general requirement of flavonoids for exerting both anti-inflammatory and antidiabetic effects is found to be the presence of a C2–C3 double bond (C-ring) and hydroxyl groups at the C3’, C4’, C5, and C7 positions of both rings A and B of a flavonoid skeleton. Furthermore, it has been demonstrated that substitution at the C3 position of a C-ring decreases the anti-inflammatory action of flavonoids while enhancing their antidiabetic activity. Correlation is discussed at length to support flavonoids possessing essential pharmacophores to demonstrate equipotent effects. The consideration of these structural features may play an important role in synthesizing better flavonoid-based drugs possessing dual antidiabetic and anti-inflammatory effects. A meta-analysis further established the role of flavonoids as antidiabetic and anti-inflammatory agents