Review of Compounds and Pharmacological Effects of Delphinium

Abstract

Plants of Delphinium are herbal medicine used in the Tibet region with whole grass as a drug, which have the effects of analgesic, antibacterial, antipyretic, and anticancer. The main bioactive compounds are alkaloids, flavonoids, and sterols. This review summarized the compounds and pharmacological effects of Delphinium and provides a reference for further research on Delphinium.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction

Delphinium of the Ranunculaceae family is widely distributed in the North temperate zone, with about 350 species worldwide. 173 species (150 endemic) of Delphinium are distributed in China [1]. Delphinium is composed of subgen. Delphinastrum, subgen. Delphinium, and subgen. Oligophyllon, in the world, of which subgen. Delphinastrum has the most species [2]. In China, there are 18 species of Delphinium used as folk medicine, which are used to treat bruises, rheumatism, toothache, and enteritis. In addition, four species of Delphinium can be used as soil pesticides for their effects of killing lice, mosquitoes, and fly larvae [3]. The main compounds of Delphinium are diterpenoid alkaloids, and most of them have physiological activities [4]. In addition, Delphinium also contains chemical constituents such as flavonoids and sterols. In recent years, with the development of analysis methods and increasing focus on Delphinium, more and more chemical constituents and pharmacological activities of Delphinium had been researched. In this paper, the chemical constituents and pharmacological effects of Delphinium were reviewed in order to improve the development and utilization of the Delphinium resources.

2. Chemical Constituents

According to the research studies, the alkaloids are the main constituents with physiological activities in Delphinium and diterpenoid alkaloids are the most characteristic constituents with toxicity [5]. In addition, flavonoids and sterols are also present [6].

2.1. Diterpenoid Alkaloids

Diterpenoid alkaloids are derived from the amination of tetracycline diterpenoids or pentacyclic diterpenoids to heterocyclic systems containing β-aminoethanol, methylamine, or ethylamine nitrogen atoms [7]. There are abundant diterpenoid alkaloids in Delphinium, which can be classified into C-18 diterpenoid alkaloids, C-19 diterpenoid alkaloids, and C-20 diterpenoid alkaloids according to the carbon skeleton configuration [5]. Characteristic quaternary carbon signal and substituent signal are important information to distinguish different diterpene alkaloids.

C-18 diterpenoid alkaloids are the diterpenoid alkaloids whose C-18 are mostly substituted by C(4)-H/OH or the ester group, and a few of them contain 3,4-epoxide. According to the oxygen-containing groups on C-7, they can be sorted into two types (Figure 1): lappacinitine-type and ranaconitine-type, and C-7 of the ranaconitine-type has an oxygen-substituent group. C₄ (δ_c 30–40, s), C₈ (δ_c 73–84, s), and C₁₁ (δ_c 47–55, s) are C-18’s characteristic signals [8]. Characteristic signal of the ranaconitine-type on C-7 is at δ_c 91–93 (s), and the characteristic signal of the lappacinitine-type on C-7 is at δ_c 45–48 (s).

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Most C-19 diterpene alkaloids are natural diterpenoid alkaloids and belong to pentacyclic diterpene alkaloids. According to the oxygen-containing groups on C-7 and the difference of skeleton, they can be classified into six types (Figure 2): lycoctonine-type, aconitine-type, 7,17-seco type (δ_c8 137–139, s; δ_c10 48–49, s; δ_c14 216–218, s), lactone-type, pyro-type (δ_c8,15 146–147, s), and rearranged-type (δ_c8 40–55, s; δ_c10 44–45, s; δ_c14 210–211, s) [8]. The majority of C-19 diterpenoid alkaloids are lycoctonine-type and aconitine-type. The differences between them are that C-7 (δ_c 87–93) of the lycoctonine-type has an oxygen-substituent group and others do not have [9]. And, C-19 diterpenoid alkaloids isolated from Delphinium are mostly lycoctonine-type [10]. C-19 diterpene alkaloids contain oxygen substituent (δ_H3.0–5.0; δ_c 70–90) and methoxy substituent (δ_H3.2–3.6, s; δ_c 55–59, q). C₄ (δ_c 37–41, s), C₈, and C₁₁ (δ_c 47–51, s) are C-19 characteristic signals [8].

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C-20 diterpenoid alkaloids are tetracyclic diterpenes with a carbon skeleton of 20 carbon atoms and have a trans-a-ring alkaloid that connects C-19 to C-20 in N-ethyl or N-β-hydroxyl ethyl [11]. Compared with C-18 and C-19, C-20 diterpene alkaloid skeletons are complex, and most of them have exocyclic double bond structures. At present, 22 types of C-20 diterpenoid alkaloids were found [12]. The C-20 diterpenoid alkaloids isolated from Delphinium mainly belong to atisine-type, veatchine-type, hetisine-type, hetidine-type, denudatine-type, delnudine-type [13], and vakognavine-type (Figure 3) [14, 15]. C₄ (δ_c 30–40, s), C₈ (δ_c 30–50, s), C₁₁ (δ_c 30–40, s), C₁₆ (δ_c-143, s), and C₁₇ (δ_H-5, brs; δ_c-110, t) are C-20’s characteristic signals. C₆ (δ_c 17–20, s), C₇ (δ_c 31–35, s), C₁₀ (δ_c 36–40, s), C₁₄ (δ_c 25–26, s), and C₂₀ (δ_c 50–54, s) are characteristic signals of atisine-type, and C₆ (δ_c −24, s), C₇ (δ_c −43, s), C₁₀ (δ_c 48–51, s), C₁₄ (δ_c 36–39, s), and C₂₀ (δ_c −69, s) are characteristic signals of hetidine-type [16].

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At present, 155 alkaloids were isolated from Delphinium, and the details are shown in Tables 1–3 and Figures 4–6. Based on the references listed in Tables 1–3, it can be summarized that D. anthriscifolium varietas and D. elatum and its varietas have been further studied in chemistry.

Table 1

C-18 diterpenoid alkaloids isolated from Delphinium.

No.	Compound	Type	Source	Molecular formula	Reference
1	Anthriscifolcine A	Ranaconitine	D. anthriscifolium var. savatieri	C26H38NO7	[17]
2	Anthriscifolcine B	Ranaconitine	D. anthriscifolium var. savatieri	C24H37NO6	[17]
3	Anthriscifolcine C	Ranaconitine	D. anthriscifolium var. savatieri	C25H37NO7	[17]
4	Anthriscifolcine D	Ranaconitine	D. anthriscifolium var. savatieri	C26H39NO7	[17]
5	Anthriscifolcine E	Ranaconitine	D. anthriscifolium var. savatieri	C24H37NO6	[17]
6	Anthriscifolcine F	Ranaconitine	D. anthriscifolium var. savatieri	C25H37NO8	[18]
7	Anthriscifolcine G	Ranaconitine	D. anthriscifolium var. savatieri	C25H37NO7	[18]
8	Naviconine	Lappacinitine	D. naviculare var. lasiocarpum W. T. Wang.	C31H40N2O9	[19]
9	Anthriscifolcone A	Ranaconitine	D. anthriscifolium var. majus	C27H39NO8	[20]
10	Anthriscifolcone B	Ranaconitine	D. anthriscifolium var. majus	C23H33NO7	[20]
11	Grandifline A	Ranaconitine	D. grandiflorum Linn	C22H33NO7	[21]
12	Tuguaconitine	Ranaconitine	D. grandiflorum	C23H35NO7	[22]
13	Linearilin	Ranaconitine	D. linearilobum (Trautv.) N. Busch	C24H39NO8	[23]
14	Anthriscifoltine A	Ranaconitine	D. anthriscifolium var. majus	C30H45NO9	[24]
15	Anthriscifoltine B	Ranaconitine	D. anthriscifolium var. majus	C28H43NO8	[24]
16	Anthriscifoltine C	Ranaconitine	D. anthriscifolium var. majus	C29H43NO9	[25]
17	Anthriscifoltine D	Ranaconitine	D. anthriscifolium var. majus	C32H41NO9	[25]
18	Anthriscifoltine E	Ranaconitine	D. anthriscifolium var. majus	C25H35NO8	[25]
19	Anthriscifoltine F	Ranaconitine	D. anthriscifolium var. majus	C23H33NO7	[25]
20	Anthriscifoltine G	Ranaconitine	D. anthriscifolium var. majus	C23H31NO7	[25]

Table 2

C-19 diterpenoid alkaloids isolated from Delphinium.

No.	Compound	Type	Source	Molecular formula	Reference
21	Anthriscifoldine A	Lycoctonine	D. anthriscifolium var. savatieri	C25H37NO7	[17]
22	Anthriscifoldine B	Lycoctonine	D. anthriscifolium var. savatieri	C25H39NO7	[17]
23	Anthriscifoldine C	Lycoctonine	D. anthriscifolium var. savatieri	C27H41NO7	[17]
24	Naviculine	Lycoctonine	D. naviculare var. lasiocarpum W. T. Wang.	C26H42NO7+	[19]
25	Naviconitine	Aconitine	D. naviculare var. lasiocarpum W. T. Wang.	C34H46N2O9	[19]
26	Grandifline B	Lycoctonine	D. grandiflorum Linn	C25H39NO8	[21]
27	Grandifline C	Lycoctonine	D. grandiflorum Linn	C25H40NO7+	[21]
28	Olivimine	Lycoctonine	D. grandiflorum	C24H37NO7	[22]
29	Hohenackeridine	Lycoctonine	D. grandiflorum	C22H31NO7	[22]
30	14-O-Methyldelphinifoline	Lycoctonine	D. grandiflorum	C24H39NO7	[22]
31	N-Deethyldelphatine	Lycoctonine	D. grandiflorum	C24H39NO7	[22]
32	Browniine	Lycoctonine	D. grandiflorum	C25H41NO7	[22]
33	14-Dehydrobrowniine	Lycoctonine	D. grandiflorum	C25H39NO7	[22]
34	Linearilobin	Aconitine	D. linearilobum (Trautv.) N. Busch	C37H46N2O9	[23]
35	Melpheline	Lycoctonine	D. elatum	C24H37NO6	[26]
36	19-Oxoisodelpheline	Lycoctonine	D. elatum	C25H37NO7	[26]
37	N-Deethyl-19-oxoisodelpheline	Lycoctonine	D. elatum	C23H33NO7	[26]
38	N-Deethyl-19-oxodelpheline	Lycoctonine	D. elatum	C23H33NO7	[26]
39	N-Formyl-4,19-secopacinine	Lycoctonine	D. elatum cv. Pacific Giant	C25H37NO7	[27]
40	Iminoisodelpheline	Lycoctonine	D. elatum cv. Pacific Giant	C23H33NO6	[27]
41	Iminodelpheline	Lycoctonine	D. elatum cv. Pacific Giant	C23H33NO6	[27]
42	Iminopaciline	Lycoctonine	D. elatum cv. Pacific Giant	C24H35NO6	[27]
43	6-Dehydroeladine	Lycoctonine	D. elatum cv. Pacific Giant	C24H35NO6	[27]
44	Elapacidine	Lycoctonine	D. elatum cv. Pacific Giant	C24H37NO6	[27]
45	Yunnanensine A	Rearranged-type	D. yunnanense	C37H48N2O9	[28]
46	Iliensine A	Lycoctonine	D. iliense	C40H55NO14	[29]
47	Iliensine B	Lycoctonine	D. iliense	C26H41NO8	[29]
48	Pseudophnine A	Lycoctonine	D. pseudoaemulans C. Y. Yang et B. Wang	C25H40NO7+	[30]
49	Pseudophnine B	Lycoctonine	D. pseudoaemulans C. Y. Yang et B. Wang	C24H38NO7+	[30]
50	Pseudophnine C	Lycoctonine	D. pseudoaemulans C. Y. Yang et B. Wang	C27H42NO7+	[30]
51	Pseudophnine D	Lycoctonine	D. pseudoaemulans C. Y. Yang et B. Wang	C26H40NO7+	[30]
52	Pseudorenines A	Lycoctonine	D. pseudoaemulans C. Y. Yang et B. Wang	C39H53N2O11+	[30]
53	Pseudorenines B	Lycoctonine	D. pseudoaemulans C. Y. Yang et B. Wang	C39H53N2O11+	[30]
54	Pseudonidine A	Lycoctonine	D. pseudoaemulans C. Y. Yang et B. Wang	C24H35NO7	[30]
55	Pseudonidine B	Lycoctonine	D. pseudoaemulans C. Y. Yang et B. Wang	C29H45NO8	[30]
56	Navicularine	Lycoctonine	D. naviculare var. lasiocarpum	C27H43NO8	[31]
57	Shawurensine	Lycoctonine	D. shawurense W. T. Wang	C37H52N2O11	[32]
58	Sharwuphinine B	Lycoctonine	D. shawurense W. T. Wang	C26H40NO7+	[33]
59	Ajacisine A	Lycoctonine	D. ajacis L.	C31H44N2O9	[34]
60	Ajacisine B	Lycoctonine	D. ajacis L.	C32H46N2O9	[34]
61	Ajacisine C	Lycoctonine	D. ajacis L.	C31H42N2O8	[34]
62	Ajacisine D	Lycoctonine	D. ajacis L.	C30H42N2O8	[34]
63	Ajacisine E	Lycoctonine	D. ajacis L.	C30H42N2O8	[34]
64	Caerudelphinine A	Lycoctonine	D. caeruleum Jacq.ex Camb	C25H39NO8	[35]
65	Grandiflodine B	Lycoctonine	D. grandiflorum	C33H48N2O10	[36]
66	Majusine A	Lycoctonine	D. majus W. T. Wang	C32H44N2O9	[37]
67	Majusine B	Lycoctonine	D. majus W. T. Wang	C24H37NO6	[37]
68	Majusine C	Lycoctonine	D. majus W. T. Wang	C26H37NO8	[37]
69	Davidisine A	Lycoctonine	D. davidii Franch.	C23H37NO7	[38]
70	Davidisine B	Lycoctonine	D. davidii Franch.	C24H37NO8	[38]
71	Laxicymine 1	Lycoctonine	D. laxicymosum var. pilostachyum W. T. Wang	C24H35NO7	[39]
72	Laxicymisine 2	Lycoctonine	D. laxicymosum var. pilostachyum W. T. Wang	C24H37NO7	[39]
73	Laxicyminine 3	Lycoctonine	D. laxicymosum var. pilostachyum W. T. Wang	C24H35NO6	[39]
74	Tiantaishansine	Lycoctonine	D. tiantaishanense W. J. Zhang et G. H. Chen	C22H33NO7	[40]
75	Tiantaishannine	Lycoctonine	D. tiantaishanense W. J. Zhang et G. H. Chen	C26H39NO7	[40]
76	Tiantaishanmine	Lycoctonine	D. tiantaishanense W. J. Zhang et G. H. Chen	C25H35NO7	[40]
77	Trifoliolasine A	Lycoctonine	D. trifoliolatum Finet et Gagnep	C35H50N2O9	[41]
78	Trifoliolasine B	Lycoctonine	D. trifoliolatum Finet et Gagnep	C36H52N2O9	[41]
79	Trifoliolasine C	Lycoctonine	D. trifoliolatum Finet et Gagnep	C40H57N3O11	[41]
80	14-Demethyl-14-isobutyrylanhweidelphinine	Lycoctonine	D. pentagynum Lam.	C38H48N2O11	[42]
81	14-Demethyl-14-acetylanhweidelphinine	Lycoctonine	D. pentagynum Lam.	C36H44N2O11	[42]
82	Giraldine G	Lycoctonine	D. giraldii	C40H57N3O11	[43]
83	Giraldine H	Lycoctonine	D. giraldii	C41H59N3O11	[43]
84	Giraldine I	Aconitine	D. giraldii	C22H35NO3	[43]
85	Giraldine D	Lycoctonine	D. giraldii	C24H37NO6	[44]
86	Giraldine E	Lycoctonine	D. giraldii	C25H39NO7	[44]
87	Giraldine F	Lycoctonine	D. giraldii	C23H33NO6	[44]
88	Campylocine	Lycoctonine	D. campylocentrum Maxim.	C25H37NO7	[45]
89	Campylotine	Lycoctonine	D. campylocentrum Maxim.	C24H37NO7	[45]
90	Davidiisine A	Lycoctonine	D. davidii Franch	C23H37NO7	[46]
91	Davidiisine B	Lycoctonine	D. davidii Franch	C24H37NO8	[46]
92	Ajadelphine	Lycoctonine	D. honanense var. piliteram W. T. Wang	C25H39NO7	[47]
93	Aconine	Aconitine	D. honanense var. piliteram W. T. Wang	C25H41NO9	[47]
94	Siwanine E	Lycoctonine	D. honanense var. piliteram W. T. Wang	C28H39NO9	[47]
95	Grandiflorine III	Aconitine	D. grandiflorum L.	C26H39NO9	[48]
96	Isotalatizidine	Aconitine	D. grandiflorum L.	C23H37NO5	[48]
97	14-O-Methyl isotalatizidine	Aconitine	D. grandiflorum L.	C24H39NO5	[48]
98	Anthranoyllycoctonine	Lycoctonine	D. grandiflorum L.	C32H46N2O8	[48]
99	Deoxylycoctonine	Lycoctonine	D. grandiflorum L.	C26H43NO6	[48]
100	Umbrosine	Lycoctonine	D. grandiflorum L.	C24H39NO6	[48]
101	Anthriscifolrine A	Lycoctonine	D. anthriscifolium var. majus	C25H37NO6	[49]
102	Anthriscifolrine B	Lycoctonine	D. anthriscifolium var. majus	C27H41NO8	[49]
103	Anthriscifolrine C	Lycoctonine	D. anthriscifolium var. majus	C27H41NO9	[49]
104	Anthriscifolrine D	Lycoctonine	D. anthriscifolium var. majus	C27H39NO9	[49]
105	Anthriscifolrine E	Lycoctonine	D. anthriscifolium var. majus	C26H39NO8	[49]
106	Anthriscifolrine F	Lycoctonine	D. anthriscifolium var. majus	C25H39NO7	[49]
107	Tianshanisine A	Lycoctonine	D. tianshanicum W. T. Wang	C30H41NO6	[50]
108	Tianshanisine B	Lycoctonine	D. tianshanicum W. T. Wang	C23H37NO5	[50]
109	Tianshanisine C	Lycoctonine	D. tianshanicum W. T. Wang	C25H39NO6	[50]
110	Tianshanisine D	Lycoctonine	D. tianshanicum W. T. Wang	C23H35NO5	[50]
111	Tianshanisine E	Lycoctonine	D. tianshanicum W. T. Wang	C23H35NO7	[50]
112	Elapacigine	Lycoctonine	Delphinium elatum cv. Pacific Giant	C23H31NO6	[51]
113	N-Deethyl-N-formylpaciline	Lycoctonine	Delphinium elatum cv. Pacific Giant	C25H37NO7	[51]
114	N-Deethyl-N-formylpacinine	Lycoctonine	Delphinium elatum cv. Pacific Giant	C24H33NO7	[51]
115	N-Formyl-4,19-secoyunnadelphinine	Lycoctonine	Delphinium elatum cv. Pacific Giant	C24H35NO7	[51]

Table 3

C-20 diterpenoid alkaloids isolated from Delphinium.

No.	Compound	Type	Source	Molecular formula	Reference
116	Yunnanensine B	Hetisine	D. yunnanense	C28H37NO7	[28]
117	Yunnanensine C	Hetisine	D. yunnanense	C26H35NO6	[28]
118	Grandiflodine A	Hetisine	D. grandiflorum	C22H28N2O3	[36]
119	Majusimine A	Vakognavine	D. majus W. T. Wang	C45H47NO15	[37]
120	Majusimine B	Vakognavine	D. majus W. T. Wang	C43H45NO14	[37]
121	Majusimine C	Vakognavine	D. majus W. T. Wang	C41H43NO13	[37]
122	Majusimine D	Vakognavine	D. majus W. T. Wang	C34H37NO12	[37]
123	Majusidine A	Hetisine	D. majus W. T. Wang	C22H29NO5	[37]
124	Majusidine B	Hetisine	D. majus W. T. Wang	C25H33NO4	[37]
125	Tiantaishandine	Hetisine	D. tiantaishanense W. J. Zhang et G. H. Chen	C29H33NO5	[40]
126	2-Dehydrodeacetylhetero phylloidine	Hetidine	D. pentagynum Lam.	C21H25NO3	[42]
127	Davidiisine C	Hetidine	D. davidii Franch	C21H33NO4	[46]
128	12-Epinapelline	Veatchine	D. honanense var. piliteram W. T. Wang	C22H33NO3	[47]
129	Anthriscifolsine B	Hetisine	D. anthriscifolium var. majus	C24H31NO7	[49]
130	Anthriscifolsine C	Hetisine	D. anthriscifolium var. majus	C30H43NO7	[49]
131	Anthriscifolmine A	Denudatine	D. anthriscifolium var. savatieri	C25H37NO5	[52]
132	Anthriscifolmine B	Denudatine	D. anthriscifolium var. savatieri	C25H37NO6	[52]
133	Anthriscifolmine C	Hetisine	D. anthriscifolium var. savatieri	C29H31NO7	[52]
134	Trichodelphinines A	Hetisine	D. tichophorum Franch	C26H35NO5	[53]
135	Trichodelphinines B	Hetisine	D. tichophorum Franch	C24H33NO4	[53]
136	Trichodelphinines C	Hetisine	D. tichophorum Franch	C27H37NO5	[53]
137	Trichodelphinines D	Hetisine	D. tichophorum Franch	C24H31NO5	[53]
138	Trichodelphinines E	Hetisine	D. tichophorum Franch	C26H33NO5	[53]
139	Trichodelphinines F	Delnudine	D. tichophorum Franch	C28H33NO4	[53]
140	Flexiosine	Hetisine	D. flexuosum M. Bieb.	C36H43NO9	[54]
141	Tatsienenseine A	Vakognavine	D. tatsienense Franch	C43H45NO13	[55]
142	Tatsienenseine B	Hetisine	D. tatsienense Franch	C24H31NO4	[55]
143	Tatsienenseine C	Hetisine	D. tatsienense Franch	C24H31NO3	[55]
144	13-(2-Methyl butyryl) azitine	Atisine	D. scabriflorum	C25H37NO3	[56]
145	Tatsienensine	Hetisine	D. tatsienense	C19H25NO2	[57]

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2.2. Amide Alkaloids

The typical groups of amide alkaloids are acyl groups. 9 amide alkaloids were isolated from Delphinium, and the details are shown in Table 4 and Figure 7.

Table 4

Amide alkaloids isolated from Delphinium.

No.	Compound	Type	Source	Molecular formula	Reference
146	Benzoic acid 2-[(4-methoxy-2-methyl-1,4-dioxobutyl) amino]-methyl ester	Amide	D. grandiflorum Linn	C14H17NO5	[21]
147	N-Cinnamoyl-2-phenylethylamine	Amide	D. grandiflorum L.	C17H17NO	[48]
148	Delamide A	Amide	D. brunonianum	C13H13NO4	[58]
149	Delamide B	Amide	D. brunonianum	C14H17NO6	[58]
150	Delamide C	Amide	D. brunonianum	C13H15NO5	[58]
151	Delamide D	Amide	D. brunonianum	C13H15NO5	[58]
152	Delamide E	Amide	D. brunonianum	C13H15NO5	[58]
153	Benzoic,4-[(3,4-dimethoxybenzoyl) amino]-3-hydroxy-methyl ester	Amide	D. brunonianum Royle	C17H17NO6	[59]
154	Benzoic acid 2-[(4-methoxy-3-methyl-1,4-dioxobutyl) amino]-methyl ester	Amide	D. brunonianum Royle	C14H17NO5	[59]

[figure omitted; refer to PDF]

2.3. Other Alkaloids

Except diterpene alkaloids and amide alkaloids, one other alkaloid (No.155, anthriscifolsine A, C₂₉H₃₁NO₇, [49]) was isolated from D. anthriscifolium var. majus. The structure is shown in Figure 8.

[figure omitted; refer to PDF]

2.4. Other Compounds

Delphinium also contains compounds such as flavonoids and sterols. In recent years, other compounds isolated from Delphinium had also been reported, and a total of 13 nonalkaloids (Table 5 and Figure 9) were isolated from Delphinium.

Table 5

Other compounds isolated from Delphinium.

No.	Compound	Type	Source	Molecular formula	Reference
156	β-Carotene		D. grandiflorum Linn	C34H56NO4	[21]
157	3,5-Dihydroxy-4′-methoxyflavon-7-yl-O-β-D-glucopyranosyl-(1⟶4)-α-L-rhamnopyranoside	Flavonoid	D. grandiflorum Linn	C21H18NO8	[21]
158	β-D-Galactopyranoside,4-hydroxyphenyl		D. grandiflorum Linn	C11H12NO5	[21]
159	β-Sitosterol	Sterol	D. honanense var. piliteram W. T. Wang	C29H50O	[47]
160	4′,7-Dimethoxy-5-hydroxyflavone	Flavonoid	D. grandiflorum L.	C17H14O5	[48]
161	Kaempferol-7-O-α-L-pyranorhamnoside	Flavonoid	D. grandiflorum L.	C21H20O10	[60]
162	5,7,3′,4′-Tetrahydroxy-8-methoxyflavone	Flavonoid	D. grandiflorum L.	C16H12O7	[60]
163	Tachioside	Phenolics	D. grandiflorum L.	C13H18O8	[60]
164	6-Methoxycoumarin	Coumarin	D. grandiflorum L.	C10H8O3	[60]
165	para-Hydroxybenzoic acid		D. brunonianum Royle	C7H6O3	[59]
166	Benzoic acid		D. brunonianum Royle	C7H6O2	[59]
167	Cinnamic acid		D. brunonianum Royle	C9H8O2	[59]
168	Dibutyl phthalate		D. brunonianum Royle	C16H22O4	[59]

[figure omitted; refer to PDF]

3. Biological Activities

Plants of Delphinium are used with whole grass as medicine. According to the ancient Tibetan medicine Jingzhubencao, plants of Delphinium had analgesic, anti-inflammatory, and insecticidal effects [9]. Literature studies showed that plants of Delphinium have many pharmacological effects including antibacterial, antiepileptic, detoxification, and Alzheimer’s disease treatment. In this section, this paper reviews the research studies on the antibacterial, analgesic, anti-inflammatory, antidepressant, and anticancer effects of Delphinium.

3.1. Antibacterial Activity

Hari et al. found that anthriscifoldine C (5.0 mg/mL) from D. brunonianum had a good inhibiting effect on Bacillus subtilis, Escherichia coli, and Salmonella flexnari, and its MIC were 24.0 µM, 23.4 µM, and 24.2 µM, respectively, in vitro [61]. Ren et al. carried out the bacteriostatic test on the total alkaloids extracted from the roots of Delphinium and found that the MIC of the total alkaloids extracted on S. aureus and Aspergillus niger was 50 mg/mL in vitro [62].

3.2. Analgesic Activity

Zaheer et al. used the eddy current hot plate method and the tail flick reaction method to evaluate the analgesic activity of D. denudatum on Wistar albino rats. The experimental results showed that the response time of rats given D. denudatum ethanol extract and methanol fraction was longer than that of the propylene glycol group, and the effects of the high doses of the ethanol extract (600 mg/kg) and methanol fraction (400 mg/kg) were equal to that of the positive control group, indicating that D. denudatum had a good analgesic activity [63]. Nesterova et al. investigated chronic immune inflammation which was induced by injecting 0.1 mL of complete Freund’s in outbred male rats, and the results showed that the 40% alcohol extract (0.12 mL/kg) and total alkaloids (0.05 mg/kg) of Delphinium could significantly reduce the frequency of joint swelling in outbred male rats. On the 14th day, the rats in the total alkaloids (0.05 mg/kg) treatment group of Delphinium had no pain when their joints were bended, which indicated a good analgesic effect of Delphinium [64]. Through the hot-plate method and the acetic acid writhing method, Suslov et al. found that the water extract (0.5 g/kg) and the alcohol extract (0.25 g/kg) of D. grandiflorum L. var. leiocarpum could prolong the pain threshold of mice, which was similar to the effect of acetaminophen (0.2 g/kg), and performed a good analgesic effect [65].

3.3. Anti-Inflammatory Activity

Nesterova et al. found that the alkaloids and flavonoids in Delphinium had a good inhibitory effect on the inflammatory response through the experiment of the mice peritonitis model in the inflammatory exudation phase in vivo. Aqueous fraction of flavonoids (25.0 mg/kg) had a good therapeutic effect on the edema reaction caused by histamine (0.1%), and alkaloids (0.05 mg/kg) showed a good anti-inflammatory effect on the inflammatory reaction caused by 5-hydroxytryptamine (0.5 mg/kg) [66]. Andreeva and Liu established an acute inflammation model with increased capillary permeability induced by acetic acid in ICR male mice, and the results showed that the high- (1.5 g/kg), medium- (1.0 g/kg), and low-dose groups (0.5 g/kg) of the total flavonoids extracted from D. grandiflorum with ethanol had good anti-inflammatory activity [67].

3.4. Spiritual Influence

3.4.1. Antidepressant Activity

Ebrahimzadeh et al. demonstrated that the extract (250 mg/kg, 500 mg/kg, and 1000 mg/kg) of D. elbursense had good antidepressant activity by using the forced swimming experiment and the tail suspension experiment in mice. The results revealed that the extract at 1000 mg/kg had the same inhibitory activity as imipramine at 15 mg/kg in the control group [68].

3.4.2. Antianxiety Activity

Mohammad et al. found that the D. denudatum extract (200 and 400 mg/kg) had a certain therapeutic effect on anxiety in Wistar albino rats and a better synergistic effect toward the Amaranthus spinosus extract (100 mg/kg) [69].

3.5. Anticancer Activity

Zheng et al. used the MTT method to determine the antihepatoma activity of the ethyl acetate extract from D. caeruleum in vitro. After giving 25, 50, 100, and 200 μg/mL of HepG2 cells for 12, 24, and 48 hours, they found that the ethyl acetate extract from D. caeruleum had good antiliver cancer activity and had a good dose-effect and time-effect relationship on HepG2 cells and had less toxicity to L-02 cells. IC₅₀ of the ethyl acetate extract from D. caeruleum on HepG2 cells was 28.8 μg/mL [70].

3.6. Antipulmonary Fibrosis Activity

In the study on pulmonary fibrosis induced by bleomycin in SD rats, Lin et al. found that after 14 days of gavage with 4 g/kg, 2 g/kg, and 1 g/kg extracts of D. trichophorum, the expression of collagen in the tissues during the pathological process of pulmonary fibrosis could be inhibited and the symptoms of pulmonary fibrosis in rats could be improved [71].

3.7. Antifeedant Activity

Shan et al. determined the antifood activity of 12 alkaloids isolated from D. naviculare var. lasiocarpum on Spodoptera exigua, and the results showed that the chemical shawurensine had a strong antifeedant activity with an EC₅₀ of 0.45 mg/cm² [31]. González and Guadaño extracted 5 alkaloids from Delphinium for activity determination against Spodoptera littoralis and Leptinotarsa decemlineata by choice feeding assays, and the results showed that cardiopetamine had the strongest activity against S. littoralis with the EC₅₀ of 5.48 nmol/cm² and 15-acetylcardiopetamine had the strongest activity against L. decemlineata with the EC₅₀ of 12.86 nmol/cm² [72].

3.8. Antiparasite Activity

Reina et al. found that delphigraciline extracted from D. gracile had antileishmanicidal activity in vitro, and its IC₅₀ was 7.3 μg/mL [73].

4. Summary and Analysis

Delphinium is rich in germplasm resources and has a wide range of pharmacological effects. In recent years, 168 compounds were isolated from plants of Delphinium, including 155 alkaloids and 13 nonalkaloids. The alkaloids in the genus Delphinium are mainly diterpene alkaloids, including 20 C-18 diterpenoid alkaloids, 95 C-19 diterpenoid alkaloids, and 30 C-20 diterpenoid alkaloids. The study of chemical composition for Delphinium mainly focuses on D. anthriscifolium varietas, D. elatum, D. grandiflorum, D. brunonianum, D. tiantaishanense, and D. pseudoaemulans. Although there are many research studies, the pharmacological effects on the antibacterial, analgesic, anti-inflammatory, antidepressant, anticancer, antipulmonary fibrosis, antifeedant, and antiparasite effects of Delphinium are mainly on the crude extracts and few on compounds.

5. Future Prospects

The genus Delphinium is rich in new and novel compounds, but the current research is only focused on several species. In the future, more new compounds should be investigated from other species in depth. The pharmacological effects of Delphinium are extensive, but the current research is limited to extracts, so it is necessary to focus on the effects of the compounds from Delphinium and the structure-activity relationship in the future.

Authors’ Contributions

Sitan Chen and Lijun Meng contributed equally to this work.

Acknowledgments

This work was supported by the Basic Project in Science and Technology Agency of Kaifeng City (1908007).

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