Trypsin inhibitors are studied in a variety of models for their anti-obesity and anti-inflammatory bioactive properties. Our group has previously demonstrated the satietogenic effect of tamarind seed trypsin inhibitors (TTI) in eutrophic mouse models and anti-inflammatory effects of other trypsin inhibitors. In this study, we evaluated TTI effect upon satiety, biochemical and inflammatory parameters in an experimental model of metabolic syndrome (MetS). Three groups of n = 5 male Wistar rats with obesity-based MetS received for 10 days one of the following: (1) Cafeteria diet; (2) Cafeteria diet + TTI (25 mg/kg); and (3) Standard diet. TTI reduced food intake in animals with MetS. Nevertheless, weight gain was not different between studied groups. Dyslipidemia parameters were not different with the use of TTI, only the group receiving standard diet showed lower very low density lipoprotein (VLDL) and triglycerides (TG) (Kruskal–Wallis, p < 0.05). Interleukin-6 (IL-6) production did not differ between groups. Interestingly, tumor necrosis factor-alpha (TNF-α) was lower in animals receiving TTI. Our results corroborate the satietogenic effect of TTI in a MetS model. Furthermore, we showed that TTI added to a cafeteria diet may decrease inflammation regardless of weight loss. This puts TTI as a candidate for studies to test its effectiveness as an adjuvant in MetS treatment.

Objective: This study evaluated the effect of a protein, the isolated Trypsin Inhibitor (TTI) from Tamarindus indica L. seed, as a CCK secretagogue and its action upon food intake and leptin in obese Wistar rats. Methods: Three groups of obese rats were fed 10 days one of the following diets: Standard diet (Labina®) + water; High Glycemic Index and Load (HGLI) diet + water or HGLI diet + TTI. Lean animals were fed the standard diet for the 10 days. Food intake, zoometric measurements, plasma CCK, plasma leptin, relative mRNA expression of intestinal CCK-related genes, and expression of the ob gene in subcutaneous adipose tissue were assessed. Results: TTI decreased food intake but did not increase plasma CCK in obese animals. On the other hand, TTI treatment decreased CCK-1R gene expression in obese animals compared with the obese group with no treatment (p = 0.027). Obese animals treated with TTI presented lower plasma leptin than the non-treated obese animals. Conclusion: We suggest that TTI by decreasing plasma leptin may improve CCK action, regardless of its increase in plasma from obese rats, since food intake was lowest.

: The increasing prevalence of obesity and, consequently, chronic inflammation and its complications has increased the search for new treatment methods. The effect of the purified tamarind seed trypsin inhibitor (TTIp) on metabolic alterations in Wistar rats with obesity and dyslipidemia was evaluated. Three groups of animals with obesity and dyslipidemia were formed, consuming a high glycemic index and glycemic load (HGLI) diet, for 10 days: Obese/HGLI diet; Obese/standard diet; Obese/HGLI diet + TTIp (730 μg/kg); and one eutrophic group of animals was fed a standard diet. Rats were evaluated daily for food intake and weight gain. On the 11th day, animals were anesthetized and sacrificed for blood and visceral adipose tissue collection. TTIp treated animals presented significantly lower food intake than the untreated group (p = 0.0065), TG (76.20 ± 18.73 mg/dL) and VLDL-C (15.24 ± 3.75 mg/dL). Plasma concentrations and TNF-α mRNA expression in visceral adipose tissue also decreased in obese animals treated with TTIp (p < 0.05 and p = 0.025, respectively) with a negative immunostaining. We conclude that TTIp presented anti-TNF-α activity and an improved lipid profile of Wistar rats with dyslipidemia and obesity induced by a high glycemic index and load diet regardless of PPAR-γ induction.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia. Proteins in plant sources that enable the maintenance of the glycemic profile may be of interest in the context of T2DM. However, their mechanisms of action are unclear, unlike other bioactive compounds. This systematic review identified and described the mechanisms of action of isolated and purified proteins and peptides extracted from vegetables on the reduction of blood glucose in T2DM in experimental studies. The research was done in PubMed, ScienceDirect, Scopus, Web of Science, Embase and Virtual Health Library (VHL) databases in March 2019. The initial search retrieved 916 articles, and, after reading the title, abstract and keywords, 24 articles were eligible for full reading. Then, five articles were eligible to build this systematic review. The evaluation of the evidence and the strength of the recommendations of the studies was evaluated with the SYstematic Review Center for Laboratory animal Experimentation-SYRCLE. Studies with proteins or peptides extracted from soybean (Glycine max), corn (Zea mays), peas (Pisum sativum), costus (Costus igneus) and ginseng (Panax ginseng) were found, and all of them decreased glycemia but not by the same mechanisms. The mechanism of action of proteins extracted from Glycine max, Pisum sativum, Costus igneus were similar, acting in the insulin-mediated pathways. The peptide derived from Zea mays increased GLP-1 expression, and the peptide from Panax ginseng reduced NF-kB signaling, both resulting in stimulating the release of insulin. Therefore, bioactive proteins and peptides of plant sources act through biochemical pathways, in the modulation of insulin resistance and the hyperglycemic state. These compounds are promising in scientific research on T2DM, because there is a probable similarity of these proteins with insulin, which enables them to act as insulin-like molecules.

Several studies have sought new therapies for obesity and liver diseases. This study investigated the effect of the trypsin inhibitor isolated from tamarind seeds (TTI), nanoencapsulated in chitosan and whey protein isolate (ECW), on the liver health status of the Wistar rats fed with a high glycemic index (HGLI) diet. The nanoformulations without TTI (CW) and ECW were obtained by nanoprecipitation technique, physically and chemically characterized, and then administered to the animals. The adult male Wistar rats (n = 20) were allocated to four groups: HGLI diet + water; standard diet + water; HGLI diet + ECW (12.5 mg/kg); and HGLI diet + CW (10.0 mg/kg), 1 mL per gagave, for ten days. They were evaluated using biochemical and hematological parameters, Fibrosis-4 Index for Liver Fibrosis (FIB-4), AST to Platelet Ratio Index (APRI) scores, and liver morphology. Both nanoparticles presented spherical shape, smooth surface, and nanometric size [120.7 nm (ECW) and 136.4 nm (CW)]. In animals, ECW reduced (p < 0.05) blood glucose (17%), glutamic oxalacetic transaminase (39%), and alkaline phosphatase (24%). Besides, ECW reduced (p < 0.05) APRI and FIB-4 scores and presented a better aspect of hepatic morphology. ECW promoted benefits over a liver injury caused by the HGLI diet.

The objectives of this study were to evaluate the hypoglycemic effect of the trypsin inhibitor isolated from tamarind seeds (TTI) in an experimental model of T2DM and the in silico interaction between the conformational models of TTI 56/287 and the insulin receptor (IR). After inducing T2DM, 15 male Wistar rats were randomly allocated in three groups (n = 5): 1—T2DM group without treatment; 2—T2DM group treated with adequate diet; and 3—T2DM treated with TTI (25 mg/kg), for 10 days. Insulinemia and fasting glucose were analyzed, and the HOMA-IR and HOMA-β were calculated. The group of animals treated with TTI presented both lower fasting glucose concentrations (p = 0.0031) and lower HOMA-IR indexes (p = 0.0432), along with higher HOMA-β indexes (p = 0.0052), than the animals in the other groups. The in silico analyses showed that there was an interaction between TTIp 56/287 and IR with interaction potential energy (IPE) of −1591.54 kJ mol−1 (±234.90), being lower than that presented by insulin and IR: −894.98 kJ mol−1 (±32.16). In addition, the presence of amino acids, type of binding and place of interaction other than insulin were identified. This study revealed the hypoglycemic effect of a bioactive molecule of protein origin from Tamarind seeds in a preclinical model of T2DM. Furthermore, the in silico analysis allowed the prediction of its binding in the IR, raising a new perspective for explaining TTI’s action on the glycemic response.

The study aimed to evaluate the nanoparticles (ECW) containing tamarind trypsin inhibitor (TTI) concerning the storage effect under different conditions on antitrypsin activity and the bioactive potential in a preclinical model. ECW was exposed to different pH and temperatures to evaluate the interaction between TTI and its encapsulating agents, monitored by antitrypsin activity. Wistar rats (n = 25) with obesity induced by diet were divided into groups: untreated; treatment with nutritionally adequate diet; treatment with nutritionally adequate diet and ECW/12.5 mg/kg; treatment with ECW/12.5 mg/kg; and treatment with TTI/25 mg/kg. The groups were evaluated over ten days with regards to satiety, zoometric, biochemical, and inflammatory parameters, using ten times less TTI (2.5 mg/kg) contained in ECW. TTI was protected and encapsulated in ECW without showing residual inhibitory activity. Only at gastric pH did ECW show antitrypsin activity. At different temperatures, it showed high antitrypsin activity, similar to TTI. The animals treated with ECW had significantly reduced body weight variation (p < 0.05), and only TTI treatment reduced the inflammatory parameters significantly (p < 0.05). The study showed that by using lower concentrations of TTI in ECW it was possible to perceive promising effects with perspectives of use in functional products for managing obesity and its complications.