Formation, physicochemical properties, and biological activities of theabrownins.

Theabrownins (TBs) are heterogeneous mixtures of water-soluble brown tea pigments, and important constituents to evaluate the quality of dark tea. TBs have numerous hydroxyl and carboxyl groups and are formed by the oxidative polymerization of tea polyphenols. Many biological activities attributed to TBs, including antioxidant, anti-obesity, and lipid-regulating, have been demonstrated. This review summarizes the research progress made on the formation mechanism and physicochemical properties of TBs. It also discusses their protective effects against various diseases and associated potential molecular mechanisms. Additionally, it examines the signaling pathways mediating the bioactivities of TBs and highlights the difficulties and challenges of TBs research as well as their research prospects and applications.

Mulberry leaf and its effects against obesity: A systematic review of phytochemistry, molecular mechanisms and applications.

BACKGROUND: Obesity and hyperlipidemia can induce a variety of diseases, and have become major health problems worldwide. How to effectively prevent and control obesity has become one of the hot-spots of contemporary research. Mulberry leaf is the dried leaf of Morus alba L., which is approved by the Ministry of Health as a "homology of medicine and food", rich in diverse active constituents and with a variety of health effects including anti-obesity and anti-hyperlipidemia activities. PURPOSE: The review attempts to summarize and provide the molecular basis, mechanism, safety and products for further exploration and application of mulberry leaf on the treatment on the control of weight gain and obesity. METHODS: This review is conducted by using ScienceDirect, PubMed, CNKI and Web of Science databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Based on the research progress of domestic and foreign scholars, the effective phytochemicals, molecular mechanisms and product applications of mulberry leaf in the prevention and treatment of obesity and related metabolic diseases were summarized. CONCLUSION: Mulberry leaf has excellent medicinal and health care value in obesity treatment. However, its pharmacodynamic substance basis and molecular mechanisms need to be further studied.

Antioxidant and Anti-Obesity Effects of Juglans mandshurica in 3T3-L1 Cells and High-Fat Diet Obese Rats.

Juglans mandshurica Maxim. walnut (JMW) is well-known for the treatment of dermatosis, cancer, gastritis, diarrhea, and leukorrhea in Korea. However, the molecular mechanism underlying its anti-obesity activity remains unknown. In the current study, we aimed to determine whether JMW can influence adipogenesis in 3T3-L1 preadipocytes and high-fat diet rats and determine the antioxidant activity. The 20% ethanol extract of JMW (JMWE) had a total polyphenol content of 133.33 ± 2.60 mg GAE/g. Considering the antioxidant capacity, the ABTS and DPPH values of 200 µg/ml of JMWE were 95.69 ± 0.94 and 79.38 ± 1.55%, respectively. To assess the anti-obesity activity of JMWE, we analyzed the cell viability, fat accumulation, and adipogenesis-related factors, including CCAAT-enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP1c), peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). We found that total lipid accumulation and triglyceride levels were reduced, and the fat accumulation rate decreased in a dose-dependent manner. Furthermore, JMWE suppressed adipogenesis-related factors C/EBPα, PPARγ, and SREBP1c, as well as FAS and ACC, both related to lipogenesis. Moreover, animal experiments revealed that JMWE could be employed to prevent and treat obesity-related diseases. Hence, JMWE could be developed as a healthy functional food and further explored as an anti-obesity drug.

Comparing and contrasting different herbal products intended for the management of obesity approved in the Palestinian markets.

BACKGROUND: The use of conventional medical therapies has proven to have many setbacks and safety concerns that need further improvement. However, herbal medicine has been used for over 2000 years, and many studies have proven the use of herbs to be effective and safe. This article discussed the efficacy of different herbal products used in the management of obesity. To evaluate the efficacy of seven herbal-based weight loss products currently available on the Palestinian market, using in vitro assays to screen for antioxidants, anti-amylase, and anti-lipase effects for each product. METHOD: Pancreatic lipase and salivary amylase inhibitory activities, as well as antioxidant analysis, were tested in vitro on a variety of herbal products. Then the IC50 was measured for each test. RESULTS: The anti-lipase assay results, IC50 values in (µg/mL) of each of the seven products (Product A, product B, product C, product D, product E, product F, and product G) were 114.78, 532.1, 60.18, 53.33, 244.9, 38.9, and 48.97, respectively. The IC50 value for orlistat (Reference) was 12.3 µg/ml. On the other hand, the IC50 value for alpha amylase inhibition of the seven products (Product A, product B, product C, product D, product E, product F, and product F) were 345.93, 13,803.84 (Inactive), 73.79, 130.91, 165.95, 28.18, and 33.11 µg/ml respectively, while acarbose (Reference) was 23.38 µg/ml. The antioxidant activity (IC50 values) for the seven products (Product A, product B, product C, product D, product E, product F, and product F) were 1258.92, 707.94, 79.43, 186.20, 164.81, 17.53, and 10.47 µg/ml respectively. While the IC50 value for Trolox was 2.70 µg/ml. CONCLUSION: It can be concluded that the seven products showed varied anti-lipase, anti-amylase, and antioxidant effects. However, products F and G showed superiority in all categories.

Anti-obesity carbonic anhydrase inhibitors: challenges and opportunities.

The mitochondrial isoforms VA/VB of metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) are involved in metabolic processes, such as de novo lipogenesis and fatty acid biosynthesis. We review the drug design landscape for obtaining CA VA/VB-selective/effective inhibitors, starting from the clinical observations that CA inhibitory drugs, such as the antiepileptics topiramate and zonisamide, or the diuretic acetazolamide induce a significant weight loss. The main approaches for designing such compounds consisted in drug repurposing of already known CA inhibitors (CAIs); screening of synthetic/natural products libraries both in the classical and virtual modes, and de novo drug design using the tail approach. A number of such studies allowed the identification of lead compounds diverse from sulphonamides, such as tropolones, phenols, polyphenols, flavones, glycosides, fludarabine, lenvatinib, rufinamide, etc., for which the binding mode to the enzyme is not always well understood. Classical drug design studies of sulphonamides, sulfamates and sulfamides afforded low nanomolar mitochondrial CA-selective inhibitors, but detailed antiobesity studies were poorly performed with most of them. A breakthrough in the field may be constituted by the design of hybrids incorporating CAIs and other antiobesity chemotypes.

Antiobesity drug-likeness properties and pancreatic lipase inhibition of a novel low molecular weight lutein oxidized product, LOP6.

Elevated expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), a key regulator of adipogenesis, leads to lipid accumulation and obesity. Although orlistat is effective for obesity, flatus with discharge, faecal urgency, oily evacuation and other allied side effects limit its usage. Thus, natural product-based drug intervention is the future of research and development of novel treatment. We synthesized and characterized total lutein oxidized products (LOPs) by exposing lutein to direct sunlight with a solar intensity of 5.89 kW h m-2 day-1 and at 31 ± 2 °C for 1-10 days. Total LOPs were analyzed on C18 and structural elucidation was carried on LCMS/MS-TOF. The pancreatic lipase inhibition kinetics was estimated. The binding effects of LOP6 (fragmented peak 6) on PPAR-γ, pancreatic lipase, pharmacokinetic properties and inhibition studies were analysed. Histological evaluation of liver and adipose tissues was performed to confirm the antiobesity effect of total LOPs. The yield of extracted lutein purified from shade-dried marigold flower petals was 6%. Total LOPs were formed on the 10th day upon exposure of lutein to direct sunlight. Total LOPs on the C18 column fragmented into eight oxidized products (LOP1 to LOP8). The total LOPs showed significant inhibition of pancreatic lipase activity with an IC50 of 1.6953 µg ml-1, and Km and Vmax of 3.05 µg and 1.19 µg s-1 respectively following mixed type of inhibition. The LOP6 [4-((1E,3E,5E)-3,7-dimethylocta-1,3,5,7-tetraen-1-yl)-3,5,5-trimethylcyclohex-3-enol] with an approximate molecular mass of 274.25 showed a binding energy of -5.40 kcal mol-1 with a Ki of 109.43 µM for PPAR-γ and a docking score of -5.35 kcal mol-1 with a Ki of 119.4 µM for pancreatic lipase. The IC50 of LOP6 was 11.8420 µg ml-1, and Km and Vmax were 2.519 µg and 1.294 µg s-1. The pharmacokinetic properties such as solubility, permeability, bioavailability, and topological polar surface area when tested with LOP6 were significantly better than those of lutein alone. The histological examination of the liver and adipose tissue revealed that all three doses of total LOPs were effective in alleviating the ballooning and vesicular degeneration of hepatocytes and invasion of inflammatory cells in the adipose tissue. Total LOPs and LOP6 inhibited pancreatic lipase activity in vitro. LOP6 showed a better docking score for PPAR-γ and pancreatic lipase in comparison to orlistat. Histological data showed that the total LOPs exerted antiobesity activity. Thus, LOPs might provide a novel treatment approach for obesity.

Seabuckthorn polysaccharide ameliorates high-fat diet-induced obesity by gut microbiota-SCFAs-liver axis.

Obesity has been reported to be associated with gut microbiome dysbiosis. seabuckthorn fruits have traditionally been used in Tibetan foods and medicines for thousands of years. Seabuckthorn polysaccharide (SP) is one of the main functional components in seabuckthorn fruits. However, the effects of SP on a high-fat diet (HFD)-induced obesity have not yet been elucidated. The purpose of this study is to explore the amelioration effect of SP on obesity induced by HFD and to reveal its mechanism of gut microbiota and its metabolites. Results showed that 12-week SP (0.1%, w/w) dietary supplementation could significantly reduce body weight gain, serum lipid level and liver triglycerides level in obese mice. Notably, the SP treatment elevated p-AMPKα and PPARα proteins expression stimulated the phosphorylation of ACC1 and inhibited the protein expression of FAS, PPARγ, and CD36 in the mice liver. Further, SP also reorganized the gut microbiome by up-regulating the proportion of Muribaculaceae_unclassified, Bifidobacterium, Rikenellaceae_RC9_gut_group, Alistipes, and Bacteroides, and down-regulating the abundance of Lactobacillus, Firmicutes_unclassified, Dubosiella Bilophila, and Streptococcus in HFD-induced obese mice. Moreover, the production of microbial metabolites short-chain fatty acids (SCFAs) in feces has also increased. In addition, correlation analysis results showed that obesity-ameliorating effects of SP were highly associated with levels of SCFAs in feces. Therefore, the regulation of SP on liver lipid metabolism may be due to the variation of the gut microbiome and raised production of SCFAs. These results indicate that SP could play the part of a potential nutraceutical for ameliorating obesity through regulation of the gut-liver axis.

Litchi chinensis seed prevents obesity and modulates the gut microbiota and mycobiota compositions in high-fat diet-induced obese zebrafish.

Obesity continues to be a global public health challenge. Litchi chinensis seed is rich in bioactive ingredients with pharmacological effects, such as hypoglycemic activity and anti-oxidation. This study aimed to assess the potential anti-obesity effects of L. chinensis seed and the changes of gut microbiota and mycobiota compositions in obese zebrafish induced by a high-fat diet. The anti-obesity effects were supplemented and validated in high-fat diet-induced obese mice. In this study, various chemical components of L. chinensis seed water and ethanol extracts were detected using UHPLC-QE-MS, and both extracts showed strong in vitro antioxidant activities. Network pharmacology analysis showed the potential of the extracts to improve obesity. Litchi chinensis seed powder, water and ethanol extracts decreased the weight of obese zebrafish, improved lipid accumulation and lipid metabolism, regulated appetite, and inhibited cell apoptosis and inflammation of the liver and intestine. They showed similar effects in obese mice, and also reduced the weight of fat tissues, regulated insulin resistance and glucose metabolism, and improved the intestinal barrier. Additionally, L. chinensis seed modulated the compositions of gut microbiota and mycobiota in zebrafish, with the regulation of the proportion of bacteria that produce short-chain fatty acids or affect intestine health, including Cetobacterium, Trichococcus, Aeromonas, Staphylococcus, and Micrococcaceae, and the proportion of fungi that produce mycotoxins or have special metabolic capacities, including Penicillium, Candida, Rhodotorula, and Trichoderma. Spearman's correlation analysis revealed the potential link between zebrafish obesity parameters, gut bacteria and fungi. Overall, these findings indicated that L. chinensis seed effectively improved obesity.

Oolong tea extract alleviates weight gain in high-fat diet-induced obese rats by regulating lipid metabolism and modulating gut microbiota.

Obesity is a serious global health issue, and the societal interventions during the COVID-19 pandemic may have perturbed energy homeostasis, which affects the condition of obesity. Tea is a traditional beverage in Asia and has been shown to provide many beneficial health effects. Oolong tea is semifermented, with its chemical composition comprising features of green (unfermented) and black (fermented) tea. Although green tea has anti-obesity properties, studies on the anti-obesity ability of oolong tea are still scarce. In this study, we analyzed the chemical composition of oolong tea extract (OTE) and investigated the effects of OTE on high-fat diet-induced obese rats. OTE contained more (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, and (-)-gallocatechin-3-gallate than theaflavins and theasinensins. Rats fed with a high-fat diet (HFD) and treated with 0.5% OTE exhibited significantly reduced body weight and visceral fat weight compared with the HFD-only group. OTE also decreased adipocyte size, lipogenesis-related protein sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) protein expression and increased thermogenesis-related protein peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and uncoupling protein 1 (UCP1) protein expression in epididymal adipose tissue compared with the HFD group. Moreover, the OTE groups had a significantly higher abundance of Candidatus arthromitus and Hydrogenoanaerobacterium and a lower abundance of Ruminococcus1, Oscillibacter, and Odoribacter compared with the HFD group. All these results show that OTE can alleviate weight gain by regulating lipid metabolism and modulating the distribution of the gut microbiota to decrease lipid accumulation in adipose tissue.

Antioxidant, Anti-Obesity, Nutritional and Other Beneficial Effects of Different Chili Pepper: A Review.

Fruits and vegetables are important components of a healthy diet. They are rich sources of vitamins and minerals, dietary fibre and a host of beneficial non-nutrient substances including plant sterols, flavonoids and other antioxidants. It has been reported that reduced intake of fruits and vegetables may increase the risk of non-communicable diseases (NCDs). Chili pepper, is a common and important spice used to enhance taste and nutrition. Over the years, reports have shown its potential as antioxidant and an anti-obesity agent. Obesity is a serious health concern as it may initiate other common chronic diseases. Due to the side effects of synthetic antioxidants and anti-obesity drugs, scientists are now focusing on natural products which produce similar effects to synthetic chemicals. This up-to-date review addresses this research gap and presents, in an accessible format, the nutritional, antioxidant and anti-obesity properties of different chili peppers. This review article serves as a reference guide for use of chili peppers as anti-obesity agents.

Anti-Obesity Effects of a Mixture of Atractylodes macrocephala and Amomum villosum Extracts on 3T3-L1 Adipocytes and High-Fat Diet-Induced Obesity in Mice.

Since the potential of (3:1) mixtures of Atractylodes macrocephala and Amomum villosum extracts has been proposed in the management of obesity, the purpose of present study was to investigate the effects of AME:AVE (3:1) mixture on weight loss, obesity-related biochemical parameters, adipogenesis and lipogenesis related proteins in 3T3-L1 cells and HFD-induced obesity in a mouse model. Treatment with AME:AVE (3:1) mixture inhibited lipid accumulation. Furthermore, the treatment with 75 and 150 mg/kg of AME:AVE (3:1) significantly decreased the body weight gain, white adipose tissue (WAT) weight, and plasma glucose level in HFD-induced obese mice. Moreover, treatment with 75 and 150 mg/kg AME:AVE (3:1) also significantly lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in liver. AME:AVE (3:1) treatment significantly decreased the expression of proteins related to adipogenesis and lipogenesis in 3T3-L1 adipocytes and WAT of HFD-induced obese mice. These results suggest that the AME:AVE herbal mixture (3:1) has anti-obesity effects, which may be elicited by regulating the expression of adipogenesis and lipogenesis-related proteins in adipocytes and WAT in HFD-induced obesity in mice.

Novel anti-adipogenic effect of CF3-allylated indole in 3T3-L1 cells.

Indole derivatives from various plants are known to have health benefits because of their anti-cancer, anti-oxidant, anti-inflammatory, and anti-tubercular effects. However, their effects on adipogenesis have not been fully elucidated yet. Herein, we show that a newly synthesized indole derivative, CF3-allylated indole, [(E)-1-(pyrimidin- 2-yl)-2-(4,4,4- trifluorobut-2-enyl)-1H-indole], effectively inhibits adipogenesis. We found that CF3-allylated indole inhibited lipid accumulation and suppressed the expression of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator activated receptor γ (PPARγ) in 3T3-L1 cells. The inhibitory effect of CF3-allylated indole primarily occurred at the early phase of adipocyte differentiation by increasing intracellular cyclic adenosine monophosphate (cAMP) levels and enhancing protein kinase A (PKA) and adenosine monophosphate-activated protein kinase (AMPK) signaling. Conversely, depletion of PKA or treatment with a protein kinase A inhibitor (H89) reversed such inhibitory effects of CF3-allylated indole on adipogenesis and PPARγ expression. These results suggest that CF3-allylated indole inhibits early stages of adipogenesis by increasing phosphorylation of PKA/AMPK, leading to decreased expression of adipogenic genes in 3T3-L1 cells. These results indicate that CF3-allylated indole has potential for controlling initial adipocyte differentiation in metabolic disorders such as obesity.

Centranthus ruber (L.) DC. and Tropaeolum majus L.: Phytochemical Profile, In Vitro Anti-Denaturation Effects and Lipase Inhibitory Activity of Two Ornamental Plants Traditionally Used as Herbal Remedies.

Ornamental plants often gain relevance not only for their decorative use, but also as a source of phytochemicals with interesting healing properties. Herein, spontaneous Centranthus ruber (L.) DC. and Tropaeolum majus L., mainly used as ornamental species but also traditionally consumed and used in popular medicine, were investigated. The aerial parts were extracted with methanol trough maceration, and resultant crude extracts were partitioned using solvents with increasing polarity. As previous studies mostly dealt with the phenolic content of these species, the phytochemical investigation mainly focused on nonpolar constituents, detected with GC-MS. The total phenolic and flavonoid content was also verified, and HPTLC analyses were performed. In order to explore the potential antiarthritic and anti-obesity properties, extracts and their fractions were evaluated for their anti-denaturation effects, with the use of the BSA assay, and for their ability to inhibit pancreatic lipase. The antioxidant properties and the inhibitory activity on the NO production were verified, as well. Almost all the extracts and fractions demonstrated good inhibitory effects on NO production. The n-hexane and dichloromethane fractions from T. majus, as well as the n-hexane fraction from C. ruber, were effective in protecting the protein from heat-induced denaturation (IC50 = 154.0 ± 1.9, 270.8 ± 2.3 and 450.1 ± 15.5 µg/mL, respectively). The dichloromethane fractions from both raw extracts were also effective in inhibiting pancreatic lipase, with IC50 values equal to 2.23 ± 0.02 mg/mL (for C. ruber sample), and 2.05 ± 0.02 mg/mL (T. majus). Obtained results support the traditional use of these species for their beneficial health properties and suggest that investigated plant species could be potential sources of novel antiarthritic and anti-obesity agents.

Soluble Polysaccharide Derived from Laminaria japonica Attenuates Obesity-Related Nonalcoholic Fatty Liver Disease Associated with Gut Microbiota Regulation.

In this study, the effects of a polysaccharide derived from Laminaria japonica (LJP) on obesity were investigated in mice fed a high-fat diet (HFD). LJP significantly attenuated obesity-related features, lowering serum triglycerides, glucose, total cholesterol and low-density lipoprotein cholesterol levels. HFD-induced liver steatosis and hepatocellular ballooning were significantly attenuated by LJP. Additionally, LJP was found to significantly modulate hepatic gene expressions of AMPK and HMGCR, which are key regulators of lipid and cholesterol metabolism. We further found that LJP ameliorated HFD-induced gut microbiota (GM) dysbiosis by significantly reducing the obesity-related Firmicutes to Bacteroidetes ratio, meanwhile promoting the growth of Verrucomicrobia at the phylum level. At the genus level, propionate-producing bacteria Bacteroides and Akkermansia were elevated by LJP, which might explain the result that LJP elevated fecal propionate concentration. Taken together, these findings suggest that dietary intake of LJP modulates hepatic energy homeostasis to alleviate obesity-related nonalcoholic fatty liver disease associated with GM regulation.

Anti-Cancer and Medicinal Potentials of Moringa Isothiocyanate.

Moringa oleifera (M. oleifera), which belongs to the Moringaceae family, is a common herb, rich in plant compounds. It has a variety of bioactive compounds that can act as antioxidants, antibiotics, anti-inflammatory and anti-cancer agents, etc., which can be obtained in different body parts of M. oleifera. Isothiocyanates (ITCs) from M. oleifera are one class of these active substances that can inhibit cancer proliferation and promote cancer cell apoptosis through multiple signaling pathways, thus curbing cancer migration and metastasis, at the same time they have little adverse effect on normal cells. There are multiple variants of ITCs in M. oleifera, but the predominant phytochemical is 4-(α-L-rhamnosyloxy)benzyl isothiocyanate, also known as moringa isothiocyanate (MIC-1). Studies have shown that MIC-1 has the possibility to be used clinically for the treatment of diabetes, neurologic diseases, obesity, ulcerative colitis, and several cancer types. In this review, we focus on the molecular mechanisms underlying the anti-cancer and anti-chronic disease effects of MIC-1, current trends, and future direction of MIC-1 based treatment strategies. This review combines the relevant literature of the past 10 years, in order to provide more comprehensive information of MIC-1 and to fully exploit its potentiality in the clinical settings.

18:0 Lyso PC Derived by Bioactivity-Based Molecular Networking from Lentil Mutant Lines and Its Effects on High-Fat Diet-Induced Obese Mice.

Lentil (Lens culinaris; Fabaceae), one of the major pulse crops in the world, is an important source of proteins, prebiotics, lipids, and essential minerals as well as functional components such as flavonoids, polyphenols, and phenolic acids. To improve crop nutritional and medicinal traits, hybridization and mutation are widely used in plant breeding research. In this study, mutant lentil populations were generated by γ-irradiation for the development of new cultivars by inducing genetic diversity. Molecular networking via Global Natural Product Social Molecular Networking web platform and dipeptidyl peptide-IV inhibitor screening assay were utilized as tools for structure-based discovery of active components in active mutant lines selected among the lentil population. The bioactivity-based molecular networking analysis resulted in the annotation of the molecular class of phosphatidylcholine (PC) from the most active mutant line. Among PCs, 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (18:0 Lyso PC) was selected for further in vivo study of anti-obesity effect in a high-fat diet (HFD)-induced obese mouse model. The administration of 18:0 Lyso PC not only prevented body weight gain and decreased relative gonadal adipose tissue weight, but also attenuated the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and leptin in the sera of HFD-induced obese mice. Additionally, 18:0 Lyso PC treatment inhibited the increase of adipocyte area and crown-like structures in adipose tissue. Therefore, these results suggest that 18:0 Lyso PC is a potential compound to have protective effects against obesity, improving obese phenotype induced by HFD.

Anti-Obesity Effects of Matoa (Pometia pinnata) Fruit Peel Powder in High-Fat Diet-Fed Rats.

Fruit peels, pericarps, or rinds are rich in phenolic/polyphenolic compounds with antioxidant properties and potentially beneficial effects against obesity and obesity-related non-communicable diseases. This study investigated the anti-obesity effects of matoa (Pometia pinnata) and salak (Salacca zalacca) fruit peel. Neither matoa peel powder (MPP) nor salak peel powder (SPP) affected the body weight, visceral fat weight, or serum glucose or lipid levels of Sprague-Dawley rats when included as 1% (w/w) of a high-fat diet (HFD). However, MPP significantly decreased the hepatic lipid level. MPP at a dose of 3% (w/w) of the HFD decreased body weight, visceral fat, and serum triglyceride levels as well as the hepatic lipid content. The inhibitory effect of MPP on hepatic lipid accumulation was not enhanced when its concentration was increased from 1% to 3% of the HFD. The anti-obesity effect of matoa was partly explained by the inhibitory effect of the matoa peel extract on fatty acid-induced secretion of ApoB-48 protein, a marker of intestinal chylomicrons, in differentiated Caco-2 cell monolayers. We identified hederagenin saponins that are abundant in MPP as potential anti-obesity substances. These results will contribute towards the development of functional foods with anti-obesity effects using the matoa fruit peel.

Trifluoromethylated Flavonoid-Based Isoxazoles as Antidiabetic and Anti-Obesity Agents: Synthesis, In Vitro α-Amylase Inhibitory Activity, Molecular Docking and Structure-Activity Relationship Analysis.

Diabetes mellitus is a major health problem globally. The management of carbohydrate digestion provides an alternative treatment. Flavonoids constitute the largest group of polyphenolic compounds, produced by plants widely consumed as food and/or used for therapeutic purposes. As such, isoxazoles have attracted the attention of medicinal chemists by dint of their considerable bioactivity. Thus, the main goal of this work was to discover new hybrid molecules with properties of both flavonoids and isoxazoles in order to control carbohydrate digestion. Moreover, the trifluoromethyl group is a key entity in drug development, due to its strong lipophilicity and metabolic stability. Therefore, the present work describes the condensation of a previously synthesized trifluoromethylated flavonol with different aryl nitrile oxides, affording 13 hybrid molecules indicated as trifluoromethylated flavonoid-based isoxazoles. The structures of the obtained compounds were deduced from by 1H NMR, 13C NMR, and HRMS analysis. The 15 newly synthesized compounds inhibited the activity of α-amylase with an efficacy ranging from 64.5 ± 0.7% to 94.7 ± 1.2% at a concentration of 50 µM, and with IC50 values of 12.6 ± 0.2 µM-27.6 ± 1.1 µM. The most effective compounds in terms of efficacy and potency were 3b, 3h, 3j, and 3m. Among the new trifluoromethylated flavonoid-based isoxazoles, the compound 3b was the most effective inhibitor of α-amylase activity (PI = 94.7 ± 1.2% at 50 µM), with a potency (IC50 = 12.6 ± 0.2 µM) similar to that of the positive control acarbose (IC50 = 12.4 ± 0.1 µM). The study of the structure-activity relationship based on the molecular docking analysis showed a low binding energy, a correct mode of interaction in the active pocket of the target enzyme, and an ability to interact with the key residues of glycosidic cleavage (GLU-230 and ASP-206), explaining the inhibitory effects of α-amylase established by several derivatives.

Novel ß-mannanase/GLP-1 fusion peptide high effectively ameliorates obesity in a mouse model by modifying balance of gut microbiota.

We constructed a novel ß-mannanase/GLP-1 fusion peptide, termed MGLP_1, and evaluated its ability to ameliorate obesity in a high-fat/high-sugar diet (HFSD)-induced mouse model. Eight-wk MGLP_1 treatment notably reduced obesity, as reflected by significant changes of body weight, serum triglyceride level, fatty liver and adipose tissue distribution. Amelioration of HFSD-induced gut dysbiosis by MGLP_1 was evidenced by reduced abundance ratio of bacterial phyla Firmicutes to Bacteroidetes, enhanced abundance of beneficial probiotic genera (Bifidobacterium, Lachnospiraceae, Ileibacterium), and reduced abundance of harmful genera (Clostridium, Romboutsia). Mechanisms of weight loss were investigated by comparing effects of treatment with MGLP_1 vs. prebiotics manno-oligosaccharides (MOS). MGLP_1 ameliorated gut microbiota imbalance by enhancing carbohydrate catabolism, whereas MOS promoted glycan synthesis and metabolism. Our findings, taken together, indicate that MGLP_1 fusion peptide has strong potential for amelioration of obesity by modifying relationships between gut microbiota and lipid and glucose metabolism.