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doi:10.1038/nindia.2017.74 Published online 4 July 2017

Indian spice in the fight against TB

K. S. Jayaraman



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Researchers have reported another new medicinal use for curcumin, the bioactive component of Indian kitchen spice turmeric (Curcuma longa). Nanoparticles of curcumin could offer a potential new treatment for tuberculosis (TB) that would be less prone to the development of drug resistance, they report1.

"Indian Yellow gold” curcumin has been shown to be effective against many inflammatory and infectious diseases. But its use as a drug has remained limited due to its low bioavailability and rapid elimination from the body. "Enhancing its bioavailability has been the main challenge,” says Gobardhan Das at the Centre for Molecular Medicine in Jawaharlal Nehru University, New Delhi and corresponding author of the study.

To overcome this limitation, Das and his team developed a simple one-step process to generate curcumin nanoparticles of about 200-nm in size and tested them in experimental mice. They noticed a 5-fold increase in bioavailability of curcumin in mice receiving the nanoparticles as compared to mice receiving curcumin in its natural form.

Currently recommended therapy for TB involves months of treatment with antibiotics such as Isoniazid (INH). The TB organism Mycobacterium tuberculosis (or M. tb) acquires drug-resistance due to premature withdrawal by patients. Prolonged INH treatment also induces liver toxicity. Importantly, patients receiving such treatment become susceptible to re-infection and disease reactivation.

These problems were overcome by nanoparticle-formulated curcumin given along with INH in M. tb infected mice.

"We observed that mice treated with both curcumin nanoparticles and INH exhibited a dramatically accelerated clearance of the microorganisms in both lung and spleen," the report says. Also, curcumin nanoparticles "drastically reduced hepatotoxicity induced by (INH) and significantly reduced the time needed for antibiotic therapy to obtain sterile immunity, thereby reducing the possibility of generating drug-resistant variants of the organism."

Most interestingly, according to the authors, "co-treatment of nanoparticle-formulated curcumin along with anti-tubercular antibiotics enhanced T cell-mediated immunity" and protected the mice from reactivation of TB. "In sharp contrast, animals that previously received only INH displayed increased susceptibility to re-infection."

"Therefore, adjunct therapy of nano-formulated curcumin with enhanced bioavailability may be beneficial to treatment of tuberculosis and possibly other diseases," Das told Nature India. "The curcumin nanoparticles are stable and can be administered both orally as well as intraperitoneally and, therefore, have greater potential for therapeutic use under different conditions."

"TB being a major scourge in India, any strategy to decrease duration of treatment and prevent resistance development and side effects would be welcome," Govindarajan Padmanaban, a biochemist at the Indian Institute of Science in Bengaluru who has extensively studied curcumin's properties told Nature India.

"Curcumin has a potential to be used as an adjunct drug for a large number of diseases, if not all," Padmanabhan said.

Padmanabhan, however, noted a few gaps in the current study. "Nano curcumin is administered through injection, which may not be feasible for prolonged treatment. It would be necessary to demonstrate similar efficacy in oral treatment," he said.

"The studies carried out in mouse models need to be taken further with the more susceptible guinea pig model using the aerosol route of infection. Ultimately, it is necessary to demonstrate efficacy in clinical trials.


References

1. Tousif, S. et al. Nanoparticle-formulated curcumin prevents post-therapeutic disease reactivation and reinfection with Mycobacterium tuberculosis following isoniazid therapy. Front. Immunol. (2017) doi: 10.3389/fimmu.2017.00739