curcumin and Tuberculosis

Tuberculosis, caused by Mycobacterium tuberculosis, is amongst the foremost infectious diseases. Treatment of tuberculosis is a complex process due to various factors including a patient's inability to persevere with a combined treatment regimen, the difficulty in eradicating the infection in immune-suppressed patients, and multidrug resistance (MDR). Extensive research circumscribing molecules to counteract this disease has led to the identification of many inhibitory small molecules. Among these are chalcone derivatives along with curcumin analogs. In this review article, we summarize the reported literature regarding anti tubercular activity of chalcone derivatives and synthetic curcumin analogs. Our goal is to provide an analysis of research to date in order to facilitate the synthesis of superior antitubercular chalcone derivatives and curcumin analogs.

Topics: Antitubercular Agents; Chalcone; Curcumin; Humans; Mycobacterium tuberculosis; Tuberculosis

To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC) formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced hepatotoxicity.. Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched (25%) CL and a hydro-ethanolic extract enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result.. Incidence and severity of hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs 2/316, P<0.0001). Mean aspartate transaminase (AST) (195.93+/-108.74 vs 85+/-4.24, P<0.0001), alanine transaminase (ALT) (75.74+/-26.54 vs 41+/-1.41, P<0.0001) and serum bilirubin (5.4+/-3.38 vs 1.5+/-0.42, P<0.0001). A lesser sputum positivity ratio at the end of 4 wk (10/67 vs 4/137, P=0.0068) and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment (9/152 vs 2/278, P=0.0037) was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group (P<0.0001).. The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.

Topics: Adult; Antitubercular Agents; Blood Sedimentation; Body Weight; Chemical and Drug Induced Liver Injury; Curcuma; Drug Therapy, Combination; Ethambutol; Female; Hemoglobins; Humans; Isoniazid; Liver Diseases; Male; Middle Aged; Patient Compliance; Plant Preparations; Pyrazinamide; Rifampin; Tinospora; Treatment Outcome; Tuberculosis

Topics: Animals; Autophagy; Curcumin; Isoniazid; Macrophages; Mice; Mycobacterium tuberculosis; Tuberculosis

Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.

Topics: Animals; Anti-Inflammatory Agents; Antitubercular Agents; Brain; Brain-Derived Neurotrophic Factor; Curcumin; Disease Models, Animal; Inflammation; Lung; Male; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Pulmonary

Tuberculosis (TB) infection triggers the innate and adaptive immune responses. Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma longa L. extracts exhibit various immunomodulatory effects.. This study aimed to determine the effects of 3 extracts used in Traditional Chinese Medicine (TCM) on cytokine production in peripheral blood mononuclear cells (PBMCs) obtained from patients with TB.. The research team performed an in vitro study with self controls.. The study took place at the Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taiwan.. 18 patients diagnosed with pulmonary TB were enrolled in the study.. Purified protein derivative (PPD)-stimulated PBMCs were cultured for 48 h in the presence and absence of 0.05 or 0.1 mg/mL of herbal extracts.. Cytokine levels of interferon (IFN)-γ, interleukin (IL)-10, IL-12, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 in the culture supernatant were measured.. C longa L., E ulmoides Oliv. and G pentaphyllum (Thunb.) Makino extracts decreased IFN-γ production in PPD-stimulated PBMCs. C longa L. extract did not exhibit a marked and consistent effect on the production of IL-10, IL-12, TNF-α and TGF-β1. E ulmoides Oliv. extract increased the production of IL-10, TNF-α and TGF-β1. G pentaphyllum (Thunb.) Makino extract increased the production of IL-10, IL-12, TNF-α and TGF-β1.. These results show that G pentaphyllum (Thunb.) Makino might enhance cell immunity since it increased the production of IL-12 and TNF-α with dose effect.

Topics: Curcuma; Cytokines; Eucommiaceae; Gynostemma; Humans; Leukocytes, Mononuclear; Plant Extracts; Tuberculosis

Tuberculosis (TB) is one of the deadliest diseases, causing ∼2 million deaths annually worldwide.

Topics: Adjuvants, Immunologic; Animals; BCG Vaccine; Curcumin; Female; Immunization; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Nanoparticles; Tuberculosis

Combination of isoniazid (INH) and rifampicin (RFP) causes liver injury frequently among tuberculosis patients. However, mechanisms of the hepatotoxicity are not entirely understood. Protoporphyrin IX (PPIX) accumulation, as an endogenous hepatotoxin, resulting from isoniazid and rifampicin co-therapy (INH/RFP) has been reported in PXR-humanized mice. Aminolevulinic acid synthase1 (ALAS1), ferrochelatase (FECH) and breast cancer resistance protein (BCRP) play crucial roles in PPIX synthesis, metabolism and transport, respectively. Herein, this study focused on the role of INH/RFP in these processes. We observed PPIX accumulation in human hepatocytes (L-02) and mouse livers. FECH expression was initially found downregulated both in L-02 cells and mouse livers and expression levels of ALAS1 and BCRP were elevated in L-02 cells after INH/RFP treatment, indicating FECH inhibition and ALAS1 induction might confer a synergistic effect on PPIX accumulation. Additionally, our results revealed that curcumin alleviated INH/RFP-induced liver injury, declined PPIX levels and induced FECH expression in both L-02 cells and mice. In conclusion, our data provide a novel insight in the mechanism of INH/RFP-induced PPIX accumulation and evidence for understanding pathogenesis of INH/RFP-induced liver injury, and suggest that amelioration of PPIX accumulation might be involved in the protective effect of curcumin on INH/RFP-induced liver injury.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Curcumin; Isoniazid; Liver; Mice; Photosensitizing Agents; Protoporphyrins; Rifampin; Tuberculosis

With the worldwide emergence of highly drug-resistant tuberculosis (TB), novel agents that have direct antimycobacterial effects or that enhance host immunity are urgently needed. Curcumin is a polyphenol responsible for the bright yellow-orange colour of turmeric, a spice derived from the root of the perennial herb Curcuma longa. Curcumin is a potent inducer of apoptosis-an effector mechanism used by macrophages to kill intracellular Mycobacterium tuberculosis (MTB).. An in vitro human macrophage infection model was used to determine the effects of curcumin on MTB survival.. We found that curcumin enhanced the clearance of MTB in differentiated THP-1 human monocytes and in primary human alveolar macrophages. We also found that curcumin was an inducer of caspase-3-dependent apoptosis and autophagy. Curcumin mediated these anti-MTB cellular functions, in part, via inhibition of nuclear factor-kappa B (NFκB) activation.. Curcumin protects against MTB infection in human macrophages. The host-protective role of curcumin against MTB in macrophages needs confirmation in an animal model; if validated, the immunomodulatory anti-TB effects of curcumin would be less prone to drug resistance development.

Topics: Apoptosis; Curcumin; Humans; Macrophages, Alveolar; Models, Immunological; Mycobacterium tuberculosis; NF-kappa B; Protective Agents; Tuberculosis

The Mycobacterium tuberculosis 19-kDa lipoprotein (P19) is both cell wall-associated and secreted and is a candidate virulence factor that could cause the apoptosis of human macrophages infected with M. tuberculosis. P19 induces TLR2 activation, resulting in the upregulation of death receptors and ligands, followed by a death-receptor signaling cascade. The mechanisms by which P19 induces macrophage apoptosis are not fully characterized. Curcumin, a natural polyphenol, exhibits a variety of pharmacological effects such as antioxidant, anti-inflammatory and antitumor properties. In the present study, we investigated the effect of curcumin on P19-induced apoptosis in human macrophage cells and the underlying mechanisms. The results showed that both P19 and curcumin inhibit the growth of macrophages in a dose- and time-dependent manner. A low dose of curcumin (10 or 20 µM) attenuated both the macrophage cell growth inhibition and the increase in the expression of IL-6 and TNF-α induced by P19. Curcumin also decreased the phosphorylation of JNK and p38 that were induced by P19. However, JNK but not p38 inhibitors reversed the effect of P19 on the growth inhibition of macrophages. These data suggest that curcumin may protect macrophages from P19-induced cell apoptosis via a TLR2-mediated JNK-dependent pathway.

Topics: Apoptosis; Bacterial Proteins; Cell Line; Curcumin; Humans; Inflammation; Interleukin-6; Lipoproteins; Macrophages; MAP Kinase Signaling System; Mycobacterium tuberculosis; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Receptors, Death Domain; Signal Transduction; Toll-Like Receptor 2; Tuberculosis; Tumor Necrosis Factor-alpha

Curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3), the curcuminoid constituents of the medicinal plant Curcuma longa L., have been structurally modified to 55 analogs and antimycobacterial activity against Mycobacterium tuberculosis has been evaluated. Among the highly active curcuminoids, the isoxazole analogs are the most active group, with mono-O-methylcurcumin isoxazole (53) being the most active compound (MIC 0.09 microg/mL). It was 1131-fold more active than curcumin (1), the parent compound, and was approximately 18 and 2-fold more active than the standard drugs kanamycin and isoniazid, respectively. Compound 53 also exhibited high activity against the multidrug-resistant M. tuberculosis clinical isolates, with the MICs of 0.195-3.125 microg/mL. The structural requirements for a curcuminoid analog to exhibit antimycobacterial activity are the presence of an isoxazole ring and two unsaturated bonds on the heptyl chain. The presence of a suitable para-alkoxyl group on the aromatic ring which is attached in close proximity to the nitrogen function of the isoxazole ring and a free para-hydroxyl group on another aromatic ring enhances the biological activity.

Topics: Antitubercular Agents; Curcuma; Curcumin; Humans; Isoxazoles; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis