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

Table 2.

Natural products presented in this review as per study design and Rheumatoid arthritis (RA)-related effects reported.

Natural Product Study Design Comparator Effects Described
Punica granatum Linn. # In vitro (LPS-induced RAW264.7) N/A *

  1. NO inhibition (tannin-related)
In vivo (CIA mice—dose: 100 mg/kg b.wt.) N/A *

  1. Reduction in paw edema
In vivo (FCA rats—doses: 50 or 75 mg/kg b.wt.) Dexamethasone (5 mg/kg)

  1. Improvement in arthritic score, body weight, paw volume and joint diameter
Tripterygium wilfordii # In vivo (CIA rats—doses: 2.5 or 5 mg/100 g b.wt. plant extract or 4 μg/100 g b.wt. isolated triptolide) N/A *

  1. Improvement in bone erosion, paw swelling and total protein concentration in the SFs

  2. Inhibition of the DPPI activity in the serum
Schefflera octophylla (Lour.) Harms In vivo (mice—doses examined in the hot plate test: 300, 600 and 1200 mg/kg b.wt.) N/A *

  1. Improvement in the pain threshold
In vivo (mice—doses examined in the xylene-induced ear edema test: 300, 600 and 1200 mg/kg b.wt.) Indomethacin (10 mg/kg)

  1. Reduced ear edema
In vivo (FCA rats—doses: 150, 300 or 600 mg/kg of the ethanol extract or doses: 75, 150, and 300 mg/kg of the chloroform fraction) Leflunomide (6 mg/kg)

  1. Reduction in paw swelling and pain

  2. Improvement in body weight and arthritis score

  3. Downregulation of TNF-α, IL-1β and IL-6 expression levels
Phoenix dactylifera L. In vitro N/A *

  1. Antioxidant activity (DPPH)
In vivo (CIA rats—dose: 30 mg/kg b.wt.) Indomethacin (10 mg/kg)

  1. Reduction in paw and ear edema
Ribes orientale, Ribes alpestre Decne In vivo (FCA rats—doses: 50, 100 or 200 mg/kg b.wt.) Piroxicam (10 mg/kg)

  1. Improvement in arthritis score and paw edema

  2. Downregulation of PGE2, COX-2, IL-1β IL-6, NF-κB and TNF-α expression levels

  3. Upregulation of IL-4, IL-10 expression levels
In vivo (FCA rats—dose: 200 mg/kg b.wt.) Piroxicam (10 mg/kg)

  1. Reduction in paw volume and thickness

  2. Improvement in arthritic score

  3. Downregulation of IL-1β, TNF-α, IL-6, COX-2, PGE2 and NF-κB

  4. Antioxidant activity (DPPH, FRAP)
Paullinia pinnata L. In vitro (LPS-induced RAW 264.7—doses: 10, 30 and 100 μg/mL) N/A *

  1. Reduction in NO, TNF-α and IL-1β production
In vivo (FCA rats—doses: 100, 200 and 300 mg/kg) Diclofenac (5 mg/kg)

  1. Antioxidant properties (NO inhibition)

  2. Reduction in paw swelling and pain
Camellia sinensis (L.) In vitro N/A *

  1. Inhibition of TNF-α and IL-1 (related to the component epigallocatechin-3-gallate)
In vivo (CIA mice—dose: 400 mg/kg b.wt.) N/A*

  1. Alleviation of joint deformity, tissue swelling, pannus formation and neutrophils infiltration

  2. Antioxidant activity (NO inhibition)
Smilax glabra In vitro (LPS-induced RAW 264.7) N/A*

  1. Reduction in TNF-α, and IL-6 expression levels Inhibition of ERK and JNK
In vitro (LPS-induced THP-1) N/A*

  1. Reduction in IL-1 expression levels

  2. Antioxidant activity (NO inhibition, iNOS expression)
Circaea mollis Sieb. & Zucc In vivo (FCA rats—doses: 170, 680 or 1350 mg/kg b.wt.) Aspirin (35 mg/kg)

  1. Improvement in arthritis score

  2. Reduction in paw swelling and pain score

  3. Downregulation of serum TNF-α and IL-1β Increase in serum IL-10 production
Clematis orientalis Linn In vivo (FCA rats—dose: 200 mg/kg b.wt.) Piroxicam (10 mg/kg)

  1. Reduction in paw volume and joint thickness

  2. Downregulation of IL-1β, TNF-α, IL-6, COX-2 PGE2 and NF-κΒ expression levels
Ephedra gerardiana In vivo (FCA rats—dose: 200 mg/kg b.wt.) Piroxicam (10 mg/kg)

  1. Reduction in paw swelling

  2. Improvement in arthritis score

  3. Downregulation of PGE2, IL-1β, IL-6, NF-κΒ and TNF-α expression levels
In vitro (10μl of ethanol or butanol extract) N/A *

  1. Antioxidant activity (DPPH, NO)
Bawei Longzuan In vivo (CIA rats—doses: 1.25, 2.5 and 5 g/kg b.wt.) Dexamethasone (0.25 mg/kg)

  1. Reduction in paw swelling and arthritis score

  2. Downregulation of IL-1β, TNF-α, IL-6 and IFN-γ serum levels
Matteuccia struthiopteris, Osmunda japonica, Matteuccia orientalis, Pteridium aqui-linum In vitro (LPS-induced RAW264.7) N/A *

  1. Reduction in IL-1β

  2. Antioxidant properties (DPPH, TEAC, ABTS)
Doses: 2.5, 5, 10, 20, 40, 80 and 160 mg/mL
Tamarix ramosissima Ledeb In vitro (RA-FLS) N/A *

  1. Inhibition of cellular apoptosis

  2. Improvement in the activated caspase-3/7 levels and sub-G1 fraction in the cell cycle
Eupatorium japonicum Thunb. In vitro (RA-FLS—dose: 37.5 μg/mL) N/A *

  1. Induction of ROS-mediated apoptosis

  2. Reduction in IL-1β expression and MMP-9 transcription

  3. Inhibition of NF-κB and p38 activation

* N/A: Comparator was either not reported or not applicable for the setting of investigation. # Clinical trials identified in the context of RA.

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