Sulfonated (1 → 6)-ß-d-Glucan (Lasiodiplodan): A Promising Candidate against the Acyclovir-Resistant Herpes Simplex Virus Type 1 (HSV-1) Strain.

Herpes simplex virus type 1 (HSV-1) is a persistent human pathogen, and the emergence of strains resistant to Acyclovir (ACV, reference drug) shows the urgency to develop new treatments. We report the antiherpetic mechanism of the action of lasiodiplodan (LAS-N, (1 → 6)-ß-d-glucan) and its sulfonated derivative (LAS-S3) in vitro and in vivo. LAS-S3 showed anti-HSV-1 action with high selectivity indices for HSV-1 KOS (88.1) and AR (189.2), sensitive and resistant to ACV, respectively. LAS-S3 inhibited >80% of HSV-1 infection in different treatment protocols (virucidal, adsorption inhibition, and post-adsorption effects), even at low doses, and showed a preventive effect and DNA and protein synthesis inhibition. The antiherpetic effect was confirmed in vivo by the cosmetic LAS-S3-CRÈME decreasing cutaneous lesions of HSV-1, including the AR strain. LAS-S3 possessed a broad-spectrum mechanism of action acting in the early and post-adsorption stages of HSV-1 infection, and LAS-S3-CRÈME is a potential antiherpetic candidate for patients infected by HSV-1-resistant strains.

Baccharis dracunculifolia methanol extract enhances glucose-stimulated insulin secretion in pancreatic islets of monosodium glutamate induced-obesity model rats.

CONTEXT: Obesity is the main risk factor for type 2 diabetes mellitus. Secondary metabolites with biological activities and pharmacological potential have been identified in species of the Baccharis genus that are specifically distributed in the Americas. OBJECTIVE: This study evaluated the effects of methanol extracts from Baccharis dracunculifolia DC. Asteraceae on metabolic parameters, satiety, and growth in monosodium glutamate (MSG) induced-obesity model rats. MATERIALS AND METHODS: MSG was administered to 32 newborn rats (4 mg/g of body weight) once daily for 5 consecutive days. Four experimental groups (control, control + extract, MSG, and MSG + extract) were treated for 30 consecutive days with 400 mg/kg of B. dracunculifolia extract by gavage. Biochemical parameters, antioxidant activity, total extract phenolic content (methanolic, ethanolic, and acetone extractions), and pancreatic islets were evaluated. RESULTS: High levels of phenolic compounds were identified in B. dracunculifolia extracts (methanol: 46.2 ± 0.4 mg GAE/L; acetate: 70.5 ± 0.5 mg GAE/L; and ethanol: 30.3 ± 0.21 mg GAE/L); high antioxidant activity was detected in B. dracunculifolia ethanol and methanol extracts. The concentration of serum insulin increased 30% in obese animals treated with extract solutions (1.4-2.0 µU/mL, p < 0.05). Insulin secretion in pancreatic islets was 8.3 mM glucose (58%, p < 0.05) and 16.7 mM (99.5%, p < 0.05) in rats in the MSG + extract and MSG groups, respectively. DISCUSSION AND CONCLUSION: Treatment with B. dracunculifolia extracts protected pancreatic islets and prevented the irreversible cellular damage observed in animals in obesity and diabetes models.

Toxicological assessment of ß-(1-->6)-glucan (lasiodiplodan) in mice during a 28-day feeding study by gavage.

Studies evaluating the toxicity caused by fungal exopolysaccharides of the ß-(1-->6)-D-glucan type are rare. In this study, the toxicological effects of sub-chronic treatments with lasiodiplodan (ß-(1-->6)-D-glucan from Lasiodiplodia theobromae MMPI) were evaluated in mice through the assessment of biochemical, hematological, and histopathological alterations. Thirty-two mice (16 male, 16 female) were used in this study divided in two groups; one group received lasiodiplodan (50 mg/kg body weight) daily for 28 days via gavage, and another (control group) received saline during the same period. Blood samples were collected via cardiac puncture for hematological and biochemical analyses. Liver, heart, kidney, and spleen were collected for histopathological analysis. Statistical analysis was performed through one-way analysis of variance and only p < 0.05 F-values were presented. Significant reduction in blood glucose in the male group (35%; p < 0.01), transaminases activity in both sexes (AST and ALT; ~35%; p < 0.05), and urea (20%; p < 0.01) in the female group was observed with the lasiodiplodan treatment. The results showed that sub-chronic treatments with lasiodiplodan did not generate hematological and histopathological alterations leading to signs of toxicity in healthy mice, independent of gender.

Relationship Between Hormonal Mechanisms of Diabetes Mellitus and Hypothyroidism Post-Bariatric Surgery.

BACKGROUND: Obesity, diabetes mellitus may be related to the health, the relationship and the physiological capacity of the production of thyroid hormones (TH), triiodothyronine (T3) and thyroxine (T4). OBJECTIVES: The main aims of this review are to describe the relationship between obesity, appetite, weight management, hormonal mechanisms of diabetes mellitus and hypothyroidism post-bariatric surgery. METHODOLOGY: An in-depth literature search was conducted to identify scientific studies, which analyzed the correlation between diabetes mellitus and hypothyroidism post-bariatric surgery. RESULTS: Bariatric surgery decreases hypothyroidism, reduces the need for pharmacological action (such as levothyroxine), controls the weight and body fat and increases the sensitivity to leptin and insulin. CONCLUSION: The reduction of the stomach and intestine by bariatric surgery is an evolutionary and beneficial action, because it may lead to a drastic decrease on numbers of conditions such as diabetes, obesity, hypothyroidism, and others. Thus, new studies should also focus on patients' post-operatory conditions, such as lifetime, regulation and functioning of organs after reduced nutrition, and consumption and delivery of nutrients to health maintenance.

Carboxymethylation of (1 → 6)-ß-glucan (lasiodiplodan): Preparation, characterization and antioxidant evaluation.

D-Glucans possess immunomodulatory activities and potential for the development of new therapeutic agents. Biological activities can be enhanced in these biopolymers through chemical derivatization, e.g., carboxymethylation. This work presents the carboxymethylation, characterization and the evaluation of antioxidant activities of the exocellular (1 → 6)-ß-D-glucan produced by Lasiodiplodia theobromae MMPI. Thermal analysis indicated that the native and carboxymethylated polysaccharides presented four stages of mass-loss. The first stage occurred at 125°C (loss of water) with two consecutive events of mass loss (200-400°C) attributed to polymer degradation and the fourth stage between 425 and 620°C (final decomposition). Scanning electron microscopy analysis indicated that the gross morphological features of lasiodiplodan were ruptured following carboxymethylation. X-ray diffractometry analysis demonstrated that the native and carboxymethylated polysaccharides presented a non-crystalline structure. Carboxymethylation contributed to improving the polysaccharide's water solubility and antioxidant capacity.