Effect of herbal combination of triphala and garcinia cambogia extracts on anthropometric measurements and lipid profile in high fat diet induced obesity in rats

Background: Obesity, occurring at epidemic rates globally, is a major risk factor for DM and CVD. Despite advances in understanding its pathogenesis, the pharmacotherapy for obesity remains limited for achievable weight loss, safety and tolerability of the medicines. Almost all approved medications for long term use in obesity treatment result in health issues. Due to the ADRs associated with many antiobesity drugs, the drug trials have focused on screening herbal medicines that are reportedly used in the treatment of obesity and which have minimal side effects.Methods: In this study rats were divided into eight groups of six rats each. In the first approach, the rats were first made obese by feeding HFD for three weeks. In the second, treatment with the herbal extracts was given simultaneously with the HFD to the experimental rats. Rat were fed HFD for six weeks along with treatment of herbal extracts and the effect on their body weight, daily food intake and lipid-profile were evaluated.Results: Results showed that rats fed HFD for a six week period, supplemented with herbal preparations of triphala and G. cambogia presented with significant reduction in body weight, energy intake, and improved the lipid-profile as compared to the rats fed with HFD group.Conclusions: Our findings suggest that triphala and G. cambogia can counter the effects of HFD intake and have the potential for use as antiobesity agents with desirable body weight, food intake, fluid intake, and lipid-profile modulating properties

Effect of herbal combination of triphala and Garcinia cambogia extracts on liver function test and kidney function test in high fat diet induced obesity in rats

Background: Obesity, a global epidemic, is a major risk factor for diabetes mellitus and cardio vascular diseases. Despite advances, the pharmacotherapy for obesity remains limited. Almost all medications for long term management of obesity have health issues. Due to the adverse drug reactions (ADRs) associated with many antiobesity medicines, the clinical trials are focussing on screening herbal medicines for use in the treatment of obesity, which have minimal ADRs.Methods: Rats were divided into eight groups of six each. The rats were first made obese by feeding high fat diet (HFD) for three weeks. Then treatment with the herbal extracts was given simultaneously with the HFD to the experimental groups. Rats were fed HFD for six weeks along with herbal extracts and the effect on their liver function test and kidney function test were evaluated.Results: The rats fed HFD and supplemented with herbal preparations of Triphala and G. cambogia for six weeks, showed significant improvement in liver function test and kidney function test related parameters as compared to the control group rats fed with HFD alone.Conclusions: Triphala and G. cambogia can counter the effects of HFD intake and have the potential for use as anti-obesity agents with desirable liver function test and kidney function test related parameters modulating properties

EFFECTS OF NITROXAZEPINE ON DIASTOLIC BLOOD PRESSURE IN MILD HYPERTENSIVE PATIENTS -A SHORT TERM CLINICAL STUDY

Abstract: In a double blind short term clinical study, nitroxazcpine has been found to be superior over placebo in reducing the diastolic blood pressure in mild hypertensive patients. In short term open clinical trial design nitroxazepine (25 mg PO, HS) has been found to be superior and better tolerated than diazepam (5 mg PO, HS). In open clinical trial design. nitroxazepine (25 mg PO, HS) reduced the diastolic blood pressure to the target level (100 mm Hg and less) effecti'.'ely controlling the uncontrolled hypertensive patients receiving maintenance dose of beta blockers. There was no such beneficial effect in patients receiving maintenance doses of other antihypertensive drugs (piLot studyl. Adverse drug reactions like disturbed sleep in one, uneasiness in 3, palpitation in one and dryness of mouth in one patient have been observed

Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe

Ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme (DUB), is a potential drug target in various cancers, and liver and lung fibrosis. However, bona fide functions and substrates of UCHL1 remain poorly understood. Herein, we report the characterization of UCHL1 covalent inhibitor MT16-001 based on a thiazole cyanopyrrolidine scaffold. In combination with chemical proteomics, a closely related activity-based probe (MT16-205) was used to generate a comprehensive quantitative profile for on- and off-targets at endogenous cellular abundance. Both compounds are selective for UCHL1 over other DUBs in intact cells but also engage a range of other targets with good selectivity over the wider proteome, including aldehyde dehydrogenases, redox-sensitive Parkinson’s disease related protein PARK7, and glutamine amidotransferase. Taken together, these results underline the importance of robust profiling of activity-based probes as chemical tools and highlight the cyanopyrrolidine warhead as a versatile platform for liganding diverse classes of protein with reactive cysteine residues which can be used for further inhibitor screening, and as a starting point for inhibitor development

Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2.

Proteolysis-Targeting Chimeras (PROTACs) are heterobifunctional small-molecules that can promote the rapid and selective proteasome-mediated degradation of intracellular proteins through the recruitment of E3 ligase complexes to non-native protein substrates. The catalytic mechanism of action of PROTACs represents an exciting new modality in drug discovery that offers several potential advantages over traditional small-molecule inhibitors, including the potential to deliver pharmacodynamic (PD) efficacy which extends beyond the detectable pharmacokinetic (PK) presence of the PROTAC, driven by the synthesis rate of the protein. Herein we report the identification and development of PROTACs that selectively degrade Receptor-Interacting Serine/Threonine Protein Kinase 2 (RIPK2) and demonstrate in vivo degradation of endogenous RIPK2 in rats at low doses and extended PD that persists in the absence of detectable compound. This disconnect between PK and PD, when coupled with low nanomolar potency, offers the potential for low human doses and infrequent dosing regimens with PROTAC medicines

Deletion of a Malaria Invasion Gene Reduces Death and Anemia, in Model Hosts

Malaria parasites induce complex cellular and clinical phenotypes, including anemia, cerebral malaria and death in a wide range of mammalian hosts. Host genes and parasite ‘toxins’ have been implicated in malarial disease, but the contribution of parasite genes remains to be fully defined. Here we assess disease in BALB/c mice and Wistar rats infected by the rodent malaria parasite Plasmodium berghei with a gene knock out for merozoite surface protein (MSP) 7. MSP7 is not essential for infection but in P. falciparum, it enhances erythrocyte invasion by 20%. In vivo, as compared to wild type, the P. berghei Δmsp7 mutant is associated with an abrogation of death and a decrease from 3% to 2% in peak, circulating parasitemia. The Δmsp7 mutant is also associated with less anemia and modest increase in the size of follicles in the spleen. Together these data show that deletion of a single parasite invasion ligand modulates blood stage disease, as measured by death and anemia. This work is the first to assess the contribution of a gene present in all plasmodial species in severe disease

Genome wide linkage study, using a 250K SNP map, of Plasmodium falciparum infection and mild malaria attack in a Senegalese population

Multiple factors are involved in the variability of host's response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genomewide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP) genome scan (Affimetrix GeneChip Human Mapping 250K-nsp) was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT) method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value = 5 x 10(-5) and 96 x 10(-5) respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value = 1.5 x 10(-4)). Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31-q33 region (p-value = 3.7 x 10(-5)). This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection. Furthermore, we detected one gene associated with malaria infection in the 5q31-q33 region

Pain in platin-induced neuropathies: A systematic review and meta-analysis

INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe