|Year : 2021 | Volume
| Issue : 4 | Page : 211-220
Rare and precious chinese materia medica: Pseudobulbus cremastrae seu pleiones
Hisayoshi Norimoto1, Chiaki Murayama2, Feng Zhao3, Hong- Yan Wei4
1 Association of Promoting Sustainable Use of Medicinal Resources, Kusazu City, Shiga 525-0058, Japan; PuraPharm International Ltd., Hong Kong Science Park, Hong Kong 999077, China; PuraPharm Japan Corporation, Toyama City, Toyama 930-0866, Japan; PuraPharm Research Institute, Pharmaceutical Co., Ltd., Nanning 5300007, Guangxi, China
2 Association of Promoting Sustainable Use of Medicinal Resources, Kusazu City, Shiga 525-0058; PuraPharm Japan Corporation, Toyama City, Toyama 930-0866, Japan
3 Gold Sparke (Guizhou) Chinese Medicine Co., Ltd., Danzhai 557500, Guizhou, China
4 PuraPharm Research Institute, Pharmaceutical Co., Ltd., Nanning 5300007, Guangxi, China
|Date of Submission||16-Sep-2021|
|Date of Acceptance||26-Nov-2021|
|Date of Web Publication||28-Dec-2021|
Dr. Hisayoshi Norimoto
Association of Promoting Sustainable Use of Medicinal Resources, Kusazu City, Shiga 525-0058; PuraPharm International Limited, Hong Kong Science Park, Hong Kong 999077; PuraPharm Japan Corporation, Toyama City, Toyama, 930-0866; PuraPharm Research Institute, Pharmaceutical Co., Ltd., Nanning 5300007, Guangxi
Source of Support: None, Conflict of Interest: None
Shan Ci Gu (山慈菇 Pseudobulbus Cremastrae seu Pleiones), a rare and precious traditional Chinese medicine, has attracted attention for the treatment of various cancers and bacterial infections. According to the Pharmacopoeia of the People's Republic of China, Pseudobulbus Cremastrae seu Pleionesis sourced from the pseudobulbs of three plants in the Orchidaceae family: Cremastra appendiculata (D. Don) Makino, Pleione bulbocodioides (Franch.) Rolfe, and Pleione yunnanensis Rolfe. Extracts from Pseudobulbus Cremastrae seu Pleiones are used for the treatment of tumors, burns, and frostbite. The aims of this review are to provide information on the historical and herbological origins of Pseudobulbus Cremastrae seu Pleiones, to summarize research conducted on its phytochemical and biological activities over the last twenty years, and to detail planting efforts.
Keywords: Biological activity, Cremastra appendiculata, phytochemistry, planting, Pleione bulbocodioides, Pleione yunnanensis, Shan Ci Gu, Pseudobulbus Cremastrae seu Pleiones
|How to cite this article:|
Norimoto H, Murayama C, Zhao F, Wei HY. Rare and precious chinese materia medica: Pseudobulbus cremastrae seu pleiones. Chin Med Cult 2021;4:211-20
|How to cite this URL:|
Norimoto H, Murayama C, Zhao F, Wei HY. Rare and precious chinese materia medica: Pseudobulbus cremastrae seu pleiones. Chin Med Cult [serial online] 2021 [cited 2022 May 23];4:211-20. Available from: https://www.cmaconweb.org/text.asp?2021/4/4/211/334095
| Introduction|| |
Traditional Chinese medicines (TCMs) have been widely used in China for thousands of years. Nowadays, the use of TCMs is rapidly increasing not only in tandem with the economic growth in China but also facilitated by national policies. In the last 10 years, huge growth has been seen in the TCMs market and their pharmaceutical development, including cultivation and processing. Demand for rare TCMs such as Panax ginseng, Ganoderma lucidum, Cordyceps sinensis, Fritillaria, and Shan Ci Gu (山慈菇 Pseudobulbus Cremastrae seu Pleiones) for use in healthcare has increased. These materials typically command high prices.
Pseudobulbus Cremastrae seu Pleiones is a rare TCM that has attracted attention for the treatment of various cancers and bacterial infections. According to the Zhong Guo Yao Dian (《中国药典》Chinese Pharmacopoeia), Pseudobulbus Cremastrae seu Pleiones is extracted from pseudobulbs of Cremastra appendiculata (D. Don) Makino, Pleione bulbocodioides (Franch.) Rolfe, and Pleione yunnanensis Rolfe in the Orchidaceae family [Figure 1] and is prescribed for the treatment of tumors, burns, and frostbite. In Chinese, C. appendiculata (D. Don) Makino is commonly referred to as Mao Ci Gu (Mao means hairy), and P. bulbocodioides (Franch.) Rolfe, and P. yunnanensis Rolfe are commonly referred to as Bing Qiu Zi (which means ice ball). Dried bulbs of Tulipa edulis (Miq.) Baker, which is commonly known in Chinese as Guang Ci Gu (Guang means smooth), are also sold in markets as Pseudobulbus Cremastrae seu Pleiones at a cheaper price than the above three species or mixed with authentic Pseudobulbus Cremastrae seu Pleiones. This plant is a perennial herb in the genus Tulipa and the family Liliaceae.
|Figure 1: Cremastra appendiculata (D. Don) Makino (a) Pleione bulbocodioides (Franch.) Rolfe (b) and P. yunnanensis Rolfe (c) (by Feng Zhao)|
Click here to view
Owing to its high ornamental and medicinal value, several orchid species that can be used to produce medicines, such as Shan Ci Gu (Pseudobulbus Cremastrae seu Pleiones) and Bai Ji (hyacinth orchid, Bletilla striata (Thunb.) Reichb. f.), have become rare and endangered. Therefore, artificial cultivation has been investigated actively, and a method for massive propagation from seeds and meristems has been successfully developed and applied to C. appendiculata, P. yunnanensis, and Bai Ji in Guizhou, China. Among them, the phytochemical and biological activities of Bletilla striata harvested from these plantations have been evaluated.
The aims of this review are to provide information on the historical and herbological origins of Pseudobulbus Cremastrae seu Pleiones, its source plants, cultivation, phytochemical and biological activities.
| History and Herbological Origin of Pseudobulbus Cremastrae seu Pleiones|| |
Pseudobulbus Cremastrae seu Pleiones was first listed in the Ben Cao Shi Yi (《本草拾遗》 Supplement to Materia Medica) which was published in the Tang Dynasty and has been used as an antidote for the treatment of abscess (i.e., carbuncles and furuncles), scrofulosis, snake bites, and worm bites. However, the origins of Pseudobulbus Cremastrae seu Pleiones are confused in the herb market because it is derived from many different plants and their records in ancient and modern literature with the same name. The earliest studies on the origin of Shan Ci Gu were performed in 1980s and involved systematic investigation of the historical and herbological origins of Pseudobulbus Cremastrae seu Pleiones in China and Japan. It was concluded that the correct sources of Pseudobulbus Cremastrae seu Pleiones were Cremastra. variabilis (Bl.) Nakai (C. appendiculata (D. Don) Makino), and P. bulbocodioides (Franch.) Rolfe.
According to morphological descriptions in the Zhen Lei Ben Cao (《证类本草》 Materia Medica Arranged According to Pattern) which was published in the Song Dynasty, Pseudobulbus Cremastrae seu Pleiones used in the Tang Dynasty was sourced from C. variabilis (Bl.) Nakai and P. bulbocodioides (Franch.) Rolfe [Figure 2]. From the Song Dynasty to Ming Dynasty, Pseudobulbus Cremastrae seu Pleiones was sourced from several other plants in addition to C. variabilis (Bl.) Nakai and P. bulbocodioides (Franch.) Rolfe. For example, illustrations and/or morphological descriptions recorded in the Ben Cao Gang Mu (《本草纲目》 Compendium of Materia Medica), Ben Cao Hui Yan (《本草汇言》 Treasury of Words on the Materia Medica) and Ben Cao Yuan Shi (《本草原始》 Origins of Materia Medica) of the Ming Dynasty, as well as the Zhi Wu Ming Shi Tu Kao (《植物名实图考》Illustrated Reference of Botanical Nomenclature) of the Qing Dynasty indicate that Pseudobulbus Cremastrae seu Pleiones was sourced from Lycoris plants in the Amaryllidaceae family, Dioscorea plants in the Dioscoreaceae family, and Amana edulis (Miq.) Honda in the Liliaceae family, respectively. In addition, Lycoris plants in the Amaryllidaceae family and Erythronium japonicum Dence. were used in ancient Japan, which suggests that Japanese herbalists in the Edo period (1603–1867) did not have accurate information and/or knowledge about the origin of Pseudobulbus Cremastrae seu Pleiones.
|Figure 2: Historical and Herbological Origins of Pseudobulbus Cremastrae seu Pleiones|
Click here to view
The identification of the correct sources of Pseudobulbus Cremastrae seu Pleiones as C. variabilis (Bl.) Nakai (C. appendiculata (D. Don) Makino), and P. bulbocodioides (Franch.) Rolfe is supported by recent studies on botanical descriptions in Chinese ancient literature. It should be noted that Amana. edulis (Miq.) Honda, formerly known as Tulipa edulis (Miq.) Baker, is a plant in the Liliaceae family. Dried bulbs of this plant are named Guang Ci Gu because the soft hairs on the surface are removed. On the basis of literature investigations, some researchers have argued that T. edulis should be listed as an authentic source of Pseudobulbus Cremastrae seu Pleiones. Since 1995, C. appendiculata, P. bulbocodioides, and P. yunnanensis have been listed formally in the Pharmacopoeia of the People's Republic of China as the authentic sources of Pseudobulbus Cremastrae seu Pleiones.
| Cremastra appendiculata (D. Don) Makino|| |
Cremastra appendiculata is an orchid species in the genus Cremastra. This genus was established by J. Lindley (1833) using a plant collected by N. Wallich in Nepal. It was previously described by D. Don (1825) as Cymbidium appendiculatum. However, Lindley apparently did not agree with the placement of this orchid in the Cymbidium genus and renamed the species Cremastra wallichiana. Nomenclature rules at the time were different and allowed for this change. Under current nomenclature rules, the correct name is C. appendiculata (D. Don) Makino. The generic name for this species is derived from the Greek words kremannymi (hanging) and astron (star) because of its physical features.
Plant description and distribution
The Cremastra genus comprises seven species of plant. Among them, C. appendiculata is the most common and widely distributed species. It is found in forests at an altitude of 300–2900 m in most regions south of the Yellow River, including Guizhou, Guangxi, Guangdong, and Yunnan provinces of China, Thailand, Vietnam, and Japan (Hokkaido, Honshu, Shikoku, and Kyushu)., This plant is a terrestrial herb with tuberous, clustered pseudobulbs, each of which bears a single, large elliptical leaf (of 20–30 leaves by 4–6 cm) that is plicated with three ribs and a long petiole. The floral scape arises from the side of the pseudobulb and carries a dozen floppy, scented, tubular flowers (up to 4 cm long) that look similar to lilies. These flowers do not open widely, and together looking rather like a stand. The flowers are yellow to orange with a white lip, and the lip and petals have bluish-violet spots. Flowering occurs from May to June, and fruiting from September to December. The common name of the plant in Chinese is Dujuan Lan and in Japanese is Saihai Ran.
This species has relatively wide green leaves that suggest high photosynthetic ability, but is usually found in the understory of humid and highly shaded forests. Therefore, it is unlikely to exert its photosynthetic ability to a sufficient level to support its own growth, which suggests that mycobionts may support the growth of this orchid in its natural habitat. Yagame et al. found that saprobic Psathyrellaceae fungi in the Agaricales order induced seed germination of the photosynthetic orchid C. appendiculata. This was the first report of Psathyrellaceae fungi as mycobionts associated with photosynthetic orchids, and it suggested that C. appendiculata may depend on mycobionts to obtain sufficient nutrients for growth even in the adult stage. This ecological feature could contribute to the survival of this orchid under the highly shaded forest canopy.
Phytochemistry and biological activity
Numerous phytochemical studies have been conducted on C. appendiculata in recent decades by two research groups. A total of 108 natural chemical constituents, including 37 new compounds, have been isolated from C. appendiculata. Most of these compounds have been identified as phenanthrenes, biphenanthrenes, phenanthrene glucosides, bibenzyls, and terpenoids. Phenanthrenes are a relatively uncommon class of polycyclic aromatic metabolites that are thought to form by oxidative coupling of the aromatic rings of stilbene precursors. Although phenanthrenes are considered to constitute a relatively small group of natural products, a fairly large numbers of phenanthrenes with promising biological activities have been isolated from vascular plants, mainly in the Orchidaceae family.
From 2005 to 2008, Xue et al. isolated eight novel compounds and sixteen known compounds from an ethanolic extract of the tubers of C. appendiculata.,,, The new compounds identified were as follows: three monophenanthrenes, viz. 1-hydroxy-4,7-dimethoxy-1-(2-oxopropyl)-1H-phenanthren-2-one (1), 1,7-dihydroxy-4-methoxy-1-(2-oxopropyl)-1H-phenanthren-2-one (2), and 2-hydroxy-4,7-dimethoxyphenanthrene (3); two biphenanthrenes, viz. 2, 7, 2'-trihydroxy-4,4',7'- trimethoxy-1,1'-biphenanthrene (4),and 2,2'-dihydroxy- 4, 7, 4',7'-tetramethoxy-1,1'-biphenanthrene (5); one triphenanthrene, viz. 2, 7, 2',7',2''-pentahydroxy-4,4',4'',7''-tetramethoxy-1, 8, 1',1''-triphenanthrene (6); and two new terpenoids, viz. (−)-cadin-4,10 (15)-dien-11-oic acid (7) and (−)-ent-12β-hydroxykaur-16-en-19-oic acid, 19-O-β-D-xylopyranosyl-(1>6)-O-β-D-glucopyranoside (8). The known compounds were identified as isohircinol (9), flavanthrinin (10), p-hydroxyphenylethyl alcohol (11), 3,4-dihydroxyphenylethyl alcohol (12), daucosterol (13), β-sitosterol (14), cirrhopetalanthrin (15), 7-hydroxy-4-methoxyphenanthrene-2-O-β-D-glucoside (16), 4-(2-hydroxyethyl)-2-methoxyphenyl-1-O-β-D-glucopyranoside (17), tyrosol 8-O-β-D-glucopyranoside (18), vanilloloside (19), p-hydroxybenzaldehyde (20), sucrose (21), adenosine (22), cirrhopetalanthin (23), and (+)-24,24-dimethyl-25,32-cyclo-5α-lanosta-9 (11)-en-3β -ol (24). Among these compounds, 9–22 were isolatedfor the first time from this plant, and 9 was obtained from natural source for the first time.
The bioactivities of these compounds were evaluated against human colon cancer (HCT-8), hepatoma (Bel7402), stomach cancer (BGC-823), lung adenocarcinoma (A549), breast cancer (MCF-7), and ovarian cancer (A2780) cell lines.,, Only two of the compounds (15 and 24) showed non-selective moderate cytotoxicity with half-maximal inhibitory concentration (IC50) values of 8.4–13.3 µmol/L and selective cytotoxicity against human breast cancer cell lines with an IC50 value of 3.18 μmol/L.,
From 2013 to 2021, Liu et al. identified 15 new phenanthrenes in a high-polarity extract of C. appendiculata tubers. These compounds were 1-(3′-methoxy-4′-hydroxybenzyl)-4-methoxyphenanthrene-2,7-diol (25), 1-(3′-methoxy-4′-hydroxybenzyl)-7-methoxy-9,10-dihydrophenanthrene-2,4-diol (26), 1-(3′-methoxy-4′-hydroxybenzyl)-4-methoxyphenanthrene-2, 6, 7-triol (27), cremaphenanthrenes A–E (28–32), cremaphenanthrene F–G (33 and 34), and cremaphenanthrenes L–P (35–39). This was the first report of the isolation of biphenanthrene atropisomers (33 and 34) from the plant kingdom.
Thirteen known compounds were obtained from petroleum ether and ethyl acetate extracts and they were identified as p-hydroxybenzaldehyde (20), 4,4'-dimethoxy-9,9', 10, 10'-tetrahydro-(1,1'-biphenant hrene)-2,2', 7, 7'-tetrol (40), 4,4', 7, 7'-tetrahydroxy-2,2'- dimethoxy-1,1'-biphenanthrene (41), 3,5-dihydroxy-2,4-dimethoxyphenanthrene (42), physcion (43), chrysophanol (44), emodin (45), genkwanin (46), quercetin (47), quercetin 3'-O-β-D-glucopyranoside (48), 3-methoxy-4-hydroxy phenylethanol (49), syringic acid(50), and vanillin (51). Seven known phenanthrenes were isolated from an ethanolic extract and identified as 2, 7, 7′-trihydroxy-4,4′-dimethoxy-9′,10′-dihydro-1,2′-biphenanthreneether (blestrin C, 52), 2, 7, 7′-trihydroxy-4,5′-dimethoxy-9′,10′-dihydro-1,2′-biphenanthreneether (blestrin D, 53), 4, 7, 4′-trimethoxy-9′,10′-dihydro-(1,1′-biphenanthrene)-2,2′,7′-triol (54), phochinenin B (55), 2, 7, 2′-trihydroxy-4,4′,7′-trimethoxy-1,1′-biphenanthrene (56), 2,2′-dihydroxy-4,4′, 7, 7′-tetramethoxy-1,1′-biphenanthrene (57), and 1-(4′-hydroxybenzyl)-4-methoxyphenanthrene-2,7-diol (58). Among these compounds, 40–42 and 44–51 were reported from this genus for the first time.
The bioactivities of these known compounds were investigated against colon (HCT-116), cervix (Hela), liver (HepG2), and breast (MDA-MB-231) human cancer cell lines and against A549 and MCF-7. Compounds 25–27 showed potent cytotoxicity against HCT-116 and MDA-MB-231 cell lines. The IC50 values against HCT-116 and MDA-MB-231 were 37.44 μmol/L and 10.42 μmol/L (25), 33.18 μmol/L and 11.92 μmol/L (26), and 14.22 μmol/L and 52.84 μmol/L (27), respectively. Compounds 28–32, 35, and 52–57 showed moderate or weak cytotoxicity toward HCT-116, MCF-7, MDA-MB-231, and Hela cell lines., The new biphenanthrene atropisomers, cremaphenanthrene F (33) and G (34), showed butyrylcholinesterase inhibition with IC50 values of (14.62 ± 2.15) μ mol/L and (79.56 ± 0.78) μmol/L, respectively; however, they were inactive against acetylcholinesterase. These results suggest that compound 33 could act as a selective butyrylcholinesterase inhibitor for Alzheimer's disease prevention and treatment.
Between 2004 and 2016, numerous other groups also investigated the phytochemistry and biological activity of C. appendiculata tubers, including Liu et al.,, Zhang et al., Wang et al., Ikeda et al., and Shim et al.
Liu et al. isolated and identified two new phenanthrene glucosides named 2'-hydroxy-4,4',7'-trimethoxy-1, l'-biphenanthrene-2,7-di-O-β-D-glucoside (59) and 1-(4-hydroxybenzyl)-4-methoxy-2,7-dihydroxy-phenanthrene-8-O-β-D-glucoside (60). They have also identified the following 11 known compounds in ethyl acetate extracts of C. appendiculata tubers: cirrhopetalanthrin (15), 7-hydroxy-2,4-dimethoxy-phenanthrene (61), coelonin (62), shancigusin I (63), 4-O-β-D-glucopyranosyl cinnamate (64), bulbocodin D (65), blestriarene A (66), militarine (67), gastrodin (68), 3-hydroxyphenylpropionic acid (69), and cinnamic acid (70)., Among these compounds, 63–65, 69, and 70 were isolated from this plant for the first time.
Zhang et al. isolated the following seven known compounds from ethyl acetate extracts of C. appendiculata tubers for the first time: fumaric acid (71), dimethylhexyl phthalate (72), l-pyroglutamic acid (73), 2-furoic acid (74), vanillic acid (75), p-coumaric acid (76), and protocatechuic acid (77).
Wang et al. obtained thirty four compounds, including eleven novel phenanthrenes, from high-polarity fractions (ethyl acetate and/or water) of C. appendiculata. The chemical structures of the novel phenanthrenes were identified as 1-(4-β-D-glucopyranosyloxybenzyl) 4-methyl (2R)-2-isobutylmalate (78), 1-(4-β-D-glucopyranosyloxybenzyl) 4-ethyl (2R)-2-isobutylmalate (79), 1-(4-β-D-glucopyranosyloxybenzyl) 4-methyl (2R)-2-benzylmalate (80), 1,4-bis (4-β-D-glucopyranosyloxybenzyl)(2R)-2-benzylmalate (81), 7-hydroxy-4-methoxy-9,10-dihydrophenanthrene-2-O-β-D-glucopyranoside (82), 7-hydroxy-5-methoxy-9,10-dihydrophenanthrene-2-O-β-D-glucopyranoside (83), 4-methoxy-9,10-dihydrophenanthrene-2,7-di-O-β-D-glucopyranoside (84), 4,4'-dimethoxy-9,10-dyhydro- [6,1'-biphenanthrene]-2,2', 7, 7'-tetraol (85), (2,3-trans)-2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-10-methoxy-2, 3, 4, 5-tetrahydro-phenanthro [2,1-b] furan-7-ol (86), (2,3-trans)-3-[(2,7-dihydroxy-4-methoxy-phenanthren-1-yl) methyl]-2-(4-hydroxy-3-methoxyphenyl)-10-methoxy-2, 3, 4, 5-tetrahydro-phenanthro [2,1-b] furan-7-ol (87), and (2,3-trans)-3-[2-hydroxy-6-(3-hydroxyphenethyl)-4-methoxybenzyl]-2-(4-hydroxy-3-methoxyphenyl)-10-methoxy-2, 3, 4, 5-tetrahydro-phenanthro [2,1-b] furan-7-ol (88). Among these compounds, the structures of 87 and 88 were unusual as dimers because they possessed a phenanthrene or bibenzyl unit connected to C-3 of the 2, 3, 4, 5-tetrahydro-phenanthrol [2,1-b] furan moiety. This was a novel discovery among the natural products isolated from plants in the Orchidaceae family. The 23 known compounds were identified as flavanthrinin (10), adenosine (22), coelonin (62), blestriarene A (66), militarine (67), gastrodin (68), (−)-(2R,3S)-1-(4-β-D-glucopyranosyloxybenzyl)-4-methyl-2-isobutyltartrate (89), loroglossin (90), 7-hydroxy-2,4-dimethoxy-9,10-dihydrophenanthrene (91), 4,7-dihydroxy-1-p-hydroxybenzyl-2-methoxy-9,10-dihydrophenanthrene (92), 2-hydroxy-5,7-dimethoxyphenanthrene (93), 1-p-hydroxybenzyl-4-methoxyphenanthrene-2,7-diol (94), batatasin III (95), 3,3',5-trihydroxybibenzyl (96), 3,3'-dihydroxy-4-(p-hydroxybenzyl)-5-methoxybibenzyl (97), 3, 3'-dihydroxy-2-(p-hydroxybenzyl)-5-methoxybibenzyl (98), 3',5-dihydroxy-2-(p-hydroxybenzyl)-3-methoxybibenzyl (99), blestriarene B (100), blestriarene C (101), gymconopin C (102), blestrianol A (103), pleionesin C (104), and shanciol H (105). Among these compounds, 66, 89, 91, 92, 97, 100, and 102–105 were isolated from C. appendiculata tubers for the first time. The cytotoxicity of all compounds was evaluated against A549 and Bel7402 cell lines. Compound 88 showed moderate cytotoxic activity (IC50 of 16.0 μM) against the A549 cell line, and all compounds were inactive towards Bel7402 cells (IC50 >50 μM).
A new pyrrolizidine alkaloid called cremastrine (106) was isolated by Ikeda et al. and a homoisoflavanone called5, 7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-6-methoxychroman-4-one (107) was isolated by Shim et al. from C. appendiculata bulbs. Total synthesis of compound 106 was achieved in seven steps through construction of enantiopure idolizidines, pyrrolo [1,2-a] azepines, and pyrrolo [1,2-a] azocines for the synthesis of pyrrolizidine alkaloids from commercial materials with 25.2% overall yield. Biological evaluation of compound 106 and the unnatural analog indicated that both were pan- muscarinic receptors (mAChRs) functional antagonists. Compound 107 had inhibitory activities against angiogenesis, retinal neovascularization, UVB-induced skin inflammation, mast cell activation and allergic responses. To further explore the potential of homoisoflavanones as a treatment for neovascular eye disease, a novel isomer of compound 107 was synthesized (5,6-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-7-methoxychroman-4-one, code: SH-11052). This compound had antiproliferative activity against human umbilical vein endothelial cells and ocular disease-relevant human retinal microvascular endothelial cells.
| Pleione bulbocodioides (Franch.) Rolfe|| |
Pleione D. Don is a genus of mostly terrestrial Asian orchids that contains approximately 22 species, and is closely related to the Coelogyne and Bletilla genera., This genus is named after Pleione who was the mother of the Pleiades (the seven daughters of Atlas) in Greek mythology. Species of this genus are mainly found in China, Vietnam, Myanmar, Bangladesh, and Northeast India at an elevation of 600–4200 m. Most Pleione species are flowering in springat the beginning of their growth cycle. Because of their high ornamental and medicinal value, Pleione species have attracted much attention commercially. In China, the dry pseudobulbs from P. bulbocodioides P. yunnanensis and C. appendiculata are used as sources of the TCM Pseudobulbus Cremastrae seu Pleiones.
Plant description and distribution
Pleione bulbocodioides is found in Yunnan, China, where it grows near shaded rocks or in raised beds. This species flowers during late spring (April–June), and fruits in July. The flower up to approximately 8cm high and 10cm wide, is bright pink with red spots, lamellae in the callus, and splashes within the lip.
Phytochemistry and biological activity
Early phytochemical research on P. bulbocodioides was conducted in the 1990s by Tagaki's group.,,,,,, Twenty novel compounds were isolated from P. bulbocodioides tubers and their chemical structures were elucidated as follows: one dihydrophenanthropyran, namely shanciol (108); one polyphenol, namely pleionol (109); one bichroman, namely 6,6′-dihydroxy-4,4′-dimethoxy-3,3′-bichroman (110, pleionin A); two flavan-3-ols, namely 4′-hydroxy-3′,5′,7-trimethoxy-5-(3′′-hydroxyphenethyl) flavan-3-ol (111, shanciol A) and 4′-hydroxy-3′,7-dimethoxy-5-(3′′-hydroxyphenethyl) flavan-3-ol (112, shanciol B); four bibenzyls, namely bulbocodin (113), bulbocol (114), bulbocodins C (115) and D (65);, two bibenzyl glucosides, namely 3′-hydroxy-5-methoxybibenzyl-3-O-β-D-glucopyranoside (116) and 3′5-dimethoxybibenzyl-3-O-β-D-glucopyranoside (117); two dihydrophenanthropyrans, namely shanciol E (118) and F (119); five stilbenoids, namely shancilin (120), shancidin (121), shanciguol (122), shanciols C (123) and D (124); and two lignans, namely sanjidins A (125) and B (126). Ten known compounds were identified as coelonin (62), batatasin III (95), 3′-O-methylbatatasin III (127), 3,3′-dihydroxy-4-(p-hydroxybenzyl)-5-methoxybibenzyl (128), 3,3′-dihydroxy-2-(p-hydroxybenzyl)-5-methoxybibenzyl (129), 3′,5-dihydroxy-2-(p-hydroxybenzyl)-3-methoxybibenzyl (130), lusianthridin (131), bletilol A (132), bletilol B (133), and bletilol C (134). The absolute configurations of bletilol B (133) were determined to be 11S and 12S using Horeau's partial resolution method and chemical correlations.
From 2007 to 2012, several research groups worked on phytochemical studies of P. bulbocodioides tubers. Liu et al.,,,,,,, reported the isolation and identification of the following eight novel α, β-unsaturated butyrolactone derivatives: 4-(4′′-hydroxybenzyl)-3-(3′-hydroxy-phenethyl) furan-2 (5H)-one (135), 3-(3′-hydroxyphenethyl) furan-2 (5H)-one (136), (3-hydroxy-9-(4′-hydroxy-3′-methoxyphenyl)-11-methoxy-5, 6, 9, 10-tetrahydrophenanthro [2,3-b] furan-10-yl) (137), shanciol G (138), shanciol H (105), 2-(4′′-hydroxybenzyl)-3-(3′-hydroxyphenethyl)-5-methoxy-cyclohexa-2,5-diene-1,4-dione (139), 9-(4′-hydroxy-3′-methoxyphenyl)-10-(hydroxymethyl)-11-methoxy-5, 6, 9, 10-tetrahydrophenanthro [2,3-b] furan-3-ol (140), and 2-(4′′-hydroxybenzyl)-3-(3′-hydroxyphenethyl)-5-methoxy-cyclohexa-2,5-diene-1,4-dione (141). Twelve known compounds were also obtained and identified as gastrodin (68), 3-hydroxybenzic acid (142), p-dihydroxy benzene (143), gymconopin D (144), methyl-(4-OH)-phenylacetate (145), shanciol F (146), batatansin III (147), amentoflavone (148), kayaflavone (149), p-hydroxybenzaldehyde (20), p-hydroxybenzoic acid (150), and 4-oxopentanoic acid (151).,
From 2013 to 2020, elution–extrusion countercurrent chromatography was tested as a rapid and efficient method for preparative separation of the high-polarity compounds gastrodin (68) and benzyl ester glucosides from P. bulbocodioides tubers. Two new compounds, (E)-4-β-D-glucopyranosyloxycinnamic acid 9-(4-β-D-glucopyranosyloxybenzyl) ester (152) and (Z)-2-(2-methylpropyl) butenedioic acid bis (4-β-D-glucopyranosyloxybenzyl) ester (153), were isolated together with three known major components, militarine (67), gastrodin (68), and dactylorhin A (154). Cui et al. also established a simple and quick high-performance liquid chromatography method to accurately determine militarine (67) and dactylorhin A (154) in P. bulbocodioides. Due to its good reproducibility, this method is used for quality control.
Li et al., isolated five novel compounds, including four pyrrolidone-substituted bibenzyls and a prenylated flavone, along with 29 known compounds from the pseudobulbs of P. bulbocodioides. The novel compounds were elucidated as dusuanlansins A–D (155–158) and 3, 5, 7, 3'-tetrahydroxy-8,4'-dimethoxy-6-(3-methylbut-2-enyl) flavone (159). The former group of compounds are two pairs of epimers of pyrrolidone-substituted bibenzyls, and they were separated successfully using an LOD-RH C18 column. Their absolute configurations were elucidated by electronic circular dichroism. The known compounds were identified as 2, 5, 2′,5′-tetrahydroxy-3-methoxybibenzyl (160), batatasin III (95), 2, 5, 2′,3′-tetrahydroxy-3-methoxybibenzyl (161), bauhinol C (162), batatasin III-3-O-glucoside (163), arundinin (164), isoarundinin I (165), isoarundinin II (166), blestritin B (167), bulbocodin D (65), 5-O-methylshanciguol (168), blestriarene B (100), 4,4′, 7, 7′-tetrahydroxy-2,2′-dimethoxy-9,9′, 10, 10′-tetrahydro-1,1′-biphenanthrene(169), phoyunnanin A (170), 1-(4-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol (171), 1-(4-hydroxybenzyl) 4,7-dimethoxy-9,10-dihydrophenanthrene-2-ol (172), 2,2′-dihydroxy-4, 7, 4′,7′-tetramethoxy-1,1′-biphenanthrene (173), militarine (67), bletillin A (174), 3, 5, 3′-trihydroxy-8,4′-dimethoxy-7-(3-methylbut-2-enyloxy) flavone (175), isorhamnetin-3,7-di-O-β-D-glucopyranoside (176), 3′-O-methylquercetin-3-O-β-D-glucopyranoside (177), 4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (178), 2,7-dihydroxy-4-methoxy-9,10-dihydrophenanthrene (179), lirioresinol B (180), sanjidin A (125), dactylorhin A (154), gastrodioside (181), and phenyl-β-D-glucopyranoside (182).,
Li's research group further isolated twenty eight novel compounds and thirty six known compounds from high polarity fractions of P. bulbocodioides.,,, The novel compounds and their absolute configurations were identified by NMR analysis and/or MS combined with experimental and theoretical electronic circular dichroism analyses. They were shown as follows: eight phenanthrenequinones (four pairs of enantiomers), namely bulbocodioidins A (9R, 9S) (183 and 184), B (9R, 9S) (185 and 186), C (9R, 9S) (187 and 188), and D (10R, 10S) (189 and 190); four pairs of racemic bi (9,10-dihydro) phenanthrene and phenanthrene/bibenzyl atropisomers, namely M-bulbocodioidin E (191) and P-bulbocodioidin E (192), M-bulbocodioidin F (193) and P-bulbocodioidin F (194), M-bulbocodioidin G (195) and P-bulbocodioidin G (196), and M-bulbocodioidin H (197) and P-bulbocodioidin H (198); ten glucosyloxybenzyl succinate derivatives, namely pleionosides A–J; (199–208); and two phenylpropanoid glycosidic compounds (a pair of epimers), namely pleionosides K (209) and L (210). Compounds 183–190 possessed a 9 (10) H-phenanthren-10 (9)-one structure, which is rare in natural products. The thirty six known compounds identified were monbarbatain A (211), 2, 7, 2′-trihydroxy-4,4′,7′-trimethoxy-1,1′- biphenanthrene (212), blestriarene A (66), pleionesin B (213), shanciol H (105), 17-hydroxy-7′-(4′-hydroxy-3′-methoxyphenyl)-4-methoxy-9, 10, 7′,8′-tetrahydrophenanthro [2,3-b] furan-8'-yl methyl acetate (214), 1-p-hydroxybenzyl-4-methoxy phenanthrene-2, 7-diol (94), 1-p-hydroxybenzyl-4-methoxy-9,10-dihydrophenanthrene-2,7-diol (215), hircinol (216), coelonin (62), gigantol (217), batatasin II (218), syringaresinol (219), ergosta-4, 6, 8, 22-tetraen-3-one (220), asloroglossin (221), grammatophylloside A (222), cronupapine (223), (−)-(2R,3S)-1-(4-β-D-glucopyranosyloxybenzyl)-4-methyl-2-isobutyltartrate (224),vandateroside II (225), grammatophylloside B (226), bis[4-(β-D-glucopyranosyloxy)-benzyl] (S)-2-isopropylmalate (227), gymnoside I (228), militarine (67), dactylorhin A (154), gastrodin (68), (−)-(2R,3S)-1-[(4-O-β-D-glucopyranosyloxy) benzyl]-4-methyl-2-isobutyltartrate (229), loroglossin (90), (−)-(2S)-1-[(4-O-β-D-glucopyranosyloxy) benzyl]-2-isopropyl-4-[(4-O-β-D-glucopyranosyloxy) benzyl] malate (230), syringaresinolmono-O-β-D-glucoside (231), (7S,8R)-dehydrodiconiferyl alcohol-9′-O-β-D-glucopyranoside (232), 5-methoxyl bibenzyl-3,3′-di-O-β-D-glucopyranoside (233), 3′-hydroxyl-5-methoxyl bibenzyl-3-O-β-D-glucopyranoside (234), blestrianol A (103), pleionesin E (235), pleionesin D (236), and 3,3′-dihydroxy-2,6-bis (p-hydroxybenzyl)-5-methoxybibenzyl (237). Among these compounds, 66, 211, 212, 216, 219, 220, and 221–227 were isolated from this genus for the first time.,
Biological investigations showed that compound 178 exhibited potent anti-inflammatory activity toward Lipopolysaccharide (LPS)-induced NO production in BV-2 microglial cells with an IC50 value of 5.44 μM. The cytotoxic effects of the isolated new phenanthrenequinones were evaluated in several human cancer cell lines, and compounds 183 and 189 exhibited marked cytotoxic activity.
Furthermore, three novel glucosyloxybenzyl succinate derivatives (201, 202, and 204) exhibited potent hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro, with cell survival rates of 31.89% (201), 31.52% (202), and 31.97% (204) at 10 μM (positive control: bicyclol, 31.90%). Compound 198, a phenanthrene/bibenzyl atropisomer, displayed cytotoxic activity against colon cancer (HCT-116), liver cancer (HepG2), and breast cancer (MCF-7) cell lines with IC50 values of 7.6, 3.8, and 3.4 μM, respectively. Compound 235 showed cytotoxic activity against the MCF-7 breast cancer cell line with an IC50 value of 5.4 μM.
The two phenylpropanoid glycosidic compounds 209 and 210 exhibited moderate hepatoprotective activity against APAP-induced HepG2 cell damage in vitro, with cell survival rates of 25.83% (209) and 28.82% (210) at 10 μM. They also displayed antioxidant activity against H2O2-induced toxicity in human SK-N-SH cells, with increases in viability at 10 μM of 24.9% (209) and 34.6% (210).
| Pleione yunnanensis Rolfe|| |
Pleione yunnanensis (also known as the Yunnan Pleione) can be easily distinguished from other Pleione because it has rounded petals, a lip with broad rounded side lobes, and pale-colored flowers with five white lamellae.
Plant description and distribution
Pleione yunnanensis is terrestrial or lithophytic and it grows in grassy meadows and open pine forests at elevations of 1100–3500 m in Tibet, Yunnan, Sichuan, and Guizhou province of China, as well as northern Myanmar., The flowering period is between April and May, and the fruiting period is between September and October.
Phytochemistry and biological activity
There are fewer phytochemical studies or biological investigations on P. yunnanensis before 2009 than on C. appendiculata and P. bulbocodioides. To date, two research groups have published several reports about P. yunnanensis.
Dong et al. and Cui et al. have isolated 29 novel compounds and 49 known compounds in 70%–95% ethanolic extracts of P. yunnanensis tubers.,,, The novel compounds have been identified are as follows: four new bibenzyl derivatives, i.e., shancigusins A–D (238–241); three new dihydrophenanthrofurans, i.e., pleionesins A–C (242–244); five new glucosides, i.e., shancigusins E–I (245–249); and nine new glucosyloxybenzyl-2-hydroxy-2-isobutylsuccinates, i.e., pleionosides M–U (250–258).
The known compounds are identified as 2,6-bis (4-hydroxybenzyl)-3,3′,5-trihydroxybibenzyl (259), 3,3′-dihydroxy-2,6-bis (4-hydroxybenzyl)-5-methoxybibenzyl (260), 3′,5-dihydroxy-2-(4-hydroxybenzyl)-3-methoxybibenzyl (261), 3,3′-dihydroxy-2-(4-hydroxybenzyl)-5-methoxybibenzyl (262), 3,3′-dihydroxy-4-(4-hydroxybenzyl)-5-methoxybibenzyl (263); shanciol H (105), shanciol F (146), 3′-hydroxy-5-methoxybibenzyl-3-O-β-D-glucopyranoside (264), 3′,5-dimethoxy-3-O-β-D-glucopyranoside (265), 3-hydroxy-3′,5-dimethoxybibenzyl (266), 3,3′-dihydroxy-5-methoxybibenzyl (267), 2,7-dihydroxy-1-(4-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene (268), 4,7-dihydroxy-1-(4-hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene (269), 2,7-dihydroxy-4-methoxy-9,10-dihydrophenanthrene (179), 4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (178), 2,7-dihydroxy-1-(4-hydroxybenzyl)-4-methoxyphenanthrene (270), 2,2′, 7, 7′-tetrahydroxy-4,4′-dimethoxy-1,1′-biphenanthrene (blestriarene C) (101), militarine (67), dactylorhin A (154), gymnoside I (228),β-sitosterol (14), daucosterol (13), (−)-syringaresinol (219), succinic acid (271), and adenosine (22), 4,7-dihydroxy-1-(p-hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene (272), (2,3-trans)-2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-10-methoxy-2, 3, 4, 5-tetrahydro-phenanthro [2,1-b] furan-7-ol (86), pleionesin B (213), blestriarene A (66), batatasin III (95), 3, 3'-dihydroxy-2-(p-hydroxybenzyl)-5-methoxybibenzyl (98), 3',5-dihydroxy-2-(p-hydroxybenzyl)-3-methoxybibenzyl (99), 3,3'-dihydroxy-2,6-bis (4-hydroxybenzyl)-5-methoxybibenzyl (273), triphyllol (274), pholidotin (275), (E)-p-hydroxycinnamic acid (276), (E)-ferulic acid (277), and (E)-ferulic acid hexacosyl ester (278), Shancigusin H (248), dactylorhin A (158), gymnoside III (279), dactylorhin E (280), 1-[4-(β-D-glucopyranosyloxy) benzyl]-4-methyl-(R)-2-hydroxy-2-isobutylsuccinate (281), gymnoside I (228), loroglossin (90), bis (4-hydroxybenzyl) ether (282), 4-hydroxybenzyl alcohol (283), 4-hydroxybenzoic acid (284), and 4-hydroxybenzyl methylether (285). Among these compounds, 66, 259–263, and 274–278 were isolated from this plant for the first time. Biological investigations showed that compounds 254, 255, 248, and 281 had significant in vitro hepatoprotective activity against d-galactosamine-induced toxicity in HL-7702 cells. The cell viability increased by 27%, 22%, 19%, and 31%, respectively, compared with the model group (bicyclol, 14%) at 10 μmol/L. Compounds 253, 258, and 158 exhibited moderate hepatoprotective activity against APAP-induced toxicity in HepG2 cells and increased cell viability by 9%, 16%, and 12%, respectively, compared with the model group (bicyclol, 9%) at 10 μmol/L.,
[TAG:2]Cultivation and Production of Pseudobulbus Cremastrae seu Pleiones [/TAG:2]
Increase in global consumer demand for natural medicines and the rapid industrial development of TCMs have endangered wild Chinese herbal resources. Data analysis has shown that 1800–2100 medicinal species are facing extinction in China. Currently, artificial cultivation of TCMs is used to ease pressure on natural reserves and increase wild medicinal resources. However, artificial cultivation requires a massive area of cultivable land and is not suitable for mountainous regions. Recently, another cultivation method, called natural fostering, has been suggested in China. This method involves planting herbs in forests to imitate their natural habitats. It resolves the land-area issue, decreases stress on the environment, and provides economic development in isolated mountainous areas. Natural fostering of C. appendiculata and P. yunnanensis has been investigated in Guizhou for many years and a successful method for mass propagation from their seeds and meristems has been developed [Figure 3]. Presently, seeding of TCMs such as C. appendiculata and P. yunnanensis is an area of rapid commercial growth in Guizhou.
|Figure 3: Plantations of Cremastra appendiculata (D. Don) Makino (a) and Pleione yunnanensis Rolfe (b) in greenhouse (seeds collected from wild) and their seeding from their meristems (c and d), and plantations under forests (e and f, planting with seeding from their meristems) (by Feng Zhao)|
Click here to view
| Conclusions|| |
Approximately 280 natural products, including 122 novel compounds, with potentially useful biological activity, have been isolated from the original source plants of Pseudobulbus Cremastrae seu Pleiones. Studies on the biological activities of these compounds conducted in recent years have improved understanding of the actions of Pseudobulbus Cremastrae seu Pleiones and its clinical application. Furthermore, these studies have identified various compounds that could be used as lead compounds or promising candidates for drug development. To date, most studies on the biological activities of these compounds have been conducted in vitro. Obviously, further research is required to systematically move these compounds to clinical trials. Planting of C. appendiculata and P. yunnanensis by mass propagation from their seeds and meristems could be an effective model to resolve supply issues, to meet market needs and to protect the environment.
The authors are deeply grateful to Miss Yin-Wong Charmaine Chan (PuraPharm International Limited) for assistance in the literature search and English translation.
This project was supported by the Special Fund of the Guangxi Zhuang Autonomous Region for Specially-invited Experts of China (No. 2019B24).
This article does not contain any studies with human or animal subjects performed by either of the authors.
All authors participated in manuscript review and writing. All authors have read and approved the final version of the manuscript, and agree with the order of presentation of the authors.
Conflict of interest
| References|| |
Wang WY, Zhou H, Wang YF, Sang BS, Liu L. Current policies and measures on the development of traditional Chinese medicine in China. Pharmacol Res 2021;163:105187.
Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China. Vol. 1. Beijing: China Medical Science Press; 2020. p. 32-3. Chinese.
Nishidono Y, Ishii T, Okada R, Norimoto H, Murayama C, He D, et al.
Effect of heat processing on the chemical constituents and NO-suppressing activity of Bletilla Tuber. J Nat Med 2020;74:219-28.
Lin CC, Namba T. Historical and herbological studies on the traditional Japanese and Chinese crude drugs. On the “Shān-cí-gū”. Yakushigaku Zasshi 1985;20:88-98.
Bing QZ, Znag BG. The botanical identification of Shan Ci Gu (Pseudobulbus Cremastrae seu Pleiones) in Chinese ancient literature. J Syst Evol 2008;46:785-92.
Li G, Song X, Han B, Fang S. Evolution of the origin of strain of Shancigu (Rhizoma Pleionis). Chinese Journal of Medical History 2015;45:137-40. Chinese.
Dalström S, Gyeltshen N, Höijer T. Cremastra: Little known and confusing, hence a botanist's delight. Orchids 2012:180-1.
Yukawa T. Cremastra aphylla
(Orchidaceae), a new mycoparasitic species from Japan. Ann Tsukuba Bot Garden 1999;18:59-60.
Teoh ES. Genus: Calanthe to Cyrtosia, Medicinal Orchids of Asia. Switzerland: Springer International Publishing; 2015. p. 171-250.
Yagame T, Funabiki E, Nagasawa E, Fukiharu T, Iwase K. Identification and symbiotic ability of Psathyrellaceae
fungi isolated from a photosynthetic orchid, Cremastra appendiculata
(Orchidaceae). Am J Bot 2013;100:1823-30.
Tóth B, Hohmann J, Vasas A. Phenanthrenes: A promising group of plant secondary metabolites. J Nat Prod 2018;81:661-78.
Kovács A, Vasas A, Hohmann J. Natural phenanthrenes and their biological activity. Phytochemistry 2008;69:1084-110.
Xue Z, Li S, Wang S, Wang Y, Yang Y, Shi J, et al.
Mono-, Bi-, and triphenanthrenes from the tubers of Cremastra appendiculata
. J Nat Prod 2006;69:907-13.
Li S, Xue Z, Wang SJ, Yang YC, Shi JG. Terpenoids from the tuber of Cremastra appendiculata
. J Asian Nat Prod Res 2008;10:685-91.
Xue Z, Li S, Wang SJ, Yang YC, He DX, Ran GL, et al.
Studies on chemical constituents from the corm of Cremastra appendiculata
. China Journal of Chinese Materia Medica 2005;30:511-3. Chinese.
Xia WB, Xue Z, Li S, Wang SJ, Yang YC, He DX, et al.
Chemical constituents from tuber of Cremastra appendiculata
. China Journal of Chinese Materia Medica 2005;30:1827-30. Chinese.
Liu L, Li J, Zeng KW, Li P, Tu PF. Three new phenanthrenes from Cremastra appendiculata
(D. Don) Makino. Chin Chem Lett 2013;24:737-9.
Liu L, Li J, Zeng KW, Jiang Y, Tu PF. Five new biphenanthrenes from Cremastra appendiculata
. Molecules 2016;21:1089.
Liu L, Yin QM, Gao Q, Li J, Jiang Y, Tu PF. New biphenanthrenes with butyrylcholinesterase inhibitory activitiy from Cremastra appendiculata
. Nat Prod Res 2021;35:750-6.
Liu L, Li J, Zeng KW, Jiang Y, Tu PF. Five new benzylphenanthrenes from Cremastra appendiculata
. Fitoterapia 2015;103:27-32.
Liu L, Ye J, Li P, Tu PF. Chemical constituents from tubers of Cremastra appendiculata
. China Journal of Chinese Materia Medica 2014;39:250-3. Chinese.
Liu XQ, Li XP, Yuan WK, Yuan QY, Qin BH. Two new phenanthrene glucosides from Cremastra appendiculata
and their cytotoxic activities. Nat Prod Commun 2016;11:477-9.
Yuan QY, Liu XQ. Chemical constituents from Cremastra appendiculata
. Journal of Chinese Medicinal Materials 2015;38:298-301. Chinese.
Zhang Y, Huang B, Zhao Z, Zhou Y. Study on the chemical constituents from the ethyl acetate extracts of Cremastra appendiculata
. Journal of Chinese Medicinal Materials 2011;34:1882-3. Chinese.
Wang Y, Guan SH, Meng YH, Zhang YB, Cheng CR, Shi YY, et al.
Phenanthrenes, 9,10-dihydrophenanthrenes, bibenzyls with their derivatives, and malate or tartrate benzyl ester glucosides from tubers of Cremastra appendiculata
. Phytochemistry 2013;94:268-76.
Ikeda Y, Nonaka H, Furumai T, Igarashi Y. Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata
. J Nat Prod 2005;68:572-3.
Shim JS, Kim JH, Lee J, Kim SN, Kwon HJ. Anti-angiogenic activity of a homoisoflavanone from Cremastra appendiculata
. Planta Med 2004;70:171-3.
Hahn KN, Fadeyi OO, Cho HP, Lindsley CW. Synthesis and biological evaluation of cremastrine and an unnatural analogue. Tetrahedron Lett 2012;53:3577-80.
Kim JH, Kim JH, Yu YS, Jun HO, Kwon HJ, Park KH, et al.
Inhibition of choroidal neovascularization by homoisoflavanone, a new angiogenesis inhibitor. Mol Vis 2008;14:556-61.
Kim JH, Kim KH, Kim JH, Yu YS, Kim YM, Kim KW, et al.
Homoisoflavanone inhibits retinal neovascularization through cell cycle arrest with decrease of cdc2 expression. Biochem Biophys Res Commun 2007;362:848-52.
Hur S, Lee YS, Yoo H, Yang JH, Kim TY. Homoisoflavanone inhibits UVB-induced skin inflammation through reduced cyclooxygenase-2 expression and NF-kappaB nuclear localization. J Dermatol Sci 2010;59:163-9.
Lee YS, Hur S, Kim TY. Homoisoflavanone prevents mast cell activation and allergic responses by inhibition of Syk signaling pathway. Allergy 2014;69:453-62.
Basavarajappa HD, Lee B, Fei X, Lim D, Callaghan B, Mund JA, et al.
Synthesis and mechanistic studies of a novel homoisoflavanone inhibitor of endothelial cell growth. PLoS One 2014;9:e95694.
Sympli HD, Choudhury MG, Borah VV. A review of the unexplored medicinal orchids of the genus Pleione. MIOS J 2018;19:3-12.
Li B, Masea Y, Yuriko Y, Shuzo T. Shanciol, a dihydrophenanthropyran from Pleione bulbocodioides
. Phytochemistry 1996;41:625-8.
Li B, Noriko M, Masea Y, Shuzo T. A polyphenol and two bibenzyls from Pleione bulbocodioides
. Cheminform 1998;47:1637-40.
Li B, Masea Y, Shuzo T. Lignans and a bichroman from Pleione bulbocodioides
. Phytochemistry 1997;44:341-3.
Li B, Noriko M, Masea Y, Shuzo T. Flavan-3-ols and dihydrophenanthropyrans from Pleione bulbocodioides
. Phytochemistry 1998;47:1125-9.
Li B, Noriko M, Masea Y, Shuzo T. Four stilbenoids from Pleione bulbocodioides
. Phytochemistry 1998;48:327-31.
Li B, Noriko M, Masea Y, Shuzo T. Two bibenzyl glucosides from Pleione bulbocodioides
. Phytochemistry 1997;44:1565-7.
Li B, Masea Y, Shuzo T. Stilbenoids from Pleione bulbocodioides
. Phytochemistry 1996;42:853-6.
Liu XQ, Gao WY, Guo YQ, Zhang TJ, Yan LL. Two new α, β-unsaturated butyrolactone derivatives from Pleione bulbocodioides
. Chin Chem Lett 2007;18:1075-7.
Liu XQ, Gao WY, Guo YQ, Zhang TJ, Yan LL. A new phenanthro [2, 3-b] furan from Pleione bulbocodioides
. Chin Chem Lett 2007;18:1089-91.
Liu XQ, Guo YQ, Gao WY, Zhang TJ, Yan LL. Two new phenanthrofurans from Pleione bulbocodioides
. J Asian Nat Prod Res 2008;10:453-7.
Liu XQ, Yuan QY, Guo YQ. A new bibenzyl derivative from Pleione bulbocodioides
. Chin Chem Lett 2008;19:559-61.
Liu XQ, Yuan QY, Guo YQ. Two new stilbenoids from Pleione bulbocodioides
. J Asian Nat Prod Res 2009;11:116-21.
Yuan QY, Liu XQ. Chemical constituents from Pleione bulbocodioides
. Journal of Chinese Medicinal Materials 2012;35:1602-4. Chinese.
Wang Y, Guan SH, Feng RH, Zhang JX, Li Q, Chen XH, et al.
Elution-extrusion counter-current chromatography separation of two new benzyl ester glucosides and three other high-polarity compounds from the tubers of Pleione bulbocodioides
. Phytochem Anal 2013;24:671-6.
Cui BS, Song J, Li S, Ma L, Shi JG. Determination of dactylorhin A and militarine in three varieties of Cremastrae
pseudobulbus by HPLC. China Journal of Chinese Materia Medica 2013;38:4347-50. Chinese.
Li Y, Zhang F, Wu ZH, Zeng KW, Zhang C, Jin HW, et al.
Nitrogen-containing bibenzyls from Pleione bulbocodioides
: Absolute configurations and biological activities. Fitoterapia 2015;102:120-6.
Li Y, Wu ZH, Zeng KW, Zhao MB, Jiang Y, Li J, et al.
A new prenylated flavone from Pleione bulbocodioides
. J Asian Nat Prod Res 2017;19:738-43.
Shao SY, Wang C, Han SW, Sun MH, Li S. Phenanthrenequinone enantiomers with cytotoxic activities from the tubers of Pleione bulbocodioides
. Org Biomol Chem 2019;17:567-72.
Wang C, Shao SY, Han SW, Li S. Atropisomeric bi(9,10-dihydro) phenanthrene and phenanthrene/bibenzyl dimers with cytotoxic activity from the pseudobulbs of Pleione bulbocodioides
. Fitoterapia 2019;138:104313.
Han S, Wang C, Cui B, Sun H, Zhang J, Li S. Hepatoprotective activity of glucosyloxybenzyl succinate derivatives from the pseudobulbs of Pleione bulbocodioides
. Phytochemistry 2019;157:71-81.
Han SW, Shao SY, Sun H, Li S. Two new phenylpropanoid glycosidic compounds from the pseudobulbs of Pleione bulbocodioides
and their hepatoprotective activity. Nat Prod Res 2020;30:1-8.
Wang C, Han SW, Cui BS, Wang XJ, Li S. Chemical constituents from Pleione bulbocodioides
. China Journal of Chinese Materia Medica 2014;39:442-7. Chinese.
Han SW, Wang C, Cui BS, Li S. Studies on glucosyloxybenzyl 2-isobutylmalates of Pleione bulbocodioides
. China Journal of Chinese Materia Medica 2015;40:908-14. Chinese.
Dong HL, Wang CL, Guo SX, Yang JS. New bibenzyl derivatives from the tubers of Pleione yunnanensis
. Chem Pharm Bull (Tokyo) 2009;57:513-5.
Dong H, Wang C, Li Y, Guo S, Yang J. Complete assignments of (1) H and(13) C NMR data of three new dihydrophenanthrofurans from Pleione yunnanensis
. Magn Reson Chem 2010;48:256-60.
Dong HL, Liang HQ, Wang CL, Guo SX, Yang JS. Shancigusins E-I, five new glucosides from the tubers of Pleione yunnanensis
. Magn Reson Chem 2013;51:371-7.
Wang XJ, Cui BS, Wang C, Li S. Chemical constituents from Pleione yunnanensis
. China Journal of Chinese Materia Medica 2014;39:851-6. Chinese.
Han SW, Wang XJ, Cui BS, Sun H, Chen H, Ferreira D, et al.
Hepatoprotective Glucosyloxybenzyl 2-Hydroxy-2-isobutylsuccinates from Pleione yunnanensis
. J Nat Prod 2021;84:738-49.
Huang L, Guo L, Cui G. Basic theory research of traditional Chinese medicine resources. Res Inform Tradit Chin Med 2005;7:29.
[Figure 1], [Figure 2], [Figure 3]