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<p>Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by persistent joint inflammation, cartilage degradation, and systemic complications. Phytochemicals such as curcumin, resveratrol, phenolic acids, flavonoids, lignans, and organosulfur compounds have demonstrated significant disease-modifying potential through modulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and key signaling pathways (NF-κB, MAPK, PI3K/AKT/mTOR). Curcumin, for example, regulates immune homeostasis by restoring the Th17/Treg balance and inhibiting NF-κB and mTOR signaling, while resveratrol suppresses angiogenesis via VEGF inhibition and induces apoptosis in fibroblast-like synoviocytes. Despite their pharmacological promise, poor aqueous solubility, rapid metabolism, and low systemic bioavailability limit clinical translation. Advances in nanoformulation technologies—including polymeric nanoparticles, liposomes, micelles, solid lipid nanoparticles, and stimuli-responsive carriers—have markedly improved phytochemical stability, pharmacokinetics, targeted delivery, and therapeutic efficacy. Analytical characterization methods such as dynamic light scattering, zeta potential analysis, FTIR, HPLC, and TEM facilitate precise formulation optimization and evaluation of biological interactions. Preclinical studies reveal that nano-curcumin can achieve efficacy comparable to methotrexate, while resveratrol-loaded gold nanoparticles enhance anti-inflammatory effects and joint-specific accumulation. This review integrates mechanistic insights, formulation strategies, and analytical approaches, highlighting the opportunities and regulatory considerations for translating nano-phytochemicals into clinically viable RA therapies.</p> Graphical abstract <p></p>

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Phytochemicals and nanoformulation strategies for rheumatoid arthritis: mechanistic insights, therapeutic advances, and translational challenges

  • 期刊论文

  • 发表日期：

    2025年12月8日

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  • Mohsen Rahmanian,
  • Sarah Khosropanah,
  • Sepehr Hoseinzadeh Moghaddam,
  • Abulfazl Vatankhah,
  • Ali Haghbin,
  • Fatemeh Oroojalian,
  • Kasim Sakran Abass,
  • Prashant Kesharwani,
  • Amirhossein Sahebkar

摘要

Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by persistent joint inflammation, cartilage degradation, and systemic complications. Phytochemicals such as curcumin, resveratrol, phenolic acids, flavonoids, lignans, and organosulfur compounds have demonstrated significant disease-modifying potential through modulation of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and key signaling pathways (NF-κB, MAPK, PI3K/AKT/mTOR). Curcumin, for example, regulates immune homeostasis by restoring the Th17/Treg balance and inhibiting NF-κB and mTOR signaling, while resveratrol suppresses angiogenesis via VEGF inhibition and induces apoptosis in fibroblast-like synoviocytes. Despite their pharmacological promise, poor aqueous solubility, rapid metabolism, and low systemic bioavailability limit clinical translation. Advances in nanoformulation technologies—including polymeric nanoparticles, liposomes, micelles, solid lipid nanoparticles, and stimuli-responsive carriers—have markedly improved phytochemical stability, pharmacokinetics, targeted delivery, and therapeutic efficacy. Analytical characterization methods such as dynamic light scattering, zeta potential analysis, FTIR, HPLC, and TEM facilitate precise formulation optimization and evaluation of biological interactions. Preclinical studies reveal that nano-curcumin can achieve efficacy comparable to methotrexate, while resveratrol-loaded gold nanoparticles enhance anti-inflammatory effects and joint-specific accumulation. This review integrates mechanistic insights, formulation strategies, and analytical approaches, highlighting the opportunities and regulatory considerations for translating nano-phytochemicals into clinically viable RA therapies.

Graphical abstract