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

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Despite the successes in the development of diagnosis and treatment of this disease, it still poses a significant threat to humanity, especially in countries with an average and low level of healthcare development (Maiolini, 2020). The newest World Health Organization, Global Tuberculosis Report (2023) revealed that the reported global number of people newly diagnosed with TB was 7.5 million in 2022. This is the highest number since WHO began global TB monitoring in 1995, above the pre-COVID baseline. Globally in 2022, M. tuberculosis caused an estimated 1.30 million deaths. Also, the number of people with multidrug-resistant(MDR) or rifampicin-resistant tuberculosis increased with 450,000 new cases (World Health Organization, Global Tuberculosis Report, 2023). Moreover, the last decade has seen an increase in the number of cases of extremely drug-resistant tuberculosis (XDR-TB), defined as MDR-TB with additional resistance to at least one of the fluoroquinolones and one of the drugs administered in the form of injections (amikacin, kanamycin, capreomycin) used in MDR-TB treatment regimens. In the era of global population movements, the emergence of MDR-TB and XDR-TB makes the fight against tuberculosis an ongoing challenge (World Health Organization, Global Tuberculosis Report, 2019). Current treatment recommendations require the use of combinations of different drugs for periods ranging from 6 months to 9–20 months (MDR-TB). However, in the case of XDR tuberculosis, or when the treatment results are not satisfactory, the duration of treatment may be much longer (World Health Organization, Global Tuberculosis Report, 2019). Failure in antituberculosis therapy is caused mainly by its long duration, complicated drug regimens, strong side effects of antituberculosis drugs, and their interactions with drugs used in other disease units (Shehzad, 2013). What is more, in 2021, for the first time in 9 years, the estimated number of deaths from tuberculosis increased, which was caused by limited access to health care due to the COVID-19 pandemic. As a result, an estimated half of the infections went undiagnosed and untreated. The report also indicates that there has been a reduction in funding for tuberculosis treatment and BCG vaccines in children. The COVID-19 pandemic outbreak in 2020 disrupted essential health services and placed an additional burden on people with tuberculosis (World Health Organization, Global Tuberculosis Report, 2021). Nevertheless, the fight against tuberculosis is still ongoing and plant products play an important role in it.

Plants are essential for human living. Besides providing food for people and feed for animals, plants create a natural environment, produce oxygen, and supply various raw materials. Since ancient times people used plants for their benefits, including disease prevention and cure. The plant kingdom is an invaluable source of biologically active molecules, which nowadays are searched very rapidly, due to the access to the huge and systematically updated databases and the application of numerous bioinformatic tools. Moreover, the connection between different medical conditions and diet was already confirmed.

In the case of tuberculosis, Scopus database search results revealed that the first report for “tuberculosis and food” is from 1896, while for “tuberculosis and plants” from 1924 (Figure 1). Since that time the slow but consistent increase in the number of articles published on this topic is visible, suggesting that the link between plant/food and tuberculosis treatment exists. The significant rise in the number of publications combining “tuberculosis and food/plant” started in 2000, with the trend only slightly different for “food” and for “plant.” In both cases, years 2020–2022 yielded more than 200 publications each year, underlining the great interest in plant products and tuberculosis. Interestingly, Scopus search for the combination of terms “antimycobacterial AND plants” returns results published since 1987 (Figure 1). The “antimycobacterial” means in vitro or in vivo activity against mycobacteria, suggesting that since the nineties of the last century, researchers focused their interests on the screening of plant extracts and searching for new drug leads of plant origin. Based on the available literature sources few directions in which plants contribute to the management of tuberculosis were described (Figure 2).

The great interest and effort is put into screening of crude plant extracts, fractions, and isolated molecules against different M. tuberculosis strains. However, active or very active molecules represent only a small percentage of the checked pool. For this reason, the future focus should be placed on the combinations of natural compounds with antibiotics. Not only for the reason of direct synergistic antimycobacterial activity, but more importantly, for numerous other activities described as adjuvant in the course of tuberculosis. The body of evidence proving immunomodulation and hepatoprotection caused by plant secondary metabolites is growing; however, the clinical recommendations still have to be elaborated. The administration of plant extracts in tuberculosis is recognized in Eastern medicine; however, in Western treatment regimens plants still play a marginal role. Nevertheless, the significance of gut microbiota in the infection caused by M. tuberculosis is currently being investigated, hence the importance of prebiotics in the management of this disease may be strengthened in the near future, also contributing to the importance of natural plants in the management of tuberculosis.