Vikram Patial

In situ functionalized nanobiocomposites dressings of bamboo cellulose nanocrystals and silver nanoparticles for accelerated wound healing

An innovative approach was adopted where in situ synthesized silver nanoparticles (AgNPs) from leaf extract mediated reduction of AgNO3 were simultaneously impregnated into the matrix of cellulose nanocrystals (CNCs) isolated from Dendrocalamus hamiltonii and Bambusa bambos leaves, for formation of nanobiocomposites (NCs) in film and ointment forms. Here, use of plant CNCs was chosen as an alternate to bacterial cellulose for wound dressings. NCs possessing water absorption capacity and strong antibacterial activity showed synergistic effect on in vivo skin wound healing and documented faster and significant wound closure in treated mice. NCs exhibited lesser inflammation and early vasculogenesis at day 3 coupled with increased fibroblasts and collagen content at day 8 leading to faster neo-epithelization by day 14. Highly effective, biocompatible, and easy to apply NCs wound dressings (ointment and films) containing low amounts of Ag (0.05±0.01wt%) are potential candidates for effective skin repair.

Synergistic effect of curcumin and piperine in suppression of DENA-induced hepatocellular carcinoma in rats

Curcumin has been reported to suppress different types of clinical and experimentally-induced tumors, but due to less absorption and quick metabolism it show poor bioavailability. The present study was envisaged to investigate the possible synergistic effect of combined treatment of curcumin with piperine in suppression of diethylnitrosamine (DENA)-induced hepatocellular carcinoma (HCC) in rats, owing to permeability enhancing effect of latter. HCC was induced by supplying DENA (0.01%) in drinking water for 10 weeks. The rats were treated with curcumin (100mg/kg; p.o.) per se and curcumin along with piperine (20mg/kg; p.o.) for 4 weeks post HCC induction. The combined treatment significantly attenuated the morphological, histopathological, biochemical, apoptotic and proliferative changes in the liver and serum in comparison to curcumin per se and vehicle control group. The results of present study concluded that curcumin in combination with piperine shows better suppression of DENA-induced HCC in contrast to curcumin per se.

A bimodal molecular imaging probe based on chitosan encapsulated magneto-fluorescent nanocomposite offers biocompatibility, visualization of specific cancer cells in vitro and lung tissues in vivo

Multifunctional hybrid nanocomposite material, consists of chitosan encapsulated iron oxide (as MRI contrasting agent), CdS (as fluorescent probe) nanoparticles and podophyllotoxin (as anticancer drug) was synthesized and characterized. The TEM studies suggested the size of the NPs to be in the range of 80-100 nm. These nanocomposites were treated with different cancer cell lines viz., KB, C6 and A549 cells. Fluorescence imaging and Perls Prussian blue staining confirmed the presence of these nanocomposites inside both KB and C6 cells but not in A549 cells. Cytotoxicity experiments revealed that these biopolymer coated nanocomposites showed minimal toxicity towards cancerous cells. Further the intraperitoneal administration of one of the nanoformulations to Wistar rats suggested deposition of these nanocomposites in the lungs. The hematological, biochemical and histopathological analysis confirmed that these nanocomposites are safe to use as a novel dual mode imaging material.

In vivo diabetic wound healing potential of nanobiocomposites containing bamboo cellulose nanocrystals impregnated with silver nanoparticles

In diabetes, hyperglycemic state immensely hinders the wound healing. Here, nanobiocomposites (NCs) developed by impregnation of in situ prepared silver nanoparticles in the matrix of bamboo cellulose nanocrystals were investigated for their ability to hasten the progress of healing events in streptozotocin induced diabetic mice model. Wounds treated with topically applied NCs (hydrogels) showed full recovery (98-100%) within 18days post wounding in contrast to the various control groups where incomplete healing (88-92%) was noticed. Biochemical estimations documented a marked decrease in the levels of pro-inflammatory cytokines IL-6 and TNF-α leading to decreased inflammation in NCs treated mice. Significantly increased expression of collagen and growth factors (FGF, PDGF, VEGF) upon NCs treatment resulted in improved re-epithelialization, vasculogenesis and collagen deposition as compared to control groups. Hence, developed nanobiocomposites showcased potential to serve as highly effective and biocompatible wound dressings for diabetic patients.

A low toxic synthetic dendrimer conjugated podophyllotoxin nanodevice with potent antitumor activity against the DMBA/TPA induced mouse skin carcinogenesis model

Natural podophyllotoxin (PODO) is an anticancer drug that functions as an anti-mitotic agent and inhibits tubulin polymerization. However, high toxicity and low bioavailability limit its anticancer applications. To minimize toxicity and enhance solubility under physiological conditions, we conjugated PODO to a poly(amidoamine) (PAMAM) dendrimer to generate sustained-release nanodevices (D-PODO). Free PODO and its dendrimer conjugates were screened for toxicity in Swiss albino mice, and the dose-dependent antitumor activity of D-PODO was evaluated in a two-stage mouse skin carcinogenesis model. The results showed that 8 mg kg−1 D-PODO was nontoxic, whereas the same dose of PODO was highly toxic, as indicated by mortality, biochemical and histopathological studies. An antitumor therapeutic study using D-PODO in tumor-bearing mice revealed a 50–60% inhibition of skin tumor formation. Histopathology and immunohistochemistry studies revealed that D-PODO treatment reduced epithelial hyperplasia, and induced apoptosis by increasing the Bax to Bcl-2 ratio and reducing NF-κB expression. Importantly, the D-PODO conjugate was less toxic than PODO, and inhibited skin tumor progression effectively.

Crocin Attenuates Kindling Development and Associated Cognitive Impairments in Mice via Inhibiting Reactive Oxygen Species-Mediated NF-κB Activation

Crocin is a pharmacologically active carotenoid pigment mainly present in the stigmas of Crocus sativus L. (Iridaceae). It has been well explored in experimental animal models of cognitive impairments, depression, anxiety and epilepsy. This study was designed to understand the effect of crocin on pentylenetetrazol (PTZ)‐induced kindling development and its associated cognitive deficit in mouse. Crocin treatment at 5, 10 and 20 mg/kg p.o. doses showed a marked reduction in severity of PTZ‐induced seizures. There was an increase in novel object preference index and discrimination ratio in the crocin‐treated groups in the novel object recognition test. Its treatment also increased percentage spontaneous alternations in T‐maze test at all the tested doses. Histopathological examination by Nissl staining showed a reduction in dark neurons in the hippocampal pyramidal layer of crocin‐treated animals in contrast to vehicle control, indicating a decrease in neuronal damage. Biochemical estimations showed a significant increase in superoxide dismutase activity and reduced reactive oxygen species (ROS) in the hippocampus of crocin‐treated animals. Immunohistochemistry results revealed attenuation in the levels of nuclear factor‐κB (NF‐κB) and phosphorylated NF‐κB in the hippocampal sections of crocin‐treated animals. The results of this study concluded that crocin treatment increased seizure threshold, thus inhibiting PTZ‐induced kindling development and improving cognitive functions. The effect was found to be due to suppression of seizure‐induced ROS generation and its linked NF‐κB pathway‐associated neuronal damage.

Antioxidant and hepatoprotective effect of polyphenols from apple pomace extract via apoptosis inhibition and Nrf2 activation in mice

Industrial apple pomace, a biowaste generated during apple processing, is rich in cell wall polysaccharides and phenolics. These biologically active compounds are reported to be highly beneficial from the nutritional and health point of view. In the present study, the total phenolic content in the apple pomace aqueous extract (APE) was estimated and evaluated for its possible antioxidant and hepatoprotective efficacy in carbon tetrachloride (CCl4)-induced liver injury mice model. The aqueous extract exhibited 2,2-diphenyl-2-picrylhydrazyl free radical scavenging activity in vitro. Under in vivo study, mice were treated with APE (200 mg and 400 mg/kg body weight) for 2 weeks prior to the administration of CCl4 (30% v/v). The serum liver injury markers alanine transaminase, aspartate transaminase, and alkaline phosphatase were significantly lowered by APE in a dose-dependent manner. The levels of antioxidant parameters superoxide dismutase (SOD), reduced glutathione (redGSH), and lipid peroxidation were also improved by APE in liver homogenate. Histopathological studies revealed that APE treatment significantly lowered the CCl4-induced necrotic changes in the liver. Furthermore, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling assay showed that CCl4-induced apoptosis in the liver was significantly inhibited by APE in a dose-dependent manner. Immunohistochemistry results showed higher expression of nuclear erythroid 2-related factor 2 (Nrf2) in the liver of the APE-treated mice, a key regulator of antioxidative response. In conclusion, the results of the present study revealed the hepatoprotective efficacy of APE by inhibiting CCl4-induced apoptosis, which is due to its antioxidant activity and the ability to induce Nrf2 protein expression.

A multifunctional magneto-fluorescent nanocomposite for visual recognition of targeted cancer cells

A multifunctional hybrid nanocomposite material of iron oxide nanoparticles and CdS quantum dots was synthesized by a direct amide coupling reaction. The prepared nanoparticles were characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and zeta potential studies. The TEM studies suggested that the sizes of the particles were in the range of 13.5 ± 1 nm. The energy dispersive x-ray (EDX) analysis confirmed the presence of Fe, Cd and S in the nanocomposites. To check the utility of this nanocomposite as a molecular imaging probe, these nanoparticles were further conjugated with folic acid. The folic acid conjugated nanocomposites were treated with rat glioma cells (C6, folic acid receptor over-expressing cell lines), human lung adenocarcinoma epithelial cells (A549, folic acid receptor negative cell lines) and normal mouse splenocytes for cell uptake and cytotoxicity studies. The nanoparticle internalization to C6 cells was confirmed by green fluorescence emission from these cells. Prussian blue staining studies suggested the intracellular presence of iron oxide. Further it was found that folic acid conjugated nanocomposites were significantly toxic to C6 cells only after 48 h but not to A549 cells or splenocytes. These studies indicated that the prepared nanocomposites have the potential to be used as delivery agent for magnetic and fluorescent materials towards folic acid receptor over-expressing cells and thus can find their application in the field of in vitro imaging diagnosis.

Cytocompatible Anti-microbial Dressings of S yzygium cumini Cellulose Nanocrystals Decorated with Silver Nanoparticles Accelerate Acute and Diabetic Wound Healing

The ever increasing incidences of non-healing skin wounds have paved way for many efforts on the convoluted process of wound healing. Unfortunately, the lack of relevance and success of modern wound dressings in healing of acute and diabetic wounds still remains a matter of huge concern. Here, an in situ three step approach was embraced for the development of nanocomposite (NCs) dressings by impregnating silver nanoparticles (AgNPs) onto a matrix of cellulose nanocrystals (CNCs) isolated from Syzygium cumini leaves using an environmental friendly approach. Topical application of NCs (ointments and strips) on acute and diabetic wounds of mice documented enhanced tissue repair (~99% wound closure) via decrease in inflammation; increase in angiogenesis, collagen deposition, and rate of neo-epithelialization that ultimately led to formation of aesthetically sound skin in lesser time than controls. Due to the synergistic action of CNCs (having high water uptake capacity) and AgNPs (anti-microbial agents), NCs tend to increase the expression of essential growth factors (FGF, PDGF and VEGF) and collagen while decreasing the pro-inflammatory factors (IL-6 and TNF-α) at the same time, thus accelerating healing. The results suggested the potential of these developed anti-microbial, cytocompatible and nanoporous NCs having optimized AgNPs concentration as ideal dressings for effective wound management.

Picrorhiza kurroa Enhances β-Cell Mass Proliferation and Insulin Secretion in Streptozotocin Evoked β-Cell Damage in Rats

Autoimmune destruction of insulin producing pancreatic β-cells leads to insulin insufficiency and hyperglycemia in type 1 diabetes mellitus. Regeneration of β-cells is one of the proposed treatment for type 1 diabetes and insulin insufficiency. Picrorhiza kurroa is a medicinal herb and is traditionally being used for the treatment of various diseases. Previous studies reported the hypoglycemic potential of P. kurroa. However, its potential role in β-cell induction in insulin secretion have not been fully investigated. Here, we characterized the hydro alcoholic extract of P. kurroa rhizome (PKRE) and further studied its β-cell regeneration and induction of insulin secretion potential in streptozotocin (STZ) induced diabetic rats as well as in insulin producing Rin5f cells. 1H-NMR revealed the presence of more than thirty metabolites including picroside I and II in PKRE. Further, we found that PKRE treatment (100 and 200 mg/kg dose for 30 days) significantly (p ≤ 0.05) protected the pancreatic β-cells against streptozotocin (STZ) evoked damage and inhibited the glucagon receptor expression (Gcgr) in hepatic and renal tissues. It significantly (p ≤ 0.05) enhanced the insulin expression and aids in proliferation of insulin producing Rin5f cells with elevated insulin secretion. Furthermore it significantly (p ≤ 0.05) increased insulin mediated glucose uptake in 3T3L1 and L6 cells. On the contrary, in diabetic rats, PKRE significantly (p ≤ 0.05) decreased high blood glucose and restored the normal levels of serum biochemicals. Altogether, our results showed that PKRE displayed β-cell regeneration with enhanced insulin production and antihyperglycemic effects. PKRE also improves hepatic and renal functions against oxidative damage.