Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5572_Библиотеки_им_академика_М_И_Перельмана
.pdf
Herbal Medicine fortheManagement ofAnxiety, Depression, andInsomnia
https://t.me/medicina_free
269
15. Viana MDM, da Silva Neto GJ, de Lima AA, Leite AB, Souza IT,
Santana AEG, Campesatto EA, Moreira MSA.Citrus limon (L.)
Burm f. Essential oil has anxiolytic and sedative properties by modulating GABAA-receptors human and animal health. Braz Arch
Biol Technol. 2020;63:1.
16. Mittal S, Gupta P, Nigam V.Evaluation of antidepressant-like effect
of Clitoria ternatea Linn. Res J Pharm Technol. 2021;14:6437–41.
17. Motti R, de Falco B.Traditional herbal remedies used for managing
anxiety. Horticulturae. 2021;7:523.
18. Pannu A, Sharma PC, Thakur VK, Goyal RK. Emerging role
of avonoids as the treatment of depression. Biomol Ther.
2021;2021(11):1825.
19. Uncini Manganelli RE, Tomei PE.Ethnopharmacobotanical studies
of the Tuscan archipelago. J Ethnopharmacol. 1999;65:181–202.
20. Guarino C, De Simone L, Santoro S. Ethnobotanical study of
the Sannio area, Campania. South.Italy. Ethnobot Res Appl.
2008;6:255–317.
21. Tuttolomondo T, Licata M, Leto C, Bonsangue G, Letizia Gargano
M, Venturella G, La Bella S. Popular uses of wild plant species
for medicinal purposes in the Nebrodi Regional Park (north-eastern
Sicily, Italy). J Ethnopharmacol. 2014;157:21–37.
22. Pieroni A, Nebel S, Quave C, Munz H, Heinrich
M. Ethnopharmacology of liakra: traditional weedy vegetables of the Arbereshe of the vulture area in southern Italy. J
Ethnopharmacol. 2002;81:165–85.
23. Licata M, Tuttolomondo T, Leto C, Virga G, Bonsangue G,
Cammalleri I, Gennaro MC, La Bella S.A survey of wild plant species for food use in Sicily (Italy)–results of a 3-year study in four
regional parks. J Ethnobiol Ethnomed. 2016;12:12.
24. Abourashed EA, Koetter U, Brattstrom A. In vitro binding
experiments with a valerian, hops and their xed combination
extract (Ze91019) to selected central nervous system receptors.
Phytomedicine. 2004;11:633–8.
25. Kim HK, Son KH, Chang HW, Kang SS, Kim HP.Amentoavone,
a plant biavone: a new potential anti-inammatory agent. Arch
Pharm Res. 1998;21:406–10.
26. Ishola I, Chatterjee M, Tota S, Tadigopulla N, Adeyemi OO, Palit
G, Shukla R.Antidepressant and anxiolytic effects of amentoavone isolated from Cnestis ferruginea in mice. Pharmacol Biochem
Behav. 2012;103:322–31.
27. Salehi B, Venditti A, Shari-Rad M, Kregiel D, Shari-Rad
J, Durazzo A, Lucarini M, Santini A, Souto EB, Novellino
E, et al. The therapeutic potential of Apigenin. Int J Mol Sci.
2019;20:1305.
28. Li R, Wang X, Qin T, Qu R, Ma S. Apigenin ameliorates chronic
mild stress-induced depressive behavior by inhibiting interleukin-1β
production and NLRP3 inammasome activation in the rat brain.
Behav Brain Res. 2016;296:318–25.
29. Weng L, Guo X, Li Y, Yang X, Han Y.Apigenin reverses depressionlike behavior induced by chronic corticosterone treatment in mice.
Eur J Pharm. 2016;774:50–4.
30. Ishisaka M, Kakefuda K, Yamauchi M, Tsuruma K, Shimazawa
M, Tsuruta A, Hara H.Luteolin shows an antidepressantlike effect
via suppressing endoplasmic reticulum stress. Biol Pharm Bull.
2011;34(9):1481–6.
31. Liu B, Xu C, Wu X, Liu F, Du Y, Sun J, Tao J, Dong J.Icariin
exerts an antidepressant effect in an unpredictable chronic mild
stress model of depression in rats and is associated with the
regulation of hippocampal neuroinammation. Neuroscience.
2015;294:193–205.
32. Wei K, Xu Y, Zhao Z, Wu X, Du Y, Sun J, Yi T, Dong J, Liu
B.Icariin alters the expression of glucocorticoid receptor, FKBP5
and SGK1in rat brains following exposure to chronic mild stress.
Int J Mol Med. 2016;38:337–44.
33. Gong MJ, Han B, Wang SM, Liang SW, Zou ZJ. Icariin reverses
corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) andmetabolic
network disturbances revealed by NMR based metabonomics in
rats. J Pharm Biomed Anal. 2016;123:63–73.
34. Butterweck V, Hegger M, Winterhoff H. Flavonoids of St.
John’s wort reduce HPA axis function in the rat. Planta Med.
2004;70:1008–11.
35. Park S, Sim Y, Han P, Lee J, Suh H.Antidepressantlike effect of
kaempferol and quercitirin, isolated from Opuntia cus-indica var.
Saboten Exp Neurobiol. 2010;19:24–30.
36. Domitrovi’C R, Rashed K, Cvijanovi’C O, Vladimir-Kneževi’C S,
Škoda M, Višni’C A.Myricitrin exhibits antioxidant, antiinammatory and antibrotic activity in carbon tetrachloride-intoxicated
mice. Chem Biol Interact. 2015;230:21–9.
37. Meyer E, Mori MA, Campos AC, Andreatini R, Guimarães FS,
Milani H, de Oliveira RMW.Myricitrin induces antidepressant-like
effects and facilitates adult neurogenesis in mice. Behav Brain Res.
2017;316:59–65.
38. Terao J, Yamaguchi S, Shirai M, Miyoshi M, Moon JH, Oshima S,
Inakuma T, Tsushida T, Kato Y.Protection by quercetin and quercetin 3-O-beta-D-glucuronide of peroxynitrite-induced antioxidant
consumption in human plasma low-density lipoprotein. Free Radic
Res. 2001;35:925–31.
39. Rinwa P, Kumar A.Quercetin suppress microglial neuroinammatory response and induce antidepressent-like effect in olfactory bulbectomized rats. Neuroscience. 2013;255:86–98.
40. Holzmann I, Silva LM, Corrêa da Silva JA, Steimbach VM, De
Souza MM. Antidepressant-like effect of quercetin in bulbectomized mice and involvement of the antioxidant defenses, and the
glutamatergic and oxidonitrergic pathways. Pharm Biochem Behav.
2015;136:55–63.
41. Pauff JM, Hille R. Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin. J Nat Prod.
2009;72:725–31.
42. Petacci F, Freitas SS, Brunetti IL, Khalil NM.Inhibition of peroxidase activity and scavenging of reactive oxygen species by astilbin
isolated from Dimorphandra mollis (Fabaceae, Caesalpinioideae).
Biol Res. 2010;43:63–74.
43. Lv QQ, Wu WJ, Guo XL, Liu RL, Yang YP, Zhou DS, Zhang JX,
Liu JY. Antidepressant activity of astilbin: involvement of monoaminergic neurotransmitters and BDNF signal pathway. Biol
Pharm Bull. 2014;37:987–95.
44. Ren Z, Yan P, Zhu L, Yang H, Zhao Y, Kirby BP, Waddington JL,
Zhen X.Dihydromyricetin exerts a rapid antidepressantlike effect in
association with enhancement of BDNF expression and inhibition
of neuroinammation. Psychopharmacology. 2018;235:233–44.
45. Liua L, Liu C, Wang Y, Wang P, Li Y, Li B. Herbal medicine
for anxiety, depression and insomnia. Curr Neuropharmacol.
2015;13:481–93.
46. Khanum F, Razack S.Anxiety-herbal treatment: a review. Res Rev
Biomed Biotechnol. 2010;1(2):71–89.

Role ofHerbal Medicines
https://t.me/medicina_free
fortheTreatment ofArthritis
VafaBaradaranRahimi andVahidRezaAskari
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 ofcinale 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-inammatory, 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, Table1 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 Table2.
1.1 Nigella sativa andIts 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-inammatory, analgesic, antianxiety, nephroprotective, as well as anti-arthritis activities
[86, 87].
Keywords
Rheumatoid arthritis · Osteoarthritis · Herbal medicine ·
Inammation
V. BaradaranRahimi
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
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
A. K. Dhara, S. C. Mandal (eds.), Role of Herbal Medicines, https://doi.org/10.1007/978-981-99-7703-1_14
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

272
https://t.me/medicina_free
V. BaradaranRahimi 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 signicant 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-10in 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, antiinammatory, and immunomodulatory effects. However, the
results of ve clinical studies did not show a signicant
improvement in RA patients [88].
Collectively, further clinical studies are necessary to
explain and conrm the anti-RA activities of N. sativa and
thymoquinone.
2 Zingiber ocinale andIts Constituents
6-Gingerols and6-Shogaols
Zingiber ofcinale (Z. ofcinale), 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. ofcinale has antiemetic, anti-oxidant, anti-inammatory, antidiabetic, cardioprotective, as well as anti-arthritis activities. The phenolic
constituents of Z. ofcinale are mainly responsible for its
several effects, including 6-gingerol and 6-shogaol [90, 91].

Role ofHerbal Medicines fortheTreatment ofArthritis
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 inltration 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 798mg/kg/day;
Table 1 Protective effects of herbal medicines against animal models of arthritis
injection in rats
Thymoquinone 5mg/kg; orally over 21days Arthritis following collagen
CFA-caused arthritis in rats
Thymoquinone 10mg/kg; given I.P.During
CFA-caused arthritis in rats
20days
Thymoquinone 5mg/kg; given orally for
Pristine-caused arthritis in female
28days
Thymoquinone 2mg/kg; injected I.P.Over
rats
15days
Arthritis following streptococcal
cell wall in female rats
CFA-caused arthritis in rats
26 and 28mg/kg/day); I.P.For
28days
Zingiber ofcinale extract and essential
oil
Zingiber ofcinale rhizomes powder 200mg/kg; given orally over
Collagen-induced arthritis in rats
28days
50, 100, and 200mg/kg;
70% Hydroalcoholic extract of
Gouty arthritis induction by
monosodium urate crystal in mice
injected I.P.Over 26days
rhizomes of Zingiber ofcinale
three continuous days
6-shogaol 30mg/kg; injected I.P.During
Collagen-induced arthritis in rats
orally over18 days
6-shogaol 6.2mg/kg; orally over 28days CFA-caused arthritis in rats
Curcumin 100 and 200mg/kg; given
Collagen-caused arthritis in mice
Curcumin 100mg/kg; administered for
22days

274
https://t.me/medicina_free
V. BaradaranRahimi and V. R. Askari
[14]
↓ redness and paw edema, arthritis score, penetration of
inammatory 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 inammatory joints
↓ inammation, swelling, and bone erosion
↑ apoptosis rate of OCP cells
Extract or constituent type Dose/Concentration An overview of the study model Results Ref
Curcumin 200mg/kg; orally for 3weeks Collagen-induced arthritis in rats
Table 1 (continued)
Curcumin 50mg/kg; orally for 28days Collagen-caused arthritis in mice
CFA-induced arthritis in rats
Curcumin 1 and 2g/kg; taken orally over
knee osteoarthritis in rats
14days
Curcumin 20mg/kg; orally for 14days Monosodium iodoacetate- induced
rats
gout in mice
Curcumin 50mg/kg; orally for 60days Zymosan-induced osteoarthritis in
Curcumin 150mg/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 200mg/kg; given
Collagen-caused arthritis in rats
Collagen-caused arthritis in rats
during 28days
6mg/kg; taken orally over
Total alkaloids of Tripterygium wilfordii 0.25, 0.5, and 1g/kg; orally
Tripterygium wilfordii glycosides
Collagen-induced arthritis in rats
21days
45μg/kg/d; orally for 28days
Triptolide
Collagen-caused arthritis in rats
45μg/kg; orally for 51days
Triptolide
TNF transgenic mice with RA
3.3, 10, and 33μg/kg/d; for
6weeks
Triptolide 0.4mg/kg; orally for 14days Adjuvant arthritis model in rats
Triptolide
TNF transgenic mice with RA
10 and 33μg/kg/day, orally for
Triptolide
42days

Role ofHerbal Medicines fortheTreatment ofArthritis
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
CFA-induced arthritis in rats
topical
over a period of 21days
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 50–200mg/kg; taken orally
CFA-caused arthritis in rats
Ethanolic extract of P.Granatum 500–750mg/kg; taken orally
CFA-induced arthritis in rats
Adjuvant-caused arthritis in mice
over 4weeks
50 and 75mg/kg; taken orally
for continuous 28days
4weeks
Butanol fraction of P. granatum rind
extract
Ellagic acid 700mg/kg; given orally over
mice
Ellagic acid 50mg/kg; orally for 20days Arthritis induction by adjuvant in
CFA-induced arthritis in rats
Ellagic acid 25–100mg/kg; orally during
21days
CIA in mice
CIA in mice
50mg/kg; injected I.P.During
14days
27days of treatment
Punicalagin
Punicalagin 10–20mg/kg; injected I.P.Over
CIA in rats
orally over 21days
Boswellia serrate gum resin extract 100 and 200mg/kg; taken
CIA in rats
21days
Boswellia serrate gum resin extract 40–80mg/kg; taken orally for

276
https://t.me/medicina_free
V. BaradaranRahimi 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 30mg/kg; administered I.P. Gouty arthritic in mice following
Table 1 (continued)
monosodium urate crystal
consumption
CFA-caused arthritis in rats
CFA-caused arthritis in rats
orally over 45days
for 14days
Boswellic acid 20–40mg/kg; administered
Crocin 10 and 20mg/kg; taken orally
CFA-induced arthritis in rats
Crocin 6.25–25mg/kg; given orally
CIA in mice
over 28days
Crocin 10, 20, and 40mg/kg; given
CIA in mice
orally during a period of
14days
1week
Crocin 50mg/kg; injected I.P. for
Meniscectomy surgery-induced
osteoarthritis in rats
days
Crocin 50–100mg/kg; injected I.P. Adjuvant-caused arthritis in rats
Crocin 30mg/kg; taken orally over ten
Arthritis by CFA in rats
for 21days
Berberine 75 and 150mg/kg; taken orally
CFA-caused arthritis in rats
orally during a period of
14days
Berberine 40, 80, and 160mg/kg; taken

Role ofHerbal Medicines fortheTreatment ofArthritis
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
fh
T
+
CXCR5
+
, CD4
h
+
↑ 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 14days of treatment
Extract or constituent type Dose/Concentration An overview of the study model Results Ref
Berberine 40, 80, and 160mg/kg; taken
CIA in mice
CIA in rats
28days
Berberine 1mg/kg/day; injected I.P.Over
Berberine 100–200mg/kg; given orally
over 14days
Berberine 200mg/kg; orally for 42days CIA in rats
Glucocorticoid-induced
osteoporosis in rats
12weeks of treatment
Berberine 15–60mg/kg; orally during
CIA in rats
100, 200, 300mg/kg; orally for
20days
Aqueous extract or roots of Withania
somnifera
CIA in rats
300mg/kg; taken orally over
45days
Aqueous extract or roots of Withania
somnifera
250–500mg/kg/day CFA-induced arthritis in rats
70% ethanolic extract of roots of
Withania somnifera
2.7g/kg; orally for 45days CIA in rats
70% ethanolic extract of
Eucommia ulmoides

278
https://t.me/medicina_free
V. BaradaranRahimi 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
4g/kg; orally for 4weeks CIA in rats
Knee osteoarthritis in rat
4g/kg; orally for 2weeks CIA in rats
4weeks
, CRP C-reactive protein, TLR toll-like receptor, NF-κB nuclear factor-kappa B, HNE 4-hydroxynonenal,
2
, 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 6mL/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 inammatory 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 ofHerbal Medicines fortheTreatment ofArthritis
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 difculty
↓ 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.
• 500mg two times/daily for 30days
• Placebo
• 500mg 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
• 500mg two times/daily for 8 weeks
treatment
• Placebo
• 1500mg /daily over 12weeks of
Nigella sativa oil
• Placebo
Zingiber ofcinale rhizomes
powder
• 1000mg /daily for 12weeks
Zingiber ofcinale rhizomes
• Placebo
• 30mg/daily over 30days
• Placebo
powder
95% hydroethanolic extract of
Zingiber ofcinale
• 250mg/daily for 6weeks
• Placebo
• 180mg /daily for 8weeks
• Placebo
• 500mg+diclofenac 50mg twice/daily
Zingiber ofcinale rhizomes
powder
Curcumin
Curcumin
for 28days
• Diclofenac 50mg twice/daily
• 120mg to 1500mg for 4–36weeks
• Placebo
Curcumin
• 250mg twice daily
• 500mg twice daily for 90days
• Placebo
• 120mg to 1500mg for 4–36weeks
Curcumin
Curcumin
• Placebo
Соседние файлы в папке Библиотека им академика М.И. Перельмана
