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Herbal Medicine fortheManagement ofAnxiety, Depression, andInsomnia

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Role ofHerbal Medicines

https://t.me/medicina_free

fortheTreatment ofArthritis

VafaBaradaranRahimi andVahidRezaAskari

Abstract

The use of herbal medicines has extensively propagated in almost every country worldwide and also in developed countries. Nowadays, various herbal therapies are wellstudied and used to treat many chronic and acute disorders, including rheumatoid arthritis and osteoarthritis. This chapter focuses on the promising anti-arthritis effects of Nigella sativa and its major ingredient thymoquinone, Zingiber ofcinale and its constituents 6-gingerols and 6-shogaols, Curcuma longa and its main component cur- cumin, Tripterygium wilfordii Hook and its major constit- uent triptolide, Punica granatum and its major constituents ellagic acid and punicalagin, Boswellia serrata and its major constituent boswellic acid, Crocus sativus and its main constituent crocin, Berberis vulgaris and its main ingredient berberine, Withania somnifera, and Eucommia ulmoides. We reviewed different animal models and clinical studies of rheumatoid arthritis and osteoarthritis. The important mechanisms responsible for the anti-arthritis properties of these herbal medicines were mainly antioxidative, anti-inammatory, and anti- apoptotic, regulating M1/M2 balance, T cell suppression, suppressing TLR4/NF-κB, and mTOR signaling pathways.

1 Introduction

Herbal medicines with promising anti-arthritis effects are illustrated in Fig.1. Additionally, Table1 reviewed the protective effects of herbal medicines against animal models of arthritis. Additionally, clinical studies supporting the antiarthritis effects of the mentioned herbal medicines are presented in Table2.

1.1 Nigella sativa andIts Major Ingredient

Thymoquinone

Nigella sativa (N. sativa), popularly named black cumin, is an annual owering herb member of Ranunculaceae [85]. Its small and black seeds have been administered in many traditional foods and also as traditional medicine. Thymoquinone is the major active constituent of N. sativa seeds. Several pieces of evidence support that N. sativa has antitussive, anti-oxidant, anti-cancer, anti-inammatory, analgesic, antianxiety, nephroprotective, as well as anti-arthritis activities [86, 87].

Keywords

Rheumatoid arthritis · Osteoarthritis · Herbal medicine · Inammation

V. BaradaranRahimi Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran e-mail: baradaranrv@mums.ac.ir

V. R. Askari (*) Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran e-mail: askariv@mums.ac.ir

1.2 Animal Studies

In the arthritis model caused by complete Freund’s adjuvant (CFA) injection, treatment with N. sativa oil notably decreased paw volume and arthritis score while improving spontaneous locomotor activity and anxiety-like behavior in rats [1].

1.2.1 Thymoquinone

In collagen-induced arthritis (CIA), thymoquinone notably diminished arthritis scoring, paw volume, articular elastase activity, myeloperoxidase (MPO) activity, malondialdehyde (MDA), and nitric oxide (NO) levels while enhancing glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities in rat joints. Thymoquinone also

271

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V. BaradaranRahimi and V. R. Askari

Fig. 1 Herbal medicines with promising anti-arthritis effects

diminished interleukin (IL)-1β and 6, tumor necrosis factoralpha (TNF-α), interferon-gamma (IFN-γ), and prostaglandin E2 (PGE2) levels while increasing IL-10 levels in joints of CIA rats [2].

In CFA-induced arthritis in rats, thymoquinone markedly attenuated arthritis scoring, histopathological scoring, C-reactive protein (CRP) level, toll-like receptor (TLR)2 and 4, IL-1, nuclear factor-kappa B (NF-κB), and TNF-αmRNA expression [3]. Similarly, thymoquinone strikingly mitigated arthritis scoring, IL-1β, TNF-α, PGE2 levels, and alkaline phosphatase activity following CFA-induced arthritis [4].

Furthermore, in pristine-induced arthritis in female rats, thymoquinone provided a signicant decrement in paw weight and histopathological score [5].

1.3 Clinical Studies

N. sativa oil notably diminished disease activity score (DAS-

28), swollen joints number, the duration of morning stiffness, and VAS pain score in female rheumatoid arthritis (RA) patients [61]. Similarly, N. sativa oil markedly reduced high sensitivity (hs)-CRP, the score of DAS-28, and swollen joint numbers in female RA patients. Moreover, N. sativa oil modulated T lymphocytes by decreasing CD8+ T cell percentage and CD4+/CD8+ while increasing the percentage of

CD4+CD25+ T cells in RA patients [62]. Hadi et al. supported that N. sativa oil meaningfully alleviates MDA and NO while elevating IL-10in RA patients [63].

In addition, Khabbazi and co-workers conducted a metaanalysis on 19 animal, cellular, and clinical studies. They emphasized that N. sativa remarkably improved RA in animal and cellular studies through anti-oxidative, antiinammatory, and immunomodulatory effects. However, the results of ve clinical studies did not show a signicant improvement in RA patients [88].

Collectively, further clinical studies are necessary to explain and conrm the anti-RA activities of N. sativa and thymoquinone.

2 Zingiber ocinale andIts Constituents

6-Gingerols and6-Shogaols

Zingiber ofcinale (Z. ofcinale), popularly named ginger, is a perennial, herbaceous plant and member of ingiberaceae [89]. Its roots are widely used as a spice and also in folk medicine worldwide. Besides that, Z. ofcinale has antiemetic, anti-oxidant, anti-inammatory, antidiabetic, cardioprotective, as well as anti-arthritis activities. The phenolic constituents of Z. ofcinale are mainly responsible for its several effects, including 6-gingerol and 6-shogaol [90, 91].

Role ofHerbal Medicines fortheTreatment ofArthritis

https://t.me/medicina_free

[1]

↓ paw volume and arthritis score

[2]

Improved spontaneous locomotor activity and anxiety-

like behavior

↓ arthritis scoring, paw volume

↓articular elastase activity, MPO activity, MDA, and NO

levels

↑ GSH and IL-10 level

[3]

↑ SOD and CAT activities in joints

↓ IL-1β, IL-6, TNF-α, IFN-γ, and PGE2

↓ arthritis and histopathological

[4]

↓ CRP level

↓ TLR2 and 4, IL-1, NF-κB, and TNF-α

↓ arthritis scoring

↓HNE, IL-1β, TNF-α, and PGE2 levels

↓ alkaline phosphatase activity

[5]

[6, 7]

[8]

↓ paw weight

↓histopathological score

↓arthritic index, joint swelling, and cartilage destruction

index

↓ paw edema

[9]

↓ IL-1β, −6, and −4, and TNF-α levels

↑ IL-10 level

↓ clinical scores, arthritic incidence, joint temperature

and swelling, and cartilage destruction

↓ ESR, IL-1β, IL-6, IL-2, TNF-α, and anti-CII antibody

levels

[10]

↓ paw volume

↓ lysosomal enzymes activities, lipid peroxidation, and

[11]

TNF-α levels

↑ Gpx, SOD, and CAT activities

↓ knees swelling and edema, leukocyte inltration into

the synovial cavity

[12]

↓ VCAM-1 level

↓ arthritis score, histopathological changes in the joints

↓ TNF-α, IL-17, IL-1β, and TGF-β levels

↓ IκBα degradation

273

(continued)

[13]

↓ COX-2 expression

↓ clinical score, histology score

↓ MMP-1, 3, 9, and 13

↓ anti-collagen type II antibodies

↓ TNF-α, IL-1β, −6, -33, -15, -16, and -33

↓ IFN-γ, IP-10, MIP-α, and MCP-1

CFA-induced arthritis in rats

orally over 25 days of treatment

Extract or constituent type Dose/Concentration An overview of the study model Results Ref

NSO 1596, and 798mg/kg/day;

Table 1 Protective effects of herbal medicines against animal models of arthritis

injection in rats

Thymoquinone 5mg/kg; orally over 21days Arthritis following collagen

CFA-caused arthritis in rats

Thymoquinone 10mg/kg; given I.P.During

CFA-caused arthritis in rats

20days

Thymoquinone 5mg/kg; given orally for

Pristine-caused arthritis in female

28days

Thymoquinone 2mg/kg; injected I.P.Over

rats

15days

Arthritis following streptococcal

cell wall in female rats

CFA-caused arthritis in rats

26 and 28mg/kg/day); I.P.For

28days

Zingiber ofcinale extract and essential

oil

Zingiber ofcinale rhizomes powder 200mg/kg; given orally over

Collagen-induced arthritis in rats

28days

50, 100, and 200mg/kg;

70% Hydroalcoholic extract of

Gouty arthritis induction by

monosodium urate crystal in mice

injected I.P.Over 26days

rhizomes of Zingiber ofcinale

three continuous days

6-shogaol 30mg/kg; injected I.P.During

Collagen-induced arthritis in rats

orally over18 days

6-shogaol 6.2mg/kg; orally over 28days CFA-caused arthritis in rats

Curcumin 100 and 200mg/kg; given

Collagen-caused arthritis in mice

Curcumin 100mg/kg; administered for

22days

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V. BaradaranRahimi and V. R. Askari

[14]

↓ redness and paw edema, arthritis score, penetration of

inammatory cells into the synovium

[15]

↓ TNF-α, IL-1β, MMP-1, and -3

↓ mTOR, p70S6K, and 4E-BP1 expression

↓ arthritis scores, paw edema

↓ TNF-α, IL-6, IL-17

↓ p-PI3K/PI3K, and p-AKT/AKT ratios

[16]

[17]

↑ SOD, CAT, and Gpx activities

↑ MSRA gene expression and protein level

↓ TNF-α, IL-1β, MMP-3, COMP

↑ SOD and collagen II levels

↓ TLR4, COX-2, and p-p65 expression levels

[18]

↑ number of chondrocytes

↑ collagen 2, SOX-5, and Indian hedgehog expression

[19]

↓ paw and ankle joint swelling, MPO activity

↓ p-p65 and p-p50 phosphorylation

[20]

↑ IκBα protein level

↓ COX-2, TLR4, MyD88, and NLRP3 expression

↓ ankle circumference, penetration of neutrophils in knee

joints

↓ TNF-α, IL-1β, and elastase levels

↓ NLRP3, pro-caspase-1, caspase-1, pro- IL-1β, and

IL-1β expression

[21]

↓ paw swelling

[22]

↓ TNF-α, IL-6 and -8, and NF-kB

↓ paw volume, arthritis score

[23]

↓histopathological damages

↓anti-typeIIcollagen antibodies, and IL-1β

↓ paw thickness, arthritis score

[24]

↓ MPO, COX-2, iNOS

↓ oxidative stress

↓ arthritis score

[25]

[26]

↓ TNF-α, IL-1β and -6, MMP-3 and -9, URI1, and

FRAT1 mRNA expression

↑ PI3K/AKT

↓ VEGFA and C1QTNF3

↓ arthritis score

↓ TNF-α, IL-1β, IL-α levels

[27]

↑ arthritis detumescence percentages

↑ apoptosis rates of OCP and T lymphocytes

↓ arthritis symptoms, joint swelling

↓ OC cell levels of inammatory joints

↓ inammation, swelling, and bone erosion

↑ apoptosis rate of OCP cells

Extract or constituent type Dose/Concentration An overview of the study model Results Ref

Curcumin 200mg/kg; orally for 3weeks Collagen-induced arthritis in rats

Table 1 (continued)

Curcumin 50mg/kg; orally for 28days Collagen-caused arthritis in mice

CFA-induced arthritis in rats

Curcumin 1 and 2g/kg; taken orally over

knee osteoarthritis in rats

14days

Curcumin 20mg/kg; orally for 14days Monosodium iodoacetate- induced

rats

gout in mice

Curcumin 50mg/kg; orally for 60days Zymosan-induced osteoarthritis in

Curcumin 150mg/kg; administered I.P. Monosodium urate-induced acute

Acute gout caused by monosodium

urate in rats

I.P.Over seven days

Curcumin 100, 150, and 200mg/kg; given

Collagen-caused arthritis in rats

during 28days

6mg/kg; taken orally over

Total alkaloids of Tripterygium wilfordii 0.25, 0.5, and 1g/kg; orally

Tripterygium wilfordii glycosides

Collagen-induced arthritis in rats

21days

45μg/kg/d; orally for 28days

Triptolide

Collagen-caused arthritis in rats

45μg/kg; orally for 51days

Triptolide

TNF transgenic mice with RA

3.3, 10, and 33μg/kg/d; for

6weeks

Triptolide 0.4mg/kg; orally for 14days Adjuvant arthritis model in rats

Triptolide

TNF transgenic mice with RA

10 and 33μg/kg/day, orally for

Triptolide

42days

Role ofHerbal Medicines fortheTreatment ofArthritis

https://t.me/medicina_free

[28]

↓ paw volume, histopathological damages, MPO activity

↓ TNF-α, and IL-1β levels

[29]

↓ paw volume

↓ MDA, TNF-α levels

↓ TNF-R1, TNF-α, IL-1β, IL-6, and NF-κB expression

[30]

levels

↑ GSH and SOD activity

↓ paw volume, arthritic score

↓ histological damages

↓ MDA, RF, TNF-α, and IL-1β

[31]

[32]

↓ arthritic score, paw volume, and joint diameter

↓ ESR level

↓ paw edema, histopathological damages

↓ TNF-α, IL-1β, and IL-17 levels

↑ IL-10 and IFN-γ levels

[33]

↓ paw edema

↓ CHI3L1, NF-κB, IL-1β, MMP-9, VEGF, and Caspase-3

protein expression

↓ MDA and NO levels

[34]

↑ GSH level

↓ paw swelling, arthritis index, and pathological damages

[35]

[36]

↓ TNF-α, IL-1β, and IL-6, MTA1, and HDAC1

↑ Nur77

↓ paw volume, clinical arthritis score, histology score

↓ TNF-α and IL-6 levels

↓ paw thickness, arthritis score, and bone destruction

↓changed macrophages from the M1 to the M2

phenotype

↓ iNOS, TNF-α, IL-1β and −6

↑Arginase-1 and IL-10 expression

[37]

↓ NLRP3 and caspase-1 expression

↓ paw diameter, clinical severity score

↓ elastase, MPO, MDA, and NO

↑ GSH level, SOD, and CAT activity

↓ TNF-α, IL-1β and −6, IFN-γ, and PGE2

↑ IL-10 levels

275

(continued)

[38]

↓ arthritis index, paw volume, pain, motility score, stair

climbing, and histopathological damages

↓ collagen antibodies, CRP, and ESR levels in serum

↑ Hyaluronan and cartilage oligomeric matrix protein in

synovial uid

CFA-induced arthritis in rats

topical

over a period of 21days

Extract or constituent type Dose/Concentration An overview of the study model Results Ref

P. granatum rind extract 5%, 2.5%, and 1%, w/w;

P. granatum rind extract 50–200mg/kg; taken orally

CFA-caused arthritis in rats

Ethanolic extract of P.Granatum 500–750mg/kg; taken orally

CFA-induced arthritis in rats

Adjuvant-caused arthritis in mice

over 4weeks

50 and 75mg/kg; taken orally

for continuous 28days

4weeks

Butanol fraction of P. granatum rind

extract

Ellagic acid 700mg/kg; given orally over

mice

Ellagic acid 50mg/kg; orally for 20days Arthritis induction by adjuvant in

CFA-induced arthritis in rats

Ellagic acid 25–100mg/kg; orally during

21days

CIA in mice

50mg/kg; injected I.P.During

14days

27days of treatment

Punicalagin

Punicalagin 10–20mg/kg; injected I.P.Over

CIA in rats

orally over 21days

Boswellia serrate gum resin extract 100 and 200mg/kg; taken

CIA in rats

21days

Boswellia serrate gum resin extract 40–80mg/kg; taken orally for

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V. BaradaranRahimi and V. R. Askari

[39]

↓ paw thickness, lysosomal enzymes

↓ MDA, and TNF-α levels

[40]

[41]

↑ SOD, GPx, and CAT activities

↓ paw edema, ESR, and MDA levels

↑ anti-oxidant enzymes

↓ paw swelling

↓ Exoglycosidases, Cathepsin-D, alkaline phosphatase,

acid phosphatase, and tartrate-resistant acid phosphatase

activities

↓ TNF-α, IL-1β, IL-6, NF-kB, COX-2, PGE2, and ROS

[42]

↑ GSH, SOD, and CAT

↓ paw swelling, arthritis score

[43]

↓ iNOS and NO levels

↓ TNF-α, IL-1β, and IL-6 levels

↓ arthritis score, paw thickness, histological score

↓ MMP-1, −3, and −13, TNF-α, IL-6, −17, and −8, and

CXCL8

[44]

[45]

↓ mean clinical score

↓ TNF-α, IL-1β, and −6 levels

↓ pain

↓ TNF-α and IL-1β levels

↓ Wnt5a/β-catenin pathway

↓ GFAP and Iba-1 levels

[46]

↓ joint pain

↓ ROS, lipid peroxidation, JNK

↑ GSH and GPx activities

↓ IL-6 level, citrate synthase activity, and MHC IIα

expression

[47]

↓ paw swelling, arthritis index score

↓ IL-6 and -17, anti-IL-17 antibody

↑ IL-10, TGF-β, and anti-IL-10 antibody

[48]

↓ paw swelling, arthritis global assessment, and

histopathological damages

↓ TNF-α, IL-1β and-6, and iNOS

↑ IL-10, TGF-β1, and Arg1

↓ Th17/Treg ratio

↓ numbers of Th17

↑ number of Treg

↑ p-AMPK expression

↓ p-p65, p-IκBα and COX-2

Extract or constituent type Dose/Concentration An overview of the study model Results Ref

Boswellic acid 30mg/kg; administered I.P. Gouty arthritic in mice following

Table 1 (continued)

monosodium urate crystal

consumption

CFA-caused arthritis in rats

orally over 45days

for 14days

Boswellic acid 20–40mg/kg; administered

Crocin 10 and 20mg/kg; taken orally

CFA-induced arthritis in rats

Crocin 6.25–25mg/kg; given orally

CIA in mice

over 28days

Crocin 10, 20, and 40mg/kg; given

CIA in mice

orally during a period of

14days

1week

Crocin 50mg/kg; injected I.P. for

Meniscectomy surgery-induced

osteoarthritis in rats

days

Crocin 50–100mg/kg; injected I.P. Adjuvant-caused arthritis in rats

Crocin 30mg/kg; taken orally over ten

Arthritis by CFA in rats

for 21days

Berberine 75 and 150mg/kg; taken orally

CFA-caused arthritis in rats

orally during a period of

14days

Berberine 40, 80, and 160mg/kg; taken

Role ofHerbal Medicines fortheTreatment ofArthritis

https://t.me/medicina_free

[49]

↓ TNF-α, IL-1β, -6, and -17, MCP-1, and IFN-γ

↓ proportion of M1 macrophages

↑ IL-10, IL-4, TGF-β1

↑ proportion of M2 macrophages

[50]

cells

CXCR5

, CD4

↑ p-AMPK expression

↓ HIF-1α expression in synovial macrophages

↓ number of CD4+T

↓ CD28, CD154 expression

[51]

[52]

Treg cells

↑ Foxp3

↓ paw swelling, arthritis index, histological score, joint

destruction

↓ RANKL, TNF-α, IL-1β, and IL-6

↓ proportion of Th17 cells, IL-17 levels, and

phosphorylation STAT3

↓ arthritis score

[53]

↓ anti-CII total IgG, IgG1, IgG2a

↓ TNF-α, IL-1β, -6, and -17, VEGF

↓ VEGF and CD34

↓ p-ERK, p-p38, and p-JNK

↑bone mineral density, trabecular number and thickness,

mineral apposition rate, bone formation rate/total tissue

area, and bone formation rate/trabecular bone surface

[54]

↓ trabecular separation, and osteoclast number/trabecular

bone volume

↓ arthritic index, rheumatoid factor

[55]

↑ GSH and ferric ability of plasma

↓ anti-cyclic citrullinated peptide antibody, ANA,

anti-collagen type II, CRP, MDA, and GST

↓ clinical severity, histological score

[56]

↓ TNF-α, IL-1β and -6, NF-kB, MMP-8, and iNOS levels

↑ IL-10 levels

↓ paw swelling, arthritic score

↓ ESR, CRP, and rheumatoid factor

↓ IL-1β, -6, and -17a, TNF-α, and RANKL, MDA

↑ IL-4, INF-γ, and osteoprotegerin

↑ CAT and SOD activities

(continued)

[57]

↓ paw volume, arthritis index, pathological score

↓ Th17-positive cell numbers

↓ TNF-α, IL-1β, and IL-17

↓ RANKL mRNA levels

↑ IL-10 and OPG mRNA level

277

CFA-caused arthritis in rats

orally over 14days of treatment

Extract or constituent type Dose/Concentration An overview of the study model Results Ref

Berberine 40, 80, and 160mg/kg; taken

CIA in mice

CIA in rats

28days

Berberine 1mg/kg/day; injected I.P.Over

Berberine 100–200mg/kg; given orally

over 14days

Berberine 200mg/kg; orally for 42days CIA in rats

Glucocorticoid-induced

osteoporosis in rats

12weeks of treatment

Berberine 15–60mg/kg; orally during

CIA in rats

100, 200, 300mg/kg; orally for

20days

Aqueous extract or roots of Withania

somnifera

CIA in rats

300mg/kg; taken orally over

45days

Aqueous extract or roots of Withania

somnifera

250–500mg/kg/day CFA-induced arthritis in rats

70% ethanolic extract of roots of

Withania somnifera

2.7g/kg; orally for 45days CIA in rats

70% ethanolic extract of

Eucommia ulmoides

278

https://t.me/medicina_free

V. BaradaranRahimi and V. R. Askari

AMP-

chitinase-

[58]

↓ ankle swelling

↓ TNF-α, IL-1β, and IL-17 levels

[59]

↓ RANKL/OPG ratio

↓ MMP-9, p65 NF-κB, and p-IKKαβexpression

↓ paw volume, ankle joint score

[60]

↓ TNF-α, IL-6, IL-17, IL-1β, and NO levels

↓ histopathological damages

↓ MMP-1, −3, and −13

4g/kg; orally for 4weeks CIA in rats

Knee osteoarthritis in rat

4g/kg; orally for 2weeks CIA in rats

4weeks

, CRP C-reactive protein, TLR toll-like receptor, NF-κB nuclear factor-kappa B, HNE 4-hydroxynonenal,

, COMP cartilage oligomeric matrix protein, MyD88 myeloid differentiation factor 88, NLRP3 NLR family pyrin domain containing 3, iNOS

Extract or constituent type Dose/Concentration An overview of the study model Results Ref

70% ethanol extract, ethyl acetate

fraction, and n-butyl alcohol fraction of

Eucommia ulmoides

70% ethanol extract of Eucommia

Table 1 (continued)

ulmoides

Aqueous extract of Eucommia ulmoides 6mL/kg/day; orally during

NSO Nigella sativa oil, CFA complete Freund’s adjuvant, MPO myeloperoxidase, MDA malondialdehyde, NO nitric oxide, GSH glutathione, SOD superoxide dismutase, CAT catalase, IL interleu-

kin, TNF-α tumor necrosis factor alpha, IFN-γ interferon gamma, PGE2 prostaglandin E

ESR erythrocyte sedimentation rate, Gpx glutathione peroxidase, VCAM vascular cell adhesion molecule, MMP matrix metalloproteinases, IP-10 IFN-gamma-inducible protein 10, MIP macro-

inducible nitric oxide synthase, URI1 unconventional prefoldin RPB5 interactor 1, FRAT1 frequently rearranged in advanced T cell lymphomas-1, VEGF vascular endothelial growth factor,

phage inammatory proteins, MCP-1 -α, monocyte chemoattractant protein-1, mTOR mammalian target of rapamycin, p70S6K p70S6 kinase, 4E-BP1 eukaryotic initiation factor 4E binding

protein 1, MSRA methionine sulfoxide reductase A

C1QTNF3 A and C1q and tumor necrosis factor related protein 3, OCP osteoclast precursor cells, OC osteoclast, TNF-R1 tumor necrosis factor receptor 1, RF rheumatoid factor, CHI3L1

heavy chain, HIF-1α hypoxia inducible factor 1α, STAT3 signal transducer and activator of transcription 3, ANA anti-nuclear antibody, GST glutathione-S-transferase activity, AMPK

activated protein kinase, OPG osteoprotegerin

3- like protein-1, MTA1 metastasis-associated gene 1, HDAC1 histone deacetylase 1, ROS reactive oxygen species, GFAP glial brillary acidic protein, JNK c-Jun N-terminal kinase, MHC myosin

Role ofHerbal Medicines fortheTreatment ofArthritis

https://t.me/medicina_free

[61]

[62]

T cell

ratio

/CD8

T cell

CD25

[63]

[64]

279

(continued)

[65]

[66]

[67]

[68]

[69]

[70]

[71]

[70]

↓ disease activity score, number of

swollen joints, morning stiffness

duration, VAS pain score

↓ hs-CRP level

↓ DAS-28 score

Placebo, controlled clinical trial on female

RA patients

A randomized, double-blinded, placebo-

controlled, parallel-group clinical trial on

↓ CD4

↓swollen joint numbers

↓ CD8

female RA patients

↓ MDA and NO

↑ IL-10 level

↑ CD4

A randomized, double-blind, placebo-

controlled clinical trial on RA patients

↓ DAS-28 arthritis score

↓ T-bet, RORγt, and NF-kB gene

expression

A randomized, double-blind, placebo-

controlled clinical trial on RA patients

↑ FoxP3, GAT A3, and PPAR-γ gene

expression

↓ VAS pain score

↑ satisfaction with treatment

↓ VAS and gelling pain score

↓ VAS pain score, WOMAC pain score,

morning stiffness, and difculty

↓ VAS pain score

↓need for NSAIDs consumption

A randomized placebo-controlled clinical

trial on knee osteoarthritis patients

A randomized placebo-controlled clinical

trial on osteoarthritis patients

A randomized placebo-controlled clinical

trial on knee osteoarthritis patients

A randomized, double-blind,placebo-

controlled prospective study on knee

osteoarthritis patients

↓ pain, need for rescue analgesics, need

for histamine 2 blockers

↓ side effects

↑ quality of life

↓ VAS pain score

↓ WOMAC-pain, physical function, and

stiffness

↓ ESR level

↓ oxidative stress markers

↑ anti-oxidative stress markers

↓ VAS pain score

↓ DAS 28 score

↓ CRP, rheumatoid factor, and ESR

A prospective, randomized, open-label

parallel-group study on knee osteoarthritis

patients

A meta-analysis consisting of 20 clinical

studies involving 1927 patients with

osteoarthritis

A randomized, double-blind, placebo-

controlled, two-dose,three-arm, and

parallel-study on rheumatoid arthritis

levels

↓ DAS 28 score

↓ rheumatoid factor

↓ ESR and CRP levels

patients

A meta-analysis of six clinical studies

involving 326 patients with rheumatoid

arthritis.

• 500mg two times/daily for 30days

• Placebo

• 500mg two times/daily for 8 weeks

• Placebo

Extract type or plant part Study design Study model Results Ref

Nigella sativa oil

Table 2 Clinical studies of the anti-arthritis effects of herbal medicines

Nigella sativa oil

• 500mg two times/daily for 8 weeks

treatment

• Placebo

• 1500mg /daily over 12weeks of

Nigella sativa oil

• Placebo

Zingiber ofcinale rhizomes

powder

• 1000mg /daily for 12weeks

Zingiber ofcinale rhizomes

• Placebo

• 30mg/daily over 30days

• Placebo

powder

95% hydroethanolic extract of

Zingiber ofcinale

• 250mg/daily for 6weeks

• Placebo

• 180mg /daily for 8weeks

• Placebo

• 500mg+diclofenac 50mg twice/daily

Zingiber ofcinale rhizomes

powder

Curcumin

for 28days

• Diclofenac 50mg twice/daily

• 120mg to 1500mg for 4–36weeks

• Placebo

Curcumin

• 250mg twice daily

• 500mg twice daily for 90days

• Placebo

• 120mg to 1500mg for 4–36weeks

Curcumin

• Placebo

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