Molineria recurvata Ameliorates Streptozotocin-Induced Diabetic Nephropathy through Antioxidant and Anti-Inflammatory Pathways.

Molineria recurvata (MR) has been traditionally used to manage diabetes mellitus in India. However, the molecular mechanism of MR on the diabetic-induced nephropathy has not been clearly investigated. Thus, this study investigates the protective effects of the MR extract on nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was instigated by a single intraperitoneal injection of STZ (45 mg/kg) in male Sprague-Dawley rats. Once the diabetes was successfully induced, the MR extract (200 mg/kg/day) or metformin (200 mg/kg/day) was orally administered for 14 days. Renal function, morphology changes and levels of inflammatory cytokines were measured. Blood glucose concentrations were considerably reduced in STZ-induced diabetic rats following treatment with the MR extract. The administration of the MR extract substantially restored the abnormal quantity of the oxidative DNA damage marker 8-hydroxy-2'-deoxy-guanosine (8-OHdG), malondialdehyde, glutathione, oxidized glutathione, superoxide dismutase, catalase, interleukin (IL)-1ß, IL-6, IL-10, and transforming growth factor-ß (TGF-ß). The urinary excretion of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), selenium binding protein 1 (SBP1), and pyruvate kinase M2 (PKM2) was significantly reduced in diabetes rats after administration of the MR extracts. In the kidneys of STZ-induced diabetic rats, the MR extracts markedly downregulated the expression of fibronectin, collagen-1, and α-smooth muscle actin (α-SMA). In particular, the MR extracts markedly increased the level of SIRT1 and SIRT3 and reduced claudin-1 in the kidney. These results suggest that the MR extracts exhibits therapeutic activity in contrast to renal injury in STZ-induced diabetic rats through repressing inflammation and oxidative stress.

Modulatory potential on immune system of a new alkaloid isolated from Coccinea cordifolia root.

In this study, a new alkaloid was isolated from methanolic extract of Coccinea cordifolia root using flash chromatography and was subjected to spectral analysis like 1H NMR, 13C NMR, FTIR analysis and GCMS for confirming the structure of the isolated alkaloid. The isolated alkaloid was also subjected to immunomodulatory assays to verify its role in the claims against the plant. It was found that the isolated compound at a dose of 2.5 mg/kg has shown competitive immunomodulatory potential when evaluated by carbon clearance, delayed type hypersensitivity and haemagglutination titer models and using Levamisole at a dose of 50 mg/kg as the standard drug.

Glycogen-gold nanohybrid escalates the potency of silymarin.

In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl4-induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1ß and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma Cmax supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly.

Bioactive Fraction of Annona reticulata Bark (or) Ziziphus jujuba Root Bark along with Insulin Attenuates Painful Diabetic Neuropathy through Inhibiting NF-κB Inflammatory Cascade.

The present study explains the neuroprotective ability of bioactive fractions of Annona reticulata bark (ARB) and Ziziphus jujuba root bark (ZJ) along with insulin against diabetic neuropathy. By using different solvents of increasing polarity ARB and ZJ were undergone for bioactive guided fractionation. The neuroprotective ability of the all the plant fractions were tested against H2O2 induced toxicity in SHSY5Y neuroblastoma cell lines and DRG neuronal cells. Among all the fractions tested, the methanol extract of ARB and ZJ (ARBME and ZJME) and its water fractions (ARBWF and ZJWF) exhibited significant neuroprotection against H2O2 induced toxicity in SHSY5Y cells and DRG neuronal cells. Further both the active fractions were tested against streptozotocin (55 mg/kg i.p.) induced diabetic neuropathy in male Wistar rats. Body weight changes, blood glucose levels and pain threshold through hot plate, tail immersion, cold plate and Randall-Sillitto methods were measured throughout the study at weekly interval. After completion of the drug treatment period, all the animals were sacrificed to measure the sciatic nerve lipid peroxidation, antioxidative enzyme levels (SOD, catalase, and GSH) and cytokine levels (IL-1ß, IL-6, IL-10, TNF-α, iNOS, and NFκB) through ELISA and western blotting analysis. Results of this study explain that ARBME, ZJME, ARBWF, and ZJWF along with insulin potentially attenuate the thermal, mechanical hyperalgesia and cold allodynia in diabetic neuropathic rats, where insulin treatment alone failed to diminish the same. Reduction of sciatic nerve oxidative stress, NF-κB and iNOS mediated inflammatory cascade and normalization of abnormal cytokine release confirms the possible mechanism of action. The present study confirms the neuroprotective ability of ARB and ZJ against painful diabetic neuropathy through inhibiting oxidative stress and NF-κB inflammatory cascade.

Protective Effect of Bioactivity Guided Fractions of Ziziphus jujuba Mill. Root Bark against Hepatic Injury and Chronic Inflammation via Inhibiting Inflammatory Markers and Oxidative Stress.

The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae) is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer, and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark (ZJRB) against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME) was performed using different solvents of increasing polarity viz. hexane (ZJHF), chloroform (ZJCF), ethyl acetate (ZJEAF), water (ZJWF), and residue (ZJMR). In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD, and CAT) and cytokine levels (TNF-α, Il-1ß, and Il-10) in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of ZJRB as good therapeutic agent for liver toxicity and chronic inflammation.

Bioactive Guided Fractions of Annona reticulata L. bark: Protection against Liver Toxicity and Inflammation through Inhibiting Oxidative Stress and Proinflammatory Cytokines.

Herbal medicine is popularized worldwide due to its ability to cure the diseases with lesser or no side effects. North Eastern part of India comes under one of the world biodiversity hotspots which is very rich in traditional herbal medicine. Annona reticulata L. (Annonaceae) is one such plant used for the treatment of inflammatory diseases, liver ailments and diabetes by traditional healers. The present study was aimed to scientifically validate this folk knowledge and to develop an herbal remedy through evaluating bioactive guided fractions of A. reticulata (AR) bark against hepatotoxicity and inflammation using in vitro and in vivo models. Results of this study demonstrates that among all fractions of AR bark, methanol extract and its water fraction possess strong anti-oxidant ability and showed protection against CCl4 induced toxicity in HepG2 cell lines and rats. Both the fractions also exhibit dose dependent anti-inflammatory activity against carrageenan induced inflammation in rats. Water fraction showed potent response in the entire tests conducted than methanol extract, which states that polar components of the AR bark methanol extract were responsible for these activities. Further, from the experiments conducted to elucidate the mechanism of action, the results revealed that AR bark showed liver protection and anti-inflammatory response through inhibiting the oxidative stress and inflammatory cytokines.

Chemical Composition and Anti-Candidiasis Mediated Wound Healing Property of Cymbopogon nardus Essential Oil on Chronic Diabetic Wounds.

Poor wound healing is one of the major complication of diabetic patients which arises due to different factors like hyperglycemia, oxidative stress, vascular insufficiency and microbial infections. Candidiasis of diabetic wounds is a difficult to treat condition and potentially can lead to organ amputation. There are a few number of medications available in market to treat this chronic condition; which demands for alternative treatment options. In traditional system of medicine like Ayurveda, essential oil extracted from leaves of Cymbopogon nardus L. (Poaceae) has been using for the treatment of microbial infections, inflammation and pain. In this regard, we have evaluated anti-Candida and anti-inflammatory activity mediated wound healing property of C. nardus essential oil (EO-CN) on candidiasis of diabetic wounds. EO-CN was obtained through hydro-distillation and subjected to Gas chromatography-mass spectroscopy (GC-MS) analysis for chemical profiling. Anti-Candida activity of EO-CN was tested against Candida albicans, C. glabrata and C. tropicalis by in vitro zone of inhibition and minimum inhibitory concentration (MIC) assays. Anti-candidiasis ability of EO-CN was evaluated on C. albicans infected diabetic wounds of mice through measuring candida load on the 7th, 14th, and 21st day of treatment. Further progression in wound healing was confirmed by measuring the inflammatory marker levels and histopathology of wounded tissues on last day of EO-CN treatment. A total of 95 compounds were identified through GC-MS analysis, with major compounds like citral, 2,6-octadienal-, 3,7-dimethyl-, geranyl acetate, citronellal, geraniol, and citronellol. In vitro test results demonstrated strong anti-Candida activity of EO-CN with a MIC value of 25 µg/ml against C. albicans, 50 µg/ml against C. glabrata and C. tropicalis. EO-CN treatment resulted in significant reduction of candida load on diabetic wounds. Acceleration in wound healing was indicated by declined levels of inflammatory cytokines at wounded area in EO-CN treated animals compared to non-treated group, which was further confirmed by histopathological examination. This study suggests that through significant anti-Candida and anti-inflammatory activity, EO-CN attenuates the growth of the fungus on diabetic wounds and simultaneously reduces the inflammation which leads to acceleration of the wound healing process.

Antioxidant and Hepatoprotective Potentiality of Randia dumetorum Lam. Leaf and Bark via Inhibition of Oxidative Stress and Inflammatory Cytokines.

Randia dumetorum Lam. (RD) (Rubiaceae) is traditionally used by some tribes of Assam and Manipur of North East India for the treatment of liver ailments. In this context, to scientifically validate this indigenous traditional knowledge, we have evaluated the antioxidant and hepatoprotective activity of RD leaf and bark. The methanol extracts of RD leaf and bark were evaluated for in vitro antioxidant activity which exhibited good antioxidant activity in terms of reducing power assay, total antioxidant assay and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay. Total phenolic and flavonoid content were found to be 112 ± 3.24 mg and 138 ± 2.46 mg gallic acid equivalents/g extract and 2.6 ± 0.26 mg and 3.34 ± 0.31 mg rutin equivalents/g extract respectively for RD leaf and bark methanol extracts. The in vivo hepato protective activity of the RD leaf and bark extract was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in male wistar rats. CCl4 administration induced hepatic damage in rats resulted in increased levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, thiobarbituric acid reacting substances, albumin, bilirubin, TNF-α, IL-1ß and decreased levels of total protein and antioxidant enzymes like superoxide dismutase, catalase, and glutathione reductase. RD leaf and bark methanol extracts pre-treatment exhibited protection against CCl4 induced hepatotoxicity by reversing all the abnormal parameters to significant levels. Histopathological results revealed that RD leaf and bark extracts at 400 mg/kg protects the liver from damage induced by CCl4. The results of this study scientifically validate the traditional use of RD leaf and bark for the treatment of liver ailments.

Curcumin-docetaxel co-loaded nanosuspension for enhanced anti-breast cancer activity.

PURPOSE: A curcumin-docetaxel co-loaded nanosuspension with increased anti-breast cancer activity was developed. Curcumin is a potential anticancer agent with p-glycoprotein (p-gp) inhibiting activity may be co-administered with docetaxel as a nanosuspension to enhance its anticancer effect by increasing the oral bioavailability and decreasing drug efflux. METHODS: Nanosuspensions of curcumin and docetaxel were prepared by precipitation-homozenisation technique and evaluated for particle size, polydispersity, zeta potential and drug release. The in vitro MTT assay was conducted using MCF-7 for anti-breast cancer activity. The in vivo biodistribution by radiolabeling and tumor inhibition study was conducted in mice. RESULTS: Homogenous nanosuspensions of 80 ± 20 nm were obtained with increased solubility. The drugs as nanosuspensions showed higher cytotoxicity on MCF-7 cell line compared to their suspensions due to the increased in vitro cellular uptake. Due to this increased solubility, sensitization of tumor cells and inhibition of p-gp the in-vivo results showed greater tumor inhibition rate of up to 70% in MCF-7 treated mice. Histopathological results showed higher apoptotic activity and reduced level of angiogenesis. CONCLUSIONS: The in vitro and in vivo study of the nanosuspensions has shown that Co-administration of Curcumin as a p-gp inhibitor with docetaxel may have the potential to increase the anti-breast cancer efficacy of both drugs.

Fiber from ramie plant (Boehmeria nivea): A novel suture biomaterial.

The quest for developing an ideal suture material prompted our interest to develop a novel suture with advantageous characters to market available ones. From natural origin only silk, cotton and linen fibers are presently available in market as non-absorbable suture biomaterials. In this study, we have developed a novel, cost-effective, and biocompatible suture biomaterial from ramie plant, Boehmeria nivea fiber. Field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and thermo gravimetric analysis (TGA) results revealed the physicochemical properties of raw and degummed ramie fiber, where the former one showed desirable characteristics for suture preparation. The braided multifilament ramie suture prepared from degummed fiber exhibited excellent tensile strength. The suture found to be biocompatible towards human erythrocytes and nontoxic to mammalian cells. The fabricated ramie suture exhibited significant antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus; which can be attributed to the inherent bacteriostatic ability of ramie plant fiber. In vivo wound closure efficacy was evaluated in adult male wister rats by suturing the superficial wound incisions. Within seven days of surgery the wound got completely healed leaving no rash and scar. The role of the ramie suture in complete wound healing was supported by the reduced levels of serum inflammatory mediators. Histopathology studies confirmed the wound healing ability of ramie suture, as rapid synthesis of collagen, connective tissue and other skin adnexal structures were observed within seven days of surgery. Tensile properties, biocompatibility and wound closure efficacy of the ramie suture were comparable with market available BMSF suture. The outcome of this study can drive tremendous possibility for the utilization of ramie plant fiber for various biomedical applications.

Leucas aspera inhibits the Dalton's ascitic lymphoma in Swiss albino mice: A preliminary study exploring possible mechanism of action.

BACKGROUND: North East India is a rich source of medicinal plants and a number of plant extracts are used by tribal peoples living in this area for various disorders. L.aspera is such a plant, traditionally used as an antitumor agent. AIM: In the present study, aerial parts of L.aspera were investigated for antitumor activity in Dalton's lymphoma (DAL) bearing mice. The ability of plant extract in free radical scavenging, neoangiogenesis inhibition and macrophage stimulation were also checked. MATERIALS AND METHODS: Based on the preliminary in vitro cytotoxicity studies ethyl acetate fraction of L.aspera (EALA) was selected for the detailed study. DAL ascites tumor model was performed to check the antitumor activity of EALA (200 and 400mg/kg of body weight). Hematological and histopathological parameters were estimated. Antioxidant levels, neoangiogenesis and peritoneal macrophage count were also determined. RESULTS: In vitro MTT and Trypan blue assay results showed the cytotoxic effect of EALA in DAL cells lines. EALA treatment resulted in significant decrease in ascites tumor volume and viable cell count. Hematological and liver antioxidant parameters were normalised by EALA treatment. It was also found that EALA treatment inhibits neovascularisation and produce macrophage stimulation in treated mice. CONCLUSION: The results showed that EALA is a promising anticancer agent and its activity is comparable to the standard drug 5-Flouro uracil (5-FU).

Kinetic modeling on drug release from controlled drug delivery systems.

In this paper we review the mathematical models used to determine the kinetics of drug release from drug delivery systems. The quantitative analysis of the values obtained in dissolution/release rates is easier when mathematical formulae are used to describe the process. The mathematical modeling can ultimately help to optimize the design of a therapeutic device to yield information on the efficacy of various release models.