Study of anti-fatigue activity of polysaccharide from fruiting bodies of Armillaria gallica.

Fatigue is a common physiological response that is closely related to energy metabolism. Polysaccharides, as excellent dietary supplements, have been proven to have a variety of pharmacological activities. In this study, A 23.007 kDa polysaccharide from Armillaria gallica (AGP) was purified and performed structural characterization, including analysis of homogeneity, molecular weight and monosaccharide composition. Methylation analysis is used to analyze the glycosidic bond composition of AGP. The mouse model of acute fatigue was used to evaluate the anti-fatigue effect of AGP. AGP-treatment improved exercise endurance in mice and reduced fatigue symptoms caused by acute exercise. AGP regulated the levels of adenosine triphosphate, lactic acid, blood urea nitrogen and lactate dehydrogenase, muscle glycogen and liver glycogen of acute fatigue mice. AGP affected the composition of intestinal microbiota, the changes of some intestinal microorganisms are correlated with fatigue and oxidative stress indicators. Meanwhile, AGP reduced oxidative stress levels, increased antioxidant enzyme activity and regulated the AMP-dependent protein kinase/nuclear factor erythroid 2-related factor 2 signaling pathway. AGP exerted an anti-fatigue effect through modulation of oxidative stress, which is related to intestinal microbiota.

Ciprofloxacin and pegylated G-CSF combined therapy mitigates brain hemorrhage and mortality induced by ionizing irradiation.

Introduction: Brain hemorrhage was found between 13 and 16 days after acute whole-body 9.5 Gy 60Co-γ irradiation (IR). This study tested countermeasures mitigating brain hemorrhage and increasing survival from IR. Previously, we found that pegylated G-CSF therapy (PEG) (i.e., Neulasta®, an FDA-approved drug) improved survival post-IR by 20-40%. This study investigated whether Ciprofloxacin (CIP) could enhance PEG-induced survival and whether IR-induced brain hemorrhage could be mitigated by PEG alone or combined with CIP. Methods: B6D2F1 female mice were exposed to 60Co-γ-radiation. CIP was fed to mice for 21 days. PEG was injected on days 1, 8, and 15. 30-day survival and weight loss were studied in mice treated with vehicles, CIP, PEG, or PEG + CIP. For the early time point study, blood and sternums on days 2, 4, 9, and 15 and brains on day 15 post-IR were collected. Platelet numbers, brain hemorrhage, and histopathology were analyzed. The cerebellum/pons/medulla oblongata were detected with glial fibrillary acidic protein (GFAP), p53, p16, interleukin-18 (IL-18), ICAM1, Claudin 2, ZO-1, and complement protein 3 (C3). Results: CIP + PEG enhanced survival after IR by 85% vs. the 30% improvement by PEG alone. IR depleted platelets, which was mitigated by PEG or CIP + PEG. Brain hemorrhage, both surface and intracranial, was observed, whereas the sham mice displayed no hemorrhage. CIP or CIP + PEG significantly mitigated brain hemorrhage. IR reduced GFAP levels that were recovered by CIP or CIP + PEG, but not by PEG alone. IR increased IL-18 levels on day 4 only, which was inhibited by CIP alone, PEG alone, or PEG + CIP. IR increased C3 on day 4 and day 15 and that coincided with the occurrence of brain hemorrhage on day 15. IR increased phosphorylated p53 and p53 levels, which was mitigated by CIP, PEG or PEG + CIP. P16, Claudin 2, and ZO-1 were not altered; ICAM1 was increased. Discussion: CIP + PEG enhanced survival post-IR more than PEG alone. The Concurrence of brain hemorrhage, C3 increases and p53 activation post-IR suggests their involvement in the IR-induced brain impairment. CIP + PEG effectively mitigated the brain lesions, suggesting effectiveness of CIP + PEG therapy for treating the IR-induced brain hemorrhage by recovering GFAP and platelets and reducing C3 and p53.

Extrato de Echinodorus grandiflorus apresenta efeito renoprotetor em ratos com nefrotoxicidade aguda induzida pela ciclofosfamida / Extract of Echinodorus grandiflorus presents renoprotetic effect on rats with acute nephrotoxicity induced by cyclophosphamid / El extracto de Echinodorus grandiflorus tiene un efecto renoprotector en ratas con nefrotoxicidad aguda inducida por ciclofosfamida

Pelas características anatômicas e fisiológicas dos rins, a lesão renal aguda tem sua origem nefrotóxica pela alta circulação local, o que favorece a alta concentração de substâncias tóxicas e seus metabólitos no tecido. A lesão renal aguda é uma complicação comum em internações hospitalares e principalmente em internações em unidades de terapia intensiva. A ciclofosfamida, um quimioterápico utilizado no tratamento de doenças autoimunes e neoplasias sólidas, pode causar nefrotoxicidade com disfunção glomerular e tubular. O uso de plantas medicinais, pelas suas potentes ações antioxidantes, tem sido usado para prevenção ou tratamento de lesões celulares induzidas pelo desequilíbrio entre enzimas antioxidantes e oxidantes. Por esse motivo, o objetivo do experimento foi avaliar o potencial efeito protetor da Echinodorus grandiflorus na prevenção da nefrotoxidade induzida pela ciclofosfamida. Para isso, foi realizado o experimento com a utilização de 35 ratos machos, Wistar, divididos em seis grupos experimentais, sendo administrado a ciclofosfamida na dose de 150mg/kg nos grupos G2 a G6 e diferentes doses da Echinodorus grandiflorus, com posterior análise de parâmetros sanguíneos e histológicos. A administração de ciclofosfamida na dose de 150mg/kg de massa corporal, em dose única, foi capaz de induzir a nefrotoxicidade aguda em todos os ratos. O extrato bruto de Echinodorus grandiflorus apresentou potencial efeito renoprotetor ao uso da ciclofosfamida, na dose de 300mg/kg de massa corporal, sendo possível observar redução dos efeitos nefrotóxicos do quimioterápico, pela redução dos danos tubulares e pela diminuição dos espaços capsulas, nitidamente encontradas alterados no grupo que recebeu apenas ciclofosfamida, denotando resultados promissores para utilização desta planta medicinal na prevenção da nefrotoxicidade induzida pelo fármaco. Contudo, novos estudos dos efeitos renoprotetor do chapéu de couro, poderão elucidar os mecanismos envolvidos na ação do extrato bruto do chapéu de couro. A utilização de extrato bruto de plantas medicinais torna-se um adjuvante aos tratamentos pelo baixo custo e pela facilidade de acesso das diferentes populações as plantas desde que devidamente orientados pelos profissionais habilitados.

Due to the anatomical and physiological characteristics of the kidneys, acute kidney injury has its nephrotoxic origin due to the high local circulation, which favors the high concentration of toxic substances and their metabolites in the tissue. Acute kidney injury is a common complication in hospital admissions and especially in intensive care unit admissions. Cyclophosphamide, a chemotherapy drug used in the treatment of autoimmune diseases and solid neoplasms, can cause nephrotoxicity with glomerular and tubular dysfunction. The use of medicinal plants, due to their potent antioxidant actions, has been used for the prevention or treatment of cellular injuries induced by the imbalance between antioxidant and oxidant enzymes. For this reason, the aim of the experiment was to evaluate the potential protective effect of Echinodorus grandiflorus in preventing cyclophosphamide-induced nephrotoxicity. For this, the experiment was carried out with the use of 35 male Wistar rats, divided into six experimental groups, being administered cyclophosphamide at a dose of 150mg/kg in groups G2 to G6 and different doses of Echinodorus grandiflorus, with subsequent analysis of parameters blood and histology. The administration of cyclophosphamide at a dose of 150mg/kg of body weight, in a single dose, was able to induce acute nephrotoxicity in all rats. The crude extract of Echinodorus grandiflorus showed a potential renoprotective effect with the use of cyclophosphamide, at a dose of 300mg/kg of body mass, and it was possible to observe a reduction in the nephrotoxic effects of the chemotherapy, due to the reduction of tubular damage and the reduction of capsule spaces, clearly found altered in the group that received only cyclophosphamide, showing promising results for the use of this medicinal plant in the prevention of drug-induced nephrotoxicity. However, further studies of the renoprotective effects of the leather hat may elucidate the mechanisms involved in the action of the crude extract of the leather hat. The use of raw extract of medicinal plants becomes an adjuvant to treatments due to the low cost and ease of access of different populations to plants, provided that they are properly guided by qualified professionals.

Debido a las características anatómicas y fisiológicas de los riñones, la lesión renal aguda tiene su origen nefrotóxico por la elevada circulación local, que favorece la alta concentración de sustancias tóxicas y sus metabolitos en el tejido. La lesión renal aguda es una complicación frecuente en los ingresos hospitalarios y principalmente en las unidades de cuidados intensivos. La ciclofosfamida, un quimioterápico utilizado en el tratamiento de enfermedades autoinmunes y neoplasias sólidas, puede causar nefrotoxicidad con disfunción glomerular y tubular. El uso de plantas medicinales, debido a sus potentes acciones antioxidantes, se ha utilizado para la prevención o el tratamiento de lesiones celulares inducidas por el desequilibrio entre enzimas antioxidantes y oxidantes. Por este motivo, el objetivo del experimento era evaluar el posible efecto protector del Echinodorus grandiflorus en la prevención de la nefrotoxicidad inducida por la ciclofosfamida. Para ello, se realizó el experimento utilizando 35 ratas Wistar macho, divididas en seis grupos experimentales, administrándoseles ciclofosfamida a una dosis de 150mg/kg en los grupos G2 a G6 y diferentes dosis de Echinodorus grandiflorus, con posterior análisis de sangre y parámetros histológicos. La administración de ciclofosfamida a una dosis de 150mg/kg de masa corporal, en dosis única, fue capaz de inducir nefrotoxicidad aguda en todas las ratas. El extracto crudo de Echinodorus grandiflorus presentó un potencial efecto renoprotector al uso de ciclofosfamida, a una dosis de 300mg/kg de masa corporal, siendo posible observar una reducción de los efectos nefrotóxicos de la quimioterapia, por la reducción del daño tubular y por la disminución de los espacios capsulares, encontrándose claramente alterados en el grupo que recibió solamente ciclofosfamida, denotando resultados promisorios para el uso de esta planta medicinal en la prevención de la nefrotoxicidad inducida por el fármaco. Sin embargo, nuevos estudios sobre los efectos renoprotectores del sombrero de cuero podrían dilucidar los mecanismos implicados en la acción del extracto crudo de sombrero de cuero. El uso de extractos crudos de plantas medicinales se convierte en un coadyuvante de los tratamientos por su bajo coste y la facilidad de acceso de las diferentes poblaciones a las plantas desde que son guiadas adecuadamente por profesionales cualificados.

A comprehensive overview on the effects of green tea on anthropometric measures, blood pressure, glycemic and lipidemic status: An umbrella review and meta meta-analysis study.

AIM: The aim of this meta-review was to establish the effects of green tea (GT) intake on some cardiometabolic risk factors including anthropometric measures, blood pressure as well as blood glucose and lipids using evidence from previous systematic reviews and meta-analyses. DATA SYNTHESIS: Articles were identified via searches in PubMed, Embase, and the Cochrane Library, Web of Knowledge database from the index date of each database through January 31, 2021. A total of 13 meta-analyses were finally included in the synthesis. Meta-meta-analysis revealed significant effects of GT on weight and waist circumference with weighted mean difference (WMD) of -0.89 (95% CI -1.43 to -0.34, p < 0.001) and -1.01 (95% CI -1.63 to -0.39, p < 0.001), systolic and diastolic blood pressure, with WMDs of -1.17 (95% CI -2.18 to -0.16) and -1.24 (95% CI -2.07 to -0.4), respectively. There was similar effect on fasting blood glucose (WMD, -1.3, 95% CI -2.09 to -0.51, p < 0.001) but not on other glycemic indicators. The findings also revealed a significant effect size of total cholesterol and LDL-C (WMD -4.93; 95% CI -6.41 to -3.46, p < 0.001, WMD -4.31; 95% CI -6.55 to -2.07, p < 0.001, respectively). CONCLUSION: Regular consumption of GT and probably its bioactive constituents as supplements have beneficial effects on different health aspects including weight, blood pressure, blood glucose and lipids. However, these effects might be influenced by several factors such as the amount and frequency of consumption, health/disease condition and life style including dietary habits and physical activity.

[Efficacy of the Extract from Fermentation of Soybean and Rice Bran on Hyperglycemia].

In recent years, lifestyle-related diseases such as hypertension and diabetes have been on the rise. These conditions can cause serious conditions such as myocardial and cerebral infarctions. Therefore, proper control of blood pressure and blood glucose levels is important issues in preventive medicine. Traditional fermented foods have been shown to have various functions, and their effects on lifestyle-related diseases have attracted particular attention. In this study, we investigated the effects of fermented soybeans and rice bran (OE-1) and supplements containing OE-1 on blood glucose levels and weight changes. We identified an inhibitory effect on elevated blood glucose levels upon administration of OE-1, and this effect was thought to be due to digestive enzyme inhibition. These effects of foods containing OE-1 are expected to have a positive effect on the prevention and improvement of lifestyle-related diseases as health foods.

Jinlida granules ameliorate the high-fat-diet induced liver injury in mice by antagonising hepatocytes pyroptosis.

CONTEXT: Jinlida (JLD) as a traditional Chinese medicine formula has been used to treat type 2 diabetes mellitus (T2DM) and studies have shown its anti-obesity effect. OBJECTIVE: To investigate the therapeutic effects of JLD in a mouse model of non-alcoholic fatty liver (NAFL). MATERIALS AND METHODS: C57BL/6J mice were divided into three groups and fed a low-diet diet (LFD), high-fat diet (HFD), or HFD + JLD (3.8 g/kg) for 16 weeks, respectively. The free fatty acids-induced lipotoxicity in HepG2 cells were used to evaluate the anti-pyroptotic effects of JLD. The pharmacological effects of JLD on NAFL were investigated by pathological examination, intraperitoneal glucose and insulin tolerance tests, western blotting, and quantitative real-time PCR. RESULTS: In vivo studies showed that JLD ameliorated HFD-induced liver injury, significantly decreased body weight and enhanced insulin sensitivity and improved glucose tolerance. Furthermore, JLD suppressed both the mRNA expression of caspase-1 (1.58 vs. 2.90), IL-1ß (0.93 vs. 3.44) and IL-18 (1.34 vs. 1.60) and protein expression of NLRP3 (2.04 vs. 5.71), pro-caspase-1 (2.68 vs. 4.92) and IL-1ß (1.61 vs. 2.60). In vitro, JLD inhibited the formation of lipid droplets induced by 2 mM FFA (IC50 = 2.727 mM), reduced the protein expression of NLRP3 (0.74 vs. 2.27), caspase-1 (0.57 vs. 2.68), p20 (1.67 vs. 3.33), and IL-1ß (1.44 vs. 2.41), and lowered the ratio of p-IKB-α/IKB-α (0.47 vs. 2.19). CONCLUSION: JLD has a protective effect against NAFLD, which may be related to its anti-pyroptosis, suggesting that JLD has the potential as a novel agent in the treatment of NAFLD.

Icariin attenuates thioacetamide­induced bone loss via the RANKL­p38/ERK­NFAT signaling pathway.

There is an increasing incidence of destructive bone disease caused by osteoclast proliferation. This is characterized by reduced bone mass and imbalance of bone homeostasis. Icariin (ICA), a flavonoid compound isolated from Epimedium, has anti­osteoporosis activity and inhibits the formation of osteoclasts and bone resorption. The purpose of the present study was to investigate the protective effect of ICA on osteoclastic differentiation induced by thioacetamide (TAA) and its possible mechanism in Sprague Dawley (SD) rats. In the present study, SD rats were intraperitoneally injected with TAA (300 mg/kg) for the bone loss model, treated with ICA (600 mg/kg, intragastric gavage) in the ICA group and TAA+ICA group for treatment of bone loss for 6 weeks. Indexes associated with bone metabolism, such as alkaline phosphatase, N­terminal telopeptide of type­I collagen (NTX­I), calcium (Ca), phosphorus (P) and magnesium (Mg) in the serum, were detected. Osteoclast differentiation of femoral tissues was detected by hematoxylin and eosin and tartrate­resistant acid phosphatase staining. The femoral bone mass was evaluated using a three­point bending test and micro computed tomography. Western blotting was used to detect the expression levels of osteoclast­related proteins in each group. In the rats treated with TAA, the serum concentrations of Ca, P and Mg were decreased, the serum concentration of NTX­I was increased, osteoclast differentiation of the femur was increased, femur bone stress and bone mass were decreased and the bone loss and osteoclast formation were reduced after ICA treatment. In addition, ICA inhibited the protein expression of receptor activator of nuclear factor κ­Β ligand (RANKL), receptor activator of nuclear factor κ­B (RANK), p38, ERK, c­Fos and nuclear factor of activated T cells 1 (NFATc1) in the femur of rats treated with TAA. The results suggested that ICA may inhibit osteoclast differentiation by downregulating the RANKL­p38/ERK­NFAT signaling pathway and prevent TAA­induced bone loss. The results are helpful to understand the mechanism of osteoclast differentiation induced by TAA, as well as the antiresorptive activity and molecular mechanism of ICA, and to provide new ideas for the treatment of osteolytic diseases.

Protective Effects of Green Tea Supplementation against Lead-Induced Neurotoxicity in Mice.

The use of natural products as therapeutic agents is rapidly growing recently. In the current study, we investigated the protective effects of green tea supplementation on lead-induced toxicity in mice. Forty albino mice were divided into four groups as follows: A: control group; B: green tea receiving group; C: lead-intoxicated group; and D: lead-intoxicated group supplemented with green tea. At the end of the experiment, the animals were tested for neurobehavioral and biochemical alterations. Green tea was analyzed through Gas Chromatography-Mass Spectrometry (GC/MS) analysis. We found that supplementation with green tea ameliorated the lead-associated increase in body weight and blood glucose. Green tea supplementation also changed the blood picture that was affected due to lead toxicity and ameliorated lead-induced dyslipidemia. The group of mice that were supplemented with green tea has shown positive alterations in locomotory, anxiety, memory, and learning behaviors. The GC/MS analysis revealed many active ingredients among which the two most abundant were caffeine and 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester. We concluded that green tea supplementation has several positive effects on the lead-induced neurotoxicity in mice and that these effects may be attributed to its main two active ingredients.

Effect of Heat-Treated Garlic (Allium sativum L.) on Growth Parameters, Plasma Lipid Profile and Histological Changes in the Ileum of Atherogenic Rats.

Dietary supplementation with raw garlic has a preventive and healing effect in cardiovascular diseases, but it could also damage the intestinal mucosa, resulting in impairment of nutrient absorption. Garlic processing, including heat treatment, changes the content and biological activity of garlic, so it is crucial to find food-processing methods that will preserve the health-promoting properties of garlic while minimizing its negative impact on the digestive system. Therefore, in this study, the effect of garlic (Allium sativum L.) on growth parameters, plasma lipid profile, and morphological parameters in the ileum of Wistar rats subjected to various types of heat treatment (90 s blanching garlic, 10 min boiling in water, 10 min pan frying without fat, microwave heating fresh garlic, 90 s blanching and microwave heating garlic, 10 min boiling in water and microwave heating garlic, and 10 min pan frying without fat and microwave heating garlic) was determined in an atherogenic diet (containing 1% addition of cholesterol). In the conducted research, it was found that the diet supplemented with heat-treated garlic used in the atherogenic diet improved the consumption and growth parameters of rats, depending on the type and time of its use. The highest consumption was recorded in atherogenic groups supplemented with garlic subjected to a longer (10 min) heat treatment and was then heated in a microwave oven. Garlic subjected to the shortest heat treatment proved to be most effective, and a significant improvement in the lipid profiles of rats' plasma with atherogenic was observed. Extending the time of heat treatment of garlic and, additionally, its microwaving significantly weakened the action of garlic in the body, but still retained its hypolipidemic effect. The greatest influence on the structural changes in the mucosa of the rats' iliac intestine, manifested by degeneration of the mucosa, shortening the length of the intestinal villi, damage to the brush border, and thus impairment of the intestinal absorption, was exerted by supplementing the atherogenic diet with garlic subjected to short-term heat treatment. Among the processes used, blanching was the least favorable, and the long-lasting thermal processes (cooking, frying for 10 min) had a positive effect on the mucosa of the rats' intestines. The results obtained in this study confirm that the selection of an appropriate method of thermal processing of garlic may allow for the maintenance of preventive and therapeutic efficacy of garlic in cardiovascular diseases, while ensuring the safety of its long-term use in the context of degenerative changes in the gastrointestinal tract.

Saponin-rich extract of Tribulus terrestris alleviates systemic inflammation and insulin resistance in dietary obese female rats: Impact on adipokine/hormonal disturbances.

Tribulus terrestris saponins (TTS) have been longley used as an overall tonic and recent studies showed they influence inflammatory conditions. We examined the ameliorative effect of a commercial formula of a saponin-rich extract of TT in a model of dietary obesity in female rats focusing on their ability to control the inflammatory burden, insulin resistance (IR), adipokine expression and the related reproductive system pathologies. Female rats were fed with high fat diet (HFD) for 14 weeks to launch diet-induced obesity; they were assigned as: the obese control female rats (OFR) which received no treatment and TTS (5 and 10 mg/kg/day) treated rats; they were compared to a normal rat group. We determined the IR index, serum/tissue inflammatory cytokines, and adipose tissue adipokine expression and examined the secondary ovarian pathologies. Body weight gain, serum triglycerides and IR (>5-fold) in the OFR group were greater than the normal group; TTS lessened these parameters compared with the OFR group. TTS, at 10 mg/kg dose, ameliorated mRNA expression of leptin and visfatin genes in addition to serum inflammatory cytokine levels. Moreover, TTS corrected the hyperprolactinemia and other hormonal disturbances and ameliorated the ovarian pathologies. This study highlighted that the anti-inflammatory properties of TTS helped in alleviation of IR and body weight gain in OFR. Upon correction of obesity manifestations, the gonadal hormone dysregulations and ovarian pathologies were subsequently ameliorated. We can consider TTS as a promising candidate that may alleviate the inflammatory burden, IR and adipokine expression in obesity and hence prevent the secondary gonadal complications in female subjects if appropriate clinical studies are available.

Effect of a freeze-dried coffee solution in a high-fat diet-induced obesity model in rats: Impact on inflammatory response, lipid profile, and gut microbiota.

Coffee beans contain high polyphenol content, which have the potential to modulate the intestinal microbiota, and possibly attenuate weight gain and the associated dyslipidemia. This study investigated the effect of freeze-dried coffee solution (FCS) consumption on physiological parameters, lipid profile, and microbiota of Wistar rats fed a high-fat diet (HF) or control diet (CT). FCS combined with a high-fat diet increased the fecal and cecal Bifidobacterium spp. population and decreased the cecal Escherichia coli population and intestinal Il1b mRNA level. Regardless of the diet type, FCS increased the serum high-density lipoprotein cholesterol (HDL-C); however, it did not affect body weight, food intake, low-density lipoprotein, triglycerides, fecal bile acids, and intestinal Il6 mRNA levels. The high-fat diet increased weight gain, hepatic cholesterol and triglycerides, fecal bile acids, and the fecal and cecal Lactobacillus spp. population, and reduced food intake, the fecal E. coli population, and intestinal Il6 mRNA level. The results suggest that FCS consumption exhibits positive health effects in rats fed a high-fat diet by increasing Bifidobacterium spp. population and HDL-C reverse cholesterol transport, and by reducing Il1b mRNA level. However, FCS administration at a dose of 0.39 g/100 g diet over an eight-week period was not effective in controlling food intake, and consequently, preventing weight gain in rats of high-fat diet-induced obesity model.

Effect of Standardized Hydrangea serrata (Thunb.) Ser. Leaves Extract on Body Weight and Body Fat Reduction in Overweight or Obese Humans: A Randomized Double-Blind Placebo-Controlled Study.

Obesity is a major health problem that is caused by body fat accumulation and that can lead to metabolic diseases. Owing to several side effects of the currently used antiobesity drugs, natural plants have risen as safe and potential candidates to alleviate obesity. We have previously reported the antiobesity effect of Hydrangea serrata (Thunb.) Ser. leaves extract (WHS) and its underlying mechanisms. As an extension of our preclinical studies, this study aimed to investigate the effect of WHS on body weight and body fat reduction in overweight or obese humans. A total of 93 healthy overweight or obese males and females, aged 19-65 years, with body mass indexes (BMIs) ≥ 25 and <32 kg/m2, were recruited and received either an oral administration of 600 mg of WHS, or placebo tablets for 12 weeks. Daily supplementation with WHS decreased body weights, body fat masses, and BMIs compared with the placebo-treated group. The hip circumferences, visceral fat areas, abdominal fat areas, and visceral-to-subcutaneous ratios decreased after WHS supplementation. No significant side effects were observed during or after the 12 weeks of WHS intake. In conclusion, WHS, which has beneficial effects on body weight and body fat reduction, could be a promising antiobesity supplement that does not produce any side effects.

Anticarcinogenic activity of methanol extract of Melastoma malabathricum leaves is attributed to the presence of phenolics compounds and the activation of endogenous antioxidant system / Actividad anticancerígena del extracto metanólico de hojas de Melastoma malabathricum atribuida a la presencia de compuestos fenólicos y a la activación del sistema antioxidante endógeno

Melastoma malabathricum (M. malabathricum) extracts have been reported to exert various pharmacological activities including antioxidants, anti-inflammatory and antiproliferative activities. The objective of the present study was to determine the anticarcinogenic activity of its methanol extract (MEMM) against the azoxymethane (AOM)-induced early colon carcinogenesis in rats. Rats were randomly assigned to five groups (n=6) namely normal control, negative control, and treatment (50, 250 or 500 mg/kg of MEMM) groups. Colon tissues were harvested for histopathological analysis and endogenous antioxidant system determination. MEMM was also subjected to HPLC analysis. Findings showed that MEMM significantly (p<0.05) reversed the AOM-induced carcinogenicity by: i) reducing the formation of aberrant crypt foci (ACF) in colon tissues, and; ii) enhancing the endogenous antioxidant activity (catalase, superoxide dismutase and glutathione peroxidase). Moreover, various phenolics has been identified in MEMM. In conclusion, MEMM exerts the in vivo anticarcinogenic activity via the activation of endogenous antioxidant system and synergistic action of phenolics.

Se ha informado que los extractos de Melastoma malabathricum (M. malabathricum) ejercen diversas actividades farmacológicas, incluidas actividades antioxidantes, antiinflamatorias y antiproliferativas. El objetivo del presente estudio fue determinar la actividad anticancerígena de su extracto de metanol (MEMM) contra la carcinogénesis de colon temprana inducida por azoximetano (AOM) en ratas. Las ratas se asignaron al azar a cinco grupos (n=6), a saber, los grupos de control normal, control negativo y tratamiento (50, 250 o 500 mg/kg de MEMM). Tejidos de colon fueron recolectados para análisis histopatológico y determinación del sistema antioxidante endógeno. MEMM también se sometió a análisis de HPLC. Los hallazgos mostraron que MEMM invirtió significativamente (p<0.05) la carcinogenicidad inducida por AOM al: i) reducir la formación de focos de criptas aberrantes (ACF) en los tejidos del colon, y; ii) potenciar la actividad antioxidante endógena (catalasa, superóxido dismutasa y glutatión peroxidasa). Además, se han identificado varios fenólicos en MEMM. En conclusión, MEMM ejerce la actividad anticancerígena in vivo mediante la activación del sistema antioxidante endógeno y la acción sinérgica de los fenólicos.

Dehydroevodiamine suppresses inflammatory responses in adjuvant-induced arthritis rats and human fibroblast-like synoviocytes.

Dehydroevodiamine (DHE) is an effective natural active substance extracted from Euodiae Fructus, which is a widely used herbal drug in traditional Chinese medicine. The focus of this study was to test the possibility of using DHE in the treatment of rheumatoid arthritis (RA) diseases. A rat model of adjuvant-induced arthritis (AIA) was generated using Complete Freund's Adjuvant (CFA). Body weight changes, arthritis scores, ankle pathology, tumor necrosis factor-alpha (TNF-α), interleukin-1ß(IL-1ß), interleukin-6 (IL-6), and interleukin-17 (IL-17) secretion, as well as matrix metalloproteinase (MMP) expression in joint tissue, were measured as indicators of viability of DHE medicated AIA rats. Human fibroblast-like synoviocytes (MH7A cells) were connected to check these impacts. The results confirmed that DHE administration had an excellent therapeutic impact on the AIA rat model, substantially relieving joint swelling, inhibiting synovial pannus hyperplasia, and decreasing joint scores. In addition, the serum enzyme-linked immunosorbent assay (ELISA) showed that DHE treatment reduced the expression of pro-inflammatory factors in AIA rats. The immunohistochemical results showed that DHE treatment could reduce the synthesis of MMPs such as matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-3 (MMP-3) in the ankle tissue of AIA rats. In vitro, DHE inhibited cell proliferation, mRNA transcription, protein synthesis of proinflammatory factors such as IL-1ßand IL-6, and matrix metalloproteinases such as MMP-1 and MMP-3. Furthermore, DHE inhibited the phosphorylation levels of p38, JNK, and ERK proteins in TNF-α-treated MH7A cells.This work assessed the effect of DHE in AIA rats and revealed its mechanism in vitro.

Reversal of insulin resistance by Ficus benghalensis bark in fructose-induced insulin-resistant rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Bark of Ficus benghalensis L. (family: Moraceae), commonly known as Banyan is recorded as Nyagrodha in Ayurvedic Pharmacopeia of India to manage burning sensation, obesity, diabetes, bleeding disorders, thirst, skin diseases, wounds, and dysmenorrhoea. However, the effect of F. benghalensis bark over glycolysis, gluconeogenesis, and appetite regulation in insulin-resistant pathogenesis has not been reported yet. AIM OF THE STUDY: The present study aimed to investigate the effect of hydroalcoholic extract of F. benghalensis bark in gluconeogenesis, glycolysis, and appetite regulation in fructose-induced insulin resistance in experimental rats. MATERIALS AND METHODS: Male Wister rats were supplemented with fructose in drinking water (10% w/v for 42 days and 20% w/v for next 12 days; a total of 54 days); insulin resistance was confirmed via the elevated area under the curve of the glucose during oral glucose tolerance test after 54 days and was subjected with extract treatment for next 30 days. After 30 days of treatment, animals were fasted to perform oral glucose and insulin tolerance test to estimate glucose and insulin levels. The blood sample was collected for biochemical estimation and the liver homogenate was prepared to estimate hepatic enzymes and enzymatic and non-enzymatic anti-oxidant biomarkers followed by histopathological evaluation. Also, glycogen content was quantified in gastrocnemius muscle and liver homogenates. Further, reported bioactives from the F. benghalensis were retrieved from the ChEBI database and docked against hexokinase, phosphofructokinase, glucose-6-phosphatase, lactate dehydrogenase, and fructose-1,6-biphosphatase to identify the probable lead hits against the enzymes involved in gluconeogenesis. RESULTS: Treatment with the F. benghalensis bark extract significantly increased the body weight and food intake and significantly decreased fructose supplemented water intake. Further, treatment with extract significantly increased the exogenous glucose clearance and well responded to the exogenous insulin. Further, extract treatment improved lipid metabolism, ameliorated plasma leptin, and multiple enzymatic and non-enzymatic antioxidant biomarkers. Likewise, it also improved gluconeogenesis mediated pathogenesis of non-alcoholic fatty liver injury. Additionally, molecular docking also identified mucusisoflavone A and B as lead hits in downregulating gluconeogenesis. CONCLUSION: Hydroalcoholic extract of F. benghalensis bark may prevent insulin resistance by downregulating gluconeogenesis and improving the appetite in fructose-induced insulin-resistant rats.

Effectiveness of the fruit of Rosa odorata sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils in the protection and the healing of ethanol-induced rat gastric mucosa ulcer based on Nrf2/NF-κB pathway regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa odorata Sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils (Rosaceae), is also known as "GU-GONG-GUO", the root of which has been recognized as common ethnodrug from the Yi nationality for treating inflammatory bowel disease. The aim of the present study was to investigate the preventive and curative effects of extract from the fruits of Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils (FOE) in vitro and in vivo as well as elucidate the potential mechanisms of the action involved. MATERIALS AND METHODS: Male Wistar rats were applied to ethanol-induced gastric ulcer model. They were divided into six groups: control, model (GU), positive (Magnesium aluminate chewable tablets, 125 mg/kg), FOE low (125 mg/kg), middle (250 mg/kg) and high (500 mg/kg) doses groups. Histopathology observation of gastric tissues was detected by hematoxylin and eosin (H&E) staining. The expression of Nrf2, HO-1, Keap1, NF-κB p65 and IKKα/ß in gastric tissues were evaluated by immunohistochemistry (IHC). The levels of cytokines in serum and tissues were measured by Enzyme-linked immunosorbent assay (ELISA). The expression of Nrf2, HO-1, Keap1, NF-κB p65, IKKα/ß, PCNA and COX2 proteins were ulteriorly assessed by Western blotting to elucidate the molecular mechanism of FOE's protective effect on gastric ulcer. RESULTS: MTT detection showed that LPS reduced RAW264.7 cell survival, and FOE blocked the inhibition of RAW264.7 cell growth induced by LPS. When RAW264.7 cells were treated with both FOE (100 µg mL-1) and LPS (5 µg mL-1) for 24 h, compared with the model group, the level of NO, TNF-α, IL-6, IL-1ß and MDA significantly decreased, and the activity of SOD was significantly reduced. Obvious pathological injuries in the GU model group were observed, which was improved after treatments with FOE. The contents of pro-inflammatory factors in serum and tissues were decreased by 25% whereas prostaglandin E2 (PGE2) and epidermal growth factor (EGF) were increased by 30% in a dose-dependent manner after FOE (500 mg/kg) treatments. In addition to the promotion effects of superoxide dismutase (SOD), FOE (500 mg/kg) also attenuated the levels of nitric oxide (NO) and malondialdehyde (MDA) by 20%. Likewise, the expression of NF-κB p65, IKKα/ß and Keap1 were suppressed after treatments with FOE whereas Nrf2 and HO-1 showed the opposite trend, which mechanisms were found to be associated with Nrf2/NF-κB signaling pathways. CONCLUSION: The study demonstrated that FOE is able to protect against GU via inhibiting NF-κB signaling pathway and activating Nrf2 signaling pathway, which might provide a stronger theoretical basis for the treatment of GU.

Polar fraction from Parkinsonia aculeata aerial parts extract improves imbalanced metabolic profile and reduces proinflammatory interleukin levels in white adipose tissue in obese rats induced by western diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinsonia aculeata L. (Cesalpineaceae) is a medium tree found in the Xingó region (semi-arid area) in Northeast of Brazil, recognised by local population as an antidiabetic agent. According information from local community, the commonly traditional preparation is prepared as an infusion of the aerial part of the plant and consumed over the day to manage diabetes-related complications. Previous studies have described Parkinsonia aculeate as a product with both hypoglycemic and hypotriglyceridemic effects. AIM OF THE STUDY: The objective of this study was to evaluate the effects of polar fraction obtained from the hydroethanolic extract of Parkinsonia aculeata (PfrHEPA) on the lipid profile of animals that consumed a westernized diet. MATERIALS AND METHODS: Thirty-six Wistar rats (45-55 g) were fed either with standard control(C) or westernized diet(W) for 120 days. The food intake, body weight evolution and body size were also analyzed. From 120 to 150 days, they were orally treated according to their group with vehicle (distillated water, 10 mL/kg), PfrHEPA at three doses (35, 70 and 140 mg/kg/day) or Gemfibrozil (140 mg/kg/day) for 30 days. RESULTS: The animals fed with westernized diet showed dyslipidemia when compared to animals receiving a standard diet. Treatment with PfrHEPA (140 mg/kg), even with the continued consumption of westernized diet by animals (from 120 to 150 days) promoted a significant reduction in total cholesterol, LDL and triglyceride levels, in relation to untreated W group. PfrHEPA 140 mg/kg reduced the key serum lipids and glycaemia as well as inflammatory cytokines known as important risk factors of cardiovascular diseases. CONCLUSIONS: The observed evidence may contribute to the control of metabolic parameters as dyslipidemia corroborating the ethnopharmacological information concerning the antihyperlipidemic and hypoglycemic activities of P. aculeata.

Peptide-YY3-36/glucagon-like peptide-1 combination treatment of obese diabetic mice improves insulin sensitivity associated with recovered pancreatic ß-cell function and synergistic activation of discrete hypothalamic and brainstem neuronal circuitries.

OBJECTIVE: Obesity-linked type 2 diabetes (T2D) is a worldwide health concern and many novel approaches are being considered for its treatment and subsequent prevention of serious comorbidities. Co-administration of glucagon like peptide 1 (GLP-1) and peptide YY3-36 (PYY3-36) renders a synergistic decrease in energy intake in obese men. However, mechanistic details of the synergy between these peptide agonists and their effects on metabolic homeostasis remain relatively scarce. METHODS: In this study, we utilized long-acting analogues of GLP-1 and PYY3-36 (via Fc-peptide conjugation) to better characterize the synergistic pharmacological benefits of their co-administration on body weight and glycaemic regulation in obese and diabetic mouse models. Hyperinsulinemic-euglycemic clamps were used to measure weight-independent effects of Fc-PYY3-36 + Fc-GLP-1 on insulin action. Fluorescent light sheet microscopy analysis of whole brain was performed to assess activation of brain regions. RESULTS: Co-administration of long-acting Fc-IgG/peptide conjugates of Fc-GLP-1 and Fc-PYY3-36 (specific for PYY receptor-2 (Y2R)) resulted in profound weight loss, restored glucose homeostasis, and recovered endogenous ß-cell function in two mouse models of obese T2D. Hyperinsulinemic-euglycemic clamps in C57BLKS/J db/db and diet-induced obese Y2R-deficient (Y2RKO) mice indicated Y2R is required for a weight-independent improvement in peripheral insulin sensitivity and enhanced hepatic glycogenesis. Brain cFos staining demonstrated distinct temporal activation of regions of the hypothalamus and hindbrain following Fc-PYY3-36 + Fc-GLP-1R agonist administration. CONCLUSIONS: These results reveal a therapeutic approach for obesity/T2D that improved insulin sensitivity and restored endogenous ß-cell function. These data also highlight the potential association between the gut-brain axis in control of metabolic homeostasis.

Removal of anti-nutritional factors of rapeseed protein isolate (RPI) and toxicity assessment of RPI.

We prepared a detoxified rapeseed protein isolate (RPI) by phytase/ethanol treatment based on alkaline extraction and acidic precipitation. Contents of protein, fat, ash, moisture, crude fiber, glucosinolates, phytic acid, and phenolics and color were determined. To evaluate the safety of detoxified RPI, five groups of C57 mice (detoxified RPI [10 and 20 g kg-1]; commercial soybean protein isolate (SPI) [10 g kg-1]; non-detoxified RPI [10 g kg-1]; control) were used in the acute-toxicity test. Bodyweight and pathology parameters were recorded at different time points, followed by macroscopic examination, organ-weight measurement and microstructure examination. After pretreatment of rapeseed meals with phytase (enzyme : substrate ratio, 1 : 5 mg g-1) for 1.5 h and two-time ethanol extraction for precipitated protein, the chemical characteristics in RPI were protein (88.26%), fat (0.57%), ash (2.72%), moisture (1.90%), crude fiber (0.77%), glucosinolates (0 µmol g-1), phytic acid (0.17%), phenolics (0.36%) and whiteness (73.38). Treatment resulted in significant removal of anti-nutritional factors (ANFs) and increased whiteness in detoxified RPI compared with non-detoxified RPI, and lower than in cruciferin-rich canola protein isolate (Puratein®). Experimental-related effects on bodyweight, clinical observations, or clinicopathology, in mice treated with detoxified RPI were not observed except for a decreased thyroid gland/parathyroid gland index in mice treated with non-detoxified RPI. Furthermore, the no-observed-effect level (NOEL) was 10 g kg-1 of detoxified RPI, whereas the no-observed-adverse-effect-level (NOAEL) was the highest fed level of 20 g kg-1 of detoxified RPI. Overall, detoxified RPI prepared by the combined treatment of phytase and ethanol was considered safe under the conditions tested, in which the contents of the main ANFs were reduced significantly.

Acute toxicity and safety profile evolution of aqueous extracts of Sanren decoction using in vivo models.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanren decoction (SRD) is a well-known traditional Chinese medicine prescription containing eight kinds of materials. SRD has been used mainly in China for more than 200 years for the treatment of respiratory disorders that co-occur with a bad fever after midday. AIM OF THE STUDY: To evaluate the acute and 28-day subacute toxicity of an aqueous extract of SRD using in vivo methods. MATERIALS AND METHODS: To determine acute toxicity, SRD was administered by gavage at a dosage of 58.5 g/kg/day to male and female mice for 7 days. To determine subacute toxicity, SRD was administered at 3.3, 6.5, or 13 g/kg/day to male and female rats for 28 days. The general behavior, body weight, biochemical and hematological parameters, organ coefficients and pathological morphology of the treated animals were analyzed. RESULTS: Neither acute nor subacute concentrations of SRD caused significant changes in the body weights, general behavior, hematology and biochemical parameters, organ weights, or histopathological appearances of the liver, kidney, spleen, brain, lung or heart in mice or rats. CONCLUSIONS: The administration of SRD can be considered safe within the conditions of this study.