18KHT01, a Potent Anti-Obesity Polyherbal Formulation

Obesity is a life-threatening metabolic disorder necessitating urgent development of safe and effective therapy. Currently, limited such therapeutic measures are available for obesity. The present study was designed to develop a novel, safe and effective herbal therapy for the management of obesity. A polyherbal formulation (18KHT01) was developed by homogeneously mixing a specific proportion of crude Quercus acutissima (acorn jelly powder), Camellia sinensis (dry leaf buds), and Geranium thunbergii (dry aerial part) along with Citrus limon (fruit juice). Synergistic antioxidant, antiadipogenic, and anti-obesity activities were evaluated by in vitro as well as in vivo studies. In vitro experiments revealed strong synergistic antioxidant and anti-adipogenic activities of 18KHT01. Molecular assessment of 18KHT01 showed significant down-regulation of vital adipogenic factors such as PPARγ, C/EBPα, aP2, SREBP-1c, FAS, and LPL. Based on the results of the preliminary toxicity study, 75 and 150 mg/kg, twice daily doses of 18KHT01 were administered to evaluate anti-obesity activity in diet-induced obese (DIO) C57BL/6J mice model. The major obesity-related parameters such as body weight, weight gain, food efficiency ratio, as well as serum lipid profile were significantly reduced by 18KHT01 with potential synergism. Also, the high-fat diet-induced insulin resistance was suggestively alleviated by the formulation, and thus ameliorated fasting blood glucose. Histological evaluation of liver and white adipose tissue revealed that the significant reduction of fat depositions and thus reduction of these tissue weights. Synergy evaluation experiments exhibited that the 18KHT01 offered strong synergism by improving efficacy and reducing the toxicity of its ingredients. Overall results evidenced the 18KHT01 as a safe and potent anti-obesity herbal therapy.

Evaluation of Anti-Obesity Activity of an Herbal Formulation (F2) in DIO Mice Model and Validation of UPLC-DAD Method for Quality Control

Obesity is considered a chronic metabolic disorder that can be associated with multiple medical complications. Currently, there is no or limited curative therapy for obesity. This study focused on the assessment of anti-obesity activity and UPLC standardization of a polyherbal formulation (F2). An anti-obesity activity was investigated using the diet-induced obese (DIO) mice model, where obesity was developed in C57BL/6J mice by providing a high-fat diet (HFD) for five weeks without treating drugs. After the successful development of obesity, the obese mice were treated with F2 for seven weeks with continuing HFD feeding. The major obesity-related parameters such as body weight gain, food efficiency ratio, serum lipid profile, and white adipose tissue (WAT) mass were found to be significantly reduced in F2 treated obese mice. These results were supported by the down-regulation of specific adipogenic transcription factors (PPARγ, SREBP-1c, and ap2) in epididymal WAT. Histological evaluation of liver and WAT also revealed reduced fat deposition in the tissues by F2 compared to the HFD control group. The overall observations indicated that the F2 exhibited pronounced obesity-controlling activity through the inhibition of adipocyte differentiation and triglyceride accumulation in the tissues, and serum lipid depletion. In addition, F2 ameliorated obesity-induced insulin resistance. Furthermore, the UPLC-DAD method for quality control of F2 was validated and standardized using five reference compounds: astragalin, ellagic acid, fisetin, fustin, and sulfuretin.

Caloric Restriction Prevents Metabolic Dysfunction and the Changes in Hypothalamic Neuropeptides Associated with Obesity Independently of Dietary Fat Content in Rats

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.

Functional Foods for Management of Diarrhea and Malnutrition in Rats Emphasizing on Nucleotides Role

Background: Diarrhea and malnutrition are major health problems in developing countries. Inflammation, high oxidative stress, poor nutritional status, and fatty liver were encountered during such diseases. Patents for diarrhea and malnutrition management (WO2007/130882A2, WO00/37106A1, WO2014/152420, and CA2987364A1) were published. Objective: The objective was to introduce anti-diarrhea functional foods with a preventive effect on malnutrition. Methods: Two processing techniques were applied for preparing functional foods (formula 1 ingredients were made into cookies followed by grinding; formula 2 ingredients were pre-cooked, dried, and mixed in powder form) that were evaluated in a rat model of diarrhea with malnutrition (DM). Formula 2 was also assessed when mixed with nucleotides. The ingredients were edible plants that possess an anti-diarrheal effect with high protein sources (legumes and casein). Results: Induction of diarrhea with malnutrition, high oxidative stress, inflammation, accumulation of liver fat, and histopathological changes were demonstrated in DM control compared to normal control. The functional foods produced variable improvement in growth curves, food efficiency ratio, hemoglobin, hematocrit and plasma zinc, protein, albumin, globulin, lipase activity, and MDA. Formula 1 was superior in improving intestinal histopathology while formula 2 was more efficient in elevating plasma iron. Formula 2 with nucleotides was the best in improving growth curves, alkaline phosphatase, and reducing liver fat. Intestinal mucosa reduced glutathione and nitrite showed an efficient significant reduction on treatment with formula 2 with or without nucleotides. The formulas showed an anti-diarrheal effect by improving feces weight and moisture content. Conclusion: Studied functional foods showed an anti-diarrheal effect and malnutrition improvement with different degrees.

Hypolipidemic and antioxidant activities of oil from Antarctic krill (Euphausia superba)

Background: This study aims to determine the hypolipidemic and antioxidant activities of oil from Antarctic krill (AK) (Euphausia superba) in rats.Methods: Thirty-six rats were randomly assigned to three groups fed with diets containing high-fat (HF), AK oil (AKO) or normal fat for 6 weeks.Results: Compared with the HF group, the AKO-diet group had decreased body weight gain, food efficiency ratio, plasma triacylglycerol and total cholesterol but increased faecal fat and cholesterol, plasma low-density lipoprotein cholesterol level and plasma phenoloxidase activity, superoxide dismutase (SOD) activity and glutathione peroxidase activity of rats.Conclusions: These results indicated that AKO is a suitable alternative for hypolipidemic and antioxidant source for humans.

Antiobesity, Regulation of Lipid Metabolism, and Attenuation of Liver Oxidative Stress Effects of Hydroxy-α-sanshool Isolated from Zanthoxylum bungeanum on High-Fat Diet-Induced Hyperlipidemic Rats

Zanthoxylum bungeanum is a traditional Chinese medicine (TCM) used to relieve pain, dispel dampness, stop diarrhea, and prevent itching. The aim of this study was to investigate the antiobesity and hypolipidemic effects of hydroxy-α-sanshool (HAS) isolated from Z. bungeanum on hyperlipidemic rats. Wistar rats (n=48) were randomly divided into six groups: (1) normal diet rats (ND), (2) high-fat diet- (HFD-) treated rats, (3) HFD+fenofibrate-treated rats (HFD+FNB), (4) HFD+low dose of HAS-treated rats (HFD+LD, 9 mg/kg), (5) HFD+middle dose of HAS-treated rats (HFD+MD, 18 mg/kg), and (6) HFD+high dose of HAS-treated rats (HFD+HD, 36 mg/kg). The body weight and food intake of the rats were recorded during the treatment period. After 4 weeks of HAS treatment, abdominal adipose tissues were observed and total cholesterol (T-CHO), triglycerides (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and low-density lipoprotein (LDL) cholesterol (LDL-C) of serum and liver tissues were determined. Furthermore, histochemical examinations using oil red O and hematoxylin-eosin staining (H&E) were carried out and levels of malondialdehyde (MDA) and glutathione (GSH) and activities of superoxide dismutase (SOD) in the liver were determined. After HFD feeding, the body weight gain and food efficiency ratio of HFD rats were significantly enhanced (p<0.05vs. ND rats) and HAS treatment (18 and 36 mg/kg) significantly decreased the body weight gain and food efficiency ratio (p<0.05vs. HFD rats). In addition, HAS treatment could decrease the abdominal adipose tissues and liver adipocytes. Furthermore, HAS treatment significantly decreased the T-CHO, TG, and LDL-C, whereas it increased HDL-C (p<0.05vs. HFD rats) in serum and the liver. HAS treatment increased the GSH level and SOD activity in the liver (p<0.05vs. HFD rats), whereas it decreased the levels of MDA (p<0.05vs. HFD rats). mRNA analyses suggested that HAS treatment increases the expression of Pparg (proliferator-activated receptor γ) and Apoe (peroxisome apolipoprotein E). Immunohistochemistry and Western blotting indicated that HAS stimulation increased the levels of PPARγ and APOE in the liver, as a stress response of the body defense system. These results revealed that HAS exerts antiobesity and hypolipidemic activities in HFD rats by reducing liver oxidative stress and thus could be considered as a potential candidate drug to cure or prevent obesity and hyperlipidemia.

Assessment and Biomonitoring of the Effect of Rapeseeds Oil on Wister Rat Organs

Rapeseed oil is one of the important and cheapest vegetable oil in Bangladesh and many other countries. It is commonly used as cooking oil in Bangladesh particularly in rural areas and also used as other food items. This study evaluated the physiological effects of four type’s rapeseeds namely Mustard (Wild), Mustard (hybrid), Rai (Wild), Rai (hybrid) oil on six strains of bacteria in addition to studying the effects of two varieties of rapeseeds oil Mustard (Wild) and Rai (hybrid) oil on Wistar rat’s organs including liver, kidney, heart and skeletal muscles. Firstly, we examined the effects of these Rapeseeds oil on bacteria and found that these Rapeseeds oils possess antibacterial activities. Six bacterial strains such as B. subtilis, S. lutea, X. campestris, E. coli, K. Pneumonia, P. denitrificans was used to test the effect of these rapeseeds oil and observed that rapeseed oil showed inhibition against tested microorganisms in a concentration-dependent manner. Finally, the effects of oil obtained from these two varieties were investigated after feeding rats for 8 weeks. Male Wistar rats were divided into three groups, each group contains 4 rats. Group A was considered as control diet group, while Group B was mustard (Wild) oil group and Group C was Rai (hybrid) oil group. Group A was containing 0.6 gram oil plus 14.4gm diet. We found that rats of both experimental groups exhibit weight loss, reduction of food efficiency ratio and increase cardiac and hepatic enzymes including CK-MB, ALP, SGPT and SGOT compared to the rats fed controlled diet. Furthermore, we also found that the body weight loss, food efficiency ratio markedly decreased and tested enzymes increased in rats fed Mustard (Wild) oil compared to rat fed Rai (hybrid) oil.

Amelioration of chronic fluoride toxicity by calcium and fluoride-free water in rats

The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Ca+F − ; low-Ca (0·25 %) diet (LCD), Ca − F − ; NCD +100 parts per million (ppm) F water, Ca+F+; LCD +100 ppm F water, Ca − F+. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Ca+F+ and Ca − F+ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca − F+. Reduced serum 25-hydroxy-vitamin D3, increased 1,25-dihydroxy-vitamin D3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca − F − and Ca − F+. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca − F+/Ca+F − and Ca − F+/Ca+F+ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Ca+F+/Ca+F+ and Ca − F+/Ca+F+) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.