Total Saponin Fraction of <italic style="font-style: italic">Dioscorea Nipponica</italic> Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling

ZHOU Qi; SUN Hui-juan; ZHANG Xi-wu

doi:10.1007/s11655-022-3729-y

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Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling

Original Article | Updated：2023-11-23

- Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling
- Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling
- 中国结合医学杂志（英文版） 2023年29卷第11期页码：1007-1017
- Affiliations：
  
  1.Research Institute of Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin (150040), China
  2.Graduate School, Heilongjiang University of Chinese Medicine, Harbin (150040), China
- Author bio：
  
  Prof. ZHANG Xi-wu, E-mail: zxw506zxw@163.com
- Funds：
  
  Joint Guidance Project of Heilongjiang Natural Science Foundation(LH2021H099);Start Fund of Postdoctoral Research in Heilongjiang Province(LBH-Q19188);Outstanding Youth Development Fund of Heilongjiang University of Chinese Medicine(2019JC06);Project of Heilongjiang Administration of Traditional Chinese Medicine(ZHY202094);Graduate Innovative Scientific Research Project of Heilongjiang University of Chinese Medicine(2020yjscx057);Natural Science Foundation of Heilongjiang Province (Key project)(ZD2020H006)
- DOI：10.1007/s11655-022-3729-y
  中图分类号：
- 纸质出版日期：2023-11，
  
  网络出版日期：2023-01-06，
  
  录用日期：2021-12-20
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Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling[J]. 中国结合医学杂志（英文版）, 2023,29(11):1007-1017.

ZHOU Qi, SUN Hui-juan, ZHANG Xi-wu. Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling[J]. Chinese Journal of Integrative Medicine, 2023,29(11):1007-1017.
Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling[J]. 中国结合医学杂志（英文版）, 2023,29(11):1007-1017. DOI： 10.1007/s11655-022-3729-y.

ZHOU Qi, SUN Hui-juan, ZHANG Xi-wu. Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling[J]. Chinese Journal of Integrative Medicine, 2023,29(11):1007-1017. DOI： 10.1007/s11655-022-3729-y.

摘要

目的:

研究穿山龙总皂苷对痛风大鼠M1/M2巨噬细胞极化及花生四烯酸通路的影响.

方法:

72只SD大鼠随机分为4组

分别为空白组、模型组、穿山龙总皂苷组 (160 mg/kg) 和塞来昔布组 (43.3 mg/kg)

每组18只. 踝关节注射单尿酸钠晶体 (Monosodium urate crystal

MSU) 诱导大鼠痛风模型. 分别在给药第3

8天收集血液及踝关节滑膜组织样本. 通过苏木精和伊红 (Hematoxylin and eosin

HE) 染色观察滑膜组织病理变化. 通过实时聚合酶链反应 (Real-time polymerase chain reaction

qPCR) 和Western blot检测花生四烯酸信号通路表达情况. 采用流式细胞术评估外周血M1型和M2型巨噬细胞比例. 通过酶联免疫吸附法(Enzyme-linked immunosorbent assay

ELISA)检测血清白细胞介素(Interleukine

IL)-1β、肿瘤坏死因子(Tumor necrosis factor

TNF)-α、IL-4、IL-10、前列腺素E2

(Prostaglandin E2

PGE2)、白三烯B4 (Eukotriene B4

LTB4)表达.

结果:

HE染色显示穿山龙总皂苷显著改善痛风大鼠滑膜组织炎症情况. qPCR和Western blot结果显示

在给药第3、5、8天

穿山龙总皂苷降低了大鼠踝关节滑膜组织中环氧化酶(Cyclooxygenase

COX)2、微粒体前列腺素E合酶-1衍生类花生四烯酸(Microsomal prostaglandin E synthase-1 derived eicosanoids

mPGES-1)、5-脂氧合酶(5-lipoxygenase

5-LOX)、Smad3、核苷酸结合寡聚化结构域样受体蛋白3 (Nucleotide-binding oligomerization domain-like receptor protein 3

NALP3)和诱导型一氧化氮合酶(Inducible nitric oxide synthase

iNOS)的mRNA及蛋白表达(

0.01). 穿山龙总皂苷在给药第3和5天降低COX1 mRNA和蛋白表达

第8天升高其表达(

0.01). 在给药第3天降低CD68蛋白表达(

0.01)

在第5和8天降低CD68 mRNA和蛋白表达(

0.01). 在给药第3、5、8天

穿山龙总皂苷升高Arg1和CD163的mRNA和蛋白表达(

0.01). 流式细胞术结果显示穿山龙总皂苷降低外周血中M1型巨噬细胞比例

升高M2型巨噬细胞比例(

0.05或

0.01). ELISA结果显示

在给药第3、5、8天

穿山龙总皂苷降低血清IL-1β、TNF-α、LTB4水平(

0.01)

在第3、8天降低PGE2水平 (

0.05或

0.01) . 在给药第8天

穿山龙总皂苷升高血清IL-4水平

而在第5天和第8天升高IL-10水平(

0.05或

0.01).

结论:

穿山龙总皂苷对痛风大鼠的抗炎作用可能是通过花生四烯酸信号通路影响巨噬细胞M1/M2极化实现的.

Abstract

Objective:

To explore the mechanism of effects of total saponin fraction from

Dioscorea Nipponica

Makino (TSDN) on M1/M2 polarization of monocytes/macrophages and arachidonic acid (AA) pathway in rats with gouty arthritis (GA).

Methods:

Seventy-two Sprague Dawley rats were randomly divided into 4 groups (

=18 in each): normal

model

TSDN at 160 mg/kg

and celecoxib at 43.3 mg/kg. Monosodium urate crystal (MSU) was injected into the rats' ankle joints to induce an experimental GA model. Blood and tissue samples were collected on the 3rd

5th

and 8th days of drug administration. Histopathological changes in the synovium of joints were observed via hematoxylin and eosin (HE) staining. The expression levels of arachidonic acid (AA) signaling pathway were assessed via real-time polymerase chain reaction (qPCR) and Western blot. Flow cytometry was used to determine the proportion of M1 and M2 macrophages in the peripheral blood. An enzyme-linked immunosorbent assay (ELISA) was used to detect interleukine (IL)-1β

tumor necrosis factor- alpha (TNF-α)

IL-4

IL-10

prostaglandin E

(PGE

)

and leukotriene B4 (LTB4).

Results:

HE staining showed that TSDN improved the synovial tissue. qPCR and Western blot showed that on the 3rd

5th and 8th days of drug administration

TSDN reduced the mRNA and protein expressions of cyclooxygenase (COX)2

microsomal prostaglandin E synthase-1 derived eicosanoids (mPGES-1)

5-lipoxygenase (5-LOX)

recombinant human mothers against decapentaplegic homolog 3 (Smad3)

nucleotide-binding oligomerization domain-like receptor protein 3 (NALP3)

and inducible nitric oxide synthase (iNOS) in rats' ankle synovial tissues (

0.01). TSDN decreased COX1 mRNA and protein expression on 3rd and 5th day of drug administration and raised it on the 8th day (both

0.01). It lowered CD68 protein expression on days 3 (

0.01)

as well as mRNA and protein expression on days 5 and 8 (

0.01). On the 3rd

5th

and 8th days of drug administration

TSDN elevated the mRNA and protein expression of Arg1 and CD163 (

0.01). Flow cytometry results showed that TSDN decreased the percentage of M1 macrophages while increasing the percentage of M2 in peripheral blood (

0.05 or

0.01). ELISA results showed that on the 3rd

5th

and 8th days of drug administration

TSDN decreased serum levels of IL-1β

TNF-α

and LTB4 (

0.01)

as well as PGE

levels on days 3rd and 8th days (

0.05 or

0.01); on day 8 of administration

TSDN increased IL-4 serum levels and enhanced IL-10 contents on days 5 and 8 (

0.05 or

0.01).

Conclusion:

The anti-inflammatory effect of TSDN on rats with GA may be achieved by influencing M1/M2 polarization through AA signaling pathway.

关键词

Keywords

gouty arthritisDioscorea nipponica Makinoarachidonic acidsignaling pathwayM1/M2 polarizationChinese medicine

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Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling

Total Saponin Fraction of Dioscorea Nipponica Makino Improves Gouty Arthritis Symptoms in Rats via M1/M2 Polarization of Monocytes and Macrophages Mediated by Arachidonic Acid Signaling

DOI：10.1007/s11655-022-3729-y

摘要

Abstract

关键词

Keywords

references