RESUMEN
Probiotics are known to stimulate, modulate, and regulate host immune response by regulating specific sets of genes and improve glucose homeostasis through regulating dipeptidyl peptidase (DPP-IV) activity, but the mechanism behind their protective role is not clearly understood. Therefore, the present study was designed to isolate indigenous lactic acid bacterial (LAB) strains from different fermented food samples, vegetables, and human infant feces exhibiting anti-inflammatory, antioxidant, and DPP-IV inhibitory activity. A total of thirty-six Gram-positive, catalase-negative, and rod-shaped bacteria were isolated and screened for their anti-inflammatory activity using lipopolysaccharide (LPS)-induced inflammation on the murine (RAW264.7) macrophages. Among all, sixteen strains exhibited more than 90% reduction in nitric oxide (NO) production by the LPS-treated RAW264.7 cells. Prioritized strains were characterized for their probiotic attributes as per the DBT-ICMR guidelines and showed desirable probiotic attributes in a species and strain-dependent manner. Accordingly, Lacticaseibacillus rhamnosus LAB3, Levilactobacillus brevis LAB20, Lactiplantibacillus plantarum LAB31, Pediococcus acidilactici LAB8, and Lactiplantibacillus plantarum LAB39 were prioritized. Furthermore, these strains when co-supplemented with LPS and treated on RAW264.7 cells inhibited the mitogen-activated protein kinases (MAPKs), i.e., p38 MAPK, ERK1/2, and SAPK/JNK, cyclooxygenase-2 (COX-2), relative to the LPS-alone-treated macrophages. LAB31 and LAB39 also showed 64 and 95% of DPP-IV inhibitory activity relative to the Lacticaseibacillus rhamnosus GG ATCC 53103, which was used as a reference strain in all the studies. Five prioritized strains ameliorated the LPS-induced inflammation by downregulating the JNK/MAPK pathway and could be employed as an alternative bio-therapeutic strategy in mitigating gut-associated inflammatory conditions. The potential mechanism of action of prioritized LAB strains in preventing the LPS-induced inflammation in RAW 264.7 macrophage cells.
Asunto(s)
Lactobacillales , Humanos , Animales , Ratones , Lactobacillales/metabolismo , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/uso terapéutico , Ácido Láctico , Óxido NítricoRESUMEN
BACKGROUND: Insulin resistance plays an important role in the pathogenesis of NAFLD. Pharmacological treatment of patients with NAFLD is still evolving. Insulin sensitizing drugs like metformin may be effective in these patients. Twenty five adult patients with NAFLD who did not achieve normalization of alanine transaminases (ALT) after 6 months of lifestyle interventions and UDCA were treated with metformin 500mg tid for 6 months. Insulin resistance was determined by HOMA- IR. Liver function tests were done monthly and patients were defined having no response, partial response or complete biochemical response depending on the change in ALT. Results were compared with 25 patients with NAFLD from the same cohort treated only with lifestyle interventions (disease controls). RESULTS: Thirteen (52%) patients had class III (n = 5) or class IV (n = 8) disease amounting to histological NASH. Of these 13 patients none had severe inflammation and none had stage 4 fibrosis (cirrhosis). All 25 patients with NAFLD had insulin resistance in comparison to healthy controls. In comparison to disease controls (127.5 +/- 41.8 vs. 118 +/- 21.6 p = NS), all patients treated with metformin had partial biochemical response (mean ALT 122.2 +/- 26.8 vs 74.3 +/- 4.2 p < 0.01) and 14 (56%) of them achieved complete normalization of ALT. CONCLUSIONS: Metformin is effective to achieve biochemical response in patients with NAFLD who do not respond to lifestyle interventions and UDCA.