benzofurans and Arthritis

A fast, sensitive, and reliable ultra-high performance liquid chromatography with tandem mass spectrometry method has been developed and validated for the simultaneous quantitation and pharmacokinetic study of five phthalides (senkyunolide A, ligustilide, butylidenephthalide, 3-butylphthalide, and levistilide A) in rat plasma after oral administration of Huo Luo Xiao Ling Dan (HLXLD) or Angelica sinensis--Ligusticum chuanxiong herb pair (DG-CX) between normal and arthritis rats. After extraction from blood, the analytes and internal standard were subjected to ultra-high performance liquid chromatography with a Shim-pack XR-ODS column (75 × 3.0 mm(2) , 2.2 μm particles) and mobile phase was composed of methanol and water (containing 0.05% formic acid) under gradient elution conditions, with an electrospray ionization source in the positive ionization and multiple reaction monitoring mode. The lower limits of quantification were 0.192-0.800 ng/mL for all the analytes. Satisfactory linearity, precision, accuracy, mean extraction recovery, and acceptable matrix effect have been achieved. The validated method was successfully applied to a comparative pharmacokinetic study of five bioactive components in rat plasma after oral administration of HLXLD or DG-CX alone, respectively, between normal and arthritic rats. The results showed that there were unlike characters of pharmacokinetics among different groups.

Topics: Administration, Oral; Animals; Arthritis; Benzofurans; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Freund's Adjuvant; Male; Medicine, Chinese Traditional; Molecular Structure; Plant Extracts; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

To determine the role of 5-LO regulation of IL-1 in synovial tissues, we examined the effects of 5-LO inhibitors compared with standard IL-1 synthesis inhibitors on IL-1 production by human synovial tissue explants from patients with inflammatory arthropathies. MK886, L-656,224, PF-5901, and tepoxalin all inhibited IL-1 production in concentrations up to 10 microM, whereas other 5-LO inhibitors (ICI-211,965, zileuton), as well as IL-1 synthesis inhibitors (IX-207,887, tenidap), were inactive. LT products, thus regulate IL-1 production and inhibition thereof is one strategy for inhibiting this cytokine.

Topics: Arthritis; Benzofurans; Culture Media; Culture Techniques; Humans; Hydrocortisone; Indoles; Interleukin-1; Leukotriene Antagonists; Lipoxygenase Inhibitors; Quinolines; Synovial Membrane

A series of 5-acyl-3-substituted-benzofuran-2(3H)-ones and their respective ring-opened o-hydroxy acids were synthesized. The antiinflammatory activity was evaluated in terms of their ability to improve adjuvant induced arthritis in rats. Their effect on the production of both cyclooxygenase (CO) and lipoxygenase (LO) metabolites of arachidonic acid in guinea pig peritoneal polymorphonuclear neutrophils (PMNs) was also examined. No correlation between the antiinflammatory activity and increasing stability of the lactones could be found. The degree of activity in general shown by the benzofuranones was similar to that of their corresponding o-hydroxy acids. This, coupled with the evidence from studies on opening of the lactone ring, suggests an in vivo transformation of the former into the latter. Benzofuranones displayed a dual inhibition of CO and LO products, while a moderate reduction in CO metabolites was shown by their acids.

Topics: Animals; Anti-Inflammatory Agents; Arachidonic Acid; Arachidonic Acids; Arthritis; Arthritis, Experimental; Benzofurans; Female; Guinea Pigs; Lipoxygenase; Neutrophils; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred Strains; Structure-Activity Relationship

Benzbromarone, a potent uricosuric agent, is a benzofuran derivative with a bromine on the 3rd and 5th positions of the benzene ring. Readily absorbed after oral administration, it is promptly dehalogenated in the liver and excreted via the biliary system. Peak drug concentration usually precedes maximal uricosuria following a single dose of 40 mg of benzbromarone, since benzarone, one of the two metabolites, likewise has a uricosuric action. Longterm studies in 24 gouty patients indicate that the drug is well tolerated. It has not produced any skin rash or renal colic. Renal hemodynamics, blood picture, and liver enzymes were unchanged. Since it is eliminated by the biliary tract, it may cause diarrhoea in some patients. Being a very potent uricosuric agent, it is not advocated in patients with a history of uric acid lithiasis. The uricosuric effect is not liable to be counteracted when used in conjunction with hyperuricemic diuretics. The drug is particularly useful in patients with chronic gouty arthritis and tophi, either refractory or allergic to probenecid, sulfinpyrazone, or allopurinol.

Topics: Adult; Aged; Arthritis; Benzbromarone; Benzofurans; Chemical Phenomena; Chemistry; Chronic Disease; Gout; Humans; Hydrochlorothiazide; Kinetics; Middle Aged; Probenecid; Sulfinpyrazone; Uric Acid

The antiinflammatory activity of R-803 (alpha-methyl-3-phenyl-7-benzofuranacetic acid), a new nonsteroidal drug, has been demonstrated. The oral administration of R-803 inhibits carrageenan-induced edema of the rat's paw, ultraviolet-induced erythema of guinea-pig skin, adjuvant-induced and 6-sulfonamidoindazole-induced arthritides of the rat at doses in the range of 1.0 to 6.0 mg/kg. It also inhibits the cotton pellet-induced granuloma in the rat at higher doses.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Benzofurans; Edema; Erythema; Female; Granuloma; Guinea Pigs; Male; Radiation Injuries, Experimental; Rats; Ultraviolet Rays

Topics: Adult; Allopurinol; Anemia; Arthritis; Benzofurans; Gout; Humans; Hyperlipidemias; Hypothyroidism; Hypoxanthines; Kidney Calculi; Male; Metabolism, Inborn Errors; Pedigree; Pentosyltransferases; Uric Acid; Uricosuric Agents

Topics: Adrenalectomy; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Benzofurans; Butyrates; Carrageenan; Dose-Response Relationship, Drug; Edema; Fever; Freund's Adjuvant; Inflammation; Male; Mycobacterium; Phenylbutazone; Rats; Rats, Inbred Strains; Time Factors; Yeasts

Topics: Adult; Aged; Arthritis; Benzofurans; Female; Gout; Humans; Male; Middle Aged; Uric Acid