T-006

The rising concerns pertaining to the safety of synthetic supplements in livestock production have encouraged the exploration of potential alternatives. This study investigated the growth, gut microbiota, blood chemistry, immune indices, meat quality, and antioxidant status in broiler chickens supplemented with Crescentia cujete leaf (CCL), Launaea taraxacifolia leaf (LTL), and a combination of antibiotic (70% oxytetracycline + 30% neomycin) and tert-Butylhydroxyanisole. One-day-old Ross 308 chicks (n = 420) were randomly assigned to either T-1, basal diet (BD) only; T-2, BD + 0.4 g/kg antibiotic + 0.13 g/kg tert-butylhydroxyanisole; T-3, BD + 2.5 g/kg LTL; T-4, BD + 5 g/kg LTL; T-5, BD + 2.5 g/kg CCL; or T-6, BD + 5 g/kg CCL for 42 days. Each dietary group had seven replicates with ten chicks per replicate. Body weight gain and carcass weight were higher (P < 0.05) in the T-2, T-4, T-5, and T-6 birds compared with those of other birds. At 1-21 days, the T-2 and T-4 birds consumed more feed than the T-1 and T-3 birds. At 22-42 days, the T-4 birds consumed more (P < 0.05) feed than the T-1 and T-3 birds. During 1-42 days, the T-1 and T-3 birds consumed less (P < 0.05) feed than other birds. At 22-42 days and 1-42 days, the T-1 had lower feed efficiency (P < 0.05) than other birds except for the T-3 birds. The CCL and LTL birds had lower (P < 0.05) serum LDL cholesterol and higher HDL cholesterol compared with other birds. Hematology, splenic interleukin-1β, immunoglobulin M, ileal and caecal total aerobic bacteria counts, caecal Lactobacillus spp., and meat physicochemical properties were unaffected by diets. The T-1 birds had higher (P < 0.05) ileal and caecal Clostridium spp., E. coli, and Salmonella spp. compared with birds fed other diets. The CCL and LTL birds had higher ileal Lactobacillus counts. Splenic IL-10 was higher (P < 0.05) in the T-2, T-4, and T-6 birds compared with that in other birds. Dietary supplementation with CCL, LTL, and a combination of antibiotic and tert-butylhydroxyanisole repressed (P < 0.05) splenic tumor necrosis-α and immunoglobulin G. The T-1 breast meat had lower glutathione peroxidase and catalase. The T-4 meat had higher (P < 0.05) superoxide dismutase, glutathione peroxidase, catalase, and total antioxidant capacity compared with other meats. On day 3 postmortem, meats obtained from birds supplemented with CCL, LTL, and a combination of antibiotic and tert-butylhydroxyanisole had lower (P < 0.05) carbonyl and malondialdehyde contents than the meat from the non-supplemented birds. The 5 g/kg CCL and 5 g/kg LTL could be used as antimicrobial and antioxidant in broiler diets.

T-006, a small-molecule compound derived from tetramethylpyrazine (TMP), has potential for the treatment of neurological diseases. In order to investigate the effect of T-006 prophylactic treatment on an Alzheimer's disease (AD) model and identify the target of T-006, we intragastrically administered T-006 (3 mg/kg) to Alzheimer's disease (AD) transgenic mice (APP/PS1-2xTg and APP/PS1/Tau-3xTg) for 6 and 8 months, respectively. T-006 improved cognitive ability after long-term administration in two AD mouse models and targeted mitochondrial-related protein alpha-F1-ATP synthase (ATP5A). T-006 significantly reduced the expression of phosphorylated-tau, total tau, and APP while increasing the expression of synapse-associated proteins in 3xTg mice. In addition, T-006 modulated the JNK and mTOR-ULK1 pathways to reduce both p-tau and total tau levels. Our data suggested that T-006 mitigated cognitive decline primarily by reducing the p-tau and total tau levels in 3xTg mice, supporting further investigation into its development as a candidate drug for AD treatment.