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

doi:10.19852/j.cnki.jtcm.2022.03.007

Journal of Traditional Chinese Medicine ›› 2022, Vol. 42 ›› Issue (3): 408-416.DOI: 10.19852/j.cnki.jtcm.2022.03.007

• Research Article • Previous Articles Next Articles

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

LI Zhiyong¹^,²(), ZHU Na³, LI Jianliang⁴, FENG Liang⁵, JIANG Yanyan⁶, LI Caifeng⁷, LIN Ling³, HUANG Xiulan³

1 Postdoctoral mobile station of environmental biology, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China
2 Center for Analytical Chemistry of Chinese Materia Medica, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
3 Pharmacological Department, School of Pharmacy, Minzu University of China, Beijing, 100081, China
4 Aerosol preparation research center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
5 School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China
6 Department of Chinese Materia Medica Chemistry, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
7 Academician work station, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, 330004, China

Accepted:2021-05-21 Online:2022-06-15 Published:2022-05-20
Contact: LI Zhiyong
About author:Prof. LI Zhiyong, Postdoctoral Mobile Station of Environmental Biology, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. lizhiyong7899@sina.com,Telephone: +86-871-65916664
Supported by:
Natural Science Foundation of China: Study on the Mechanism of Adjusting Yin and Eliminating Toxicity in Tujia Medicine to Treat Vascular Dementia based on Angiogenesis-regulation by Angiogemic Switch and Nrf2/ARE pathway(81473793);Youth Talent Project from Beijing Education Commission: Optimization of Prescription of Tianzhu San, a Tujia medicine, based on Identification and Targeted Separation of Active Ingredients(YETP1293)

Abstract

Abstract:

OBJECTIVE: To evaluate the compatibility of Tianma (Rhizoma Gastrodiae, TM), Yanlingcao (Trillium tschonoskii Maxim, YLC) and Bingpian (Borneolum Syntheticum, BP), and their efficacy in the treatment of cerebral ischemic stroke.

METHODS: Network pharmacology was used to determine the compatibility of TM, YLC, and BP, and their potential mechanism. The middle cerebral artery occlusion (MCAO) rat model was used to evaluate the curative effect of the six combinations of TM, YLC, and BP (TZB1-TZB6) on cerebral ischemia, by using the weight matching method to form. The potential component changes of TM and YLC in the blood and brains of rats were analyzed using ultra performance liquid chromatography-mass spectrometry. Finally, molecular docking linked the results of animal experiments and network pharmacology, determining the potential component contributors of TM and YLC to treating ischemic stroke.

RESULTS: TZB reduced the cerebral infarct volume and protected the nerve cells in MCAO rats. The components of TM and YLC were also identified in the blood and brain homogenate, and BP can facilitate the entry of the components of TM and YLC into the blood and brain. Diosgenin, pennogenin, and gastrodin induced effective binding activities with adenosine receptor a1.

CONCLUSION: We investigate an approach that improves the means of folk prescription combined with multi technology that maybe promote the transformation of Chinese medicinal prescription into component-based Chinese medicine.

Key words: infarction,middle cerebral artery, brain ischemia, molecular docking simulation, Adenosine receptor a1, network pharmacology

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.

Figures/Tables 8

Table 1 Dose distribution of TM, YLC, and BP (g/kg)

Component number	1	2	3
Selected column	A	C	B
Column number	TM	YLC	BP
TZB1	5	2.05	0.049
TZB2	6.14	4	0.076
TZB3	7.68	1.63	0.12
TZB4	9.6	3.2	0.039
TZB5	12	1.31	0.061
TZB6	15	2.56	0.096

Figure 1 BOILED-Egg of compounds; Venn diagram of targets and PPI network of stroke Tianma (Rhizoma Gastrodiae, TM), Yanlingcao (Trillium tschonoskii Maxim, YLC) and Bingpian (Borneolum Syntheticum, BP). A: BOILED-Egg of TM, active/total compounds: 24/34; B: BOILED-Egg of YLC, active/total compounds: 18/38; C: BOILED-Egg of BP, active/total compounds: 12/28; D: Venn diagram of targets; E: protein-protein interaction network of stroke.

Figure 2 KEGG pathways of the core targets relevant to TZB treating stroke KEGG: Kyoto Encyclopedia of Genes and Genomes; TZB: Tianma (Rhizoma Gastrodiae, TM), Yanlingcao (Trillium tschonoskii Maxim, YLC) and Bingpian (Borneolum Syntheticum, BP). A: protein-protein interaction network of the core targets relevant to TZB treating stroke; B: KEGG pathways with the top 20 biological processes screened and classified.

Figure 3 Interaction map between the known targets of stroke and the potential targets related with TZB TZB:Tianma (Rhizoma Gastrodiae, TM), Yanlingcao (Trillium tschonoskii Maxim, YLC) and Bingpian (Borneolum Syntheticum, BP). A: herb-potential target network of TZB treating stroke; B: protein-protein interaction network of the identified common targets related to TZB treating stroke.

Figure 4 TTC staining of the coronal brain sections and infarct volume of MCAO rats TZB: Tianma (Rhizoma Gastrodiae, TM), Yanlingcao (Trillium tschonoskii Maxim, YLC) and Bingpian (Borneolum Syntheticum, BP). A: effects of TZB1-TZB6 on the cerebral infarcted area in the brain of MCAO rats; B: effect of TZB1-TZB6 on the infarct volume of MCAO rats. Data were presented as means with a standard error of the mean (n = 6). aP < 0.05 vs model group.

Figure 5 Effect of TZB1-TZB6 on the histopathological changes of cerebral infarction in MCAO rats (n = 6) TZB:Tianma (Rhizoma Gastrodiae, TM), Yanlingcao (Trillium tschonoskii Maxim, YLC) and Bingpian (Borneolum Syntheticum, BP). A: Nissl staining, ×20; B: HE staining, ×20; C: the bottom showed number of nerve cells in the cerebral infarcted area of MCAO rats treated with TZB1-TZB6, aP < 0.05 vs model group.

Table 2 Best docking conformation between proteins and candidate compounds (kcal/mol)

Bounded protein	Compound	Energy	VDW	H bond
ADORA1	Diosgenin	-122.625	-87.4461	-35.179
ADORA1	Gastrodin	-98.9025	-94.4058	-4.49667
ADORA1	Pennogenin	-104.379	-99.9267	-4.45278
AGTR1	β-Ecdysterone	-92.3166	-75.2538	-17.0628
F2R	Diosgenin	-145.613	-126.238	-19.3751
NR3C1	β-Ecdysterone	-112.741	-91.3191	-21.422
PLG	Caproic Acid	-70.1235	-43.649	-22.4803

Figure 6 Molecular docking of diosgenin, pennogenin, gastrodin and ADORA1 A: Visualization diagram of diosgenin docked with adenosine receptor a1 (ADORA1); B: Visualization diagram of pennogenin docked with ADORA1; Visualization diagram of gastrodin docked with ADORA1; a: best docking posture; b: 3D drawing; c: 2D drawing.

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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

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