
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

39029075
MD-D-23-07335
00077
10.1097/MD.0000000000039000
3
3900
Research Article
Clinical Trial/Experimental Study
PTGS2 as target of compound Huangbai liquid in the nursing of pressure ulcer
Guo Dongmei MD 857551565@qq.com
a
Ma Yanhong MD runse6662022@163.com
b
Zhang Nan MD 13131231066@163.com
c
Zhang Yan MD zhangyan231229@163.com
d*
https://orcid.org/0000-0003-2124-0583
Guo Suzhi MD guosuzhi2022@163.com
b
a Department of Nursing, Baoding Second Hospital, Baoding City, China
b Department of ICU, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
c Department E of Cardiology, Baoding Second Hospital, Baoding City, China
d Department of Hepatobiliary Surgery, Baoding Second Hospital, Baoding City, China.
* Correspondence: Yan Zhang, Department of Hepatobiliary Surgery, Baoding Second Hospital, Baoding City, China (e-mail: zhangyan231229@163.com).
19 7 2024
19 7 2024
103 29 e3900026 8 2023
02 1 2024
28 6 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

Objective:

Pressure ulcer refers to ulceration and necrosis caused by local skin and cell tissues being compressed for a long time, continuous ischemia, hypoxia, and malnutrition. However, role of prostaglandin-endoperoxide synthase 2 (PTGS2) in the management of pressure ulcers in with compound Huangbai liquid is still unclear.

Methods:

Traditional Chinese medicine components and related targets of compound Huangbai liquid were collected through traditional Chinese medicine systems pharmacology (TCMSP) and Batman-traditional Chinese medicine database. Disease-related targets were obtained using the Gene Cards database. The protein-protein interaction (PPI) network was constructed using the Search tool for retrieval of interacting genes (STRING) and analyzed by Cytoscape to obtain the core components. To evaluate the clinical efficacy of the compound Huangbai liquid in the treatment of pressure ulcers, 40 patients with pressure ulcers were selected and divided into an observation group and a control group, with 20 individuals in each group. The observation group received treatment with compound Huangbai liquid.

Results:

Sixty-five components and 480 targets of compound Huangbai liquid were obtained from TCMSP and Batman - traditional Chinese medicine databases. Two hundred seventy-three pressure ulcer-related targets were obtained. Seventy-two potential targets of compound Huangbai pigment in treatment of pressure ulcer were obtained, and 2 unrelated targets were deleted. There were 70 nodes and 1167 edges in PPI network. Gene ontology (GO) function is involved in biological processes such as reactive oxygen species metabolism and cellular response to chemical stress. Cellular components such as platelet α granules lumen and membrane rafts were involved. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that compound Huangbai liquid in treatment of pressure ulcer. The clinical results indicate that the compound Huangbai liquid has a good therapeutic effect on pressure ulcers.

Conclusion:

PTGS2 may be a target for treatment of pressure ulcers with compound Huangbai liquid, providing a new direction for its treatment.

compound Huangbai liquid
molecular targets
pressure ulcer
PTGS2
OPEN-ACCESSTRUE
==== Body
pmc1. Introduction

Pressure ulcers are caused by prolonged pressure on local tissues.[1] Vertical pressure, friction, and shear force have an impact on the formation of pressure ulcers. Systemic nutrient deficiency, obstruction, and insufficient nutrient intake cause blood circulation disorders leading to pressure ulcers.[2] Pressure ulcers can cause local pain, and itching can occur in combination with infection. The treatment of pressure ulcers includes drug therapy, physical therapy, traditional Chinese medicine topical therapy and surgery.[3] From a nursing perspective, the difficulty coefficient of pressure ulcers increases. However, the cause and nursing mechanism of pressure ulcers are not clear. Therefore, it is important to a deep study on the molecular mechanism of compound Phelloderma var. in the nursing of pressure ulcers.

Compound Huangbai liquid is a compound preparation with main ingredients are Phellodendron, fructus forsythia, dandelion, honeysuckle, centipede and other traditional Chinese medicine preparations, resulting in a red-brown potion.[4] Compound Huangbai liquid is a combination of anti-itch, anti-inflammatory, and properties. It possesses heat-clearing and detoxifying, swelling reduction, and antibacterial effects. It is suitable for inflammatory skin diseases, herpes zoster, acne, rosacea, paronychia, and other conditions. Unlike general Western medicine antibiotics, compound Huangbai liquid does not target specific strains and can be used for long-term treatment.[5]

Network pharmacology is a new discipline based on theory of systems biology, which analyzes network of biological systems.[6] Network pharmacology emphasizes the multi-pathway regulation of signaling pathways to improve the therapeutic effects of drugs and reduce toxic and side effects. This approach aims to enhance the success rate of clinical trials for new drugs and save costs in drug research and development.[7] Network pharmacology is widely used in traditional Chinese medicine and provides new insights into the study of complex systems in traditional Chinese medicine.[8]

Prostaglandin-endoperoxide synthase 2 (PTGS2) is an induced response gene. Prostaglandin-endoperoxidase synthase (PTGS) is an enzyme in prostaglandin biosynthesis, and it serves dual roles as a dioxygenase and peroxidase.[9] Through comprehensive bioinformatics analysis, PTGS2 has been identified as a biomarker for acute myocardial infarction.[10] However, the relationship between PTGS2 and compound Huangbai liquid and pressure ulcers remains unclear.

The study aims to utilize network pharmacological technology to explore and identify PTGS2 as a potential molecular target of compound Huangbai liquid. Subsequently, potential enrichment analysis and pathway analysis will be conducted to understand its role in pressure ulcer. Public datasets were be employed to validate the involvement of PTGS2 in pressure ulcers.

2. Methods

2.1. The traditional Chinese medicine components and related targets of compound Huangbai liquid were collected

In the traditional Chinese medicine systems pharmacology (TCMSP) database[11] to retrieve the 5 kinds of traditional Chinese medicine of compound Huangbai liquid, cortex phellodendri, fructus forsythiae, dandelion, honeysuckle, centipede, with Oral Bioavailability ≥ 30% and Drug likeness ≥ 0.18 were selected as screening conditions to obtain chemical components and corresponding targets of each traditional Chinese medicine. If TCMSP database without corresponding to traditional Chinese medicine (TCM), is to use Batman - TCM database[12] search, target selection conditions for “score cutoff = 20.” Integrate the results of the 2 databases that will predict target import UniProt protein database (http://www.uniprot.org/)[13] into a “Gene symbol” format.

2.2. Disease-related target acquisition

GeneCards database (www.genecards.org/) is an integration of genome, transcriptome and comprehensive database of information such as proteomics,[14] with the keyword “Pressure ulcers” screening related target gene information, set the selection criteria “score > 10.”

2.3. Acquisition of protein-protein interaction network and core components

The intersection of traditional Chinese medicine and disease targets was taken to obtain potential therapeutic targets of compound Huangbai liquid in treatment of skin pressure ulcer. Search tool for retrieval of interacting genes (STRING)[15] potential therapeutic targets in the input, model select Multiple Proteins, Organis choose Homo Sapiens, confidence to choose 0.7, delete the network independent targets, TSV files of protein-protein interaction (PPI) were obtained and imported into Cytoscape[16] to visualize network.

The MCODE program built into Cytoscape was used to perform cluster analysis of therapeutic targets, and target containing the largest cluster was taken as the core target. The MCC algorithm in cytoHubba program built into Cytoscape was used to obtain top 5 targets as hub genes of this study.

The intersection of the targets corresponding to each compound of traditional Chinese medicine and core targets was taken, and the drug components without core targets were excluded as active components. The degree value of the network was calculated by Cytoscape, and the top 5 compounds were obtained as the core components.

2.4. Enrichment analysis

Under the condition of “P < .05,” gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of obtained core targets were performed by R package clusterProfiler.[17] GO enrichment and the signaling pathways potentially related to pressure ulcer in KEGG enrichment were screened. The R package ggplot2 was used to display top 10 results.

The core target imports TRRUST2.0 database (https://www.grnpedia.org/trrust/),[18] for prediction of transcription factor. Finally, the Cytoscape was used to draw multi-dimensional network of “active ingredient-target-KEGG pathway-disease.”

2.5. Molecular docking

From the research collaboratory for structural bioinformatics database[19] search key targets in 3-dimensional structure of protein, to download and store it for protein data bank (PDB) file format. From zinc database (https://zinc.docking.org/)[20] to get key Chinese native medicine ingredients of 3-dimensional molecular structure, using software conversion for PDB protein file format. PyMOL software[21] was used to remove all water molecules in the protein structure and add hydrogen atoms. The original small molecule ligand in the docking pocket was removed, and the processed protein was also saved in PDB file format. The AutoDock Vina 1.1.2[22] was used for molecular docking study between processed proteins and core components, the minimum binding energy between the 2 was calculated. Finally, PyMOL software was used to visualization several docking complexes with the lowest binding energy.

2.6. Clinical verifications

A total of 40 patients with pressure ulcers were selected and divided into an observation group and control group, 20 cases in each group. The observation group was treated with compound Huangbai liquid. To verify the clinical effect of Huangbai compound liquid on pressure ulcers. Used the Braden Scale for pressure ulcer risk assessment included 6 indicators: Sensory perception, Friction and shear, Moisture, Activity, Mobility, and Nutrition. A lower total score indicated a higher risk of pressure ulcers.

3. Results

3.1. Traditional Chinese medicine components and targets of compound Huangbai liquid

A total of 65 components and 480 targets of compound Huangbai liquid were obtained from TCMSP and BATANT-TCM databases. These included 24 types of golden cypress, 19 types of Forsythe, 16 types of Lonicera japonicum, 8 types of dandelion, and 5 types of centipede. One component was shared between Phellodendron and honeysuckle, 2 components were shared among Phellodendron, honeysuckle and Forsytha flos, and 2 components were shared between forsythia and honeysuckle. Specific information about the compounds is provided in Table 1.

Table 1 Information on the chemical composition of Chinese medicines.

Compound	Molecular formula	Origin	
Berberine	C20H18NO4	Phellodendri Chinrnsis Cortex	
Coptisine	19H14NO4	Phellodendri Chinrnsis Cortex	
Phellavin_qt	C26H30O12	Phellodendri Chinrnsis Cortex	
delta 7-stigmastenol	C29H48O	Phellodendri Chinrnsis Cortex	
Phellopterin	C17H16O5	Phellodendri Chinrnsis Cortex	
Dehydrotanshinone II A	C19H16O3	Phellodendri Chinrnsis Cortex	
Rutaecarpine	C18H13N3O	Phellodendri Chinrnsis Cortex	
Skimmianin	C14H13NO4	Phellodendri Chinrnsis Cortex	
Chelerythrine	C21H18ClNO4	Phellodendri Chinrnsis Cortex	
Worenine	C20H16NO4	Phellodendri Chinrnsis Cortex	
Cavidine	C21H23NO4	Phellodendri Chinrnsis Cortex	
Magnograndiolide	C15H22O4	Phellodendri Chinrnsis Cortex	
Palmatine	C21H22NO4	Phellodendri Chinrnsis Cortex	
Fumarine	C41H63NO14	Phellodendri Chinrnsis Cortex	
Isocorypalmine	C20H23NO4	Phellodendri Chinrnsis Cortex	
Phellamurin_qt	C26H30O11	Phellodendri Chinrnsis Cortex	
(S)-Canadine	C20H21NO4	Phellodendri Chinrnsis Cortex	
Poriferast-5-en-3beta-ol	C29H48O2	Phellodendri Chinrnsis Cortex	
Berberrubine	C19H16ClNO4	Phellodendri Chinrnsis Cortex	
Campesterol	C28H48O	Phellodendri Chinrnsis Cortex	
Thalifendine	C19H15NO4	Phellodendri Chinrnsis Cortex	
Wogonin	C16H12O5	Forsythiae Fructus	
(2R,3R,4S)-4-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-2,3-dimethylol-tetralin-6-ol	C20H24O6	Forsythiae Fructus	
(3R,4R)-3,4-bis[(3,4-dimethoxyphenyl)methyl]oxolan-2-one	C13H22O	Forsythiae Fructus	
(+)-Pinoresinol monomethyl ether	C48H50O16	Forsythiae Fructus	
PHILLYRIN	C27H34O11	Forsythiae Fructus	
ACon1_001697	C27H34O11	Forsythiae Fructus	
(+)-pinoresinol monomethyl ether-4-D-beta-glucoside_qt	C27H34O11	Forsythiae Fructus	
3beta-Acetyl-20,25-epoxydammarane-24alpha-ol	C30H52O3	Forsythiae Fructus	
Mairin	C30H48O3	Forsythiae Fructus	
FORSYTHINOL	C21H24O6	Forsythiae Fructus	
(-)-Phillygenin	C21H24O6	Forsythiae Fructus	
Hyperforin	C35H52O4	Forsythiae Fructus	
Onjixanthone I	C16H14O6	Forsythiae Fructus	
Arctiin	C27H34O11	Forsythiae Fructus	
Bicuculline	C20H17NO6	Forsythiae Fructus	
Mandenol	C20H36O2	Lonicerae Japonicae Flos	
Ethyl linolenate	C20H34O2	Lonicerae Japonicae Flos	
Eriodyctiol (flavanone)	C15H12O6	Lonicerae Japonicae Flos	
secologanic dibutylacetal_qt	C13H28O3	Lonicerae Japonicae Flos	
beta-carotene	C40H56	Lonicerae Japonicae Flos	
ZINC03978781	C35H58O6	Lonicerae Japonicae Flos	
Chryseriol	C16H12O6	Lonicerae Japonicae Flos	
5-hydroxy-7-methoxy-2-(3,4,5-trimethoxyphenyl)chromone	C19H18O7	Lonicerae Japonicae Flos	
Centauroside_qt	C34 H46 O19	Lonicerae Japonicae Flos	
Loniceracetalides B_qt	C17H26O10	Lonicerae Japonicae Flos	
Dinethylsecologanoside	C22H26O6	Lonicerae Japonicae Flos	
Taraxasterol	C30H50O	Taraxacum Mongolicum	
Chrysanthemaxanthin	C40H56O3	Taraxacum Mongolicum	
Choline	C5H14NO+	Taraxacum Mongolicum	
Scopoletin	C10H8O4	Taraxacum Mongolicum	
Flavoxanthin	C40H56O3	Taraxacum Mongolicum	
Esculetin	C9H6O4	Taraxacum Mongolicum	
Caffeicacid	C9H8O4	Taraxacum Mongolicum	
Taraxerol	C30H50O	Taraxacum Mongolicum	
Histamine	C5H9N3	Centipede	
Leucine	C6H13NO2	Centipede	
Tyrosin	C12H17NO3	Centipede	
L-Histidine	C6H9N3O2	Centipede	
Cholesterol	C27H46O	Centipede	
Beta-sitosterol	C30H52O	Phellodendri Chinrnsis Cortex, Forsythiae Fructus, Lonicerae Japonicae Flos	
Quercetin	C15H10O7	Phellodendri Chinrnsis Cortex, Forsythiae Fructus, Lonicerae Japonicae Flos	
Stigmasterol	C29H48O	Phellodendri Chinrnsis Cortex, Lonicerae Japonicae Flos	
Kaempferol	C15H10O6	Forsythiae Fructus, Lonicerae Japonicae Flos	
Luteolin	C15H10O6	Forsythiae Fructus, Lonicerae Japonicae Flos	

3.2. Pressure ulcer related targets

In the Genecards database, the search condition of “score > 10” was set, and a total of 273 disease targets were obtained after standardized processing in the UniProt database.

3.3. PPI network and core components

In this study, 72 potential targets of compound Huangbai liquid in the treatment of pressure ulcers were obtained, and 2 unrelated targets were removed. The PPI network analysis revealed 70 nodes and 1167 edges (Fig. 1A and B). Molecular complex detection cluster analysis showed that 40 targets clustered into the largest category as core targets of compound Huangbai liquid in treatment of skin pressure ulcer (Fig. 1C). Figure 1D shows that the top 5 targets scored by MCC algorithm of cytoHubba plug-in are interleukin-1β, tumor necrosis factor (TNF), interleukin-6, prostaglandin-endoperoxide synthase 2 (PTGS2), and protein kinase B1. These targets serve as hub targets for this study.

Figure 1. PPI network of potential therapeutic targets that Fufang Huangbai acting on Pressure ulcer (A) PPI Network of potential therapeutic targets. (B) PPI network of core targets. (C) PPI network of hub genes. PPI = protein-protein interaction.

By intersecting of compound targets with the core targets, a total of 49 active ingredients were obtained. An active ingredient-core target network was constructed, and the degree value of each target was calculated. The top 5 compounds were Quercetin, Luteolin, Wogonin, Kaempferol and Rutaecarpine (Fig. 2).

Figure 2. Ranking of core ingredients (Top5).

3.4. GO, KEGG and transcription factor analysis

The GO function analysis revealed the involvement of compound Huangbai liquid in various biological processes, including reactive oxygen species metabolism, cellular response to chemical stress, and other biological processes. Cellular components such as platelet α granules lumen and membrane rafts were involved. It is involved in the molecular functions such as growth factor receptor binding and cytokine activity (Fig. 3A). KEGG enrichment results indicated that compound Huangbai liquid in treatment of pressure ulcers may exert its effect through pathway such as the AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, cytokine receptor interaction, TNF signaling pathway, interleukin 17 signaling pathway, etc (Fig. 3B). Figure 3C shows that top 10 transcription factors are NFKB1, RELA, STAT3, etc. Multi-dimensional network of “active ingredient-target-KEGG signaling pathway-disease” was constructed. In the figure, green represents active ingredient, red represents core target of disease, light blue represents the signaling pathway, and blue represents the disease (Fig. 4).

Figure 3. The results of enrichment analysis (Top10). (A) GO enrichment. (B) KEGG enrichment. (C) Transcription factors. GO = gene ontology, KEGG = Kyoto Encyclopedia of Genes and Genomes.

Figure 4. Active ingredients-Targets-KEGG signaling pathway-Disease multi-dimensional network. KEGG = Kyoto Encyclopedia of Genes and Genomes.

3.5. Molecular docking result

It is generally believed that lower the intermolecular binding energy, higher the receptor-ligand affinity and more stable conformation. Affinity (kcal/mol) less than −4.25 kcal/mol: a certain binding activity. Less than −5.0 kcal/mol: a good binding activity. Less than −7 kcal/mol: a strong binding activity. This study showed that the binding activities of core components and key target proteins were all < −5 kcal/mol, which had good binding activity (Table 2). Some of the results were visualized (Fig. 5).

Table 2 The results of molecular docking.

Target	PDB-ID	Ligand	Affinity (kcal/mol)	
PTGS2	1PXX	Original ligand	−3.5	
		Quercetin	−5.6	
		Kaempferol	−5.8	
		Luteolin	−5.1	
		Wogonin	−5.4	
		Rutaecarpine	−5.2	
IL-1B	1RWN	Original ligand	−4.2	
		Quercetin	−5.5	
		Kaempferol	−6.0	
		Luteolin	−5.1	
		Wogonin	−5.1	
		Rutaecarpine	−5.3	
TNF-α	6OP0	Original ligand	-2.3	
		Quercetin	−5.4	
		Kaempferol	−5.7	
		Luteolin	−5.6	
		Wogonin	−5.2	
		Rutaecarpine	−5.4	
IL6	1ALU	Original ligand	−3.0	
		Quercetin	−5.7	
		Kaempferol	−5.9	
		Luteolin	−5.6	
		Wogonin	−5.0	
		Rutaecarpine	−5.3	
AKT1	4GV1	Original ligand	−5.2	
		Quercetin	−7.0	
		Kaempferol	−7.8	
		Luteolin	−8.0	
		Wogonin	−6.3	
		Rutaecarpine	−5.8	
AKT1 = protein kinase B1, IL6 = interleukin-6, PDB = protein data bank, PTGS2 = prostaglandin-endoperoxide synthase 2, TNF = tumor necrosis factor.

Figure 5. Molecular docking 3D diagram.

3.6. The clinical result

Compound Huangbai liquid has good clinical effect on pressure ulcer. After the treatment of pressure ulcer, the scores of sensory perception, friction and shear, moisture, activity, mobility, and nutrition were significantly increased (P < .05) (Table 3).

Table 3 Clinical effect of compound Huangbai liquid on patients with pressure ulcer.

Groups	Risk assessment (scores)	
Sensory perception	Friction and shear	Moisture	Activity	Mobility	Nutrition	
Observation group	3.50 ± 0.513	3.55 ± 0.510	3.10 ± 0.308	3.40 ± 0.503	3.45 ± 0.510	3.15 ± 0.366	
Control group	1.55 ± 0.510	1.20 ± 0.410	1.10 ± 0.308	1.20 ± 0.410	1.15 ± 0.366	1.15 ± 0.366	
P	<.0001	<.0001	<.0001	<.0001	<.0001	<.0001	

4. Discussion

Pressure ulcers refer to localized skin and cellular tissue compression over a prolonged period, leading to local ulcer damage caused by malnutrition.[23] The common population affected by pressure ulcers is those who are bedridden for an extended period, an initially, the skin usually shows erythematous blisters, followed by the formation of open ulcers. Pressure ulcers should be treated promptly, otherwise, they can easily result in necrosis of local cells and tissues.[24] In-depth exploration of molecular mechanism of pressure ulcers is of outmost importance for targeted drug research. The main result of this study is that there are 72 potential targets for the treatment of pressure ulcers with compound Huangbai liquid, among which prostaglandin-endoperoxide synthase 2 (PTGS2) is the key target of this study.

Compound Huangbai liquid has anti-inflammation, sterilizing, and anti-infection effects. It is suitable for various types of bacterial and viral infections. It can reduce the exudation of skin lesions and promote wound healing. Compound Huangbai liquid is rich in flavonoids and polyphenols, which have obvious anti-inflammatory and analgesic effects. It can relieve inflammation and pain symptoms by inhibiting the release of inflammatory factors and reducing the transmission of pain signals.[25] Compound Huangbai liquid also contains a variety of antioxidant substances, which can effectively inhibit the production of free radicals and maintain the normal metabolism and health of cells. Compound Huangbai liquid can regulate the internal environment and improve immunity, thus achieving anti-inflammatory, antibacterial effects, symptoms relief, and promoting rehabilitation. It also has certain immunomodulatory effects, which are beneficial in improving immunity and preventing infections.[26] Compound Huangbai liquid also contains a variety of natural plant extracts, such as clove, angelica dahurica, mint, etc, which have broad-spectrum antibacterial and anti-inflammatory effects. Compound Huangbai liquid can effectively kill a variety of bacteria and viruses, especially common diseases like respiratory tract infections and digestive tract infections.[27]

PTGS2 is one of enzymes involved in the new synthesis of prostaglandins, which is usually induced by inflammatory stimuli.[28] PTGS2 can be induced in other cell types by various stimuli.[29] PTGS2 plays a specific role in inflammatory responses, participating in both aseptic and infectious inflammation and the generation of lytic interaction products.[30] PTGS2 also play a key role in development.[31] It is expressed in response to a variety of cellular challenges and stressors and contributes to skin metabolism.[32] PTGS2 is primarily regulated at the transcriptional level. It is an inducible enzyme that plays a role in inflammatory cascade by producing prostaglandins.[33] PTGS2 can contribute to the improvement of chronic inflammation.[34] PTGS2 inhibitors are commonly used anti-inflammatory drugs with pleiotropic endogenous effects.[35]

PTGS2 is involved in the initial step of synthesizing various important mediators that participate in the initiation and resolution of inflammation. Upon activation, it produces prostaglandins that are implicated in the neurodegenerative processes of various diseases.[36] PTGS2 is dynamically regulated during the onset and resolution of acute inflammation. Increased PTGS2 levels during the initial stage of inflammation lead to prostaglandin E2 (PGE2), which is associated with edema and increased leukocyte trafficking. Subsequent waves of PTGS2 expression produce PGD2 and its degradation products. Inhibiting of PTGS2 during early inflammation blocks leukocyte infiltration, while inhibition PTGS2 during later stages inflammation promotes leukocyte aggregation.[37] PTGS2 is an inducible enzyme that plays a role in inflammatory cascade by producing prostaglandins.[33] It possesses various biological activities, such as inhibiting cell apoptosis and immune surveillance, promoting cell proliferation, and angiogenesis.[38] The clinical treatment of pressure ulcers primarily focuses on improving blood circulation and restoring normal tissue activity. Inflammation can contribute to the formation of blisters in pressure ulcers and even tissue necrosis,[39,40] and PTGS2 is closely associated with inflammation. Therefore, PTGS2 may play a role in pressure ulcers by influencing angiogenesis and inflammation.

Under normal physiological conditions, most tissue cells do not express it, but the process of pathological reactions such as inflammation or swelling and pain is small, and its expression is up-regulated by some cell factors, growth factors, inflammatory mediators, pain promoting factors, hypoxia, hormones and other stimulating factors.PTGS2 is an important rate-limiting enzyme that determines the production of PGE2, which mediates inflammatory responses and is one of the most important regulators of metabolism.[41] PTGS2 can mediate its pro-inflammatory effects through a variety of mechanisms. In addition, PTGS2 can also induce production of vascular endothelial growth factor, which promotes angiogenesis.[42] Therefore, compound Huangbai liquid may play a role in the nursing and treatment of pressure ulcers through PTGS2.

Although this paper has carried out rigorous bioinformatics analysis, there are still some shortcomings. Animal experiments with overexpression or knockdown of the gene were not performed in this study to further verify the function. In the future, clinical studies should be designed with more rigorous and methodologically sound approaches. Ensuring an adequate sample size and employing randomized controlled trials or similar designs will be crucial to minimize biases. Consideration should be given to conducting research across multiple healthcare institutions to enhance external validity.

In summary, PTGS2 may be a molecular target for treatment of pressure ulcers with compound Huangbai fluid, providing a new direction for its treatment.

Author contributions

Conceptualization: Yanhong Ma, Dongmei Guo.

Data curation: Dongmei Guo, Nan Zhang, Yan Zhang, Suzhi Guo.

Formal analysis: Dongmei Guo, Nan Zhang, Yan Zhang, Suzhi Guo.

Investigation: Yan Zhang, Suzhi Guo.

Methodology: Nan Zhang, Yan Zhang, Suzhi Guo.

Project administration: Yan Zhang, Yanhong Ma.

Software: Yan Zhang, Suzhi Guo.

Supervision: Dongmei Guo, Yanhong Ma.

Writing – original draft: Dongmei Guo.

Writing – review & editing: Yan Zhang.

Abbreviations:

GO gene ontology

KEGG Kyoto Encyclopedia of Genes and Genomes

PDB protein data bank

PGE2 prostaglandin E2

PPI protein-protein interaction

PTGS2 prostaglandin-endoperoxide synthase 2

STRING search tool for the retrieval of interacting genes

TCM traditional Chinese medicine

TCMSP traditional Chinese medicine systems pharmacology

TNF tumor necrosis factor

The authors have no funding and conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

How to cite this article: Guo D, Ma Y, Zhang N, Zhang Y, Guo S. PTGS2 as target of compound Huangbai liquid in the nursing of pressure ulcer. Medicine 2024;103:29(e39000).
==== Refs
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