ERDOSTEINE: AN EFFECTIVE ANTIOXIDANT FOR PROTECTING COMPLETE FREUND’S ADJUVANT INDUCED ARTHRITIS IN RATS

Objective: The objective of this study was to evaluate the protective effect of Erdosteine on complete freund’s adjuvant (CFA) induced arthritic rats. Methods: Wistar Albino rats of 100–250 g were divided into five groups (n=6) and administered with 0.1 ml of CFA subcutaneously into the left hind paw except the negative control group. The standard group received methotrexate (MTX) 0.075 mg/kg body weight orally. Besides, the test groups received Erdosteine orally at a dose 10 mg/kg and 20 mg/kg bodyweight for 12 days. The changes in body weight, paw volume, hematological parameters, radiographical, and histological findings were the indicators to evaluate the efficacy of the test product. Discussion: Significant change in the body weight, paw volume, radiographical, hematological, and histological parameters were observed which supports the remarkable reduction of the arthritic development in the standard and test groups compared to the untreated group. However, the test group (Erdosteine) with the dose 20 mg/kg shows to be more potent than the test group (Erdosteine) with a dose 10 mg/kg and the standard group (MTX) to reduce the arthritic effect. Results: The test group with 20 mg/kg Erdosteine showed much better outcome than the standard group at significant (p<0.05). Therefore, Erdosteine acting as an anti-inflammatory and anti-oxidant is effective at a dose 20 mg/kg in treating the progression of rheumatoid arthritis in rats

Fabrication of 108^{108}Cd target for the astrophysical p-process studies

The detailed process of preparing enriched $^{108}$Cd targets on mylar and copper backing using the vacuum evaporation technique is described. These targets were employed in an experiment to measure the proton capture cross-section at energies significantly below the Coulomb barrier, for the astrophysical p-process studies. Due to the low melting point and high vapor pressure of cadmium, some adjustments were implemented in the Telemark multipocket e-beam setup. The target thickness was determined through the measurement of alpha particle energy loss from a triple alpha source and also by RBS measurements. The thickness of the $^{108}$Cd films varies between 290 to 660 $\mu$g/cm$^2$, with a non-uniformity of approximately 10$\%$. X-ray Photoelectron Spectroscopy (XPS) and X-ray Fluorescence (XRF) analyses were conducted to examine the presence of impurities and to assess surface morphology, phase, and chemical composition

Dopamine Regulates Angiogenesis in Normal Dermal Wound Tissues

Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA) is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities

RP-HPLC METHOD DEVELOPMENT, VALIDATION, AND QUANTIFICATION OF LORNOXICAM IN LIPID NANOPARTICLE FORMULATIONS

Objective: A simple, reliable, sensitive and validated reversed phase-high performance liquid chromatography (RP-HPLC) method was developed for quantification of lornoxicam (LX) in rat plasma.Methods: Solid lipid nanoparticle (SLN) and nanostructured lipid carriers (NLC) gel formulations containing lornoxicam were prepared using high-speed homogenization followed by ultra-sonication. Pharmacokinetic study of formulated LX loaded SLN and NLC were performed on Wister albino rats.Results: The chromatographic separation was performed on hypersil octadecylsilane (ODS)-18 column using a mobile phase of 10 mmol. Phosphate buffer (pH, 4.5) and acetonitrile (65:35 v/v). Elute was monitored at 377 nm with a flow rate of 1 ml/min. Calibration curve was linear over the concentration range of 25.38–2046.45 ng/ml. Retention times of LX and internal standard (piroxicam) were 9.3 and 10.2 min, respectively. Maximum plasma drug concentration, the area under the plasma drug concentration versus time curve and elimination half-life for LX loaded SLN gel were found 6381.51±971.27ng/ml, 19917.21±7111.24 ng h/ml and 7.27±1.21h and 8558.13±1564.08 ng/ml, 21317.99±4568.71 ng/ml and 6.22±2.16 h. respectively. In vivo in vitro correlation study, the fraction of drug dissolved from nanoparticle in pH 7.4 was plotted against the fraction of drug absorbed and a linear correlation (R2= 0.9987) was obtained.Conclusion: A novel simple, simple, sensitive, precise, rapid, accurate, and economical and reliable RP-HPLC method was developed and validated for the estimation of LX in rat plasma

Inhibition of stemness and EMT by taxifolin ruthenium-p-cymene complex via downregulating the SOX2 and OCT4 expression on lung cancer

Lung carcinoma is perhaps the most often reported cancer incidence throughout the world. The flavonoid metal complexes have exhibited a potential chemotherapeutic effect. This study investigated the chemotherapeutic effect of taxifolin ruthenium-p-cymene complex against lung carcinoma through MTT assay, transwell migration assay, sphere formation assay, western blot, histopathology, immunohistochemistry, and TUNEL assay. The in silico study determined the target proteins of the complex. The synthesized organometallic complex was characterized via various spectroscopical techniques. The complex exhibited strong binding affinity for PI3K, EGFR, and β-catenin. The complex promoted apoptosis and inhibited the colony formation of the cancer cells. Moreover, the cancer cell migration and cancer stemness were reduced with decreased SOX2 and OCT4 expression. The complex induced cell cycle arrest at sub G0/G1 phase, S phase and G2/M phase and promoted caspase-3 mediated apoptosis. The in vivo study demonstrated successful restoration of lung tissue due to the treatment with the complex in benzo-α-pyrene induced lung cancer model. Additionally, the expression of p53 and caspase-3 was increased with significant downregulation of Akt, mTOR and β-catenin. In conclusion, the complex inhibited cancer cell viability, stemness, and EMT in both in vitro and in vivo model systems through the alteration of PI3K/Akt/mTOR/EGFR pathway and expression of stem cell markers including SOX2 and OCT4 that eventually abrogated the EMT mediated metastasis of cancer cells

Evaluation of the role of erythropoietin and methotrexate in multiple sclerosis

Background : Erythropoietin, originally recognized for its role in erythropoiesis, has been shown to improve neurological outcome after stroke. Low-dose methotrexate is effective against certain inflammatory diseases, such as severe psoriasis and rheumatoid arthritis as well as Crohn's disease. Immunosuppressive effect of methotrexate also reduces the proportion of patients with chronic progressive multiple sclerosis with modest clinical benefits. Combination of erythropoietin and methotrexate can target neuroinflammation along with immunosupression. Objective : To evaluate the role of erythropoietin and methotrexate in experimental autoimmune encephalomyelitis, a commonly used animal model of several degenerative human diseases like multiple sclerosis. Materials and Methods : In the present study, C57BL/J6 mice were immunized with 200 mg of myelin basic protein (MBP) emulsified in complete Freund's adjuvant (CFA) supplemented with 1 mg/ml of killed mycobacterium tuberculosis (MBP: CFA in 1:1 ratio). These animals were given a combination of methotrexate and erythropoietin. Neurological function tests were scored daily by grading of clinical signs. Cerebral histopathology was performed to detect inflammatory infiltrates and demyelination. Results : Treatment with erythropoietin and methotrexate significantly improved the neurological function recovery, reduced inflammatory infiltrates, and demyelination as compared to controls possibly by stimulating oligodendrogenesis and down-regulating proinflammatory infiltrates. Conclusion : The findings suggest an adjunctive use of methotrexate in demyelinating disease

Nanostructured Lipid Carriers (NLC)-Based Gel for the Topical Delivery of Aceclofenac: Preparation, Characterization, and In Vivo Evaluation

The aim of this study was to prepare nanostructured lipid carriers (NLC)-based topical gel of aceclofenac for the treatment of inflammation and allied conditions. Stearic acid as the solid lipid, oleic acid as the liquid lipid, pluronic F68 as the surfactant, and phospholipon 90G as the co-surfactant were used. NLCs were prepared by melt-emulsification, low-temperature solidification, and high-speed homogenization methods. Characterization of the NLC dispersion was carried out through particle size analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and an in vitro release study. The anti-inflammatory effect of the NLC gel was assessed by the rat paw edema technique and compared to marketed aceclofenac gel. The NLC dispersions exhibited d90% between 233 nm and 286 nm. All of the NLC showed high entrapment efficiency ranging from 67% to 82%. The particle size of NLC was further confirmed by the SEM study. The result of DSC showed that aceclofenac was dispersed in NLC in an amorphous state. Both the entrapment and release rate were affected by the percentage of oleic acid, but the method of preparation affected only the entrapment efficiency. The nanoparticulate dispersion was suitably gelled and assessed for in vitro permeation. Finally, NLC-based gels were found to possess superior (almost double) the anti-inflammatory activity compared to the marketed product. The anti-inflammatory activity of NLC gel showed a rapid onset of action, as well as a prolonged duration of action as compared with the marketed gel