Klymollins T–X,Bioactive Eunicellin-Based Diterpenoids from the Soft Coral Klyxum molle

Five new eunicellin-based diterpenoids, klymollins T–X (1–5), along with two known compounds (6 and 7) have been isolated from the soft coral Klyxum molle. The structures of these new metabolites were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. Compound 5 was found to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. Furthermore, compounds 4 and 7 were shown to exhibit cytotoxicity against a limited panel of human cancer cell lines.     

Antinociceptive and anti-inflammatory activity from algae of the genus Caulerpa

Marine natural products have been the focus of discovery for new products of chemical and pharmacological interest. The aim of this study was to evaluate the antinociceptive activity of the methanolic (ME), acetate (AE), hexanic (HE) and chloroform (CE) extracts obtained from Caulerpa mexicana, and ME, CE and HE obtained from Caulerpa sertularioides. These marine algae are found all over the world, mainly in tropical regions. Models such as the writhing test, the hot plate test and formalin-induced nociception test were used to evaluate antinociceptive activity in laboratory mice. In the writhing test, all the extracts were administered orally at a concentration of 100 mg/kg, and induced high peripheral antinociceptive activity, with a reduction in the nociception induced by acetic acid above 65%. In the hot plate test, treatment with extracts from C. sertularioides (100 mg/kg, p.o.) did not significantly increase the latency of response, although the ME, AE and HE from C. mexicana showed activity in this model. This result suggests that these extracts exhibit antinociceptive activity. In the formalin test, it was observed that ME, AE and HE obtained from C. mexicana reduced the effects of formalin in both phases. On the other hand only CE from C. sertularioides induced significant inhibition of the nociceptive response in the first phase. To better assess the potential anti-inflammatory activity of the extracts, the carrageenan-induced peritonitis test was used to test Caulerpa spp. extracts on cell migration into the peritoneal cavity. In this assay, all extracts evaluated were able to significantly inhibit leukocyte migration into the peritoneal cavity in comparison with carrageenan. These data demonstrate that extracts from Caulerpa species elicit pronounced antinociceptive and anti-inflamatory activity against several nociception models. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in the Caulerpa species.     

Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale)

Ginger roots have been used to treat inflammation and have been reported to inhibit cyclooxygenase (COX). Ultrafiltration liquid chromatography mass spectrometry was used to screen a chloroform partition of a methanol extract of ginger roots for COX-2 ligands, and 10-gingerol, 12-gingerol, 8-shogaol, 10-shogaol, 6-gingerdione, 8-gingerdione, 10-gingerdione, 6-dehydro-10-gingerol, 6-paradol, and 8-paradol bound to the enzyme active site. Purified 10-gingerol, 8-shogaol and 10-shogaol inhibited COX-2 with IC₅₀ values of 32 μM, 17.5 μM and 7.5 μM, respectively. No inhibition of COX-1 was detected. Therefore, 10-gingerol, 8-shogaol and 10-shogaol inhibit COX-2 but not COX-1, which can explain, in part, the anti-inflammatory properties of ginger.     

Ex vivo COX-1 and COX-2 inhibition in equine blood by phenylbutazone,flunixin meglumine,meloxicam and firocoxib: Informing clinical NSAID selection

Newer cyclo-oxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs), such as firocoxib, are proposed to reduce inhibition of cyclo-oxygenase-1 (COX-1) and avoid undesirable side effects, while continuing to inhibit inflammation associated with COX-2. However, COX selectivity is typically based on in vitro testing, which may not provide sufficient information critical for treatment selection. This study investigated the pharmacokinetics and ex vivo COX-1 and COX-2 inhibition of phenylbutazone, flunixin meglumine, meloxicam and firocoxib. Horses (n = 3) were administered one of the four drugs, in a randomised cross-over design, with 3-week washout periods. For each drug, three doses were given and sampling performed. Drug plasma concentrations, thromboxane B₂ (TXB₂) and prostaglandin E₂ (PGE₂) were determined. After one dose, TXB₂ and PGE₂ levels were significantly higher in horses administered firocoxib compared to flunixin meglumine. Following the third dose, TXB₂ levels in horses administered firocoxib and meloxicam were significantly higher compared to flunixin meglumine or phenylbutazone; all drugs reduced PGE₂ to a similar degree. The mean plasma half-lives were 5.97 ± 0.47, 4.74 ± 0.14, 8.24 ± 3.74 and 47.42 ± 7.41 h for phenylbutazone, flunixin meglumine, meloxicam and firocoxib, respectively. Firocoxib and meloxicam exhibited significantly less COX-1 inhibition compared to flunixin meglumine and phenylbutazone; all drugs inhibited COX-2. The plasma half-life of firocoxib was longer than the other NSAIDs, including meloxicam. Data from this study have important clinical relevance and should be used to inform practitioners’ drug selection of a COX-1 sparing or traditional NSAID and dose selection and to provide knowledge of the duration for the four NSAIDs studied.     

Anti-inflammatory effect of sulforaphane on LPS-stimulated RAW 264.7 cells and ob/ob mice

BackgroundSulforaphane (SFN) is an isothiocyanate compound present in cruciferous vegetables. Although the anti-inflammatory effects of SFN have been reported, the precise mechanism related to the inflammatory genes is poorly understood.ObjectivesThis study examined the relationship between the anti-inflammatory effects of SFN and the differential gene expression pattern in SFN treated ob/ob mice.MethodsNitric oxide (NO) level was measured using a Griess assay. The inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were analyzed by Western blot analysis. Pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RNA sequencing analysis was performed to evaluate the differential gene expression in the liver of ob/ob mice.ResultsThe SFN treatment significantly attenuated the iNOS and COX-2 expression levels and inhibited NO, TNF-α, IL-1β, and IL-6 production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA sequencing analysis showed that the expression levels of 28 genes related to inflammation were up-regulated (> 2-fold), and six genes were down-regulated (< 0.6-fold) in the control ob/ob mice compared to normal mice. In contrast, the gene expression levels were restored to the normal level by SFN. The protein-protein interaction (PPI) network showed that chemokine ligand (Cxcl14, Ccl1, Ccl3, Ccl4, Ccl17) and chemokine receptor (Ccr3, Cxcr1, Ccr10) were located in close proximity and formed a “functional cluster” in the middle of the network.ConclusionsThe overall results suggest that SFN has a potent anti-inflammatory effect by normalizing the expression levels of the genes related to inflammation that were perturbed in ob/ob mice.     

复方蒲公英注射液解热镇痛抗炎作用研究

考察复方蒲公英注射液解热镇痛抗炎效果。解热试验取健康家兔10只,随机分为2组,每只兔背部皮下注射2,4-二硝基苯酚2%水溶液30 mg/kg,待体温升高超过1℃,分别按0.5 mL/kg腹腔注射生理盐水和复方蒲公英注射液,给药后30、60、90、120 min分别测量直肠温度;镇痛试验取昆明系小白鼠50只,随机均分为5组,分别为生理盐水组（0.05mL）、阿司匹林组（4%阿司匹林溶液0.05 mL）、复方蒲公英注射液低（0.05 mL）、中（0.1 mL）、高剂量组（0.2 mL）。连续经口给药3 d,于末次给药30 min后,每只小白鼠腹腔注射0.6%冰醋酸（0.1 mL/10 g）,记录注射致痛剂后20 min内各鼠的扭体次数;抗炎试验取昆明系小白鼠50只,随机分为5组,分别为生理盐水对照组（0.05 mL/10 g）、双黄连组（0.05 mL/10 g）、复方蒲公英低（0.05 mL/10 g）、中（0.1 mL/10 g）、高（0.2 mL/10 g）剂量组。连续腹腔注射给药5 d,在第5天注射后12 h,在小鼠右耳两侧均匀涂以二甲苯0.05 mL,左耳作为对照,2 h后处死,用直径0.5 cm打孔器取其左右耳片,称重,评价药物对二甲苯刺激耳廓的抗炎效果。结果提示,复方蒲公英注射液具有较好的解热抗炎作用,而无明显镇痛作用。     

Bioactive cembrane-based diterpenoids from the soft coral Sinularia triangular

Chemical examination of the Taiwanese soft coral Sinularia triangular led to the isolation of five cembrane-based diterpenoids 1-5, including two new metabolites, triangulenes A (1) and B (2). The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and 2D NMR ((1)H-(1)H COSY, HMQC, HMBC, and NOESY) spectroscopy. Metabolites 3 and 5 exhibited moderate cytotoxicity to human tumor cell lines CCRF-CEM and DLD-1. Furthermore, 3-5 displayed significant in vitro anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Metabolites 4 and 5 also effectively reduced the expression of the COX-2 protein in the macrophages.     

查尔酮的结构修饰及抗癌、抗炎活性研究进展

查尔酮类化合物是广泛存在于自然界中一种黄酮类化合物,具有抗癌、抗炎症、抗菌、抗寄生虫、抗病毒等生物活性,是一类很具有前途的药物模板。重点阐述了近年来查尔酮类化合物的抗癌、抗炎症活性以及构效关系研究进展。结果表明查尔酮类化合物药理活性广泛、安全、结构简单且制备方便,是一个良好的药物开发先导物。     

Bioavailability and Tolerability of Topical and Oral Diclofenac Sodium Administration in Healthy Ponies

Aiming to characterize the bioavailability and assess the safety of topical and oral treatment of diclofenac sodium in healthy ponies, 18 animals were divided in three groups: one treated with topical (group I, n = 6), the second with oral diclofenac (group II, n = 6) at 2.5 mg/kg for 3 days, and the third group received 2.2 mg/kg oral phenylbutazone (group III, n = 6) also for 3 days to serve as positive control. To evaluate bioavailability, blood samples were collected before and at 0, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 60, 72, 96, 120, and 144 hours after starting treatment. To evaluate diclofenac sodium concentration in the synovial fluid, samples of six ponies (group I, n = 3; group II, n = 3) were collected at 6, 12, and 24 hours after starting the treatment.