scholarly journals Anti-Obesity Properties of Calocybe Indica in Zebra fishes with Short-Term High-Fat Diet Induction

2021 ◽  
Vol 14 (01) ◽  
pp. 411-423
Author(s):  
Anushree Nagaraj ◽  
Sarah Andrea Wilson ◽  
Lalitha Vaidyanathan
Keyword(s):  
Side Effects ◽  
Normal Control ◽  
Whole Body ◽  
Standard Drug ◽  
Alcoholic Fatty Liver ◽  
Synthetic Drugs ◽  
Cholesterol Levels ◽  
Calocybe Indica ◽  
Complex Health Problems ◽  
Coa Reductase

Obesity, a disease involved with complex health problems, is indicated by increased BMI, triglyceride and cholesterol levels. Obese individuals are found to be highly susceptible to develop non-alcoholic fatty liver disease,cardiovascular diseases, and also type 2 diabetes mellitus. Synthetic drugs used for treating obesity have been found to be associated with side effects such as anxiety,sleeplessness,hypertension, and drug addiction. Research on natural productspossessing therapeutic biological activitieshasdiscoveredtheir potential to minimize or even completely eliminate such side effects. Medicinal properties ofCalocybe indica include antidiabetic, hypertensive, anticancer, anti-inflammatory, antibacterial, and hepatoprotective effects; however, its anti-obesity activity is obscure.In this study, the anti-obesity effects of Calocybe indicawere investigated using a diet-induced obese Zebrafish modeland compared with standard drug Atorvastatin.Results show that 200µg of C. indica was able to effectively bring down triglyceride levels (12.5± 0 mg/ml; normal control 12.7 ± 0.7 mg/ml), cholesterol (210± 15.9 mg; normal control =70.4± 0)and HMG COA Reductase levels (0.9± 0.03; normal = 1.2 ± 0.01). Excessive fat accumulation in the liver (steatohepatitis) reduced after treatment with C. indica to a greater extent than by treatment with standard drug Atorvastatin. 100 µg of C. indica was found to be optimum in decreasing the levels of the liver enzymes, AST (177.1±5.7 IU/L; normal control =177.7±43.02 IU/l), ALT (365.5±2.9 IU/L; normal control= 355.5±34.4 IU/l), and ALP (2.3±1.1μmoles of phenol liberated/mg of protein/min; normal control = 0.7±1.2 μmoles of phenol liberated/mg of protein/min).Whole-body Oil Red O staining of the zebrafishes showed that with increasing concentration of C. indica, the accumulation of triglycerides and lipids decreased.

Biological consequences of statins in Candida species and possible implications for human health

2007 ◽  
Vol 35 (6) ◽  
pp. 1529-1532 ◽  
Author(s):  
K. Wikhe ◽  
C. Westermeyer ◽  
I.G. Macreadie
Keyword(s):  
Mitochondrial Dna ◽  
Side Effects ◽  
Candida Species ◽  
Candida Glabrata ◽  
Fungal Species ◽  
Fungal Colonization ◽  
Preliminary Screening ◽  
Cholesterol Levels ◽  
Essential Enzyme ◽  
Coa Reductase

The statins, simvastatin and atorvastatin are the most widely prescribed drugs. Statins lower cholesterol levels through their action on HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, an essential enzyme for the biosynthesis of cholesterol. Fungal HMG-CoA reductases are also inhibited by statins, resulting in reduced levels of ergosterol (the fungal equivalent of cholesterol) and concomitant growth inhibition. This effect occurs in a range of fungal species and possibly affects fungal colonization of people on statin therapy. Furthermore, it may suggest that statins could have a role in new antifungal therapies. Possibly associated with the reduction in ergosterol levels, statins also inhibit respiratory growth. In the yeast, Candida glabrata, passage with statins dramatically increased the frequencies of petite mutants that were devoid of mitochondrial DNA, suggesting that statins caused a defect in the maintenance of mitochondrial DNA. These observations in C. glabrata may provide further insights into side effects of statins in humans undergoing treatment for hypercholesterolaemia. In addition, C. glabrata may be highly useful for the preliminary screening of agents to reduce statin side effects.

scholarly journals Gastroprotective effect of leaves of Breyniavitis-Idaea

2020 ◽  
Vol 11 (2) ◽  
pp. 2519-2524
Author(s):  
Poojitha M ◽  
Saravanakumar A S ◽  
Satyanarayana S V
Keyword(s):  
Side Effects ◽  
Chemical Constituents ◽  
Gastric Volume ◽  
Gastric Ulcers ◽  
Antiulcer Activity ◽  
Standard Drug ◽  
Synthetic Drugs ◽  
Pylorus Ligation ◽  
Dose Dependent ◽  
Ligation Method

Due to the lure backs of synthetic drugs that are being used medical field has turned over to the traditional medicine which are devoid of side effects and major adverse effects. So that Herbal drugs were seen as probable replacements for the handling of PUD without showing side effects and equaling the treatment efficacy. The literature review on investigations of antiulcer activity of various plant drug, the present investigation was carried out to investigate the antiulcer potential, chemical constituents present in the methanol extract of traditional plant Breyniavitis-idaea. Gastric ulcers in experimental animals were brought by four different models like  Ethanol(Alcohol)  induced, NSIDS (Indomethacin) induced, Pylorus ligation method and Cold resistant stress induced method by comparing with the standard drug namely omeprazole (20mg/kg) which exhibited the dose dependent capacity of the extract (125mg/kg,250mg/kg, 500mg/kg) and also the biochemical parameters like ALP, GSH, pH and Gastric volume contents were estimated in all the selected groups (Design of Experiment). The results obtained from the study has helped to identify that 500mg/kg of plant extract has gastro protective effect in all the chosen models in comparison to the omeprazole (20mg/kg) standard drug. Owing to the prevalence of different phytoconstituents like poly phenols and flavonoids shown the dose dependent potent gastroprotective activity.

Rheumatoid Arthritis: History, Stages, Epidemiology, Pathogenesis, Diagnosis and Treatment

2017 ◽  
Vol 9 (02) ◽  
Author(s):  
Abeer Fauzi Al-Rubaye ◽  
Mohanad Jawad Kadhim ◽  
Imad Hadi Hameed
Keyword(s):  
Rheumatoid Arthritis ◽  
Medicinal Plants ◽  
Systemic Disease ◽  
Modern Medicine ◽  
Whole Body ◽  
Internal Organs ◽  
Synthetic Drugs ◽  
Relieve Pain ◽  
Medicinal Treatment ◽  
Natural Drugs

The pharmacological mechanisms of the medicinal plants traditionally used for RA in Persian medicine are discussed in the current review. Further investigations are mandatory to focus on bioefficacy of these phytochemicals for finding novel natural drugs. Rheumatoid arthritis is chronic, progressive, disabling autoimmune disease characterized by systemic inflammation of joints, damaging cartilage and bone around the joints. It is a systemic disease which means that it can affect the whole body and internal organs such as lungs, heart and eyes. Although numbers of synthetic drugs are being used as standard treatment for rheumatoid arthritis but they have adverse effect that can compromise the therapeutic treatment. Unfortunately, there is still no effective known medicinal treatment that cures rheumatoid arthritis as the modern medicine can only treat the symptoms of this disease that means to relieve pain and inflammation of joints. It is possible to use the herbs and plants in various forms in order to relieve the pain and inflammation in the joints. There are so many medicinal plants that have shown anti rheumatoid arthritis properties. So the plants and plant product with significant advantages are used for the treatment of rheumatoid arthritis. The present review is focused on the medicinal plants having anti rheumatoid arthritis activity

Synthesis and Investigation of Therapeutic Potential of Isoform-Specific HDAC8 Inhibitors for the Treatment of Cutaneous T Cell Lymphoma

2019 ◽  
Vol 19 (7) ◽  
pp. 916-934 ◽  
Author(s):  
Appavoo Umamaheswari ◽  
Ayarivan Puratchikody ◽  
Natarajan Hari
Keyword(s):  
Side Effects ◽  
Inhibitory Activity ◽  
Hydroxamic Acid ◽  
Histone Deacetylase Inhibitors ◽  
Therapeutic Potential ◽  
In Vitro Assays ◽  
Normal Cells ◽  
Standard Drug ◽  
In Silico Studies ◽  
Hdac8 Inhibitors

Background:The available treatment option for any type of cancer including CTCL is chemotherapy and radiation therapy which indiscriminately persuade on the normal cells. One way out for selective destruction of CTCL cells without damaging normal cells is the use of histone deacetylase inhibitors (HDACi). Despite promising results in the treatment of CTCL, these HDACi have shown a broadband inhibition profile, moderately selective for one HDAC class but not for a particular isotype. The prevalence of drug-induced side effects leaves open a narrow window of speculation that the decreased therapeutic efficacy and observed side effects may be most likely due to non specific HDAC isoform inhibition. The aim of this paper is to synthesis and evaluates HDAC8 isoform specific inhibitors.Methods:Based on the preliminary report on the design and in silico studies of 52 hydroxamic acid derivatives bearing multi-substituent heteroaromatic rings with chiral amine linker, five compounds were shortlisted and synthesized by microwave assisted approach and high yielding synthetic protocol. A series of in vitro assays in addition to HDAC8 inhibitory activity was used to evaluate the synthesised compounds.Results:Inhibitors 1e, 2e, 3e, 4e and 5e exerted the anti-proliferative activities against CTCL cell lines at 20- 100 µM concentrations. Both the pyrimidine- and pyridine-based probes exhibited μM inhibitory activity against HDAC8. The pyrimidine-based probe 1e displayed remarkable HDAC8 selectivity superior to that of the standard drug, SAHA with an IC50 at 0.1µM.Conclusion:Our study demonstrated that simple modifications at different portions of pharmacophore in the hydroxamic acid analogues are effective for improving both HDAC8 inhibitory activity and isoform selectivity. Potent and highly isoform-selective HDAC8 inhibitors were identified. These findings would be expedient for further development of HDAC8-selective inhibitors.

scholarly journals A QM/MM Evaluation of the Missing Step in the Reduction Mechanism of HMG-CoA by Human HMG-CoA Reductase

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1085
Author(s):  
Paula Mihaljević-Jurič ◽  
Sérgio F. Sousa
Keyword(s):  
Mevalonate Pathway ◽  
Atomic Level ◽  
Amino Acid Residues ◽  
Protonation State ◽  
Primary Target ◽  
Cholesterol Levels ◽  
The Subject ◽  
Electron Reduction ◽  
Dynamics Simulations ◽  
Coa Reductase

Statins are important drugs in the regulation of cholesterol levels in the human body that have as a primary target the enzyme β-hydroxy-β-methylglutaryl-CoA reductase (HMGR). This enzyme plays a crucial role in the mevalonate pathway, catalyzing the four-electron reduction of HMG-CoA to mevalonate. A second reduction step of this reaction mechanism has been the subject of much speculation in the literature, with different conflicting theories persisting to the present day. In this study, the different mechanistic hypotheses were evaluated with atomic-level detail through a combination of molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The obtained Gibbs free activation and Gibbs free reaction energy (15 kcal mol−1 and −40 kcal mol−1) show that this hydride step takes place with the involvement of a cationic His405 and Lys639, and a neutral Glu98, while Asp715 remains in an anionic state. The results provide an atomic-level portrait of this step, clearly demonstrating the nature and protonation state of the amino acid residues involved, the energetics associated, and the structure and charge of the key participating atoms in the several intermediate states, finally elucidating this missing step.

scholarly journals Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 253 ◽  
Author(s):  
Yu-Sheng Chen ◽  
Hsuan-Miao Liu ◽  
Tzung-Yan Lee
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Dysfunction ◽  
Ursodeoxycholic Acid ◽  
White Adipose Tissue ◽  
Whole Body ◽  
Bile Acid Metabolism ◽  
Obese Mice ◽  
Alcoholic Fatty Liver ◽  
Tissue Macrophage ◽  
Stat3 Phosphorylation

Obesity has been shown to play a role in the pathogenesis of several forms of metabolic syndrome, including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. Ursodeoxycholic acid (UDCA) has been shown to possess antioxidant and anti-inflammatory properties and prevents mitochondrial dysfunction in the progression of obesity-associated diseases. The aim of the study was to evaluate the mechanisms of UDCA during obesity-linked hepatic mitochondrial dysfunction and obesity-associated adipose tissue macrophage-induced inflammation in obese mice. UDCA significantly decreased lipid droplets, reduced free fatty acids (FFA) and triglycerides (TG), improved mitochondrial function, and enhanced white adipose tissue browning in ob/ob mice. This is associated with increased hepatic energy expenditure, mitochondria biogenesis, and incorporation of bile acid metabolism (Abca1, Abcg1 mRNA and BSEP, FGFR4, and TGR5 protein). In addition, UDCA downregulated NF-κB and STAT3 phosphorylation by negative regulation of the expression of SOCS1 and SOCS3 signaling. These changes were accompanied by decreased angiogenesis, as shown by the downregulation of VEGF, VCAM, and TGF-βRII expression. Importantly, UDCA is equally effective in reducing whole body adiposity. This is associated with decreased adipose tissue expression of macrophage infiltration (CD11b, CD163, and CD206) and lipogenic capacity markers (lipofuscin, SREBP-1, and CD36). Furthermore, UDCA significantly upregulated adipose browning in association with upregulation of SIRT-1-PGC1-α signaling in epididymis adipose tissue (EWAT). These results suggest that multi-targeted therapies modulate glucose and lipid biosynthesis fluxes, inflammatory response, angiogenesis, and macrophage differentiation. Therefore, it may be suggested that UDCA treatment may be a novel therapeutic agent for obesity.

scholarly journals Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

2021 ◽  
Vol 22 (13) ◽  
pp. 6949
Author(s):  
Siarhei A. Dabravolski ◽  
Evgeny E. Bezsonov ◽  
Mirza S. Baig ◽  
Tatyana V. Popkova ◽  
Alexander N. Orekhov
Keyword(s):  
Heart Diseases ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Liver Mitochondria ◽  
Atherogenic Dyslipidemia ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Cholesterol Levels ◽  
Mitochondrial Lipid ◽  
Cardioprotective Effects

The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.

Proposed trial: safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease (NAFLD) and associated insulin resistance in adolescents who are overweight or obese adolescents — rationale and protocol

2015 ◽  
Vol 93 (5) ◽  
pp. 522-530 ◽  
Author(s):  
Brandy Wicklow ◽  
Kristy Wittmeier ◽  
Geert W. t’ Jong ◽  
Jonathon McGavock ◽  
Marni Robert ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Liver ◽  
Outcome Measures ◽  
Side Effect ◽  
Controlled Trial ◽  
Whole Body ◽  
Secondary Outcome ◽  
Side Effect Profile ◽  
Obese Adolescent ◽  
Alcoholic Fatty Liver

Non-alcoholic fatty liver (NAFL) disease (NAFLD) affects 30% of overweight adolescents and increases the risk of type 2 diabetes mellitus (T2D). Resveratrol is a naturally occurring compound with potential to reverse NAFL and its associated insulin resistance in adults. The use of resveratrol to reduce risk for T2D through its effect on NAFL has not been examined to date in youth. This paper provides a literature review and protocol for a 30 day proof of principle trial of resveratrol in a population of adolescents at risk for T2D. This randomized double-blind controlled trial is designed with the primary objective of evaluating a twice daily supplementation of 75 mg of resveratrol for safety and tolerability in overweight and obese adolescent subjects (13 to <18 years of age) with NAFL. Secondary objectives are to determine the effect size of the intervention on hepatic steatosis and whole body insulin sensitivity. Adolescents in the intervention arm (n = 10) will receive oral supplementation of resveratrol 75 mg twice daily (with breakfast and dinner) for a total daily dose of 150 mg for the duration of 30 days. The comparison group (n = 10) will receive a placebo twice daily for 30 days. Both cases and controls will receive a standardized lifestyle intervention program. Subjects in both groups will be followed for an additional 30 days post intervention for total study duration of approximately 60 days. Primary outcome measures include a primary side effect profile determined by participant interview, a side effect profile determined by serum biochemistry and vital signs. Secondary outcome measures include an oral glucose tolerance test, liver and cardiac fat content measured by magnetic resonance spectroscopy, anthropometric measures of overweight/obesity, inflammatory markers, and cardiac function and morphology measured with ultrasonography. Additional outcome measures include serum concentrations of resveratrol, compliance to protocol, physical activity, and nutritional assessment. This study will determine the safety and tolerability of resveratrol in an overweight adolescent population and inform the design of a larger randomized controlled trial.

Self-limiting benign paroxysmal positional vertigo following use of whole-body vibration training plate

2009 ◽  
Vol 124 (7) ◽  
pp. 796-798 ◽  
Author(s):  
I Amir ◽  
E Young ◽  
A Belloso
Keyword(s):  
Side Effects ◽  
Literature Review ◽  
Benign Paroxysmal Positional Vertigo ◽  
Whole Body Vibration ◽  
Whole Body ◽  
Body Vibration ◽  
Positional Vertigo ◽  
Vibration Training ◽  
Whole Body Vibration Training ◽  
Paroxysmal Positional Vertigo

AbstractObjective:We describe a case of benign paroxysmal positional vertigo which occurred after use of a whole-body vibration training plate.Method:Case report and literature review concerning the secondary causes of benign paroxysmal positional vertigo and the physiological effects of whole-body vibration training plates.Results:A 44-year-old woman was referred with classic symptoms of benign paroxysmal positional vertigo following use of a whole-body vibration training plate, a popular form of fitness equipment widely used in sports, rehabilitation and beauty treatments. The condition resolved spontaneously after several days. There have been reports of negative side effects in users of this equipment, such as dizziness, headache and a sensation of imbalance; however, there have been no reported cases involving vertigo. Based on a literature review, this equipment may cause side effects, including vertigo, by generating forces that can increase the original amplitude of internal organs, which may potentially cause labyrinthine trauma or dislocation of otoconia, leading to benign paroxysmal positional vertigo.Conclusions:We suggest that whole-body vibration training plates may potentially induce benign paroxysmal positional vertigo. Manufacturers may need to make users of this equipment aware of this risk, and remind them to use it with caution.

scholarly journals The Burden of Survivorship on Hematological Patients—Long-Term Analysis of Toxicities after Total Body Irradiation and Allogeneic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5640
Author(s):  
Michael Oertel ◽  
Jonas Martel ◽  
Jan-Henrik Mikesch ◽  
Sergiu Scobioala ◽  
Christian Reicherts ◽  
...  
Keyword(s):  
Stem Cell ◽  
Side Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Total Body Irradiation ◽  
Whole Body ◽  
Total Body

Total body irradiation is an effective conditioning modality before autologous or allogeneic stem cell transplantation. With the whole body being the radiation target volume, a diverse spectrum of toxicities has been reported. This fact prompted us to investigate the long-term sequelae of this treatment concept in a large patient cohort. Overall, 322 patients with acute leukemia or myelodysplastic syndrome with a minimum follow-up of one year were included (the median follow-up in this study was 68 months). Pulmonary, cardiac, ocular, neurological and renal toxicities were observed in 23.9%, 14.0%, 23.6%, 23.9% and 20.2% of all patients, respectively. The majority of these side effects were grades 1 and 2 (64.9–89.2% of all toxicities in the respective categories). The use of 12 Gray total body irradiation resulted in a significant increase in ocular toxicities (p = 0.013) and severe mucositis (p < 0.001). Renal toxicities were influenced by the age at transplantation (relative risk: 1.06, p < 0.001) and disease entity. In summary, total body irradiation triggers a multifaceted, but manageable, toxicity profile. Except for ocular toxicities and mucositis, a 12 Gray regimen did not lead to an increase in long-term side effects.

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