Interruptins A and B exhibited anti-diabetic, anti-inflammatory, and anti-oxidative effects. This study aimed to investigate the therapeutic ability of extract enriched by interruptins A and B (EEI) from an edible fern Cyclosorus terminans on insulin resistance and non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obese rats and elucidate their possible mechanisms. HFD-induced obese rats were treated with EEI for 2 weeks. Real-time polymerase chain reaction (PCR) was used to examine the molecular basis. We found that EEI supplementation significantly attenuated body and liver weight gain, glucose intolerance, and insulin resistance. Concurrently, EEI increased liver and soleus muscle glycogen storage and serum high-density lipoprotein (HDL) levels. EEI also attenuated NAFLD, as indicated by improving liver function. These effects were associated with enhanced expression of insulin signaling genes (Slc2a2, Slc2a4, Irs1 and Irs2) along with diminished expression of inflammatory genes (Il6 and Tnf). Furthermore, EEI led to the suppression of lipogenesis genes, Srebf1 and Fasn, together with an increase in fatty acid oxidation genes, Ppara and Cpt2, in the liver. These findings suggest that EEI could ameliorate HFD-induced insulin resistance and NAFLD via improving insulin signaling pathways, inflammatory response, lipogenesis, and fatty acid oxidation.

Context: Interruptins A and B derivatives from edible fern Cyclosorus terminans have been reported properties including anti-bacterial, anti-cancer, anti-oxidation, anti-inflammatory, and antidiabetic activities. Unfortunately, studies on its safety are still scarce. Aims: To evaluate the acute oral toxicity of interruptin-rich extract (IRE) from C. terminans in Wistar rats and examine the antidiabetic potential of IRE in vitro. Methods: IRE was evaluated cytotoxicity by MTT assay and potency of glucose consumption in hepatocyte and skeletal muscle cells. IRE was evaluated for acute toxicity in Wistar rats by following OECD 420 guidelines. Wistar rats were single oral administrated of 2000 mg/kg IRE and further observed for 14 days. LCMS was assessed for verifying IRE absorption into the bloodstream. Hematological, biochemical parameters and microscopic examination of heart, liver and kidney were evaluated. Results: IRE demonstrated no cytotoxicity toward hepatocytes and skeletal muscle cells and facilitated glucose consumption into cells. In the acute toxicity study, on day 14, after a single oral administration of 2000 mg/kg IRE, no mortality and behavioral alterations. There was no change in metabolic parameters. Histopathology of heart, liver and kidney showed normal architecture. Conclusions: Thus, LD50 of IRE was considered superior to 2000 mg/kg. Hence the extract can be utilized safely and could provide a capability for diabetic control.

Background: Childhood obesity is a significant global health concern. Butyrylcholinesterase (BChE) has been shown to play a role in lipid metabolism. This study aimed to assess BChE activity, obesity-related and lipid-related indices, and dyslipidemia in obese and non-obese children, and to investigate the associations of these parameters with obesity among Thai children. Methods: The study included 661 Thai children, consisting of 338 with obesity and 323 with a normal weight. Anthropometric measurements, metabolic parameters, obesity- and lipid-related indices, and BChE activity were evaluated. Results: The obese group exhibited significantly higher BChE activity and obesity-related and lipid-related indices compared to the non-obese group (p < 0.01). Additionally, metabolic parameters—including glucose levels, triglyceride-glucose (TyG) index, and TyG-related indices—as well as the lipid profile, which included triglycerides (TG), non-high-density lipoprotein cholesterol (non-HDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), were all significantly elevated in the obese group (p < 0.01). Obesity was associated with dyslipidemia (p < 0.01). Moreover, BChE activity showed a positive correlation with obesity-related and lipid-related indices, along with several metabolic parameters (p < 0.002). The upper stratum of BChE activity (OR = 5.356), the non-HDL-C/HDL-C ratio (OR = 2.185), and the TG/HDL-C ratio (OR = 1.703) were found to be effective in evaluating and predicting the risk of obesity, even after adjusting for potential covariates (p < 0.01). Conclusions: These findings indicate a significant relationship between obesity and increased BChE activity, lipid-related indices, and dyslipidemia in Thai children. Therefore, changes in BChE activity may be considered a factor associated with obesity, enhancing its potential as a marker for obesity assessment.

Interruptin B from the fern Cyclosorus terminans has been indicated as a ligand of peroxisome proliferator-activated receptor (PPAR)-α and -γ that is known to regulate glucose homeostasis. Interruptin B was previously been implicated to promote glucose consumption into adipocytes. This study aimed to examine the anti-diabetic impact of interruptins A and B on glucose uptake and glycogen synthesis in mouse hepatocytes. Cell viability of FL83B hepatocytes affected by interruptins A and B was determined. The glucose consumption after 12–24 h treatment with compounds was evaluated by glucose oxidase method. The glycogen content was assessed after 24 h incubation using anthrone method. The mechanism regarding glucose consumption was investigated by coincubation of interruptins A or B with PPAR-γ antagonist bisphenol A diglycidyl ether (BADGE) and by protein expression on PPAR-γ, -α, glucose transporter 2 (GLUT2), and phosphorylated-insulin receptor substrate-1 (P-ISR-1) through Western blotting technique. Our study demonstrated that interruptins A and B were non-toxic toward FL83B hepatocytes. They remarkably stimulated glucose consumption and glycogen storage in a time- and dose-dependent manner. However, their increased glucose uptake was diminished by BADGE treatment. Moreover, interruptins A and B stimulated protein expression of PPAR-γ, -α, GLUT2, and phosphorylated-IRS-1. These findings support the anti-diabetic potential of interruptins A and B by modulation of the PPARs pathway.

Background/Objectives: The fern “Cyclosorus terminans” (C. terminans) or “Maiden Fern” contains interruptin A and interruptin B. This plant could attenuate obesity, insulin resistance, and fatty liver in rats fed a high-fat/calorie diet. However, the benefits of C. terminans to the gut remain unknown. We investigated the protective effect of C. terminans extract against gut dysfunction in rats exposed to a high-fat/calorie diet. Methods: Male Wistar rats were assigned to receive either (1) a normal diet treated with vehicle, (2) a high-fat/calorie diet treated with vehicle, (3) a high-fat/calorie diet treated with 100 mg per kg per day (mg·kg⁻¹·day⁻¹) of C. terminans extract, or (4) a high-fat/calorie diet treated with 200 mg·kg⁻¹·day⁻¹ of C. terminans extract. The rats were euthanized after 12 weeks of treatment to enable feces and colon tissue collection. Results: Both 100 and 200 mg·kg⁻¹·day⁻¹ of C. terminans extract reduced body weight (−10.49%; p = 0.030 and −10.54%; p = 0.037, respectively) and ameliorated gut inflammation, gut barrier disruption, changes in short-chain fatty acid levels, and gut dysbiosis caused by high-fat/calorie diet. Conclusions: C. terminans extract attenuated an increase in body weight and exerted prophylactic effects against gut pathologies induced by high-fat/calorie diet.