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. 2021 Apr 13;10(4):599. doi: 10.3390/antiox10040599

Table 3.

Natural compounds presented in this review as per study design and reported RA-related effects.

Natural Compound Study Design Comparator Effects Described
Sulforaphane In vitro (LPS-induced murine splenocytes, PBMCs) N/A *

  1. Decreased the differentiation of LPS-stimulated cells and germinal-center B cells

  2. Attenuated the production of IL-6, TNF-α, IL-17, and IgG in human PBMCs

  3. Concentration- and time-dependence of the inactivation of MIF tautomerase activity
In vitro (RAW 264.7)—concentrations: 0.2–10 µM (0.1% acetonitrile) N/A *

  1. Reduction in inflammation, cartilage damage, and bone erosion in the joint

  2. Reductions in expression of IL-6-, IL-17-, and TNF-α in the joints
In vivo (CIA mice—dose: 12.8 mg/mL/kg) N/A *

  1. Decreased production of TNF-α, IL-6, INF-γ

  2. Reduction in synovial inflammatory infiltration
In vivo (FCA rats—dose: 5 mg/kg) N/A *

  1. Reduced joint swelling and damage

  2. Increased levels of IL-6, and recruitment of Ly6C+ and Ly6G+

  3. Down-regulation of CD11b and CD62L on synovial fluid Ly6G+
In vitro (FCA-mice—dose: 10 mg/kg) N/A *

  1. Increased activity of TrxR
Sinomenine In vitro (LPS-stimulated RAW264.7) N/A *

  1. Reduction in the secretion of IL-6, GMCSF, IL-1a, IL-1b, TNF-α, and Eotaxin-2
In vivo (CIA mice—doses: 50 or 100 mg/kg) N/A *

  1. Reduction in inflammatory cell infiltration and synovial hyperplasia

  2. Reduction in arthritis scores, paw swelling and cartilage damage
Taraxasterol In vitro (IL-1β-stimulated RA-FLS—doses: 0.3 to 30μM) N/A *

  1. Suppression of TNF-α, IL-6, and IL-8

  2. Reduced production of MMP-1 and MMP-3 Inhibition of the IL-1β-mediated NF-κB p65 nuclear translocation
In vivo (CIA mice—dose: 10mg/kg) N/A *

  1. Reduction in TNF-α, IL-6 and IL-8 expression in joint tissues

  2. Modulation of IKKα/β and IκBα phosphorylation and IκBα degradation
In vitro (LPS-induced RAW264.7—doses: 5, 25, 50, and 100 μg/mL) N/A *

  1. Reduction in TNF-α and IL-6 levels
Curcumin In vitro (LPS-induced RAW264.7) N/A *

  1. Inhibition of the degradation of IκBα

  2. Reduction in COX-2 production

  3. Induction of macrophage apoptosis
In vivo (CIA rats—doses: 100 or 200 mg/kg) MTX (0.3 mg/kg)

  1. Reduction in joint swelling, arthritis score, synovial hyperplasia score, and pannus formation score

  2. Modulation of TNF-α, IL-17, IL-1β and TGF-β levels in CIA rat synovium
Morin In vivo (CIA rats—dose: 30 mg/kg b.wt.) Indomethacin (3 mg/kg)

  1. Reduction in TNF-α, IL-1β, IL-17, IL-6, MCP-1, and PGE2 in serum

  2. Modulation of RANKL, and transcription factors NF-κB p65 and AP-1

  3. Improvement in paw edema, bone collagen levels, cartilage erosion and synovial hyperplasia

  4. Inhibition of iNOS

  5. Reduction in Lipid peroxidation and NO levels
Combination therapy (indomethacin + morin)
Resveratrol In vivo (AIA rats—dose: 12.5 mg/kg) N/A *

  1. Reduction in knee swelling

  2. Reduction in the histological score of synovial tissue

  3. Improvement in the expression of LC3 signals Mitigation of the p65 expression

  4. Reduction in articular cartilage degradation

  5. Reduction in IL-1β, CRP and PGE2 levels
Allylpyrocatechol In vivo (CIA rats—doses: 5, 10, or 20 mg/kg) N/A *

  1. Reduction in paw edema, bone damage and cartilage degradation

  2. Reduction in plasma TNF-α and IL-6 levels

  3. Reduction in paw edema

  4. Inhibition of TNF-α, and IL-6 expression

  5. Diminish cachexia, splenomegaly, and oxidative stress
In vivo (CIA rats—dose: 20 mg/kg) MTX (1.5 mg/kg)
Combination therapy
Epicatechin-3-O-β-d-allopyranoside In vivo (CIA rats—doses: 50 or 100 mg/kg) N/A *

  1. Suppression of arthritis symptoms and improvement in disease severity

  2. Downregulation of IL-17 and TNF-α levels

  3. Improvement in IL-10 and IL-4 levels
Paeonol In vitro (IL-1β-stimulated RA-FLS—dose: 0.1–100μΜ) N/A *

  1. Reduction in TNF-α, IL-6, IL-1β, and the expressions of MMP-1/MMP-3

  2. Inhibition of TLR4 expression and NF-κB p65 activation
In vivo (CIA mice—dose: 10 mg/kg) N/A *

  1. Improvement in clinical arthritis scores

  2. Reduction in TNF-α, IL-6, MMP-1 and MMP-3 production in the ankle joints

  3. Antioxidant activity
Madecassoside In vivo (AIA rats—dose: 25 mg/kg) Dexamethasone (0.5 mg/gr)

  1. Modulation of body weight loss, polyarthritis index score

  2. Reduction in paw swelling
In vitro (IL-1β-stimulated RA-FLS—doses: 10 or 30 μmol/l) N/A *

  1. Inhibition of the migration and invasion (via modulating the expression of MMP-13) of IL-1β-induced FLS

  2. Modulation of the mRNA expression levels of MMP-2, MMP-3, MMP-9 and MMP-13

  3. Downregulation of the translocation and phosphorylation of NF-κB
Silibinin In vitro (RA-FLS—doses: 0, 50, 100, and 200 μM) N/A *

  1. Suppression of cell viability and NF-κB pathway

  2. Reduction in Sirtuin1

  3. Improvement in the apoptotic RA-FLS Inhibition of the TNF-α-induced IL-6 and IL-1β production and phosphorylation of NF-κB p65 and IκBα
In vivo (CIA rats—doses: 50, 100 and 150 mg/kg) N/A *

  1. Improvement in arthritis score

  2. Reduction in TNF-α, IL-1β and IL-6 levels

  3. Antioxidant properties
Brazilin In vitro (RA-FLS—dose: 25μg/mL) N/A *

  1. Reduction in LPS-induced or TNF-induced NF-κB activation and the secretion of inflammatory cytokines
Germacrone In vivo (CIA mice—dose: 20 mg/kg) N/A *

  1. Reduction in arthritis score

  2. Reduction in TNF-α and IFN-γ levels in serum and synovial tissues

  3. Improvement in IL-4 levels

  4. Reduction in the Th1/Th2 ratio

  5. Improvement in IκB expression

  6. Antioxidant activity
Betulinic acid In vitro (RA-FLS—doses: of 0, 2.5, 5, and 10 mM) N/A *

  1. Inhibition of the migration, invasion and reorganization of the actin cytoskeleton of RA-FLS

  2. Downregulation of the mRNA expression of IL-1β, IL-6, IL-8 and IL-17A
In vivo (CIA mice—dose: 20 mg/kg) N/A *

  1. Reduction in the TNF-α-induced activation of NF-κB signal pathway and the NF-κB nuclear accumulation

  2. Reduction in arthritis score and paw swelling
Triptolide In vivo (CIA rats—doses: 10, 20 or 40 mg/kg) N/A *

  1. Reduction in joint swelling

  2. Reduction in IL-1β and IL-6 serum levels

* N/A: Comparator was either not reported or not applicable for the setting of investigation.