Ethnomedicinal Uses, Phytochemistry and Pharmacology of Dorema Species (Apiaceae): A Review

Abstract

The application of antique medical instructions, practices, skills and knowledge has been considered as the most affordable treatment in many developing countries. The use of these preparations and prescriptions over generations has made a useful and valuable guide for drug discovery in modern medicine. Medical herbs have been of a high importance for this purpose. The genus Dorema, of Apiaceae family (Umbelliferae) has a wide use in ethnobotany and traditional medicine around the world. It has been used as a treatment for CNS disease, convulsion, upper respiratory tract problems, gastrointestinal disorder and high blood sugar. Furthermore, phytochemical investigations have reported Dorema species to contain a wide range of constituents including terpenes, coumarins and phenolic compounds. The current review summarizes comprehensive information regarding botany, phytochemistry andpharmacological aspects of Dorema spp.

INTRODUCTION

The genus Dorema D. Don, belongs to the Apiaceae family (Umbelliferae) with important medicinal and aromatic species. It contains a total of 12 accepted species worldwide (http://www.theplantlist.org). Among them 7 are represented in Iran [1]. The genus has been used as a food additive as well as for various medicinal purposes in traditional and folklore medicine around the world [2].

Dorema ammoniacum, commonly known as “Ushaq” or “Vasha”, is considered as one of the most studied species [3]. Being rich in ammoniacum, a medicinal gum-resin, it has been mentioned in Islamic Traditional Medicine (ITM) as a treatment for various disorders, such as gastrointestinal, upper respiratory tract and central nervous systems problems [3-5]. Furthermore, numerous chemical compounds including terpenes, coumarins and phenolic compounds have been isolated from Dorema species and a wide range of pharmacological activities including anti-microbial, anti-inflammatory, antioxidant, cytotoxicity, anticonvulsant, anti-diabetic and hypolipidemic activities have been reported from this genus in modern medicine [6].

In the current review we present a comprehensive report on ethnobotanical and traditional uses, phytochemical compounds and pharmacological activities of the genus Dorema.

BOTANY

1. Botanical description of Dorema spp.

Dorema species are large monocarpic perennial plant, with thickened storage roots, and have large simple umbels with regular flowers, bisexual and staminate, the bisexual on upper branches and the staminate on lower, rarely flowers mixed; Involucre of few caducous leaflets, or lacking; calyx 5-toothed, indistinct; petals are yellow, cream- colored or greenish yellow, nerve darker, ovate- elongate, with inward curved tip; The stigmas are truncate or thickened; stylopodium is flat, fleshy with lobed broadened margin, becoming cup-shaped; ovary is cylindrical, faintly ribbed. Fruit with free carpophore, dorsally piano- compressed, elliptic, with filiform protruding ribs, 2 lateral ribs fusing with unthicken, whitish margin. Geographically, Dorema is distributed in the Caucasus and the southern parts of Central Asia. It also grows in Iran, Afghanistan and Baluchistan. Its northernmost representative (Dorema microcarpum Korovin.) appears in Central Asia, its southern limit lies in Tien Shan. Dorema is typical in arid conditions and most species occur in dry foothills and hills, some grow in deserts.

They are confined to calcareous soils, often mixed with rock debris. One species, Dorema sabulosum Litv. is a typical psammophyte [7, 8]. According to The Plant List, there are 25 scientific plant names of species rank for the genus Dorema, of these 12 are accepted species names (http://www.theplantlist.org). In Iran, the genus Dorema is represented by seven species, namely, D. aitchisonii Korovin ex Pimenov, D. ammoniacum D.Don, D. aucheri Boiss., D. aureum Stocks, D. glabrum Fisch. & C.A. Mey., D. hyrcanum Koso-Pol. and D. kopetdaghense Pimenov which among them D. aucheri Boiss. is endemic to Iran. Dorema kopetdaghensePimenovin Flora Iranica, treated as a synonym of D. hyrcanum Koso-Pol. However, phylogenetic analysis of nrDNA internal transcribed spacer (ITS) sequences showed that these two species should be retained as separate species [1, 9, 10]. Table 1 summarizes all synonyms of Dorema species based on the website “TPL” (http://www.theplantlist.org).

Table 1.

Scientific names and synonyms of reported Dorema species worldwide [according to The Plant List (2013)]

No	Dorema species (Accepted names)	Synonyms
1	D. aitchisonii Korovin ex Pimenov
2	D. ammoniacum D.Don	D. gummiferum (Jaub. & Spach) K.M.Korol. D. hirsutum Lofius ex I.G.Borshch.
3	D. aucheri Boiss.	D. robustum Lofius ex I.G.Borshch.
4	D. aureum Stocks
5	D. badhysi Pimenov
6	D. balchanorum Pimenov
7	D. glabrum Fisch. & C.A.Mey.
8	D. hyrcanumKoso-Pol.	D. gummiferum auct.
9	D. karatavienseKorovin
10	D. kopetdaghense Pimenov
11	D. microcarpum Korovin	D. namanganicum K.M. Korol.
12	D. sabulosum Litv.	D. sabulosum var. borszczowii Litv.

2. Threats and conservation priorities

The genus Dorema, contains monocarpic perennial species, so that only once produces flowers during the life cycle and only reproduces through seeds. These plants are potentially endangered and vulnerable taxa [11]. Some of these taxa such as D. aucheri are narrow-range endemics which occur only in a few specialized niches. D. aucheri is considered as a unique endemic species which is intensively collected. Overexploitation of this plant has caused a significant decrease in its population in the area [12]. Furthermore, some others are sub-endemics with threatened species including D. ammoniacum, and D. kopetdaghense. Today, D. kopetdaghense is also considered as endangered in the IUCN Red List of threatened Species [13]. It has been used in traditional medicine from ancient times [2].

Dorema ammoniacum commonly known as “Ushaq” or “Vasha” is one of the most important industrial and medicinal plants of Iran which has been used in ethnobotanical since ancient times. It is endangered due to superfluous and unsustainable harvesting methods [3, 4]. Dorema glabrum is another endangered species that grows in loamy or rocky slopes of Nakhichevan, Autonomous Republic- Azerbaijan, Armenia and Iran [1, 10]. The plant has immense applications as an herbal remedy or food additive in these regions. Over harvesting from wild populations and destructive collecting methods, are considered as serious threats that often lead to disappearance of these taxa, and must be avoided. There is an urgent need for conservation priorities and management strategies for all taxa assigned to a threat category through seed and gene banking, and planting in botanical gardens. Otherwise, we will lose these natural treasures within the next few decades.

PHYTOCHEMICAL CONSTITUENTS

The instrumental analysis was revealed that a range of various compounds were identified in Dorema species, including essential oil structure that made up hydrocarbon molecules and classified as terpenes, alcohols, esters, aldehydes, ketones and phenols, also contain phenolic and coumarin compounds (Table 2). These phytochemicals derived from different parts of Dorema species such as flower, fruit, leaf, stem and root.

Table 2.

Chemical composition from different parts of Dorema species

	Name of compound	Structure	Species	Plant part	Ref
		Essential oil components
1	α-pinene		D. ammoniacum D. aucheri D. glabrum	Aerial parts Flower Stem Seed Leaf Root Leaves Aerial parts Stem Seed Aerial parts	[14-18] [19, 20] [21]
2	camphene		D. ammoniacum D. aucheri	Flower Stem Root Seed Stem	[14] [19, 20]
3	β-pinene		D. ammoniacum D. aucheri	Flower Stem Root Seed Stem	[14] [19, 20]
4	β-myrcene		D. aucheri D. glabrum D. ammoniacum	Seed Stem Aerial part Flower Stem Root Leaves	[19, 20] [21] [14, 17, 18]
5	p-cymene		D. ammoniacum	Aerial parts Flower stem Root	[14, 15, 18]
6	limonene		D. ammoniacum D. aucheri D. glabrum	Flower stem Seed Root Leaf Leaves Aerial parts Seed Stem Aerial parts	[14, 16, 18] [19, 20] [21]
7	β-phellandrene		D. ammoniacum	Aerial parts Root	[15]
8	1,3,8-p-menthatriene		D. ammoniacum	Aerial part	[22]
9	p-mentha-1,8-diene		D. ammoniacum	Fruit	[22]
10	(E)-β-ocimene		D. ammoniacum D. aucheri D. glabrum	Flower Stem Root Leaves Aerial parts Aerial parts	[14, 18] [19] [21]
11	(Z)-β-ocimene		D. glabrum D. ammoniacum	Aerial parts Stem Leaves	[21] [18]
12	terpinolene (δ-terpinene)		D. ammoniacum D. aucheri	Aerial parts Flower Root Stem Leaf Leaves Aerial parts Seed Stem	[14, 15, 17-19] [19, 20]
13	terpinene-4-ol		D. aucheri	Aerial part	[20]
14	thymol methyl ether		D. ammoniacum D. aucheri	Flower stem Root Seed Aerial parts	[14, 16] [19]
15	thymol		D. ammoniacum D. aucheri	Seed Stem Aerial part Seed Stem	[16] [20]
16	methyl geranate		D. aucheri	Aerial part	[19]
17	carvacrol methyl ether		D. ammoniacum D. glabrum	Flower Stem Root Root	[14] [23]
18	carvacrol		D. aucheri D. ammoniacum	Stem Seed Stem Seed	[20] [16]
19	methyleugenol		D. ammoniacum	Seed	[16]
20	bornyl acetate		D. ammoniacum D. aucheri	Flower Stem Root Leaves Aerial parts Seed Stem	[14, 18] [19, 20]
21	fenchyl acetate		D. glabrum	Aerial parts	[21]
22	endo-fenchol		D. ammoniacum	Leaf	[18]
23	α-fenchyl Acetate		D. glabrum	Root	[23]
24	α-cubebene		D. ammoniacum D. aucheri	Flower Fruit Stem Root Aerial parts	[14, 22] [19]
25	β-cubebene		D. aucheri	Aerial parts	[20]
26	β-elemene		D. aucheri	Aerial parts	[20]
27	α-copaene		D. ammoniacum D. aucheri D. glabrum	Flower Fruit Stem Seed Leaves Root Aerial parts Seed Stem Root	[14, 16, 22] [19, 20] [23]
28	β-copaene		D. aucheri	Aerial parts	[22]
29	aristolene		D. ammoniacum	Flower stem	[14]
30	β-patchoulene		D. aucheri	Aerial parts	[19]
31	α-gurjunene		D. ammoniacum	Flower stem	[14, 16]
32	β-gurjunene		D. ammoniacum D. aucheri	Flower Stem Root Aerial parts Seed Stem	[14] [19, 20]
33	β-caryophyllene		D. ammoniacum D. aucheri	Flower stem Seed Root Leaf Aerial parts Seed Stem	[14, 16, 17] [19, 20, 24]
34	caryophyllene		D. ammoniacum	Aerial parts	[15]
35	α-santalene		D. aucheri	Aerial parts	[19]
36	aromadendrene		D. ammoniacum D. aucheri	Flower stem Seed Root Aerial parts	[14, 16] [19]
37	α-guaiene		D. ammoniacum	Flower stem Root	[14]
38	benzyl butanoate		D. ammoniacum	Root	[14]
39	α-himachalene		D. ammoniacum	Flower stem Root	[14]
40	allo-aromadendrene		D. ammoniacum	Flower stem Root	[14]
41	dehydroaromadendrane		D. ammoniacum	Flower stem Root	[14, 16]
42	α-amorphene		D. ammoniacum D. aucheri	Flower stem Root Seed Stem	[14] [20]
43	δ-amorphene		D. ammoniacum	Flower stem Root	[14]
44	β-selinene		D. ammoniacum D. aucheri	Flower stem Seed Root Seed Stem	[14, 16] [20]
45	α-selinene		D. ammoniacum D. aucheri	Aerial part Flower Root Stem Seed Stem	[14, 15] [20]
46	viridiflorene		D. aucheri	Aerial part	[19]
47	α-muurolene		D. ammoniacum D. glabrum	Flower, stem Root Root	[14] [23]
48	γ-muurolene		D. ammoniacum	Stem	[16]
49	cadalene		D. glabrum	Root	[23]
50	δ-cadinene		D. ammoniacum D. aucheri D. glabrum	Flower seed Stem Aerial parts Seed Stem Root	[14, 16, 17] [18, 20, 24] [23]
51	γ-cadinene		D. aucheri D. ammoniacum	Aerial parts Seed Stem	[19] [16]
52	cadina-1,4-diene		D. aucheri	Aerial part	[19]
53	trans-cadina-1(2),4-diene		D. ammoniacum	Stem	[16]
54	β-sesquiphellandrene		D. ammoniacum	Seed	[16]
55	ledol		D. ammoniacum	Stem	[16]
56	liguloxide		D. ammoniacum	Flower Root Stem	[14]
57	(E)-nerolidol		D. ammoniacum D. glabrum	Flower Root Leaf Stem Seed Root	[14, 16, 17] [23]
58	3-n-butyl phthalide		D. ammoniacum	Root	[14]
59	2-pentylfuran		D. glabrum	Aerial parts	[21]
60	myristicin		D. glabrum	Aerial parts	[21]
61	elemicin		D. glabrum	Aerial parts	[21]
62	methyl heptenone		D. ammoniacum	Aerial parts	[15]
63	trans-sesquisabinene hydrate		D. aucheri	Aerial parts	[19]
64	γ-eudesmol		D. ammoniacum D. aucheri	Seed Stem Aerial parts	[16] [19]
65	α-eudesmol		D. ammoniacum D. aucheri	Seed Stem Aerial parts	[16] [19, 24]
66	β-eudesmol		D. ammoniacum	Seed Stem	[16]
67	sesquicineol-2-one		D. ammoniacum	Seed Stem	[16]
68	germacrene D-4-ol		D. aucheri	Aerial part	[19]
69	α-cadinol		D. ammoniacum D. aucheri D. glabrum	Stem Seed Aerial parts Root	[16] [19] [23]
70	δ-cadinol		D. glabrum	Root	[23]
71	spathulenol		D. ammoniacum D. aucheri	Fruit Seed Stem Seed Stem	[16, 22] [20]
72	caryophyllene oxide		D. ammoniacum D. aucheri	Fruit Seed Stem Leaf Seed Stem	[16, 17, 22] [20]
73	4-methylene-5-hexenal		D. ammoniacum	Stem	[18]
74	6-methyl-5-hepten-2-one		D. ammoniacum	Stem	[18]
75	allyl tiglate		D. ammoniacum	Stem	[18]
76	nerolidyl acetate		D. ammoniacum	Stem	[16]
77	ammoresinol		D. ammoniacum	Aerial parts	[25]
78	nonanol		D. ammoniacum	Aerial parts	[15]
79	camphor		D. ammoniacum	Aerial parts	[15]
80	trans-2-caren-4-ol		D. ammoniacum	Fruit	[22]
81	β-cyclocitral		D. ammoniacum	Fruit	[22]
82	piperitenone oxide		D. ammoniacum	Fruit	[22]
83	(E)-2-nonenal		D. ammoniacum	Stem	[18]
84	β-citronellol		D. ammoniacum	Aerial parts	[15]
85	β-damascenone		D. ammoniacum	Aerial parts	[15]
86	cedr-8[15]-ene		D. ammoniacum	Aerial parts	[15]
87	cubenol		D. aucheri D. glabrum	Aerial parts Root	[19] [23]
88	thujopsene		D. ammoniacum	Aerial parts	[15]
89	ylangene		D. glabrum D. aucheri	Aerial parts Seed Stem	[21] [20]
90	nerylacetone		D. ammoniacum	Aerial parts	[15, 17]
91	geranyl acetone		D. glabrum	Aerial parts Root	[21] [23]
92	(E)-tagetone		D. ammoniacum	Fruit	[22]
93	(Z)-tagetone		D. ammoniacum	Fruit	[22]
94	(Z)-ocimenone		D. ammoniacum	Fruit	[22]
95	(E)-ocimenone		D. ammoniacum	Fruit	[22]
96	α-bisabolene		D. ammoniacum	Aerial parts	[15]
97	β-bourbonene		D. aucheri D. ammoniacum	Seed Stem Fruit	[20] [22]
98	italicene		D. ammoniacum	Fruit	[22]
99	di-epi-α-cedrene		D. ammoniacum	Fruit	[22]
100	α-longipinene		D. ammoniacum	Fruit	[22]
101	α-cedrene		D. ammoniacum	Aerial parts	[15]
102	β-cedrene		D. glabrum D. ammoniacum	Aerial parts Fruit	[21] [22]
103	β-barbatene		D. ammoniacum	Fruit	[22]
104	α-humulene		D. aucheri D. ammoniacum	Aerial parts Seed Stem Fruit	[17, 18] [22]
105	ar-curcumene		D. ammoniacum	Fruit	[22]
106	germacrene D		D. aucheri D. ammoniacum	Aerial parts Stem Seed Seed Stem Fruit	[17, 18] [16, 22]
107	germacrene B		D. aucheri D. glabrum	Aerial parts Aerial parts Root	[19] [21, 23]
108	bicyclogermacrene		D. ammoniacum	Fruit Seed	[16, 22]
109	cuparene		D. glabrum D. aucheri D. ammoniacum	Aerial parts Sead Stem Fruit	[21] [20] [24]
110	α-cadinene		D. ammoniacum	Fruit Stem	[16, 22]
111	2-nonanone		D. ammoniacum	Stem	[16]
112	(Z)-hexadec-11-enal		D. ammoniacum	Stem	[16]
113	hexadecanal		D. ammoniacum	Stem	[16]
114	ethyl linoleate		D. ammoniacum	Stem	[16]
115	(Z,E)-farnesal		D. ammoniacum	Aerial parts	[15]
116	pentadecanal		D. ammoniacum	Aerial parts	[15]
117	dodecyl methacrylate		D. ammoniacum	Aerial parts	[15]
118	17-octadecenal		D. ammoniacum	Aerial parts	[15]
119	13-tetradecenal		D. ammoniacum	Aerial parts	[15]
120	tetradecanal		D. glabrum D. ammoniacum	Aerial parts Stem Seed	[21] [16]
121	trans-sesquilavandulol		D. ammoniacum	Seed Stem	[16]
122	neophytadiene		D. ammoniacum	Aerial parts	[15, 17]
123	neocembren		D. ammoniacum	Aerial parts	[15]
124	(E)-5-undecen-3-yne		D. ammoniacum	Fruit	[22]
125	(Z)-(E)-farnesene		D. ammoniacum	Aerial parts	[22]
126	trans-β-farnesene		D. ammoniacum	Seed	[16]
127	n-hexadecanoic acid		D. ammoniacum D. aucheri	Aerial parts	[15] [19]
128	kopetdaghin A		D. kopetdaghense	Aerial parts	[2, 26]
129	kopetdaghin B		D. kopetdaghense	Aerial parts	[26]
130	kopetdaghin C		D. kopetdaghense	Aerial parts	[2, 26]
131	kopetdaghin D		D. kopetdaghense	Aerial parts	[2, 26]
132	kopetdaghin E		D. kopetdaghense	Aerial parts	[2, 26]
133	hexadecan		D. aucheri	Aerial parts	[21]
134	decanol		D. ammoniacum	Stem	[18]
135	heptadecanoic acid		D. ammoniacum	Fruit	[22]
136	oleic acid		D. ammoniacum	Aerial parts	[15]
137	2,5-dimethyltetrahydrofuran		D. ammoniacum	Leaf Stem	[17]
138	methylbenzene		D. ammoniacum	Leaf Stem	[17]
139	cyclohexane, 1,3-dimethyl, trans		D. ammoniacum	Leaf Stem	[17]
140	valeraldehyde		D. ammoniacum	Leaf Stem	[17]
141	octane		D. ammoniacum	Leaf Stem	[17]
142	imidazole-5-carboxylic acid, 2-amino		D. ammoniacum	Leaf Stem	[17]
143	butyl acetate		D. ammoniacum	Leaf Stem	[17]
144	cyclohexane, 1,2-dimethyl, cis		D. ammoniacum	Leaf Stem	[17]
145	N,N-dimethyl cyclobutane-1,1-bis(methylamine)		D. ammoniacum	Leaf Stem	[17]
146	furfural		D. ammoniacum	Leaf Stem	[17]
147	deuteroacetone		D. ammoniacum	Leaf Stem	[17]
148	styrene		D. ammoniacum	Leaf Stem	[17]
149	1-methyldodecylamine		D. ammoniacum	Leaf Stem	[17]
150	aziridine, 1-(2-buten-2-yl)		D. ammoniacum	Leaf Stem	[17]
151	sabinene		D. ammoniacum	Leaf Stem	[17]
152	decane		D. ammoniacum	Leaf Stem Seed	[17, 18]
153	acetamide, 2-chloro		D. ammoniacum	Leaf Stem	[17]
154	2-butylamine		D. ammoniacum	Leaf Stem	[17]
155	phenyl acetaldehyde		D. ammoniacum	Leaf Stem	[17]
156	2-amino-4-hydroxypteridine-6-carboxylic acid		D. ammoniacum	Leaf Stem	[17]
157	benzenamine, N-methyl-2-(2-propenyl)		D. ammoniacum	Leaf Stem	[17]
158	undecane		D. ammoniacum	Leaf Stem Seed	[17, 18]
159	limonene oxide		D. ammoniacum	Leaf Stem	[17]
160	isopropyl isocyanate		D. ammoniacum	Leaf Stem	[17]
161	2-hexanamine, 4-methyl		D. ammoniacum	Leaf Stem	[17]
162	2,6-dimethyl-4-pyrone		D. ammoniacum	Leaf Stem	[17]
163	dodecane		D. ammoniacum	Leaf Stem	[17]
164	2,4-hexadiene, 3-methyl		D. ammoniacum	Leaf Stem	[17]
165	β-fenchyl alcohol		D. ammoniacum	Leaf Stem	[17]
166	homarine		D. ammoniacum	Leaf Stem	[17]
167	2-(N,N-dimethyl hydrazino) cyclohexane carbonitrile		D. ammoniacum	Leaf Stem	[17]
168	phenol, 4-(2-aminopropyl)		D. ammoniacum	Leaf Stem	[17]
169	2-oxo-3-methyl-cis-perhydro-1,3-benzoxazine		D. ammoniacum	Leaf Stem	[17]
170	trans-carveol		D. ammoniacum	Leaf Stem	[17]
171	benzene, (2-fluoro-2-methoxycyclopropyl)		D. ammoniacum	Leaf Stem	[17]
172	2(1H)-naphthalenone, octahydro-8a-methyl, trans		D. ammoniacum	Leaf Stem	[17]
173	p-methoxyamphetamine		D. ammoniacum	Leaf Stem	[17]
174	2-cyclohexen-1-one, 2-methyl-5-(1-methylethenyl)		D. ammoniacum	Leaf Stem	[17]
175	2-methyl amphetamine		D. ammoniacum	Leaf Stem	[17]
176	2-methoxy amphetamine		D. ammoniacum	Leaf Stem	[17]
177	tridecane		D. ammoniacum D. glabrum	Leaf Stem Aerial parts	[17] [21]
178	benzenemethanol, alpha-(1-aminoethyl)		D. ammoniacum	Leaf Stem	[17]
179	naphthalene, 1,2-dihydro-1,1,6-trimethyl		D. ammoniacum	Leaf Stem	[17]
180	rimantadine		D. ammoniacum	Leaf Stem	[17]
181	heptadecane		D. ammoniacum	Leaf Stem	[17]
182	calarene		D. ammoniacum	Leaf Stem	[17]
183	1-[a-(1-adamantyl) benzylidene] thiosemicarbazide		D. ammoniacum	Leaf Stem	[17]
184	benzenemethanol, 3-hydroxy-alpha-[(methylamino) methyl]		D. ammoniacum	Leaf Stem	[17]
185	1 S-cis-calamenene		D. ammoniacum	Leaf Stem	[17]
186	calamenene		D. glabrum	Root	[23]
187	aptrol (4-Methylamphetamine)		D. ammoniacum	Leaf Stem	[17]
188	farnesol		D. ammoniacum D. aucheri	Leaf Stem Seed Seed Stem	[17, 18] [20]
189	benzenemethanol, 4-hydroxy-alpha-[(methylamino) methyl]		D. ammoniacum	Leaf Stem	[17]
190	N-methyl-propylamine		D. ammoniacum	Leaf Stem	[17]
191	pentadecane		D. ammoniacum	Leaf Stem	[17]
192	2-hexanamine, 5-methyl		D. ammoniacum	Leaf Stem	[17]
193	benzenemethanol, 2-(2-aminopropoxy)-3-methyl		D. ammoniacum	Leaf Stem	[17]
194	2-propanamine		D. ammoniacum	Leaf Stem	[17]
195	2-aminononadecane		D. ammoniacum	Leaf Stem	[17]
196	methanimidamide, N,N-dimethyl-N-phenyl		D. ammoniacum	Leaf Stem	[17]
197	methylpent-4-enylamine		D. ammoniacum	Leaf Stem	[17]
198	cyclobutanol		D. ammoniacum	Leaf Stem	[17]
199	hexahydro farnesyl acetone		D. ammoniacum	Leaf Stem	[17]
200	n-hexylmethylamine		D. ammoniacum	Leaf Stem	[17]
201	ethylene bromohydrin		D. ammoniacum	Leaf Stem	[17]
202	didodecyl phthalate		D. ammoniacum	Leaf Stem	[17]
203	3-propoxyamphetamine		D. ammoniacum	Leaf Stem	[17]
204	glycine, N-(N-acetyl-L-alanyl) butyl ester		D. ammoniacum	Leaf Stem	[17]
205	2-propenamide		D. ammoniacum	Leaf Stem	[17]
206	2-heptanol, 6-amino-2-methyl		D. ammoniacum	Leaf Stem	[17]
207	benzene ethanamine, 4-fluoro-beta,3-dihydroxy-N-methyl		D. ammoniacum	Leaf Stem	[17]
208	1H-Indole-3-ethanamine, 6-fluoro-beta-methyl		D. ammoniacum	Leaf Stem	[17]
209	nonadecane		D. ammoniacum	Leaf Stem	[17]
210	eicosane		D. ammoniacum	Leaf Stem	[17]
211	cyclotrisiloxane, hexamethyl		D. ammoniacum	Leaf Stem	[17]
212	diglucosyl caffeoyl ester		D. glabrum	Fruit Seed	[27]
213	4-O-β-D-glucopyranosylcaffeic acid		D. glabrum	Fruit Seed	[27]
214	azeroside A		D. glabrum	Root	[26-28]
215	echisoside		D. glabrum	Root	[26-28]
216	pleoside		D. glabrum	Root	[26-28]
217	hyrcanoside		D. glabrum	Root	[26-28]
218	azeroside B		D. glabrum	Root	[26-28]
219	7,8-dihydroferulic acid-4-O-β-D-glucopyranoside		D. glabrum	Root	[29, 30]
220	ferulic acid-4-O-β-D-glucopyranoside		D. glabrum	Root	[30, 32]
221	4-methoxy-6-hydroxyacetophenone-2-O-β-D-gentiobioside		D. hyrcanum	Root	[33]
222	1(2-Hydroxy-4-methoxy)- 3,7,11- trimethyl-3-vinyl-6(E), 10 dodecadiene- 1- dione		D. hyrcanum	Root	[33]
223	chlorogenic acid		D. glabrum	Root	[30]
224	cynarin		D. glabrum	Root	[30]
225	4,5-diCQA (4,5-dicaffeoylquinic acid)		D. glabrum	Root	[30]
226	6,7,8-trihydroxycoumarin		D. glabrum	Root	[30, 34]
227	2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin		D. hyrcanum	Root	[33]
228	2,3-dihydro-7-methoxy-2R*,3R*dimethyl-2-[4,8-dimethyl-2283(E),7-nonadienyl]-furo[3,2-c]coumarin		D. hyrcanum	Root	[33]
229	umbelliferone 7-O-β-D-glucoside (skimmin)		D. glabrum	Fruit Seed	[27]

ETHNOBOTANICAL USES OF DDorema spp.

Among 12 species of Dorema, seven have been used in ethnobotany for many decades as a remedy for various human and animal illnesses. These applications of individual Dorema species are shown in Table 3. The most popular species, with the highest number of citations were D. ammoniacum and D. aucheri.

Table 3.

Some of the most important ethnobotanical and traditional uses of Dorema species in different countries

No	Dorema species	Vernacular name	Country	Part used	Ethnobotanical and traditional uses	Ref
1	D. aitchisonii	-	The former Soviet Union	Shoot	The water extract from the young shoots is used to treat diseases of the stomach.	[7]
2	D. ammoniacum	Kandal	Iran	Gum, root	Cystitis, digestive, treatment of colic, treatment of furuncles, expectorant, anthelmintic, emmenagogue, anticovulsion	[6]
		Koma	Iran	Resin	Antacid, digestive, treatment of colic, furuncles, expectorant, anthelmintic, emmenagogue and anticovulsion	[46]
		Anghuzeh	Iran	Latex	Asthma, expectorant, bronchitis, stomachache	[37]
		Ammoniacum	Jordan	Resin	Incense, blood sugar reduction	[35]
		Kama eshterk	Iran	Gum	Healing infected wound and infection, acne and abscess	[36]
		Ganda ferooza	Afghanistan	Flowers	Treatment of diarrhea, peptic ulcer and other gastric diseases	[41]
		Ooshi	Pakistan	Gum	Abortifacient	[47]
		Oshagh	Iran	Gum	Analgesic, antidote for toxins, laxative, sciatic pain	[38]
		Kama eshterk	Iran	Gum	Improvement of infectious wounds and infection, abscess in sheep and goats	[48]
3	D. aucheri	Kal	Iran	Latex	Asthma, expectorant, bronchitis, making gum	[37]
		Bilhar	Iran	Young aerial part	Parasites of digestive system, constipation, use as vegetable, young stems are pickled	[12]
		Kama, Eshterk, Balhareshterk	Iran	Gum	Healing infected wound and infection, gasteralgia	[36]
		Balhar, Kama, eshterk	Iran	Gum	Improvement of infectious wounds and infection in sheep	[48]
		Zou	Iran	Root	Burn healing, cornicide	[43]
4	D. aureum	Oshtork	Iran	Gum	Abortion, infection	[49]
5	D. glabrum	-	Azerbaijan Republic	Gum-resin	Diuretic and anti-diarrheal agent as well as for the treatment of bronchitis and catarrh, cure of cancer	[15]
6	D. hyrcanum	-	The former Soviet Union	Resin	As plasters to stop bleeding and to treat injuries in horses.	[7]
7	D. sabulosum	Ilyan	Uzbekistan	Root and stem	Roots used as diuretic and for head and respiratory organs. tincture from green stem used as a remedy for head and heart illnesses.	[45]

Dorema ammoniacum has been historically reputed in the folk medicine as a natural remedy for a variety of diseases and known as a rich source of a medicinal gum-resin commonly known as ammoniacum or gum ammoniac. The gum-resin is found in cavities in stems, roots and petioles [5]. In Persia, D. ammoniacum (commonly known as Kandal, Vasha and Ushagh.), has a broad spectrum ethnobotanical applications such as anticolic, antifuruncle, expectorant, anthelmintic, emmenagogue agent, anticonvulsant, analgesic, antidote for toxins and laxative. Also, it has been used for treating asthma, bronchitis, stomachache, high blood sugar, infected wounds and infections, acne, abscess, and sciatic pain [6, 35-38].

Western and Indian herbalists recommended it as an antispasmodic, expectorant, diaphoretic and emmenagogue agent and also for treatment of catarrh, asthma, chronic bronchitis and persistent coughing [39, 40].

Jordanian herbalist recommended the usage of the resin of D. ammoniacum as incense and blood sugar reducer [35].

In Afghanistan, herbal medicine has been used under the name of Unani medicine for centuries. In different parts of Kabul, there are numerous Unani or Loqmani pharmacies locally called “Attari” where Hakims are prescribing the flowers of D. ammoniacum for the treatment of diarrhea, peptic ulcer, and other gastric diseases [41].

In Pakistan, D. ammoniacum has been used to treat dysentery and skin diseases by local people particularly in Baluchistan province [42].

In Iranian folk medicine, D. aucheri is used against asthma, bronchitis, parasites of digestive system, constipation, burns and infected wounds young leaves and branches are used for making a locally popular pickle called “Bilhar Pickle” and soups [12, 36, 37, 43].

Based on the folk beliefs of Azerbaijan and Armenian people, Dorema species can treat many abnormalities especially catarrh, bronchitis and diarrhea and also can act as diuretic [44]. Besides, they use D. glabrum for many illnesses especially various types of cancer [23].

In former times, some Dorema species were consumed in the former Soviet Union. The resins of D. hyrcanum were used by the local population as plasters to stop bleeding and to treat injuries in horses. The water extract from the young shoots of D. aitchisonii is used to treat diseases of the stomach [7].

In Uzbekistan, milky latex from the roots of D. sabulosum is used as diuretic and for head and respiratory organs. Tincture from green stem is useful for head and heart diseases [45].

NATURE OF D. ammoniacum DESCRIBED IN ITM

In all of ITM literatures the Mizaj (temperament) of Dorema is mentioned as hot and dry [50-57]. Avicenna and other ITM scientists believed that Dorema is a purgative (for bile, yellow bile, and phlegm), resolvent (mohallel), desiccant, deobstruent (mofatteh), laxativeand attractive agent [50-57].

Droma ammoniacum has been known as a rich source of ammoniacum or gum ammoniac. This medicinal gum-resin has been described by Dioscorides as following:

“It is also called “agasyllon”, “criotheos”, or “heliastrus”, and the Romans call it “gutta”. Its smell is similar to castor odor with bitter taste.it has a good color, is not woody, without stones, similar to frankincense in little clots, clear and thick, without filth, this type is called “thrausma” and its earthy or stony kind is called “phurama” [51].

USES OF D. ammoniacum IN ITM

According to ITM texts, D. ammoniacum, D. aucheri and D. aureum are the most usable species with similar effects, so in the following sections, we have only mentioned and categorized D. ammoniacum medicinal activities on target organs according to the text books, listed in Table 4.

Table 4.

Major ITM books and their authors that described medicinal properties of Dorema spp.

Book	Language	Author	Living period
Al-Qânun fi al-Tibbe	Arabic	Ibn Sina	980-1037 A.D.
Zakhireh khârazmshâhi	Persian	Jorjâni	1042-1136 A.D.
Al-Aghrâz al-Tibbe wa al-Mabâhethi al-Alâiiah	Persian	Jorjâni	1042-1136 A.D.
Al-Jâmee le Mofradât al-Adwiah wa al-Aghziah	Arabic	Ibn Al-Baytâr	1193-1248 A.D.
Tadhkirat Oli al-Albâb wa al-Jâme le al-Ajb al-Ujâb	Arabic	Antaki	1535-1599 A.D.
Hadiqat al-Azhâr fi Mâhiyyat al-ushb wa al-uqqâr	Arabic	Ghasani	1547-1611 A.D.
Al-Mujaz fi'l-Tibb	Arabic	Ibn Nafis Qarshi	1213- 1288 A.D.
Tohfah al-Momenin	Persian	Husseini Tonekaboni	17th century
Makhzan al-Adwiah	Persian	Aqili Khorasani	18th century

1. Liver and spleen

One of the most traditional uses of Dorema is in liver and spleen disorders.

The liniment of D. ammoniacum with vinegar (acetum) on the skin of spleen and liver is an effective remedy for hepatitis, splenitis and sclerosis of liver and stiffness of spleen. Oral administration of this combination has the same effect for mentioned disease. Besides, Dorema has been used for treating liver obstructions [52, 55, 57].

2. Gastrointestinal system

In the most of the investigated ITM books, Dorema spp. has been recommended as an anthelmintic agent against gastrointestinal worms and tinea [52, 54, 55, 57], as a laxative for treating constipation [56] and as a purgative agent for cleansing the stomach from the phlegmatic excreta [53, 58]. In addition, many ITM scientists believed that Dorema spp. treats hemorrhoids and anal disorders because of its deobstuent effect on the rectal veins [54, 57].

3. Upper respiratory tract

The therapeutic properties of Dorema spp. on theupper respiratory tract are paid attention by many scientists in ITM. They described it as a good remedy for orthopnea, dyspnea, diphtheria and specifically asthma. Ibn Nafis Qarashi in his book (Al-Mujaz fi’l-Tibb) recommended that a linctus of Dorema with honey or mucilage of barley is useful for the mentioned diseases, as well as scrofula [55]. This mixture is frequently mentioned in other ITM books such as Makhzan al-Adwiah, Tohfah al-Momeninand etc. [52, 54, 55, 57]. The above mixture was used for purgation of the lungs from phlegmatic humors, too [52, 57].

4. Eyes

In all ITM records, treating ocular problems by Dorema preparations have been reported. A collyrium (kohl) of Dorema was used for improving the thickness of eyelids, treating trachoma, leukoma (opacity of the cornea) ophthalmia and stye [52, 55, 57, 58]. Dorema is an effective remedy for moisturizing roughness of eyelids [52, 55, 58]. In addition, it dries up eye moisture [52, 55, 57].

5. Central nervous systems

Due to descanting effects of Dorema, it was described as a purgation agent to clean the brain from phlegm and other humors [52]. Taking a combination of Dorema with honey or beer is a useful remedy for epilepsy and insensibility (numbness) spasms [52, 57]. Also gurgling a warm watery solution of the plant is suitable for cleaning the brain from waste phlegm and humors, dizziness, paralysis, facial paralysis and vertigo [52].

6. Genitourinary system

Dorema spp. has diuretic and emmenagogic properties, therefore, it has been used as a treatment for dysuria and as an abortifacient agent [52, 54, 55]. Dorema preparations have also been reported to be useful for nephrolith and cystolith [52, 57]. Some ITM scientists have recommended it as a remedy for the hardness of testicles and orchitis as well [52].

7. Skin

Dorema has been described to have the property of improving complexion; Therefore, it was particularly used for vitiligo, melisma and freckles [52, 57]. For this purpose, the herb was applied with olive oil on the affected area. Furthermore, many ITM scientists such as Ibn Nafis Qarshi and Jorjani have mentioned the plant as a cure for various types of wounds, ulcers and specifically scars; as Jorjani has written:” Dorema plaster wears away decayed flesh and regenerates new one” [52, 55, 57].

8. Joints and muscles

There are several records on the traditional use of Dorema spp. for joints. For instance, Jorjani has mentioned it for sciatic nerve pain (sciatica). It is also claimed as a cure for arthralgia and stiffness of joints, particularly when prescribed topically with honey [52, 55].

PHARMACOLOGICAL ASPECTS

So far, various pharmacological activities have been reported from Dorema spp., includinganti-microbial, anti-bacterial, anti-plasmodial, anti-fungal, cytotoxic, anti-inflammatory, free radical scavenging, hypolipidemic, anticonvulsant and anti-diabetic activities, as well as effects on pituitary gonad axis hormones. These reports have been mentioned in Tables 5 and 6.

Table 5.

In vitro studies of Dorema spp.

Species	Part used	Type of extraction	Activity	Tested pathogen/cell	Result(s)	Ref
D. aucheri	Gum	Dichloromethane, methanol extract	Anti-microbial activity	E. coli, K. pneumoniae, P. aeruginosa, C. albicans	MIC: 20 and 40 mg/mL	[59]
D. ammoniacum	Oleogum resin	Dichloromethane and methanol extract	Anti-bacterial and anti-fungal	G+ and G–	C: 500 and 1000 µg/mL	[60]
D. ammoniacum	Aerial parts	Methanol extract	Anti-microbial activity	S. aureus Enterococcus sp. C. albicans E. coli	MIC:78 µg/mL	[61]
D. aucheri	Aerial parts	Methanol extract	Anti-microbial and anti-oxidative	B. cereus, S. aureus, E. coli S. enterica	MIC: 10-50 mg/mL	[62]
D. ammoniacum	Ripe fruit	Essential oil	Anti-microbial activity	B. subtilis S. epidermidis	MIC: 3.75 mg/mL	[22]
D. aucheri	Leaf	Ethanol extract	Anti-bacterial activity	S. pyogenes P. aeruginosa	MIC and MBC. 30 and 40 mg/mL	[63]
D. aucheri	Aerial parts	Hydro-alcoholic extract	Cytotoxicity	Artemia urmiana larve (lethaling brine shrimp)	LC50 76.50 ± 0.60 μg/mL	[64]
D. kopetdaghense	Aerial parts	Kopetdaghins A, C and E	Anti-inflammatory effect	J774A.1 murine macrophages	IC50: 474.1 ± 0.9, 496.4 ± 0.7 and 514.3 ± 0.4 μg/mL	[2]
D. aucheri	Aerial parts	Water/ethanol extract	Anti-coccidial effects	Fecal samples	lowest (1.60) and the highest body weight (1.75) FCR	[65]
D. aucheri	Roots	EtOAc extract	No scavenging, and anti-bacterial activities	E. coli, S. flexneri S. aureus B. subtilis	MIC: 0.156, E. coliIC50: 113.74 ± 0.21and 597.64 ± 0.33 μg/mL	[66]
D. aucheri	Aerial parts	Hydroalcoholic and aqueous extracts	Genotoxicity evaluation	HepG2 cell line	Genotoxic effect: 500 μg/mL	[67]
D. glabrum	Root	n-hexane extracts	Apoptosis and cell cycle arrest	Cancer cells	IC50: 6.4,4.6 μg/mL	[68]
D. glabrum	Seed	Methanol extracts	Apoptotic effects	WEHI-164 cells	Apoptosis and antiproliferative properties	[69]
D. ammoniacum	Oleogum resin	Methanol extracts	Cytotoxic effects	Saccaromyces cerevisiae	IC12: 3.14 mg/mL	[70]
D. aucheri	Aerial part	Methanol extracts	Cytotoxic activity	HepG2 and A549 cells	IC50: 20.09, 48.65 μg/mL	[71]
D. glabrum	Seed	Methanol extracts	Cytotoxic effects	WEHI-164 cells, mouse Fibrosarcoma cell line and L929 normal cells	IC50: 50 μg/mL in 36 hours	[72]
D. glabrum	Seeds	Methanol extract	Geno/cytotoxicty and apoptotic	CAOV-4 cells	IC50: 99.7, 87.3, 70.03 μg/mL at 48 h	[73]
D. glabrum	Roots	Essential oil	Free radical scavenging	DPPH assay	RC50: 2.24 mg/mL	[23]
D. glabrum	Aerial parts	Methanol fraction	Antioxidant	DPPH assay	IC50: 53.3 ± 4.7 μg/mL	[21]

Table 6.

In vivo studies of Dorema spp.

Species	Parts used	Type of extraction	Activity	Study design	Result(s)	Ref
D. aucheri	Leaves	Hydroalcoholic extract	Hypolipidemic	Diabetic rats model; orally; 200 mg/kg for 4 weeks; a randomized controlled clinical trial	Useful in treatment of diabetes, remarkable change in serum lipid profiles	[73]
D. hyrcanum	Roots	Methanol extract	Antiplasmodial effect	Mice model; injection ; 10 mg/mL for 4 days 4-day suppressive test against nicd strain of in mice	Good suppression plasmodium berghei infection activity, inhibiting 68.1% of the parasite growth	[33]
D. aucheri	Leaves	Ethanol95%	Hepatotoxicity	Albino mice model; injections; 3.2 mL/kg; three times every 48 hours	Inflammation of the liver tissue, cell proliferation, cholestasis, and a great release of liver enzymes	[74]
D. aucheri	Aerial parts	Essential oil	Anti-diabetic effect	Patients with type ii diabetes; randomized clinical trial; 500 mg for 45 days	Biological effects through PPAR-γ activation	[24]
D. urmiana	Aerial parts	Hydro alcohol extract	Cytotoxicity	Larvae of artemia urmiana; 24 hours; 12 mg rutin/g extract	lc50 76.50 ± 0.60 μg/mL potent brine shrimp lethality	[64]
D. aucheri	Leaves	Water/ethanol 95° mixture	Anti-coccidial	Chickens model; orally; after 22 day of age; 30 mg/kg	Effective in control of coccidiosis	[65]
D. ammoniacum	Gum	Water extract	Anticonvulsant activity	Male albino mice model; 700 mg/kg; injection	Showed significant anticonvulsant activity	[75]
D. aucheri	Root	Hydroalcoholic extract	Effects on pituitary gonad axis hormones	Adult male rat model; orally; 200 mg/kg for 28 days	Increased lh concentrations	[76]

CONCLUSION

Ethnobotanical and traditional medicines are considered as valuable approaches for discovering new medicines because of antiquity medical usage of them over generations. In the current review, the beneficial properties and applications of Dorema spp. Was investigated in ITM books and modern pharmacological studies. The genus Dorema, especially D. ammoniacum known as “ushaq” has been used in folklore and Islamic traditional medicine as a treatment for a wide range of disorders, such as gastrointestinal, upper respiratory tract and central nervous systems’ problems. Besides, many pharmacological activities including anti-microbial, anti-inflammatory, antioxidant, cytotoxicity, anticonvulsant, anti-diabetic and hypolipidemic activities have been reported in modern medicine. These species contain various constituents such as terpenes, coumarins and phenolic compounds. However, more studies, particularly clinical trials, are necessary to fill existing gaps in our knowledge of various aspects of these species.