Tesofensine, a novel antiobesity drug, silences GABAergic hypothalamic neurons.

Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here, we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. Using various techniques, we investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induces a greater weight loss in obese rats than lean rats, while differentially modulating the neuronal ensembles and population activity in LH. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensine's food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensine's appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound.

Clinical Evaluation of a Novel, Patented Green Coffee Bean Extract (GCB70®), Enriched in 70% Chlorogenic Acid, in Overweight Individuals.

OBJECTIVE: Obesity and overweight are challenging health problems of the millennium that lead to diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and atherosclerosis. Green coffee bean exhibited significant promise in healthy weight management, potentiating glucose-insulin sensitization and supporting liver health. The safety and efficacy of a novel, patented water-soluble green coffee bean extract (GCB70® enriched in 70% total chlorogenic acid and <1% caffeine) was investigated in 105 participants for 12 consecutive weeks. An institutional review board and Drugs Controller General (India) (DCGI) approvals were obtained, and the study was registered at ClinicalTrials.gov. METHOD: Body weight, body mass index (BMI), waist circumference, lipid profile, plasma leptin, glycosylated hemoglobin (HbA1c), and total blood chemistry were assessed over a period of 12 weeks of treatment. Safety was affirmed. RESULTS: GCB70 (500 mg BID) supplementation significantly reduced body weight (approximately 6%; p = 0.000**) in approximately 97% of the study population. About a 5.65% statistically significant reduction (p = 0.000**) in BMI was observed in 96% of the study volunteers. Waist circumference was significantly reduced by 6.77% and 6.62% in 98% of the male and female participants, respectively. Plasma leptin levels decreased by 13.6% in 99% of the study population as compared to the baseline value. Upon completion of 12 weeks' treatment, fasting glucose levels decreased by 13.05% (p = 0.000**) in 79% of the study population. There was a statistically significant decrease in HbA1c levels in both male and female participants (p = 0.000**), while 86.7% of the study participants showed a statistically significant decrease in thyroid-stimulating hormone (TSH) levels (p = 0.000**). The mean decrease in TSH levels on completion of the treatment was 14.07% in the study population as compared to baseline levels. Total blood chemistry analysis exhibited broad-spectrum safety. CONCLUSIONS: This investigation demonstrated that GCB70 is safe and efficacious in healthy weight management.

Alternativas fitoterápicas no controle da obesidade / Phytotherapy alternatives in obesity control / Alternativas herbales en el control de la obesidad

Nos últimos anos, a obesidade vem aumentando consideravelmente entre adultos e crianças e, segundo a OMS, estima-se que em 2025 o número de obesos ultrapasse a 2,3 milhões em todo o mundo. O indivíduo obeso apresenta maiores riscos de desenvolver doenças crônicas não transmissíveis, como diabetes, doenças cardiovasculares, dislipidemias e ainda alguns tipos de cânceres. O tratamento para a obesidade é variado e inclui mudanças no estilo de vida como: hábitos alimentares e prática de atividade física, tratamento medicamentoso, cirurgia bariátrica e fitoterápicos com o potencial de auxiliar no tratamento. O objetivo deste trabalho foi realizar uma revisão bibliográfica a fim de avaliar os benefícios da utilização de medicamentos fitoterápicos como auxiliar no tratamento da obesidade, seus principais ativos, mecanismos de ação e sua utilização popular. Dentre as plantas pesquisadas e que demonstraram potencial para atuar no tratamento da obesidade encontram-se Camelia sinensis, Citrus aurantium, Hibiscus sabdariffa, Coffea arabica, Ephedra sinica, Zingiber oficinale e Senna alexandrina. Os principais mecanismos de ação envolvidos no potencial anti-obesidade das plantas medicinais são a capacidade de controle do apetite e ingestão de energia, estímulo da termogênese, inibição da lipase pancreática e redução da absorção de gordura, diminuição da lipogênese e aumento da lipólise. Desta forma, conclui-se que as plantas selecionadas neste estudo apresentaram efeitos positivos nos parâmetros bioquímicos e físicos, podendo ser incluídas nos protocolos como coadjuvantes nos tratamentos de emagrecimento.

In recent years, obesity has increased considerably among adults and children and according to the WHO, it is estimated that in 2025 the number of obese people will exceed 2.3 million worldwide. The obese individual is at greater risk of developing non-communicable chronic diseases, such as diabetes, cardiovascular disease, dyslipidemia and even some types of cancer. The treatment for obesity is varied, including changes in lifestyle such as eating habits and physical activity, drug treatment, bariatric surgery and phytotherapy with the potential to aid in the treatment. The objective of this work was to carry out a literature review, evaluating the benefits of using herbal medicines as an aid in the treatment of obesity, their main assets, mechanisms of action and their popular use. Among the plants researched and that have shown potential to act in the treatment of obesity are Camelia sinensis, Citrus aurantium, Hibiscus sabdariffa, Coffea arabica, Ephedra sinica, Zingiber officiale and Senna alexandrina. The main mechanisms of action involved in the antiobesity potential of medicinal plants are the ability to control appetite and energy intake, thermogenesis stimulation, pancreatic lipase inhibition and reduction of fat absorption, lipogenesis decrease and lipolysis increase. Thus, it is concluded that the plants selected in this study showed positive effects on biochemical and physical parameters, and can be included in the protocols as adjuvants in weight loss treatments.

En los últimos años, la obesidad ha aumentado considerablemente entre adultos y niños y, según la OMS, se estima que en 2025 el número de obesos superará los 2,3 millones en todo el mundo. Los individuos obesos tienen un mayor riesgo de desarrollar enfermedades crónicas no transmisibles, como la diabetes, las enfermedades cardiovasculares, las dislipidemias e incluso algunos tipos de cáncer. El tratamiento de la obesidad es variado e incluye cambios en el estilo de vida como: hábitos alimenticios y práctica de actividad física, tratamiento farmacológico, cirugía bariátrica y medicamentos a base de hierbas con potencial para ayudar en el tratamiento. El objetivo de este trabajo fue realizar una revisión bibliográfica para evaluar los beneficios del uso de las hierbas medicinales como ayuda en el tratamiento de la obesidad, sus principales activos, mecanismos de acción y su uso popular. Entre las plantas investigadas y que mostraron potencial para actuar en el tratamiento de la obesidad están Camelia sinensis, Citrus aurantium, Hibiscus sabdariffa, Coffea arabica, Ephedra sinica, Zingiber oficinale y Senna alexandrina. Los principales mecanismos de acción implicados en el potencial antiobesidad de las plantas medicinales son la capacidad de controlar el apetito y la ingesta de energía, estimular la termogénesis, inhibir la lipasa pancreática y reducir la absorción de grasas, disminuir la lipogénesis y aumentar la lipólisis. Por lo tanto, se concluye que las plantas seleccionadas en este estudio mostraron efectos positivos sobre los parámetros bioquímicos y físicos, y pueden ser incluidas en los protocolos como coadyuvantes en los tratamientos de pérdida de peso.

Anti-diabetic potential of ß-boswellic acid and 11-keto-ß-boswellic acid: Mechanistic insights from computational and biochemical approaches.

ß-Boswellic acid (ß-BA) and 11-keto-ß-boswellic acid (ß-KBA) are crucial bioactive compounds, mostly isolated from frankincense. These compounds are known for their potent anticancer and anti-inflammatory activities. Herein, we have explored the complete anti-diabetic potential of ß-BA and ß-KBA with detailed parameters. This research revealed that treatment with ß-BA and ß-KBA at a dose of 1, 2, and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and specifically the concentration of blood glucose level (BGL) in diabetic animals, which indicated that the ß-BA and ß-KBA possess strong anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the antioxidant effects. The biochemical analysis revealed that these compounds improve an abnormal level of several biochemical parameters like serum lipid values including total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) to a normal level and the high-density lipoprotein cholesterol level (HDL-C). To understand the mechanism of action of ß-BA and ß-KBA, their most probable biological targets were searched through the inverse docking approach. Our computational analysis reflects that among other probable targets, the Dipeptidyl peptidase 4 (DPP-4) enzyme could be one of the possible binders of ß-BA and ß-KBA to produce their anti-diabetic activities. These in-silico results were validated by an in-vitro experiment. It indicates that the anti-diabetic effects of ß-BA and ß-KBA are produced by the inhibition of DDP-4. Thus, these anti-diabetic, antioxidant, and anti-hyperlipidemic effects of ß-BA and ß-KBA suggest these compounds as potential therapeutics for diabetic conditions.

Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice.

Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-γ, TNF-α, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients.

Supplementary selenium in the form of selenylation α-D-1,6-glucan ameliorates dextran sulfate sodium induced colitis in vivo.

The deficiency of selenium has been found in clinical IBD patients and supplementation selenium is recognized as beneficial for colitis treatment. In this study, an organic selenium compound-selenylation α-D-1,6-glucan (sCPA) was prepared, and the effect of sCPA on DSS induced colitis mice was investigated. The results suggested that sCPA prevented the weight loss, colon length shortening, and stool loose of colitis mice. It protected colon mucosal barrier by promoting tight junction protein ZO-1 and Occludin expression. Moreover, sCPA reduced oxidative stress via regulating SOD and MDA levels, and decreased the contents of inflammatory proteins NF-κB and NLRP3 and adjusted TNF-α, IFN-γ, IL-1ß, and IL-10 inflammatory cytokines. Furthermore, sCPA repaired intestinal microbiota composition especially Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria that altered by DSS in colitis mice. Meanwhile, SCFAs produced by gut microbiota were restored by sCPA close to the level in the normal group. In conclusion, these findings indicated that the sCPA might be a potential dietary selenium supplementation for the prevention and treatment of colitis.

Yeast Beta-Glucans Ingestion Does Not Influence Body Weight: A Systematic Review and Meta-Analysis of Pre-Clinical Studies.

Dietary fiber supplementation has been studied as a promising strategy in the treatment of obesity and its comorbidities. A systematic review and meta-analysis were performed to verify whether the consumption of yeast beta-glucan (BG) favors weight loss in obese and non-obese rodents. The PICO strategy was employed, investigating rodents (Population), subjected to the oral administration of yeast BG (Intervention) compared to animals receiving placebo (Comparison), evaluating body weight changes (Outcome), and based on preclinical studies (Study design). Two reviewers searched six databases and the grey literature. We followed the PRISMA 2020 guidelines, and the protocol was registered on PROSPERO (CRD42021267788). The search returned 2467 articles. Thirty articles were selected for full-text evaluation, and seven studies remained based on the eligibility criteria. The effects of BG intake on body weight were analyzed based on obese (n = 4 studies) and non-obese animals (n = 4 studies). Even though most studies on obese rodents (75%) indicated a reduction in body weight (qualitative analysis), the meta-analysis showed this was not significant (mean difference -1.35 g-95% CI -5.14:2.45). No effects were also observed for non-obese animals. We concluded that the ingestion of yeast BG barely affects the body weight of obese and non-obese animals.

The use of Caralluma fimbriata as an appetite suppressant and weight loss supplement: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Obesity prevalence has increased during the past few decades, causing a pandemic with an influx in other co-morbidities. Many factors influence weight gain in an obesogenic environment therefore strategies for treating obesity may vary from conventional dietary and physical activity interventions to pharamacotherapy. A shift in unconventional strategies as herbal products for treating obesity have been investigated and one such plant extract is Caralluma fimbriata (C. fimbriata). Further, the studies included were systematically reviewed to gather evidence on potential effects of C. fimbriata as an appetite suppressant and weight loss supplement. METHODS: A systematic review of clinical trials reporting the effects of C. fimbriata as appetite suppression and anti-obesity supplement was reported according to PRISMA guidelines. Data were obtained by searching three databases: PubMed®, Web of Science® and SciVerse Scopus® for studies published until 30th April 2020. RESULTS: A total of 7 articles studying C. fimbriata satisfied the inclusion and exclusion criteria and were sourced from various countries including Australia (3), Cuba (1), India (2) and Spain (1). Almost all studies recruited adults who were overweight or obese with a BMI > 25 kg/m2 (n = 5), with the exception of two studies, one that recruited healthy adults with a BMI average of 26.5 kg/m2 and the second one utilised a population of children and adolescents with Prader-Willis Syndrome (PWS). Parameters assessing obesity, biochemical and appetite factors were analysed by carrying out a meta-analysis. Compared to placebo controlled group, C. fimbriata extract significantly reduced WC by 1.59 cm (95% CI, - 3.07 to - 0.10, p = 0.041) and WHR by 0.06 (95% CI, - 0.12 to - 0.01, p = 0.05) although no significant effects were seen on BW, BMI and HC. Biochemical and appetite parameters outcome on C. fimbriata consumption had no significant changes. Any side effects of individuals who ingested the extract were reported by few studies of which most common effects were constipation, diarrhoea, nausea and rashes. CONCLUSION: Appetite parameters showed no significant changes and metabolic parameters did not improve with C.fimbriata supplementation therefore it is unlikely to recommend C. fimbriata as a weight loss supplement and an appetite suppressant.

Effectiveness of Ascophyllum nodosum and Fucus vesiculosus on Metabolic Syndrome Components: A Real-World, Observational Study.

INTRODUCTION: Gdue is a nutraceutical obtained from the association of two marine algae, Ascophyllum nodosum and Fucus vesiculosus, in addition to chromium picolinate, which could be useful for the treatment of dysglycemia, overweight, and the other components of the metabolic syndrome. The aim of the study was to assess the real-world effectiveness and safety of Gdue when administered to subjects with one or more components of the metabolic syndrome. METHODS: A longitudinal, retrospective, observational study, conducted among primary care physicians, nutritionists, and specialists from various disciplines. The impact of 180 days of administration of Gdue was assessed on body weight, waist circumference, fasting blood glucose, HbA1c, lipid profile, and blood pressure levels. The likelihood of experiencing a first major cardiovascular event over ten years was estimated using Italian risk charts. General linear models for repeated measures were applied to assess changes in the parameters of interest during the follow-up. Results are expressed as estimated marginal means with their 95% confidence interval. RESULTS: Overall, 505 patients were enrolled by 282 physicians. After 6 months of treatment with Gdue, body weight was reduced on average by 7.3 kg (-8.0; -6.6), waist circumference by 7.5 cm (-8.2; -6.8), fasting blood glucose by 16.3 mg/dL (-17.8; -14.7), HbA1c by 0.55% (-0.62; -0.49), systolic and diastolic blood pressure by 7.1 mmHg (-8.3; -6.0) and 4.2 mmHg (-5.0; -3.5), respectively, LDL cholesterol by 18.2 mg/dL (-21.2; -15.3), and triglycerides by 39 mg/dL (-45; -32). HDL cholesterol was significantly increased by 2.9 mg/dL (0.7; 5.0). The 10-year risk of cardiovascular events significantly decreased by 1.8%, corresponding to a relative risk reduction of 27.7%. CONCLUSION: Our real-world study shows that 6 months of treatment with Gdue have an impact on all the components of the metabolic syndrome, thus offering the potential for decreasing the cardiovascular risk associated with metabolic syndrome.

Possible Role of Butyrylcholinesterase in Fat Loss and Decreases in Inflammatory Levels in Patients with Multiple Sclerosis after Treatment with Epigallocatechin Gallate and Coconut Oil: A Pilot Study.

(1) Background. Multiple sclerosis (MS) is characterised by the loss of muscle throughout the course of the disease, which in many cases is accompanied by obesity and related to inflammation. Nonetheless, consuming epigallocatechin gallate (EGCG) and ketone bodies (especially ß-hydroxybutyrate (ßHB)) produced after metabolising coconut oil, have exhibited anti-inflammatory effects and a decrease in body fat. In addition, butyrylcholinesterase (BuChE), seems to be related to the pathogenesis of the disease associated with inflammation, and serum concentrations have been related to lipid metabolism. Objective. The aim of the study was to determine the role of BuChE in the changes caused after treatment with EGCG and ketone bodies on the levels of body fat and inflammation state in MS patients. (2) Methods. A pilot study was conducted for 4 months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Fat percentage and concentrations of the butyrylcholinesterase enzyme (BuChE), paraoxonase 1 (PON1) activity, triglycerides, interleukin 6 (IL-6), albumin and ßHB in serum were measured. (3) Results. The intervention group exhibited significant decreases in IL-6 and fat percentage and significant increases in BuChE, ßHB, PON1, albumin and functional capacity (determined by the Expanded Disability Status Scale (EDSS)). On the other hand, the control group only exhibited a decrease in IL-6. After the intervention, BuChE was positively correlated with the activity of PON1, fat percentage and triglycerides in the intervention group, whereas these correlations were not observed in the control group (4). Conclusions. BuChE seems to have an important role in lipolytic activity and the inflammation state in MS patients, evidenced after administering EGCG and coconut oil as a ßHB source.

Anti-Fibrotic and Anti-Angiogenic Activities of Osbeckia octandra Leaf Extracts in Thioacetamide-Induced Experimental Liver Cirrhosis.

Chronic liver inflammation has become a major global health concern. In the absence of clinical surrogate markers to diagnose inflammatory liver disease, the intervention with effective drugs in modern medicine tends to be late. In Sri Lanka, traditional medical practitioners prescribe herbal preparations from Osbeckia octandra for the prevention and treatment of liver disorders. To test the efficacy of such treatments, we have administered thioacetamide (TAA) to male Wistar rats to induce chronic liver damage (disease control; DC) and examined how various leaf extracts: crude leaf suspension (CLS), boiled leaf extract (BLE), sonicated leaf extract (SLE), methanol leaf extract (MLE) and hexane leaf extract (HLE) of O. octandra ameliorate TAA-induced liver disease. The CLS, BLE and SLE treatments in cirrhotic rats significantly attenuated disease-related changes, such as liver weight and hepato-enzymes. The mRNA levels of Tnf-α were significantly decreased by 3.6, 10 and 3.9 times in CLS, BLE and SLE compared to DC. The same treatments resulted in significantly lower (19.5, 4.2 and 2.4 times) α-Sma levels compared to DC. In addition, Tgf-ß1 and Vegf-R2 mRNA expressions were significantly lower with the treatments. Moreover, BLE expressed a strong anti-angiogenic effect. We conclude that CLS, BLE and SLE from O. octandra have potent hepatic anti-fibrotic effects in TAA-induced liver cirrhosis.

Grape-Seed Proanthocyanidin Extract Reverts Obesity-Related Metabolic Derangements in Aged Female Rats.

Obesity and ageing are current issues of global concern. Adaptive homeostasis is compromised in the elderly, who are more likely to suffer age-related health issues, such as obesity, metabolic syndrome, and cardiovascular disease. The current worldwide prevalence of obesity and higher life expectancy call for new strategies for treating metabolic disorders. Grape-seed proanthocyanidin extract (GSPE) is reported to be effective in ameliorating these pathologies, especially in young animal models. In this study, we aimed to test the effectiveness of GSPE in modulating obesity-related pathologies in aged rats fed an obesogenic diet. To do so, 21-month-old rats were fed a high-fat/high-sucrose diet (cafeteria diet) for 11 weeks. Two time points for GSPE administration (500 mg/kg body weight), i.e., a 10-day preventive GSPE treatment prior to cafeteria diet intervention and a simultaneous GSPE treatment with the cafeteria diet, were assayed. Body weight, metabolic parameters, liver steatosis, and systemic inflammation were analysed. GSPE administered simultaneously with the cafeteria diet was effective in reducing body weight, total adiposity, and liver steatosis. However, the preventive treatment was effective in reducing only mesenteric adiposity in these obese, aged rats. Our results confirm that the simultaneous administration of GSPE improves metabolic disruptions caused by the cafeteria diet also in aged rats.

Therapeutic effects of Gambi-jung for the treatment of obesity.

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.

Studying the pharmacogenomic effect of cranberry extract on reducing body weight using collaborative cross mice.

The non-dialyzable material (NDM) of polyphenol-rich cranberry extract (CRE) powder (NDM-CRE) was studied for its effect of inducing body weight (BW) loss in 13 different mouse lines with well-defined genetically diverse backgrounds, named the collaborative cross (CC). From the age of 8 weeks, the mice were maintained on a high-fat diet (HFD) for 18 weeks, to induce obesity, and BW was measured biweekly. From week 12, CRE was injected intraperitoneally (IP) (50 mg kg-1) 3 times a week per mouse for a 6 week period. Statistical analysis results have shown a significant increase in body weight between week 0 and week 12; the increase in BW of 13 lines of mice on HFD was in the range of 10.41% to 68.65% for males and 9.78% to 64.74% for females. After injecting NDM-CRE extract, our analysis has shown an induced change in BW between week 12 and week 18. In males, NDM-CRE caused a significant decrease in BW of 5 out of the 13 lines in the range of -5.68% to -16.69% and a significant increase of 8.31% in BW of one male line, whereas in seven lines there was no significant decrease (-2.14% to -4.09%). In females, NDM-CRE caused a significant decrease in BW of 5 out of the 13 lines in the range of -3.90% to -11.83%, whereas in eight lines there were no significant changes in BW and it ranged between -1.50% and 4.90%. The broad-sense heritability (H2) and genetic coefficient of variation (CVg) were estimated and found to be between 0.71 and 0.81 for H2, and 0.18 and 0.24 for CVg of females and males, respectively, with respect to the efficacy of NDM-CRE on body weight reduction. Our results have shown that hosts with different genetic backgrounds respond differently to body weight increase, as well as to NDM-CRE treatment for body weight reduction. These results provide a platform for assessing more CC lines and mapping genes underlying the efficacy of the NDM-CRE treatment as a way of understanding pharmacogenomics.

Ophiocordyceps lanpingensis polysaccharides alleviate chronic kidney disease through MAPK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiocordyceps lanpingensis (O. lanpingensis) is a traditional ethno-medicine distributed in Eastern Himalayas, which has been used by local minorities to prevent and treat urinary diseases for hundreds of years. However, the corresponding active components and related pharmacological mechanism of such medication are not clear yet. AIMS OF THE STUDY: This study was performed to investigate the effects and potential mechanisms of O. lanpingensis polysaccharides (OLP) in the treatment of chronic kidney disease (CKD) based on our previous research results. MATERIALS AND METHODS: Methylation analysis was used to investigate the monosaccharide composition and glycosidic linkages in OLP. The animals were divided into the control group, CKD model group, losartan group and three different doses of OLP groups. The CKD mouse model was established by the adenine gavage. The histological changes of renal tissue were observed by Hematoxylin-eosin and Masson staining. Biochemical indicators, including blood urea nitrogen (BUN), serum creatinine (Scr), serum phosphorus (P), plasma calcium (Ca), reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) were measured to evaluate the alleviation of CKD by OLP. Moreover, the expression levels of a series of cytokines related to the inflammation, apoptosis and fibrosis were analyzed to explore the possible mechanisms of OLP to treat CKD. RESULTS: OLP is composed of three kinds of monosaccharides. There are eight kinds of glycosidic linkages in OLP, among which →4)-Glcp-(1→ is the main linkage. OLP could significantly attenuate CKD in mice and the tubulointerstitial damage was recovered to almost normal after the treatment of OLP. Compared with the CKD model group, the levels of Scr, BUN, MDA, P in OLP treatment groups were significantly decreased; and the levels of SOD and Ca were increased after OLP treatment. Furthermore, OLP could reduce the oxidative stress of the renal tissues, decrease the expression levels of pro-inflammatory factors through TLR4-mediated MAPK and NF-κB pathway, inhibit the apoptosis of renal cells by MAPK pathway, and relieve the renal fibrosis by down-regulating the expression of TGF-ß1. CONCLUSIONS: OLP is composed of three kinds of monosaccharides and →4)-Glcp-(1→ is the main glycosidic linkage in the polysaccharide. OLP could ameliorate CKD in mice by declining the oxidative stress, inflammation, apoptosis and fibrosis in the kidneys. The study provided some evidences for the potential application of OLP in alleviating CKD.

Efficacy of dietary supplements containing isolated organic compounds for weight loss: a systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND/OBJECTIVES: A systematic review with meta-analysis was conducted to synthesise evidence on the efficacy of dietary supplements containing isolated organic compounds for weight loss. SUBJECTS/METHODS: Four electronic databases (Medline, Embase, Web of Science, Cinahl) were searched until December 2019. Sixty-seven randomised placebo-controlled trials of dietary supplements containing isolated organic compounds for weight loss were included. Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid and fructans, comparing mean weight difference post-intervention between participants receiving the dietary supplement or placebo. RESULTS: Statistically significant weight differences compared to placebo were observed for chitosan (-1.84 kg; 95% confidence interval [CI] -2.79, -0.88; p < 0.01), glucomannan (-1.27 kg; 95%CI -2.45, -0.09; p = 0.04), and conjugated linoleic acid (-1.08 kg; 95%CI -1.61, -0.55; p < 0.01). None met our threshold for clinical significance (≥2.5 kg). There was no statistically significant effect on weight for fructans compared to placebo (p = 0.24). For dietary supplements with an inadequate number of trials for meta-analysis, a statistically and borderline clinically significant weight difference compared to placebo was found for modified cellulose, manno-oligosaccharides (in males), blood orange juice extract, and three multiple-ingredient dietary supplements. These were only reported in one trial of each. Thus, more evidence is needed before recommending them for weight loss. CONCLUSIONS: While some dietary supplements containing isolated organic compounds warrant further investigation to determine efficacy and safety, there is currently insufficient evidence to recommend any of these dietary supplements for weight loss.

Efficiency of Red Onion Peel Extract Capsules on Obesity and Blood Sugar.

BACKGROUND AND OBJECTIVE: Red onions are one of the most consumed vegetable crops in Egypt, their peel is rich in antioxidants that reduce the risk of diabetes and weight is lost. The study aimed to extract bioactive compounds present in Egyptian Red Onion Peels Waste (ROPE), increasing their efficiency and protecting them using nano-encapsulation as new emerging technology. MATERIALS AND METHODS: Extraction of the bioactive compounds in the Egyptian red onion peels was carried out to study their antioxidant activity before and after nano-emulsions and micro-capsules, their physical and morphological characteristics with their different nano-forms and their application in sponge cake products. The biological evaluation was also studied using rats and statistical analysis. RESULTS: The results showed that the ethanol extracts high content of bioactive compounds compared to water extract and that the use of nano-technique as a new emerging technology in form of nano-emulsion using sodium alginate with diameter size between 8.3-13.6 nm. Results also indicated that there was an improvement in the efficiency of antioxidant activity at high-temperature degrees during baking, with a melting point of up to 223.64°C, with an improvement in the blood sugar levels of diabetic rats and a significant decrease in body weight. CONCLUSION: Nano treatments had a protective effect on liver, safety towards kidneys, lowering blood sugar, improving the efficiency comparing to the other samples and were more acceptable to the consumer.

Exploration of SQC Formula Effect on Type 2 Diabetes Mellitus by Whole Transcriptome Profile in Rats.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that has turned out to be a pandemic all over the world. In China, some traditional Chinese herbal formulas have enjoyed a high reputation in T2DM treatment for centuries. METHODS: In this study, ShenQi compound (SQC) is proposed, a formula that has been performed on T2DM clinical therapeutics in China for many years. The efficacy of SQC in a diabetic rat model by measuring food and water intake and examining islet microcirculatory index involves islets microvessel quantity and density, islets size, pancreatic microvascular wall thickness is evaluated. Meanwhile, gene microarray experiments were performed to explore the molecular mechanism of SQC treatment. In addition, a western medicine, metformin, was employed as a comparison. RESULTS: The results indicated that SQC could effectively improve polydipsia, polyphagia and weight loss caused by diabetes as well as pancreatic tissue damage and vascular injury for T2DM. Meanwhile, the gene microarray experiments indicated that SQC may improve the T2DM by affecting the biological functions related to detection of chemical stimulus involved in sensory perception of smell, G-protein coupled receptor signaling pathway, cytoplasmic translation. In addition, SQC presented curative effect by the regulated function associated with translation, while metformin presented curative effect by the regulated function associated coagulation. CONCLUSION: SQC is an effective therapeutic drug on T2DM, and presents curative effect by regulated function associated with translation.

Risks Associated with the Use of Garcinia as a Nutritional Complement to Lose Weight.

Nowadays, obesity is one of the great nutritional problems facing public health. The prevalence of this pathology has increased in a worrying way over recent years, currently reaching epidemic proportions. In this context, nutritional supplements are presented as a therapeutic alternative to which more and more people are turning to. Nutritional supplements to lose weight based on the Garcinia plant, specifically on Garcinia cambogia, are commonly used. The active principle of this plant to which these properties have been attributed, is hydroxycitric acid (HCA). The aim of the present review is to gather reported data concerning the effectiveness of nutritional supplements based on Garcinia extracts on weight loss and their possible negative effects. Contradictory results have been observed regarding the effectiveness of the supplements. While statistically significant weight loss was observed in some studies, no changes were found in others. Regarding safety, although Garcinia supplements have been revealed as safe in the vast majority of the studies carried out in animal models and humans, some cases of hepatotoxicity, serotonin toxicity and mania have been reported. In conclusion, the results suggest that Garcinia-based supplements could be effective in short-term weight loss, although the data are not conclusive. In addition, the safety of the complement should be further studied.

Daily supplementation with the Lab4P probiotic consortium induces significant weight loss in overweight adults.

This 9-month randomised, parallel, double-blind, single-centre, placebo-controlled study (PROBE, ISRCTN18030882) assessed the impact of probiotic supplementation on bodyweight. Seventy overweight Bulgarian participants aged 45-65 years with BMI 25-29.9 kg/m2 received a daily dose of the Lab4P probiotic comprising lactobacilli and bifidobacteria (50 billion cfu/day). Participants maintained their normal diet and lifestyle over the duration of the study. The primary outcome was change from baseline in body weight and secondary outcomes included changes in waist circumference, hip circumference and blood pressure. A significant between group decrease in body weight (3.16 kg, 95% CI 3.94, 2.38, p < 0.0001) was detected favouring the probiotic group. Supplementation also resulted in significant between group decreases in waist circumference (2.58 cm, 95% CI 3.23, 1.94, p < 0.0001) and hip circumference (2.66 cm, 95% CI 3.28, 2.05, p < 0.0001) but no changes in blood pressure were observed. These findings support the outcomes of a previous shorter-term Lab4P intervention study in overweight and obese participants (PROMAGEN, ISRCTN12562026). We conclude that Lab4P has consistent weight modulation capability in free-living overweight adults.