Anti-Inflammatory and Analgesic Effects of TRPV1 Polypeptide Modulator APHC3 in Models of Osteo- and Rheumatoid Arthritis
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Yulia A Logashina1,2, Yulia A Palikova3, Viktor A Palikov3
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, Russia.
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.
Insights
Sea anemone polypeptide APHC3 shows potent anti-inflammatory and analgesic effects, effectively reducing arthritis symptoms and joint degradation. It offers a promising alternative to NSAIDs for managing inflammatory pain and conditions like osteoarthritis.
Area of Science:
- Pharmacology
- Immunology
- Biochemistry
Background:
- Arthritis is a prevalent inflammatory condition characterized by joint degradation, pain, and functional disability.
- The Transient Receptor Potential Vanilloid 1 (TRPV1) channel is a key target for managing inflammatory diseases.
- Polypeptide APHC3, a TRPV1 antagonist from *Heteractis crispa*, exhibits anti-inflammatory and analgesic properties.
Purpose of the Study:
- To evaluate the anti-inflammatory efficacy of polypeptide APHC3 in preclinical models of arthritis.
- To compare the therapeutic effects of APHC3 with non-steroidal anti-inflammatory drugs (NSAIDs).
Main Methods:
- Monosodium iodoacetate (MIA)-induced osteoarthritis and complete Freund's adjuvant (CFA)-induced rheumatoid monoarthritis models were used.
- Subcutaneous administration of APHC3 (0.1 mg/kg) and reference NSAIDs (diclofenac, ibuprofen, meloxicam).
- Assessment of joint swelling, functional disability, grip strength, thermal/mechanical hypersensitivity, IL-1b concentration, and joint histology.
Main Results:
- APHC3 significantly reversed joint swelling, disability, and hypersensitivity, comparable or superior to NSAIDs.
- Protracted APHC3 treatment reduced synovial IL-1b levels and inflammatory joint changes.
- APHC3 administration prevented further cartilage degradation in arthritis models.
Conclusions:
- Polypeptide APHC3 demonstrates significant anti-inflammatory and analgesic potential for arthritis.
- APHC3 effectively alleviates arthritis symptoms and inhibits disease progression, offering a promising therapeutic candidate.
