Attenuation of arthritis in rodents by a novel orally-available inhibitor of sphingosine kinase

Fitzpatrick, Leo R.; Green, Cecelia; Frauenhoffer, Elizabeth E.; French, Kevin J.; Zhuang, Yan; Maines, Lynn W.; Upson, John J.; Paul, Emmanuel M.; Donahue, Henry J.; Mosher, Timothy J.; Smith, Charles D.

doi:10.1007/s10787-010-0060-6

Cited by 48 publications

(38 citation statements)

References 31 publications

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“…The arthritic rats showed soft-tissue swelling around the ankle joints, during the acute period of arthritis, was considered to be due to oedema of periarticular tissues, such as ligaments and joint capsules. Several authors have reported that there is profound swelling in contralateral paw and similar pathological changes have also been observed in the present study (Fitzpatrick et al 2011;Schopf et al 2006). There was significant reduction in swelling of inflamed area in the rats treated with lupeol as well as indomethacin, indicating the anti-inflammatory property of lupeol.…”

Section: Discussionsupporting

confidence: 91%

Lupeol, a triterpenoid isolated from Calotropis gigantea latex ameliorates the primary and secondary complications of FCA induced adjuvant disease in experimental rats

Venkatesan

Subramanian

2011

Inflammopharmacol

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that affects 1% of the adult population worldwide. Calotropis gigantea is a xerophytic, latex producing medicinal plant widely distributed in nature. Different parts of the plant have been traditionally used for the treatment of various ailments including arthritis. In the present study, we have isolated and characterized lupeol, a pentacyclic triterpene from the dialyzable fraction of the latex and evaluated the anti-arthritic properties of lupeol in Freund's Complete Adjuvant (FCA) induced arthritis in rats. Lupeol (50 mg/kg b.w/day) was administered orally to AA rats for 4 weeks. The alterations in body weight gain, paw volume, RBC, WBC, Hb, EPO, ESR, platelets and PCV were recorded. The activities of serum AST, ALT and ALP were also assayed. The levels of lipid profile were estimated. The levels of pro-inflammatory cytokines as well as anti-inflammatory cytokines such as TNF-α, IL-1β, IL-6 and IL-10 were also analyzed. The results of present study indicate the anti-inflammatory and anti-arthritic activity of lupeol present in the C. gigantea latex.

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Section: Discussionsupporting

confidence: 91%

Lupeol, a triterpenoid isolated from Calotropis gigantea latex ameliorates the primary and secondary complications of FCA induced adjuvant disease in experimental rats

Venkatesan

Subramanian

2011

Inflammopharmacol

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“…However, the efficacy of SK inhibitors has not yet been tested in an animal model of OA. ABC294640 is a novel chemical compound that selectively inhibits SK2 and also improves experimental rheumatoid arthritis in rodents [17,18] . Therefore, we hypothesized that ABC294640 might also attenuate various features of MIA-induced OA, including apoptosis [10] .…”

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confidence: 99%

Experimental Osteoarthritis in Rats Is Attenuated by ABC294640, a Selective Inhibitor of Sphingosine Kinase-2

et al. 2011

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Background/Aims: Osteoarthritis (OA) is a progressive degenerative disease characterized by cartilage degradation and chondrocyte apoptosis, which may involve aberrant sphingolipid metabolism. ABC294640 is a compound that selectively inhibits sphingosine kinase-2, a key enzyme in the sphingolipid pathway. Our goal was to assess the pharmacological effects of ABC294640 in the monosodium iodoacetate (MIA) model of OA. Methods: MIA (3 mg) was injected into the right knee joint to induce osteoarthritis in rats. Subsequently, the rats were treated with vehicle, ABC294640 or tramadol over a 28-day period. To assess pain, incapacitance readings were obtained weekly. MIA-injected knee joints were evaluated for histological damage, cartilage degradation and chondrocyte apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling histochemistry). Results: The percent weight bearing in vehicle/MIA rats significantly (p < 0.01) decreased from 48.8 ±0.8 (day 0) to 41.9 ±2.9 (day 28). In contrast, these values in ABC294640-treated rats were virtually the same on days 0 and 28. Knee joint histology scores were less severe in ABC294640-treated rats. Cartilage proteoglycan staining was more prominent in ABC294640/MIA animals than in vehicle/MIA rats. The percentage of apoptotic chondrocytes was decreased from 39.5% (vehicle treatment) to 25.8% (ABC294640 treatment). Conclusion: ABC294640 attenuated the knee joint histological damage and pain associated with MIA-induced OA in rats.

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“…еже-дневно, с перерывом на выходные, проводили клиниче-ский осмотр животных с оценкой тяжести развития пато-логии в баллах. При отсутствии изменений инъецирован-ной лапы присваивалась оценка «0», при наличии слабо-выраженного отека -«1», при наличии отека и слабовы-раженного покраснения -«2», при наличии значительно-го отека и сильно выраженного покраснения -«3», при наличии сильно выраженного отека и покраснения, затрагивающих все суставы инъецированной лапы, и/или при генерализации процесса (вовлечение суставов контр латеральной лапы, суставов в основании хвоста, передних лап) -оценка «4» [28].…”

Section: потенцирование регенеративных процессов хряща и эффективностunclassified

Human Placenta Hydrolyzates in Reconstructive Therapy of Connective Tissue of Cartilage and Joints

Громова¹,

Торшин²,

Диброва³

et al. 2017

Med. sov.

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Attenuation of arthritis in rodents by a novel orally-available inhibitor of sphingosine kinase

Abstract: Our results suggest that ABC249640 is an orally available drug candidate with a good pre-clinical efficacy profile for the prevention and/or treatment of RA.

Cited by 48 publications

References 31 publications

Lupeol, a triterpenoid isolated from Calotropis gigantea latex ameliorates the primary and secondary complications of FCA induced adjuvant disease in experimental rats

Lupeol, a triterpenoid isolated from Calotropis gigantea latex ameliorates the primary and secondary complications of FCA induced adjuvant disease in experimental rats

Experimental Osteoarthritis in Rats Is Attenuated by ABC294640, a Selective Inhibitor of Sphingosine Kinase-2

Human Placenta Hydrolyzates in Reconstructive Therapy of Connective Tissue of Cartilage and Joints

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