n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels

Abstract

Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n-hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg) demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1).

The Effect of Ursolic Acid from Plantago Lanceolata Leaves on Leukocytes Migration and Chemokines Level

“…Interestingly, ursolic acid reduced the MCP-1 level with a higher potency than IL-8. This result was in line with the previous study demonstrating that MCP-1 is the main chemokine responsible for leukocyte migration (Fakhrudin et al, 2017;Takahashi et al, 2009). This suggests that ursolic acid might be further examined for its efficacy against inflammatoryrelated diseases in which MCP-1 plays crucial roles such as diabetic nephropathy (Tesch, 2008), cardiovascular diseases (Epstein et al, 2009), rheumatoid arthritis (Ellingsen et al, 2000), and angiogenesis (Chang et al, 2005).…”

“…NF-ĸB represents a promising target in inflammation and this protein regulate the production of pro-inflammatory cytokines and mediate inflammatory development. In the previous study, we found that the n-hexane insoluble fraction (HIF) of P. lanceolata dichloromethane extract is the active fraction with anti-inflammatory activity in mice (Fakhrudin et al, 2017). In this study, we isolated the major compound from the HIF and evaluated its anti-inflammatory activity by employing thioglycollate-induced mice peritonitis as pharmacological evidence.…”

“…The HIF and HSF were evaluated for their anti-inflammatory activities and the chemical profiles of both fractions were presented in our previous study (Fakhrudin et al, 2017). The HIF demonstrates a higher activity compared with the HSF at 400mg/kg BW (Figure 1 and Table I).…”

“…Further separation of the extract with nhexane yielded n-hexane insoluble (HIF) and nhexane soluble (HSF) that represent relatively non-polar and polar fractions, respectively. An anti-inflammatory study of HIF in a murine model showed that HIF exerted anti-inflammatory activity by inhibiting cyclooxygenase-2 (COX-2) activity and reducing chemokine levels (Fakhrudin et al, 2017). However, the anti-inflammatory compound responsible for the activity has not been identified.…”

Новые Терапевтические Возможности Фитопрепаратов При Лечении Острых Респираторных Инфекций У Детей

“…Подорожник является одним из 200 наиболее хорошо охарактеризованных и описанных видов семейства Plantaginaceae и официнальным фармацевтическим средством в Европейской фармакопее [16]. Основные активные фармацевтические ингредиенты листьев подорожника (каталпол, аукубин и актеосайд) относятся к группе фенилэтаноидных и иридоидных гликозидов, обеспечивают противовоспалительный [12], антиоксидантный [13,36], иммуномодулирующий [18], а также ряд других эффектов [20,29].…”