Recent updates on correlation between reactive oxygen species and synbiotics for effective management of ulcerative colitis.

Ulcerative colitis (UC) is presently considered a multifactorial pathology, which may lead to persistent inflammatory action of the gastrointestinal tract (GIT) because of an improperly managed immunological reactivity to the intestinal microbiota found in the GIT. The immune response to common commensal microbes plays an essential role in intestinal inflammation related to UC synbiotics, and it is an important element in the optimal therapy of UC. Therefore, synbiotics, i.e., a mixture of prebiotics and probiotics, may help control the diseased state. Synbiotics alleviate the inflammation of the colon by lowering the reactive oxygen species (ROS) and improving the level of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Prebiotic supplementation is not a common practice at the moment, despite numerous research findings proving that the benefits of both probiotics and prebiotics encourage their continued existence and positioning in the GIT, with positive effects on human health by managing the inflammatory response. However, the fact that there have been fewer studies on the treatment of UC with different probiotics coupled with selected prebiotics, i.e., synbiotics, and the outcomes of these studies have been very favorable. This evidence-based study explores the possible role of ROS, SOD, and synbiotics in managing the UC. The proposed review also focuses on the role of alteration of gut microbiota, antioxidant defense in the gastrointestinal tract, and the management of UC. Thus, the current article emphasizes oxidative stress signaling in the GI tract, oxidative stress-based pathomechanisms in UC patients, and UC therapies inhibiting oxidative stress' effects.

Role of TREM2 in Alzheimer's Disease and its Consequences on ß- Amyloid, Tau and Neurofibrillary Tangles.

Alzheimer's Disease (AD) is age-related neurodegenerative disorder recognized by a steadily gradual cognitive decline that has devastating personal and socioeconomic implications. Recently, some genetic factors for AD have been identified which attracted wide attention of researchers in different areas of AD biology and possible new therapeutic targets. Alternative forms of triggering receptor expressed on myeloid cells 2 (TREM2) genes are examples of such risk factors, which contribute higher risk for developing AD. Comprehending TREM2 function pledge to provide salient insight into how neuroinflammation contributes to AD pathology. The dearth of microglial TREM2 shepherd to augmented tau pathology is couple with frequent enhancement of activated neuronal stress kinases. The involvement of TREM2 in the regulation of tau-associated innate immune response of the CNS has clearly demonstrated through these findings. However, whether decrease level of TREM2 assists pathology of tau through changed clearance and pathological escalation of tau or through direct contact between microglia and neuron and any alternative possible mechanisms need to examine. This review briefly summarizes distinct functional roles of TREM2 in AD pathology and highlights the TREM2 gene regulation. We have also addressed the impact of TREM2 on ß-amyloid plaques and tau pathology in Alzheimer's disease.

Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer's disease.

Berberine (a protoberberine isoquinoline alkaloid) has shown promising pharmacological activities, including analgesic, anti-inflammatory, anticancer, antidiabetic, anti-hyperlipidemic, cardioprotective, memory enhancement, antidepressant, antioxidant, anti-nociceptive, antimicrobial, anti- HIV and cholesterol-lowering effects. It is used in the treatment of the neurodegenerative disorder. It has strong evidence to serve as a potent phytoconstituent in the treatment of various neurodegenerative disorders such as AD. It limits the extracellular amyloid plaques and intracellular neurofibrillary tangles. It has also lipid-glucose lowering ability, hence can be used as a protective agent in atherosclerosis and AD. However, more detailed investigations along with safety assessment of berberine are warranted to clarify its role in limiting various risk factors and AD-related pathologies. This review highlights the pharmacological basis to control oxidative stress, neuroinflammation and protective effect of berberine in AD, which will benefit to the biological scientists in understanding and exploring the new vistas of berberine in combating Alzheimer's disease.

Transfersomes as versatile and flexible nano-vesicular carriers in skin cancer therapy: the state of the art.

Introduction: The skin acts as a barrier and prevents transcutaneous delivery of therapeutic agents. Transfersomes are novel vesicular systems that are several times more elastic than other vesicular systems. These are composed of edge activator, phospholipids, ethanol, and sodium cholate and are applied in a non-occlusive manner. Areas covered: This article covers information such as merits/demerits of transfersomes, regulatory aspects of materials used in preparation, different methods of preparation, mechanism of action, review of clinical investigations performed, marketed preparations available, research reports, and patent reports related to transfersomes. Expert opinion: Research over the past few years has provided a better understanding of transfersomal permeation of therapeutic agents across stratum corneum barrier. Transfersomes provides an essential feature of their application to variety of compositions in order to optimize the permeability of a range of therapeutic molecules. This is evidenced by the fact that there are several Transfersome products being processed in advanced clinical trials. It is noteworthy that a number of Transfersome products for dermal and transdermal delivery will gain a global market success in near future.

Study of Antimicrobial and Cytotoxic Potential of the Oyster Mushroom Pleurotus ostreatus cv. Florida (Agaricomycetes).

This work was undertaken to evaluate in vitro antimicrobial and cytotoxic potential of Pleurotus ostreatus cv. Florida. Mushroom basidiocarps were extracted in water:ethanol (1:1, v/v), and the resulting extract was subjected to antimicrobial studies against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella oxytoca, Bacillus subtilis, and Candida albicans. Cytotoxic potential on viable human leukocytes was studied. In vitro results showed excellent antimicrobial and cytotoxic potentials of the mushroom extract. Thus, functional properties of P. ostreatus cv. Florida could be used in the search for novel therapeutics.

Preliminary investigation for wound healing and anti-inflammatory effects of Bambusa vulgaris leaves in rats.

BACKGROUND: Bambusa vulgaris (Family: Poaceae) used in Ayurveda for paralytic complaints, inflammatory disorders and externally to skin disorders. It has various medicinal uses with good nutritional composition and a rich source of vitamins, proteins, amino acid, beta-carotene and phenolic compounds. OBJECTIVE: The present study was aimed to evaluate wound healing and anti-inflammatory potential of ethanol extract of B. vulgaris leaves in rats. MATERIALS AND METHODS: The B. vulgaris leaves were evaluated for wound healing on incision and excision wound methods. Anti-inflammatory effect was evaluated by measurement of paw edema in carrageenan-induced inflammation in rats. Ethyl acetate (BVL-A) and aqueous (BVL-B) fractions from the ethanol extract of leaves were screened for wound healing effects by measuring tensile strength and biochemical parameters in incision wound method. The wound contraction area, antioxidant status and histopathological studies were done in excision wound method. RESULTS: Tensile strength and hydroxyproline level of 5% w/w ointment of BVL-A and BVL-B treated groups were found significantly (P < 0.01) higher and comparable to the reference group. The histopathological study showed the proliferation of collagen, fibrous tissue, and capillaries with epidermal covering at the margin of the wound. The percent inhibition of paw edema was significantly decrease by increasing concentration of BVL-A and BVL-B fractions. In addition, it was found that B. vulgaris possesses antioxidant properties, by its ability to increase antioxidants level. CONCLUSIONS: The results obtained in the present study were indicated that ethyl acetate fraction of B. vulgaris leaves inhibits paw edema and accelerates cutaneous wound healing.

Exploration of a Library of 3,4-(Methylenedioxy)aniline-Derived Semicarbazones as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase: Design, Synthesis, and Evaluation.

A library of 3,4-(methylenedioxy)aniline-derived semicarbazones was designed, synthesized, and evaluated as monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors for the treatment of neurodegenerative diseases. Most of the new compounds selectively inhibited MAO-B and AChE, with IC50 values in the micro- or nanomolar ranges. Compound 16, 1-(2,6-dichlorobenzylidene)-4-(benzo[1,3]dioxol-5-yl)semicarbazide presented a balanced multifunctional profile of MAO-A (IC50 =4.52±0.032 µm), MAO-B (IC50 =0.059±0.002 µm), and AChE (IC50 =0.0087±0.0002 µm) inhibition without neurotoxicity. Kinetic studies revealed that compound 16 exhibits competitive and reversible inhibition against MAO-A and MAO-B, and mixed-type inhibition against AChE. Molecular docking studies further revealed insight into the possible interactions within the enzyme-inhibitor complexes. The most active compounds were found to interact with the enzymes through hydrogen bonding and hydrophobic interactions. Additionally, in silico molecular properties and ADME properties of the synthesized compounds were calculated to explore their drug-like characteristics.

Hyaluronic acid embedded cellulose acetate phthlate core/shell nanoparticulate carrier of 5-fluorouracil.

Aim of this research was to prepare hyaluronic acid-modified-cellulose acetate phthalate (HAC) core shell nanoparticles (NPs) of 5-fluorouracil (5-FU). HAC copolymer was synthesized and confirmed by fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. HAC NPs with 5-FU were prepared using HAC copolymer and compared with 5-FU loaded cellulose acetate phthalate (CAP) NPs. NPs were characterized by atomic force microscopy (AFM), particle size, zeta potential, polydispersity index, entrapment efficiency, in-vitro release, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). HAC NPs were found slower release (97.30% in 48h) than (99.25% in 8h) CAP NPs. In cytotoxicity studies, showed great cytotoxic potential of 5-FU loaded HAC NPs in A549, MDA-MD-435 and SK-OV-3 cancer cellline. HAC NPs showing least hemolytic than CAP NPs and 5-FU. Area under curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and time to reach maximum plasma concentration Tmax), were observed 4398.1±7.90µgh/mL, 145.45±2.25µg/L, 45.74±0.25h, 72±0.50h, respectively of HAC NPs and 119.92±1.78µgh/mL, 46.38±3.42µg/L, 1.2±0.25h, 0.5±0.02h were observed in plain 5-FU solution. In conclusion, HAC NPs is effective deliver carrier of 5-FU for lung cancer.

Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon.

Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.

In-vitro and in-vivo assessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil.

The aim of this research was transdermal delivery of 5-fluorouracil (5-FU) using dextran-coated cellulose acetate phthalate (CAP) nanoparticulate formulation. CAP nanoparticles were prepared using drug-polymer ratio (1:1 to 1:3) and surfactant ratio (2.5, 5 and 10%). Dextran coating was made using aminodextran. The results showed that the optimized CAP nanoparticles (CNs) and dextran-coated CAP nanoparticles represented core-corona nanoparticles with the mean diameter of 75 ± 3 and 79 ± 2 nm, respectively, and entrapment efficiency was 82.5 ± 0.06 and 78.2 ± 0.12, respectively. Dextran-coated nanoparticles (FDCNs) and CAP nanoparticles (FCNs) showed in vitro 5-FU release upto 31 h and 8 h, respectively. Moreover, the cumulative amount of 5-FU penetrated through excised skin from FDCNs was 2.94 folds than that of the FU cream. Concentration of 5-FU in epidermis and dermis were also studied. In dermis, concentration of 5-FU was found higher in case of FDCN formulation than plain FU cream. FDCNs were found more hemocompatible in comparison to FCNs. The hematological data recommended that FDCNs formulation was less immunogenic compared to FU creams formulation. In blood level study, FDCNs exhibited 153, 12, 16.66 and 16.24-fold higher values for area under the curve, Tmax, Cmax and mean residence time (MRT) compared with those of FU cream, respectively. The in-vitro cytotoxicity was assessed using the MCF-7 by the MTT test and was compared to the plain 5-FU solution. All the detailed evidence showed that FDCNs could provide a promising tuning as a transdermal delivery system of 5-FU.

Antioxidant Potential of White Oyster Culinary-Medicinal Mushroom, Pleurotus florida (Higher Basidiomycetes).

The present work was focused to evaluate in vitro antioxidant of Pleurotus florida. The hydroethanolic extract was prepared by macerating basidiocarp with water:ethanol (1:1). The antioxidant potential was evaluated by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity, reducing power, chelating effects on ferrous ions, total antioxidant capacity, and lipid peroxidation inhibitory activity. Further total flavonoid and phenolic content was also estimated. The comparison between different antioxidant assays was done by correlation coefficient. The results from the antioxidant assays showed that hydroethanolic extract (HEE) might act as radical scavenger to a certain extent. The distinct scavenging activities of HEE can be due to the diverse phytochemical constituents. Being a rich source of antioxidants, P. florida can be used as an accessible source of natural antioxidants with consequential health benefits.

Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon.

Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

Antidiabetic potential of polysaccharides from the white oyster culinary-medicinal mushroom Pleurotus florida (higher Basidiomycetes).

This study was designed to examine the antihyperglycemic potential of the polysaccharide fraction of Pleurotus florida. Hyperglycemia was induced by streptozotocin (50 mg/kg intraperitoneal). Single- and multiple-dose studies were performed to assess the antihyperglycemic potential of the P. florida polysaccharides (PFPs). Organisation for Economic Co-operation and Development guideline 423 was followed to study the acute toxicity of PFP. PFP was found to be nontoxic up to 4000 mg/kg. In this investigation, 200- and 400-mg/kg doses of PFP were used. Blood glucose, serum cholesterol, triglycerides, urine glucose and ketones, and glycosylated hemoglobin were estimated, and biological markers were determined. Treatment with PFP (200 and 400 mg/kg) significantly lowered glucose concentrations compared to the control group. Serum cholesterol, triglycerides, and urine glucose and ketones in animals treated with PFP also decreased. There was a significant decrease in the concentrations of malondialdehyde and nitric oxide, whereas concentrations of superoxide dismutase, catalase, and reduced glutathione were restored. Therefore, these results suggest that PFPs may ameliorate hyperglycemia and hypercholesteremia associated with diabetes. Thus PFPs could be used as adjunct therapy along with first-line therapy in type 2 diabetes mellitus.

All Madelung deformities are not endocrine.

Madelung deformity is a rare inherited disorder associated with endocrine disorders like Turner's syndrome, pseudohypoparathyroidism, but can be seen with short stature homeobox deficiency conditions such as Leri-Weill dyschondrosteosis (LWD) and Langers mesomelic dysplasia. It has also been reported following trauma to the distal radius epiphysis neoplasia mucopolysaccharidosis (MPS) and achondroplasia. Madelung deformity is an abnormality of distal radial epiphysis where in progressive ulnar and volar tilt of the articular surface occurring in association with distal subluxation of ulna. A 13-year-old girl was referred to us for evaluation of bilateral deformity of wrist and short stature. There was ulnar deviation and dorsal tilt of bilateral hands without history of pain to the joint trauma and family history of similar illness. On X-ray, wrist showed malformed distal radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of Madelung deformity. X-ray spine was normal. Ultrasound abdomen showed normal uterus and ovary and her follicle stimulating hormone. Luteinizing hormone was normal and so was urine MPS screening. Based on the above points the diagnosis of LWD was made.

Experimental evaluation of analgesic and anti-inflammatory potential of Oyster mushroom Pleurotus florida.

BACKGROUND: Edible mushrooms have been used as flavorful foods and as health nutritional supplements for several centuries. A number of bioactive molecules have been identified in numerous mushroom species. OBJECTIVE: To evaluate the analgesic and anti-inflammatory potential of Oyster Mushroom Pleurotus florida using various experimental models in Wistar rats. MATERIALS AND METHODS: Acute toxicity studies were performed whereby dose of 250 mg/ kg and 500 mg/kg was selected for present study, Analgesic activity was determined using hot plate method, tail flick method, acetic acid induced writhing and formalin induced pain in rats, while carrageenan was used to induce inflammation and anti-inflammatory studies were performed. RESULTS: HEE showed significant (P < 0.01) analgesic and anti-inflammatory response against all experimental models. CONCLUSION: These studies conclude that Pleurotus florida possesses analgesic and anti- inflammatory potential which might be due to presence of myochemicals like flavonoids, phenolics and polysaccharides.

In vitro H(+) -K(+) ATPase inhibitory potential of methanolic extract of Cissus quadrangularis Linn.

OBJECTIVE: This study was undertaken to study in vitro H(+) -K(+) ATPase inhibitory potential of methanolic extract of Cissus quadrangularis Linn. MATERIALS AND MATHODS: Total phenolic and flavonoid contents from extract was quantified and H(+) -K(+) ATPase inhibition assay was performed in presence of different concentrations of standard (omeprazole) and methanol extract. RESULTS: Extract showed significant (*P < 0.05) proton pump inhibitory activity in the goat gastric mucosal homogenate which was comparable to standard. CONCLUSIONS: These findings showed that methanolic extract of C. quadrangularis Linn. is potent inhibitor of proton pump.

In vitro prevention of cataract by Oyster Mushroom Pleurotus florida extract on isolated goat eye lens.

OBJECTIVES: The aim of the present work was to evaluate the in vitro effect of Pleurotus florida extract cataract induced by glucose. MATERIALS AND METHODS: Goat eye lenses were divided into four groups. Group I lenses were incubated in artificial aqueous humor with glucose concentration 5.5 mM (normal control). Group II lenses were incubated with glucose concentration 55 mM (toxic control). Group III and IV lenses incubated with glucose concentration 55 mM were incubated along with hydroethanolic extract of P. florida 250 µg/ml and 500 µg/ml and subjected to morphological and biochemical evaluation. RESULTS: Group II lenses showed high amount of malondialdehyde (MDA) soluble and insoluble protein and decreased catalase and glutathione levels, while lenses treated with P. florida extract showed significant (P < 0.05) reduction in MDA, increased level of catalase (P < 0.001), glutathione (P < 0.005) and total and soluble protein. CONCLUSIONS: Hydroethanolic extract of P. florida showed prevention of in vitro glucose induced cataract. Thus, the goat lens model could be used for testing of various anticataract agents.

Tamarindus indica: Extent of explored potential.

Tamarindus is a monotypic genus and belongs to the subfamily Caesalpinioideae of the family Leguminosae (Fabaceae), Tamarindus indica L., commonly known as Tamarind tree is one of the most important multipurpose tropical fruit tree species in the Indian subcontinent. Tamarind fruit was at first thought to be produced by an Indian palm, as the name Tamarind comes from a Persian word "Tamar-I-hind," meaning date of India. Its name "Amlika" in Sanskrit indicates its ancient presence in the country. T.indica is used as traditional medicine in India, Africa, Pakistan, Bangladesh, Nigeria,and most of the tropical countries. It is used traditionally in abdominal pain, diarrhea and dysentery, helminthes infections, wound healing, malaria and fever, constipation, inflammation, cell cytotoxicity, gonorrhea, and eye diseases. It has numerous chemical values and is rich in phytochemicals, and hence the plant is reported to possess antidiabetic activity, antimicrobial activity, antivenomic activity, antioxidant activity, antimalarial activity, hepatoprotective activity, antiasthmatic activity, laxative activity, and anti-hyperlipidemic activity. Every part of the plant from root to leaf tips is useful for human needs. Thus the aim of the present review is to describe its morphology, and explore the phytochemical constituents, commercial utilization of the parts of the plant, and medicinal and pharmacologic activities so that T. indica's potential as multipurpose tree species can be understood.