To investigate the mechanism of Illicium henryi injection on rheumatoid arthritis based on JAK/STAT signaling pathway
Chinese Medicinal Pharmacology|更新时间:2022-04-01
|
To investigate the mechanism of Illicium henryi injection on rheumatoid arthritis based on JAK/STAT signaling pathway
Journal of Beijing University of Traditional Chinese MedicineVol. 45, Issue 3, Pages: 267-274(2022)
作者机构:
北京中医药大学东直门医院 北京 100700
作者简介:
Prof. CHAI Limin, Ph.D., Doctoral supervisor. Dongzhimen Hospital, Beijing University of Chinese Medicine, No.5, Haiyuncang, Dongcheng District, Beijing 100700, China. E-mail: liminchai@hotmail.com
基金信息:
Second Batch of Scientific Research Project of the National TCM Clinical Research Base of State Administration of Traditional Chinese Medicine(JDZX2015191)
Huijie ZHANG, Limin CHAI, Juan LIU, et al. To investigate the mechanism of Illicium henryi injection on rheumatoid arthritis based on JAK/STAT signaling pathway[J]. Journal of Beijing University of Traditional Chinese Medicine, 2022, 45(3): 267-274.
DOI:
Huijie ZHANG, Limin CHAI, Juan LIU, et al. To investigate the mechanism of Illicium henryi injection on rheumatoid arthritis based on JAK/STAT signaling pathway[J]. Journal of Beijing University of Traditional Chinese Medicine, 2022, 45(3): 267-274.DOI: 10.3969/j.issn.1006-2157.2022.03.010.
To investigate the mechanism of Illicium henryi injection on rheumatoid arthritis based on JAK/STAT signaling pathway
We aimed to investigate the mechanisms underlying the effects of Illicium henryi injection on rheumatoid arthritis (RA).
Methods
2
Male DBA/1 mice were randomly divided into: (i) the normal group
(ii) the model group
(iii) the leflunomide group
and (iv) the Illicium henryi injection group (
n
= 8 mice per group). A collagen-induced arthritis (CIA) mouse model was established by multipoint injection of bovine type Ⅱ collagen emulsifier in the tail and back. Mice in the normal group and model group were given normal saline. Mice in the leflunomide group were given leflunomide (3 mg/kg) by gavage. Mice in the Illicium henryi injection group were intraperitoneally injected with Illicium henryi injection (0.3 mL/kg) once a day for 28 consecutive days. Joint inflammatory scores were recorded every 7 days after the intervention to measure the degree of joint swelling. After 28 days
HE staining was used to observe the histopathological morphology and record the histopathological score of the ankle joint. Safranin O staining was used to observe the degree of damage to articular cartilage and score the loss of staining. The protein expression levels of JAK2
p-JAK2
STAT6
and p-JAK6 in synovial tissues were determined by Western blot.
Results
2
Compared with the model group
the arthritis index score was lower in the Illicium henryi injection group (
P
<
0.05)
the foot joint was thinner (
P
<
0.05
P
<
0.01)
the pathological changes of the joint were less severe
and the expression and phosphorylation of JAK2 and STAT6 in synovium were lower (
P
<
0.05
P
<
0.01).
Conclusion
2
Illicium henryi injection has anti-inflammatory and immunomodulatory effects on CIA mice through inhibiting the phosphorylation and expression of JAK2 and STAT6 and regulating the JAK/STAT signaling pathway.
关键词
Keywords
references
ZHANG ZH , CAO Y , YUAN Q , et al . Shexiang-Wulong Pills attenuate rheumatoid arthritis by alleviating inflammation in a mouse model of collagen-induced arthritis [J/OL]. Evidence-Based Complementary and Alternative Medicine , 2019 , 2019 : 5308405 [ 2021-01-23 ]. https://www.hindawi.com/journals/ecam/2019/5308405/ https://www.hindawi.com/journals/ecam/2019/5308405/ .
ALETAHA D , SMOLEN JS . Diagnosis and management of rheumatoid arthritis:a review [J]. JAMA , 2018 , 320 ( 13 ): 1360 - 1372 .
LIN YJ , ANZAGHE M , SCHULKE S . Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis [J]. Cells , 2020 , 9 ( 4 ): 880 - 880 .
MALEMUD C J . The role of the JAK/STAT signal pathway in rheumatoid arthritis [J]. Therapeutic Advances in Musculoskeletal Disease , 2018 , 10 ( 5/6 ): 117 - 127 .
CIOBANU DA , POENARIU IS , CRINGUS LI , et al . JAK/STAT pathway in pathology of rheumatoid arthritis(Review) [J]. Experimental and therapeutic medicine , 2020 , 20 ( 4 ): 3498 - 3503 .
PTACEK J , HAWTIN RE , SUN DM , et al . Diminished cytokine-induced Jak/STAT signaling is associated with rheumatoid arthritis and disease activity [J/OL]. Plos one , 2021 , 16 ( 1 ): 0244187 [ 2021-05-12 ]. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244187 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244187 .
LI JY , WEI Y , LI X , et al . Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice [J]. BMC Complementary and Alternative Medicine , 2017 , 17 ( 1 ): 12 - 23 .
RAUBER S , LUBER M , WEBER S , et al . Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells [J]. Nature Medicine , 2017 , 23 ( 8 ): 938 - 944 .
CRISPINO N , CICCIA F . JAK/STAT pathway and nociceptive cytokine signaling in rheumatoid arthritis and psoriatic arthritis [J]. Clinical and experimental rheumatology , 2021 : 39 ( 3 ): 668 - 675 .
YAN ZQ , GIBSON SA , BUCKLEY JA , et al . Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases [J]. Clinical immunology , 2018 , 189 : 4 - 13 .
MCINNES IB , SCHETT G . Cytokines in the pathogenesis of rheumatoid arthritis [J]. Nature Reviers Immunology , 2007 , 7 ( 6 ): 429 - 442 .
SIMON LS , TAYLOR PC , CHOY EH , et al . The Jak/STAT pathway: A focus on pain in rheumatoid arthritis [J]. Seminars in Arthritis and Rheumatism , 2020 , 51 ( 1 ): 278 - 284 .
CHARLES M . Negative regulators of JAK/STAT signaling in rheumatoid arthritis and osteoarthritis [J]. International Journal of Molecular Sciences , 2017 , 18 ( 3 ): 484 .
THOMAS EJ , MATHIEU GV , PASCAL S , et al . Inhibition of JAK/STAT signaling in rheumatologic disorders: The expanding spectrum [J]. Joint Bone Spine , 2020 , 87 ( 2 ): 119 - 129 .
KIU H , NICHOLSON SE . Biology and significance of the JAK/STAT signalling pathways [J]. Growth factors , 2012 , 30 ( 2 ): 88 - 106 .
OMATA Y , FRECH M , LUCAS S , et al . Type 2 innatelymphoid cells inhibit the differentiation of osteoclasts and protect from ovariectomy-induced bone loss [J/OL]. Bone , 2020 , 136 : 115335 [ 2021-01-07 ]. https://www.sciencedirect.com/science/article/pii/S8756328220301150 https://www.sciencedirect.com/science/article/pii/S8756328220301150 .
CHEN Z , BOZEC A , RAMMING A , et a1 . Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis [J]. Nature Reviews Rheumatology , 2019 , 15 : 9 - 17 .
SINGH S , SINGH S . JAK-STAT inhibitors: Immersing therapeutic approach for management of rheumatoid arthritis [J/OL]. International immunopharmacology , 2020 , 86 : 106731 [ 2021-03-17 ]. https://www.sciencedirect.com/science/article/pii/S1567576920311851 https://www.sciencedirect.com/science/article/pii/S1567576920311851 .
QIU ML , MO LS , Li JX , et al . Effects of miR-150-5p on the growth and SOCS1 expression of rheumatoid arthritis synovial fibroblasts [J]. Clinical Rheumatology , 2020 , 39 ( 3 ): 909 - 917 .