Glucomannan is a promising isoniazid's enhancer that inducing macrophage phagocytosis.

Isoniazid (INH) is a frontline antituberculosis agent effective against Mycobacterium tuberculosis (Mtb), but the increasing challenge of avoiding multidrug-resistant tuberculosis, including INH resistance, necessitates innovative approaches. This study focused on enhancing macrophage phagocytosis to overcome INH resistance. Glucomannan, an immunomodulatory polysaccharide, emerged as a potential macrophage activator. Our objective was to characterize the glucomannan-INH mixture and assess its impact on INH efficacy and macrophage activity. Detailed examination of the glucomannan from Amorphophallus muelleri (0.05%-0.2%) was performed in several methods. INH sensitivity tests were carried out with the Mtb strain H37RV on Löwenstein-Jensen medium. Murine macrophage (RAW264.7) viability and activity were evaluated through MTT and latex bead phagocytosis assays. Ultraviolet-wavelength spectrophotometry was used to analyze chemical structure changes. Glucomannan (0.05%-0.2%) significantly enhanced murine macrophage viability and activity. When glucomannan was combined with INH, the IC50 value was greater compared to INH only. Phagocytosis assays revealed heightened macrophage activity in the presence of 0.05% and 0.1% glucomannan. Importantly, glucomannan did not compromise INH efficacy or alter its chemical structure. This study underscores the potential of glucomannan, particularly with a lower molecular weight, as a promising enhancer of INH, boosting macrophage phagocytosis against INH-resistant Mtb. These findings challenge the assumptions about the impact of glucomannan on drug absorption and prompt potential reevaluation. While specific receptors for glucomannan in macrophage phagocytosis require further exploration, the complement receptors are proposed to be potential mediators.

Characterization of chemokine and cytokine expression pattern in tuberculous lymphadenitis patient.

Introduction: C-C chemokine receptor-2 (CCR-2) and C-C chemokine ligand-5 (CCL-5) play an important role in the migration of monocytes, macrophages, dendritic cells, and activated T cells against Mycobacterium tuberculosis (M.tb). Meanwhile, signal transducer and activator of transcription 3 (STAT-3) and suppressor of cytokine signaling 3 (SOCS-3), activated by interleukin (IL)-6 and IL-10 in tuberculosis (TB) infection, play an important role in phagocytosis, inflammation, and granulomatous-forming processes that may lead to TB treatment success or failure. However, there are no data about the expression of those markers in tuberculous lymphadenitis. The characterization of those markers is very critical to put a fundamental basis to understand the homing mechanism of tuberculous lymphadenitis. Aim of study: The specific objective of this study is to characterize the expression pattern of CCR-2-CCL-5, IL-6, IL-10, STAT-3, and SOCS-3 in tuberculous lymphadenitis. Methods: The study was performed on 27 cases of tuberculous lymphadenitis node biopsies. The diagnosis of tuberculous lymphadenitis was based on the clinical criteria and the presence of the histological feature characteristic of TB granulomas. Afterward, immunohistochemistry was stained with CCR-2, CCL-5, IL-6, IL-10, STAT-3, and SOCS-3. A semiquantitative analysis of IHC images was performed to examine protein expression in stained preparations. The expression was also manually counted. Results: Compared with the normal area, both lymphocytes and macrophages expressed strongly CCR-2-, CCL-5, and IL-6, while IL-10, STAT-3-, and SOCS-3- were expressed lowly. There was a strong positive correlation between CCR-2 with IL-6 (p = 0,83) and IL-10 (p = 0,83). Conclusion: The chronic infection process of tuberculous lymphadenitis was characterized by the expression of IL-10low, STAT-3low, SOCS-3low, CCR-2high, CCL-5high, and IL-6high. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT05202548.

Managing spondylitis tuberculosis in a patient with underlying diabetes and hypothyroidism: A case report.

BACKGROUND: Tuberculosis (TB) remains one of the highest Asia's health problems. Spondylitis TB in diabetes mellitus (DM) and hypothyroidism patients is a rare case of extrapulmonary tuberculosis. However, there is a lack of therapeutic guidelines to treat spondylitis TB, particularly with type 2 DM (T2DM) and hypothyroidism as comorbidities. Here we present a case of spondylitis TB with T2DM and hypothyroidism in a relatively young patient and its therapeutic procedure. CASE SUMMARY: We report the case of a 35-year-old male patient from Surabaya, Indonesia. Based on anamnesis, physical examination, and magnetic resonance imaging, the patient has been categorized in stage II of spondylitis TB with grade 1 paraplegia. Surprisingly, the patient also had a high HbA1c level, high thyroid stimulating hormone, and low free T4 (FT4), which indicated T2DM and hypothyroidism. A granulomatous process was observed in the histopathological section. The antituberculosis drugs isoniazid and rifampicin were given. In addition, insulin, empagliflozin, and linagliptin were given to control hyperglycemia conditions, and also levothyroxine to control hypothyroidism. CONCLUSION: The outcome was satisfactory. The patient was able to do daily activities without pain and maintained normal glycemic and thyroid levels. For such cases, we recommend the treatment of spondylitis TB by spinal surgery, together with T2DM and hypothyroidism therapies, to improve the patients' condition. Prompt early and non-invasive diagnoses and therapy are necessary.

Influence of extraction methods of bay leaves (Syzygium polyanthum) on antioxidant and HMG-CoA Reductase inhibitory activity.

OBJECTIVE: Bay leaf, one of the plants in Indonesia that has been shown to have activities to reduce cholesterol in the blood. HMG-CoA Reductase inhibition is one of many mechanisms in lowering the level of cholesterol in the blood. Here, we reported the inhibitory activity of HMG-CoA Reductase of bay leaves ethanol extracts that we suspected to be the mechanism of action of bay leaves in reducing cholesterol in the blood. In this research we also investigated the correlation between the inhibitory activities, the total phenol content and antioxidant activities of bay leaves (Syzygium polianthum) ethanol extracts. METHODS: The inhibitory activity of HMG-CoA Reductase was determined kinetically at 340 nm using simvastatin as positive control. In vitro scavenging assays of 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric ion reducing antioxidant power (FRAP), and beta-carotene method were used to determine the antioxidant activities. The total phenolic content was determined by Folin-Ciocalteu's method. RESULTS: The IC50 of bay leaves ethanolic extract obtained by percolation and soxhlet extraction method towards HMG-CoA Reductase enzyme activity were 49.50 ± 0.700 µg/mL and 15.50 ± 0.707 µg/mL, respectively, while the IC50 of simvastatin was 0.00238 ± 0.00004 µg/mL. The antioxidant activity and total phenolic content of bay leaves ethanolic extract obtained by Soxhlet extraction method was higher compared to the percolation method (DPPH and beta-carotene assay results). The 3D linear analysis showed that there was a high correlation between the inhibition activities of HMG-CoA Reductase pattern of both extract types and the total phenol pattern and also the antioxidant pattern of these extracts. CONCLUSION: The result showed that the bay leaves ethanolic extract have a potent activity to reduce the cholesterol serum level by inhibition of HMG-CoA Reductase activity. The activity was due to the phenolic compounds in the extracts as well as the antioxidant activity of the extracts.

Phytochemical screening and preliminary clinical trials of the aqueous extract mixture of Andrographis paniculata (Burm. f.) Wall. ex Nees and Syzygium polyanthum (Wight.) Walp leaves in metformin treated patients with type 2 diabetes.

BACKGROUND: Our previous preclinical study showed that the extract mixture (EM) of Andrographis paniculata (Burm. f.) Wall. ex Nees (AP) and Syzygium polyanthum (Wight.) Walp (SP) leaves had antidiabetic effects and were beneficial on alloxan-induced diabetic rats. PURPOSE: The objectives of this study were to: 1) identify the phytochemical compounds present in aqueous extract of AP and SP and 2) examine the benefits of the EM of AP and SP leaves in lowering blood glucose in the presence of standard antidiabetic treatment using metformin in type 2 diabetic patients in Indonesian Traditional Medicine Polyclinic of Dr. Soetomo General Hospital in Surabaya. METHODS: Phytochemical analysis of aqueous leaf extract of AP and SP was performed using standard chemical tests, TLC, and GC-MS. Furthermore, a total of 54 subjects with T2DM participated in this study and were randomly assigned to either the intervention group supplemented with the extract mixture of AP and SP at a dose 900  mg/day for 8 weeks, or the control group which received placebo tablets in a randomized placebo-controlled double-blinded parallel clinical trial. Both groups received metformin at dose 1000  mg/day. Body weight, blood pressure, fasting blood glucose, postprandial glucose, haemoglobin A1c, triglycerides, total cholesterol, low density lipoprotein, high density lipoprotein, and markers of liver and kidney damage were measured. RESULTS: The results of phytochemical analysis showed that the glycosides, terpenoids, alkaloids, flavonoids, saponins, and tannins were found to be present in the extract mixture. GC-MS analyses of AP and SP showed the presence of 19 and 12 peaks, respectively. Methyl ester of 9-octadecenoic and eicosanoic acid were determined as the main constituents of both species. Moreover, the results of clinical study suggested that the extract mixture improved the decrease of fasting blood glucose and postprandial glucose, significantly lowered body mass index compared with the control group. The EM appeared beneficial for SGPT values and uric acid levels. CONCLUSION: Overall, the results of this study suggested the potential beneficial effects of the extract mixture for use as complementary medicine alongside conventional treatment of metformin. The extract mixture contained many highly potent compounds for treating T2DM and preventing short- and long-term risk complications of diabetes.

Crude Ethanol Extract of Pithecellobium ellipticum as a Potential Lipid-Lowering Treatment for Hypercholesterolaemia.

If left untreated, hypercholesterolaemia can lead to atherosclerosis, given time. Plants from the Fabaceae family have shown the ability to significantly suppress atherosclerosis progression. We selected four extracts from Pithecellobium ellipticum, from the Fabaceae family, to be screened in a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) assay. The ethanol extract, at a concentration of 500 µ g/mL, exhibited superior inhibition properties over the other extracts by demonstrating 80.9% inhibition, while 0.223 µ g/mL of pravastatin (control) showed 78.1% inhibition towards enzymatic activity. These findings led to the fractionation of the ethanol extract using ethyl acetate : methanol (95 : 5), gradually increasing polarity and produced seven fractions (1A to 7A). Fraction 7A at 150 µ g/mL emerged as being the most promising bioactive fraction with 78.7% inhibition. FRAP, beta carotene, and DPPH assays supported the findings from the ethanol extract as it exhibited good overall antioxidant activity. The antioxidant properties have been said to reduce free radicals that are able to oxidize lipoproteins which are the cause of atherosclerosis. Phytochemical screenings revealed the presence of terpenoid, steroid, flavonoid, and phenolic compounds as the responsible group of compound(s), working individually or synergistically, within the extract to prevent binding of HMG-CoA to HMG-CoA reductase.

In vitro 5-LOX inhibitory and antioxidant activities of extracts and compounds from the aerial parts of Lopholaena coriifolia (Sond.) E. Phillips & C.A. Sm.

The aim of this study was to investigate the antioxidant and anti-inflammatory potentials of crude extracts of Lopholaena coriifolia (Sond.) E. Phillips & C.A. Sm. and its isolated compounds. Separation and structure elucidation of Lopholaena coriifolia (Sond.) E. Phillips & C.A. Sm. were conducted using chromatographic and spectroscopic method. The antioxidant activities of the extracts in this study were determined by the ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ß-carotene bleaching assays meanwhile the anti-inflammatory activity was evaluated using the 5-lipoxygenase assay. Seven known compounds quercetin 3-O-glucoside (1), naringenin 7-O-glucoside (2), seneciphylline-O-glucoside (3), chrysoeriol (4), retrorsine (5), adonifiline (6) and 5,4'-di-O-methyl alpinumisoflavone (7) were isolated from ethanol extract of Lopholaena coriifolia (Sond.) E. Phillips & C.A. Sm. The ethanol and water extracts of Lopholaena coriifolia (Sond.) E. Phillips & C.A. Sm. elicited potent antioxidant and anti-inflammatory properties. Amongst the isolated compounds quercetin 3-O-glucoside gave strong antioxidant activity and adonifiline strongly inhibited 5-lipoxygenase activity.

Antibacterial and antioxidant activities of Synedrella nodiflora (L.) Gaertn. (Asteraceae).

The hexane, ethyl acetate, ethanol and water extracts of Synedrella nodiflora (L.) Gaertn. (Asteraceae) were assessed for their antibacterial and antioxidant capacities. The antioxidant capacities were evaluated using the ferric reducing antioxidant power (FRAP) and ß-carotene bleaching assays. The antimicrobial activities were assessed using the classical pour-plate disc diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and death kinetic assays, against six bacterial strains. The ethanol extract displayed significant antioxidant capacities both in the FRAP and ß-carotene bleaching assays. The ethanol extract abrogated the growth of all the bacteria tested. Folin-Ciocalteu and aluminium chloride spectrometry assays indicated the presence phenolic compounds, including flavonoids in the ethanol extract.