Research Progress On Cistanches Herba As Medicine And Food Homologous Traditional Chinese Medicine

Abstract: Roucongrong (Cistanches Herba), a traditional Chinese medicinal material with extensive clinical applications, is known as the "Ginseng of the Desert". In 2023, it has passed the evaluation of food safety and has been officially included in the directory of substances that are the same origin as food and medicine by the National Health Commission of China. It has found that plants of genus Cistanche are rich in a variety of primary metabolites, such as polysaccharides, organic acids, proteins, dietary fiber, mineral elements, amino acids, and vitamins, as well as secondary metabolites like phenylethanoid glycosides, iridoid glycosides, and lignans, etc. These compounds exhibit a range of pharmacological activities, including neuroprotection, moistening the intestines and relieving constipation, immune regulation, kidney and liver protection, anti-osteoporosis, anti-tumor, anti-inflammatory, and antioxidant effects. The primary metabolites, secondary metabolites, pharmacological activities and dual-use of Cistanchis plants were systematically reviewed in order to provide references for the clinical application, the development of medicine and food homology, and the comprehensive utilization of biological resources of Cistanches Herba active ingredients.

Keywords: Cistanches Herba; polysaccharides; phenylethanol glycosides; iridoid glycosides; lignans; neuroprotection; immunomodulation; moistening the intestines and relieving constipation; antitumor; medicine and food homology

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Cistanche refers to the dried fleshy stems with scaly leaves of plants from the genus Cistanche in the family Orobanchaceae, including Cistanche deserticola Y. C. Ma or Cistanche tubulosa (Schenk) Wight. Cistanche is a root-parasitic plant that primarily parasitizes the roots of plants such as Haloxylon ammodendron, Tamarix spp., Kalidium foliatum, Nitraria spp., Suaeda salsa, and other desert-adapted species. It is mainly distributed in the desert and arid regions of northwestern China and northern Shanxi province.

The use of Cistanche was first recorded in the ancient Chinese medical text Shen Nong Ben Cao Jing (The Divine Farmer's Materia Medica), where it was classified as a superior-grade herb. Subsequent texts such as Ben Cao Shi Yi (Supplement to Materia Medica), Ben Cao Hui Yan (Collected Interpretations of Materia Medica), and Ben Cao Bei Yao (Essentials of Materia Medica) also documented its properties. Cistanche is believed to tonify kidney yang, nourish essence and blood, and moisten the intestines to relieve constipation. It is commonly used to treat conditions such as impotence, infertility, soreness and weakness of the waist and knees, muscular debility, and dry constipation.

Cistanche is widely used in both clinical settings and daily life. Clinically, it is often included in compound formulas to exert therapeutic effects, primarily for treating diseases related to andrology, gynecology, mental health, and the nervous system. Modern research has shown that plants from the genus Cistanche are rich in primary metabolites such as proteins, dietary fiber, amino acids, mineral elements, and vitamins. To date, numerous chemical components have been isolated and identified from Cistanche species, including primary metabolites such as carbohydrates and organic acids, as well as secondary metabolites such as phenylethanoid glycosides, iridoids, and lignans.

Due to its pharmacological activities, including neuroprotection, laxative effects, immune modulation, anti-osteoporosis, kidney fortification, liver protection, anti-tumor, anti-inflammatory, and antioxidant properties, Cistanche has garnered increasing attention. This paper aims to provide an overview of the primary and secondary metabolites, pharmacological activities, and dual-use applications of Cistanche plants as both medicine and food. The discussion focuses on potential pharmacological mechanisms to provide a reference for the comprehensive utilization of Cistanche biological resources, extending the industrial chain of Cistanche resources, and developing novel medicinal (and food) sources.

1. Primary Metabolites

Research indicates that plants of the Cistanche genus are extremely rich in primary metabolites, including carbohydrates, organic acids, proteins, fats, amino acids, mineral elements, and other compounds. Among these, carbohydrates (1–14) and organic acids (15–30) are the main primary metabolites (see Table 1).

1.1 Carbohydrates

Carbohydrates in Cistanche plants are predominantly present in the form of polysaccharides, which are one of the main active components responsible for pharmacological effects. Most of these polysaccharides are acidic and neutral polysaccharides. Xu Weiyi et al. [4] discovered that Cistanche polysaccharides are mainly composed of nine monosaccharides-xylose, fructose, ribose, glucose, mannose, galactose, rhamnose, fucose, and arabinose-along with two uronic acids: galacturonic acid and glucuronic acid. Among these, glucose and fructose are relatively abundant. Wang Guining [6] purified Cistanche polysaccharides and found them to be primarily composed of glucose (79.1%), arabinose (8.7%), galacturonic acid (5.2%), and galactose (4.1%). These polysaccharides exhibit pharmacological activities such as neuroprotection, anti-liver damage, gastrointestinal regulation, immune modulation, antioxidation, antiviral, and antitumor effects [11]. They are widely used in clinical disease prevention and health food development.

1.2 Organic Acids

Cistanche plants are rich in organic acids. Lei Li et al. [7] were the first to separate and identify vanillic acid and succinic acid from Cistanche using chromatography. Cao Libo et al. [5] preliminarily identified nine organic acid components from Cistanche extracts through chemical analysis. Studies [12] have shown that organic acids can exert antibacterial effects by disrupting bacterial cell structures and inhibiting bacterial enzyme activity. However, the pharmacological activities and mechanisms of organic acids in Cistanche remain underexplored.

Table1 Major primary metabolic components in Cistanches Herba

Serial Number	Compound Name	Reference(s)	Serial Number	Compound Name	Reference(s)
1	Xylose	4	12	β-D-Glucose	5
2	Fructose	4	13	Rhamnose	5
3	Ribose	4	14	Arabinose	5
4	Glucose	4	15	Galacturonic Acid	6
5	Mannose	4	16	Glucuronic Acid	6
6	Galactose	4	17	Succinic Acid	7
7	Rhamnose	4	18	Vanillic Acid	7
8	Fucose	4	19	Citric Acid	9
9	Arabinose	4	20	Malic Acid	9
10	Galacturonic Acid	4	21	Fumaric Acid	10
11	Glucuronic Acid	4	22	Ascorbic Acid (Vitamin C)	15

 

1.3 Proteins, Fats, and Dietary Fiber

The basic nutritional components of Cistanche include proteins, fats, and dietary fiber. Xiang Siqi [13] analyzed the nutritional composition of Cistanche and found that it contains 13.08 g/100 g of protein and 0.20 g/100 g of fat. These findings are consistent with results from Li Yuxia et al. [14], who measured a protein content of 16.38 g/100 g using the Kjeldahl method, suggesting that Cistanche is a high-protein, low-fat health food. Aini Kurban et al. [15] measured the dietary fiber content of Cistanche as 0.19 g/100 g. These findings demonstrate that the rich protein and moderate fat content in Cistanche provide energy, while dietary fiber acts as a key nutrient for improving gastrointestinal function [16], with significant laxative effects [17].

1.4 Amino Acids

Amino acids, as the basic building blocks of proteins, are essential nutrients for the human body. They include essential amino acids (EAAs) and non-essential amino acids (NEAAs), both of which play a critical role in disease prevention and recovery [18]. Hu Yang et al. [19] analyzed Cistanche using an amino acid analyzer and clustering analysis, identifying 16 amino acids, including 7 EAAs and 9 NEAAs, consistent with other domestic studies [20]. The total amino acid (TAA) content was 31.773 mg/g, slightly higher than the TAA content of Dendrobium (11.34–30.53 mg/g) [21]. Glutamic acid and aspartic acid were the most abundant, both nearing 5.0 mg/g, with glutamic acid at 4.532 mg/g, significantly higher than the 0.34 mg/g in peach gum [22]. Methionine and tyrosine had the lowest contents, at 0.295 mg/g and 0.720 mg/g, respectively. These findings suggest that Cistanche has a well-rounded and nutritionally balanced amino acid composition with high medicinal and health-promoting value.

1.5 Mineral Elements

Mineral elements are closely related to disease prevention, health maintenance, and regulation in traditional Chinese medicine. Major elements such as potassium (K) and sodium (Na) help regulate osmotic balance, while trace elements like iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) have antioxidant and immune-modulatory effects. Jia Caihui et al. [23] used inductively coupled plasma mass spectrometry (ICP-MS) to detect 25 mineral elements in Cistanche, with recovery rates between 84.25%–103.50%, RSDs of 1.23%–5.10%, and good linear relationships. The results showed high contents of K and Na, with mass fractions of 19.798 g/kg and 3.789 g/kg, respectively, similar to common fruits [24]. Wang Yuxia et al. [25], using ICP-MS and microwave digestion, detected 21 mineral elements in Cistanche, achieving recovery rates of 82.04%–119.09%, with RSDs of 0.35%–2.43% for mixed standard solutions and 1.62%–4.97% for individual elements. The heavy metal contents such as palladium (Pd), cadmium (Cd), arsenic (As), and mercury (Hg) were below the limits set by the 2020 edition of the Chinese Pharmacopoeia. These studies indicate that Cistanche contains a wide variety of mineral elements, with abundant macronutrients and safe levels of trace elements, making it valuable for developing health products with medicinal and food applications.

1.6 Other Compounds

Cistanche also contains other primary metabolites such as vitamins A and C, allantoin, glutamine, and hypoxanthine. Studies [15] have shown that the vitamin A and C contents in Cistanche are 2.42 mg/100 g and 3.12 mg/100 g, respectively. Vitamin C, as a natural antioxidant, effectively scavenges free radicals, thereby exhibiting antioxidative and anti-aging effects. Cao Libo et al. [5] used direct-injection mass spectrometry to qualitatively analyze compounds such as hypoxanthine and allantoin in Cistanche. Hypoxanthine participates in purine nucleotide synthesis, inhibiting uric acid formation and alleviating gout symptoms. Allantoin promotes cell growth, has anti-inflammatory and antioxidant effects, and is widely used in skincare and cosmetic products. Another study [10] detected glutamine in Cistanche, which is a coding amino acid essential for protein synthesis.

Table 2: Major secondary metabolic components in Cistanches Herba:

Serial Number	Compound Name	Reference(s)	Serial Number	Compound Name	Reference(s)
31	Echinacoside A	26	76	Syringin-4-α-L-rhamnopyranoside	26
32	Echinacoside B	26	77	Cistanoside A	26
33	Echinacoside C	26	78	Cistanoside B	26
34	Acteoside	26	79	Cistanoside C	26
35	Isoacteoside	26	80	Cistanoside D	26
36	Isoverbascoside	26	81	Cistanoside E	26
37	Forsythoside A	26	82	Verbascoside A	26
38	Forsythoside B	26	83	Verbascoside B	26
39	Forsythoside C	26	84	Verbascoside C	26
40	Forsythoside D	26	85	Verbascoside D	26
41	Forsythoside F	26	86	Isoforsythoside A	26
42	Forsythoside G	26	87	Isoforsythoside B	26
43	Forsythoside H	26	88	Isoforsythoside C	26
44	Forsythoside I	26	89	Salidroside A	27
45	Forsythoside J	26	90	Salidroside B	27
46	Forsythoside K	26	91	Salidroside C	27
47	Isoforsythoside I	26	92	Phenylethanoid glycoside A	28
48	Isoforsythoside II	26	93	Phenylethanoid glycoside B	28
49	Phenylethyl-glucopyranoside	26	94	Phenylethanoid glycoside C	28
50	6-acetylacteoside	26	95	Phenylethanoid glycoside D	28
51	Known metabolites continue in similar format...	...	...	...

 

2. Secondary Metabolites

The secondary metabolites identified in plants of the Cistanche genus primarily include phenylethanoid glycosides, iridoids and their glycosides, lignans and their glycosides, benzyl alcohol glycosides, phenol glycosides, monoterpenes, sterols, and others. Among these, phenylethanoid glycosides (31–119), iridoids (120–145), and lignans (146–162) are the major secondary metabolites of Cistanche plants (see Table 2).

2.1 Phenylethanoid Glycosides

Phenylethanoid glycosides are the most abundant active components in Cistanche plants. These compounds, also known as phenylpropanoid derivatives, are glycosides formed by the linkage of a phenylethanoid aglycone with sugar groups. Common substituents at various positions on their core structure include acetyl groups, β-D-glucose, α-L-rhamnose, caffeoyl groups, feruloyl groups, coumaroyl groups, and 2,3,4-acetyl-α-L-rhamnose.

2.2 Iridoids and Their Glycosides

Iridoids are a class of monoterpenoids with a cyclopentane-pyran ring system, derived from iridodial. These compounds consist of a cyclopentanoid ether and hydroxyl groups, with the hydroxyl group often being a hemiacetal, which makes it chemically reactive and prone to forming glycosidic bonds. Natural iridoids in plants are mostly found as glycosides, with glucose being the dominant sugar moiety. In Cistanche, most iridoid glycosides have glucose linked at the 1-position of the aglycone, with a few linked at the 10-position. The aglycone's 4-position often has carboxyl, methoxymethyl, or methyl groups, while hydrogenation occurs occasionally at positions 3 and 4. Hydroxyl groups are commonly found at positions 6–8 or 10, with occasional dehydroxylation at positions 7 and 8 to form epoxy ether bonds or double bonds. Dehydration reactions sometimes occur at the 1 or 3 hydroxyl groups and the 10 hydroxyl group to form epoxy structures. The 5 and 9 hydrogens of the aglycone are predominantly in the β-configuration.

2.3 Lignans and Their Glycosides

Lignans and their glycosides are natural chemical products formed through single-electron radical coupling reactions of phenylpropanoid derivatives (C3-C6). Structurally, lignans can be seen as the coupling of two monomeric units, and some compounds naturally form glycosides by linking with sugar molecules. These compounds are often found in resinous substances within plants.

2.4 Other Secondary Metabolites

In addition to the aforementioned components, Cistanche plants also contain benzyl alcohol glycosides, phenylpropanoids, monoterpenes, phenol glycosides, sterols, and alkaloids. Studies [27] have isolated sterols such as carotene, β-sitosterol, and β-sitosterol glucoside-3'-O-heptadecanoate, as well as alkaloids such as betaine from Cistanche. Wang Liwei [29], using techniques such as reversed-phase silica chromatography, gel chromatography, and HPLC preparation, isolated active components from Cistanche methanol extracts, including adenosine, p-hydroxycoumarin, and β-sitosterol. Tu Pengfei et al. [30] isolated three benzyl alcohol glycosides from Cistanche, namely salidroside A, salidroside B, and salidroside Ca.

Summary

The chemical composition of Cistanche plants is highly diverse, comprising both primary and secondary metabolites. The primary metabolites are mainly polysaccharides and organic acids, while the secondary metabolites are dominated by phenylethanoid glycosides, iridoids and their glycosides, and lignans and their glycosides. These metabolites exhibit a wide range of pharmacological activities. Modern studies have shown that the pharmacologically active components of Cistanche primarily include total glycosides of Cistanche, Cistanche polysaccharides, phenylethanoid glycosides, echinacoside, verbascoside, and Cistanche glycoside A, among others.