title: Anti-inflammatory sesquiterpenes from Costus speciosus rhizomes.
abstract: BACKGROUND
  Costus speciosus (Koen ex. Retz.) Sm. (crepe ginger, family Costaceae) is an ornamental plant used in traditional medicine for the treatment of inflammation, rheumatism, bronchitis, fever, headache, asthma, flatulence, constipation, helminthiasis, leprosy, skin diseases, hiccough, anemia, as well as burning sensation on urination.
  
  
  OBJECTIVE
  The present study is designed to isolate and identify the active compounds from C. speciosus rhizomes and measure their anti-inflammatory activities.
  
  
  METHODS
  The n-hexane-CHCl3 soluble fraction of the MeOH extract of C. speciosus rhizomes has been subjected to a repeated column chromatography, including normal silica gel and RP-18 column to give eight compounds. The structures of these compounds were established by UV, IR, 1D ((1)H and (13)C), and 2D ((1)H-(1)H COSY, NOESY, HSQC, and HMBC) NMR experiments and HRESIMS data. In addition, the anti-inflammatory activity of compounds 1-8 was evaluated by measuring the levels IL-6, IL-1β, TNF-α, COX-2, lipoxgenase-5, and PGE2 using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The n-hexane-CHCl3 soluble fraction afforded a new eudesmane acid, specioic acid (8), along with seven known compounds, 22,23-dihydrospinasterone (1), dehydrodihydrocostus lactone (mokko lactone) (2), dehydrocostus lactone (3), stigmasterol (4), arbusculin A (5), santamarine (douglanin) (6), and reynosin (7). Compounds 1, 4, and 5-7 were isolated for the first time C. speciosus. Compounds 1-4 displayed potent anti-inflammatory activity, while 7 and 8 showed moderate activity. Compounds 1-8 exhibited a concentration-related decrease in the levels of IL-1β, IL-6, TNF-α, PGE2, lipoxgenase-5, and COX-2. Compounds 5 and 6 did not significantly decrease levels of different cytokines, PGE2, lipoxgenase-5, and COX-2 from PHA treatment at 1 µM. However, all tested compounds significantly decreased cytokines, PGE2, lipoxgenase-5, and COX-2 levels at concentration 100 µM. It is noteworthy that compounds 1-4 had the highest activity, where it lowered levels of cytokines, PGE2, lipoxgenase-5, and COX-2 to the extent that was no statistical difference from the control group. Thus, they decreased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) with decreased level of the target enzymes (COX-2 and lipoxgenase-5) and subsequent reduction of its inflammatory product (PGE2).
  
  
  CONCLUSIONS
  Good anti-inflammatory activities exhibited of the isolated compounds from C. speciosus corroborate the usefulness of this plant in the traditional treatment of inflammation and related symptoms.
authors.affiliation: Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors.forename: Ahmed A M
authors.initials: AA
authors.lastname: Al-Attas
authors.affiliation: Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
authors.forename: Nagwa S
authors.initials: NS
authors.lastname: El-Shaer
authors.affiliation: Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.
authors.forename: Gamal A
authors.initials: GA
authors.lastname: Mohamed
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah Al Munawwarah 30078, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. Electronic address: sabrinshaur@gmail.com.
authors.forename: Sabrin R M
authors.initials: SR
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abbasia, Cairo 11566, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Esmat
mesh_terms: D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D029770:Costus; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D058945:Lipoxygenases / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D027343:Rhizome; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D010936:Plant Extracts; D012717:Sesquiterpenes; D058945:Lipoxygenases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: Anti-inflammatory activity; Costaceae; Costus speciosus; Eudesmane acid; Sesquiterpenes