Mukesh Doble

Synergism between natural products and antibiotics against infectious diseases

Antibiotics have been effective in treating infectious diseases, but resistance to these drugs has led to the emergence of new and the reemergence of old infectious diseases. One strategy employed to overcome these resistance mechanisms is the use of combination of drugs, such as beta-lactams together with beta-lactamase inhibitors. Several plant extracts have exhibited synergistic activity against microorganisms. This review describes in detail, the observed synergy and mechanism of action between natural products including flavonoids and essential oils and synthetic drugs in effectively combating bacterial, fungal and mycobacterial infections. The mode of action of combination differs significantly than that of the same drugs acting individually; hence isolating a single component may lose its importance thereby simplifying the task of pharma industries.

Biofilm formation, bacterial adhesion and host response on polymeric implants—issues and prevention

Several polymeric materials find application in biomedical implants and devices due to their superior physicochemical properties. The main requirement for these polymers is that they should be biocompatible, which means they prevent bacterial adhesion and are blood compatible. Many parameters contribute to the degree of biocompatibility. This paper discusses the mechanism of the formation of biofilms and lists the factors that influence the bacterial adhesion and haemocompatibility. Polymer surfaces are also modified to enhance adsorption of host cells. The physical, chemical and biological techniques are meant to modify the surface of the biomaterial but at the same time retain the key properties. The various polymer treatment processes have advantages and disadvantages and a few techniques have been proved to be both highly effective at treatment and found suitable for various in vivo environments. The current research focus pertaining to smart materials, biodegradable polymers, combinatorial chemistry, computational modelling and newer analytical techniques to understand polymer-cell interaction holds promise in designing better, cost effective and biocompatible polymers.

Synergistic interaction of eugenol with antibiotics against Gram negative bacteria

Eugenol, the principal chemical component of clove oil from Eugenia aromatica has been long known for its analgesic, local anesthetic, anti-inflammatory, and antibacterial effects. The interaction of the eugenol with ten different hydrophobic and hydrophilic antibiotics was studied against five different Gram negative bacteria. The MIC of the combination was found to decrease by a factor of 5-1000 with respect to their individual MIC. This synergy is because of the membrane damaging nature of eugenol, where 1mM of its concentration is able to damage nearly 50% of the bacterial membrane. Eugenol was also able to enhance the activities of lysozyme, Triton X-100 and SDS in damaging the bacterial cell membrane. The hydrophilic antibiotics such as vancomycin and beta-lactam antibiotics which have a marginal activity on these gram negative bacteria exhibit an enhanced antibacterial activity when pretreated with eugenol. Reduced usage of antibiotics could be employed as a treatment strategy to slow down the onset of antibiotic resistance as well as decrease its toxicity. Experiments performed with human blood cells indicated that the concentration of eugenol used for the combination studies were below its cytotoxic values. Pharmacodynamic studies of the combinations need to be performed to decide on the effective dosage.

Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes

The present study analyses the effect of two plant phenolic compounds, namely chlorogenic acid and ferulic acid, and a plant alkaloid, berberine, alone and also in combination with two commercial oral hypoglycemic drugs (OHD), namely metformin and 2,4-thiazolodinedione (THZ), on the uptake of 2-deoxyglucose (2DG) by L6 myotubes. 2-DG uptake is determined using an enzymatic assay. All the three natural products enhance the uptake of 2DG in time- and dose-dependent manner. A combination of different concentrations of chlorogenic acid and metformin or THZ, has a synergistic effect in the uptake of 2DG with a maximum of 5.0- and 5.3-times respectively, with reference to the base value (without the drugs or the natural products). Ferulic acid in combination with metformin or THZ has also shown a synergistic effect and the 2DG uptake increases by 4.98- and 5.11-fold when compared to the control respectively. Whereas, berberine, in combination with either metformin or THZ, has shown an additive effect with maximum 2DG uptake of 4.1- and 4.7-times from the base value, respectively. The synergistic interaction has been explained with the use of combination index and isobologram. Expression of GLUT4 and PPAR-gamma gene were elevated in chlorogenic acid and berberine treated cells, whereas expression of GLUT4 and PI3K transcripts were significantly enhanced in ferulic acid treated cells. The studies indicate that chlorogenic acid enhances glucose uptake by increasing GLUT4 expression via PI3K independent pathway whereas ferulic acid increases glucose uptake by PI3K dependent pathway. The current findings suggest that the phytochemicals can replace the commercial drugs in part, which could lead to a reduction in toxicity and side effects of the later.

A target based therapeutic approach towards diabetes mellitus using medicinal plants.

Diabetes mellitus (DM) is not one disease but is a heterogonous group of syndromes. Contrary to the popular belief DM is a metabolic disorder characterized by increased blood glucose level (hyperglycemia) and this is because of insufficient or inefficient insulin secretary response. Glucose is the main energy source for the body, and in the case of DM, management of glucose becomes irregular. There are around 410 experimentally proven medicinal plants having antidiabetic properties but the complete mechanism of action is available only for about 109. There are several medicinal plants whose extract modulate glycolysis, Krebs cycle, gluconeogenesis, HMP shunt pathway, glycogen synthesis and their degradation, cholesterol synthesis, metabolism and absorption of carbohydrates, and synthesis and release of insulin. This paper provides a comprehensive review of the mode of action of medicinal plants that exhibit anti-diabetic properties.

Biocompatibility studies on polyaniline and polyaniline-silver nanoparticle coated polyurethane composite.

Biocompatibility of medical grade polyurethane coated with polyaniline (PANi) and polyaniline-silver nanoparticle composite (PANi-AgNp) is reported here. These modified films showed 23 and 18% of 3T3 L1 cell death when compared to 41% with virgin polyurethane (PU) after 48h of incubation, respectively. All the surfaces elucidated inflammatory response in the form of enhanced expressions of the proinflammatory cytokines genes, TNF-α and IL-6. But these values were less (by 20%) on modified films than on the bare PU. Attachment of Pseudomonas and Bacillus were markedly less on PANi-AgNp coated surface (by 90.6 and 50.5%, respectively) when compared to the uncoated PU. As the CFU counts decreases on the nanoparticle coated PU, the adsorbed carbohydrate as well as protein content on to the surface of polymer decreases accordingly, indicating less attachment. A 20% reduction in the thickness of biofilm was observed in PANi-AgNp coated PU surface. A very strong positive correlation is observed between the contact angles of the polymers and the various biological parameters (namely colony forming units, protein, carbohydrate, cell death and inflammatory response), indicating hydrophilic surfaces prevent bacterial biofilm as well as are compatible to cells when compared to hydrophobic surfaces. Coating PU with PANi and PANi+AgNp renders the surface conductive, suggesting potential application in electrochemical biosensors. In addition, these modifications make the surface more biocompatible than the original PU.

Design of biocomposite materials for bone tissue regeneration

Several synthetic scaffolds are being developed using polymers, ceramics and their composites to overcome the limitations of auto- and allografts. Polymer-ceramic composites appear to be the most promising bone graft substitute since the natural bone itself is a composite of collagen and hydroxyapatite. Ceramics provide strength and osteoconductivity to the scaffold while polymers impart flexibility and resorbability. Natural polymers have an edge over synthetic polymers because of their biocompatibility and biological recognition property. But, very few natural polymer-ceramic composites are available as commercial products, and those few are predominantly based on type I collagen. Disadvantages of using collagen include allergic reactions and pathogen transmission. The commercial products also lack sufficient mechanical properties. This review summarizes the recent developments of biocomposite materials as bone scaffolds to overcome these drawbacks. Their characteristics, in vitro and in vivo performance are discussed with emphasis on their mechanical properties and ways to improve their performance.

Mannosylerythritol lipids: a review

Mannosylerythritol lipids (MELs) are surface active compounds that belong to the glycolipid class of biosurfactants (BSs). MELs are produced by Pseudozyma sp. as a major component while Ustilago sp. produces them as a minor component. Although MELs have been known for over five decades, they recently regained attention due to their environmental compatibility, mild production conditions, structural diversity, self-assembling properties and versatile biochemical functions. In this review, the MEL producing microorganisms, the production conditions, their applications, their diverse structures and self-assembling properties are discussed. The biosynthetic pathways and the regulatory mechanisms involved in the production of MEL are also explained here.

Mechanism of action of natural products used in the treatment of diabetes mellitus

Diabetes mellitus (DM) is a metabolic disorder caused by insufficient or inefficient insulin secretary response and it is characterized by increased blood glucose levels (hyperglycemia). DM is a heterogonous group of syndromes. Glucose is the main energy source for the body, and in the case of DM, management of glucose becomes irregular. There are three key defects in the onset of hyperglycemia in DM, namely increased hepatic glucose production, diminished insulin secretion, and impaired insulin action. Conventional drugs treat diabetes by improving insulin sensitivity, increasing insulin production and/or decreasing the amount of glucose in blood. This article provides a comprehensive review of the mode of action of most popular hypoglycemic herbs, such as ginseng, bitter melon, fenugreek, banaba, Gymnema sylvestre and Coptis chinensis. The herbs act by increasing insulin secretion, enhancing glucose uptake by adipose and skeletal muscle tissues, inhibiting intestinal glucose absorption and inhibiting hepatic glucose production. Although evidence from animals and humans consistently supports the therapeutic effect of these phytomedicines, multicenter large-scale clinical trials have not been conducted to evaluate the safety and efficacy of these herbal medicines and their interaction with conventional drugs when administered simultaneously.

Synthesis, antioxidant evaluation, and quantitative structure–activity relationship studies of chalcones

Synthesis, antioxidant activity, and quantitative structure–activity relationship (QSAR) of 25 of chalcone derivatives is reported here. They were synthesized by Claisen–Schmidt reaction and were characterized by FTIR, NMR, and mass spectroscopy. Antioxidant activity is evaluated through four different methods namely, superoxide radical-scavenging, hydrogen peroxide scavenging, reducing power, and DPPH radical-scavenging assays. Generally, compounds with –SCH3 and –OCH3 in the para position of the A-ring and –OH in the B-ring were more active than others. In few cases some of the compounds were more active than ascorbic acid or butylated hydroxytoluene. QSAR was developed correlating the antioxidant activity with the structural features of the compounds and the predictive capability of the models was estimated using internal and external validation methods. All the predictions were within the 99% confidence level. Spatial, structural, and lipophilic properties of the compounds determine their antioxidant properties.