Botanical, Traditional Use, Phytochemical, and Toxicological of Arisaematis rhizoma

1. Introduction

Arisaematis rhizoma (hereafter referred to as AR) is a tuber of the Arisaema plant of the Araceae family [1]. There are about 115 genera and more than 2,000 species in the Araceae family that are widely distributed all over the world, with more than 92% of them produced in the tropics. Among them, there are more than 90 species in the provinces of North and South China, 59 of which are endemic to China [2]. AR was first recorded as a herbal medicine in Shennong materia classic [3]. The tuber of Pinellia pedatisecta Schott was used as AR until the Song Dynasty (Kaibao Materia Medica) [4]. In the current market circulation, Pinellia palmata was widely used as a substitute for AR. The rhizomes of Arisaema erubescens (Wall.) Schott, Arisaema amurense Maxim, and Arisaema heterophyllum Blume are all used as AR [5]. Because of its toxicity, AR was listed as one of the 28 toxic traditional Chinese medicine in clinical. If it is intended for oral administration, the processed AR (Arisaematis rhizome preparatum and Arisaema cum Bile) were preparation must be performed by an experienced individual. Previous works showed that AR contains lectins, alkaloids, flavonoids, steroids, terpenes, glycosides, amino acids, lignin, phenylpropanoids, and polysaccharides. In addition, many studies have found that AR has a wide range of pharmacological activities, including anti-tumor, anti-convulsant, anti-inflammatory, anti-bacterial, anti-arrhythmic, sedative and analgesic, anti-coagulant, and killing properties against the Oncomelania snail. Besides, AR is commonly recognized as a poisonous plant, and previous investigations have reported that the needle-like calcium oxalate crystals and lectins are the major toxic components of this plant [6].

This review is a collection of all possible studies on Arisaema, published in scientific journals, papers, and books. Using the papers related to Arisaematis, such as ScienceDirect, Wiley Online Library, Springer Link, Web of Science, CNKI, and WanFang Database. In this paper, the traditional uses, botany, phytochemistry, pharmacology, and toxicology of Arisaema were reviewed. Finally, the existing problems and research directions of the research on Arisaematis are discussed.

2. Traditional Usages and Modern Indications

AR has more than 2,000 years of history in China as a traditional medicinal plant [7]. It was found that AR had the functions of drying dampness and resolving phlegm, dispelling wind and calming nerves, and eliminating swelling and resolving knots. It can be used to treat apoplectic phlegm, mouth and eyes askew, hemiplegia, wind phlegm vertigo, epilepsy, convulsion, tetanus, scrofula, carbuncle, fall, and fold injury. Its external use can be used to treat carbuncle, snakebite, and other diseases. “The classic of Materia Medica” [8] record: “AR is mainly used for wind phlegm.” According to the compendium of “Materia Medica in the Ming Dynasty” [9], AR in the sky are spicy and numb, so they can cure wind and disperse blood; the temperature is dry, so they can overcome dampness and remove saliva; the nature is tight and poisonous, so they can attack accumulation and remove swelling, so they can cure tongue erosion.” At the same time, the toxicity of AR was indicated as “the AR is poisonous” in “the classic of Materia Medica” and “the Chongyuan of Materia Medica” [10]. Therefore, in clinical use, a unique Chinese processing method was created processing AR with alum and ginger in which the toxicity of AR decreases, while the effect of drying dampness and resolving phlegm increases.

At present, AR has become an important traditional Chinese medicine, which is commonly used in the treatment of tumors, rheumatoid arthritis, coronary heart disease, epilepsy, and other diseases [11]. At the same time, in order to better meet the clinical needs, the formulation of powder, pill, tablet, and other forms has been formed (Table 1).

3. Botanical Aspects

Three plants of AR consist of A. erubescens (Wall.) Schott., Arisaema amurense Maxim., and A. heterophyllum Blume; all of them are perennial herbs of about 40–90 cm high. Its petiole is vertical and cylindrical and is about 40–55 cm long with a sheathed lower part. The base is covered with a transparent long membrane sheath and white green or purple spots on the long membrane sheath are present. The tuber is oblate with a straight diameter of about 2.5 to 5.5 cm. The outer skin of the tuber is yellow brown. The leaves are all split into leaflets, which are similar to palmate compound leaves, with 7–23 lobes that are lanceolate or long lanceolate in shape. This is about 13 to 19 cm in length and 1.5 to 2.5 cm in width. From the apex to the end, they are awn-shaped, whole, narrow, and wedge-shaped at the base, and the veins are feathery. Both sides of the leaves are smooth and glabrous, green above, and light green below (Figure 1) [12]. The flowers are dioecious, with a thick inflorescence axis, fleshy spikes, and club-like appendages at the apex. The peduncle is about 30 to 70 cm long, and the spathes are mostly green with a few purple ones. The male flowers have many stamens, with 2–4 clustered into a cluster; the anthers are black purple; and the female flowers are dense. Each flower is composed of one pistil; the ovary is oval; and the style is short. The berries of the plant are red. The flowering period of AR is from May to June, and the fruit period is August.

The height of A. amurense Maxim. (东北天南星) is about 35–60 cm (see Figure 1(c)), and the fibrous roots above it are distributed radially. The leaves are totally divided in the shape of bird toes, with five lobes (but only three lobes in the annual Arisaema amurensis), and they are obovate or broadly obovate, with a length of 11–15 cm and a width of 6–8 cm, all of which have irregular teeth. The inflorescence is 20–40 cm long, and the spathes are green or purple, with a total length of 11–14 cm. The inflorescence has rod-shaped appendages at the top. It is in berry red, flowers from July to August, and grows in a shady and humid forest on a shady slope.

A. Heterophyllum Blume (异叶天南星) is a perennial herb (see Figure 1(e)), with a height of 15–30 cm. There is a leaf 2–4 cm in diameter, with 13–19 lobes in bird’s toe shape, a narrow tip and tapered base over the whole, lateral lobes 7–24 cm long and 2–6 cm wide, and the smallest central lobe. The flower stalk is extracted from the leaf sheath and is 30–55 cm long. The spathes is green; its lower part is tubular; and its upper part is bent downward like a helmet. With the inflorescence shape like a meat spike, the unisexual inflorescence is in the lower part of the male flower. The lower part of the bisexual inflorescence is a female flower, the upper part is a sparsely male flower, and the appendage at the top of inflorescence axis is mouse-tail-shaped, protruding. Berries are red when ripe. The flowering period is from April to May, and the fruit period is from July to September.

The dried tubers of AR are oblate and massive. The diameter is about 2 to 7 cm, and the thickness is about 1 to 2 cm. The surface is wrinkled or smooth, milky white or brown, with pitted fibrous root marks around (Figure 1(b)). A hard texture that is not easy to break, uneven section, white color, and powdered are among its characteristics. It has also pungent and spicy characteristics [1]. It is not suitable to take it as a medicine without skin removal.

The dried tubers of A. amurense Maxim. (东北天南星) are oblate (see Figure 1(d)), with a diameter of 1.5–4 cm. The tubers are marked with large and flat marks and prominent lateral buds.

The dried tubers of A. heterophyllum Blume (异叶天南星) are oblate and spherical (see Figure 1(f)), with a diameter of 1.5–4 cm, with concave marks on the tubers and a circle of obvious root marks around the tubers.

These plants grow in the wet forest on the shady slope. It is distributed in Hebei Province, Henan Province, Guangxi Province, Shaanxi Province, Hubei Province, Sichuan Province, Guizhou Province, Yunnan Province, Shaanxi Province, and other places in China.

4. Chemical Composition

The chemical composition of AR is complex, with more than 200 chemical compounds, including alkaloids, polysaccharides, lectins, amino acids, fatty acids, sterols, and lectins. In this paper, the chemical composition and the corresponding structure of AR are described in detail to provide some references for the in-depth study of the plant and provide ideas for its future research direction. It was reported that total alkaloids from AR could inhibit the proliferation and induce apoptosis of SF21 cells in a dose- and time-dependent manner, suggesting that total alkaloids from AR could induce programmed death of SF21 cells [13]. The pharmacodynamics study of total flavonoids and their main component, liphotropic side, showed that it had the effects of anti-ischemia, protecting nerve cells and analgesia [14]. Saponins are irritating to the gastric mucosa, which can reflexively increase the secretion of the trachea and bronchus and play the role of expectorant [15].

4.1. Glycosides

Glycosides, also known as gametophytes, are compounds formed by the linkage of a sugar or a derivative of a sugar with another nonsugar substance via an end group carbon atom. At present, the main glycosides isolated from Arisaematis are oxyglycosides. Nine diacylglyceryl galactosides [16] (Table 2 and Figure 2) and five cerebrosides [17] (Table 3 and Figure 3) were isolated from AR. In addition, cerebrosides have the activity of protecting the liver [18].

Table 2. Diacylglyceryl isolated from Arisaematis.

No.	Name	Ref.
1	(2S)-1-0-hexadecyl-2-O(9Z,12Z-octadecenyl)-3-O-β-d-galactopyranose glycerol	[17]
2	1-O-(9Z-octadecyl)-2-0-(9Z,12Z-octadecenyl)-3-0-d-galactopyranosylglycerol	[17]
3	1-0-hexadecyl-2-0-(9Z-octadecenyl)-3-O-β-d-galactopyranose glycerol	[17]
4	1-0-octadecyl-2-0-(9Z,12Z,5Z-octatrienyl)-3-O-β-d-galactopyranosylglycerol	[17]
5	(2S)1-0-octadecyl-2-0-(9Z,12Z-octadienyl)-3-O-[α-D-galactopyranosyl-(1″⟶6′)O-β-D-galactopyranosyl]glycerol	[17]
6	1-O-hexadecyl-2-0-(9Z,12Z-octadecadienyl)-3-0-[α-D-galactopyranosyl-(1″⟶6′)-O-β-D-galactopyranosyl]glycerol	[17]
7	1-O-hexadecyl-2-O-(9Z-octadecenyl)-3-O[α-D-galactopyranosyl-(1″⟶6′)-O-β -D-galactopyranosyl] glycerol	[17]
8	1-O-hexadecyl-2-O-(9Z,12Z,15Z-octatrienyl)-3-0-[α-D-galactopyranosyl-((1″⟶6′)-O-β-D-galactosyl]glycerol	[17]
9	1-O-(9Z,12Z-octadecadienyl)-2-O-(9Z,12Z-octadienyl)-3-0-d-galactopyranosylglycerol	[17]

Table 3. Cerebrosides isolated from Arisaematis.

No.	Name	Ref.
10	1-O-β-D-glucopyranosyl-(2S,3R,4e,8Z)-2-[(2(R)-hydroxy eicosyl)phthalamido]-4,8-octadecene-1,3-diol	[16]
11	1-O-β-D-glucopyranosyl-(2S,3R,4e,8Z)-2-[(2(R)-hydroxyoctadecyl)acylamino]-4,8-octadecadien-1,3-diol	[16]
12	1-O-β-D-glucopyranosyl-(2S,3R,4e,8Z)-2-[(2(R)-hydroxyhexadecyl)amido]4,8-octadecene-1,3-diol	[16]
13	1-O-β-D-glucopyranosyl(-2S,3R,4e,8e)-2-[(2 (R)- hydroxy eicosyl)acylamino]4,8-octadecene-1,3-diol	[16]
14	1-O-β-d-pyranoglucosyl-(2S,3R,4e,8e)-2-[(2(R)-hydroxyoctadecyl)amide]-4,8-octadecene-1,3-diol	[16]

4.2. Alkaloids

The alkaloids have many important biological functions and physiological activities, which are abundant in the tuber of Arisaematis. The main alkaloids isolated from Arisaematis are trigonelline [19, 20], colchicine [21], choline chloride [22], choline, and stachydrine [16, 17, 19, 20] (Table 4 and Figure 4).

Table 4. Alkaloids isolated from Arisaematis.

No.	Name	Ref.
15	Colchicine	[19]
16	Cholinechlorid	[20]
17	Choline	[23]
18	Stachydrine	[23]
19	Cucurbitacin	[19,20]

4.3. Fatty Acids and Sterols

Li Xuwen identified 16 fatty acids in the roots of AR by gas chromatography–mass spectrometry (GC-MS) [24] (Table 5 and Figure 5). Among them, the saturated fatty acid is the main component, while unsaturated fatty acid also has a certain proportion, accounting for 20% of the total fatty acid content. The main components include stearic acid, palmitic acid, and linoleic acid [25, 26]. Du Shushan obtained seven compounds from the petroleum ether fraction of the ethanol extract of AR [26]: triacontanoic aci, β-sitosterol [27], ethyl gallate, tetradecane, daucosterol [27–29], gallic acid, and hexadecanoic acid [30] (Table 6 and Figure 5).

Table 5. Fatty acid composition isolated from Arisaematis.

No.	Name	Ref.
20	Palmitic acid (25.21%)	[24]
21	Stearic acid (22.44%)	[24]
22	Linoleic acid (14.03%)	[24]
23	Linolenic acid (5.48%)	[24]
24	Hexadecyl heptadecanoic acid (5.11%)	[24]
25	Arachidic acid (4.49%)	[24]
26	Azelaic acid (3.05%)	[24]
27	Azelaic acid (2.51%)	[24]
28	Pentadecanoic acid (2.10%)	[24]
29	Heptadecanoic acid (1.97%)	[24]
30	Hexagoic acid- 2-isoproyl-2-methyl-5-oxo (1.72%)	[24]
31	Palmitic acid-3-hydroxy (1.20%)	[24]
32	Caprlylic acid (0.68%)	[24]
33	Tetralosanoic acid (0.63%)	[24]
34	Isooleic acid (0.49%)	[24]

Table 6. Sterols isolated from Arisaematis.

No.	Name	Ref.
35	Triacontanoic acid	[26]
36	β sitosterol	[27, 30]
37	Carotene	[28–30]
38	Stigmasterol	[30]
39	Sitosterol	[30]
40	Rapeseed sterol	[30]
41	Cholesterol	[30]

4.4. Flavonoid

Du Shushan isolated and identified six flavonoids from the tubers of AR, and all of them were flavonoid glycosides [27, 31]. Wang Guangshu also obtained six compounds from the ethanol extract of AR by macroporous resin, silica gel, and ODS column chromatography and were identified as flavonoids by physicochemical identification and spectral analysis [32] (Table 7 and Figure 6).

Table 7. Flavonoids isolated from Arisaematis.

No.	Name	Ref.
42	Schaftoside	[31, 32]
43	Isoschaftoside	[31, 32]
44	Apigenin-6-c-arabinogalactoside	[31, 32]
45	Apigenin-6,8-di-c-glucopyranoside	[31, 32]
46	Apigenin-6-c-galacto-8-c-arabinoside	[31, 32]
47	Apigenin-6,8-di-c-galactoside	[31, 32]

4.6. Amino Acids

It is rich in amino acids in AR. Wang Xing found 14 kinds of amino acids were obtained from the qualitative and quantitative analysis of AR [37] (Table 8 and Figure 7).

Table 8. Amino acids isolated from Arisaematis.

No.	Name	Ref.
48	Asparagine	[37]
49	Glutamate	[37]
50	Serine	[37]
51	Glycine	[37]
52	Histidine	[37]
53	Arginine	[37]
54	Threonine	[37]
55	Alanine	[37]
56	Proline	[37]
57	Tyrosine	[37]
58	Valine	[37]
59	Phenylalanine	[37]
60	Tryptophan	[37]
61	Lysine	[37]

4.7. Nucleosides

Yi Jinghai eight nucleoside compounds were found in AR [38] (Table 9 and Figure 8). Nucleoside components have a wide range of physiological activities, are the basic components of biological cells to maintain life activities, and participate in the DNA metabolism process, with anti-tumor, anti-viral, immune regulation, treatment of cardiovascular and cerebrovascular diseases, and other functions [39].

Table 9. Nucleosides isolated from Arisaematis.

No.	Name	Ref.
62	Uracil	[38]
63	Hypoxanthine	[38]
64	Xanthine	[38]
65	Uridine	[38]
66	Inosine	[38]
67	Guanosine	[38]
68	Thymidine	[38]
69	Adenosine	[38]

4.8. Other Chemical Components

In addition, Fu Ming obtained 8 compounds from 80% ethanol extract of rhizome of AR [40] (Table 10 and Figure 9). Zheng Xiumei obtained 10 compounds from 80% ethanol extract of AR [41] (Table 10 and Figure 9); Yang Jia identified 52 compounds from AR by GC-MS, of which 7 compounds were more than 2% [42]. Sucrose and pine disaccharide were also isolated from AR [36] (Table 10 and Figure 9). In addition, there is a water-soluble polysaccharide in AR [43]; the monosaccharide composition of AR polysaccharide is mannose, rhamnose, glucose, galactose, arabinose, and fucose [6, 43, 44].

Table 10. Other chemical compounds isolated from Arisaematis.

No.	Name	Ref.
70	Larch alcohol	[40]
71	Ferulic acid	[40]
72	P-hydroxycinnamic acid	[40]
73	P-hydroxybenzoic acid	[40]
74	Caffeic acid	[40]
75	Guaiacyl glycerol	[40]
76	Oleoresin	[40]
77	Larch resin	[41]
78	Pinoresinol	[41]
79	Isoamericanol A	[41]
80	Dehydrodiconiferyl alcohol	[41]
81	3,3′-bisdemethylpinoresinol	[41]
82	Americanol A	[41]
83	Larch resin	[41]
84	m-Cresol (5.31%)	[42]
85	Linalool L (3.69%)	[42]
86	Furan, 2, 2′ -Methylenebis (2.8%)	[42]
87	2-Furfuryl -5-Methylfuran (2.52%)	[42]
88	Styrene (2.48%)	[42]
89	Furan, 2 -(2-propenyl) (2.15%)	[42]
90	2-Furanmethanol, acetate (2.12%)	[42]
91	Sucrose	[42]
92	Disaccharide	[42]
93	Decosanoic acid (4.51%)	[30]
94	Ethyl gallate	[26]
95	Forty alkanes	[26]
96	Gallic acid	[26]
97	Hexadecanoic acid	[26]
98	Mannitol	[30]

5. Pharmacological Action

AR has been reported to have a wide range of pharmacological activities, including the effects on the central nervous system and cardiovascular system; it is also used in the clinic for anti-tumor, sedation, analgesia, anti-convulsant, anti-inflammatory, expectorant, anti-arrhythmic, and anti-coagulant. In this section, we mainly introduce and analyze the pharmacological effects of AR (Table 10).

6. Toxicity

In China, AR is traditionally and commonly recognized as a toxic plant as other plants in Araceae. Thus, the toxicities of AR have been comprehensively recorded and investigated. The toxic or irritant components of Araceae plants may be produced by special biological metabolites contained in the plants. It may include calcium oxalate needle crystal and its surface glycoprotein, and some trace polysaccharides [6, 81]. The content of calcium oxalate in the poisonous needle crystal is 90.26% [82]. The calcium oxalate needle crystal acts through special mucous cells [83], resulting in strong irritation and corrosiveness to the skin, mucous membrane, muscle, and other local tissues [84]. The toxicity of AR was mainly manifested in strong irritation to the oral cavity, throat, skin, and mucous membrane [85, 86]. After oral administration, it can cause numbness; stimulate the mucous membrane of the throat and gastrointestinal tract; and cause vomiting, abdominal pain, diarrhea, and other gastrointestinal and urinary tract irritation symptoms; when used externally, it can stimulate mucous membrane and skin, cause redness, burning sensation, blister, and even ulceration, which can affect muscle tissue.

7. Pharmacokinetic Studies

So far, the pharmacokinetic studies on the extracts and compounds of this plant are very few. The pharmacokinetic studies of AR were mainly focused on flavonoid compounds, including schaftoside and isoschaftoside. Luo Fen studied the pharmacokinetic characteristics of schaftoside and isoschaftoside. In rats, the data are as follows: AUC (0⟶t) = 143.378 ± 26.249 h·μg^–1·mL^–1, AUC (0⟶∞) = 149.106 ± 26.249 h·μg^–1·mL^–1, t_1/2 = 2.300 ± 0.756 h, C_max = 33.259 ± 3.192 μg/L, AUC (0⟶t) = 167.122 ± 95.766 h·μg^–1·mL^–1, AUC (0⟶∞) = 181.974 ± 108.915 h·μg^–1·mL^–1, t_1/2 = 2.592 ± 1.175 h, and C_max = 36.635 ± 19.53 μg/L. It can be seen from the blood concentration-time curve of the two flavonoids that the blood concentration of the two flavonoids rises obviously at 3 h, which may be related to the enterohepatic circulation, absorption, and distribution in vivo [92]. Further research is needed to support it.

8. Future Perspectives and Conclusions

To sum up, AR is a traditional Chinese medicine with a long history. It has more than 2,000 years of application history and continuous research of modern science. At present, many chemical constituents have been isolated and identified from this plant. There is no doubt that AR is an important traditional Chinese medicine, although it has certain toxicity. For this reason, in the past many years, many experts are constantly studying the south star and have made great contributions in many aspects. At the same time, in the process of continuous research, there are still some new problems and challenges, which need further research and exploration to meet the clinical needs.

First of all, as a traditional Chinese medicine, AR contains glycosides, sugars, flavonoids, alkaloids, saponins, and other chemical components with expectorant, anti-inflammatory, anti-convulsant, anti-tumor, and other pharmacological effects. There are many studies on it, and the anti-tumor effect of AR has also been widely concerned by scholars at home and abroad and has become a research hotspot in recent years. However, the material basis of other pharmacological effects is not clear, and how and what kind of effects some chemical components play are not clear. It is necessary to further study its monomer compounds and clarify the material basis through certain methods and experiments; AR has certain toxicity. Toxicity studies showed that most of them were irritant, and the long-term toxicity was not obvious. There are some problems in toxicity evaluation methods; for example, oral generated AR can stimulate the throat and make the throat smooth and hoarseness, and it is difficult to enlarge the throat so it is necessary to find a toxicity evaluation model to better evaluate the toxicity of AR. There are too few studies on the pharmacokinetics of AR, which should be paid more attention to in vivo and in vitro verification to improve the safety of the clinical medication. So that AR can be better used better for the guidance of clinical medication to lay a certain foundation.

In general, as a commonly used traditional Chinese medicine, AR still needs further study. This paper systematically and comprehensively introduces the research status of AR at home and abroad in recent years, including traditional application, phytochemistry, pharmacology, and toxicology. Although great progress has been made in its research, there are still some problems in all aspects. Therefore, we still need to make continuous efforts to develop and utilize AR.[93]

Conflicts of Interest

The authors declare that they do not have any conflicts of interest.

Authors’ Contributions

Chun-yan Qi collated documents and wrote the manuscript; Su-rong He and Xu Wu helped perform the arrangement of tables and figures; Jing Wang assisted in the revision of the manuscript; Qiao Zhang and Jing Sun provided valuable ideas; and Chong-bo Zhao provided financial supports and valuable discussion. All the authors read and approved the final manuscript.