What is angelica

Angelica is a genus of about 90 species of tall biennial and perennial herbs in the family Apiaceae (Umbelliferae), that are widely distributed in Asia, Europe, and North America. They grow to 1–3 m (3 ft 3 in–9 ft 10 in) tall, with large bipinnate leaves and large compound umbels of white or greenish-white flowers (see Figure 1). In these, a total of 45 Angelica species (32 endemic species) are distributed in China ¹⁾. Various species of Angelica have been used in the traditional systems of medicine for several centuries  to treat many ailments. Angelica essential oils have been used for the treatment of various health problems, including malaria, gynecological diseases, fever, anemia, and arthritis ²⁾. Angelica essential oils are complex mixtures of low molecular weight compounds, especially terpenoids and their oxygenated compounds. These components deliver specific fragrance and biological properties to essential oils. Previously, several scientists reported the volatile composition of different Angelica species using various extraction techniques such as steam distillation, hydrodistillation, solvent-free solid injector, and supercritical fluid extraction.

Figure 1. Angelica plant

Figure 2. Angelica root

Angelica root essential oil

Angelica essential oils exhibit several pharmacological activities, such as antioxidant, antibacterial, antifungal, antimicrobial, and insecticidal activities ³⁾.

Table 1. Angelica essential oils and their major components

S. No.	Species	Parts	Extraction Method; Extraction Time; Yield	Place of Collection	Major Components	References
1	Angelica archangelica L.	Seeds (fruits) from three habitats	Hydrodistillation; 2 h; 0.8–1.4%	Svencionys, Prienai and Vilnius districts in Lithunia	β-phellandrene (33.6–63.4%) and α-pinene (4.2–12.8%)	4)
		Fruit of two chemotypes	Steam distillation; 5 h; 0.17–0.51%	Reykjavik, Iceland	α-pinene (41.4%, 28.9%, 14.4%), bicyclogermacrene (10.1%), and β-phellandrene (37.8% and 55.2%)	5)
		Root (1–2, 3–4 and >5 mm)	Hydrodistillation; 30 min	Rome, Italy	α-pinene (23.89–32.69%) and δ-3-carene (3.41–17.07%)	6)
		Root (3 habitats)	Hydrodistillation; 2 h; 0.2–0.5%	Svencionys, Prienai and Vilnius districts in Lithuania	α-pinene (15.7–20.8%), δ-3-carene (15.4–16.9%), limonene (8.0–9.2%), β-phellandrene (13.5–15.4%), α-phellandrene (8.0–9.1%), and p-cymene (6.8–10.6%)	7)
		Root (3 different altitudes)	Hydrodistillation; 3 h; 0.28–0.35%	Uttarakashi, Rudraprayag and Pothiwasa in Uttarakhand, India	dillapiole (35.93–91.55%) and nothoapiole (0.14–62.81%)	8)
		Root	Hydrodistillation; 2 h; 0.9%	Urbino, Italy	α-pinene (21.3%), δ-3-carene (16.5%), limonene (16.4%), and α-phellandrene (8.7%)	9)
2	Angelica acutiloba (Siebold & Zucc.) Kitag.	Leaves, petiole and root	Hydrodistillation; 3 h; 0.44%	Rutgers University, New Brunswick, NJ, USA	Leaves: ligustilide (11.61%) and butylidene phthalide (7.29%) Petiole: butylidene phthalide (10.76%) Root: nonane (24.85%) and α-pinene (31.59%)	10)
		Root	Solvent free solid injector; injection time—5 min and pre-heating time—7 min)	Yeosu Province, Republic of Korea	butylidene phthalide (17.82%), furfural (13.67%), 2-furanmethanol (11.97%), 5-methyl furfural (8.50%), maltol (7.28%), and butylidene dihydro-phthalide (5.78%)	11)
		Root, stem and leaves	Steam distillation; 5 h; 0.05 (root), 0.06 (stem), and 0.12 (leaves)	Nantou, Taiwan	3n-butyl phthalide (30.8–37.9%), γ-terpinene (21.1–27.2%), p-cymene (3.6–11.6%), and cis-β-ocimene (7.0–7.4%)	12)
			Headspace-solid phase microextraction; 20 min	Nantou, Taiwan	γ-terpinene (41.2–52.1%), p-cymene (10.6–17.0%), β-myrcene (6.7–8.6%), cis-β-ocimene (4.9–7.4%), and alloocimene (4.2–5.3%)	13)
3	Angelica glauca Edgew	Whole plant	Hydrodistillation; 3 h, 0.17%	Jammu and Kashmir, Pakistan	α-phellandrene (18.0%), β-pinene (14.0%), trans-carveol (16.4%), β-caryophyllene (8.6%), and β-caryophyllene oxide (8.0%).	14)
		Aerial parts	Hydrodistillation; 3 h; 0.12%	Khillanmarg areas of Kashmir, India	α-phellandrene (13.5%), trans-carveol (12.0%), β-pinene (11.7%), thujene (7.5%), β-caryophyllene oxide (7.2%), β-caryophyllene (7.0%), γ-terpinene (6.7%), nerolidol (6.5%), and β-bisabolene (5.2%)	15)
		Root	Hydrodistillation; 5 h; 0.3% and 1.8%	Himalayan locations of Uttarakhand, India	(Z)-ligustilide (40.6–53.0%), (Z)-butylidene phthalide (20.7–32.8%), and (E)-butylidene phthalide (2.5–5.9%)	16)
4	Angelica gigas Nakai	Leaves, petiole and root	Hydrodistillation; 3 h; 0.18%	Rutgers University, New Brunswick, NJ, USA	Leaves: nonane (10.75%), α-pinene (33.07%), and germacrene (10.05%) Petiole: nonane (8.85%), α-pinene (40.59%), β-phellandrene (7.52%), and myrcene (6.38%) Root: γ-terpinene (14.08%) and ligustilide (46.63%)	17)
		Root	Hydrodistillation; 4 h	Yeosu Province, Republic of Korea	nonane (19.99%), α-pinene (44.31%), camphene (6.66%), and δ-limonene (6.26%)	18)
			Solvent-free solid injector; injection time—5 min and pre-heating time—7 min)	Yeosu Province, Republic of Korea	decursin (29.34%), decursinol angelate (16.83%), lomatin (10.25%), and marmesin (9.33%)	19)
			Simultaneous steam distillation (n-pentane/diethyl ether); 2 h; 0.31%	Gwangju, Republic of Korea	α-pinene (30.89%), 2,4,6-trimethyl heptane (13.39%), α-limonene (4.29%), and camphene (4.10%)	20)
			Steam distillation; 1 h 30 min; 0.31%	Pyeongchang, Republic of Korea	α-pinene (28.64%), β-eudesmol (14.80%), nonane (8.49%), and γ-eudesmol (5.97%)	21)
			Supercritical CO2 extraction; 1 h; 1.67%	Pyeongchang, Republic of Korea	decursin (40.13%), decursinol angelate (28.44%), and β-eudesmol (7.84%)	22)
5	Angelica sinensis (Oliv.) Diels	Root	Hydrodistillation; 8 h; 0.3%	Gansu Province, China	(Z)-ligustilide 78.61% and (Z)-butylidenephthalide 7.99%	23)
			Solvent free solid injector; injection time—5 min and pre-heating time—7 min)	Yeosu Province, Republic of Korea	butylidene dihydro-phthalide, (15.23%), butylidene phthalide (14.27%), furfural (16%), camphene (10.66%), and 4-pyridinol (7.17%)	24)
			Steam distillation; 3 h; 0.02%	Chiang Mai province, Thailand	3-N-butylphthalide, butylidenephthalide, ligustilide and di-iso-octyl phthalate	25)
6	Angelica koreana Maxim.	Root	Steam distillation; 0.28%	Jinbu, Gangwon-do, Republic of Korea	sabinene (31.85%), m-cresol (4.46%), α-pinene (4.00%), and α-bisabolol (3.63%)	26)
7	Angelica dahurica (Fisch. Ex Hoffm.) Benth. & Hook.	Root	Supercritical CO2 extraction; 2 h; 1.8%	Jilin, China	dodecyl alcohol (13.71%), elemene (7.54%), hexadecanoic acid, ethyl ester (7.32%), 1-pentadecanol (6.08%), and α-pinene (6.25%),	27)
			Hydrodistillation; 3 h; 0.45%	Beijing, China	α-pinene (46.3%), sabinene (9.3%), myrcene (5.5%), 1-dodecanol (5.2%), and terpinen-4-ol (4.9%).	28)
8	Angelica pancicii Vandas ex Velen.	Root	Hydrodistillation; 2 h	Balkan mountains, Serbia	Liquid and headspace injection modes: β-phellandrene (54.9% and 60.1%), α-pinene (14.5% and 20.1%), and α-phellandrene (4.5% and 4.3%).	29)
9	Angelica pubescentis Maxim.	Root	Hydrodistillation; 3 h; 0.65%	Beijing, China	α-pinene (37.6%), p-cymene (11.6%), limonene (8.7%), and cryptone (6.7%)	30)
10	Angelica urumiensis (Mozaffarian)	Stem	Hydrodistillation; 3 h; 0.2%	Uremia, Province West Azerbaijan, Iran	Stem: α-cadinol (9.24%), (epi)-α-cadinol (5.76%), and δ-cadenine (6.11%)	31)
11	Angelica urumiensis (Mozaffarian)	Leaves	Hydrodistillation; 3 h; 0.18%	Uremia, Province West Azerbaijan, Iran	Leaves: α-cadinol (20.2%), hexahydrofarnesyl acetone (10.03%), 1-dodecanol (7.55%), linoleic acid (6.37%) and oleic acid (5.34%)	32)
12	Angelica viridiflora (Turcz.) Benth. ex Maxim.	Aerial parts	Steam distillation; 2 h; 0.2%	Shkotovskii District, Primorsky Krai, Russia	caryophyllene oxide (61.7%) and 3,4-dimethyl-3-cyclohexan-1-carboxaldehdye (5.8%)	33)
13	Angelica cincta Boissieu	Aerial parts	Steam distillation; 2 h; 0.2%	Shkotovskii District, Primorsky Krai, Russia	α-pinene (67.2%), sabinene (5.8%) and β-pinene (4.9%)	34)

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Table 2. Angelica essential oils biological activities

S. No.	Species	Parts	Biological activity	Model	References
1	Angelica archangelica L.	Seeds	Antioxidant	Aldehyde/Carboxylic Acid Assay, DPPH radical scavenging assay, and Malonaldehyde/Gas Chromatography Assay	36)
		Fruit of two chemotypes	Cytotoxic effect	Human pancreas cancer cell line PANC-1 and the mouse breast cancer cell line Crl	37)
		Root	Anti-seizure	Maximal electroshock and pentylenetetrazol-induced seizures in mice	38)
			Anti-aflatoxigenic and antioxidant activities	Aspergillus flavus DPPH radical scavenging assay	39)
			Antimicrobial	Fusarium genus, Botrytis cinerea, and Alternaria solani, Clostridium difficile, Clostridium perfringens, Enterococcus faecalis, Eubacterium limosum, Peptostreptococcus anaerobius, and Candida albicans	40)
2	Angelica gigas Nakai	Root	Nicotine Sensitization	Repeated nicotine-induced locomotor activity and extracellular dopamine levels in the nucleus accumbens of rats	41)
			Human EEG	Increased absolute low beta (left temporal and left parietal) activity	42)
		Leaves	Immunotoxicity	Larvae of Aedes aegypti	43)
3	Angelica glauca Edgew	Whole plant	Antioxidant, antimicrobial, and phytotoxic	Bacteria: Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pasteurella multocida Fungi: Candida albicans, Microsporum canis, Aspergillus flavus and Fusarium solani. DPPH radical scavenging assay Phytotoxic activity against Lemna minor	44)
			Broncho-relaxant	Airway was induced using histamine aerosol in guinea pigs and ovalbumin aerosol in albino mice.	45)
4	Angelica sinensis (Oliv.) Diels	Root	Anti-inflammatory	Carrageenan-induced rats	46)
			Antioxidant	DPPH, ABTS scavenging, and β-carotene bleaching assays.	47)
			Anti-inflammatory	Carrageenan-induced rats and mechanism by plasma metabolomics approach	48)
			Antibacterial	Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis	49)
			Anti-inflammatory	Carrageenan-induced acute inflammation model rats	50)
			Anti-inflammatory	Lipopolysaccharide-induced inflammation rat model	51)
			Anxiolytic	Elevated plus-maze, light/dark and stress-induced hyperthermia tests	52)
				Social interaction test of anxiety and the hole-board test	53)
			Repellent	Against Aedes aegypti	54)
5	Angelica koreana Maxim.	Root	Antifungal and antioxidant	Aspergillus (A. flavus, A. fumigaus, A. niger, A. terreus and A. versicolor) and Trichophyton (T. mentagrophytes, T. rubrum and T. tonsurans) species DPPH scavenging, nitrite inhibition, and reducing power	55)
6	Angelica dahurica (Fisch. Ex Hoffm.) Benth. & Hook.	Root	Anti-inflammatory and immunomodulating properties	Xylene-induced acute ear swelling and carrageenan-induced acute paw edema in mice; anti-inflammatory and immunomodulating properties in Freund’s complete adjuvant (FCA)-induced arthritis in rats.	56)
			Enhance sensitivity of MCF-7/ADR breast cancer cells to doxorubicin	MDR human breast cancer MCF-7/ADR cells	57)
			Insecticidal	Yellow fever mosquito, Aedes aegypti, and azalea lace bugs, Stephanitis pyrioides	58)
			Antibacterial	Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis	59)
			Immunotoxicity	Larvae of Aedes aegypti	60)
7	Angelica pubescentis Maxim.	Root	Antifungal and Insecticidal	Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides, Yellow fever mosquito, Aedes aegypti, and azalea lace bugs, Stephanitis pyrioides	61)
8	Angelica anomala Avé-Lall., Angelica cartilagino-marginata var. distans, Angelica czernevia, Angelica decursiva (Miq.) Franch. & Sav., Angelica fallax H. Boissieu , Angelica japonica A. Gray	Leaves	Immunotoxicity	Larvae of Aedes aegypti	62)
9	Angelica species	Root	Penetration Enhancers for Transdermal Administration of Ibuprofen	Therapeutic efficacy of ibuprofen with essential oil was evaluated using dysmenorrheal model mice	63)
			Skin permeation of drugs	Skin permeation of ibuprofen across rat abdominal skin	64)

Note: DPPH: 1,1-diphenyl-1-picrylhydrazyl; ABTS: 2,2-azino-bis(3ethylbenzo-thiazoline-6-sulfonic acid); EEG: electroencephalographic activity; MDR: multidrug resistance.

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Angelica essential oils chemical composition

The main aim of this review is to offer an overview on the chemical composition of essential oils from different species of Angelica growing in various countries. Table 1 above shows the plant name, plant parts, extraction methods, yield, and the major components of essential oils in relation to different species of Angelica. The published reports revealed that the essential oils of the genus Angelica isolated by steam distillation or the hydrodistillation method mainly consist of monoterpene hydrocarbons. Figure 3 below depicts the chemical structure of some of the major components of essential oils from Angelica species.

In Angelica archangelica seed essential oils, β-phellandrene (33.6–63.4%) and α-pinene (4.2–12.8%) were detected as the most abundant components ⁶⁶⁾. On the other hand, α-pinene (21.3%), δ-3-carene (16.5%), limonene (16.4%), and α-phellandrene (8.7%) were the most abundant components in the essential oil of Angelica archangelica roots growing in Italy ⁶⁷⁾. Nivinskiene et al. ⁶⁸⁾ studied the essential oil composition of Angelica archangelica roots collected from three habitats (Svencionys, Prienai, and Vilnius districts in Lithuania) between 1995–2002. α-Pinene (15.7–20.8%) was the major essential oil component in two localities, whereas β-phellandrene (13.8–18.5%) and α-pinene (11.4–15.0%) were registered as the major essential oil components in the third locality. The Angelica essential oils contained 67.3–79.9% of monoterpenes, 9.6–19.4% of sesquiterpenes, and 3.9–6.3% of macrocyclic lactones. Chauhan et al. ⁶⁹⁾ found that the essential oils of Angelica archangelica rhizomes obtained from three different altitudes of western Himalaya mainly contained dillapiole (35.93–91.55%) and nothoapiole (0.1–62.8%). Further, the authors reported that the composition of essential oils varied greatly with the altitude of collection. Pasqua et al. ⁷⁰⁾ investigated the accumulation of essential oils in the roots of Angelica archangelica subsp. archangelica at different developmental stages. A high concentration of α- and β-phellandrene was found only in taproots exceeding 5 mm in diameter.

The essential oil of the Angelica glauca whole plant collected from Jammu and Kashmir mainly contains α-phellandrene (18.0%), trans-carveol (16.4%), β-pinene (14.0%), β-caryophyllene (8.6%), and β-caryophyllene oxide (8.0%) ⁷¹⁾. Agnihotri et al. ⁷²⁾ investigated the composition of essential oil from fresh aerial parts of Angelica glauca growing in Kashmir valley in higher Himalaya (India), and found that α-phellandrene (13.5%), trans-carveol (12.0%), and β-pinene (11.7%) were the major components. The essential oils from the roots of Angelica glauca collected from two alpine Himalayan locations in Uttarakhand (India) highly contain (Z)-ligustilide (40.6–53.0%) and (Z)-butylidene phthalide (20.7–32.8%) ⁷³⁾.

Kim et al. ⁷⁴⁾ determined the essential oil composition from the rhizomes of Angelica gigas, Angelica sinensis, and Angelica acutiloba by solvent-free solid injector method. Coumarin derivatives such as decursinol angelate (16.83%) and decursin (29.34%) were found to be the most abundant components, followed by lomatin (10.25%), and marmesin (9.33%) in Angelica gigas. Butylidene dihydro-phthalide, (15.23%), butylidene phthalide (14.27%), furfural (16%), and camphene (10.66%) were the main components in Angelica sinensis. Similarly, butylidene phthalide (17.82%) and furfural (13.67%) were registered as the major components in Angelica acutiloba.

Sowndhararajan et al. ⁷⁵⁾ compared the essential oil composition of Angelica gigas root by steam distillation and supercritical carbon dioxide extract. The essential oil mainly composed of monoterpene hydrocarbons (52.83%), followed by oxygenated sesquiterpenes (25.53%). In these, α-pinene (28.64%), β-eudesmol (14.80%), nonane (8.49%), and γ-eudesmol (5.97%) were the major components in the essential oil of Angelica gigas root. However, decursin (40.13%) and decursinol angelate (28.44%) were detected as the most abundant components in supercritical carbon dioxide extract. α-Pinene (30.89%) was also the major component in the essential oil of Angelica gigas extracted by simultaneous steam distillation and extraction method ⁷⁶⁾. In another study, the roots of Angelica gigas and Angelica acutiloba were collected from the field of Snyder Research and Extension Farm Rutgers University, New Jersey, and analyzed for their essential oil composition. The main constituents of the Angelica gigas root essential oil were ligustilide (47%) and γ-terpinene (14%). In the case of Angelica acutiloba root essential oil, α-pinene (32%) and nonane (25%) were the major components ⁷⁷⁾.

Chen et al. ⁷⁸⁾ compared the volatile compositions of Angelica acutiloba roots, stems, and leaves using steam distillation and headspace solid-phase microextraction. In all three parts, a total of 61 and 33 compounds were detected by steam distillation and headspace solid-phase microextraction, respectively. In the steam distillation, 3n-butyl phthalide, γ-terpinene, p-cymene, and cis-β-ocimene were the main compounds. On the other hand, γ-terpinene and p-cymene were the main compounds in headspace solid-phase microextraction. Further, the authors reported that monoterpene components were found to be higher in the headspace solid-phase microextraction sampling method when compared with steam distillation.

In the essential oil of Angelica major, α-pinene (21.8%) and cis-β-ocimene (30.4%) were found to be the most abundant components ⁷⁹⁾. The main components in Angelica dahurica essential oil were α-pinene (46.3%), sabinene (9.3%), myrcene (5.5%), 1-dodecanol (5.2%), and terpinen-4-ol (4.9%). In regards to Angelica pubescentis root essential oil, α-pinene (37.6%), p-cymene (11.6%), limonene (8.7%), and cryptone (6.7%) were found to be the major components ⁸⁰⁾. Champakaew et al. ⁸¹⁾ found that 3-N-butylphthalide, butylidene phthalide, ligustilide, and di-iso-octyl phthalate were the main components in Angelica sinensis essential oil. The composition of essential oils of the stem and leaves of Angelica urumiensis were studied by Mohammadi et al. ⁸²⁾. In the essential oil from the leaves, α-cadinol (20.2%), hexahydrofarnesyl acetone (10.03%), and 1-dodecanol (7.55%) were the major components. On the other hand, α-cadinol (9.24%) and δ-cadenine (6.11%) were the major components in the essential oil from the stem. The essential oil compositions of Angelica pancicii were compared by gas chromatography–mass spectrometry liquid injection and headspace-gas chromatography–mass spectrometry modes. In total, 40 compounds were identified in the essential oil by gas chromatography–mass spectrometry liquid injection, and 44 by headspace-gas chromatography–mass spectrometry. In both cases, the main components were β-phellandrene, α-pinene, and α-phellandrene ⁸³⁾. Caryophyllene oxide (61.7%) and α-pinene (67.2%) were detected as the most abundant components in essential oils of Angelica viridiflora and Angelica cincta aerial parts, respectively ⁸⁴⁾.

Figure 3. Angelica essential oils chemical components

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Angelica essential oils potential health benefits and uses

Antioxidant

1,1-Diphenyl-2-picrylhydrazil (DPPH) and 2,2-azino-bis(3ethylbenzo-thiazoline-6-sulfonic acid (ABTS) radical scavenging activities are extensively used measures to evaluate the antioxidant potential of plant extracts or compounds. DPPH, nitrite inhibition, and reducing power were determined to assess the antioxidant activity of Angelica koreana essential oil and its major components. m-Cresol (56.12%) showed stronger DPPH scavenging activity than essential oil (19.31%) and sabinene (4.45%) at the concentration of 16 mg/mL ⁸⁶⁾. Additionally, sabinene exhibited the strongest reducing power and nitric oxide scavenging activities than the essential oil fraction or m-cresol. Irshad et al. ⁸⁷⁾ reported that Angelica glauca essential oil exhibited good DPPH radical scavenging and peroxidation inhibition activities. Angelica seed oil showed 39% of DPPH radical scavenging activity at the concentration of 200 μg/mL ⁸⁸⁾. The antioxidant activity of Angelica sinensis was investigated by DPPH, ABTS, and beta-carotene bleaching assays. Angelica sinensis essential oil and coniferyl ferulate rich fractions 1 and 2 showed strong DPPH (IC50 of 194.7, 42.4 and 15.2 μg/mL, respectively) and ABTS (IC50 of 98.8, 15.9 and 7.8 μg/mL, respectively) radical scavenging activities. Further, coniferyl ferulate rich fractions 1 and 2 exhibited good β-carotene bleaching activity with IC50 values of 11.0 and 2.0 μg/mL, respectively ⁸⁹⁾. In another study, the DPPH radical scavenging activity of Angelica archangelica essential oil, α-terpineol, phenyl ethyl alcohol, and their combination were determined. The IC50 values of Angelica archangelica essential oil, α-terpineol, and their essential oil-based combination were 1.04, 66.6, and 3.89 μL/mL, respectively ⁹⁰⁾.

Antimicrobial

Angelica koreana essential oil and its main components, sabinene and m-cresol, showed antifungal activity against different species of Aspergillus and Trichophyton with minimal inhibitory concentrations (MICs) of 125–1000 μg/mL. In addition, essential oil exhibited synergistic activity when combined with itraconazole ⁹¹⁾. The essential oil of Angelica glauca showed appreciable antimicrobial activity against selected strains of bacteria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pasteurella multocida) and fungi (Candida albicans, Microsporum canis, Aspergillus flavus, and Fusarium solani). Among the bacterial strains tested, Escherichia coli and Staphylococcus aureus were the most sensitive bacteria with minimum inhibitory concentration (MIC) values of 141.3 and 159.3 µg/mL, respectively. In regards to fungal strains, Microsporum canis was the most sensitive organism with a MIC value of 178.1 µg/mL ⁹²⁾.

The essential oil of Angelica archangelica root showed considerable antimicrobial activity against Clostridium difficile, Clostridium perfringens, Enterococcus faecalis, Eubacterium limosum, Peptostreptococcus anaerobius, and Candida albicans. Further, Angelica archangelica essential oil showed a weaker antimicrobial activity against the intestinal microflora such as bifidobacteria and lactobacilli. In another study, the essential oil showed antifungal activity against some species of the Fusarium genus, Botrytis cinerea, and Alternaria solani ⁹³⁾. A combination of Angelica archangelica essential oil: Phenyl ethyl alcohol (PEA): α-terpineol (1:1:1) inhibited the growth of Aspergillus flavus NKDW-7 (aflatoxigenic strain) and aflatoxin B1 production at 2.25 and 2.0 μL/mL, respectively. At the concentration of 2.0 μL/mL, the combination showed a >90% decrease in ergosterol content in the plasma membrane of Aspergillus flavus ⁹⁴⁾.

Cavaleiro et al. ⁹⁵⁾ evaluated the antifungal activity of the essential oil of Angelica major and its major components, α-pinene and cis-β-ocimene, against clinically important yeasts and molds. Angelica major essential oil exhibited a broad spectrum of antifungal activity, including all tested fungi (animal and human pathogenic species or spoilage fungi): Candida spp., Candida neoformans, Aspergillus spp., and dermatophytes. α-Pinene was more active against all of the tested fungi than cis-β-ocimene. Angelica sinensis and Angelica dahurica essential oils exhibited significant antibacterial activity against three mastitis-causing pathogens: Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis ⁹⁶⁾. Tabanca et al. ⁹⁷⁾ reported that Angelica pubescentis root essential oil exhibited weak antifungal activity against Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides. In the case of Angelica dahurica root essential oil, there was no antifungal activity observed against tested fungal strains.

Insecticidal

Essential oils from the root of Angelica dahurica and Angelica pubescentis were studied as pest management prospectives. When compared with Angelica pubescentis essential oil, Angelica dahurica essential oil showed better biting deterrent and insecticidal activity against Aedes aegypti and Stephanitis pyrioides. In mosquito bioassays, components of Angelica dahurica essential oil, 1-dodecanol and 1-tridecanol, showed antibiting deterrent activity against Aedes aegypti ⁹⁸⁾. Chung et al. ⁹⁹⁾ investigated the immunotoxicity effect of essential oils from the leaves of Angelica anomala, Angelica cartilagino-marginata var. distans, Angelica czernevia, Angelica dahurica, Angelica decursiva, Angelica fallax, Angelica gigas, and Angelica japonica. Among them, the essential oil of Angelica dahurica showed a significant toxic effect against early fourth-stage larvae of Aedes aegypti, with a LC50 value of 43.12 ppm. In another study, out of 33 plant species tested, Angelica sinensis essential oil showed the best repellent activity against Aedes aegypti, with a median complete protection time of 7.0 hours ¹⁰⁰⁾.

Behavioral

Repeated administration of nicotine can produce behavioral sensitization, and this is a good model for studying drug addiction. Zhao et al. ¹⁰¹⁾ reported that the inhalation of Angelica gigas essential oil significantly ameliorated nicotine-induced behavioral sensitization by decreasing dopamine release in the nucleus accumbens and locomotor activity in repeated nicotine-induced rats. Pathak et al. ¹⁰²⁾ found that the essential oil of the Angelica archangelica root exhibited antiseizure activity against electrically and chemically-induced seizures in mice. Chen et al. ¹⁰³⁾ investigated the anxiolytic activity of Angelica essential oil in a mice model. The results revealed that the essential oil of Angelica exhibited considerable anxiolytic-like effects at the concentration of 30.0 mg/kg (orally), as measured in the elevated plus-maze, the light/dark, and the stress-induced hyperthermia tests. In addition, Angelica essential oil significantly improved the behavioral performances in the social interaction test of anxiety and the hole-board test of exploration and locomotor activity in rats ¹⁰⁴⁾. Sharma et al. ¹⁰⁵⁾ reported that the essential oil of Angelica glauca exhibited broncho-relaxant activity against histamine and ovalbumin-induced bronchoconstriction in guinea pigs by decreasing absolute blood eosinophil count, serum levels of immunoglobulin E, and the number of eosinophils and neutrophils in bronchoalveolar lavage fluid. Sowndhararajan et al. ¹⁰⁶⁾ investigated the effect of inhalation of essential oil of Angelica gigas root on electroencephalographic activity in humans. The results revealed that absolute low beta significantly increased at left temporal and left parietal region during the inhalation of the essential oil of Angelica gigas root, and these changes may contribute to the enhancement of language learning abilities in humans.

Anti-Inflammatory

Zhang et al. ¹⁰⁷⁾ used the metabonomics based on gas chromatography–mass spectrometry to study the possible anti-inflammatory mechanisms of essential oil of Angelica sinensis in rats with acute inflammation. In the carrageenan-injected rats, treatment with the essential oil of Angelica sinensis significantly restored the levels of prostaglandin E2, histamine, and 5-hydroxytryptamine in the inflammatory fluid, similar to the normal group. Gas chromatography–mass spectrometry analysis identified 14 metabolite biomarkers detected in the inflammatory fluid. Zhong et al. ¹⁰⁸⁾ evaluated the anti-inflammatory effect of essential oils obtained from processed products of Angelica sinensis. For this purpose, essential oils from stir-fried Angelica sinensis, fried Angelica sinensis with alcohol, cooked Angelica sinensis with soil, and fried Angelica sinensis with sesame oil were applied to intervene the carrageenan-induced acute inflammation of the model rats. The results showed that the essential oils of Angelica sinensis significantly inhibited the release of prostaglandin E2, histamine, 5-hydroxytryptamine, and tumor necrosis factor-α. Furthermore, Angelica sinensis exhibited an anti-inflammatory effect against the lipopolysaccharide (LPS)-induced inflammation rat model by regulating the Krebs cycle, enhancing the glucose content, and restoring the fatty acid metabolism ¹⁰⁹⁾.

Li et al. ¹¹⁰⁾ investigated the effects of Angelica sinensis essential oil on the lipopolysaccharide-induced acute inflammation rat model. Angelica sinensis essential oil exhibited anti-inflammatory and liver protection effects by inhibiting the secretion of the pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), the inflammatory mediators (histamine, 5-hydroxytryptamine, prostaglandin E2, and nitric oxide), the inflammation-related enzymes (inducible nitric oxide synthase and cyclooxygenase 2), as well as promoting the production of the anti-inflammatory cytokines interleukin-10. Wang et al. ¹¹¹⁾ reported that the essential oil of Angelica dahurica (at 100 mg/kg) showed anti-inflammatory activity against xylene-induced ear swelling and carrageenan-induced paw edema in a mice model. In addition, the essential oil significantly alleviated Freund’s complete adjuvant-induced arthritis in rats by improving hind paw swelling and reducing the serum levels of nitric oxide, tumor necrosis factor-α, prostaglandin E2, and serum nitric oxide synthase activity.

Skin permeation enhancer of drugs

It is well known that essential oils can reversibly overcome the stratum corneum barrier to improve the skin permeation of drugs. Chen et al. ¹¹²⁾ studied the penetration enhancement effect of five essential oils (clove, Angelica, Chuanxiong, Cyperus, and cinnamon) on the transdermal drug delivery of ibuprofen using dysmenorrheal model mice. Among five essential oils tested, Chuanxiong and Angelica oils effectively enhanced the transdermal drug delivery of ibuprofen. In another study, turpentine, Angelica, Chuanxiong, Cyperus, cinnamon, and clove oils (at 3% w/v) were evaluated for the potential to enhance the skin penetration of ibuprofen in rats. When compared with azone, the tested essential oils had significantly higher penetration enhancement effect and lower skin irritation potential. The results revealed that essential oils can enhance the skin permeation of ibuprofen mainly by disturbing the stratum corneum lipids ¹¹³⁾.

Angelica root benefits

Traditionally, Angelica sinensis, Angelica gigas, and Angelica acutiloba are the most important Angelica species, which are mainly found in Korea, China, and Japan, respectively ¹¹⁴⁾. In China, Angelica sinensis has been used for the treatment of various ailments such as gynecological diseases, apoplexia, constipation, malaria, chills, fever, and hemorrhoids. The plant has also been used as a hematinic for nourishing blood, regulating menstruation, and relaxing bowels ¹¹⁵⁾. In the Korean traditional medicine, Angelica root part of Angelica gigas has been to treat anemia, gynecological diseases, circulatory diseases, and arthritis. It has also been used as sedative, analgesic, and tonic agents ¹¹⁶⁾. Angelica acutiloba is traditionally used to treat gynecological diseases and anemia ¹¹⁷⁾. Angelica archangelica is commonly used in traditional medicine to cure nervousness, insomnia, stomach and intestinal disturbances, skin diseases, respiratory problems, and arthritis ¹¹⁸⁾. Angelica glauca has been used to treat bilious complaints, infantile atrophy, and constipation ¹¹⁹⁾. Angelica dahurica has been mainly used to treat headaches, rhinitis, toothaches, rheumatism, and sore throat ¹²⁰⁾. Angelica pubescentis has been used to cure rheumatoid arthritis, headache, paralysis, and insomnia ¹²¹⁾.

Summary

From the research thus far, it seems the active compounds of Angelica root are the essential oils.  Essential oils have been isolated from different plant parts of Angelica species. The most abundant components in the essential oils were α-pinene, β-pinene, α-phellandrene, β-phellandrene, δ-3-carene, sabinene, γ-terpinene, limonene, p-cymene, ligustilide, butylidene phthalide, α-cadinol, and β-eudesmol. Based on the previous reports, the essential oils from different Angelica species exhibit appreciable antioxidant, antimicrobial, insecticidal and anti-inflammatory activities. In addition, essential oils significantly enhance behavioral performances and promote the skin permeation of drugs. Among the different Angelica species, Angelica archangelica, Angelica sinensis, and Angelica dahurica were the most studied plant species in relation to the biological activities of essential oils. Now further studies including clinical trials are needed to validate and confirm Angelica essential oil biological activities in the treatment of diseases and health conditions.