Efficacy of Lushi Runzao decoction (路氏润燥汤) on ameliorating Sjogren's syndrome: a network pharmacology and experimental verification-based study

doi:10.19852/j.cnki.jtcm.2023.04.004

Abstract

Abstract:

OBJECTIVE: To investigate the possible mechanism underlying the effect of the Lushi Runzao decoction (路氏润燥汤) on Sjogren’s syndrome using network pharmacology and to verify the mechanisms via animal experiments.

METHODS: Available biological data on each drug in the Lushi Runzao decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the target proteins of Sjogren’s syndrome were retrieved from the GeneCards database. Information regarding Sjogren’s syndrome and the targets of the drugs were compared to obtain overlapping elements. This information was imported into the STRING platform to obtain a protein-protein interaction network diagram, following which a “component-target” network diagram was constructed using screened drug components and target information via Cytoscape software. The database for annotation, visualization, and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses. Pathway information predicted by network pharmacology was verified using animal experiments.

RESULTS: The Lushi Runzao decoction ameliorated Sjogren’s syndrome mainly by influencing tumor necrosis factor as well as certain cytokines and chemokines. The decoction also influenced the interleukin-17 and advanced glycosylation end products (AGE)-receptor for AGE signaling pathways.

CONCLUSION: The Lushi Runzao decoction ameliorates Sjogren’s syndrome via multiple targets and multiple signaling pathways. Network pharmacology is useful for making a comprehensive prediction regarding the efficacy of the Lushi Runzao decoction, and this information may be helpful in clinical research.

Key words: immune system diseases, tumor necrosis factors, network pharmacology, Lushi Runzao decoction, experimental verification

PANG Fengtao, LI Kesong, ZHANG Yi, TANG Xiaopo, ZHOU Xinyao. Efficacy of Lushi Runzao decoction (路氏润燥汤) on ameliorating Sjogren's syndrome: a network pharmacology and experimental verification-based study[J]. Journal of Traditional Chinese Medicine, 2023, 43(4): 751-759.

Figures/Tables 8

Figure 1 Network diagram of interaction of target proteins overlapping between Sjogren’s syndrome and the Lushi Runzao decoction

Figure 2 GO enrichment analysis of Sjogren’s syndrome and Lushi Runzao decoction

Figure 3 KEGG analysis of target genes that overlap between Sjogren’s syndrome and Lushi Runzao decoction KEGG: Kyoto Encyclopedia of Genes and Genomes; TNF: tumor necrosis factor; IL-17: interleukin 17A; AGE: advanced glycation end products; RAGE: receptor for advanced glycation endproducts; HIF-1: hypoxia inducible factor-1.

Table 1 Weight of mice during the experiment (g, $\bar{x}±s$)

Weeks	Normal (n = 10)	Model (n =10)	HCQ (n =10)	LSRZT (n =10)
0	21.77±0.76	20.00±1.11	21.67±0.99	20.14±0.94
0.5	21.67±1.01	20.26±0.97^a	21.50±1.21	20.71±1.02
1	21.71±0.99	20.33±1.03	21.65±1.04	20.85±0.99
1.5	21.89±0.83	20.50±1.12	21.73±1.20	20.96±1.19
2	21.71±0.92	20.67±0.92	21.70±1.07	21.05±1.11
2.5	21.98±1.67	20.53±1.24	21.68±1.39	21.17±0.89
3	22.02±1.09	20.47±1.09	21.67±1.05	21.33±0.95
3.5	22.13±0.79	20.66±1.20	21.71±0.97	21.14±0.93
4	22.75±0.88	20.50±1.21	21.80±1.33	21.44±0.78^b

Table 2 Water consumption of mice during the experiment (mL)

Days	Normal (n = 10)	Model (n = 10)	HCQ (n = 10)	LSRZT (n = 10)
1	25	47	50	45
2	20	50	48	47
3	15	48	52	45
4	20	50	50	45
5	20	52	48	43
6	25	49	45	42
7	26	51	46	40
8	25	50	50	40
9	25	47	49	42
10	25	48	45	40
11	20	45	43	38
12	20	50	45	39
13	25	50	40	37
14	25	48	44	35
15	25	51	43	37
16	20	48	40	38
17	20	46	40	36
18	25	49	42	35
19	25	47	38	35
20	25	50	35	32
21	27	51	36	34
22	25	48	38	35
23	25	45	35	34
24	25	49	35	30
25	25	45	32	35
26	20	47	34	35
27	20	46	32	34
28	25	48	34	30

Figure 4 Effect of Lushi Runzao decoction on pathological changes in the submandibular gland in Sjogren’s syndrome mice A: Normal; B: Model; C: HCQ; D: LSRZT; HE staining was performed in the structures. × 200. LSRZT group for 4 weeks followed by Lushi Runzao decoction (22.8 g·kg-1·d-1); HCQ group for 4 weeks followed by hydroxychloroquine (6.67 mg·kg-1·d-1); Normal group and Model group for 4 weeks followed by saline (0.2 mL). HCQ: hydroxychloroquine; LSRZT: Lushi Runzao decoction; HE: hematoxylin-eosin.

Table 3 Effect of Lushi Runzao decoction on the expression of TNF-α and IL-17 in Sjogren’s syndrome mice (pg/mL,$\bar{x}±s$)

Group	n	TNF-α	IL-17
Normal	6	44±11^a	19±2^a
Model	6	130±20	40±9
HCQ	6	74±16^b	23±7^a
LSRZT	6	54±34^a	30±4^b

Table 4 Effect of Lushi Runzao decoction on AQP1 and AQP5 levels in Sjogren’s syndrome mice ($\bar{x}±s$)

Group	n	AQP1	AQP5
Normal	6	0.0152±0.0022^a	0.0108±0.0031^a
Model	6	0.0076±0.0010	0.0028±0.0021
HCQ	6	0.0097±0.0008	0.0055±0.0016^b
LSRZT	6	0.0198±0.0018^a	0.0035±0.0017

References 26.

1.	Nocturne G. Actualités dans le syndrome de Sjögren primitif: aspects cliniques et thérapeutiques. La Revue de Médecine Interne 2019; 40: 433-9. DOI URL
2.	Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X. Primary Sjogren syndrome. BMJ 2012; 344: e3821.
3.	Zhao J. Comparison of efficacy and safety between iguratimod and hydroxychloroquine in treating Sjogren’s syndrome. Zhong Guo Yao Wu Yu Lin Chuang 2020; 20: 3627-9.
4.	Jiang Q. Lu Zhizheng’s academic thought inheritance and clinical application of regulating spleen and stomach to treat rheumatism. Beijing: Chinese Academy of Traditional Chinese Medicine, 2012: 12-8.
5.	Deng J, Yu Z, Li X, et al. The combination of acupuncture and medicine in treating primary Sjogren’s syndrome dry mouth for 55 cases. Zhong Guo Zhong Yi Yao Xian Dai Yuan Cheng Jiao Yu 2017; 15: 40-2.
6.	Zhang H, Jiang Q, Wang Z, et al. Observation on the therapeutic effect of Lushi Runzao decoction on dry eyes of primary Sjogren’s syndrome for 3 months. Shi Jie Zhong Xi Yi Jie He Za Zhi 2013; 8: 734-6.
7.	Zhang H, Jiang Q, Huang Y, et al. Comparative study on the curative effect of Lushi Runzao decoction on dry mouth symptoms of primary Sjogren’s syndrome. Shi Jie Zhong Xi Yi Jie He Za Zhi 2013; 8: 578-81.
8.	Ma Y, Hou Y, Zou L, et al. Composition analysis of different germplasm of Pseudostellaria heterophylla. Zhong Hua Zhong Yi Yao Za Zhi 2015; 30: 2149-52.
9.	Song Y, Lin D, Mei Q, et al. Research progress on chemical constituents and pharmacological effects of Radix Pseudostellariae. Zhong Guo Yao Shi 2019; 22: 1506-10.
10.	Ma Y, Liu X, Wang Y, et al. Research progress on main chemical constituents and pharmacological activities of Adenophora littoralis. Jilin Yi Yao Xue Yuan Xue Bao 2019; 40: 357-9.
11.	Liu L, Jia J, Zeng G, et al. Studies on immunoregulatory and anti-tumor activities of a polysaccharide from Salvia miltiorrhiza Bunge. Carbohydr Polym 2013; 92: 479-83. DOI URL
12.	Ding F, Wang Y, Zhang Y. Research progress on pharmacological action and clinical application of active components of Salvia miltiorrhiza Bunge. Zhong Hua Zhong Yi Yao Za Zhi 2021; 36: 659-62.
13.	Liu W, Jiang Q. Theoretical analysis of the pathogenesis of rheumatoid arthritis “dampness, heat and blood stasis”. Zhong Yi Za Zhi 2020; 61: 2148-53.
14.	Liu X, Li X, Li X, et al. The efficacy and safety of total glucosides of peony in the treatment of primary Sjögren’s syndrome: a multi-center, randomized, double-blinded, placebo-controlled clinical trial. Clin Rheumatol 2019; 38: 657-64. DOI
15.	Liu G, Wang Z, Li X, et al. Total glucosides of paeony (TGP) alleviates constipation and intestinal inflammation in mice induced by Sjögren’s syndrome. J Ethnopharmacol 2020; 260: 113056. DOI URL
16.	Feng R, Chen J, Liu C, et al. A combination of Pueraria lobata and Silybum marianum protects against alcoholic liver disease in mice. Phytomedicine 2019; 58: 152824. DOI URL
17.	Wang S, Zhang S, Wang S, Gao P, Dai L. A comprehensive review on Pueraria: insights on its chemistry and medicinal value. Biomed Pharmacother 2020; 131: 110734. DOI PMID
18.	Chen X, Yu J, Shi J. Management of diabetes mellitus with puerarin, a natural isoflavone from Pueraria lobata. Am J Chin Med 2019; 46: 1771-89. DOI URL
19.	Son Y, Kook S, Lee J. Glycoproteins and polysaccharides are the main class of active constituents required for lymphocyte stimulation and antigen-specific immune response induction by traditional medicinal herbal plants. J Med Food 2017; 20: 1011-21. DOI URL
20.	Gu SH, Kong WS, Zhang T, et al. Chemical constituents and pharmacological effects of Atractylodes macrocephala Koidz. Progress of compound clinical application. Zhong Hua Zhong Yi Yao Xue Kan 2020; 38: 69-73.
21.	Du X, Bai Y, Shen H. Hu Yinqi’s experience in treating primary Sjogren’s syndrome from toxin, blood stasis and deficiency. Zhong Yi Za Zhi 2020; 61: 1594-7.
22.	Xu X, Lü H, Li X, Su H, Zhang X, Yang J. Danshen attenuates osteoarthritis-related cartilage degeneration through inhibition of NF-κB signaling pathway in vivo and in vitro. Biochem Cell Biol 2017; 95: 644-51.
23.	Ma L, Tian G, Geng H, et al. Brief introduction of TCM pharmacology database TCMSP and its analytical application. Zhong Guo Xun Zheng Xin Xue Guan Yi Xue Za Zhi 2020; 12: 1413-6.
24.	Luo J. A brief introduction to UniProt. Sheng Wu Xin Xi Xue 2019; 17: 131-4.
25.	Zhou Y, Su S. Research methods and progress of compatibility of Traditional Chinese Medicine. Zhong Guo Shi Yan Fang Ji Xue Za Zhi 2019; 25: 202-8.
26.	Liu S, Wang W, Lu F, et al. Retro-origin and modern research review of the theory of medicinal properties of Traditional Chinese Medicine. Zhong Cao Yao 2020; 51: 5099-04.

[1]	ZHI Guoguo, SHAO Bingjie, ZHENG Tianyan, JI Shaoxiu, LI Jingwei, DANG Yanni, LIU Feng, WANG Dong. Efficacy of Ganshuang granules (肝爽颗粒) on non-alcoholic fatty liver and underlying mechanism: a network pharmacology and experimental verification [J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 122-130.
[2]	YANG Ye, CHEN Xiaoyang, YAO Junkai, HU Yueyao, WANG Wei. Efficacy of Danlou tablet (丹蒌片) on myocardial ischemia/ reperfusion injury assessed by network pharmacology and experimental verification [J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 131-144.
[3]	ZHANG Qi, CHEN Dexuan, ZHU Guixiang, ZHANG Shihu, FENG Xiao, MA Chaoqun, ZHANG Yi. Efficacy of Tounongsan decoction (透脓散方) on pyogenic liver abscess: network pharmacology and clinical trial validation [J]. Journal of Traditional Chinese Medicine, 2024, 44(1): 145-155.
[4]	REN Hui, ZHAO Lintao, GAO Kai, YANG Yuanyuan, CUI Xiaomin, HU Jing, CHEN Zhiyong, LI Ye. Deciphering the chemical profile and pharmacological mechanism of Jinlingzi powder (金铃子散) against bile reflux gastritis using ultra-high performance liquid chromatography coupled with Q exactive focus mass spectrometry, network pharmacology, and molecular docking [J]. Journal of Traditional Chinese Medicine, 2023, 43(6): 1209-1218.
[5]	YANG Xirui, ZHAO Hui, SHAN Muhammad, DONG Feixue, ZHANG Dandan, WANG Jixue, YUAN Xingxing. Efficacy of bioactive compounds of Chaihu (Radix Bupleuri Chinensis) on glaucomatous optic atrophy through interleukin-6/hypoxia inducible factor-1α signal pathway [J]. Journal of Traditional Chinese Medicine, 2023, 43(6): 1219-1226.
[6]	HAN Huagang, LI Ziqiang, OUYANG Jingfeng, WANG Tianquan, DONG Lingyan, CAO Junling. Mechanism of Lingbao Huxin Dan (灵宝护心丹) in the treatment of bradyarrhythmia complicated with coronary heart disease: a network pharmacology analysis [J]. Journal of Traditional Chinese Medicine, 2023, 43(5): 1001-1009.
[7]	JIA Lihua, KUANG Haodan, XU Yuan. Efficacy of Buzhong Yiqi decoction (补中益气汤) on benign prostatic hyperplasia and its possible mechanism [J]. Journal of Traditional Chinese Medicine, 2023, 43(3): 533-541.
[8]	JIA Lihong, TIE Defu, FAN Zhaohui, CHEN Dan, CHEN Qizhu, CHEN Jun, BO Huaben. Mechanism underlying Fanmugua (Fructus Caricae) leaf multicomponent synergistic therapy for anemia: data mining based on hematopoietic network [J]. Journal of Traditional Chinese Medicine, 2023, 43(3): 542-551.
[9]	LI Yue, WEN Shuting, ZHAO Runyuan, FAN Dongmei, ZHAO Dike, LIU Fengbin, MI Hong. Efficacy of active ingredients in Qingdai (Indigo Naturalis) on ulcerative colitis: a network pharmacology-based evaluation [J]. Journal of Traditional Chinese Medicine, 2023, 43(1): 124-133.
[10]	ZHOU Kaixuan, ZHANG Dong, BAO Huiwei, LI Lijing. Network pharmacology and molecular docking study on the effect of Kaempferol in treatment of metabolic associated fatty liver disease [J]. Journal of Traditional Chinese Medicine, 2022, 42(5): 788-794.
[11]	JIANG Zong, YAO Xiaoling, MA Wukai, TANG Fang. Molecular mechanism analysis of Miao medicine Jinwujiangu decoction (金乌健骨方) in treating osteoarthritis based on a network pharmacology approach [J]. Journal of Traditional Chinese Medicine, 2022, 42(4): 576-585.
[12]	QIAO Nan, WANG Qinnan, MA Chaoqun, CHEN Dexuan, CHEN Haidong, LU Yaoyao. Mechanism underlying efficacy of Shugan Sanjie decoction (疏肝散结汤) on plasma cell mastitis, based on network pharmacology and experimental verification [J]. Journal of Traditional Chinese Medicine, 2022, 42(3): 400-407.
[13]	LI Zhiyong, ZHU Na, LI Jianliang, FENG Liang, JIANG Yanyan, LI Caifeng, LIN Ling, HUANG Xiulan. Effcacy-oriented compatibility for Tianma (Rhizoma Gastrodiae), Yanlingcao (Trillium tschonoskii Maxim) and Bingpian (Borneolum Syntheticum) on improving cerebral ischemia stroke by network pharmacology and serum pharmacological methods [J]. Journal of Traditional Chinese Medicine, 2022, 42(3): 408-416.
[14]	WU Jiashuo, ZHANG Fangqing, LI Zhuangzhuang, JIN Weiyi, SHI Yue. Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review [J]. Journal of Traditional Chinese Medicine, 2022, 42(3): 479-486.
[15]	DENG Qianlan, LU Yueting, YAN Lijuan, LU Hualin, JIN Ruizhe, XU Yanzhi, SONG Jing, LIU Tiejun. Mechanism of Huashi Xingyu Qingre recipe (化湿行淤清热方) in treating oral lichen planus based on network pharmacology and clinical trial verification [J]. Journal of Traditional Chinese Medicine, 2022, 42(2): 304-313.

Home

Online First

Author Center

Reviewer Center

Issues

Announcement

About Us