Epidemiological and experimental studies have extensively indicated that chronic subclinical systemic inflammation (CSSI) and oxidative stress are risk factors for several chronic diseases, including cancer, arthritis, type 2 diabetes, and cardiovascular and neurodegenerative diseases. This study examined the protective effect of stingless bee honey (SBH) supplementation against lipopolysaccharide (LPS)-induced CSSI, pointing to the possible involvement of NF-κB, p38 MAPK and Nrf2 signaling. CSSI was induced in male Sprague Dawley rats by intraperitoneal injection of LPS three times per week for 28 days, and SBH (4.6 and 9.3 g/kg/day) was supplemented for 30 days. LPS-induced rats showed significant leukocytosis, and elevated serum levels of CRP, TNF-α, IL-1β, IL-6, IL-8, MCP-1, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), accompanied with diminished antioxidants. Treatment with SBH significantly ameliorated inflammatory markers, MDA and 8-OHdG, and enhanced antioxidants in LPS-induced rats. In addition, SBH decreased NF-κB p65 and p38 MAPK, and increased Nrf2 expression in the liver, kidney, heart and lung of LPS-induced rats. Furthermore, SBH prevented LPS-induced histological and functional alterations in the liver, kidney, heart and lung of rats. SBH has a substantial protective role against LPS-induced CSSI in rats mediated via amelioration of inflammation, oxidative stress and NF-κB, p38 MAPK and Nrf2 signaling.

Benzimidazole derivatives have a diverse range of biological activities, including antiulcer, antihypertensive, antiviral, antifungal, anti-inflammatory, and anticancer. Despite these activities, previous studies have revealed that some of the derivatives can induce mutations. This study aimed to screen for potential mutagenic activities of novel benzimidazole derivatives 1–4 using the Ames test and to study their structure–activity relationship (SAR). An Ames test was carried out on two strains of Salmonella typhimurium (TA98 and TA100) in the absence and presence of metabolic activation. Genetic analysis was performed prior to the Ames test to determine the genotypes of the bacterial tester strains. Both bacterial strains showed dependency on histidine with the presence of rfa mutation, uvrB deletion, and plasmid pKM101. Further, all derivatives tested showed no mutagenic activity in the absence of metabolic activation in both tester strains. However, in the presence of metabolic activation, compound 1 appeared to induce mutation at 2.5 µg/plate when tested against the TA98 strain. These results suggest that the absence of the -OH group at the ortho-position over the phenyl ring might be the cause of increased mutagenic activity in compound 1. Additionally, the presence of mutagenic activity in compound 1 when it was metabolically activated indicates that this compound is a promutagen.

Background Benzimidazole analogues have diverse range of biological activities including anti-ulcer, anti-hypertensive, anti-viral, anti-fungal, anti-inflammatory and anti-cancer. Previous studies revealed some of the analogues can induce mutation despite their biological activities. This study aims to screen for potential mutagenic activities of novel benzimidazole analogues using Ames test and study their structure-activity relationship (SAR). Methods Ames test was carried out on two strains of Salmonella typhimurium; TA98 and TA100 that carry different mutations in their various genes in histidine operon, which protocols complied with OECD 471 Guideline for Testing of Chemicals. The preliminary tests including growth curve and genetic analysis were carried out prior to Ames test in order to determine the optimum incubation hour and genotypes of the bacterial strains respectively. The bacterial growth curve was carried out by incubating the bacterial suspension for 52 hours. The optical density of the bacteria was recorded for every two hours at 660nm wavelength and the graph of optical density versus time was plotted. The genotypes of the bacterial strains used were determined by genetic analysis which includes tests on dependency on histidine and/or biotin, presence of rfa mutation, urvB deletion as well as pKM101 plasmid. All data were analysed using Two-Way ANOVA, followed by post-hoc Tukey test. The SAR was analysed based on the results of Ames test. Results The optimum incubation hour for both strains was 14 hours. Both bacterial strains show dependency on histidine with presence of rfa mutation, urvB deletion and pKM101 plasmid. Besides, all analogues tested; NN-1-5, NN-1-7, NN-1-9 and NN-1-18 show no mutagenic activity. Conclusion There was no significant difference in the mutagenic activity among all analogues despite their difference in the number and position of hydroxyl groups.