The activity of mate saponins (Ilex paraguariensis) in intra-abdominal and epididymal fat,and glucose oxidation in male Wistar rats

Ethnopharmacological relevance

Ilex paraguariensis A. St. Hilaire (mate) has traditionally been used in several South American countries to prepare tea-like beverages having stimulant effects on the CNS and appetite. In recent years, however, mate preparations have been recommended putatively as an appetite suppressant and slimming remedy. Moreover, studies carried out on either normal or diet-induced obese rats treated with mate extracts revealed anti-obesity and satiety effects, thus refuting ethnopharmacological data. In this work, the effect of mate on the intra-abdominal and epididymal fat, and glucose oxidation levels after oral administration in male Wistar rats, was studied using crude extract from leaves, unripe fruits, and a chemically well-defined purified saponin fraction (MSF).

Material and methods

Saponin, polyphenol and methylxanthine contents in MSF were analyzed by HPLC-PDA and UPLC/Q-TOF-MS. Crude extracts from mate leaves (LAE) and unripe fruits (FHE) were assayed for comparison purposes. Male Wistar rats fed with standard diet and water ad libitum were used as the control group.

Results

The fat weight and both liver and adipose glucose oxidation were reduced significantly by MSF (35, 90 and 60%, respectively), while LAE and FHE were less active. Also, a significant lowering of the blood triglycerides level was observed in rats treated with MSF and LAE. All creatinine, urea, and transaminase plasma levels remained unaffected no matter what mate preparation was considered. It is also worth pointing out that the glucose blood level was increased after treatment with FHE. This finding did not correlate either with the content of methylxanthines, polyphenols or saponins.

Conclusion

A reduction in both visceral fat weight and glucose oxidation of hepatic and adipose tissue in healthy rats fed with a standard diet could be ascribed to a purified mate saponin fraction from unripe fruits. These findings agree with former studies carried out with crude mate extracts and also suggest their potential use as an anti-obesity preparation. Nonetheless, further in vivo experiments are still required to corroborate its effect on human beings.     

Towards a better understanding of medicinal uses of the brown seaweed Sargassum in Traditional Chinese Medicine: a phytochemical and pharmacological review

Ethnopharmacological relevance

For nearly 2000 years Sargassum spp., a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including thyroid disease (e.g. goitre).

Aims of the review

To assess the scientific evidence for therapeutic claims made for Sargassum spp. in TCM and to identify future research needs.

Background and methods

A systematic search for the use of Sargassum in classical TCM books was conducted and linked to a search for modern phytochemical and pharmacological data on Sargassum spp. retrieved from PubMed, Web of Knowledge, SciFinder Scholar and CNKI (in Chinese).

Results and discussion

The therapeutic effects of Sargassum spp. are scientifically plausible and may be explained partially by key in vivo and in vitro pharmacological activities of Sargassum, such as anticancer, anti-inflammatory, antibacterial and antiviral activities. Although the mechanism of actions is still not clear, the pharmacological activities could be mainly attributed to the major biologically active metabolites, meroterpenoids, phlorotanins and fucoidans. The contribution of iodine in Sargassum for treating thyroid related diseases seem to have been over estimated.

Conclusions

The bioactive compounds in Sargassum spp. appear to play a role as immunomodulators and could be useful in the treatment of thyroid related diseases such as Hashimoto's thyroiditis. Further research is required to determine both the preventative and therapeutic role of Sargassum spp. in thyroid health.     

Placental transfer of melamine and its effects on rat dams and fetuses

In 2008, an epidemic of cases of renal failure among Chinese infants, due to melamine contamination of milk, raised international concern. Thus, numerous studies on the metabolism of melamine were broadly undertaken. However, little is known about placental transfer of melamine. In this study, the possibility of placental transfer of melamine and its effects on fetuses and pregnant dams were determined. Melamine was respectively administered at 0, 40 and 400 mg/kg body weight by daily gavage from gestation day (GD) 13 to GD 20 to control (C), low melamine (LM) and high melamine (HM) groups of pregnant female F344 rats. Rats were sacrificed 30 min after the last gavage. Melamine was not detected in any of the control and placental samples, or in amniotic fluid from the LM group. Plasma and fetal melamine concentrations in the HM group were significantly higher than in the LM group (P < 0.01). Liver enzyme determination revealed no differences among the three groups. However, plasma creatinine, plasma uric acid and blood urea nitrogen concentrations in dams were significantly increased by melamine (P < 0.05). These results show that ingested melamine affects renal function in dams and dose-dependently passes the placental barrier to reach the fetus.     

Safety and Efficacy of Edoxaban,an Oral Factor Xa Inhibitor,Versus Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty: The STARS E-3 Trial

Introduction

This phase 3 trial compared the safety and efficacy of edoxaban, an oral direct factor Xa inhibitor, with enoxaparin sodium (enoxaparin) for thromboprophylaxis after total knee arthroplasty (TKA) in patients in Japan and Taiwan.

Materials and methods

In this randomized, double-blind, double-dummy study, patients received oral edoxaban 30 mg once daily beginning 6 to 24 hours postsurgery or enoxaparin 2000 IU (equivalent to 20 mg) subcutaneously twice daily beginning 24 to 36 hours postsurgery for 11 to 14 days. The primary efficacy endpoint was the composite of symptomatic pulmonary embolism and symptomatic and asymptomatic deep vein thrombosis. Safety endpoints included the incidence of major bleeding, clinically relevant non-major (CRNM) bleeding, major bleeding or CRNM bleeding, all bleeding events, adverse events, and adverse drug reactions.

Results

Of 716 patients enrolled, 360 and 356 were randomized to receive edoxaban or enoxaparin, respectively. The primary efficacy outcome occurred in 22/299 (7.4%) and 41/295 (13.9%) patients in the edoxaban and enoxaparin groups, respectively (relative risk reduction = 46.8%), indicating non-inferiority (P < 0.001) and superiority (P = 0.010) of edoxaban versus enoxaparin. In the edoxaban and enoxaparin groups, major bleeding occurred in 4/354 (1.1%) versus 1/349 (0.3%) patients (P = 0.373); major or CRNM bleeding occurred in 22/354 (6.2%) versus 13/349 (3.7%) patients (P = 0.129), respectively.

Conclusions

Edoxaban 30 mg once daily was more effective for thromboprophylaxis than subcutaneous enoxaparin 2000 IU twice daily following TKA and demonstrated a similar incidence of bleeding events.     

Evaluation of sodium acetate as a source of alkali therapy in an experimental aerobic model of lactic acidosis due to decreased pyruvate oxidation

An “in vitro” model of one type of lactic acidosis was produced in rat hemi-diaphragms with inhibitors of pyruvate oxidation. In order to obtain this inhibition in the absence of hypoxia, two actions were sought; inhibiting the mitochondrial pyruvate transporter and lowering the rate of pyruvate diffusion into these mitochondria. α-Cyano-3-hydroxy cinnamate (CNCM) was utilized because it is a specific inhibitor of the mitochondrial pyruvate transporter. Aminooxyacetate (AOA) was employed because it leads indirectly to inhibition of the entry of cytoplasmic reducing power into mitochondria. As a result of the addition of this latter compound, pyruvate levels fell and this should decrease the rate of pyruvate diffusion into the mitochondria. Glucose was the only substrate provided to this tissue and its entry into the cells was promoted by insulin. The oxidation of U-¹⁴C glucose to ¹⁴CO₂ was significantly reduced in the presence of CNCM and AOA, presumably reflecting the inhibition of pyruvate oxidation. Under these conditions, lactate accumulated and pyruvate fell; however, there was a significant accumulation of lactate plus pyruvate during the incubation period. This “in vitro” lactic acidosis was markedly diminished when acetate was also present. These results are consistent with the hypothesis that provision of an alternate substrate to the TCA cycle for ATP synthesis could lead to a decreased rate of glycolysis and thereby to a decreased rate of lactic acid accumulation in this “in vitro” model of lactic acidosis.     

Ninety-day toxicity of photomirex in the male rat.

Photomirex (8-monohydromirex) is a demonstrated environmental contaminant and was observed in previous short-term studies to produce lesions in the liver, thyroid and testes of male rats. The present study was undertaken to confirm those observations and to determine the effects after a longer period of exposure. Male rats were fed photomirex for 13 weeks at levels of 0.20, 1.0, 5.0, 25 and 125 ppm in the diet. Deaths were observed in animals receiving the highest dose. Decreased body weight gain and food intake were also observed in that group. Liver weights were increased at 5.0 ppm photomirex and higher. Photomirex caused changes in several biochemical parameters including serum sorbitol dehydrogenase and hepatic aniline hydroxylase activities. Dose-related histological abnormalities were observed in the thyroid and liver starting at the lowest dose level. These results confirm earlier findings and show that photomirex is a potent hepato- and thyrotoxin.     

Long-term toxicity study of methylmercuric chloride in monkeys (First report)

Groups of 5 male monkeys were fed 0, 0.01, 0.03, 0.1 and 0.3 mg/kg/day of methylmercuric chloride (MMC) (as Hg) for 2 years. In the group of 0.3 and 0.1 mg/kg/day there appeared toxic signs including characteristic neurological symptoms at 62 and 182 days respectively, during which the total amount of MMC as Hg ingested was 15.3 and 15.9 mg/kg respectively. On the other hand, no toxic signs except a slight reduction in body-weight gain, were observed in the group of 0.03 and 0.01 mg/kg/day, though a total amount of 18.4 mg/kg was ingested by the group of 0.03 mg/kg/day during 2 years. Neither were there any significant alterations in the hematological and blood biochemical examinations at the two lower dose levels.The mercury content in the hair showed a good correlation with the daily dose of MMC, especially in the dose range of 0.01 to 0.1 mg/kg/day. All animals of the group of 0.1 and 0.3 mg/kg/day had mercury exceeding 100 ppm in the hair at the time of onset of toxic symptoms. The mercury content in the hair in the group of 0.03 and 0.01 mg/kg/day increased gradually, reaching the level of 82.5 and 58.4 ppm respectively on the 541st day. The study is still in progress.     

维生素E对低温暴露大鼠血清GPT、GOT和LDH活性的影响

本实验观察补充维生素E的大鼠低温暴露后血清GPT、GOT和LDH活性的变化,探索维生素E对低温暴露动物的影响。将体重70～120g雄性大鼠随机分为甲、乙、丙三组,饲以基础饲料,甲组动物每两天腹腔注射维生素E5mg(5mg/ml),5次(10天)后,将甲、丙两组移入低温室(-1±1℃)连续暴露48小时,乙组作为常温对照留在室温下(20±1℃)。低温暴露结束时,立即测定三组动物血清中GPT、GOT和LDH活性。结果是:丙组动物血清中三种酶活性最高,乙组最低,甲组稍高于乙组但明显低于丙组。说明低温暴露动物补充维生素E后血清中三种酶活性稍有改善。     

Enzymatic characterization of E.U.E. (embryonal human explants) cells adapted to hypertonic media

E.U.E. cells (general population) were submitted to biochemical and cytoenzymatic tests to compare the enzymatic profile of E.U.E. cells (controls) with that of E.U.E. adapted to hypertonic medium. The adapted cells are characterized by very high oxoreductase activity (LDH, HBDH, G-6-P DH) and very high alkaline-phosphatase activity. Clones derived from general population were also submitted to biochemical tests to characterize those more strictly related to the enzymatic profile of adapted cells. The profile of clone N. 13 resembles on this respect that of the adapted cells. The high redox activity is a prerequisite supporting energy supply for osmotic work. The increased activity of plasma membrane enzymes of the adapted cells is also demonstrable in cells exposed for short time to salinity.     

鹿血口服液对大鼠体内代谢影响的实验研究

目的：探讨鹿血口服液对体内过氧化脂质代谢和氨基酸代谢的影响。方法：取大鼠60只，随机分为对照组、中剂量鹿血口服液组和大剂量鹿血口服液组，给药一定时间后分别测定肝、血过氧化脂质、血谷丙转氨酯、血谷草转氨酶含量。结果：中剂量鹿血口服液组和大剂量鹿血口服液组中大鼠血、肝过氧化脂质台量显降低，而血谷丙转氨酶、血谷草转氨酶含量元显变化。结论：鹿血口服液对过氧化脂质代谢有显影响，可以降低体内过氧化脂质含量，对氨基酸代谢元显影响。