Cistanches Herba: A Neuropharmacology Review
Cistanche extract products

(family Orobanchaceae), commonly known as “desert ginseng” or Rou Cong Rong, is a

global genus and commonly used for its neuroprotective, immunomodulatory, anti-oxidative,

kidney impotence, laxative, anti-inflammatory, hepatoprotective, anti-bacterial, anti-

viral, and anti-tumor effects in traditional herbal formulations in North Africa, Arabic,

and Asian countries. The major bioactive compound present in this plant is phenylethanoid

glycosides. In recent years, there has been great important in scientific investigation of

the neuropharmacological effects of the bioactive compounds. The in vitro and in vivo

studies suggests these compounds demonstrate neuropharmacological activities against a

wide range of complex nervous system diseases which occurs through different mechanisms

include improving immunity function and kidney aging, anti-lipid peroxidation, scavenging

free radical, inducing the activation of caspase-3 and caspase-8. This review aims to

summaries the various neuropharmacological effects and mechanisms of Cistanches Herba

extracts and related compounds, including its efficacy as a cure for Alzheimer’s disease

and Parkinson’s disease with reference to the published literature. Which provides

guidance for further research on the clinical application of Cistanches Herba.
Introduction
Cistanches Herba, the dried stem of Cistanches species Cistanche deserticola Y.C.Ma

(Figure 1) and Cistanche raw materials,

is recorded in the Chinese Pharmacopeia (Committee, 2015). Other non-official species,

such as C. sinensis Beck and C. salsa (C. A. Mey) Beck, are also used as Cistanches Herba

in certain regions of China due to resource shortage. Cistanches Herba is one of the most

valuable herbal drugs in traditional Chinese medicine, which supplements kidney functions,

boosts the essence of blood, and moistens the large intestines to free stool (Medicine,

2005). Therefore, it is called “desert ginseng” in China because of the excellent

medicinal functions and nourishing effects (Wang et al., 2012). Cistanches Herba, a global

genus of holoparasitic desert plant, which is primarily endemic in North Africa, Arabic,

and Asian countries (Nan et al., 2013). The primary producing areas of Cistanches Herba in

China are Inner Mongolia and the provinces of Xinjiang, Gansu and Qinghai.
Several chemical groups were isolated from Cistanches Herba, including PhGs (Figure

1), lignans, iridoids, and polysaccharides (Chen et al., 2013). Pharmacological studies

demonstrated that Cistanches Herba exhibits neuroprotective, kidney impotence, laxative,

anti-inflammatory, hepatoprotective, immunomodulatory, anti-oxidative, anti-bacterial,

anti-viral, and anti-tumor effects (Hu and Feng, 2012). And our previous studies have

distinguished Cistanches Herba from different geographic origins using a combination of

DNA barcoding and UPLC-Q-TOF/MS technology.
The Consumer Price Indexdatabase of China reports that 58 drugs from 12 different

groups, including glycosides of Cistanche capsules and compound Cistanche Yizhicapsules,

are authorized for the treatment of AD. Cistanches Herba wine and tea are produced in

Alashan, Inner Mongolia, China, which might assist in Runchang catharsis and enhance the

immune, endocrine regulation, and anti-aging systems of the body. Boschnalosides used as a

therapeutic agent in Japan to treat sexual dysfunction and amnesia, and echinacoside is

used in healthcare products in the United States to improve immunity (Cheng et al., 2005).
Some researchers recently focused on the neuroprotective effects of

Cistanche health products

, but these effects have not been studied thoroughly (Table 1). This review presents

and analyzes recent developments in the neuropharmacology of Cistanches Herba and provides

a reference for the further study and clinical application of this medicinal plant.
Cistanches Herba medicines have a long history of practical use, but scientists

worldwide only began to disclose their chemical composition in the1980s. Figure 2 shows an

analysis of the related literature. The cumulative histogram shows the number of studies

increased over time, and the Chinese literature occupies the greatest proportion, which

reveals the potential research value of Cistanches Herba. Figure 2A shows that the

neuropharmacology related literature occupies the largest proportion of the nine areas of

pharmacology, and this topic has become the most important area for research. Figure 2B

exhibits the chemical research diversity of Cistanches Herba, with a substantial

proportion of research on content determination. Further research may focus on

neuropharmacology and component content.
Cistanches Herba has a long history as a medicinal plant in China and Japan because of

its wide spectrum of pharmacological activities. It is commonly called Rou Cong Rong in

Chinese, and it was first listed medicinal use as a tonic agent in the Chinese Materia

Medica Shen Nong’s Herbal Classic (Estern Han Dynasty) 2000 years ago, and later recorded

in Yao Xing Lun in 1590. The Compendium of Materia Medica (Ben Cao Gang Mu, 1619)

documented that Cistanches Herba invigorated the kidney to treat kidney deficiencies and

geriatric constipation strengthened and nourished marrow and essence, protected semen, and

moistened dryness to relax the bowels. 
These properties were also written in Ben Cao Hui Yan in 1619. A total of 200

medicinal books recorded the pharmacodynamics and use of Cistanches Herba in Chinese

history. Cistanches Herba ranks first in Chinese traditional medicine to strengthen

prescriptions, which ranks second in anti-aging prescriptions at the same time, behind

Panax ginseng in past dynasties. Modern pharmacological investigations demonstrated that

Cistanches Herba was used as a kidney-yang reinforcing Chinese medicinal tonic, but it is

also exhibits anti-aging, improves memory, and enhances immunity effects (Table 1), which

indicate that extracts or constituents from Cistanches Herba have a promising future for

the treatment of diseases, particularly nervous system disorders. However, systematic data

on the pharmacological activities of this agent is lacking. It is urgent and important to

study the pharmacological effects and mechanisms of Cistanches Herba deeply in the future.
Aging is an inevitable process of life. This process involves a series of degenerative

changes in tissues and organ functions with advancing age. Studies on aging and anti-aging

medicines have made significant progress in recent years. Therefore, anti-aging drugs are

a current and prominent issue in gerontology. The aging process reflects a confluence of

in vivo and in vitro factors. Aging is closely related to type 2 diabetes,

atherosclerosis, and AD. Aging is also related to the decreased regeneration of cells,

viscera deficiency, increased free radicals, body poisoning, and lack of rhythm when

eating (Lopez-Otin et al., 2013). Aging is an inevitable process, but delaying this

process is now possible.
Several historical Chinese herbal pharmacopeias describe that

Cistanche tubulosa supplements possesses anti-aging properties.

PhGs and oligosaccharides are two types compounds isolated from Cistanches Herba that are

the main active ingredients of this plant. In vivo studies established an aging mouse

model caused by D-galactose. The mice were divided into normal control, model, Vitamin E

and total glycoside groups, and all groups received different doses of various materials.

The results suggested that the glycosides exhibited protective effects on the hippocampal

ultrastructure, and glycosides may play a role in the delay of aging and the prevention

and treatment of senile dementia via anti-oxidation (Wang X. et al., 2015). Xu et al.

investigated the protective effect of Cistanches Herba alcohol extract on hepatic

mitochondria and established an aging rat model caused by D-galactose. Rats were

administered Cistanches Herba alcohol extract for 6 weeks. The results indicated that

Ca2+-ATP enzyme activity was enhanced, and the MDA content in the hepatic mitochondria was

reduced. These results further suggested that the Cistanches Herba alcohol extract

effectively protected hepatic mitochondria in the D-galactose aging rat model (Xu et al.,

2007). Xu and Liu (2008) examined the anti-aging effect of PhGs isolated from Cistanches

Herba. The results confirmed that the PhGs improved learning and memory, exhibited

antioxidant activity, and boosted the immune system. The results also demonstrated that

the PhGs exhibited anti-aging effects via enhancement of anti-oxidation. The mechanism may

be related to the free radical scavenging ability of PhGs. Polysaccharides of Cistanches

Herba exhibit the same function as PhGs on anti-aging (Xu et al., 2008; Zhang et al.,

2011). Zhang et al. (2014) also investigated a Cistanches Herba extraction 2014 and found

that this extract extended life span. The results of studies on echinacoside and acteoside

suggest that these components exhibit positive anti-aging effects (Zhang et al., 2008; Xie

et al., 2009). Many studies of anti-aging involve Cistanches Herba, but these works are

limited because the anti-aging mechanism is not known. There are three possible pathways

to anti-aging, including improving immunity function and kidney aging, anti-lipid

peroxidation. Immune theory of aging said that the decline of immune function is closely

related to the aging organism. Thus, the immune function of the body can indirectly

reflect the aging organism in a certain extent. The raised index of thymus and spleen,

increased content of IFN-γin serum and decreased content of IL-6, increased capacity of

peritoneal macrophage phagocytic and lymphocyte proliferation response always can improve

the immunity aging, and then delay the organism aging. The expression of p53 from human

fibroblastic cell down-regulated significantly in a dose dependent manner after treatment

with echinacoside, and which may be correlated with the up-regulation of SIRT1. The PhGs

can scavenge different ROS, including. O–2, H2O2 and ?OH, effectively and protect DNA

damage through scavenging ?OH. In addition, the PhGs also can increase the content of RNS-

NO, and then reduce the lipid peroxidation. Therefore, the real effective components of

Cistanches Herba and what a role in anti-aging are important and appealing future research

directions.
Anti-oxidative and Anti-apoptotic Activity
Cistanches Herba exhibits anti-oxidative, free radical-scavenging and anti-apoptotic

activity via different mechanisms. Recent studies demonstrated the anti-oxidant activity

of Cistanches Herba, particularly in the clearing of all types of free radicals in vivo

and in vitro, improvement in the activity of anti-oxidant enzymes in the body, and

inhibition of the formation of lipid peroxide, MDA, and brown fat (Wang et al., 2001; Wu

and Fu, 2004; Luo et al., 2012; Song, 2013). Current studies demonstrated that cell

apoptosis or programmed cell death is determined by heredity and is related to oxidation

(Martin, 2011). Deng used the MTT assay to examine cell survival rate, agarose gel

electrophoresis of DNA, and flow cytometry to detect cell apoptosis. The results suggested

that the echinacoside extracted from Cistanches Herba exhibited protective effects on TNF

α-induced SH-SY5Y cell apoptosis (Deng et al., 2005). Nerve cell protection exhibits a

close connection with the reduction of active oxygen levels in cells, inhibition of

caspasc-3 activity and maintenance of a high-energy state of mitochondrial membrane

potential. Bao et al. (2010) investigated an extract of Cistanche tubulosa and discussed

its anti-oxidant ability. These researchers conducted an in vitro study to compare the

anti-oxidative properties of methanol and ethanol extracts. The results suggested that the

two extracts exhibited high anti-oxidant ability, and 70% ethanol was the best extraction

agent of C. tubulosa to ensure improved anti-oxidant activity (Bao et al., 2010). The PhGs

from Cistanches Herba are considered the effective ingredients for anti-oxidative and

anti-apoptotic activity in recent studies. The anti-oxidant mechanism is mainly related to

the radical-scavenging activity. PhGs compounds, which are mostly provided with different

amounts of phenolic hydroxyl, can be used as hydrogen donor to reductive radicals, and

then reach to the purpose of radical scavenging. The

herbal cistanches extract powder scavenge the free radicals mainly in

two ways, including directly involving in the removal of free radicals or blocking their

production and regulating the anti-oxidant enzymes related to the free radical metabolism

in vivo, such as SOD, CAT and GPX (Ko and Leung, 2007). For another, the Glycosides of

Cistanches Herba can prevent the apoptosis of cerebellar granule neurons by inhibiting the

activities of caspase-3 and caspase-8. Therefore, the good oxidation resistance and anti-

aging ability of Cistanches Herba may be applied to cosmetics. This application may be a

new research direction in the future.
Learning and Memory Enhancement
Learning and memory are advanced functions of the brain, and these functions are

important factors in determining intelligence. Learning and memory impairment is a common

symptom in different types of encephalopathy, such as attention deficit and hyperactivity

disorder in childhood, adolescent chorea, lobar atrophy disease, neurosis, senile cerebral

arteriosclerosis, and dementia. Medicinal research demonstrated that the impairment of

learning and memory is closely related to the impairment of synaptic transmission in the

brain and the metabolism of neurotransmitters, other substances, and energy in the brain

(Chen, 1993). Modern pharmacological studies determined that Cistanches Herba

significantly improves learning and memory, and PhGs are the active chemical ingredients

of this effect.
Traditional Chinese medicine shows that learning and memory dysfunction exists in the

Yang deficiency model of the spleen and kidney. Therefore, these two models are more

suitable for the study of tonics in traditional Chinese medicine. Gao et al. (2005)

examined the effects of Cistanches Herba glycosides on the learning and memory of kidney

Yang deficiency mice. The results of this study demonstrated that the Yang deficiency

symptoms of each dose group improved, and the number of animal deaths decreased

significantly. However, the jumping latency of each dose group after hydrocortisone

administration was significantly prolonged, and the number of errors during a 5-min period

was reduced. Therefore, glycosides improved the learning and memory of kidney Yang

deficiency mice induced by hydrocortisone and reduced the death rate of these animals (Gao

et al., 2005). The current researchers established a scopolamine-induced learning and

memory impairment mouse model to investigate the effects of the PhGs of Cistanches Herba.

The results demonstrated that the PhGs of Cistanches Herba enhanced learning and memory

(Li, 2011; Liu et al., 2011). Choi et al. (2011) also demonstrated that Cistanches Herba

enhanced learning and memory via the induction of nerve growth factor. Vary factors

related to cerebrovascular disease induce vascular dementia. This condition is an acquired

intelligence-damaging syndrome of cognitive impairment, which is a primary type of senile

dementia. Ischemic cerebrovascular disease occurs frequently in many cerebrovascular

diseases induced by vascular dementia. Traditional medicine and modern pharmacology

demonstrated that PhGs play an active role in neuroprotection (Feng et al., 2013; Liu et

al., 2013; Zhu et al., 2013; Zhang, 2014). The reason why Cistanches Herba extract can

improve learning and memory is partly due to neuronal cell differentiation, neurite

outgrowth and presynaptic formation promoted. Cistanches Herba also improved cognitive

behavior related to memory ability. Therefore, Cistanches Herba is a potential candidate

for cognitive enhancement owing to its action as a nerve growth factor modulator. However,

extensive research is necessary to discover the neuroprotective mechanism deeply. Further

studies to determine the specific type of PhGs are expected to play a leading role in

improving learning and addressing memory impairment.