A Contemporary Exploration of Traditional Indian Snake Envenomation Therapies.

Snakebite being a quick progressing serious situation needs immediate and aggressive therapy. Snake venom antiserum is the only approved and effective treatment available, but for selected snake species only. The requirement of trained staff for administration and serum reactions make the therapy complicated.

Protocatechuic acid attenuates chronic unpredictable mild stress induced-behavioral and biochemical alterations in mice.

Amelioration of oxidative stress via promoting the endogenous antioxidant system and enhancement of monoamines in brain were the important underlying antidepressant mechanism of protocatechuic acid (PCA). The aim of the present study is to explore the potential antidepressant mechanism(s) PCA in chronic unpredictable mild stress (CUMS) mice. Mice were subjected to CUMS protocol for 4 weeks, and administered with PCA (100 and 200 mg/kg) and fluoxetine (20 mg/kg) for 24 days (from day 8th to 31st).

Facile synthesis of mesoporous alumina using hexadecyltrimethylammonium bromide (HTAB) as template: simplified sol-gel approach.

Herein the authors present the synthesis of surface functionalised mesoporous alumina (MeAl) for textural characterisation by a simplified sol-gel method obtained by using hexadecyltrimethylammonium bromide as a template. Etoricoxib (ETOX) was used as a model drug for the study. Alumina supported mesoporous material containing drug was characterised using instrumental technique namely Brunauer-Emmett-Teller surface area, Fourier transform-infrared, differential scanning calorimetry, transmission electron microscopy, X-ray diffraction, and field emission scanning electron microscopy.

Protocatechuic acid attenuate depressive-like behavior in olfactory bulbectomized rat model: behavioral and neurobiochemical investigations.

The main objective of the present study is to investigate potential effects of PCA in OBX induced depressive-like behavior in rat model. PCA was administered at a dose of 100 mg/kg and 200 mg/kg, by per oral in OBX and sham operated rats. Behavioral (ambulatory and rearing activity and immobility time), neurochemical [serotonin (5-HT), dopamine (DA), norepinephrine (NE) and brain derived neurotrophic factor (BDNF) expression], biochemical (MDA formation, IL-6, TNF-α and antioxidants) changes in hippocampus and cerebral cortex along with serum corticosterone were investigated.

Recent Approaches in the Development of Phytolipid Complexes as Novel Drug Delivery.

The imbalance of hydrophilicity and lipophilicity along with a large molecular size (due to a unique chemical structure) of natural compounds or plant actives poses a significant challenge for their absorption through a biological membrane and thus, alters the therapeutic efficacy. Therefore, it is desirable to have a novel approach for such formulation in order to improve the solubility and bioavailability of these phytoconstituents as a phospholipid complexation. Herbal drugs are precisely, embedded and bound by phospholipids to form vesicular structures which are amphoteric in nature.

Therapeutic potential of silymarin in chronic unpredictable mild stress induced depressive-like behavior in mice.

Silymarin, a plant-derived polyphenolic flavonoid of Silybum marianum, elicited significant antidepressant-like activity in an acute restraint stress model of depression. It improved monoamines, mainly 5-hydroxytryptamine (5-HT) levels in the cortex, dopamine (DA) and norepinephrine (NE) in the cerebellum in mice. The present study was undertaken to explore the antidepressant potential of silymarin in chronic unpredictable mild stress (CUMS) induced depressive-like behavior in mice, and to find out its probable mechanism(s) of action, mainly neurogenesis, neuroinflammation, and/or oxidative stress.

Hecogenin exhibits anti-arthritic activity in rats through suppression of pro-inflammatory cytokines in Complete Freund's adjuvant-induced arthritis.

Hecogenin is a steroidal sapogenin isolated from the leaves of Agave genus species that plays an important role in the treatment of a variety of inflammatory diseases. The aim of the present study was to evaluate the anti-arthritic activity of hecogenin in Complete Freund's adjuvant-induced arthritis in rats. The hecogenin (40 µl of 50 µg/kg, orally) and hecogenin + fluticasone (40 µl of 25 µg/kg, each, orally) was tested against Complete Freund's adjuvant-induced arthritis in rats by evaluating various parameters such as paw volume, arthritic score, joint diameter, spleen weight, thymus weight, haematological and biochemical parameters and pro-inflammatory cytokines.

Silymarin ameliorates experimentally induced depressive like behavior in rats: Involvement of hippocampal BDNF signaling, inflammatory cytokines and oxidative stress response.

Silymarin is a polyphenolic flavonoid of Silybum marianum, exhibited neuroprotection and antidepressant like activity in acute restraint stressed mice. The main objective of the present study is to investigate possible antidepressant like activity of silymarin in experimentally induced depressive behavior in rats. The depressive behaviors were induced in rats by olfactory bulbectomized (OBX) technique.

Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice.

Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice.

Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: Modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus.

Background: Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice.

Preparation and Pharmacological Evaluation of Novel Orally Active Ester Prodrugs of Ketoprofen with Non-Ulcerogenic Property.

This study investigates anti-inflammatory activity with improved pharmacokinetic and non-ulcerogenic properties of various novel synthesized prodrugs of ketoprofen in experimental animals. Prodrugs 3a, 3f and 3k were found to possess significant anti-inflammatory activity with almost non-ulcerogenic potential than standard drug ketoprofen (1) in both normal and inflammation-induced rats. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent drug ketoprofen.

Ameliorative effects of Tricholepis glaberrima in experimentally induced hepatic damage in rats: modulation of cytokines functions.

Ethnopharmacological Relevance: Tricholepis glaberrima belonging to family Asteraceae is popularly known as "Brahmadandi" in Indian system of medicine and is claimed to be effective in the treatment of various ailments such as neurological disorders, hepatic disorders, sexual dysfunction, skin disease etc. The present study was undertaken to investigate the possible role of Tricholepis glaberrima in rifampicin and Bacillus Calmette-Guerin/lipopolysaccharides (BCG/LPS) induced hepatotoxicity in rats and its possible mechanism of actions.

Materials And Methods: Hepatotoxicity was induced in rats by administration of rifampicin for 30 days and in another experiment BCG on day 1 and LPS on day 11.

Docking study of novel antihyperlipidemic thieno[2,3-d]pyrimidine; LM-1554, with some molecular targets related to hyperlipidemia - an investigation into its mechanism of action.

An investigation into the mechanism of antihyperlipidemic action of 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-one (LM-1554) was carried out through docking experiments with six different molecular targets; Niemann Pick C1 Like1 protein (NPC1L1), ATP citrate lyase (ACL), C-reactive protein (CRP), lanosterol 14α-demethylase (LDM), squalene synthase (SqS) and farnesiod X-receptor (FXR) known to be implicated in the physiology of hyperlipidemia. The interactions of LM-1554 were compared with the interactions of their respective co-crystallized native ligands at the active sites of these receptors. These comparisons are based on their docking parameters, as well as, types of interactions and vicinity with various amino acids in the active site pockets.

Some molecular targets for antihyperlipidemic drug research.

High levels of cholesterol and other lipid constituents are major risk factors in the development of atherosclerosis as well as diseases and disorders associated with it. Though, drugs of various categories acting through different mechanisms are available for antihyperlipidemic therapy, there are limitations associated with each of them, keeping the interest in discovery of newer and better antihyperlipidemic drugs alive. Identification and exploitation of novel molecular targets for discovery of new antihyperlipidemic drugs is an important area of research.

Arthritis, a complex connective and synovial joint destructive autoimmune disease: animal models of arthritis with varied etiopathology and their significance.

Animal models play a vital role in simplifying the complexity of pathogenesis and understanding the indefinable processes and diverse mechanisms involved in the progression of disease, and in providing new knowledge that may facilitate the drug development program. Selection of the animal models has to be carefully done, so that there is morphologic similarity to human arthritic conditions that may predict as well as augment the effective screening of novel antiarthritic agents. The review describes exclusively animal models of rheumatoid arthritis (RA) and osteoarthritis (OA).

Curriculum for pharmacology in pharmacy institutions in India: opportunities and challenges.

The curriculum of pharmacy institutions in India is regulated by the All India Council for Technical Education (AICTE) and the Pharmacy Council of India (PCI) at degree and diploma levels. However, it has been over two decades that the syllabi have been revised by these regulatory agencies. Considering the dynamic character of pharmacology, it is essential to prepare a syllabus that caters to the contemporary needs of the academic institutions and pharmaceutical industry, the community.

Design, synthesis & evaluation of condensed 2H-4-arylaminopyrimidines as novel antifungal agents.

A small, focussed library of condensed 2H-4-arylaminopyrimidines, with 3-diversity points, based on an initial design by molecular docking study of this scaffold at the active site of the fungal enzyme of cytochrome P450 family, lanosterol 14α-demethylase (CYP51) was synthesized through a one-pot green chemical synthetic protocol. The screening of the synthesised compounds for antifungal activity against Candida albicans, Aspergillus fumigatus &Aspergillus niger revealed activity in many of the compounds as comparable to that of fluconazole. Based on the antifungal activity and physicochemical property data of these derivatives, a meaningful SAR has been proposed.

The chemistry and biological potential of azetidin-2-ones.

Azetidin-2-ones, commonly referred as β-lactams, represent a unique ring system, with interesting chemistry and great biological potential. Besides its well known antibiotic activity, this ring system exhibits a wide range of activities, attracting the attention of researchers. The biological and pharmacological profile of azetidin-2-ones is reviewed here comprehensively with several examples under fourteen different activity heads.

Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): a critical discussion.

Liver is a primary organ involved in biotransformation of food and drugs. Hepatic diseases are a major worldwide problem. Hepatic disorders are mainly caused by toxic chemicals (alcohol), xenobiotics (carbon tetrachloride, chlorinated hydrocarbons and gases CO₂ and O₂) anticancer (azathioprine, doxorubicin, cisplatin), immunosuppressant (cyclosporine), analgesic anti-inflammatory (paracetamol, thioacetamide), anti-tubercular (isoniazid, rifampicin) drugs, biologicals (Bacillus-Calmette-Guerin vaccine), radiations (gamma radiations), heavy metals (cadmium, arsenic), mycotoxin (aflatoxin), galactosamine, lipopolysaccharides, etc.

Design, synthesis and biological evaluation of some 2-azetidinone derivatives as potential antihyperlipidemic agents.

In an effort to develop new molecules with improved antihyperlipidemic activity, eight new 2-azetidinone analogs (4a-4h) of ezetimibe were designed through in silico docking experiments with the crystal structure of the Niemann-Pick C1-like 1 protein (NPC1L1). Synthesis and further antihyperlipdemic evaluation of this series in the Triton WR 1339 induced hyperlipidemic rat model showed some of the molecules to exhibit significant lipid-lowering effects comparable to ezetimibe. Correlation between the observed biological activity and the in silico molecular docking scores of the compounds was observed.

Hepatoprotective activity of Calotropis gigantea flowers against carbon-tetrachloride-induced liver damage in mice.

Ethanol extract of Calotropis gigantea flowers (CGFE) was evaluated for its antioxidant and hepatoprotective activity to validate its use in traditional therapeutic indications. This CGFE exhibited significant antioxidant activity (at 20, 40, 60, 80 and 100 µg/ml in vitro) as evidenced by its hydroxyl, nitric oxide and hydrogen peroxide anion radical scavenging activities. This in vitro antioxidant activity was reinforced by a significant hepatoprotection (at 250 and 500 mg/kg dose) by decreasing the activity of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase.

Design, synthesis, and antihyperlipidemic evaluation of novel 2-[1-(substitutedphenyl)-4-oxo-azetidin-2-yl]-5,6-disubstitutedthieno[2,3-d]pyrimidin-4(3H)-ones.

Novel thienopyrimidine derivatives of azetidinone possessing the combined features of the cholesterol absorption inhibitor drug ezetimibe and potential antihyperlipidemic 2-substitutedthienopyrimidin-4-ones were synthesized and characterized by spectroscopic data and elemental analysis. These compounds were evaluated for their lipid-lowering activity in Wistar albino rats. Some of them showed significant lipid-lowering effects comparable to those of the standard drug, gemfibrozil, at the same dose levels.

Liposomes as potential carrier system for targeted delivery of polyene antibiotics.

The development of new therapeutic modalities involves the use of drug carrier, such as liposomes, which can modify pharmacokinetic and bio-distribution of drug profile. Polyene antibiotics incorporation into liposomes improves its availability at the site, bio-distribution and therapeutic index mainly through the engulfment of liposomes by circulating monocytes/macrophages and transportation to the site of infection. Polyene antibiotics (AmB, SJA-95, HA-1-92) and other antibiotics (streptomycin, tobramycin, quinolones, anti-tubercular and anti-cancer drugs), liposomal preparations are described with possible advantages from therapeutic efficacy and toxicity point of view.

Therapeutic potential of curcumin in experimentally induced allergic rhinitis in guinea pigs.

In the present experiments, the possible role of curcumin in ovalbumin induced allergic rhinitis in guinea pig model was investigated. Various allergic rhinitis symptoms viz sneezing, rubbing frequencies, lacrimation and nasal congestion at various humidity conditions as well as on repeated sensitization were studied. The biochemical changes like serum IgE, IL-4 and nitric oxide (NO) in nasal lavage and eosinophil peroxidase activity in nasal homogenates were determined in allergic rhinitis.