Holistic modulation of TLR4, MAPK, and apoptosis Signalings and gut microbiota by Sihuangzhili granule: A herbal strategy against avian colibacillosis
Abstract
Avian pathogenic Escherichia coli (APEC) poses a significant threat to the poultry industry due to antibiotic resistance. This study evaluated the therapeutic efficacy of the Chinese herbal formula Sihuangzhili Granule (SHZL) against avian colibacillosis in comparison to treatment with oxytetracycline. Physiological, histopathological, and biochemical analyses revealed that SHZL alleviated APEC-induced diarrhea, restored organ condition (heart, liver, and intestine), and normalized serum metabolic markers more effectively than oxytetracycline. Bioinformatic analysis identified 59 shared targets between SHZL and the disease phenotypes of pericarditis, hepatitis, and diarrhea, primarily in the TLR4, MAPK, and apoptosis pathways. Multi-tissue analyses demonstrated SHZL's superior regulation of inflammatory (IL-6, IL-1β) and apoptotic markers (BCL2, CASP8, CASP3) in the serum, heart, liver, and cecum, with targeted suppression of the TLR4/MYD88/IKKα/IκBα/NF-κB signaling pathway. Molecular docking confirmed high-affinity binding of SHZL components (coptisine, berberine) to core targets (AP-1, ERK1, IKKα). Although SHZL lacked direct antibacterial activity, it enhanced gut microbial diversity and suppressed pro-inflammatory taxa, whereas oxytetracycline exacerbated dysbiosis and sustained pathogenic proliferation. SHZL established its holistic therapeutic effect through multi-functional, multi-organ, multi-composition, and multi-dimensional regulation of the host-gut microbiota…
Read the paper
Related studies
- Bile Acid 7α-Dehydroxylating Gut Bacteria Secrete Antibiotics that Inhibit Clostridium difficile: Role of Secondary Bile Acids
- Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome
- Altered gut microbiome composition and function are associated with gut barrier dysfunction in healthy relatives of patients with Crohn's disease
- Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model
- Immune Impairment Associated with Vitamin A Deficiency: Insights from Clinical Studies and Animal Model Research
- Glyphosate-based herbicides influence antioxidants, reproductive hormones and gut microbiome but not reproduction: A long-term experiment in an avian model
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.