Research - Tuberculosis
Antimycobacterial activity against different pathogens and selectivity index of fourteen medicinal plants used in southern Africa to treat tuberculosis and respiratory ailments
J.P. Dzoyem, A.O. Aro, L.J. McGaw, J.N. Eloff
Many plants are used in traditional medicine to treat tuberculosis and other respiratory disorders in Africa. The emergence of multiple drug resistance has become a major threat and thus calls for an urgent need to search for new effective and safe anti-TB agents. The aim was to determine the antimycobacterial activity and the safety of the acetone leaf extracts of 14 plant species used in southern Africa to treat tuberculosis and pulmonary ailments.
The antimycobacterial activity was evaluated by a tetrazolium violet based broth microdilution method against three fast-growing mycobacteria species (Mycobacterium smegmatis,Mycobacterium aurum and M. fortuitum) and one pathogenic M. tuberculosis field strain. The in vitro cellular toxicity was determined using the MTT assay on Vero monkey kidney cells. The extraction yield, the LC50 and MIC values were used to determine the total activity (TA) and the selectivity index (SI) of the extracts.
Extracts had moderate to weak activity with the MIC values ranging from 0.039 to > 2.5 mg/mL. M. fortuitum appeared to be better predictor of activity against pathogenic M. tuberculosis than M. smegmatis and M. aurum. Extracts from Heteropyxis natalensis (3.3) and Hexalobus monopetalus (2.47) had the highest selectivity index.
The results substantiate the safety and in some cases the potential efficacy of the traditional use of these species against tuberculosis and pulmonary ailments.
Source : South African Journal of Botany
Link to Full Article
Anti-inflammatory and antioxidant effect of ginger in tuberculosis
Kulkarni RA, Deshpande AR.
BACKGROUND:Tuberculosis (TB) has reemerged to become the world's leading cause of death from a single infectious agent. Inflammatory cytokines play an important role during the course of the disease and may be responsible for tissue damage by lipid peroxidation. The study was aimed to explore the anti-inflammatory and antioxidant effect of ginger in pulmonary TB patients.
METHODS:A total of 69 pulmonary TB patients participated in a randomized and placebo-controlled study. The intervention group received 3 g of ginger extract daily for 1 month and placebo group was supplemented with starch capsule. Participants of both groups were taking standard antitubercular treatment during the study. The concentrations of tumor necrosis factor (TNF) alpha, ferritin and malondialdehyde (MDA) in blood samples were analyzed before and after the intervention by using enzyme-linked immunosorbent assay for TNF alpha and ferritin and spectrophotometry for MDA.
RESULTS:Ginger supplementation significantly reduced the levels of TNF alpha, ferritin and MDA in ginger supplemented group in comparison to baseline. Ginger supplementation with antitubercular treatment significantly lowered TNF alpha, ferritin and MDA concentrations in comparison to control group.
CONCLUSIONS:Ginger was found to be effective as an anti-inflammatory and antioxidant supplement along with anti-TB therapy as it possesses strong free radical scavenging property.
Source : Journal Complement Integra Medicine
Link to Abstract
A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury
Chote Luangchosiri1, Ammarin Thakkinstian2, Sermsiri Chitphuk3, Wasana Stitchantrakul3, Supanna Petraksa1 and Abhasnee Sobhonslidsuk14*
Background Hepatitis is a common adverse effect of antituberculosis drugs. Silymarin prevented drug-induced hepatoxicity in animals with anti-oxidative mechanisms but its effect in human has been unknown. We aimed to evaluate the efficacy of silymarin for preventing antituberculosis-drug induced liver injury (antiTB-DILI) in patients with tuberculosis.
Methods A double-blind randomized placebo-controlled trial was performed. Tuberculosis patients were randomly allocated to receive placebo or silymarin. The outcomes of interests were antiTB-DILI and the maximum liver enzymes at week 4. Antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione and malondialdehyde assays) were assessed. The risks of antiTB-DILI between the two groups were compared. A number need to treat was estimated.
Results A total of 55 out of 70 expected numbers of patients were enrolled. There were 1/27 (3.7 %) and 9/28 (32.1 %) patients who developed antiTB-DILI in the silymarin and the placebo groups. Risk reduction was 0.28 (0.10, 0.47), i.e., receiving silymarin was 28 % at lower risk for antiTB-DILI than placebo. This led to prevention of 28 patients from being antiTB-DILI among 100 treated patients. Median (IQR) of ALT levels at week 4 in the placebo and the silymarin group were 35.0 (15, 415) IU/L and 31.5 (20, 184) IU/L (p = 0.455). The decline of SOD level at week 4 in the silymarin group was less than the placebo group (p < 0.027).
Conclusions Silymarin reduced the incidence of antiTB-DILI. The benefit of silymarin may be explained from superoxide dismutase restoration. Larger clinical trials are required to confirm the result of our small study
Source : BMC Complementary and Alternative Medicine
Link to Full Article
All-Trans Retinoic Acid–Triggered Antimicrobial Activity against Mycobacterium tuberculosis Is Dependent on NPC2
- Matthew Wheelwright*,1,
- Elliot W. Kim*,1,
- Megan S. Inkeles†,
- Avelino De Leon‡,
- Matteo Pellegrini†,
- Stephan R. Krutzik* and
- Philip T. Liu*,‡
- *Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095;
- †Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095; and
- ‡University of California, Los Angeles and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, CA 90095
A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the mechanism is unclear. In this study, we demonstrate that vitamin A–triggered antimicrobial activity against M. tuberculosis requires expression of NPC2. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D3), the biologically active forms of vitamin A and vitamin D, respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Stimulation of primary human monocytes with ATRA did not result in expression of the antimicrobial peptide cathelicidin, which is required for 1,25D3 antimicrobial activity. In contrast, ATRA triggered a reduction in the total cellular cholesterol concentration, whereas 1,25D3 did not. Blocking ATRA-induced cellular cholesterol reduction inhibits antimicrobial activity as well. Bioinformatic analysis of ATRA- and 1,25D3-induced gene profiles suggests that NPC2 is a key gene in ATRA-induced cholesterol regulation. Knockdown experiments demonstrate that ATRA-mediated decrease in total cellular cholesterol content and increase in lysosomal acidification are both dependent upon expression of NPC2. Expression of NPC2 was lower in caseous tuberculosis granulomas and M. tuberculosis–infected monocytes compared with normal lung and uninfected cells, respectively. Loss of NPC2 expression ablated ATRA-induced antimicrobial activity. Taken together, these results suggest that the vitamin A–mediated antimicrobial mechanism against M. tuberculosis requires NPC2-dependent expression and function, indicating a key role for cellular cholesterol regulation in the innate immune response.
Source : Journal of Immunology
Link to Abstract
Vitamin D May Speed TB Recovery
Vitamin D supplementation may bolster the performance of antibiotics in patients with pulmonary tuberculosis and accelerate the resolution of inflammatory responses, researchers found.
In a randomized, controlled trial, patients who took high-dose vitamin D in addition to anti-tuberculous therapy cleared the bacterium significantly faster than those who took antimicrobials alone (HR 1.69, 95% CI 1.02 to 2.79, P=0.04), reported Adrian Martineau, PhD, of Queen Mary University of London, and colleagues in the Proceedings of the National Academy of Sciences online.
"Adding vitamin D to antibiotic therapy accelerated sputum smear conversion, augmented treatment-induced increases in lymphocyte count, and enhanced the suppressive effect of treatment on monocyte count, inflammatory markers, and circulating concentrations of chemokines," they explained.
Calcitriol, the active metabolite of vitamin D, has been shown to induce innate antimicrobial responses in vitro, and the vitamin itself was used to treat TB before antibiotics were available.
Yet the effects of vitamin D supplementation on immune response in humans hasn't been well-studied.
Martineau and colleagues conducted a longitudinal study of immune response in 95 patients on antimicrobial therapy for smear-positive pulmonary TB. Patients were randomized to adjunctive high-dose vitamin D (four doses of 2.5 mg vitamin D3 every 2 weeks) or placebo. They were assessed for a period of 8 weeks.
The group noted that many patients had markedly low vitamin D levels at baseline.
The researchers found that patients who had the additional vitamin D cleared Mycobacterium tuberculosis from their sputum faster than those who only had antibiotics. The median time to sputum smear conversion was significantly shorter with vitamin D than among controls (23 days versus 36 days, HR 1.69, 95% CI 1.02 to 2.79, P=0.04).
Monocyte counts fell more rapidly (P=0.0003) and lymphocyte counts rose faster (P=0.0364) in patients taking vitamin D, they reported.
The vitamin also accelerated the effect of anti-tuberculous therapy on 17 circulating parameters, especially affecting the chemokine CXCL9, with serum concentrations falling significantly faster in patients taking vitamin D. Serum concentrations of three other chemokines -- CXCL10, CCL3, and CCL5 -- as well as IFN-γ also fell more rapidly in supplemented patients (P≤0.0164 and P=0.0112, respectively).
In further analyses, vitamin D also appeared to suppress antigen-stimulated proinflammatory cytokine responses, in particular for IL-1 receptor agonist (IL-1RA), IL-6, IL-12, and TNF (P≤0.0437).
On the other hand, it attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α (P≤0.0323), they reported.
Martineau and colleagues also observed that vitamin D appeared to have immunomodulatory effects even in patients who had the TT and Tt genotypes of the TaqI VDR polymorphism, suggesting that benefits are not limited to those with the tt genotype, as had been previously reported.
They concluded that the findings suggest "a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality."
They added that vitamin D may also boost the response to antimicrobial therapy in patients with pneumonia and sepsis.
Coussens AK, et al "Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment" PNAS 2012; DOI: 10.1073/pnas.1200072109/-/DCSupplemental.
Source : MedPage Today
Link to Source