Abstract
Curcumin, derived from the rhizome Curcuma longa, has been scientifically proven to possess anti-inflammatory activity but is of limited clinical and veterinary use owing to its low bioavailability and poor solubility. Hence, analogs of curcuminoids with improved biological properties have been synthesized to overcome these limitations. This study aims to provide the pharmacological basis for the use of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a synthetic curcuminoid analog, as an anti-edematogenic and anti-granuloma agent. The carrageenan-induced paw edema and the cotton pellet-induced granuloma assays were used to assess the anti-inflammatory activity of DHHPD in mice. The effects of DHHPD on the histaminergic, serotonergic, and bradykininergic systems were determined by the histamine-, serotonin-, and bradykinin-induced paw edema tests, respectively. DHHPD (0.1, 0.3, 1, and 3 mg/kg, intraperitoneal) evoked significant reductions (p < 0.05) in carrageenan-induced paw edema at different time intervals and granuloma formation (p < 0.0001) by 22.08, 32.57, 37.20, and 49.25%, respectively. Furthermore, DHHPD significantly reduced paw edema (p < 0.05) induced by histamine, serotonin, and bradykinin. The present study suggests that DHHPD exerts anti-edematogenic activity, possibly by inhibiting the synthesis or release of autacoid mediators of inflammation through the histaminergic, serotonergic, and bradykininergic systems. The anti-granuloma effect may be attributed to the suppression of transudative, exudative, and proliferative activities associated with inflammation.
Highlights
Long-term regular use of commercially available non-steroidal anti-inflammatory drugs (NSAIDs) for the management of inflammation and pain can induce gastro-duodenal ulceration, abdominal pain, dyspeptic symptoms, hemorrhage, and perforation of the gastric organs, possibly resulting in hospitalization and even death [1]
No mortalities were recorded over the 7-day test period and the vital organs were normal upon post mortem examination
We investigated of DHHPD, a synthetic diarylpentanoid curcuminoid analog, on carrageenan-induced paw edema
Summary
Long-term regular use of commercially available non-steroidal anti-inflammatory drugs (NSAIDs) for the management of inflammation and pain can induce gastro-duodenal ulceration, abdominal pain, dyspeptic symptoms, hemorrhage, and perforation of the gastric organs, possibly resulting in hospitalization and even death [1] This side-effect profile of NSAIDs has prompted researchers to seek alternatives in the form of extracts and compounds derived from naturally occurring medicinal plants, rhizomes, or herbs that are available all year round, abundantly found in nature, and affordable to low-income groups. Turmeric or Curcuma longa (C. longa) consists of three main bioactive constituents: curcumin, bisdemethoxycurcumin, and demethoxycurcumin. These are referred to as curcuminoids [4]. Curcumin, which is the major constituent of turmeric, is considered to be responsible for the rhizome’s biological activity [5]
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