Immunomodulatory Activity of Diterpenes over Innate Immunity and Cytokine Production in a Human Alveolar Epithelial Cell Line Infected with Mycobacterium tuberculosis

Abstract

Background: Mexico has the largest number of the genus salvia plant species, whose main chemical compounds of this genus are diterpenes, these chemical compounds have shown important biological activities such as: antimicrobial, anti-inflammatory and immunomodulatory. Objective: This study aimed to evaluate the immunomodulatory activity of three diterpenes: 1) icetexone, 2) anastomosine and 3) 7,20-dihydroanastomosine, isolated from Salvia ballotiflora, over innate immunity and cytokine production in a human alveolar epithelial cell line infected with Mycobacterium tuberculosis. Method: The immunomodulatory activity of diterpenes over innate immunity included reactive oxygen and nitrogen species (ROS and RNS) induction in response to infection; cytokine production included TNF-α and TGF-β induction in response to infection. Results: The diterpenes anastomosine and 7,20-dihydroanastomosine showed a statically significant (p<0.01) increase of RNS after 36 h of infection and treatment of 2.0 µg/mL. Then, the ROS induction in response to infection showed a consistent statically significant (p<0.01) increase after 12 h of diterpenes treatments. The cell cultures showed an anti-inflammatory effect, in the case of TGF-β induction, in response to infection when treated with the diterpenes. On the other hand, there was not any significant effect on TNF-α release. Conclusion: the diterpenes anastomosine and 7,20-dihydroanastomosine increased the production of RNS after 36 h of infection and treatment. Besides, the three diterpenes increased the production of ROS after 12 h. This RNS and ROS modulation can be considered as an in vitro correlation of innate immunity in response to Mycobacterium tuberculosis infection; and an indicator of the damage of epithelial lung tissue. This study also showed an anti-inflammatory immune response by means of TGF-β modulation when compared with control group.

Recent research progress in the plant contribution to the management of tuberculosis

“…Likewise, the role of medicinal plants and their bioactive derivatives as alveolar NLRP3 inflammasome regulators during M. tuberculosis infection was explored, providing information about the mechanism in which they can inhibit excessive stimulation of the inflammasomes and its associated factors, and as a consequence reducing immunopathological response in the host (Mvubu & Chiliza, 2021). Later, the immunomodulatory activity of some diterpenes was confirmed in a human alveolar epithelial cell line infected with M. tuberculosis (Hernández-Herrera et al, 2023), while sinaphyl alcohol diacetate and ergosterol peroxide were proved to reduce interleukin-12 levels and Toll-like receptor-2 protein expression, and to increase the human leucocyte antigen-DR protein expression in diabetic patients with tuberculosis The other aspect related to antituberculosis immune response is the state of microbiota. Studies have shown that subjects suffering from tuberculosis and treated with classical drug regimens can have the impaired balance of intestinal flora.…”