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6TMR Modern Herbal Medicine  2019, Vol. 2 Issue (3): 140-150    DOI: 10.12032/TMRmhm2017A52
Orginal Article     
Analysis of drug use law and mechanism of prostate cancer based on data mining and network pharmacology
Yao Yang1, Ying Chen1, Zhen-ning Yang2, Guo-wei Zhang1()
1College of Chinese Medicine, Hebei University, Baoding, Hebei province, China.
2 Heibei University of Chinese Medicine, Shijiazhuang, Hebei, China.
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Abstract

Objective: Excavate the medication rule of traditional Chinese medicine in the treatment of prostate cancer, and predicting the biomolecular level mechanism of high-frequency drug compatibility. Methods: Relevant documents in CNKI, Wanfang Medical Network and VIP Chinese Biomedical Periodical Database Pubmed, EMbase were collected and collated systematically. Frequency statistics, association rule analysis and new party mining were carried out using TCMISSV2.5. BATMAN-TCM was used to analyze the interaction relationship and related pathways between high-frequency drug targets. Results: Huangqi (Astragalus membranaceus) was the single drug most used of the 102prescriptions included in the standard. There are 6 pairs of combinations with high confidence in association rule analysis. System entropy cluster analysis resulted in 20 core drug combinations and 9 new prescriptions. Through KEGG pathway analysis of Huangqi, Fuling (Poria cocos), Gancao (Glycyrrhiza uralensis) and Dihuang (Rehmannia glutinosa), it was found that the number of potential targets of the neural active ligand receptor rented pathway and purine metabolism pathway was the largest. Conclusions: Prostate cancer is mainly treated with deficiency-tonifying drugs, which are combined with drugs for promoting blood circulation, removing blood stasis, clearing heat, promoting diuresis, detoxifying and resolving hard mass. The mechanism of action of high-frequency traditional Chinese medicine may be realized by interfering with the neuroactive ligand receptor interaction pathway and purine metabolism pathway.

Highlights

This article found that deficiency-tonifying drugs, which are combined with drugs for promoting blood circulation, removing blood stasis, clearing heat, promoting diuresis, detoxifying and resolving hard mass are commonly used to treat prostate cancer. Core herbs may play their role by interfering with the neuroactive ligand-receptor interaction pathway and purine metabolic pathway.



Key wordsprostate cancer      medication law      mechanism of action      data mining      network pharmacology     
Published: 29 July 2019
Fund:  This work was funded by the National Natural Science Foundation of Hebei (No.H2018201179), Hebei University of Science and Technology (No. QN2016077), and Health and Family Planning Commission of Hebei (No. 20160388).
Cite this article:

Yao Yang, Ying Chen, Zhen-ning Yang, Guo-wei Zhang. Analysis of drug use law and mechanism of prostate cancer based on data mining and network pharmacology. 6TMR Modern Herbal Medicine, 2019, 2(3): 140-150. doi: 10.12032/TMRmhm2017A52

URL:

https://www.tmrjournals.com/mhm/EN/10.12032/TMRmhm2017A52     OR     https://www.tmrjournals.com/mhm/EN/Y2019/V2/I3/140

Figure 1. Inclusion of medical record extraction process
No. Drug Frequency No. Drug Frequency
1 Astragalus membranaceus 38 11 Zedoray turmeric 13
2 Poria cocos 35 12 Radix pseudostell 12
3 Glycyrrhiza uralensis 26 13 Rhizoma pollgonati 12
4 Rehmannia glutinosa 25 14 Phellodendron 12
5 Hedyotis diffusa 22 15 Pangolin 11
6 Barbated skullcup 21 16 Turtle shell 11
7 Atractylodes rhizome 19 17 Lanceolata 11
8 Wolfberryfruit 17 18 Tangerine Peel 10
9 Polyporus 15 19 Angelica sinensis 10
10 Coix seed 14 20 Liriope 10
Table 1 Frequency distribution of medium and high frequency drugs in prescriptions for prostate cancer (Frequency ≥10)
Item Property flavors attributive channel Frequency Item property flavors attributive channel Frequency
Four natures warm 201 Channel tropism Spleen 302
cold 199 Liver 277
calm 182 Kidney 242
cool 41 Lung 212
hot 15 Heart 177
Five flavours sweet 409 Stomach 176
bitter 277 Bladder 69
pungent 171 Large intestine 68
salty 48 Small intestine 46
acrid 26 gallbladder 25
astringent 22 pericardium 16
San jiao 1
Table 2 Distribution of property flavors attributive channel in prescriptions for treatment of prostate cancer
No. Symptom Frequency
1 deficiency of the spleen and the kidney 19
2 combination of blood stasis and toxin 15
3 damp-heat-stagnation-type 10
4 deficiency of the kidney essence 6
5 downward Flow of Damp-heat in bladder 6
6 deficiency of qi and yin of spleen and kidney 6
7 asthenia kidney yin 5
Table 3 Distribution of main symptom types of prostate cancer (Frequency ≥5)
No. Drug combination Support No. Drug combination Support
1 Astragalus membranaceus, Poria cocos 21 7 Liquorice root, Poria cocos 13
2 Poria cocos, Rehmannia glutinosa 16 8 Poria cocos, Barbated skullcup 13
3 Astragalus membranaceus , Glycyrrhiza uralensis 14 9 Heterophylly
Radix pseudostell, Milkvetch root
12
4 Largehead atractylodes rhizome, Poria cocos 14 10 Astragalus membranaceus, Rehmannia root 12
5 Astragalus membranaceus, Largehead atractylodes rhizome 13 11 Wolfberry fruit, Poria cocos 12
6 Astragalus membranaceus, Wolfberry?fruit 13
Table 4 Drug combination in prescription for prostate cancer (Support ≥12)
No. Association rules Confidence
1 Wolfberry fruit → Astragalus membranaceus 0.764705882
2 Atractylodes rhizome → Poria cocos 0.736842105
3 Wolfberry fruit → Poria cocos 0.705882353
4 Atractylodes rhizome → Astragalus membranaceus 0.684210526
5 Rehmannia glutinosa →Poria cocos 0.64
6 Barbated skullcup → Poria cocos 0.619047619
Table 5 Association rules of drugs in prescriptions for treatment of prostate cancer (Confidence ≥0.6)
Figure 2 Core drug network showcase
Drug pair Correlation coefficient Drug pair Correlation coefficient
Rehmannia glutinosa _ Antler glue 0.04563591 Turtle shell_ Seaweed 0.04032505
Antler glue _ Eupolyphaga seu Steleophaga 0.04534996 Seaweed _ Pangolin 0.04032505
Pleione rhizome _ Rehmannia glutinosa 0.0438329 Hedyotis diffusa _ Common anemarrhena 0.03942031
Rehmannia glutinosa _ Americanwater plantain 0.04371169 Astragalus membranaceus _ Safflower 0.03922832
Centipede _ Safflower 0.04225674 Astragalus membranaceus _ Chinaberry fruit 0.03922832
Rehmannia glutinosa _ Wolfberry?fruit 0.04090416 Rhubarb _ Wolfberry fruit 0.03910515
agrimony _ Radix Polygonum 0.04081935 Pleione rhizome _ Gecko 0.03866586
Centipede _Turtle shell 0.04032505 Astragalus membranaceus _ Cortex moutan 0.03854257
Centipede _ Pangolin 0.04032505
Table 6 Correlation degree of drugs in prescriptions for treatment of prostate cancer (Correlation coefficient ≥0.038)
No. Core composition No. Core composition
1 Liriope_ almond _ Coptis chinensis 11 Liriope_ Fructus Tritici Ievis _ Schisandra chinensis
2 Lanceolata_Turtle shell_ Indian strawberry 12 Lanceolata_ Donkey hide gelatin _ Plastrum testudinis
3 Lanceolata_Turtle shell_ Poria cocos 13 Poria cocos _ Safflower _ Chinaberry fruit
4 fritillaria _ Glycyrrhiza uralensis _ Zedoary turmeric 14 Fritillaria _ Coix seed _ Zedoary turmeric _Polyporus
5 Astragalus membranaceus _Aconite _ Cinnamon 15 Astragalus membranaceus _ Wolfberry?fruit _Rhizoma pollgonati
6 Coix seed _Radix pseudostell_Polyporus 16 Eupatorium _ Tangerine Peel _Radix pseudostell_ Atractylodes rhizome
7 Oyster _ Bupleurum _ Scutellaria 17 Oyster _ Bupleurum _ Curcuma longa
8 Achyranthes root _ Stings of Gleditsia sinensis Lam _ Ground beetle 18 Stings of Gleditsia sinensis Lam _ Mu tong _ Eupolyphaga seu Steleophaga
9 Turtle shell_ Rehmannia glutinosa _ Pangolin 19 Eupatorium _ Rehmannia glutinosa _ Tangerine peel _Radix pseudostell
10 Eupatorium _ Hedyotis diffusa _ Tangerine peel _ Barbated skullcup 20 Coix seed _ Hedyotis diffusa _ Zedoary turmeric _Polyporus
Table 7 Core drug combinations in prescriptions for prostate cancer
No. New prescriptions combination
1 Liriope_ Almond _ coptis chinensis_ Fructus Tritici Ievis _ Schisandra chinensis
2 Lanceolata_Turtle shell_ Indian strawberry_Donkey hide gelatin_Plastrum testudinis
3 Fritillaria _ Glycyrrhiza uralensis _ Zedoary turmeric_ Coix seed _Polyporus
4 Astragalus membranaceus _Aconite _ Cinnamon_ Wolfberry?fruit _Rhizoma pollgonati
5 Coix seed _Radix pseudostell_Polyporus_eupatorium _ Tangerine Peel _ Atractylodes rhizome
6 Oyster _ Bupleurum _ Scutellaria_Curcuma longa
7 Achyranthes root _ Stings of Gleditsia sinensis Lam _Ground beetle_ Mu tong _ Eupolyphaga seu Steleophaga
8 Turtle shell_ Rehmannia glutinosa _Pangolin_eupatorium _ Tangerine _Radix pseudostell
9 Eupatorium _ Hedyotis diffusa _ Tangerine _ Barbated skullcup _ Coix seed _ Zedoary turmeric_Polyporus
Table 8 New prescriptions for prostate cancer
No. Disease name Potential targets
1 anodyne 29
2 cardiovascular disease 11
3 pain 9
4 schizophrenia 9
5 parkinson disease 9
6 migraine 9
7 hypertension 9
8 alzheimer s disease 8
9 prostate cancer 7
10 neurodegenerative diseases 7
11 erectile dysfunction 7
Table 9 Enrichment Analysis of compatible diseases of 4 drugs (Target number ≥7)
No. KEGG pathway potential targets
hsa00190 Oxidative Phosphorylation 13
hsa00230 Purine Metabolism 33
hsa00250 Alanine, Aspartate And Glutamate Metabolism 13
hsa00330 Arginine And Proline Metabolism 13
hsa00480 Glutathione Metabolism 31
hsa00980 Metabolism Of Xenobiotics By Cytochrome P450 24
hsa00982 Drug Metabolism - Cytochrome P450 21
hsa04020 Calcium Signaling Pathway 31
hsa04022 CGMP - PKG Signaling Pathway 20
hsa04080 Neuroactive Ligand-Receptor Interaction 65
hsa04260 Cardiac Muscle Contraction 17
hsa04270 Vascular Smooth Muscle Contraction 12
hsa04724 Glutamatergic Synapse 17
hsa04725 Cholinergic Synapse 14
hsa04726 Serotonergic Synapse 19
hsa04728 Dopaminergic Synapse 14
hsa04918 Thyroid Hormone Synthesis 13
Table 10. KEGG pathway analysis (Target number ≥12)
Figure 3 Visualization of Potential Targets, Signal Pathways and Disease Networks
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