Chemical constituents of plants from the genus Neolitsea

Xia Qing; Ting Zhao; Rui-Xia Guo; Yi-Bing Wu; Qing-Wen Shi; Yu-Cheng Gu; Hiromasa Kiyota

doi:10.1515/hc-2013-0239

Open Access Published by De Gruyter March 31, 2014

Chemical constituents of plants from the genus Neolitsea

Xia Qing , Ting Zhao , Rui-Xia Guo , Yi-Bing Wu , Qing-Wen Shi , Yu-Cheng Gu and Hiromasa Kiyota

From the journal Heterocyclic Communications

https://doi.org/10.1515/hc-2013-0239

Abstract

The genus Neolitsea (Lauraceae) contains over 85 species distributed around the world. These plants have been found to be rich in sesquiterpenes, triterpenes, steroids, and alkaloids. This review summarizes the phytochemical progress and list of all the constituents isolated from the genus Neolitsea over the past few decades. Some biological activities of compounds isolated from this genus are also included.

Keywords: biological activity; chemical composition; Neolitsea; plant

Introduction

The genus Neolitsea (Lauraceae) comprises nearly 85 species that are distributed throughout tropical and subtropical Asia and America. In particular, there are 45 species widespread in South China, East China, and Southwest China. The plants of genus Neolitsea have been found to be rich in sesquiterpenes, triterpenes, alkaloids, and steroids [1, 2]. The occurrence of a small number of flavonoids, benzenoids, monoterpenes, and benzoquinone has also been reported [3]. Constituents of the Neolitsea genus (Lauraceae) have been reported to possess diverse bioactivities, such as antioxidant, antibacterial, anti-inflammatory activities, and cytotoxicity [3].

This review summarizes the phytochemical progress involving all constituents isolated from the genus Neolitsea over the past few decades. Some biological activities of compounds isolated from this genus are also included.

Chemical constituents

The reported chemical constituents from this genus include sesquiterpenes, triterpenes, alkaloids, steroids, flavonoids, essential oils, and some other compounds. Their structures are shown in the following sections, and their names and the corresponding plant sources are collected in Tables 1–5.

Table 1

Sesquiterpenes.

No.	Name	Source	Part	References
1	Linderalactone	N. zeylanica/N. villosa	Root	[1, 4]
		N. parvigemma	Stem/root	[2, 5–7]
		N. dealbata	Bark	[8]
		N. aciculata	Root/trunk	[9]
2	Linderane	N. zeylanica	Root	[1, 4]
		N. villosa	Stem	[5, 6]
		N. parvigemma	Root/trunk	[9]
		N. aciculata	Root	[10]
		N. acutotrinervia	Root	[11]
		N. buisanensis
3	Neolinderane	N. zeylanica	Root	[1]
		N. aciculata	Root/trunk	[9]
4	Zeylanine	N. zeylanica	Root	[1]
		N. aciculata	Root/trunk	[9]
		N. acutotrinervia	Root	[10]
5	Zeylanicine	N. zeylanica	Root	[1]
		N. parvigemma	Stem/root	[2, 5, 6, 12]
6	Zeylanidine	N. zeylanica	Root	[1, 6]
		N. parvigemma	Stem/root	[2, 5, 7]
		N. dealbata	Bark	[8]
7	Deacetylzeylanine	N. parvigemma	Stem	[2, 7]
8	Parvigemonol	N. parvigemma	Stem	[2]
9	Parvigemon	N. parvigemma	Stem	[2, 6]
10	Neolitrane	N. parvigemma	Stem	[2, 6, 7]
11	Pseudoneolinderane	N. parvigemma	Stem	[2,6, 7]
		N. dealbata	Bark	[8]
		N. aciculata	Root/trunk	[9]
		N. villosa	Root	[4]
12	Hiiranlactone A	N. hiiranensis	Leaf	[3]
13	Hiiranlactone B	N. hiiranensis	Leaf	[3]
14	Hiiranlactone C	N. hiiranensis	Leaf	[3]
15	Hiiranlactone D	N. hiiranensis	Leaf	[3]
16	(+)-ent-6α-Methoxyeudesm-4(15)-en-1β-ol	N. hiiranensis	Leaf	[3]
17	(+)-Villosine	N. hiiranensis	Leaf	[3]
		N. villosa	Root	[4]
18	Hiiranepoxide	N. hiiranensis	Leaf	[3]
19	(6α,7α)-4β-Hydroxy-10α-methoxyaromadendrane	N. hiiranensis	Leaf	[3]
20	Spathulenol	N. hiiranensis	Leaf	[3]
21	(-)-ent-4β-Hydroxy-10α-methoxyaromadendrane	N. hiiranensis	Leaf	[3]
22	4β,10α-Dihydroxyaromadendrane	N. hiiranensis	Leaf	[3]
23	Pipelol A	N. hiiranensis	Leaf	[3]
24	Deoxysericealactone	N. hiiranensis	Leaf	[3]
		N. sericea		[3]
25	Neoliacinolide A	N. hiiranensis	Leaf	[3]
		N. aciculata		[13]
26	Pseudoneoliacine	N. hiiranensis	Leaf	[3]
		N. acutotrinervia	Root	[10]
		N. villosa		[4]
27	β-Caryophyllene oxide	N. hiiranensis	Leaf	[3]
28	Kobusone	N. hiiranensis	Leaf	[3]
29	Caryolane-1,9-diol	N. hiiranensis	Leaf	[3]
30	trans-Phytol	N. hiiranensis	Leaf	[3]
31	Neoliacine	N. acciculata	Leaf	[14]
32	Neoliacinic acid	N. acciculata	Leaf	[15]
33	Deacetylzeylanidine	N. parvigemma	Leaf/stem	[5, 6]
34	Isolinderalactone	N. aciculata	Root/trunk	[9]
		N. villosa	Root	[4]
35	Litsealactone	N. aciculata	Root/trunk	[9]
36	Litseaculane	N. aciculata	Root/trunk	[9]
37	Zeylanane	N. aciculata	Root/trunk	[9]
		N. acutotrinervia	Root	[10]
38	Linderadine	N. aciculata	Root/trunk	[9]
		N. acutotrinervia		[4, 10]
		N. villosa	Root
39	Sericenine	N. sericea	Leaf	[16]
40	Sericenic acid	N. sericea	Leaf	[17]
41	Isosericenine	N. sericea	Leaf	[17]
42	Neosericenine	N. sericea	Leaf	[17]
43	Neolitacumone A	N. acuminatissima	Stem bark	[18]
44	Neolitacumone B	N. acuminatissima	Stem bark	[18]
45	Neolitacumone C	N. acuminatissima	Stem bark	[18]
46	1β-Acetoxyeudesma-4(15),7(11),8-trien-8,12-olide	N. acuminatissima	Stem bark	[18]
47	Acutotrine	N. acutotrinervia	Root	[10]
48	Acutotrinone	N. acutotrinervia	Root	[10]
49	Zeylaninone	N. acutotrinervia	Root	[10]
50	Acutotrinol	N. acutotrinervia	Root	[10]
51	Linderanine A	N. buisanensis	Root	[11]
52	Linderanine C	N. buisanensis	Root	[11]
53	Linderanine B	N. buisanensis	Root	[11]
54	Linderanine D	N. buisanensis	Root	[11]
55	Daibulactone A	N. daibuensis	Root	[19]
56	Daibulactone B	N. daibuensis	Root	[19]
57	Daibuoxide	N. daibuensis	Root	[19]
58	Sericealactone	N. sericea	Leaf	[8]
59	Neoliacinolide B	N. aciculata	Leaf	[13]
60	Neoliacinolide C	N. aciculata	Leaf	[13]
61	Sericealactonecarboxylic acid	N. aciculata	Leaf	[13]
62	Aciculatalactone	N. aciculata	Leaf	[13]
63	Furanogermenone	N. pallens	Leaf/bark	[20]
64	Germacrene D	N. pallens	Leaf	[20]
65	β-Caryophyllene	N. pallens	Leaf	[20]
66	10-epi-γ-Eudesmol	N. pallens	Bark	[20]
67	Curcumenol	N. pallens	Bark	[20]

Table 2

Triterpenes.

No.	Name	Source	Part	References
68	Taraxerone	N. dealbata	Bark	[8]
69	Taraxerol	N. dealbata	Bark	[8]
70	Hiiranterpenone	N. hiiranensis	Leaf	[3]
71	3β-Methoxy-24,24-dimethyllanosta-9(11),25-diene	N. pulchella	Stem	[13, 20]
72	24,24-Dimethyllanosta-9(11),25-dien-3-one	N. pulchella	Stem	[13, 20]
73	24,24-Dimethyllanosta-9(11),25-dien-3β-ol	N. pulchella	Stem	[20]
74	24ξ-Hydroxy-3β-methoxy-24,25-dimethyl-lanost-9(11)-ene	N. pulchella	Stem	[13, 20]
75	24ξ-Methoxy-24,25-dirnethyllanost-9(11)-en-3-one	N. pulchella	Stem	[20]
76	3β,24ξ-Dimethoxy-24,25-dimethyllanost-9(11)-ene	N. pulchella	Stem	[20]
77	Sericeol	N. sericea	Heartwood	[21]
78	24Z-Ethylidenelanost-8-en-3-one	N. sericea	Bark	[22]
79	24-Methylenelanost-8-en-3-one	N. sericea	Bark	[22]
80	24Z-Ethylidenelanost-8-en-3β-ol	N. sericea	Bark	[22]
81	24-Methylenelanost-8-en-3β-ol	N. sericea	Bark/stem	[22, 23]
82	Cycloartenol	N. sericea	Stem	[23]
83	24-Methylenecycloartanol	N. sericea	Stem	[23, 24]
		N. aciculata
84	24E-Ethylidenccycloartanol	N. sericea	Stem	[23]
85	24Z-Ethylidenecycloartanol	N. sericea	Stem	[23]
86	24-Methylene-25-methylcycloartanol	N. sericea	Stem	[23, 24]
		N. aciculata
87	24β-Ethyl-25-dehydrocycloartanol	N. aciculata	Stem	[24]
88	24,24-Dimethyl-25-dehydrocycloartanol	N. aciculata	Stem	[24]
89	24E-Ethylidenelanost-8-enol	N. sericea	Stem	[23]
90	24Z-Ethylidenelanost-8-enol	N. sericea	Stem	[23]
91	24-Methylene24(25)-dihydroparkeol (IXe)	N. sericea	Stem	[23, 24]
		N. aciculata
92	Parkeol	N. aciculata	Stem	[24]
93	24β-Methyllanosta-9(11),25-dien-3-ol	N. aciculata	Stem	[24]
94	24β-Ethlylanosta-9(11),25-dien-3-ol	N. aciculata	Stem	[24]
95	24,24-Dimethyllanosta-9(11),25-dien-3-ol	N. aciculata	Stem	[24]
96	24-Methylenelanosta-7,9(11)-dienol (Xe)	N. sericea	Stem	[23]
97	24-Methylenedammarenol	N. sericea	Stem	[23]
98	Lupeol	N. sericea	Stem	[23, 24]
		N. aciculata
99	Lupenone	N. fuscata	Bark	[25]
100	β-Amyrin	N. sericea	Stem	[23]

Table 3

Alkaloids.

No.	Name	Source	Part	References
101	Laurolitsine/(+)-Norboldine	N. villosa/N. sericea	Stem/leaf	[12, 26]
		N. acuminatissima	Stem bark	[18, 27]
		N. konishii/N. aurata	Bark	[28, 29]
		N. paraciculata		[30]
		N. buisanensis
102	Boldine	N. acuminatissima	Stem/leaf	[18, 31]
		N. villosa/N. parvigemma		[26, 27]
		N. konishii/N. sericea		[12, 29]
103	Isoboldine	N. acuminatissima	Stem/leaf	[18, 29]
		N. konishii/N. fuscata		[12, 25]
104	Isocorydine	N. sericea/N. aurata	Stem/leaf	[12]
105	Laurotetanine	N. aciculata/N. villosa	Stem/leaf	[26, 32]
		N. konishii/N. sericea		[29, 30]
				[12]
106	N-Methyllaurotetanine	N. acuminatissima	Stem/leaf	[18, 26]
		N. villosa/N. konishii		[12, 29]
107	(-)-Thalicsimidine	N. acuminatissima	Stem bark	[18]
108	(+)-11-Methoxynorboldine	N. aurata paraciculata	Bark	[28]
109	Hernovine	N. aurata paraciculata	Bark	[28, 33]
		N. variabillima.
110	10-O-Methylhernovine	N. aurata paraciculata	Bark	[28]
111	Lindcarpine	N. aurata paraciculata	Bark	[28]
112	N,O-Dimethylhernovine	N. aurata paraciculata	Bark	[28]
113	Glaucine	N. parvigemma	–	[31]
		N. konishii
114	Corydine	N. parvigemma	–	[31]
		N. konishii
115	Neolitsinine	N. pulchella	Leaf	[34]
116	Isomeric pulchelline	N. pulchella	Leaf	[34]
117	Corytuberine	N. konishii	–	[29]
118	Nnornuciferine	N. konishii	–	[29]
119	N-Methylhernovine	N. variabillima	Bark	[33]
120	Nuciferine	N. sericea	Bark	[30]
121	Glaziovine	N. konishii	Stem/leaf	[29]
		N. sericea/N. aurata	Stem	[12]
122	Stepharine	N. konishii	–	[29]
123	Isodomesticine	N. villosa	Stem/leaf	[12, 26]
124	Neolitacumonine	N. acuminatissima	Stem bark	[18]
125	Liriodenine	N. acuminatissima	Stem bark	[18]
126	(-)-Norushisunine	N. acuminatissima	Stem bark	[18]
127	(+)-Cassythine	N. acuminatissima	Stem bark	[18]
128	(-)-Anonaine	N. acuminatissima	Stem bark	[18, 35]
		N. aurata/N. sericea		[30]
129	Actinodaphnine	N. acuminatissima	Stem bark	[18, 31]
		N. konishii/N. sericea/N. parvigemma/N. villosa	Stem wood	[26, 29] [30]
130	(+)-11-Methoxynorcassythicine	N. aurata paraciculata	Bark	[28]
131	Nandigerine	N. aurata paraciculat N. variabillima.	Bark	[28, 33]
132	Roemerine	N. parvigemma	Leaf	[18, 31]
		N. konishii/N. sericea		[35]
		N. aurata		[30]
133	N-Methylactinodaphnine	N. parvigemma	Stem bark	[18, 31]
		N. konishii
		N. acuminatissima
134	(+)-O-Methylflavinantine	N. acuminatissima	Stem bark	[18]
135	(+)-Reticuline	N. acuminatissima	Stem bark	[18, 32]
		N. aciculata/N. villosa		[29]
136	(+)-Norjuziphine	N. villosa	Stem	[26]
137	Oxoglaucine	N. acuminatissima	Stem bark	[18, 31]
		N. parvigemma/N.konishii
138	(+)-11-Methoxynorneolitsine	N. aurata paraciculata	Bark	[28]
139	Neolitsine	N. pulchella	Leaf	[34]
140	Ovigerine	N. aurata paraciculata	Bark	[28]
141	N-Methylovigerine	N. aurata paraciculata	Bark	[28]
142	Methoxyannomontine	N. parvigemma	–	[31]
		N. konishii
143	(+)-Coclaurine	N. villosa	Stem	[26]
144	(+)-Juziphine	N. villosa	Stem	[26]
145	Pallidine	N. villosa/N. konishii	Stem	[26, 29]
146	Litsericine	N. sericea/N. aurata	Leaf	[27, 35]
		N. buisanensis		[30]
147	N-Methyllitsericine	N. aurata	–	[35]
148	Daibucarboline A	N. daibuensis	Root	[19]
149	Daibucarboline C	N. daibuensis	Root	[19]
150	DaibucarbolineB	N. daibuensis	Root	[19]
151	(6aR)-Normecambroline	N. dealbata	Bark	[36]

Table 4

Steroids.

No.	Name	Source	Part	References
152	24α-Ethylcholestan-3α-ol	N. sericea	Stem	[23]
153	24α-Ethylcholest-4-en-3-one	N. sericea	Stem	[23]
154	24α-Ethylcholesta-4,22-dien-3-one	N. sericea	Stem	[23]
155	β-Sitosterol	N. hiiranensis	Leaf	[3]
		N. parvigemma	Root	[4, 5, 11]
		N. buisanensis	Stem bark	[18]
		N. villosa	Wood	[37]
		N. acuminatissima
		N. sericea
156	Stigmasterol	N. acuminatissima	Stem bark	[18]
		N. sericea	Wood	[37]
157	β-Sitosteryl-d-glucoside	N. acuminatissima	Stem bark	[18]
158	Stigmasteryl-β-d-glucoside	N. acuminatissima	Stem bark	[18]
159	Campesterol	N. sericea	Wood	[37]
160	14α,24α-Dimethyl-5α-cholest-9(11)-en-3α-ol	N. aciculata	Stem	[38]
161	14α,24β-Dimethyl-5α-cholest-9(11)-en-3α-ol	N. aciculata	Stem	[38]
162	14α-Methyl-24α-ethyl-5α-cholest-9(11)-en-3α-ol	N. aciculata	Stem	[38]
163	24-Methylcholesterol	N. sericea	Stem	[39]
164	24β-Methyl-22-dehydrolathosterol	N. sericea	Stem	[39]
165	24α-Ethylcholestan-3β-ol	N. sericea	Stem	[39]
166	Citrostadienol	N. aciculata	Stem and branch	[40]
167	24-Methylene-31-norlanost-9(11)-enol	N. aciculata	Stem and branch	[40]
168	24α-Ethyl-31-norlanost-9(11)-enol	N. sericea	Stem and branch	[40]
169	24β-Ethyl-31-norlanosta-9(11)-25-dienol	N. sericea	Stem and branch	[40]
170	(24S)-24-Ethylcholest-4-ene-1-ol-3-one	N. sericea	Heartwood	[41]
171	(24S)-24-Ethylcholest-4-ene-6-ol-3-one	N. sericea	Heartwood	[41]

Table 5

Other compounds.

No.	Name	Source	Part	References
172	13²-Hydroxy-(13²S)-pheophytin	N. hiiranensis	Leaf	[3]
173	α-Tocopheryl quinine	N. hiiranensis	Leaf	[3]
174	α-Tocopherol	N. hiiranensis	Leaf	[3]
175	Ficaprenol-11	N. hiiranensis	Leaf	[3]
176	Linolenic acid	N. hiiranensis	Leaf	[3]
177	Syringaldehyde	N. hiiranensis	Leaf	[3]
178	Syringic acid	N. hiiranensis	Leaf	[3]
179	(+)-Lyoniresinol	N. acuminatissima	Stem bark	[18]
180	(+)-Syringaresinol	N. acuminatissima	Stem bark	[18]
181	(±)-Glaberide I	N. acuminatissima	Stem bark	[18]
182	Vanillin	N. hiiranensis	Leaf	[3]
		N. acuminatissima	Stem bark	[18]
183	Isovanillin	N. acuminatissima	Stem bark	[18]
184	p-Methoxybenzoic acid	N. acuminatissima	Stem bark	[18]
		N. hiiranensis	Leaf	[3]
185	Methylparaben	N. acuminatissima	Stem bark	[18]
186	2,6-Dimethoxy-p-benzoquinone	N. acuminatissima	Stem bark	[18]
187	Kaempferol 3-O-rhamnoside	N. pavigemma	–	[31]
		N. konishii
188	Quercetin 3-O-rhamnoside	N. pavigemma	–	[31]
		N. konishii	Leaf	[42]
		N. sericea
189	Taxifolin 3-O-rhamnoside	N. pavigemma	–	[31]
		N. konishii
190	Qercetin 3-O-β-d-glucoside	N. sericea	Leaf	[42]
191	Neoastilbin	N. sericea	Leaf	[42]
192	Isoastilbin	N. sericea	Leaf	[42]
193	Neoisoastilbin	N. sericea	Leaf	[42]
194	Docosanyl ferulate	N. pavigemma	–	[31]
		N. konishii
195	Tetracosanyl ferulate	N. pavigemma	–	[31]
		N. konishii
196	Hexacosanyl ferulate	N. pavigemma	–	[31]
		N. konishii
197	Blumenol A	N. pavigemma	–	[31]
		N. konishii
198	Roseoside	N. pavigemma	–	[31]
		N. konishii
199	N-trans-Feruloylmethoxytyramine	N. pavigemma	–	[31]
		N. konishii
200	trans-β-Ocimene	N. pallens	Fruit	[20]
201	Sabinene	N. pallens	Fruit	[20]

Sesquiterpenes (Table 1 and Figure 1)

Sesquiterpenes are the characteristic constituents within the genus Neolitsea. From 1966 to 2013, 67 compounds have been isolated. The researched plants include Neolitsea zeylanica, Neolitsea parvigemma, Neolitsea aciculata, Neolitsea acutotrinervia, Neolitsea hiiranensis, and Neolitsea sericea, among others. In 1966, six sesquiterpenes 1–6 were isolated from N. zeylanica [1]. In the course of further investigation on the chemical constituents of this plant, four novel sesquiterpenes of the furanogermacrane type 7–10 have been isolated from the stems of N. parvigemma [2]. In 2011, investigation of N. hiiranensis revealed seven new sesquiterpenoids 12–18 and 12 known sesquiterpenoids 19–30 from the leaves of this plant [3]. In 1983, Nozaki et al. isolated a new sesquiterpene dilactone 31, named neoliacine, from the leaves of N. aciculata, and they further examined chemical components of the same plant and isolated the sesquiterpene acid 32 [14, 15]. Four known furanosesquiterpene lactones 1, 2, 5, 6, along with a new derivative, deacetylzeylanidine 33, were isolated from N. parvigemma [5]. From N. sericea, three new elemane-type sesquiterpenoids 24, 41, 58 and two new germacrane-type sesquiterpenoids 39, 40 were isolated by column chromatography and thin layer chromatography [8]. In 1970, components of N. aciculata were investigated, and ten furan sesquiterpenes 1–4, 11, 34–38 were isolated from the root and trunk [9]. At the same time, neosericenine 42, an isomer of sericenine 39, along with compounds 40 and 41 were isolated from the leaf of N. sericea [16, 17]. Phytochemical investigation of Neolitsea acuminatissima resulted in the isolation of three new eudesmanolide sesquiterpenes 43–45 and a known eudesmanolide sesquiterpene 41 [18]. Investigation of N. acutotrinervia revealed numerous sesquiterpene lactones, including four known furanogermacranolides 2, 4, 37, 38, one known germacranediolide 35, and four new germacranediolides 47–50 [10]. Chen et al. have isolated two novel sesquiterpenes of the furanogermacrane type, namely parvigemone 9 and neolitrane 10, along with six known compounds 1–2, 5–6, 11, 33 from the stems of N. parvigemma [6]. Compounds 51–54 are not produced naturally in plant, but formed by oxidation of 2 [11]. Seven sesquiterpene lactones 1, 2, 11, 17, 26, 34, 38 were isolated from the roots of Neolitsea villosa, in which three compounds 17, 26, 38 are new [4]. Three new compounds 55–57 were isolated from the roots of Neolitsea daibuensis [19]. In the continuing studies on Lauraseae plants, which are widely distributed in Japan, three germacranes 25, 59, 60 and two elemanes 61, 62 have been isolated from the fresh leaves of N. aciculata Koidz [13]. The major constituents of the leaf and bark oil of Neolitsea pallens are compounds 63–67 [20].

Figure 1

Sesquiterpenoid structures.

Triterpenes (Table 2 and Figure 2)

Most of the triterpenes reported in the genus Neolitsea are tetracyclic, and a few of them are pentacyclic. These triterpenes are dammaranes, lanostanes, cycloartanes, oleananes, and lupanes. A phytochemical investigation of the crude chloroform extract of the Neolitsea dealbata bark revealed two common triterpenes 68, 69, which were reported for the first time from this plant [21]. Investigation of the ethyl acetate-soluble extract of the leaves of N. hiiranensis led to the isolation of hiiranterpenone 70 [3]. Chan and Hui isolated three C₃₂ triterpenes 71–73 by column chromatography of the light petroleum extract [23]. In addition, analysis of a larger quantity of a similar extract led to the discovery of three related minor triterpenes 74–76 [22, 23]. Compound 77, a new cycloartane, was reported from N. sericea in 1993, and further investigation of this plant revealed three new lanostanes 78–80, along with a known compound 81 [24, 43]. In 1992, several triterpenes 81–99 were isolated from the alcohol extract of N. sericea, among which 86, 93, and 94 are new compounds [39, 40]. Lupenone 100 was isolated from the stem bark of Neolitsea fuscata [25].

Figure 2

Triterpenoid structures.

Alkaloids (Table 3 and Figure 3)

In 2001, 15 alkaloids 101–103, 106, 107, 124–129, 133–135, 137 were isolated from the stem bark of N. acuminatissima. Among them, compound 124 was a new benzylisoquinoline alkaloid. Their structures were established on the basis of analysis of NMR and mass spectral data [18]. The first chemical investigation of N. villosa (Bl.) Merr. led to the isolation of ten known isoquinoline alkaloids 101, 104–106, 121, 128, 133, 136, 143, 144 from the stem of this plant [26]. In 1965, three new alkaloids 115, 139, 145 were found in the ethanolic extract of the dried leaves of Neolitsea pulchella [34]. Kozuka et al. reported the isolation and identification of two alkaloids 104, 134 from Neolitsea ariculuta in 1984 [32]. Three new oxygenated noraporphine alkaloids 130, 137, 138 along with eight known aporphine alkaloids 121, 108–112, 140, 141 were isolated from the bark of the Chinese tree, Neolitsea aurata var. paraciculata, which was the first report of chemical constituents of this plant [28]. In 1998, Chen et al. reported eight alkaloids 101, 113, 114, 128, 129, 131, 132, 142 from N. parvigemma and Neolitsea konishii, and compounds 129, 113, 114, 131, 132 were isolated for the first time from this genus [31]. In 2001, 15 alkaloids were isolated from the stem bark of N. acuminatissima. Among them, compound 123 is a new benzylisoquinoline alkaloid, whose structure was established on the basis of analysis of NMR and mass spectral data [18]. By combination of centrifugal partition chromatography and common separation methods, 12 known alkaloids were isolated from N. konishii and characterized [29]. Compounds 121 and 117 were isolated from Neolitsea buisanensis, N. sericea, and N. aurata [27, 30]. In addition, compounds 118, 131, 135 were isolated from N. aurata [35]. Lu and Su isolated three alkaloids 108, 112, 147 from Neolitsea variabillima [33]. In 2010, a new aporphine alkaloid 149 was reported from the bark of N. dealbata [36]. In 2011, Wong et al. reported three new β-carboline alkaloids 120, 148, 150 from the root of N. daibuensis [19]. A total 14 new alkaloids and 37 known alkaloids were reported from this genus.

Figure 3

Alkaloid structures.

Steroids (Table 4 and Figure 4)

Four steroids, a mixture of 155 and 156, and a mixture of 157 and 158, were isolated from N. acuminatissima [18]. Komae and Hayashi detected phytosterols (155, 156, 159) in the wood of N. sericea by using gas chromatography [37]. Neolitsea sericea and Daemia extensa (Asclepiadaceae) seem to be the only plants containing 3α-hydroxy sterols in a higher plant. Yano et al. investigated the constituents of the stem of this plant and isolated two new 4α-methylsterols and three new 3α-hydroxy-14α-methyl-Δ⁹⁽¹¹⁾ sterols; they are compounds 168 and 169, 24α- and 24β-epimers of 14α,24-dimethyl-5α-cholest-9(11)-en-3α-ol, compounds 160 and 161, and 14α-methyl-24α-ethyl-5α-cholest-9(11)-en-3α-ol 162 [38, 40]. The ethyl acetate extract from the wood of N. sericea contained two new steroidal compounds 170 and 171 [41]. Further study on the sterols from N. sericea extract led to the isolation of compounds 163–167 [39, 40].

Figure 4

Steroids (see Figure 2 for definition of the R groups).

Others (Table 5 and Figure 5)

From the fruit oil of N. pallens, Padalia et al. isolated trans-β-ocimene 200 and sabinene 201 [20]. Investigation of N. sericea var. aurata revealed occurrence of six flavone rhamnosides 187–193 [42]. In 1998, three flavonoids, kaempferol-3-O-rhamnoside 187, quercetin-3-O-rhamnoside 188, and taxifolin-3-O-rhamnoside 189, three ferulates, docosanyl ferulate 194, tetracosanyl ferulate 195, and hexacosanyl ferulate 196, two cyclohex-2-en-1-ones, blumenol A 197, and roseoside 198, and one amide, N-trans-feruloylmethoxytyramine 199 were isolated from Neolitsea pavigemma and N. konishii [31]. From the leaves of Neolitsea cassia, de Silva et al. isolated a water-soluble arabinoxylan [44]. Chang et al. isolated three lignans, (+)-lyoniresinol 179, (+)-syringaresinol 180, and (±)-glaberide I 181, four benzenoids, vanillin 182, isovanillin 183, p-methoxybenzoic acid 184, and methylparaben 185, together with one paraquinone, 2,6-dimethoxy-p-benzoquinone (186), from the stem bark of N. acuminatissima [18]. The following compounds were also isolated from the leaves of N. hiiranensis: 13²-hydroxy-(13²S)-pheophytin (172), α-tocopheryl quinine (173), α-tocopherol (174), ficaprenol-11 (175), linolenic acid (176), syringaldehyde (177), syringic acid (178), vanillin (182) and p-anisic acid (184) [3].

Figure 5

Structures of other compounds.

Biological activities

Anti-inflammatory activity

The anti-inflammatory effects of compounds 13 and 15 were evaluated by their suppression of the N-formyl- methionyl-leucyl-phenylalanine (fMLP)-induced generation of the superoxide anion, an inflammatory mediator produced by neutrophils. And the inhibitory activity against fMLP-induced superoxide production with IC₅₀ values of 21.86±3.97 and 25.78±4.77 mm, respectively [3]. Six furanogermacranes 1, 5–7, 10, 11 were tested for anti-inflammatory activities. Among them, compounds 1 and 11 show significant inhibitory effects on superoxide anion generation by human neutrophils in response to fMLP/CB: the IC₅₀ of compounds 1 and 11 were found to be 3.21 and 8.48 mg/mL, respectively [7]. Compounds 34 and 163, 7-O-methylnaringenin and prunetin, which were isolated from N. daibuensis, exhibit moderate inducible nitric oxide synthase inhibitory activity, with IC₅₀ values of 18.41, 0.30, 19.55, and 10.50 mm, respectively [19]. The essential oil of N. aciculata exhibit moderate to strong antibacterial activity against drug-susceptible and -resistant Propionibacterium acnes and Staphylococcus epidermidis, which are known as acne-causing bacteria. In addition, the essential oil reduces the P. acnes-induced secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) in THP-1 cells, highlighting its anti-inflammatory effects [45].

Antitumor activity

Neoliacine 31, a sesquiterpene lactone isolated from the leaves of N. aciculata, exhibits moderate cytotoxicity in HeLa cell culture in vitro [14]. Compounds 44, 45, and 184 selectively inhibit Hep 2,2,15 cells with IC₅₀ values in the range of 0.24–0.04 μg/mL. 2,6-Dimethoxy-p-benzoquinone is marginally cytotoxic to Hep G2 cells [18]. A known elemane-type sesquiterpene, isolinderalactone 34, shows promising antitumor activity in vitro against all tumor cells tested: KB (EDSo=2.990 ppm), P-388 (0.816 ppm), A-549 (1.420 ppm), and HI-29 (1.528 ppm) [4]. Recently, Su et al. reported the chemical components and in vitro anticancer activities of the essential oil isolated from the leaf of N. variabillima. The anticancer activities of oil were evaluated and the results showed that the oil exhibits cytotoxic activity against human oral, liver, lung, colon, melanoma, and leukemic cancer cells [46]. The presence of β-caryophyllene, τ-cadinol, and α-cadinol significantly contributes to the anticancer activity of N. variabillima leaf oil [46]. Compound 164 selectively inhibits the growth of cervical cancer cells (HeLa) with an IC₅₀ of 4.0 μm [40].

Vasoconstricting activity

Thaliporphine, isolated from N. konishii, has been found to possess vasoconstricting action and selectively inhibits expression of inducible, but not constitutive, nitric oxide synthase [29].

Antifungal and antibacterial activities

The hydro-distilled leaf essential oil of N. parvigemma exhibits antifungal activity against seven fungi, including Aspergillus clavatus, Aspergillus niger, Chaetomium globosum, Cladosporium cladosporioides, Myrothecium verrucaria, Penicillium citrinum, and Trichoderma viride. Besides, the oil also possesses anti-wood-decay activity induced by fungi Trametes versicolor, Phaneochaete chrysosporium, Phaeolus schweintizii, and Lenzites sulphureu [47]. The essential oil isolated from N. aciculata and N. sericea possesses antimicrobial activities [45, 48].

Others

The bark and leaves of N. cassia can be used for the treatment of fractures [44]. Several antiplatelet aggregation sesquiterpenes and alkaloids were also isolated from N. konishii, N. villosa, N. parvigemma, N. variabillima, and N. aurata and characterized [2]. Aporphine alkaloids, commonly present in this genus, have been shown to possess various pharmacological activities, such as choleretic and smooth muscle relaxing properties for boldine and hypotensive and hyperlipidemia-reducing properties in tested animals for dicentrine [12].

Conclusions

The genus Neolitsea includes 85 species, and some of them have been used as traditional herbal medicines. The chemical investigation of the Neolitsea genus has revealed that this genus contains numerous and complicated constituents, and many components with significant bioactivities have been isolated. This review reveals that only a few species have been investigated, with many species receiving little or no attention. Further phytochemical and biological studies should be carried out on these plants.

Corresponding authors: Qing-Wen Shi, School of Pharmaceutical Sciences, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China, e-mail: shiqingwen@hebmu.edu.cn; and Hiromasa Kiyota, Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-Naka, Kita-ku, Okayama 700-8530, Japan, e-mail: kiyota@okayama-u.ac.jp

Acknowledgments

The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (81072551, 81241101), Key Projects of Science and Technology of Hebei Province (11276103D-89). We also wish to extend our sincere thanks to Syngenta Ltd. (2013-Hebei Medical University-Syngenta-04) and JSPS KAKENHI (grant numbers 19580120, 22560112, 25450144) for financial support.

References

[1] Joshi, B. S.; Kamat, V. N.; Govindachari, T. R. Sesquiterpenes of Neolitsea zeylanica Merr.-I isolated of some constituents. Tetrahedron1967, 23, 261–265.Search in Google Scholar

[2] Chen, K. S.; Wu, Y. C. Sesquiterpenoids from Neolitsea parvigemma: isolation, oxidation products and antiplatelet actions. Tetrahedron1999, 55, 1353–1366.Search in Google Scholar

[3] Liou, B. J.; Chang, H. S.; Wang, G. J.; Chiang, M. Y.; Liao, C. H.; Lin, C. H.; Chen, I. S. Secondary metabolites from the leaves of Neolitsea hiiranensis and the anti-inflammatory activity of some of them. Phytochemistry2011, 72, 415–422.Search in Google Scholar

[4] Li, W. S.; Duh, C. Y. Sesquiterpene lactones from Neolitsea villosa. Phytochemistry1993, 32, 1503–1507.Search in Google Scholar

[5] Li, W. S. Chemical constituents of Neolitsea parvigemma. J. Nat. Prod.1990, 53, 1581–1584.Search in Google Scholar

[6] Chen, K. S.; Chang, F. R. Two novel sesquiterpenes from Neolitsea parvigemma. J. Nat. Prod.1996, 59, 704–706.Search in Google Scholar

[7] Chen, K. S.; Hsieh, P. W.; Hwang, T. L.; Chang, F. R.; Wu, Y. C. Anti-inflammatory furanogermacrane sesquiterpenes from Neolitsea parvigemma. Nat. Prod. Res. 2005, 19, 283–286.Search in Google Scholar

[8] Hayashi, N. Sesquiterpenoids in the essential oil of Neolitsea sericea. Physics Chem.1969, 33, 107–133.Search in Google Scholar

[9] Takeda, K.; Horibe, I.; Teraoka, M.; Minato, H. Sesquiterpenes of Lauraceae plants. Part 1. Components of Neolitsea aciculate Koidz. J. Chem. Soc. (C)1970, 7, 973–980.Search in Google Scholar

[10] Li, W. S. Sesquiterpene lactones from the root of Neolitsea acutotrinervia. J. Nat. Prod.1992, 55, 1614–1619.Search in Google Scholar

[11] Li, S.; Li, W. S. Terpenoids from Neolitsea buisanensis. Phytochemistry1991, 30, 4160–4162.10.1016/0031-9422(91)83488-7Search in Google Scholar

[12] Sun, S. W.; Lee, S. S.; Huang, H. M. Determination of lauraceous aporphine alkaloids by high-performance liquid chromatography. J. Pharm. Biomed. Anal. 1996, 14, 1383–1387.Search in Google Scholar

[13] Takaoka, D.; Tani, H.; Nozaki, H.; Tada, S.; Nakayama, M. Structures of highly oxygenated sesquiterpenoids of Lauraceae, Neolitsea aciculata Koidz. Tennen Yuki Kagobutsu Toronkai Koen Yoshishu1992, 34, 424–431.Search in Google Scholar

[14] Nozaki, H.; Hiroi, M.; Takaoka, D.; Nakayarna, M. Neoliacine, a novel germacranolide sesquiterpene dilactone from Neolitsea acciculata Koidz.:X-ray crystal structure. J.Chem.Soc.Chem.Commun. 1983, 19, 1107–1108.Search in Google Scholar

[15] Takaoka, D.; Nozaki, H.; Nakayama, M. Structure of neoliacinic acid, a new highly oxidized sesquiterpene from Neolitsea acciculata Koidz. J. Chem. Soc. Chem. Commun. 1987, 24, 1861–1862.Search in Google Scholar

[16] Takeda, K.; Tori, K.; Horibe, I.; Minato, H. Structure of sericenine. J. Chem. Soc. (C)1970, 7, 985.10.1039/j39700000985Search in Google Scholar

[17] Takeda, K.; Horibe, I.; Minato, H. Sesquiterpenes of Lauraceae plants. Part II. Neosericenine, a component of Neolitsea sericea Koidz. J. Chem. Soc. (C)1970, 11, 1547–1549.Search in Google Scholar

[18] Chang, F. R.; Hsieh, T. J.; Huang, T. L.; Chen, C. Y.; Kuo, R. Y.; Chang, Y. C.; Chiu, H. F.; Wu, Y. C. Cytotoxic constituents of the stem bark of Neolitsea acuminatissima. J. Nat. Prod.2002, 65, 255–258.Search in Google Scholar

[19] Wong, S. L.; Chang, H. S.; Wang, G. J.; Chiang, M. Y.; Huang, H. Y.; Chen, C. H.; Tsain, S. C.; Lin, C. H.; Chen, I. S. Secondary metabolites from the roots of Neolitsea daibuensis and their anti-inflammatory activity. J. Nat. Prod.2011, 74, 2489–2496.Search in Google Scholar

[20] Padalia, R. C.; Chanotiya, C. S.; Thakuri, B. C.; Mathela, C. S. Germacranolide rich essential oil from Neolitsea pallens. Nat. Prod. Commun. 2007, 2, 591–593.Search in Google Scholar

[21] Wu, X. J.; Vogler, B.; Jackes, B. R.; Setzer, W. N. Terpenoids from Neolitsea dealbata. Nat. Prod. Commun. 2008, 3, 129–132.Search in Google Scholar

[22] Hui, W. H.; Luk, K.; Arthur, H. R.; Loo, S. N. Structures of three C₃₂ triterpenoids from Neolitsea puchella. J. Chem. Soc. (C)1971, 16, 2826–2829.Search in Google Scholar

[23] Chan, W. S.; Hui, W. H. Further C₃₂ triterpenoids from Neolitsea puchella. J. Chem. Soc. (C)1973, 5, 490–492.Search in Google Scholar

[24] Sharma, M. C.; Ohira, T.; Yatagai, M. Sericeol, a cycloartane triterpene from Neolitsea sericea. Phytochemistry1993, 33, 721–722.Search in Google Scholar

[25] Gunatilaka, A. A. L.; Sotheeswaran, S.; Sriyani, B.; Balasubramaniam, S. Isoboldine and lupenone from Neolitsea fuscata. Planta Med. 1981, 43, 309–310.Search in Google Scholar

[26] Lee, S. S.; Wang, P. H.; Chiou, C. M.; Chen, I. S.; Chen, C. H. Isoquinoline alkaloids from Litsea garciae and Neolitsea villosa. Chin. Pharmaceut. J.1995, 47, 69–75.Search in Google Scholar

[27] Tatsuo, N.; Shozo, N. Alkaloids of lauraceous plants. III. Alkaloids isolated from the leaves of Neolitsea sericea. Yakugaku Zasshi1959, 79, 1267–1272.10.1248/yakushi1947.79.10_1267Search in Google Scholar

[28] Buchanan, M. S.; Carroll, A. R.; Pass, D.; Quinn, R. J.; Buchanan, M. S.; Carroll, A. R.; Pass, D.; Quinn, R. J. Aporphine alkaloids from the Chinese tree Neolitsea aurata paraciculata. Nat. Prod. Commun. 2007, 2, 255–259.Search in Google Scholar

[29] Lee, S. S.; Yang, H. C. Isoquinoline alkaloids from Neolitsea konishii. J. Chin. Chem. Soc. 1992, 39, 189–194.Search in Google Scholar

[30] Tatsuo, N.; Shozo, A.; Yuri, K. Alkaloids of Lauraceae plants. V. Alkaloids isolated from the trunk bark of Neolitsea sericea. Yakugaku Zasshi1966, 86, 129–134.Search in Google Scholar

[31] Chen, K. S.; Chang, F. R.; Chia, Y. C.; Wu, T. S.; Wu, Y. C. Chemical constituents of Neolitsea parvigemma and Neolitsea konishii. J. Chin. Chem. Soc.1998, 45, 103–110.Search in Google Scholar

[32] Kozuka, M.; Takeuchi, M.; Sawada, T. Alkaloid from Neolitsea aciculata. J. Nat. Prod.1984, 47, 1062.Search in Google Scholar

[33] Lu, S. T.; Su, T. L. Alkaloids of formosan Lauraceous plants. XVI. Alkaloids of Neolitsea variabillima. J. Chin. Chem. Soc. 1973, 20, 75–81.Search in Google Scholar

[34] Hui, W. H.; Loo, S. N.; Arthur, H. R. New aporphine alkaloids from Neolitsea pulchella. J. Chem. Soc. (C)1965, 3, 2285–2286.Search in Google Scholar

[35] Lu, S. T.; Su, T. L.; Wang, E. C. Studies on the alkaloids of formosan lauraceous plants. XVIII. Alkaloids of Neolitsea buisanensis Yamamoto et Kamikoti and Neolitsea aurata (Hay.) Koidz. J. Chin. Chem. Soc. 1975, 22, 349–353.Search in Google Scholar

[36] Tran, T. D.; Pham, N. B.; Fechner, G.; Quinn, R. J.; Ronald, J. Chemical investigation of drug-like compounds from the Australian tree Neolitsea dealbata. Bioorg. Med. Chem. Lett.2010, 20, 5859–5863.Search in Google Scholar

[37] Komae, H.; Hayashi, N. Palmitone and phytosterols from Neolitsea sericea. Phytochemistry1971, 10, 1953–1954.10.1016/S0031-9422(00)86477-8Search in Google Scholar

[38] Yano, K.; Akihisa, T.; Tamura, T.; Matsumoto, T. 3α-Hydroxy-14-methyl-Δ⁹⁽¹¹⁾ sterol from Neolitsea acicutala. Phytochemistry1992, 31, 2902–2904.Search in Google Scholar

[39] Yano, K.; Akihisa, T.; Kawaguchi, R.; Tamura, T.; Matsumoto, T. 24-Methylene-25-methylcycloartanol and 24α-ethyl-5α-cholestan-3α-ol from Neolitsea sericea. Phytochemistry1992, 31, 1941–1946.Search in Google Scholar

[40] Yano, K.; Akihisa, T.; Tamura, T.; Matsumoto, T. Four 4α-methylsterols and triterpene alkaloids from Neolitsea aciculata. Phytochemistry1992, 31, 2093–2098.Search in Google Scholar

[41] Sharma, M. C.; Ohira, T.; Yatagai, M. Extractives of Neolitsea sericea a new hydroxy steroidal ketone, and other compounds from the heartwood of Neolitsea sericea. Mokuzai Gakkaishi1993, 39, 939–943.Search in Google Scholar

[42] Lam, S. H.; Chen, C. K.; Wang, J. S.; Lee, S. S. Investigation of flavonoid glycosides from Neolitsea sericea var. aurata via the general method and HPLC-SPE-NMR. J. Chin. Chem. Soc. 2008, 55, 449–455.Search in Google Scholar

[43] Sharma, M. C.; Ohira, T.; Yatagai, M. Lanostane triterpenes from the bark of Neolitsea sericea. Phytochemistry1994, 37, 201–203.Search in Google Scholar

[44] de Silva, S. S. M.; Kumar, N. S. Structural studies of an arabinoxylan isolated from the leaves of Neolitsea cassia. Carbohydr. Res.1986, 152, 229–236.Search in Google Scholar

[45] Suk, K. S.; Eun, K. J.; Hyun, C. G.; Lee, N. H. Neolitsea aciculata essential oil inhibits drug-resistant skin pathogen growth and propionibacterium acnes-induced inflammatory effects of human monocyte leukemia. Nat. Prod. Commun.2011, 8, 1193–1198.Search in Google Scholar

[46] Su, Y. C.; Hsu, K. P.; Wang, E. I. C.; Ho, C. L. Composition and in vitro anticancer activities of the leaf essential oil of Neolitsea variabillima from Taiwan. Nat. Prod. Commun. 2013, 8, 531–532.Search in Google Scholar

[47] Ho, C. L.; Liao, P. C.; Wang Eugene, I. C.; Su, Y. C. Composition and antifungal activities of the leaf essential oil of Neolitsea parvigemma from Taiwan. Nat. Prod. Commun. 2011, 6, 1357–1360.Search in Google Scholar

[48] Hyun, C. G.; Yoon, W. J.; Lee, N. H. Essential oils of Neolitsea sericea having anti-inflammatory and antimicrobial activities. Korean Kongkae Taeho Kongbo2011, KR 2011036318 A 20110407.Search in Google Scholar

Received: 2013-12-17

Accepted: 2014-2-13

Published Online: 2014-3-31

Published in Print: 2014-4-1

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Chemical constituents of plants from the genus Neolitsea

Abstract

Introduction

Chemical constituents

Sesquiterpenes (Table 1 and Figure 1)

Triterpenes (Table 2 and Figure 2)

Alkaloids (Table 3 and Figure 3)

Steroids (Table 4 and Figure 4)

Others (Table 5 and Figure 5)

Biological activities

Anti-inflammatory activity

Antitumor activity

Vasoconstricting activity

Antifungal and antibacterial activities

Others

Conclusions

Acknowledgments

References

Journal and Issue

Articles in the same Issue