The drug likeness analysis of anti-inflammatory clerodane diterpenoids
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Chinese Medicine Open Access
REVIEW
The drug likeness analysis of anti‑inflammatory clerodane diterpenoids Zheling Feng, Jun Cao, Qingwen Zhang and Ligen Lin*
Abstract Inflammation is an active defense response of the body against external stimuli. Long term low-grade inflammation has been considered as a deteriorated factor for aging, cancer, neurodegeneration and metabolic disorders. The clinically used glucocorticoids and non-steroidal anti-inflammatory drugs are not suitable for chronic inflammation. Therefore, it’s urgent to discover and develop new effective and safe drugs to attenuate inflammation. Clerodane diterpenoids, a class of bicyclic diterpenoids, are widely distributed in plants of the Labiatae, Euphorbiaceae and Verbenaceae families, as well as fungi, bacteria, and marine sponges. Dozens of anti-inflammatory clerodane diterpenoids have been identified on different assays, both in vitro and in vivo. In the current review, the up-to-date research progresses of anti-inflammatory clerodane diterpenoids were summarized, and their druglikeness was analyzed, which provided the possibility for further development of anti-inflammatory drugs. Keywords: Clerodane diterpenoids, Anti-inflammation, Drug-likeness, SwissADME Background Inflammatory diseases include a vast array of disorders and defense reaction of organisms against external stimulations that are characterized by inflammation symptoms, such as allergy, autoimmune diseases, asthma, glomerulonephritis, hepatitis, inflammatory bowel disease (IBD), reperfusion injury and transplant rejection [1–3]. Long term low-grade inflammation has been considered to play a deteriorated role in many diseases, such as aging, cancer, metabolic disorders, and neurodegeneration [4–7]. The occurrence of chronic diseases has triggered prolonged inflammation that induces the expression of robust pro-inflammatory mediators and cytokines [8, 9], which lead to the pathogenesis of inflammation-associated chronic diseases. Tumor necrosis factor (TNF)-α is one of the most potent pro-inflammatory cytokines and signals [10, 11]. Through binding to its receptors, TNFR1 and TNFR2, TNF-α plays critical roles in *Correspondence: [email protected] State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macau 999078, People’s Republic of China
apoptosis, cell proliferation and immune responses [11, 12]. Interleukin-1β (IL-1β) is one of the inflammatory markers belonging to the IL-1 family of cytokines [13, 14]. IL-6 and IL-12 display a pro-inflammatory action via stimulating IL-1 secretion [15]. IL-10, as the most important anti-inflammatory cytokine, represses pro-inflammatory responses and limits inflammation-induced tissue disruptions [16, 17]. Prostaglandin E2 (PGE2) is derived from arachidonic acid produced by cyclooxygenase (COX)-1 and/or COX-2 [18], which is a principal mediator of inflammation in diseases such as rheumatoid arthritis and osteoarthritis [19]. Nitric oxide (NO) is
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