Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals

Abstract

Inflammation is one of the common events in the majority of acute as well as chronic debilitating diseases and represent a chief cause of morbidity in today’s era of modern lifestyle. If unchecked, inflammation leads to development of rheumatoid arthritis, diabetes, cancer, Alzheimer’s disease, and atherosclerosis along with pulmonary, autoimmune and cardiovascular diseases. Inflammation involves a complex network of many mediators, a variety of cells, and execution of multiple pathways. Current therapy for inflammatory diseases is limited to the steroidal and non-steroidal anti-inflammatory agents. The chronic use of these drugs is reported to cause severe adverse effects like gastrointestinal, cardiovascular, and renal abnormalities. There is a massive need to explore new anti-inflammatory agents with selective action and lesser toxicity. Plants and isolated phytoconstituents are promising and interesting sources of new anti-inflammatories. However, drug development from natural sources has been linked with hurdles like the complex nature of extracts, difficulties in isolation of pure phytoconstituents, and the yield of isolated compounds in minute quantities that is insufficient for subsequent lead development. Although various in-vivo and in-vitro models for anti-inflammatory drug development are available, judicious selection of appropriate animal models is a vital step in the early phase of drug development. Systematic evaluation of phytoconstituents can facilitate the identification and development of potential anti-inflammatory leads from natural sources. The present review describes various techniques of anti-inflammatory drug screening with its advantages and limitations, elaboration on biological targets of phytoconstituents in inflammation and biomarkers for the prediction of adverse effects of anti-inflammatory drugs. The systematic approach proposed through present article for anti-inflammatory drug screening can rationalize the identification of novel phytoconstituents at the initial stage of drug screening programs.

Nigella Sativa’s Anti-Inflammatory and Antioxidative Effects in Experimental Inflammation

“…Diclofenac is an NSAID with known anti-inflammatory and analgesic properties due to the inhibition of cyclo-oxygenase 2 COX2 and prostaglandins synthesis [ 23 ]. Diclofenac significantly reduced the paw edema in both carrageenan and FA induced inflammations, and it reduced the pain perception after mechanical or thermal stimuli in both acute and sub-acute settings [ 32 ].…”

In vitro and In vivo Models for Anti-inflammation: An Evaluative Review

“…Accurate measurement of paw edema volume is associated with several problems. Detection of Suitable for acute anti-inflammatory activity; assess fluid extravasation, leukocyte migration and biochemical parameters in the exudates [53] Tedious; severe animal stress; animals are sacrificed; may result in infection small increments in paw volume precisely using the liquid displacement method is difficult. Due to surface tension, water or mercury does not overflow immediately until a certain volume of object is immersed.…”

In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts

“…Experimentally, the inflammatory response is usually quantified by paw size increase (edema), which maximal effect is obtained approximately 4 to 6 h post CG-injection. The CG-induced inflammatory cascade can be modulated by inhibition of lipoxygenases (LOX) and/or cyclooxygenases (COX), for example, being a robust reproductive model for research of both steroidal and non-steroidal (NSAIDs) anti-inflammatory drugs [ 32 , 33 , 34 ]. Once again, the alkaloid-enriched fraction BcAEF demonstrated to be a better anti-inflammatory agent (around 1.5 to 15 fold) when compared to the ethanolic fraction BcEE [ 7 ].…”

“…Furthermore, BcAEF’s anti-inflammatory activity was assessed by the croton oil-induced ear edema model in mice ( Figure 6 ). This model allowed for the evaluation of both topical and systemic routes of steroidal and non-steroidal anti-inflammatory drugs [ 34 , 35 , 36 ]. The inflammatory reaction induced by the phorbol esters of croton oil is associated with neutrophil infiltration, alterations in cytokine production, and increased prostaglandins and leukotrienes production [ 37 , 38 ].…”

“…The inflammatory reaction induced by the phorbol esters of croton oil is associated with neutrophil infiltration, alterations in cytokine production, and increased prostaglandins and leukotrienes production [ 37 , 38 ]. Therefore, substances with LOX, COX and/or phospholipase A2 inhibitory effects can be evaluated in this model [ 34 , 39 ]. Both antitumor and anti-inflammatory activities evidenced for BcAEF could be partially related to the presence of phenanthroquinolizidine alkaloids.…”