










































CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

22  

  

 

Abstract: Purpose: Using transcriptome analysis, we want to learn how compound Danshen dripping pills (CDDP) affect diffuse intravascular 

coagulation (DIC) and what mechanisms CDDP may work by. Research Tools and Procedures: We carried out DIC animal models with various 

inducers and studied the impact of CDDP on many parameters, including survival rate, blood flow to the hepatic and gastric fundi, aberrant 

prothrombin time (PT), fibrinogen (FIB) concentration, inflammatory factors, and the damage index for the liver and kidneys. After that, 

confirmation of the primary target genes was done using whole-blood transcriptome sequencing. The results showed that CDDP increased the 

efficiency of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase, improved blood flow in the stomach and liver, increased PT 

and FIB values, decreased the elevated serum levels of interleukin-10 and tumor necrosis factor-alpha, and increased blood urea nitrogen and 

creatinine. Additionally, it improved the survival rate of the animals used in the study. According to research using whole-blood transcriptome 

sequencing, CDDP may control inflammatory response in the immune system, oxidative stress, activation and aggregation of platelets, and cell 

death in DIC. The model animals' aberrant expression of Sqstml, Ctsd, Mylk2, and Nfkbib was further enhanced by CDDP, as demonstrated by 

quantitative polymerase chain reaction (qPCR). Results: CDDP protects primary organs in DIC models by reducing inflammatory factor 

expression, increasing organ blood flow, and correcting coagulation anomalies. Not only that, but CDDP enhanced the outcome of DIC animal 

models by boosting the expression of important genes associated with the illness, namely Sqstml and Nfkbib.  

 

Keywords: Various terms such as microcirculation, disseminated intravascular coagulation, the Sqstml gene, transcriptomics, and compound 

Danshen dripping tablet are used. 

 

Chinese Traditional Medical Journal 

 

A Disseminated Intravascular Coagulation Animal Model: How Compound 

Danshen Dripping Pills Work and What They Do 
Kiran Kumar Reddy And Varun  

1,2 Academy of Acupuncture and Moxibustion, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 

350122, China 

Received on:  21 Oct 2024   Revised on: 20 Nov 2024    Accepted Date: 25 Dec 2024  
Published on: 17 Feb 2025 

 

 

 

INTRODUCTION  

Microthrombuses develop all over the place and systemic 
coagulation is activated in disseminated intravascular 
coagulation (DIC), a condition of acquired coagulation 
dysfunction. [1] One of the most dangerous outcomes for 
patients suffering from sepsis, tumors, acute leukemia, 
placental abruption, or trauma, it happens as a response to 
several disorders. Due to its high death rates and 
vulnerability to organ failure, DIC is difficult to detect and 
has a bad prognosis when treated. [2] in The coagulation 
system becomes activated and microvascular system gets 
damaged when pathogenic agents do this. the third 
Furthermore, coagulation factors have a role in  
 
the breakdown and consumption of platelets and 
coagulation factors leading to hemorrhage and thrombosis. 

According to reports, a significant number of patients in the 
intensive care unit (ICU) have signs of DIC, which may 
lead to an increased death rate. The most common cause of 
DIC is infection. [6] The new coronavirus causes the acute 
infectious illness known as coronavirus disease 2019 
(COVID-19), which impacts several organs and systems. 
Those two In addition,  
 
a number of mechanisms, including inflammation, 
immunology, cell  
 
the establishment of a clotting-inflammation-immune 
network, adhesion, and platelet activation. [4] The core 
feature of DIC is the presence of unregulated 

 

 

 



CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

 

23  

  

 

 

COVID-19 patients in critical care often present with 

abnormal coagulation function. Multiple systems, including 

coagulation, inflammation, and the immune complement 

system, are involved in coagulation dysfunction in COVID-

19 individuals, according to studies. [9] Infections may 

progress to DIC in critically sick individuals, leading to 

unfavorable health consequences. Depending on the 

treatment of underlying conditions, heparin or low-

molecular-weight heparin is now recommended as the first-

choice medicine for DIC according to worldwide treatment 

recommendations. Citations [10,11] Nevertheless, a number 

of studies have shown that heparin has no discernible impact 

on patients' long-term survival rates and carries a large risk 

of severe side effects including bleeding. Consequently, the 

creation of efficient methods for treating DIC is a pressing 

and unfulfilled therapeutic need.  

For the treatment of coronary heart disease (CHD), the 

China Food and Drug Administration has authorized 

compound Danshen dripping tablet (CDDP) during the last 

quarter of a century. Many studies have shown that CDDP 

can alleviate myocardial ischemia-induced angina symptoms 

by improving blood circulation, decreasing blood viscosity, 

protecting endothelial cells, inhibiting leukocyte adhesion 

and inflammation, and optimizing myocardial energy 

metabolism. [12] Moreover, prior research has shown that 

CDDP has pharmacological actions such enhancing 

microcirculation, preventing platelet adhesion and 

aggregation, acting as an antioxidant and anti-inflammatory, 

and safeguarding endothelial functions. [13] Myocardial 

ischemia and DIC have similar clinical and physiological 

processes, such as inflammation, impaired coagulation 

function, and platelet activation. This suggests that the 

regulatory mechanism by which CDDP protects against DIC 

and CHD is similar as well. Thus, the purpose of this study 

was to examine the effectiveness of CDDP in treating DIC 

in two separate animal models and to investigate, using 

transcriptomics as a starting point, the potential mechanism 

of CDDP's treatment of DIC. The ultimate goal is to provide 

evidence supporting CDDP's use in treating DIC and to 

provide a safe and effective option for patients suffering 

from clinical DIC. 

 

MATERIALS AND METHODS 
Animals 
Specific pathogen‑free (SPF) male Kunming mice, weighing 

20 ± 2 g, were purchased from the Beijing Weitong Lihua 

Experimental Animal Technology Co., Ltd. (animal certificate 

number: 110011110698978). SPF male Sprague–Dawley 

rats, weighing 200 ± 20 g, were purchased from the Beijing 

Vital River Laboratory Animal Technology Co., Ltd (animal 

certificate number: 110011211104397472). The animals 

were fed using the Tianjin Tasly Proud Pharmaceutical Co., 

Ltd. animal barrier system (facility license: SYXK (Tianjin) 

2017-0006). They were adapted to feeding for 3 days, during 

which their weight, head, and torso conditions, and activity 

levels were monitored. The present study was approved 

by the Committee on Animal Experimentation of the Tasly 

Academy (ethics approval code: TSL‑IACUC‑2020‑19, TSL‑ 

IACUC‑2020‑20). 

Apparatus and reagents 

The tool  
The following instruments were used: a laser speckle 
blood flow imaging system (moorFLPI-2), a semi-
automatic coagulation analyzer (Siddhi Scientific 
Instruments, LG-PABER-I), a microplate reader (TECAN, 
Infinite M200), an automatic biochemical analyzer (Hitachi 
7020), a fragment analyze biological analyzer (Thermo, 
FSv2-CE), a gene sequencing instrument (Shenzhen Huada, 
DNBSEQ-T7), a qPCR instrument (Analytik Jena, 
qTOWER3G), and a chemiluminescence imager (Shanghai 
Qianxiang, ChemiScope6200).  
Chemicals and substances  
The drug and reagents used were: CDDP (TASLY, 190117), 
nadroparin calcium injection (Aspen, 5325B), high 
molecular dextran (H20M10B88790), ulcerose 
(T20100310), sodium chloride injection (2012174C), 
lipopolysaccharide (LPS; SIGMA, 0000081275), 
prothrombin time detection kit (Taizhou Zhongqin, 
STY20101-41-9), and fibrinogen (FIB) determination kit 
(Taizhou Zhongqin, STY20401-39-5). Rat interleukin-10 
(IL-10) enzyme-linked immunosorbent assay (ELISA) kit 
(Shanghai Enzyme-linked, Nov 2020), rat tumour necrosis 
factor- alpha (TNF-) ELISA kit (Shanghai Enzyme-linked, 
Nov 2020), glutamic pyruvic transaminase (GPT) test kit 
(Nanjing Jiancheng, 20210305), glutamic oxaloacetic 
transaminase (GOT) test kit (Nanjing Jiancheng, 
20210304), creatinine (Cr) test kit (Nanjing Jiancheng, 
20210304), TransZol (Beijing TransGen ET111-01), 
reverse transcription kit (Takara, RR047A).  
Research techniques  
How the Danshen dripping tablet composition affects the 
survival rate of rats stimulated with lipopolysaccharide?  
Intraperitoneal injection of LPS into rats allowed 
researchers to reproduce the mouse model of DIC. There 
were three sets of animals used as models: those given 
CDDP-H (1660 mg/kg), those given CDDP-L (830 mg/kg), 
and those given nadroparin calcium (500 IU/kg). In order 
to mimic the DIC model, 35 mg/kg of LPS was 
intraperitoneally administered into all groups of mice 
except the control group. After modeling, mice in the 
model group received 10 mL/kg of pure water; mice in the 
CDDP group received the indicated doses of CDDP 
intragastrically; and mice in the nadroparin calcium group 
received 500 IU/kg of nadroparin calcium subcutaneously. 
At 72 hours post-modeling, we measured the survival rate 
of each group of experimental animals. 

Effect of compound Danshen dripping pill on dextran‑ 
induced microcirculatory disturbance 
The rat model of DIC microcirculation disorder was established 

by injecting 10% dextran T500 into the tail vein. The rats 

were divided into the control, model, CDDP‑H (830 mg/kg), 

CDDP‑L (415 mg/kg), and nadroparin calcium (500 IU/kg) 

groups. Different doses of CDDP were administered by gavage 



CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

 

24  

  

 

 

1.5 h before the model was replicated. Blood perfusion of 

the rat liver and gastric fundus was detected using the Moor 

FLPI‑2 laser speckle blood flow imaging system 10 min 

before dextran T500 injection and 5, 15, and 30 min after 

dextran T500 injection to investigate the effect of CDDP on 

microcirculation disorder. 

Effect of compound Danshen dripping pill on 
lipopolysaccharide‑induced animal model 
The DIC model was replicated by intraperitoneally injecting the 

rats with LPS. The rats were divided into the control, model, 

CDDP‑H and CDDP‑L, and nadroparin calcium groups. Except 

for the control group, rats in all other groups were intraperitoneally 

injected with 30 mg/kg LPS to replicate the DIC model. Rats in 

the control and model groups were intragastrically administered 

10 mL/kg of pure water immediately after modeling. Rats in the 

CDDP group were intragastrically administered 415–835 mg/ 

kg CDDP immediately after modeling. Rats in the nadroparin 

calcium group were subcutaneously injected with 500 IU/kg 

nadroparin calcium, immediately after modeling. The rats in 

each group were sacrificed 6 h after the model was replicated; 

blood and organ tissues were collected from the abdominal 

cavity after anesthesia, and the samples were processed 

according to the instructions. Hematological examination 

(prothrombin time [PT] and FIB), inflammatory factor detection 

(IL‑10 and TNF‑), and pathological examination of the liver 

and kidneys were performed. 

Transcriptomics detection and validation 
The rats in the control, model, and CDDP‑H groups (n = 5 rats 

in each group) were anesthetized with intraperitoneal injection 

of 20%, 4 mL/kg urethane administered 6 h after the model 

was replicated. Blood was collected from the abdominal aorta 

and placed in a PAXgene Blood RNA tube according to the 

instructions provided in the kit. Total RNA was extracted, and 

transcriptome sequencing was performed. The DEseq2 software 

and Metacore website were used to quantify the aforementioned 

genes and analyze them based on gene expression (correlation, 

principal component analysis, and differential gene screening). 

Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia 

of Genes and Genomes (KEGG) pathway enrichment analysis, 

and protein interaction network analysis were performed on 

differential gene data in selected samples. 

For qPCR, the RNA samples from experimental animals were 

reverse-transcribed according to the instructions provided 

in the kit. The PCR primers were designed using Primer 5.0 

software. Quantitative real‑time (qRT)‑PCR was performed 

using the SYBR Green fluorescent dye. The amplification curve 

was obtained by real‑time monitoring of the PCR using the 

dissolution curve. The Ct-value of the target gene was calculated 

using the amplification curve, and the gene expression changes 

were quantitatively calculated using the 2–ΔΔCt formula. 

Statistics 
Microsoft Excel was used to analyze and process the data. The 

experimental data obtained from each group are expressed as 

mean ± standard deviation. The two-sample equal variance 

t‑test was used to examine the significance between the groups, 

and P < 0.05 was considered statistically significant. 

 

RESULTS 
Effect of compound Danshen dripping pill on the survival 
rate of lipopolysaccharide‑induced model animals 
The survival rates of rats in the CDDP‑L, CDDP‑H, and 

nadroparin calcium groups were 8.35%, 37.5%, 87.5%, and 

25%, respectively [Figure 1A]. The results suggested that 

CDDP improved the survival rate of LPS‑induced model rats 

in a dose-dependent manner. 

Effect of compound Danshen dripping pill on dextran‑ 
induced microcirculatory disturbance 
Preadministration of 415 mg/kg CDDP significantly increased 

the 5‑min and 15‑min hepatic blood flow and 30‑min gastric 

fundus blood flow in DIC rats following 10% dextran T500 

modeling (P < 0.05). Preadministration of 830 mg/kg CDDP 

significantly increased the 5‑min and 15‑min hepatic blood 

flow and the 5‑min and 30‑min gastric fundus blood flow after 

modeling in DIC rats (P < 0.05). These findings suggested 

that CDDP plays a therapeutic role in DIC microcirculation 

disorder by improving the microcirculation in internal organs 

and increasing blood perfusion of organs [Figure 2a-c]. 

Effect of compound Danshen dripping pill on 
lipopolysaccharide‑induced rat model 

Effect of compound Danshen Dripping Pill on coagulation 
function in lipopolysaccharide‑induced model rats 
The prothrombin time (PT) in the model group was 

significantly prolonged (model vs. control; P < 0.01) and the 

FIB level was significantly decreased (P < 0.01), suggesting 

LPS‑induced coagulation abnormalities in model rats. After 

the model was replicated, different doses of CDDP improved 

LPS‑induced coagulation dysfunction. Notably, the CDDP‑H 

group showed significant improvement than that of the model 

group (P < 0.01), demonstrating an effect comparable to that 

of the nadroparin calcium group [Figure 1B]. 

Effect of compound Danshen dripping pill on inflammatory 
factors in lipopolysaccharide‑induced model animals 
Compared with the control group, the model group 

demonstrated a significant increase in serum IL-10 and 

TNF‑ levels (P < 0.05). Different doses of CDDP improved 

the LPS‑induced abnormal increase in inflammatory factors 

(P < 0.05), which was equivalent to the effect of nadroparin 

calcium, suggesting that CDDP exerts an inhibitory effect 

on inflammatory factors in LPS‑induced model animals 

[Figure 1C]. 

Effect of compound Danshen dripping pill on liver and 
kidney function of lipopolysaccharide‑induced animal 
model 
Compared with the control group, the model group demonstrated 

an abnormal increase in GPT and GOT activities and blood 



CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

 

25  

  

 

 

 
Figure 1: Lipopolysaccharide‑induced disseminated intravascular coagulation model assay. (A) The 72 h survival rate of model mice (n = 8). (B; a and b) 
Effect of compound Danshen dripping pill on PT value and FIB levels in model rats (n = 6). (C; a and b) Effect of compound Danshen dripping pill on 
inflammatory factors in model rats (n = 6). (D; a‑d) Effect of compound Danshen dripping pill on hepatic and kidney injury in model rats (n = 6) in 
comparison with control rates. #P < 0.05, ##P < 0.01; comparison with the model group, *P < 0.05, **P < 0.01. CDDP: Compound Danshen dripping pills 

 

urea nitrogen (BUN) and creatinine (Cr) levels in the model group 

(P < 0.01), suggesting that the model rats suffered a certain degree 

of liver and kidney damage. Different doses of CDDP significantly 

reduced the activities of GPT and GOT (P < 0.01) and the levels of 

BUN and Cr (P < 0.01) in rat plasma, similar to the effect exerted 

by nadroparin calcium. These results suggested that CDDP exerts a 

protective effect against LPS‑induced liver and kidney injury in 

model animals [Figure 1D]. 

Histopathological observation of the effects of CDDP on 

lipopolysaccharide-induced animal model. 

Hematoxylin and eosin staining revealed initial pathological 

damage 6 h following the intraperitoneal injection of LPS in 

animals in the model group. Different levels of CDDP reduced the 

initial pathological damage caused by LPS‑induced DIC in the 

lungs, liver, and kidneys [Figure 3]. 

In the control group, the alveolar septum wall was thin, and 

the cells were normal, whereas, in the model group, the 

alveolar septum wall was thick, with alveolar septal capillary 

dilation congestion (▲), which increased around 

the blood vessels, along with edema (★). In the control group, the 

liver cells were arranged in plates, the central vein was filled 
with red blood cells, and the portal area 

vessels and bile ducts were arranged normally; whereas the model 

group exhibited hepatocyte vacuolar degeneration (×), partial 

nuclear lysis, and hepatic sinusoid dilatation and congestion (on, 

without inflammatory cell infiltration. In the model group, no 

abnormalities were observed in the glomeruli, but there was an 

increase in red blood cells and congestion in the renal interstitial 

capillary (ap. Compared with the model and control group, the 

CDDP group exhibited reduced pulmonary edema and pulmonary 

perivascular space, decreased hepatocyte vacuolar 

degeneration, and improved renal interstitial capillary congestion. 

Transcriptome sequencing analysis and verification 
Transcriptome sequencing analysis 
We used the screening conditions of | log2FC | ≥1 and q ≤ 0.05 and 

found 543 common and significantly differentially expressed genes 

in the control group, model group, and CDDP group [Figure 4a]. 

 a   b  

 a   a   b  

 b   c   d  



CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

 

26  

  

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 a   b   c   d  

 

 
Figure 2: Dextran‑induced microcirculatory disturbance model assay (a) Liver blood flow in different groups. (b) Liver blood flow in different groups. 

(c) Liver and gastric fundus blood flow between 0 and 30 min after modeling in each group, #P < 0.05, ##P < 0.01; comparison with the model 
group, *P < 0.05, **P < 0.01 (n = 6). CDDP: Compound Danshen dripping pills 

 

Figure 3: Hematoxylin and eosin staining in different groups(×400). The HE staining of the organ tissues were observed under a 400x microscope. 

Hematoxylin and eosin staining in different groups. In the lung, the model group exhibits alveolar septum thickening, alveolar septum capillarydilation 

congestion (▲) and increased edema around the blood vessels (★). In the liver, the model group exhibits hepatocyte vacuolar degeneration(×), partial 
nuclear lysis, and hepatic sinusoid dilatation and congestion (▲). In the kidney, the model group exhibits increased in red blood cells andcongestion 
in the renal interstitial capillary (▲), Pulmonary edema was slightly reduced and perivascular space was reduced (). a: Control group;b: Model 
group; c: CDDP‑H group; d: Fraxiparine group. CDDP: Compound Danshen dripping pills 

 

Differential gene enrichment analysis 
The Gene Ontology (GO) enrichment analysis and KEGG pathway 

enrichment analyses were performed on the 543 genes. The results 

demonstrated that CDDP primarily participated in the regulation of 

immune inflammatory response, complement system, oxidative 

stress response, COVID-19-related coagulation disorders, 

platelet activation, aggregation, and apoptosis. It has been suggested 

that CDDP confers therapeutic 

potential against DIC by regulating the immune complement 

system, exerting anti‑inflammatory properties, promoting 

coagulation and platelet activation, countering antioxidative stress, 

and inhibiting apoptosis. 

Gene ontology enrichment analysis 
We used the Dr. Tom online system to analyze the biological 

processes, cellular components, and molecular functions of the 

 a   b  

 c  



CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

 

27  

  

 

 

 
Figure 4: Whole blood transcriptome sequencing differential gene analysis and verification. (a) Differential gene VEEN map (control vs. model vs. CDDP‑H groups); (b) 
Pathway maps enrichment analysis of differential genes (Q‑value ranked top 50); (c) Results of quantitative polymerase chain reaction assay (n = 5), in comparison 
with the control group. #P < 0.05, ##P < 0.01. CDDP: Compound Danshen dripping pills 

 

differentially expressed genes. The results demonstrated that the GO 

terms enriched by differentially expressed genes involved 2727 

biological processes, 462 cellular components, and 804 molecular 

functions. The biological processes primarily included inflammatory 

response, immune system process, response to 

lipopolysaccharides, innate immune response, neutrophil response, 

and antioxidative stress. Cellular components primarily involved the 

cytoplasm, cell fluids, ribosomes, soluble fibrin, and mitochondria. 

The molecular functions included protein labeling, ubiquitin 

protein ligation, cytokine receptor activation, IL-1 receptor activation, 

complement component C3b binding, and Toll-like receptor binding. 

These results indicated a strong connection between differentially 

expressed genes and the coagulation–immune system, suggesting that 

CDDP exerts its therapeutic effect on DIC through the above 

pathways. 

KEGG enrichment analysis 
The KEGG pathway enrichment analysis was performed on the 

differentially expressed genes using the MetaCore database 

(https://portal. genego. com/). The top 50 pathways with the 

smallest Q-values, that is, the most significant enrichment, were 

selected for display. In addition, the top 50 pathways were found to 

be the immune response complement pathway, IL-6-induced acute 

phase response of hepatocytes, neutrophil chemotaxis, oxidative 

stress response, thrombotic microangiopathy, high mobility group 

box 1 signaling pathway, TNF‑ signaling pathway, IL-1  

signaling pathway, and COVID-19-related coagulation disorders. 

Most of these 

pathways were related to the immune response and coagulation 

system, suggesting potential pathways for the treatment of DIC using 

CDDP [Figure 4b]. 

Analysis of key targets and pathways of CDDP in the treatment 
of DIC 
The results of the transcriptome analysis, P values of differential gene 

enrichment, and functions of the enriched pathways were used to 

further classify the differentially expressed genes. The related targets 

and corresponding pathways of CDDP in the DIC model rats were 

analyzed. Comprehensive analysis revealed that CDDP exerts a 

therapeutic effect on DIC by affecting the oxidative stress response and 

acting on apoptosis-related pathways. In addition, the analysis 

revealed that CDDP exerted therapeutic potential against COVID‑19 

by affecting thrombosis [Figure 5]. 

Validation of transcriptomics analysis results 
The results of transcriptome analysis revealed that the key targets 

of CDDP in the treatment of DIC were primarily enriched in 

immune coagulation, oxidative stress, platelet activation, 

inflammasome, and apoptosis‑related pathways. Based on literature 

research, four key genes, namely, Sqstml, Ctsd, Mylk2, and Nfkbib, 

were selected for qPCR verification, and the effect of CDDP on 

LPS‑induced model animals was preliminarily observed. The 

results demonstrated that, compared with the control group, the 

model group significantly increased expression of four target 

genes, Mylk2, Nfkbib (P < 0.05), Ctsd, and Sqstml (P < 0.01), in 

the whole blood of 

 a  

 c   b  



CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

 

28  

  

 

 

 
Figure 5: Coagulation disorder‑related pathways 

 

the model rats 6 h after model replication. CDDP inhibited the 

overexpression of Mylk2, Nfkbib, Ctsd, and Sqstml to varying 

degrees. The results of qRT‑PCR were consistent with those 

of transcriptome sequencing [Figure 4c]. 

 

DISCUSSION 
 

In DIC, an acquired coagulation condition, microthrombuses 

develop all over the place and systemic coagulation is 

activated. A number of biological systems, including those 

involved in coagulation, innate immunity, inflammation, 

complement, and fibrinolysis, are disrupted by the disorder's 

severe microcirculatory abnormalities. (2, 3). According to 

clinical research, DIC symptoms are seen by 10%-30% of 

intensive care unit (ICU) patients, leading to an increased 

death rate. The main cause of DIC is infection. When it 

comes to treating infectious disorders, traditional Chinese 

medicine offers some distinct benefits. [14] Here, we looked 

at how CDDP affected the rate of survival in an animal 

model that was induced with LPS. The findings showed  

 

demonstrated the survival rate of LPS-induced model mice 

was significantly enhanced by a single oral dosage of CDDP 

at varied doses. The main clinical symptom of DIC has been 

described as organ failure due to the production of 

microthrombi in various organ microvessels. [15] By 

injecting 10% dextran T500 into the tail vein of rats, we were 

able to replicate an animal model of DIC microcirculatory 

disorder. After 5-30 minutes of model replication, we 

observed that a single oral dose of CDDP increased organ 

blood flow and continuously improved blood perfusion in the 

gastric fundus and liver, suggesting that CDDP may have 

therapeutic effects on DIC by improving microcirculation in 

these model animals.  

The etiology and clinical manifestations of DIC in LPS-

induced rats are similar to those in humans suffering from 

clinical infections. A hallmark of this paradigm is the 

development of microthrombi and extensive coagulation. 

[16] To examine CDDP's therapeutic potential, we used an 

LPS-induced DIC rat model in this investigation. Prolonged 

PT during consumptive hypocoagulation and secondary is 

seen in the majority of DIC patients, according to clinical 



CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

 

29  

  

 

findings.  

time periods including fibrinolysis (hypercoagulation). 

Another inflammatory biomarker that shows the greatest 

plasma coagulation factor level is FIB, a glycoprotein 

produced by liver cells. 17 and 18 Our results show that 

CDDP enhances normal coagulation function in LPS-

induced model animals, as it prolongs PT and reduces LPS-

induced plasma FIB level in rats. Additionally, cytokines 

including TNF and IL-1 facilitated coagulation activation, 

fibrinolysis injury, and organ damage in the LPS-induced 

DIC animal model. [15] A single oral dose of CDDP 

considerably reduced the levels of inflammatory cytokines 

like IL-10 and TNF-α in DIC model rats, as well as the 

activity of markers for liver and kidney damage like GPT 

and GOT, as well as the levels of BUN and Cr in their 

plasma, according to the results. The results indicated that 

CDDP prevents damage to the main organs by reducing 

inflammatory factor expression. Furthermore, the early 

pathological damage to the lungs, liver, and kidneys 

produced by LPS-induced DIC was ameliorated by CDDP, 

as shown by HE pathological staining. These findings 

provide promising evidence that CDDP may be useful in the 

treatment of DIC in animals by enhancing microcirculatory 

function and protecting important organs by reducing 

inflammatory factor expression.  

After that, we looked at potential CDDP targets in DIC 

therapy by sequencing the whole-blood transcriptome of 

animals across several groups. In LPS-induced DIC model 

rats, CDDP showed therapeutic potential via immunological 

modulation, anticoagulation, antiinflammation, inhibition of 

platelet activation, and cell death, according to the GO and 

KEGG enrichment analyses of the differentially expressed 

genes. We confirmed the target genes using qPCR: Sqstml, 

Ctsd, Mylk2, and Nfkbib. Our selection was based on 

experimental findings and a literature study. This prediction 

approach was confirmed to be feasible since the target genes 

were considerably elevated in the CDDP group compared to 

the model group, which was in agreement with the projected 

outcomes. CDDP skewed the expression of the innate 

immune regulating factor Sqstml. In addition, it is thought 

of as a predictor of outcome in cases of serious infections in 

humans and in animal models generated by LPS. The year 

19 Activated nuclear factor-kappaB (NF-κB) is linked to 

several organ dysfunctions, and it is known to have a 

significant role in endothelial cell damage and apoptosis 

brought on by severe infections. Patients with sepsis may 

have a better chance of surviving if the NF-B activity is 

inhibited. Among the many roles it plays in the heart and in 

the activation and aggregation of platelets, Mylk2, an 

affiliate of the myosin light chain kinase family, is 

mentioned in reference [20]. References [21,22] After 

ischemia and hypoxia, autophagy activates Ctsd, leading to 

lysosomal dysfunction. Cell apoptosis involves both internal 

and extrinsic processes, to which it contributes at various 

stages. [23] The Ctsd may also initiate cell death by directly 

activating caspase 3. This research found that CDDP 

improved the aberrant expression of  

 

The blood of rats that were induced DIC by LPS included 

Sqstml, Ctsd, Mylk2, and Nfkbib.  

In this work, we found that CDDP increased blood flow to 

the primary organs of rats with DIC, which protected those 

organs from damage. Also, it blocks cell death, controls 

inflammatory factor expression, decreases coagulation 

malfunction in DIC, and blocks platelet activation pathways. 

Supporting the expression of important genes linked to 

disease development, including Sqstml and Nfkbib, may be 

the underlying mechanism. In conclusion, CDDP has 

promise for enhancing DIC prognosis and creating a more 

efficient treatment plan. 

 

CONCLUSIONS 
This study showed that CDDP may have protective effects 

in DIC model animals by improving organ blood flow and 

coagulation abnormalities and inhibiting the expression of 

inflammatory factors. The therapeutic effects of CDDP on DIC 

model animals may be achieved by increasing the expression of 

key genes related to DIC, including Sqstml and Nfkbib, thereby 

improving the prognosis of model animals. This study only 

preliminarily explored the efficacy and mechanism of CDDP 

in the treatment of DIC, and the key targets and pathways of 

action should be further clarified and verified to explain the 

mechanism of action of CDDP in the treatment of DIC further 

clearly. 

Financial support and sponsorship 
Nil. 

Conflicts of interest 
The authors assert that the study was conducted without any 

commercial or financial affiliation that may pose a conflict 

of interest. 

 

REFERENCES 
1. Wada H, Thachil J, Di Nisio M, Mathew P, et al. Guidance for diagnosis 

and treatment of DIC from harmonization of the recommendations from 

three guidelines.: JTH 2013;11:761-767. 

2. Berthelsen LO, Kristensen AT, Tranholm M. Animal models of DIC 

and their relevance to human DIC: A systematic review. Thromb Res 

2011;128:103-16. 

3. Popescu NI, Lupu C, Lupu F. Disseminated intravascular coagulation 

and its immune mechanisms. Blood 2022;139:1973-86. 

4. Abrams ST, Su D, Sahraoui Y, Lin Z, Cheng Z, Nesbitt K, et al. Assembly 

of alternative prothrombinase by extracellular histones initiates and 

disseminates intravascular coagulation. Blood 2021;137:103-14. 

5. Adelborg K, Larsen JB, Hvas AM. Disseminated intravascular 

coagulation: Epidemiology, biomarkers, and management. Br J 

Haematol 2021;192:803-18. 

6. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat 

Rev Dis Primers 2016;2:16037. 

7. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX. Clinical characteristics 

of coronavirus disease 2019 in China. N Eng J Med 2020;382:1708‑20. 

8. Yao CL, Wei WL, Zhang JQ, Bi QR, Li JY, Khan I, et al. Traditional 

Chinese medicines against COVID-19: A global overview. World J 

Tradit Chin Med 2022;8:279-313. 

9. Vincent JL, Levi M, Hunt BJ. Prevention and management of thrombosis 

in hospitalised patients with COVID-19 pneumonia. Lancet Respir Med 

2022;10:214-20. 



CTMJ | traditionalmedicinejournals.com Chinese Traditional Medicine Journal | 2025 | Vol 8 |Issue 1 

 

30  

  

 

 

10. Zarychanski R, Abou‑Setta AM, Kanji S, Turgeon AF, Kumar A, Houston 

DS, et al. The efficacy and safety of heparin in patients with sepsis: 

A systematic review and metaanalysis. Crit Care Med 2015;43:511-8. 

11. Wang C, Chi C, Guo L, Wang X, Guo L, Sun J, et al. Heparin therapy 

reduces 28-day mortality in adult severe sepsis patients: A systematic 

review and meta-analysis. Crit Care 2014;18:563. 

12. Cheng B, Li XY, Liu KQ, Wang L, Wu WP, Xu H, et al. Chinese expert 

advice on the clinical application of compound danshen dripping pills. 

Chin J Integr Tradit Chin West Med 2017;37:17-22. 

13. Liao W, Ma X, Li J, Li X, Guo Z, Zhou S, et al. A review of the 

mechanism of action of dantonic(®) for the treatment of chronic stable 

angina. Biomed Pharmacother 2019;109:690‑700. 

14. Han JY, Li Q, Pan CS, Sun K, Fan JY. Progression of the Wei‑Qi‑Ying‑Xue 

syndrome, microcirculatory disturbances, in infectious diseases and 

treatment with traditional Chinese medicine. World J Tradit Chin Med 

2022;8:169-80. 

15. Suga Y, Akita F, Yamada S, Morishita E, Asakura H. Recombinant 

human erythropoietin attenuates hepatic dysfunction by suppressing 

hepatocellular apoptosis in lipopolysaccharide-induced disseminated 

intravascular coagulation in rats. Biomed Rep 2022;16:5. 

16. Asakura H. Classifying types of disseminated intravascular coagulation: 

Clinical and animal models. J Intensive Care 2014;2:20. 

17. Huang J, Yin XJ, Huang F. Research progress of fibrinogen related 

drugs. Pharm Res 2019;38:167‑71. 

18. Rostami M, Khoshnegah Z, Mansouritorghabeh H. Hemostatic system 

(fibrinogen level, D‑Dimer, and FDP) in severe and non‑severe patients 

with COVID-19: A systematic review and meta-analysis. Clin Appl 

Thromb Hemost 2021;27:2710760296211010973. 

19. Zhou B, Liu J, Zeng L, Zhu S, Wang H, Billiar TR, et al. Extracellular 

SQSTM1 mediates bacterial septic death in mice through insulin 

receptor signalling. Nat Microbiol 2020;5:1576‑87. 

20. Papurica M, Rogobete AF, Sandesc D, Cradigati CA, Sarandan M, 

Crisan DC, et al. The expression of nuclear transcription factor kappa B 

(NF‑B) in the case of critically Ill polytrauma patients with sepsis and 

its interactions with microRNAs. Biochem Genet 2016;54:337‑47. 

21. Zhang S, Wang J, Chen S, Yin J, Pan Z, Liu K, et al. Effects of suilysin 

on Streptococcus suis-induced platelet aggregation. Front Cell Infect 

Microbiol 2016;6:128. 

22. Feghhi S, Tooley WW, Sniadecki NJ. Nonmuscle myosin IIA regulates 

platelet contractile forces through Rho kinase and myosin light-Chain 

Kinase. J Biomech Eng 2016;138:1045061–1045064. 

23. Di YQ, Han XL, Kang XL, Wang D, Chen CH, Wang JX, et al. 

Autophagy triggers CTSD (cathepsin D) maturation and localization 

inside cells to promote apoptosis. Autophagy 2021;17:1170-92. 


