Synergistic Effect of Combined Antibiotic and Methanolic Extracts of Withania somnifera and Catharanthus roseus against MDR Salmonella enterica Serovar Typhi

Abstract

Typhoid has become the most neglected and majorly affecting disease of tropical and subtropical countries, including India, and is among the most important global health problems, as the emergence of multidrug resistance has shut down the effect of antimicrobial agents and makes it difficult to control the bacteria inside the host. Hence, there is a great need to develop some natural-based drugs, which will be new promising natural therapeutic interventions with high efficacy and lesser side effects in comparison to synthetic drugs already available for typhoid treatment. The present study completely focused on the synergistic effect of bioactive constituents of medicinal plants in combination to synthetic drugs for enhancing the bacterial eradication mechanism. The methanolic extracts of 25 medicinal plants were screened for their antisalmonella effect and out of which only 2 plants were studied further on the basis of their high effectiveness against 17 MDR isolates using well diffusion assay and MIC/MBC determination. The synergistic activity was assessed with two nonantibiotics (ibuprofen and paracetamol) and 3 antibiotics (ceftazidime chloramphenicol, and trimethoprim) using methods of growth inhibitory indices (GIIs) and fractional inhibitory concentration index (FICI). The highly effective methanolic extracts were of W. somnifera and C. roseus, and the synergism was obtained in terms of GIIs and FICI values of 0.9 and 0.3 and 0.9 and 0.5, respectively, fulfilling the criteria for both extracts, respectively. The results for combinations of plant extracts and antibiotics ceftazidime, trimethoprim, and chloramphenicol and nonantibiotics (analgesic drugs) ibuprofen and paracetamol showed good synergistic activity (100%, 88%, 50%, 45%, and 35%, respectively) against the MDR isolates of S. Typhi. The present study also suggests that in the future, combined treatment with the antibiotics and the bioactive compounds can enhance the immune system to perform better action against the external pathogens as well as in the treatment of internal pathogens, and the combinations will be the successful immune modulators.