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 . Constituents of the Neolitsea genus (Lauraceae) have been reported to possess diverse bioactivities, such as antioxidant, antibacterial, anti-inflammatory activities, and cytotoxicity .
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.
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.
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 . 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 . In 2011, investigation of N. hiiranensis revealed seven new sesquiterpenoids 12–18 and 12 known sesquiterpenoids 19–30 from the leaves of this plant . 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 . 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 . In 1970, components of N. aciculata were investigated, and ten furan sesquiterpenes 1–4, 11, 34–38 were isolated from the root and trunk . 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 . 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 . 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 . Compounds 51–54 are not produced naturally in plant, but formed by oxidation of 2 . 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 . Three new compounds 55–57 were isolated from the roots of Neolitsea daibuensis . 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 . The major constituents of the leaf and bark oil of Neolitsea pallens are compounds 63–67 .
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 . Investigation of the ethyl acetate-soluble extract of the leaves of N. hiiranensis led to the isolation of hiiranterpenone 70 . Chan and Hui isolated three C32 triterpenes 71–73 by column chromatography of the light petroleum extract . 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 .
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 . 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 . In 1965, three new alkaloids 115, 139, 145 were found in the ethanolic extract of the dried leaves of Neolitsea pulchella . Kozuka et al. reported the isolation and identification of two alkaloids 104, 134 from Neolitsea ariculuta in 1984 . 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 . 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 . 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 . By combination of centrifugal partition chromatography and common separation methods, 12 known alkaloids were isolated from N. konishii and characterized . 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 . Lu and Su isolated three alkaloids 108, 112, 147 from Neolitsea variabillima . In 2010, a new aporphine alkaloid 149 was reported from the bark of N. dealbata . In 2011, Wong et al. reported three new β-carboline alkaloids 120, 148, 150 from the root of N. daibuensis . A total 14 new alkaloids and 37 known alkaloids were reported from this genus.
Four steroids, a mixture of 155 and 156, and a mixture of 157 and 158, were isolated from N. acuminatissima . Komae and Hayashi detected phytosterols (155, 156, 159) in the wood of N. sericea by using gas chromatography . 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 . Further study on the sterols from N. sericea extract led to the isolation of compounds 163–167 [39, 40].
From the fruit oil of N. pallens, Padalia et al. isolated trans-β-ocimene 200 and sabinene 201 . Investigation of N. sericea var. aurata revealed occurrence of six flavone rhamnosides 187–193 . 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 . From the leaves of Neolitsea cassia, de Silva et al. isolated a water-soluble arabinoxylan . 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 . 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) .
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 . 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 . 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 . 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 .
Neoliacine 31, a sesquiterpene lactone isolated from the leaves of N. aciculata, exhibits moderate cytotoxicity in HeLa cell culture in vitro . 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 . 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) . 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 . The presence of β-caryophyllene, τ-cadinol, and α-cadinol significantly contributes to the anticancer activity of N. variabillima leaf oil . Compound 164 selectively inhibits the growth of cervical cancer cells (HeLa) with an IC50 of 4.0 μm .
Thaliporphine, isolated from N. konishii, has been found to possess vasoconstricting action and selectively inhibits expression of inducible, but not constitutive, nitric oxide synthase .
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 . The essential oil isolated from N. aciculata and N. sericea possesses antimicrobial activities [45, 48].
The bark and leaves of N. cassia can be used for the treatment of fractures . Several antiplatelet aggregation sesquiterpenes and alkaloids were also isolated from N. konishii, N. villosa, N. parvigemma, N. variabillima, and N. aurata and characterized . 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 .
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.
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.
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. Phytochemistry 2011, 72, 415–422.CrossrefWeb of SciencePubMedGoogle Scholar
Li, W. S.; Duh, C. Y. Sesquiterpene lactones from Neolitsea villosa. Phytochemistry 1993, 32, 1503–1507.Google Scholar
Hayashi, N. Sesquiterpenoids in the essential oil of Neolitsea sericea. Physics Chem. 1969, 33, 107–133.Google Scholar
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.Google Scholar
Li, S.; Li, W. S. Terpenoids from Neolitsea buisanensis. Phytochemistry 1991, 30, 4160–4162.Google Scholar
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 Yoshishu 1992, 34, 424–431.Google Scholar
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.CrossrefGoogle Scholar
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.CrossrefGoogle Scholar
Takeda, K.; Tori, K.; Horibe, I.; Minato, H. Structure of sericenine. J. Chem. Soc. (C) 1970, 7, 985.Google Scholar
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.Google Scholar
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.CrossrefGoogle Scholar
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.CrossrefGoogle Scholar
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.Google Scholar
Wu, X. J.; Vogler, B.; Jackes, B. R.; Setzer, W. N. Terpenoids from Neolitsea dealbata. Nat. Prod. Commun. 2008, 3, 129–132.Google Scholar
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.Google Scholar
Chan, W. S.; Hui, W. H. Further C32 triterpenoids from Neolitsea puchella. J. Chem. Soc. (C) 1973, 5, 490–492.Google Scholar
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.Google Scholar
Tatsuo, N.; Shozo, N. Alkaloids of lauraceous plants. III. Alkaloids isolated from the leaves of Neolitsea sericea. Yakugaku Zasshi 1959, 79, 1267–1272.Google Scholar
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.Google Scholar
Lee, S. S.; Yang, H. C. Isoquinoline alkaloids from Neolitsea konishii. J. Chin. Chem. Soc. 1992, 39, 189–194.Google Scholar
Tatsuo, N.; Shozo, A.; Yuri, K. Alkaloids of Lauraceae plants. V. Alkaloids isolated from the trunk bark of Neolitsea sericea. Yakugaku Zasshi 1966, 86, 129–134.Google Scholar
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.Google Scholar
Lu, S. T.; Su, T. L. Alkaloids of formosan Lauraceous plants. XVI. Alkaloids of Neolitsea variabillima. J. Chin. Chem. Soc. 1973, 20, 75–81.Google Scholar
Hui, W. H.; Loo, S. N.; Arthur, H. R. New aporphine alkaloids from Neolitsea pulchella. J. Chem. Soc. (C) 1965, 3, 2285–2286.Google Scholar
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.Google Scholar
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.CrossrefPubMedWeb of ScienceGoogle Scholar
Yano, K.; Akihisa, T.; Tamura, T.; Matsumoto, T. 3α-Hydroxy-14-methyl-Δ9(11) sterol from Neolitsea acicutala. Phytochemistry 1992, 31, 2902–2904.Google Scholar
Yano, K.; Akihisa, T.; Kawaguchi, R.; Tamura, T.; Matsumoto, T. 24-Methylene-25-methylcycloartanol and 24α-ethyl-5α-cholestan-3α-ol from Neolitsea sericea. Phytochemistry 1992, 31, 1941–1946.Google Scholar
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 Gakkaishi 1993, 39, 939–943.Google Scholar
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.Google Scholar
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.Google Scholar
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.PubMedGoogle Scholar
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.PubMedGoogle Scholar
Hyun, C. G.; Yoon, W. J.; Lee, N. H. Essential oils of Neolitsea sericea having anti-inflammatory and antimicrobial activities. Korean Kongkae Taeho Kongbo 2011, KR 2011036318 A 20110407.Google Scholar
About the article
Published Online: 2014-03-31
Published in Print: 2014-04-01