A Review of the Botany, Traditional Use, Phytochemistry, Analytical Methods, Pharmacological Effects, and Toxicity of Angelicae Pubescentis Radix

Table 5

The pharmacology of AP.

Effects	Extract/compound dose	Animal/cell line	Study design	Control	Mechanism/results	Ref
Anti-inflammatory effect	1.5 g/kg (40%, 60%, 80%) ethanol extract solution	Xylene-induced mice ears edema	In vivo	Aspirin	By inhibiting the activity of NAAA, intracellular biological activity was increased and the level of proinflammatory factors was decreased.	[93]
		Egg white-induced mice pettitoes swelling
		Tampon granulation-induced mice swelling
	0.4 mL 50% ethanol extract solution	Xylene-induced mice ears edema	In vivo	Aspirin	It plays an anti-inflammatory role by reducing the levels of inflammatory factors such as MDA and TNF-α.	[92]
		Carrageenan-induced mice swelling
	0.15 and 0.29 g/kg volatile oil of AP	Egg white-induced rat pettitoes swelling	In vivo	Hexadecadrol	It plays an anti-inflammatory role by inhibiting the release of inflammatory factors such as 5-HT.	[94]
	AP 95% ethanol extract solution (0.1 g/L, 1 g/L, 10 g/L)	LPS-induced rat peritoneal macrophages	In vitro	Celecoxib	AP inhibited COX-1 and COX-2 in varying degrees, and there was a dose-response relationship.	[99]
				Indomethacin
				DMSO
	Volatile oil of AP (10 mg/L, 50 mg/L, 250 mg/L)	LPS-induced RAW 264.7 cell	In vitro	None	By inhibiting the hydrolysis activity of NAAA and increase the level of N-PEA, downregulating the expression of TNF-α, iNOS, IL-6 mRNA, and inhibiting the release of TNF-α and NO.	[100]
	Angesesquid A and angesesquid B	Primary chondrocytes of rat intervertebral disc	In vitro	None	Inflammation is inhibited by inhibiting the release of NO.	[101]
Analgesic	1.5 g/kg (40%, 60%, 80%) ethanol extract solution	Acetic acid-induced and tail-immersion-induced writhing	In vivo	Aspirin	By inhibiting the activity of NAAA, the intracellular biological activity was increased and the level of inflammatory factors was reduced to play an analgesic role.	[93]
	0.4 mL 50% ethanol extract solution	Hot plate, acetic acid, and formalin-induced pain	In vivo	Aspirin	By inhibiting the level of MDA and inflammatory factors was reduced to play an analgesic role.	[92]
	0.15 and 0.29 g/kg volatile oil of AP	Hot plate, acetic acid -induced mice pain	In vivo	Aspirin	AP has an analgesic effect similar to that of nSAID rather than narcotic analgesics.	[94]
				Morphine hydrochloride
	Coumarins in AP	Spared nerve injury model rat	In vivo	Morphine	AP has the analgesic effect mainly related to reducing the concentration of proinflammatory cytokines of TNF-α, IL-1 β, and IL-6 and reducing the expression of TRPV1 and perk in the damaged neurons.	[94]
Cardiovascular effect	0.4 g/kg, 1.0 g/kg AP ethanol extract	ADP-induced mice platelet aggregation	In vivo	Black	AP alcohol extract can shorten the thrombus length and prolong the tail hemorrhage time of mice to inhibit ADP-induced platelet aggregation in mice.	[103]
	10 mg/kg GABA	Multiple arrhythmia models	In vivo	Black	GABA could prolong the start time, reduce the incidence of ventricular tachycardia, shorten the duration of ventricular tachycardia, reduce the mortality of ventricular fibrillation, reduce APA and APO50 and APO90.	[104]
	AP ethanol extract	Patients with vertigo	In vivo	Compound Danshen	By reducing the whole blood viscosity, plasma viscosity and red blood cell aggregation index of vertigo patients, increasing the cerebral blood flow speed to play the role of promoting blood circulation and removing stasis.	[105]
	1.28 g/ml AP 95% ethanol extract	Thoracic aortic rings in rats	In vitro	CaCl2	AP had a good diastolic effect on vasoconstriction caused by PE and KCl, and its mechanism was related to the influx of CaCl2.	[106]
	3.75–30 μg/ml AP 95% ethanol extract and osthol	Human umbilical vein endothelial cells	In vitro	None	Inhibition of angiogenesis by stagnation of endothelial cycle mainly in G0-G1.	[11]
		Human colon cancer cell
Neuroprotective effect	AP 90% ethanol extract (2.7 g/kg/d, 8.1 g/kg/d, 24.3 g/kg/d)	D-Galactose-induced mice aging model	In vivo	Model	AP’s delay of brain aging is associated with anti-free radical peroxide damage, reduction of immunosuppression of arachidonic acid metabolites, and antagonism of brain inflammation.	[95]
	12 ml/kg/d AP alcohol extract or AP water extract	Aged mice	In vivo	Black	AP could reduce the content of MDA content and the deletion of DNA fragment in natural aging mice.	[96]
	Coumarin in AP with 22.05 mg/kg/d, 66.15 mg/kg/d, 198.45 mg/kg/d	Lactacystin-induced PD rat model	In vivo	Madopar, ibuprofen	Inhibition of lipid peroxidation in serum and brain tissue, increase of antioxidant enzyme activity, and decrease of excitatory amino acid Glu content in serum and brain tissue.	[107]
	Coumarin in AP with 3 g/kg/d	Lactacystin-induced PD rat model	In vivo	Madopar, celecoxib	Coumarin in AP and AP may protect PD by inhibiting endoplasmic reticulum stress.	[108]
	AP granules 3 g/kg/d
	Compound AP granules 6.3 g/kg/d
	AP 90% ethanol extract or water extract (18 g/kg/d)	Mice aged 16 months	In vivo	Water	It can improve the activity of mitochondrial respiratory chain enzyme complex I and IV in the brain of aged mice and protect the oxidative damage of mitochondrial DNA in mice.	[109]
	2 ml/mouse AP extract	Aβ-induced rat dementia model	In vivo	Indometacin	AP can inhibit the expression of P38 MAPK in rat brain and improve the learning and memory ability of dementia model rats.	[110]
	1 g/kg or 4 g/kg AP ethanol extract	D-Galactose or sodium nitrite-induced Alzheimer’s disease mice	In vivo	Water	AP can delay the occurrence of Alzheimer’s disease by increasing SOD and reducing AChE in brain tissue.	[111]
	20 mg/ml osthol	APP/PS1 double transgenic mice	In vivo	None	Osthol can promote the survival of NT-3-BM-NSCs and enhance the cholinergic nerve function in the brain.	[112]
	10–250 mg/ml coumarin in AP	Aβ-induced mice nerve injury model	In vivo	None	By promoting the expression of CREB and BDNF, the expression of P-CREB and BDNF is increased to play a neuroprotective role.	[113]
	9, 18, 36 ng/kg AP extract	MOG35-55 peptide fragment-induced mice EVE model	In vivo	Prednisone acetate	It can alleviate demyelination injury, inhibit the secretion of proinflammatory cytokines by spleen lymphocytes, and has neuroprotective effect.	[114]
Antibacterial effect	AP petroleum ether extract	Fungus	In vitro	None	AP essential oil has different degree of bacteriostatic effect on different fungi.	[115]
	1 g/L AP ethanol extract	Penicillium italicum	In vitro	None	Isobergamolactone, sphondin, pimpinellin, and isopimpinellin in AP showed antibacterial activity.	[116]
		Penicillium digitatum
		Colletotrichum gloeosporioides
Antioxidation effects	12 ml/kg/d AP alcohol extract or AP water extract	Aged mice	In vivo	Black	AP could reduce the level of MDA in the brain tissues of mice.	[96]
	1 g/kg or 4 g/kg AP ethanol extract	D-Galactose or sodium nitrite-induced Alzheimer’s disease mice	In vivo	Water	AP could delay the occurrence of Alzheimer’s disease by increasing the level of SOD.	[111]
	0.4 ml AP 50% ethanol extract	Carrageenan-induced mice swelling	In vivo	Aspirin	AP alcohol extract could inhibit the concentration of MDA with the inhibitory rate of 23.49%.	[92]
Antitumor effect	0.3125–10 mg/ml AP aqueous solution	HMVECs	In vitro	Cyclophosphamide	AP can inhibit the proliferation of human microvascular endothelial cells. Inhibition of angiogenesis.	[97]
		SMMC-7721
Antigastric ulcer	Chloroform, petroleum ether, and ethyl acetate extracts of AP	Aspirin-ethanol solution-induced mice gastric ulcer model	In vivo	Cimetidine	The fat-soluble part of AP is the effective part against gastric ulcer.	[98]