Azadirone from Toona sinensis possesses anti-inflammatory and analgesic activities via suppressing MAPK signal pathway
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ORIGINAL ARTICLE
Azadirone from Toona sinensis possesses anti-inflammatory and analgesic activities via suppressing MAPK signal pathway Mingzhe Li 1
&
Hailong Zhang 1
Received: 28 January 2020 / Accepted: 27 March 2020 # Sociedade Brasileira de Farmacognosia 2020
Abstract This study was designed to investigate the anti-inflammatory, analgesic activity of azadirone from Toona sinensis (Juss.) M. Roem., Meliaceae, and explore its potential mechanisms. Anti-inflammatory activities of azadirone were evaluated using dimethylbenzene-induced ear edema, acetic acid–induced vascular permeability, and cotton ball granuloma in mice; in addition, its analgesic activities were investigated using acetic acid writhing, hot plate pain, and formalin pain tests. The results showed that azadirone had obvious anti-inflammatory and analgesic effects in animals. Further studies revealed that azadirone can reduce levels of TNF-α, IL-6, and IL-1 in lipopolysaccharide-stimulated RAW 264.7 cells. In addition, azadirone can downregulate COX-2 and substance P in spinal cord tissues of formalin-stimulated mice. Also, expressions of ERK, P38, and JNK in RAW 264.7 cells were suppressed by azadirone. Collectively, azadirone has promising anti-inflammatory and analgesic potentials, and its mechanism is closely related to the reduction of pro-inflammatory cytokines and the blocking of MAPK signal pathway. Keywords Analgesic . Cytokine suppression . Inflammation . Limonoid . Molecular mechanisms . Pain . Tetranortriterpene
Introduction Inflammation is a physiological and immune response to various stimulating factors or local tissue damage caused by injury, infection, and other harmful chemical agents; the main symptoms of inflammation are redness, swelling, fever, pain, and even dysfunction of tissues and organs (Li et al. 2015). Studies have also found that inflammation is related to the development of many disorders, such as tumors, cardiovascular diseases, and rheumatoid arthritis (Mantovani et al. 2008; Yalta and Yalta 2018). Furthermore, it is known that inflammation is commonly accompanied with pain due to the analgesic mediators produced in process of inflammation, such as prostaglandin E2 (PGE2) (Wang et al. 2014; Li et al. 2015). Pain and inflammation often bring about some bothersome problems in lifestyle of millions of peoples worldwide.
* Mingzhe Li [email protected] 1
Department of Anaesthesia, Beijing Luhe Hospital Affiliated to Capital Medical University, No. 82 South Xinhua Road, Beijing 101149, People’s Republic of China
Currently, the available drugs (such as ibuprofen) can be used to only control the inflammatory symptoms; however, longterm use of these drugs could result in some unwanted sideeffects. Therefore, searching for more and new antiinflammatory and analgesic agents with low toxicity is also urgent and important. Toona sinensis (Juss.) M. Roem., Meliaceae, is an important Chinese medicinal plant and has a long medicinal history for medicinal uses in Chinese folk medicine (Peng et al. 2019). It has been reported
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