Hydrocortisone decreases lethality and inflammatory cytokine and nitric oxide production in rats challenged with B. anthracis cell wall peptidoglycan

Abstract Background Lethal B. anthracis infection produces high proinflammatory peptidoglycan (PGN) burdens in hosts. We investigated whether the lethality and inflammation anthrax PGN can produce are related. Methods At 6 h before and the start of 24 h anthrax PGN infusions, rats (n = 198) were treated with diluent (controls) or one of three IV-doses of either hydrocortisone (125, 12.5 or 1.25 mg/kg) or TNF-soluble receptor (TNFsr; 2000, 1000 or 333 μg/kg), non-selective and selective anti-inflammatory agents, respectively. Results Compared to controls, hydrocortisone 125 and 12.5 mg/kg each decreased 7-day lethality (p ≤ 0.004). Hydrocortisone 125 mg/kg decreased IL-1β, IL-6, TNFα, MCP, MIP-1α, MIP-2, RANTES and nitric oxide (NO) blood levels at 4 and 24 h after starting PGN (except MCP at 24 h). Each decrease was significant at 4 h (except MIP-1α that was significant at 24 h) (p ≤ 0.05). Similarly, hydrocortisone 12.5 mg/kg decreased each measure at 4, 24 and 48 h (except TNFα at 24 h and MIP-1α at 24 and 48 h and NO at 48 h). Decreases were significant for IL-6 and NO at 4 h and RANTES at 48 h (p ≤ 0.05). Hydrocortisone 1.25 mg/kg had non-significant effects. Each TNFsr dose decreased lethality but non-significantly. However, when doses were analyzed together, TNFsr decreased lethality in a potential trend (p = 0.16) and IL-6 and NO significantly at 4 h (p = 0.05). Conclusions Peptidoglycan-stimulated host inflammation may contribute to B. anthracis lethality.

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Phytochemical screening, cytotoxicity and anti-inflammatory activities of the leaf extracts from Lawsonia inermis of Indian origin to explore its potential for medicinal uses

Medicinal Chemistry ◽

10.2174/1573406416666200221101953 ◽

2020 ◽

Vol 16 ◽

Cited By ~ 1

Author(s):

Anju Manuja ◽

Nitu Rathore ◽

Shalki Chaudhary ◽

Balvinder Kumar

Keyword(s):

Nitric Oxide ◽

Cytotoxic Activity ◽

Cytotoxic Effect ◽

Vero Cells ◽

Nitric Oxide Production ◽

Lawsonia Inermis ◽

Leaf Extracts ◽

Oxide Production ◽

Indian Origin ◽

Anti Inflammatory

Background: Lawsonia inermis Linn popularly known as the Henna has played an important role in ayurvedic or natural herbal medicines. The presence of phyto-constituents in henna, that may affect the animal or human health adversely, need to be elucidated for L. inermis Linn species grown in India. Introduction: Introduction: The aim of this research was to perform phytochemical, cytotoxicity and anti-inflammatory studies to understand the potential of leaves of Lawsonia inermis of Indian origin to provide a way forward for therapeutic use in medicine. Methods: We assessed the phytochemical profile for presence of phyto-constituents (alkaloids, carbohydrates, glycosides, steroids, flavonoids, saponins, tannins, proteins/amino acids and gums/mucilage) from various extracts of the plant leaves’. The extracts were further purified by column chromatography for the isolation of plant constituents and monitored by TLC, analyzed by Fourier transform infrared FT-IR spectroscopy, H1NMR, and GC-MS analysis. Fractions were assessed for cytotoxicity and anti-inflammatory properties at various concentrations. We assessed the anti-inflammatory activity by nitric oxide production in various leaf extracts determined by Griess assay. Results: All the spectral results suggest that the compounds from the extract contain aromatic nucleus and OH group along with methoxy group, allyl as well as vinyl group. Fractions of chloroform/methanolic (7:3) leaf extract of Lawsonia inermis confirmed the presence of the two constituents i.e. fraxetin and 1(3H)-isobenzofuranone. We observed significant difference in cytotoxicity at higher concentrations in methanol and chloroform:methanol (8:2) leaf extracts (p>0.05), we could not find any significant differences amongst other leaf extracts at different concentrations. Some leaf extracts have potential cytotoxic activity on vero cells. Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells. The nitric oxide levels decreased from 1000 µg/ml concentration to lower concentrations with varying degree. Overall the highest nitric oxide production by CHCl3 (70%)/ MeOH (30%) was observed amongst various fractions at different concentrations. Conclusion: The phytochemical, cytotoxicity and anti-inflammatory studies indicating the potential of leaves of the plant to provide a way further for their use in medicine. Fraxetin 1(3H)-isobenzofuranone structures were confirmed in fractions of CHCl3 (70%)/ MeOH (30%) extract as observed as a potent constituents. Some leaf extracts have potential cytotoxic activity on vero cells. Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells.The cytotoxicity studies indicates the presence of cytotoxic compounds in some of these extracts, warranting research for fabrication of suitable formulations comprising these constituents to reduce its dose/toxicity for the use of beneficial effects of the plant components.

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