The Protein-Rich Fraction from Spirulina platensis Exerts Neuroprotection in Hemiparkinsonian Rats by Decreasing Brain Inflammatory-Related Enzymes and Glial Fibrillary Acidic Protein Expressions.

Spirulina platensis is a cyanobacterium with high protein content and presenting neuroprotective effects. Now, we studied a protein-enriched fraction (SPF), on behavior, neurochemical and immunohistochemical (IHC) assays in hemiparkinsonian rats, distributed into the groups: SO (sham-operated), 6-hydroxydopamine (6-OHDA), and 6-OHDA (treated with SPF, 5 and 10 mg/kg, p.o., 15 days). Afterward, animals were subjected to behavioral tests and euthanized, and brain areas used for neurochemical and IHC assays. SPF partly reversed the changes in the apomorphine-induced rotations, open field and forced swim tests, and also the decrease in striatal dopamine and 3,4-dihydroxyphenylacetic acid contents seen in hemiparkinsonian rats. Furthermore, SPF reduced brain oxidative stress and increased striatal expressions of tyrosine hydroxylase and dopamine transporter and significantly reduced hippocampal inducible nitric oxide synthase, cyclooxygenase-2 and glial fibrillary acidic protein expressions. The data suggest that the protein fraction from S. platensis, through its brain anti-inflammatory and antioxidative actions, exerts neuroprotective effects that could benefit patients affected by neurodegenerative diseases, like Parkinson's disease.

Diet Supplementation with Fish-Derived Extracts Suppresses Diabetes and Modulates Intestinal Microbiome in a Murine Model of Diet-Induced Obesity.

Metabolic syndrome-related diseases affect millions of people worldwide. It is well established that changes in nutritional habits and lifestyle can improve or prevent metabolic-related pathologies such as type-2 diabetes and obesity. Previous reports have shown that nutritional supplements have the capacity to limit glucose intolerance and suppress diabetes development. In this study, we investigated the effect of dietary supplementation with fish-derived extracts on obesity and type 2 diabetes and their impact on gut microbial composition. We showed that nutritional supplements containing Fish Complex (FC), Fish Complex combined with Cod Powder (FC + CP), or Cod Powder combined with Collagen (CP + C) improved glucose intolerance, independent of abdominal fat accumulation, in a mouse model of diet-induced obesity and type 2 diabetes. In addition, collagen-containing supplements distinctly modulate the gut microbiome in high-fat induced obesity in mice. Our results suggest that fish-derived supplements suppress diet-induced type 2 diabetes, which may be partly mediated through changes in the gut microbiome. Thus, fish-derived supplements and particularly the ones containing fish collagen have potential beneficial properties as dietary supplements in managing type 2 diabetes and metabolic syndrome via modulation of the gut microbiome.

Network pharmacology integrated with experimental validation reveals the regulatory mechanism of plastrum testudinis in treating senile osteoporosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plastrum testudinis (PT) has been used in traditional Chinese medicine to treat bone diseases such as senile osteoporosis (SOP) for thousands of years. However, the underlying mechanisms remain largely unknown. AIM OF THE STUDY: This study aims to investigate the possible molecular mechanism of PT in the treatment of SOP using an integrated strategy of network pharmacology and experimental validation. MATERIALS AND METHODS: The compounds of PT and its targets were identified through the BATMAN-TCM database. The SOP-related targets were retrieved from the GeneCards database. Protein-protein interaction information was obtained by inputting the intersection targets into the STRING database. Cytoscape software was used to construct a protein-protein interaction network and a PT-compound-target-SOP network. Using Cytoscape and R software, we conducted GO function and KEGG pathway enrichment analyses. We also conducted in vivo and in vitro experiments to verify the network pharmacology findings. RESULTS: In total, 6 active compounds and 342 targets of PT were screened, of which 57 common targets were related to SOP. The GO biological process enrichment analysis identified 880 entries, mainly relating to the regulation of hormone response, the cell apoptotic process, the apoptotic signaling pathway, NF-kappaB transcription factor activity, fatty acid transportation, osteoclast differentiation, macrophage activation, and inflammatory response. The KEGG pathway enrichment analysis identified 52 entries, including 14 related signaling pathways, which mainly involved the TNF, MAPK, IL-17, AGE-RAGE, estrogen, relaxin, and other signaling pathways. Our in vivo experiments confirmed that PT alleviates SOP, while the in vitro experiments demonstrated that PT exerts a suppressive effect on osteoclast differentiation and bone resorption in a concentration-dependent manner. Furthermore, we observed that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway. CONCLUSION: Through network pharmacology and experimental validation, this study is the first to report that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway, thus exerting a suppressive effect on osteoclast differentiation and bone resorption, which may be the molecular mechanism for PT treatment of SOP.

Plastrum testudinis extract suppresses osteoclast differentiation via the NF-κB signaling pathway and ameliorates senile osteoporosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plastrum testudinis (PT) is a kind of single traditional Chinese medicine that can tonify kidney and strengthen bone. Plastrum testudinis extract (PTE) has been approved to promote the osteogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. However, the mechanism by which PTE reduces osteoclast differentiation has not yet been reported. AIM OF THE STUDY: To explore the potential of PTE as a therapeutic treatment for bone loss caused by senile osteoporosis (SOP). MATERIALS AND METHODS: We evaluated whether PTE could inhibit RANKL-induced osteoclast differentiation both in vitro and in vivo, and investigated PTE-induced phenotypes of human peripheral blood monocytes. RESULTS: We found that PTE inhibited osteoclast differentiation and bone resorption in vitro in a concentration-dependent manner and that PTE treatment is most effective during the early stages of osteoclastogenesis. Moreover, we found that PTE could block the NF-κB signaling pathway in vitro, leading to the down-regulation of osteoclast-specific genes including C-FOS and NFATC1. The results from our in vivo mouse study suggest that PTE treatment suppresses osteoclast formation and mitigates bone loss caused by SOP. Notably, we also found that PTE inhibited RANKL-induced osteoclast differentiation in human peripheral blood monocytes. CONCLUSION: Our results suggest that PTE treatment suppresses osteoclastogenesis and ameliorates bone loss caused by SOP by selectively blocking the nuclear translocation of NF-κB/p50.

Remedies of animal origin and their indications in Nikolaos Myrepsos׳ Dynameron.

ETHNOPHARMACOLOGICAL RELEVANCE: Dynameron is a Byzantine medical compendium, divided into 24 sections, in accordance with the letters of the Greek alphabet. Being the largest medical and pharmaceutical book ever written in Byzantium, Dynameron contains 2667 recipes intended to treat many pathological conditions. A lot of information convey to us through prescriptions. In addition to plants, Nikolaos Myrepsos proposes the use of many animals, animal parts and animal by-products, for the treatment of various diseases. This article presents for the first time a full account of the animal products included in Dynameron. AIM OF THE STUDY: In continuation to our previous studies, this paper focuses on the use of animal products in composite medicines described in Dynameron. An effort was made to trace down the use of similar or identical animal products in texts of earlier medical writers. Recording recipes with animals or animal products intended for use in everyday medical practice highlights the timeless belief in their healing properties. MATERIALS AND METHODS: Our main source of material is the recent digital edition of Nikolaos Myrepsos' Dynameron. This huge treatise was written in the 13th century and reflects in many ways the long medical tradition of the Greek, the Hellenistic and the Roman eras, having also received influences from the materia medica of Arabic medicine. In addition, information from dictionaries and databases were cross-checked to confirm and classify the animals and their products and to identify them. For the various pathological conditions these products are meant for, we have used the current medical terminology. RESULTS: In the present study, we could identify the therapeutic use of 93 animals. In several instances, Myrepsos suggests the use of specific organs of an animal, and for that reason he includes in his treatise 16 anatomical parts of different animals. Moreover, Dynameron comprises also 34 animal by-products, such as milk and honey. Medicines of animal origin are used in recipes concerning diseases of the respiratory, the digestive, the cardiovascular and the urinary system, as well as gynecological diseases, and ailments of the eyes, the ears and the skin. CONCLUSIONS: Of the 2667 recipes of Dynameron, 344 recipes contain medicines of animal origin, which can be detected in totally 769 citations. In addition, 626 citations for animal by-products are found in 268 recipes. Honey and milk are quoted in 2136 recipes, mostly as excipients. Dietary instructions are present on many occasions, reflecting the attitude for a healthy everyday life, similar to the modern beliefs pertaining to food as an essential factor for a good health.

Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review.

Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis and malignant tumors share similar characteristics (progressive, invasive, estrogen-dependent growth, and recurrence), animal toxins and venoms are thought to be effective against endometriosis. The objective of this study was to outline studies using toxic animal-based medicinal materials (TMM) as endometriosis treatment and to explore its clinical applicability. Preclinical and clinical studies using TMM were searched for in four databases from inception to October 2020. A total of 20 studies of TMM on endometriosis were included. In eight clinical studies, herbal medicines containing TMM were effective in relieving symptoms of endometriosis, with no side effects. In twelve experimental studies, the main therapeutic mechanisms of TMM against endometriosis were proapoptotic, antiangiogenesis, estrogen level-reducing, and possible anti-inflammatory effects. TMM are thus considered promising sources for the development of an effective treatment method for endometriosis. Further studies are needed to clarify the therapeutic mechanism of TMM against endometriosis and to provide sufficient grounds for clinical application.

Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats.

Erectile dysfunction (ED) is one of the significant complications of diabetes mellitus (DM), and CASR plays an important role in cellular antiapoptosis and NO production in the vascular endothelium by activating PKC. The present study was aimed to investigate the efficacy of Leech and Centipede Granules (LCG) through the CaSR/PLC/PKC signaling. Fifty male Sprague-Dawley rats were treated with streptozotocin to induce the DM model. After 10 weeks, an apomorphine test was used to confirm DMED. Rats with DMED were administrated with LCG and U73122 for 4 weeks. Fasting blood glucose, body weight, insulin and glucagon levels were measured. Erectile function in rats was assessed by apomorphine. Serums were measured using enzyme-linked immunosorbent assay and flow cytometry, and penile tissues were harvested for histologic and the expression of related targets analyses. After treatment, fasting blood glucose, body weight, insulin, glucagon levels, and erectile function were significantly ameliorated in the LCG groups. The LOX-1, NOX, and EMPs concentrations were significantly decreased with LCG treatment. LCG also continuously increased NO and decreased ET-1 content in penile tissues. LCG and U73122 administration also improved penile fibrosis by significantly decreasing VCAM-1, ICAM-1, and CD62P. The data also showed that LCG reduced the apoptosis level in the penis. Furthermore, the inhibited activation of the CaSR/PLC/PKC pathway was observed in DMED rats with LCG treatment. Collectively, LCG significantly ameliorated erectile function of DMED rats via increased NO generation, inhibiting endothelial cells apoptosis and penile fibrosis, which might benefit from the suppression of CaSR/PLC/PKC pathway in DMED rats.

Plastrum Testudinis Extract Mitigates Thiram Toxicity in Broilers via Regulating PI3K/AKT Signaling.

Tibial dyschondroplasia (TD) negatively affects broilers all over the world, in which the accretion of the growth plate (GP) develops into tibial proximal metaphysis. Plastrum testudinis extract (PTE) is renowned as a powerful antioxidant, anti-inflammatory, and bone healing agent. The current study was conducted to evaluate the efficacy of PTE for the treatment of thiram-induced TD chickens. Broilers (day old; n = 300) were raised for 3 days with normal feed. On the 4th day, three groups (n = 100 each) were sorted, namely, the control (normal diet), TD, and PTE groups (normal diet+ thiram 50 mg/kg). On the 7th day, thiram was stopped in the TD and PTE group, and the PTE group received a normal diet and PTE (30 mg/kg/day). Plastrum testudinis extract significantly restored (p < 0.05) the liver antioxidant enzymes, inflammatory cytokines, serum biochemicals, GP width, and tibia weight as compared to the TD group. The PTE administration significantly increased (p < 0.05) growth performance, vascularization, AKT (serine/threonine-protein kinase), and PI3K expressions and the number of hepatocytes and chondrocytes with intact nuclei were enhanced. In conclusion, PTE has the potential to heal TD lesions and act as an antioxidant and anti-inflammatory drug in chickens exposed to thiram via the upregulation of AKT and PI3K expressions.

Dietary Supplementation with Sea Bass (Lateolabrax maculatus) Ameliorates Ulcerative Colitis and Inflammation in Macrophages through Inhibiting Toll-Like Receptor 4-Linked Pathways.

Sea bass (Lateolabrax maculatus) is a kind of food material commonly consumed in daily life. In traditional Chinese medicinal books, it has been indicated that sea bass can be applied for managing many inflammation-associated conditions. However, the studies on the pharmacological mechanisms of inflammation of sea bass remain scarce. Hence, this study aims to investigate the molecular mechanisms of the anti-inflammatory activity of sea bass. Anti-inflammatory activities of sea bass were assessed using dextran sulfate sodium (DSS)-induced colitis in a mice model and lipopolysaccharide (LPS)-activated macrophages model. Low body weight and short colon length were observed in DSS-fed mice that were significantly recovered upon sea bass treatments. Moreover, the colon histopathology score showed that sea bass-treated mice had decreased crypt damage, focal inflammation infiltration and the extent of inflammation, suggesting that treatment with sea bass could attenuate intestinal inflammation. In addition, the in-vitro study conjointly indicated that sea bass could suppress the inflammatory mediators in LPS-activated macrophage by inhibiting the TLR4-linked pathway. The present findings demonstrated that sea bass has an inhibitory effect on TLR4 signaling; thus, it could be a promising candidate for treating inflammation-associated conditions. A further justification for the clinical application of sea bass in treating inflammation-associated conditions is necessary.

Freshwater clam extract reduces liver injury by lowering cholesterol accumulation, improving dysregulated cholesterol synthesis and alleviating inflammation in high-fat, high-cholesterol and cholic acid diet-induced steatohepatitis in mice.

Freshwater clam (Corbicula fluminea) is a traditional liver-protective food in Asia. Recent studies have renewed attention on high cholesterol accumulation and dysregulated cholesterol synthesis in the liver as a critical factor in the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH). In this study, we investigated the protective effects of freshwater clam extract (FCE) and its fat fraction (FCE oil) on high-fat, high-cholesterol and cholic acid (HFHC) diet-induced lean steatohepatitis in mice. Mice were fed a HFHC diet containing FCE or FCE oil for 6 weeks. FCE, but not FCE oil, feeding reduced liver injury as indicated by decreased plasma alanine aminotransferase activity. Liver total cholesterol accumulation was reduced after FCE and FCE oil treatment. Accumulation of squalene and desmosterol, the precursors of cholesterol, in the liver was reduced by FCE but not by FCE oil. The caspase-1 (p10) and interleukin (IL)-1ß (p17) protein expressions in the liver were suppressed by both FCE and FCE oil. Therefore, FCE may act as functional food that can reduce steatohepatitis and liver injury by reducing cholesterol accumulation, improving dysregulated cholesterol synthesis and attenuating inflammation.

Hominis placenta Suppresses Acute Lung Inflammation by Activating Nrf2.

Hominis placenta (HP), a dried human placenta, has been known to target liver, lung, or kidney meridians, improving the functions associated with these meridians in traditional Chinese or Asian medicine (TCM). Since recent studies implicate an HP extract in suppressing inflammation, we investigated whether an aqueous HP extract can ameliorate inflammation that occurred in the lungs. When administered with a single intratracheal lipopolysaccharide (LPS), C57BL/6 mice developed an acute neutrophilic lung inflammation along with an increased expression of pro-inflammatory cytokine genes. However, this was diminished by the administration HP extract via an intraperitoneal route 2 h after LPS treatment. Western blot and semi-quantitative RT-PCR analyses revealed that while suppressing the activity of a proinflammatory factor NF-[Formula: see text]B marginally, the HP extract strongly activated an anti-inflammatory factor Nrf2, with concomitant expression of Nrf2-dependent genes. Mechanistically, the HP extract suppressed the ubiquitin-mediated degradation of Nrf2, functioning similarly to a 26S proteasome inhibitor, MG132. Collectively, these results suggest that the HP extract suppresses inflammation in mouse lungs, which is in part related to the HP extract perturbing the ubiquitin-dependent degradation of Nrf2 and thus increasing the function of Nrf2.

Alleviation of Hippocampal Endoplasmic Reticulum Stress by Allomyrina dichotoma Larvae Extract.

In the brain, endoplasmic reticulum (ER) stress results in synaptic dysfunction and eventually leads to neurodegeneration. Allomyrina dichotoma larvae are a Chinese ethnomedicine and are widely used in East Asia. In the present study, we investigated the ability of ethanol extract of A. dichotoma larvae (ADE) to improve synaptic structure and function by activating unfolded protein response (UPR) under ER stress in animal and neuron culture models. ER stress was induced in obese mice fed a high fat diet (HFD) or by treating dissociated cultures of rat embryonic (E19) hippocampal neurons with tunicamycin (TM). Western blot and real-time or conventional RT-PCR were performed to analyze the expressions of ER stress marker proteins. In dissociated hippocampal cultures, immunocytochemistry was performed for synaptic proteins, and cultures were stained with styryl dye FM1-43 to assess presynaptic activities. In HFD-fed obese mice, ADE efficiently reduced the expressions of ER stress markers, such as, xbp-1, chop, atf4, erdi4, and eIf2a, and those of the ER chaperone/foldases Bip/grp78, Ero-1l, and PDI. Unconventionally spliced xbp-1s mRNA was not detected. In primary rat hippocampal cultures under ER stress, ADE significantly lowered the nuclear expression of CHOP, inhibited the downregulations of postsynaptic proteins, such as, GluN2A, GluN2B, and PSD-95, and maintained the pool size of recycling presynaptic vesicles. The study shows that ADE potently suppressed the induction of ER stress and maintained the structure and function of hippocampal neurons, and suggests that ADE is a potentially valuable food supplement and preventive therapeutic for ER stress-related nervous disorders.

How to design preclinical studies in nanomedicine and cell therapy to maximize the prospects of clinical translation.

The clinical translation of promising products, technologies and interventions from the disciplines of nanomedicine and cell therapy has been slow and inefficient. In part, translation has been hampered by suboptimal research practices that propagate biases and hinder reproducibility. These include the publication of small and underpowered preclinical studies, suboptimal study design (in particular, biased allocation of experimental groups, experimenter bias and lack of necessary controls), the use of uncharacterized or poorly characterized materials, poor understanding of the relevant biology and mechanisms, poor use of statistics, large between-model heterogeneity, absence of replication, lack of interdisciplinarity, poor scientific training in study design and methods, a culture that does not incentivize transparency and sharing, poor or selective reporting, misaligned incentives and rewards, high costs of materials and protocols, and complexity of the developed products, technologies and interventions. In this Perspective, we discuss special manifestations of these problems in nanomedicine and in cell therapy, and describe mitigating strategies. Progress on reducing bias and enhancing reproducibility early on ought to enhance the translational potential of biomedical findings and technologies.

Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms.

Silicosis is an occupational pulmonary fibrosis caused by inhalation of silica (SiO2) and there are no ideal drugs to treat this disease. Earthworm extract (EE), a natural nutrient, has been reported to have anti-inflammatory, antioxidant, and anti-apoptosis effects. The purpose of the current study was to test the protective effects of EE against SiO2-induced pulmonary fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. We found that treatment with EE significantly reduced lung inflammation and fibrosis and improved lung structure and function in SiO2-instilled mice. Further mechanistic investigations revealed that EE administration markedly inhibited SiO2-induced oxidative stress, mitochondrial apoptotic pathway, and epithelial-mesenchymal transition in HBE and A549 cells. Furthermore, we demonstrate that Nrf2 activation partly mediates the interventional effects of EE against SiO2-induced pulmonary fibrosis. Our study has identified EE to be a potential anti-oxidative, anti-inflammatory, and anti-fibrotic drug for silicosis.

Extracts from plastrum testudinis reverse glucocorticoid-induced spinal osteoporosis of rats via targeting osteoblastic and osteoclastic markers.

Extracts from plastrum testudinis (PTE), an important traditional Chinese medicine, have been demonstrated promotion of osteoblastic function in vitro. This study aims to investigate the protective effect of PTE on glucocorticoid-induced osteoporosis(GIOP) in vivo and analyze therapeutic targets of PTE on GIOP. SD rats were randomly assigned to two experiments: preventive and therapeutic experiments, in which rats respectively received oral PTE at the same time of glucocorticoid injection or after glucocorticoid injection inducing osteoporosis. BMD, microarchitecture, biomechanics, bone metabolism markers and histomorphology were evaluated. mRNA and protein expression of OPG, Runx2, CTSK and MMP9 were examined.Results showed bone quality and bone quantity were significantly elevated by PTE. Histomorphometry showed thicker and denser bone trabecularsand more osteoblasts and less osteoclasts in group of PTE intervention. The mRNA expression of OPG was significantly upregulated whereas expression of CTSK was significantly downregulatedin different groups of PTE intervention. Stronger immunostaining for Runx2 and weaker immunostaining for CTSK were observed in groups of PTE intervention. This demonstrated that PTE may reverse GIOP in prevention and management via targeting OPG, Runx2 and CTSK in mRNA and protein levels.

Uromastyx acanthinura as a natural treatment in a mouse model of type 2 diabetes / Uromastyx acanthinura como tratamiento natural en un modelo murino de diabetes tipo 2

Aims: Oral testimonies from North Africa attribute anti-diabetic effects to medicinal preparations of the lizard Uromastyx acanthinura (UA). No scientific evidence of such effects is currently available. The acute effects of oral administration of UA to C57Bl/6J mice with diet-induced diabetes were tested and, if effectiveness was shown, the effect of subchronic UA administration was assessed in the same model. Methods: Mice were fed a diet containing 60% fat for at least 12 weeks. To assess acute effects, different doses of UA or saline were orally administered with 2 g of glucose/kg during an oral glucose tolerance test (OGTT) on different days in a randomised crossover design. The most effective dose was then fed together with the high-fat diet for 90 days and compared to high-fat diet alone in a parallel design. Body weight (BW), food consumption, welfare, and external appearance were assessed weekly. HbA1c, OGTT, and intraperitoneal insulin tolerance tests (IPITT) were performed at baseline and after treatment. Severity of neuropathy was evaluated by cold allodynia response in the acetone test. Results: UA significantly decreased glucose levels as compared to saline 15 min after administration. After 90 days of treatment, no differences were seen in OGTT or HbA1c between the groups, while IPITT showed higher glucose levels in UA-treated animals. Although weight increase was similar in both groups, weight tended to be higher in the treated group, which had a significantly higher daily food consumption. Cold allodynia response improved in frequency and intensity in the UA group. Conclusions: Orally administered UA acutely decreased blood glucose in diabetic mice. Paradoxically, long-term administration of UA increased food consumption, weight, and insulin resistance. Improved nociceptive response suggested an effect on pain and/or neuropathy. Although additional studies are needed to elucidate the properties and potential applications of UA, our results highlight the value of ethnomedical approaches to African traditional medicine as starting point to evaluate new bioactive components (AU)

Objetivos: Testimonios orales Norteafricanos atribuyen efectos hipoglucemiantes a preparados medicinales del lagarto Uromastyx acanthinura (UA), para los que no existen evidencias científicas actualmente. El objetivo de este trabajo fue el de investigar los efectos agudos de UA administrado oralmente en ratones diabéticos C57Bl/6J inducidos por dieta grasa, y si se demostrase su efectividad evaluar el efecto de su administración subcrónica en el mismo modelo animal. Métodos: Fue administrada una dieta a los animales con un contenido graso del 60% durante al menos 12 semanas. Para evaluar los efectos agudos diferentes dosis de UA o suero salino fueron administrados conjuntamente con 2 g/kg de glucosa durante sobrecargas orales de glucosa (SOG), en diferentes días, siguiendo un diseño cruzado aleatorizado. La dosis más efectiva en esta fase fue entonces administrada mezclada en la dieta durante 90 días y comparada con dieta solo en un diseño paralelo. El peso corporal y el consumo de alimento fueron evaluados semanalmente. HbA1c, SOG, y test de tolerancia intraperitoneal a la insulina (TTIPI) fueron realizados al inicio y tras el tratamiento. La gravedad de la neuropatía fue determinada mediante la evaluación de la alodinia al frío. Resultados: El UA redujo significativamente las concentraciones de glucosa de manera aguda en comparación con el control a los 15 min tras su administración. Tras 90 días de tratamiento no se observaron diferencias en las SOG o HbA1c entre grupos, mientras que para los test de tolerancia intraperitoneal a la isulina valores más altos de glucosa fueron determinados en los animales tratados con UA. Aunque ambos grupos aumentaron su peso, este tendió a ser mayor en los tratados, que a su vez consumieron significativamente más comida por día. La respuesta a la alodinia al frío mejoró en frecuencia e intensidad en los tratados con UA. Conclusiones: El UA administrado oralmente redujo de manera aguda la glucosa en sangre en ratones con diabetes. Paradójicamente, su administración crónica aumentó el consumo de alimento, el peso y la resistencia a la insulina. La mejora en la respuesta nociceptiva sugiere un efecto en el dolor y/o la neuropatía. Aunque son necesarios más estudios para aclarar las propiedades y posibles aplicaciones de este producto, nuestros resultados subrayan el valor de los enfoques etnomédicos hacia la medicina tradicional africana como origen para la evaluación de nuevos compuestos bioactivos (AU)

Ameliorative effect of Allolobophora caliginosa extract on hepatotoxicity induced by silicon dioxide nanoparticles.

This study aims to evaluate the possible ameliorative effect of earthworm (Allolobophora caliginosa) extract (EE) against silicon dioxide nanoparticles (SiNPs)-induced liver injury in male albino rats. The effectiveness of EE was compared with silymarin as a standard hepatoprotective drug. The present work demonstrates the antioxidant activity of EE by 1,1-diphenyl-2-picrylhydrazyl assay. Administration of SiNPs, for 15 consecutive days, caused changes in most of the biochemical parameters, namely, serum aminotransferase enzymes activities (alanine transaminase and aspartate transaminase), alkaline phosphatase activity, total protein, total and direct bilirubin level, malondialdehyde, glutathione reduced, catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase. In addition, administration of SiNPs induced changes in liver tissue architecture. Administration of EE, for subsequent 30 days, to SiNPs exposure demonstrated significant ameliorative effects on nearly all the studied parameters, and such effects were compatible with those of silymarin. In addition, the administration of EE repairs, to some extent, the abnormal architecture of the liver tissue induced by SiNPs.

Gene expression profiling and inhibition of adipose tissue accumulation of G. bimaculatus extract in rats on high fat diet.

BACKGROUND: Molecular genetic mechanisms underlying the anti-inflammatory effects of ethanol extract (GB) from G. bimaculatus, a type of cricket, are not fully elucidated. G. bimaculatus was reported to be rich in unsaturated fatty acid and to decrease the omega-6/omega-3 fatty acid ratio when fed to chickens. GB may reduce the amount of fat or increase the unsaturated fatty acid ratio. METHODS: Male Wistar rats fed a high-fat diet (HFD) were orally administered with 5 groups: phosphate buffered saline (PBS, control), GB (100 mg/kg or 200 mg/kg), Pravastatin or Isaria sinclairii (IS) extract, which is reported to have fat-reducing effects, for either 1 or 2 months. GB's sero-biochemial, hematological and anti-oxidizing hepato-cellular biomarker levels were evaluated to dertermine their antilipidemic, anti-inflammatory, and anti-coagulant effect in rats after 1 or 2 month GB treatments on HFD (fat 60 %) Wistar rat. The abdominal and epididymidal fat weight were measured and the composition of fatty acid was analyzed by GC/MS. Microarray analyses were performed with a rat 28 K cDNA clone set array to identify the gene-expression profiles for the GB exposed high fat dieted Wistar rat. RESULTS: The weight and fatty acid composition of abdominal fat and epididymidal fat, total cholesterol, LDL-cholesterol, and triglyceride in GB treated rats were at lower levels than those of the control group. The anti-oxidant hepato-cellular biomarker levels, protein carbonyl content and malondialdehyde concentration in GB treated rats were significantly decreased. Compared to the control, the GB treated rat group (treated at a dose of 100 and 200 mg/kg), had 190 up-regulated genes including Gpm6a (glycoprotein m6a), Tmem14a (transmembrane protein 14A) and Fasin (fatty acid synthase), with down-regulated 235 genes including Cc121b (chemokine ligand 21b), Glycan1 (glycosylation dependent cell adhesion moleule, Serpinb1a (serine proteinase inhibitor) and Tcrb (T-cell receptor beta chain). CONCLUSION: The data suggest Fasin-related fatty acid synthesis and adipose differentiation related protein (Adfp), which is related to obesity, were upregulated by GB treatment, indicating their potential therapeutic markers for anti-atheriosclerosis or inflammation.

HISTORICAL AND CURRENT PERSPECTIVE IN THE USE OF THYROID EXTRACTS FOR THE TREATMENT OF HYPOTHYROIDISM.

OBJECTIVE: To describe the history, refinements, implementation, physiology, and clinical outcomes achieved over the past several centuries of thyroid hormone replacement strategies. METHODS: A Medline search was initiated using the following search terms: bioidentical thyroid hormone, thyroid hormone extract, combination thyroxine (T4) and tri-iodothyronine (T3) therapy, homeopathic thyroid hormone therapy, and thyroid hormone replacement. Pertinent articles of interest were identified by title (and where available abstract) for further review. Additional references were identified during a review of the identified literature. RESULTS: A rich history of physician intervention in thyroid dysfunction was identified dating back more than 2 millennia. Although not precisely documented, thyroid ingestion from animal sources had been used for centuries but was finally scientifically described and documented in Europe over 130 years ago. Since the reports by Bettencourt and Murray, there has been a continuous documentation of outcomes, refinement of hormone preparation production, and updating of recommendations for the most effective and safe use of these hormones for relieving the symptoms of hypothyroidism. As the thyroid extract preparations contain both levothyroxine (LT4) and liothyronine (LT3), current guidelines do not endorse their use as controlled studies do not clearly document enhanced objective outcomes compared with LT4 monotherapy. Among current issues cited, the optimum ratio of LT4 to LT3 has yet to be determined, and the U.S. Food and Drug Administration (FDA) does not appear to be monitoring the thyroid hormone ratios or content in extract preparations on the market. Taken together, these limitations are important detriments to the use of thyroid extract products. CONCLUSION: The evolution of thyroid hormone therapies has been significant over the extended period of time they have been in use to treat hypothyroidism. Although numerous websites continue to advocate the use of thyroid hormone extracts as a superior therapy for hypothyroidism, none of the most recent guidelines of major endocrine societies recommend thyroid extract use for hypothyroidism.