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Table 3 Summary of in vivo studies on DS

From: Mechanism-based biomarkers for the quality control of Dangkwisoo-san: a scoping review

Target Study

Animal (sex, age, body weight)

Inducer

Type of extracts

Administration

(Frequency/period)

Experimental group

Positive control

Biomarker & outcome

Reference

Bruise

Wistar rat

(male, 180–220 g)

Aq

5 ml/200 g*

(Oral, 2/day, 1 day)

Normal

Control (bruised)

DS decoction

extracts

-

Water maze test, LDH

Yeo, N. H. et al. [36]

Bruise

Wistar rat

(male, 180–220 g)

Aq

5 ml/200 g*

(Oral, 2/day, 1 day)

Normal

Control (bruised)

DS decoction

DS extracts

-

GPT, GOT, LAP, ALP

Yeo, N. H. et al. [37]

Blood stasis

Wistar rat

(male, 250 g)

Aq

200 mg/individual*

(Oral, daily, 1 day)

Normal

Control (blood stasis induced by compression for 2 h or 4 h)

DS (1 h before compression)

-

Thigh circumference

Thigh dermal temperature

Platelet

Fibrinogen

Prothrombin time

FDP

Lee, G. H. et al. [38]

Hemostasis (Bruise)

Wistar rat

(male, 200 g)

 

Aq

Decoction: 5 ml/200 g*

Extract: 150 mg/200 g*

(Oral, 2/day, 1 day)

Normal

Control (hemostasis)

DS decoction

DS extract

 

WBC, RBC, Total protein, ALP, LDH, LAP, s-GOT, s-GPT

Lee, H. Y. [39]

Subcutaneous hematoma

Wistar rat

(male, 250–300 g)

Autologous blood

Aq

125 mg/100 g*

(Oral, daily, 7 days)

Normal

Control (hematoma)

DS

 

Histological analysis (H&E staining)

Kim, K. H. [40]

Coagulation induced by endotoxin

SD rat

(male, 270–290 g)

Endotoxin

Aq

0.1 ml/individual*

(SC, daily, 3 days)

Normal

Control (endotoxin)

TGSS

ACUP

ACUP control

-

Platelets, RBC, fibrinogen, FDP, prothrombin time

Nam, S. S. et al. [41]

Coagulation induced by endotoxin

Wistar rat

(male, 200–220 g)

Endotoxin

Aq

163.2 mg/200 g*

(Oral, 4 h after endotoxin injection, 1 day)

Normal

Control (endotoxin)

DS

Dodamtang

-

Platelets, Prothrombin, FDP (fibrinogen degradation products)

Kim, T. S. et al. [42]

Blood pressure reduction effect

New Zealand white rabbit vein

Atropine

Pheniramine

Propranolol

Aq

0.5 ml/kg*, 1 ml/kg*

Control (stimulation)

DS decoction

 

Blood pressure measurement

Lew, J. H. [43]

Fracture

C57BL/6 J

(male, 7w)

-

Aq

300 mg/kg

(Oral, daily, 4 weeks)

Normal (no femur fracture)

Control

Tramadol

DS

Tramadol

(20 mg/kg)

BMP2, COX2, Col2a1, Sox9, Runx2, osterix, histological analysis

Jeon, D. H. et al. [46, 47]

Fracture

SD rat

(male, 8–10w)

-

Aq

500 mg/kg*

(Oral, daily, 14 days)

Normal

Control (fracture)

DS

Native copper

DS + Native copper

-

ALP, ALT, AST, creatinine, histological analysis, TGF-β1

Jung, I. M. [44]

Fracture

SD rat

(male, 8–10w)

-

Aq

500 mg/kg*

(Oral, daily, 14 days)

Normal

Control (fracture)

DS

ACUP

DS + ACUP

-

Osteocalcin, T-ALT, histological analysis, TGF-β1

Ahn, H. L. et al. [45]

Wound healing

Wistar rat

(male, 6w)

-

80% EtOH

200 mg/kg*

(Oral, daily, 3 weeks)

Control

DS

Terramycin

DS + Terramycin

Terramycin

Wound healing, TNF-α, IL-1β, IL-6, MMP-1, MMP-2, MMP-9, Histological analysis

Bak, J. W. et al. [48]

Acute lung inflammation

C57BL/6 J

(male, 7w)

LPS

Aq

1 g /kg

(Oral, daily, 15 days)

Normal

Control (LPS)

LPS + DS

-

Body weight, BAL fluid

Lyu, J. H. et al. [26]

Analgesic, anti-inflammation, muscle relaxation

ICR mouse (18–20 g) or SD rat (180–200 g)

Acetic acid

Carrageenin

50% EtOH

0.1*, 0.3*, 1* ml/20 g or 200 g

0.2, 0.4 ml/20 g

Control (stimulation)

DS decoction

 

Physiological response

(Paw licking time, escape time, paw edema, muscle relaxation, body temperature)

Ko, W. S. [49]

Traumatic brain injury

ICR mouse (male, 7w)

-

Aq

50, 150*, 450* mg/kg

(Oral, 2/day, 8 days)

Sham (craniotomy alone)

Control

DS

-

Beam walking test, grip strength test, NOR test, measurement of neutral injury and brain damage

Jung, J. Y. et al. (2018) [50]

Cerebral ischemic injury

C57BL/6 J

(male, 20–25 g)

-

Aq

600 mg/kg*

(Oral, 2/day, 3 days)

Veh, L-NIO

Sham, Control, DS

-

Blood pressure and resting CBF, Analysis of histology, Rotarod test, eNOS, AKT, iNOS, nNOS

Kim, J. H. et al. [51]

Liver toxicity

Wistar rat

(male, 180–200 g)

Carbon tetrachloride

Aq

Decoction:

8 mg* or 16 mg*/kg

Extract:

720 mg* or 1440 mg*/kg

(Oral, 2/day, 1 day)

Normal

Control (hepatoxicity)

DS decoction

DS extract

 

ALP, LDH, GOT, GPT, LAP, α-hydroxybutyric dehydrogenase

Lim, J. G. et al. [53]

  1. ACUP acupuncture; Aq aqueous; eNOS endothelial nitric oxide synthase; iNOS inducible nitric oxide synthase; nNOS neuronal nitric oxide synthase; BMP2, bone morphogenetic protein 2; COX2 cyclooxygenase-2; Col2a1 collagen type II alpha 1 chain; DS Dangkwisoo-san; Sox9 SRY-Box transcription factor 9; Runx2 Runt-related transcription factor 2; GPT glutamic pyruvic transaminase (ALT alanine aminotransferase); GOT glutamic oxaloacetic transaminase (AST aspartate aminotransferase); LAP leukocyte alkaline phosphatase; ALP alkaline phosphatase; LDH lactate dehydrogenase; FDP fibrinogen degradation production; MMPs matrix metalloproteinases; decoction, hot water extraction; extracts, processed after hot water extraction and weight possible
  2. * indicates concentrations and biomarkers with statistical significance (p < 0.05) in the article