Anti-Inflammatory and Analgesic Effects of TRPV1 Polypeptide Modulator APHC3 in Models of Osteo- and Rheumatoid Arthritis |
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| Authors: | Yulia A. Logashina Yulia A. Palikova Viktor A. Palikov Vitaly A. Kazakov Sviatlana V. Smolskaya Igor A. Dyachenko Nadezhda V. Tarasova Yaroslav A. Andreev |
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| Affiliation: | 1.Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia;2.Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya str. 8, bld. 2, 119991 Moscow, Russia; (S.V.S.); (N.V.T.);3.Branch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospekt Nauki, 6, 142290 Pushchino, Russia; (Y.A.P.); (V.A.P.); (V.A.K.); (I.A.D.) |
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| Abstract: | Arthritis is a widespread inflammatory disease associated with progressive articular surface degradation, ongoing pain, and hyperalgesia causing the development of functional limitations and disability. TRPV1 channel is one of the high-potential targets for the treatment of inflammatory diseases. Polypeptide APHC3 from sea anemone Heteractis crispa is a mode-selective TRPV1 antagonist that causes mild hypothermia and shows significant anti-inflammatory and analgesic activity in different models of pain. We evaluated the anti-inflammatory properties of APHC3 in models of monosodium iodoacetate (MIA)-induced osteoarthritis and complete Freund’s adjuvant (CFA)-induced rheumatoid monoarthritis in comparison with commonly used non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, and meloxicam. Subcutaneous administration of APHC3 (0.1 mg/kg) significantly reversed joint swelling, disability, grip strength impairment, and thermal and mechanical hypersensitivity. The effect of APHC3 was equal to or better than that of reference NSAIDs. Protracted treatment with APHC3 decreased IL-1b concentration in synovial fluid, reduced inflammatory changes in joints, and prevented the progression of cartilage degradation. Therefore, polypeptide APHC3 has the potential to be an analgesic and anti-inflammatory substance for the alleviation of arthritis symptoms. |
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| Keywords: | arthritis TRPV1 polypeptide modulator APHC3 cytokines inflammation non-steroidal anti-inflammatory drugs sea anemone Heteractis crispa |
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