Role of pattern recognition receptors in sensing Mycobacterium tuberculosis.

Mycobacterium tuberculosis is one of the major invasive intracellular pathogens causing most deaths by a single infectious agent. The interaction between host immune cells and this pathogen is the focal point of the disease, Tuberculosis. Host immune cells not only mount the protective action against this pathogen but also serve as the primary niche for growth. Thus, recognition of this pathogen by host immune cells and following signaling cascades are key dictators of the disease state. Immune cells, mainly belonging to myeloid cell lineage, recognize a wide variety of Mycobacterium tuberculosis ligands ranging from carbohydrate and lipids to proteins to nucleic acids by different membrane-bound and soluble pattern recognition receptors. Simultaneous interaction between different host receptors and pathogen ligands leads to immune-inflammatory response as well as contributes to virulence. This review summarizes the contribution of pattern recognition receptors of host immune cells in recognizing Mycobacterium tuberculosis and subsequent initiation of signaling pathways to provide the molecular insight of the specific Mtb ligands interacting with specific PRR, key adaptor molecules of the downstream signaling pathways and the resultant effector functions which will aid in identifying novel drug targets, and developing novel drugs and adjuvants.

Analgesic, anti-inflammatory activity and metabolite profiling of the methanolic extract of Callicarpa arborea Roxb. leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa arborea Roxb. is widely used as traditional medicine especially by the tribal people of Bangladesh in the management of wide range of ailments. In addition to Bangladesh, the leaves of this plant is utilized as a remedy to various painful and inflammatory conditions including rheumatism, toothache and stomachache in other countries of Indian subcontinent. AIM OF THE STUDY: Depending on the ethnomedicinal uses, we undertook this study to investigate the in-vivo analgesic and anti-inflammatory activities of the methanolic extract of C. arborea Roxb. leaves in Swiss albino mice as well as its chemical composition. MATERIALS AND METHODS: We evaluated the analgesic activity of Callicarpa arborea Roxb. leaves by the acetic acid induced writhing test, the hot plate test, and the formalin test. We undertook the egg albumin induced paw edema test to determine the anti-inflammatory activity of the plant. Furthermore, we conducted the phytochemical profiling by gas chromatography-mass spectrometry (GC-MS). RESULTS: In acute toxicity test, no mortality was observed at the highest dose of 2000 mg/kg b.w. Significant (p < 0.005) inhibition of acetic acid induced writhing was observed at both doses of the extract. A dose dependent increase in the response time was seen in the hot-plate test. In the formalin test, the extract significantly inhibited pain response in both early and late phase. We observed marked anti-inflammatory activity manifested by a significant (p < 0.005) reduction in egg albumin induced paw edema. We identified a total of twenty one compounds in the extract of by GC-MS analysis. CONCLUSION: Taken all into consideration we conclude that the leaves of C. arborea Roxb. possesses potent analgesic and anti-inflammatory activity, thus justifying its's ethnomedicinal use against painful and inflammatory pathological conditions.

Amaranthus spinosus Attenuated Obesity-Induced Metabolic Disorders in High-Carbohydrate-High-Fat Diet-Fed Obese Rats.

Amaranthus spinosus is a common vegetable of Bangladesh and well-known for its ethnomedicinal uses. In this study, we have evaluated the ability of powdered supplementation, methanol extract, and aqueous extract of A. spinosus in attenuating in high-carbohydrate-high-fat (HCHF) diet-induced obesity and associated metabolic disorders in female obese rates. Several parameters have been analyzed in this study including body weight, organ weight, fat deposition, glycemic status, lipid levels, hepatic and renal biomarkers, hepatic antioxidant status, and hepatosteatosis. All three samples of A. spinosus significantly reduced weight gain, organ weight, and abdominal fat deposition. Improved glucose tolerance and lipid parameters were seen in obese rats administered with A. spinosus powder, methanol extract, and aqueous extract. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatine kinase levels were normalized by the test samples. A. spinosus boosted hepatic antioxidant levels including reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Histopathology of liver tissue revealed increased fat infiltration and higher steatosis score in HCHF diet-fed obese rats which was brought down by A. spinosus. Analyzing all the results it can be concluded that this medicinal herb is beneficial in the management of obesity and obesity-induced metabolic disorders, making it a prospective food supplement.

Antioxidant properties and phenolic profiling by UPLC-QTOF-MS of Ajwah, Safawy and Sukkari cultivars of date palm.

Date palm (P. dactylifera) plays a vital role in ethnomedicinal practices in several parts of the world. There are over 2000 cultivars of date palm that differ in chemical composition and extent of bioactivity. The present study was undertaken to comparatively evaluate the antioxidant potential of three cultivars of date palm (Ajwah, Safawy and Sukkari) from Saudi Arabia and analyze their phenolic constituents in order to draw a rationale for their activity. Antioxidant activities of the date cultivars were evaluated by different quantitative methods including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging assay, total antioxidant capacity, reducing power, total phenolic (TPC), flavonoid (TFC) and tannin content (TTC), while qualitative phenolic composition was determined using ultra performance liquid chromatography coupled to quadropole time of flight mass spectrometry (UPLC-QTOF-MS). All the three date extracts showed good DPPH radical scavenging (IC50 103-177 µg/mL) and hydroxyl radical scavenging (IC50 1.1-1.55 mg/mL) activity and total antioxidant capacity (IC50 87-192 µg/mL). The reducing power was also comparable to that of ascorbic acid, used as standard in above experiments. All the three samples contain significant amount of major antioxidant components (phenolic, flavonoid and tannin) that successfully correlates with the results of radical scavenging assays. UPLC-QTOF-MS revealed a total of 22 compounds in these date cultivars classified into common phenolics, flavonoids, sterols and phytoestrogens. Significant variation in the degree of antioxidant activity of these three date cultivars can be attributed to the difference in the content and composition of phenolic compounds.

Supplementation of Heliotropium indicum Linn attenuates obesity and associated metabolic disorders in high-carbohydrate-high-fat diet-induced obese rats.

Heliotropium indicum Linn is a leafy vegetable that has been used in Bangladeshi ethnomedicinal practices. The attenuation effect of H. indicum supplementation was evaluated in high carbohydrate high-fat (HCHF) diet-induced obesity and associated disorders in 8-weeks-old female Wister rats. H. indicum significantly (p < .05) prevented weight gain and improved glucose intolerance in obese rats. It also significantly (p < .05) ameliorated lipid parameters in HCHF diet fed rats preventing hypercholesterolemia and hypertriglyceridemia, resulting in improved the artherogenic index (AI). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities were brought to normal by H. indicum. It significantly elevated superoxide dismutase (SOD) and catalase (CAT) activities as well as increased reduced glutathione (GSH) concentration in liver. The intense liver fat deposition was seen in HCHF fed rats which were relatively low in H. indicum fed rats. Therefore, H. indicum has the ability to prevent obesity and associated metabolic disorders. PRACTICAL APPLICATIONS: Obesity and associated metabolic disorders are the most common threats to public health. Modern lifestyle and food habits are the main causes behind this malice, and the introduction of functional foods in daily diet is proved to be highly beneficial. Results of this study demonstrated that H. indicum can effectively attenuate obesity and its associated metabolic complications. Therefore, the current study has the merits to promote scientific knowledge of the dietary application of H. indicum as a functional food among the community.

Phytol anti-inflammatory activity: Pre-clinical assessment and possible mechanism of action elucidation.

Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and antimicrobial. Here, we aimed to assess the PHY anti-inflammatory effect in vitro and in vivo, and to deepen knowledge on the possible mechanism of action. For this purpose, egg albumin (in vitro) test was performed by using acetyl salicylic acid (ASA) as a standard nonsteroidal anti-inflammatory drugs (NSAID). For in vivo test, male Wistar albino rats were treated (intraperitoneally) with 100 mg/kg of PHY and/or standard NSAIDs ASA (100 mg/kg) and diclofenac sodium (Diclo-Na, 10 mg/kg) to evaluate the combined effect of PHY in formalin-induced paw edema model. Furthermore, an in silico (CADD) study was accomplished to assess the effect of PHY against cyclooxygenase (COX)-1 and 2 enzymes, nuclear factor kappa B (NF-κB), and interleukin-1ß (IL-1ß). Results revealed that PHY exhibits dose-dependent anti-inflammatory effect using the egg albumin method. PHY (100 mg/kg) co-treated with ASA and/or Diclo-Na reduced paw edema better than PHY alone or NSAIDs individual groups. Computational study showed that PHY efficiently interacts with COX-1 and 2, NF-κB, and IL-1ß. In conclusion, PHY exhibits anti-inflammatory activity, possibly via COX-1 and 2, NF-κB, and IL-1ß dependent pathways.

Agathisflavone: Botanical sources, therapeutic promises, and molecular docking study.

In this article, we have summarized the biological sources and pharmacological activities of agathisflavone along with molecular docking studies to correlate the interaction of this biflavonoid and biomacromolecules involving in its biological effects observed in database-oriented scientific reports. For this, an up-to-date (from 1991 to October 2018) search was done on the databases such as PubMed, Science Direct, Web of Science, Scopus, The American Chemical Society, Clinicaltrials.gov, and Google Scholar databases. The findings suggest that agathisflavone possesses antioxidant, anti-inflammatory, antiviral, antiparasitic, cytotoxic, neuroprotective, and hepatoprotective activities. An in silico study of agathisflavone against 17 essential proteins/enzymes revealed that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are the most efficient enzymes for the interaction and binding of this biflavonoid for its anti-inflammatory activity. In conclusion, agathisflavone may be one of the promising plant-derived lead compounds in the treatment of oxidative stress, inflammatory diseases, microbial infection, hepatic and neurological diseases and disorders, and cancer. © 2019 IUBMB Life, 71(9):1192-1200, 2019.

Analgesic Activity, Chemical Profiling and Computational Study on Chrysopogon aciculatus.

Present study was undertaken to evaluate the analgesic activity of the ethanol extract of Chrysopogon aciculatus. In addition to bioassays in mice, chemical profiling was done by LC-MS and GC-MS to identify phytochemicals, which were further docked on the catalytic site of COX-2 enzymes with a view to suggest the possible role of such phytoconstituents in the observed analgesic activity. Analgesic activity of C. aciculatus was evaluated by acetic acid induced writhing reflex method and hot plate technique. Phytochemical profiling was conducted using liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS). In docking studies, homology model of human COX-2 enzyme was prepared using Easy Modeler 4.0 and the identified phytoconstituents were docked using Autodock Vina. Preliminary acute toxicity test of the ethanol extract of C. aciculatus showed no sign of mortality at the highest dose of 4,000 mg/kg. The whole plant extract significantly (p < 0.05) inhibited acetic acid induced writhing in mice at the doses of 500 and 750 mg/kg. The extract delayed the response time in hot plate test in a dose dependent manner. LC-MS analysis of the plant extract revealed the presence of aciculatin, nudaphantin and 5α,8α-epidioxyergosta-6,22-diene-3ß-ol. Three compounds namely citronellylisobutyrate; 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one and nudaphantin were identified in the n-hexane fraction by GC-MS. Among these compounds, six were found to be interacting with the binding site for arachidonic acid in COX-2 enzyme. Present study strongly supports the traditional use of C. aciculatus in the management of pain. In conclusion, compounds (tricin, campesterol, gamma oryzanol, and citronellyl isobutyrate) showing promising binding affinity in docking studies, along with previously known anti-inflammatory compound aciculatin can be held responsible for the observed activity.

Comparative study of neuropharmacological, analgesic properties and phenolic profile of Ajwah, Safawy and Sukkari cultivars of date palm (Phoenix dactylifera).

In addition to the rich nutritional value, date palm is also used in various ethnobotanical practices for the treatment of various disease conditions. Present investigation was undertaken to examine the neuropharmacological and antinociceptive effect of the ethanol extract of three date cultivars growing in Saudi Arabia, namely Ajwah, Safawy and Sukkari. Neuropharmacological effect was observed by pentobarbitone induced sleeping time, open field, and hole board test. Antinociceptive activity was tested by acetic acid induced writhing and hot plate test. The date extracts were also subjected to HPLC analysis to detect the presence of common bioactive polyphenols. All the three date extracts extended the pentobarbitone induced sleeping time, reduced locomotor activity in open field test and reduced exploratory behaviour in hole board test in mice. The extracts also reduced acetic acid induced writhing and delayed response time in hot plate test. The activities were stronger for Ajwah than the other two date cultivars. HPLC analysis indicated the presence of trans-ferulic acid in all three cultivars, while (+)-catechin and (-)-epicatechin only in Ajwah and Safawy. The observed neuropharmacological and analgesic activity could be partly due to the presence of (+)-catechin, (-)-epicatechin and trans-ferulic acid, three important plant polyphenols well known for their neuroprotective activity and their ability to exert antioxidant activity on brain cells. Present investigation also supports the ethnobotanical use of date palm to provide ameliorating effects in pain and CNS disorders.