Research On Cistanche: Regulating Human Health And Improving Chronic Diseases in Chinese Herbal Medicines

Cistanche is a traditional Chinese medicine containing multiple chemical components with tonic effects. In recent years, studies have found that it has a wide range of pharmacological effects, mainly used for neuroprotection, immunomodulation, anti - aging, anti - osteoporosis, liver protection, and more. This article reviews the research status of the chemical components and pharmacological effects of Cistanche. On this basis, based on the concept of quality markers (Q - Markers) of traditional Chinese medicine, it conducts a predictive analysis of Cistanche's Q - Markers from aspects such as the biosynthetic pathway, traditional efficacy, and different compatibility. It is speculated that phenylethanoid glycosides such as verbascoside, isoverbascoside, and echinacoside, polysaccharides such as mannitol, iridoids such as 6 - deoxyloganin and geniposidic acid, lignans such as (+)-syringaresinol - O - β - D - glucoside, organic acids such as chlorogenic acid and caffeic acid, and amino acid components such as valine, leucine, and lysine in Cistanche can be used as its quality markers, providing a certain reference for its quality evaluation.

Cistanche is the dried fleshy stem with scaly leaves of the plants Cistanche deserticola Y. C. Ma or C. tubulosa (Schenk) Wight in the Orobanchaceae family. It was first recorded in "Shennong's Classic of Materia Medica" and was classified as a top - grade herb. Since then, many classical works such as "Explications of the Classic of Materia Medica", "Compendium of Materia Medica", and "Yuehuazi's Materia Medica" have recorded it. It is a traditional precious Chinese medicinal herb in China and is known as the "Desert Ginseng".

Cistanche tastes sweet and salty, is warm in nature, and pertains to the kidney and large intestine meridians. It has the effects of tonifying kidney yang, nourishing essence and blood, and moistening the intestines to relieve constipation. It is used to treat kidney yang deficiency, deficiency of essence and blood, impotence, infertility, weakness and soreness in the lower back and knees, lack of strength in the tendons and bones, and dry constipation of the intestines. Cistanche is mainly produced in Inner Mongolia (Alxa Left Banner), Gansu (Changma), and other places.

Cistanche mainly contains chemical components such as phenylethanoid glycosides, iridoids, lignans, and saccharides. It has pharmacological effects such as neuroprotection, anti - aging, anti - liver injury, and relieving constipation. It is widely used in clinical practice of traditional Chinese medicine and has a promising development prospect. This article reviews the research progress of the chemical components and pharmacological effects of Cistanche and predicts the Q - Markers of Cistanche based on the basic requirements of quality markers (Q - Markers) of traditional Chinese medicine, providing a theoretical basis for the quality evaluation and quality control of Cistanche.

1. Chemical Components

Cistanche contains a variety of chemical components, mainly including phenylethanoid glycosides, iridoids, lignans and their glycosides, saccharides, etc. In addition, it also contains components such as benzyl alcohol glycosides, monoterpenoids, alkaloids, volatile oils, amino acids, and inorganic trace elements.

Phenylethanoid Glycosides
Phenylethanoid glycosides (PhGs) are the main components of Cistanche. Currently, Song Qingqing has isolated more than 70 compounds of this type through mass spectrometry analysis, including 4 monoglycosides, 41 diglycosides, and 25 triglycosides, such as salidroside, cistanoside C, isocistanoside C, cistanoside D, verbascoside, isoverbascoside, echinacoside, martynoside, and 2'-acetylmartynoside. Nan Zedong and others used methods such as normal - phase silica gel, gel Sephadex LH - 20, MCI, ODS, and semi - preparative high - performance liquid chromatography to isolate cis - tubuloside B, cis - cistanoside K, cis - cistanoside J, and cis - isocistanoside C from the 85% ethanol extract of the dried fleshy stem of cultivated desert Cistanche in Tazhong. Zhang Kaimei used normal - and reverse - phase silica gel column chromatography techniques to isolate 3 phenylethanoid glycoside compounds from the total glycosides of Cistanche: isoacteoside, tubuloside B, and acteoside. Zhang Jie and others used silica gel column chromatography, preparative liquid chromatography, and Sephadex LH - 20 to isolate and identify the phenylethanoid glycoside compound tubuloside A. Wang Liwei and others used separation and purification techniques such as reverse - phase silica gel chromatography, gel chromatography, and HPLC preparation to isolate 2'-acetylverbascoside, cistanoside A, and osmanthuside B. The phenylethanoid glycoside compounds in Cistanche are shown in Table 1, and the chemical structures of the main component nuclei are shown in Figure 1.

2. Pharmacological Effects

Neuroprotective Effect
Liu Mingchuan and others used biological enzymes to extract Cistanche. First, they optimized the process conditions through single - factor experiments, purified the extract with a spiral - wound membrane, and freeze - dried it to obtain the Cistanche extract. Then, they conducted antioxidant activity tests. Finally, they used in - vivo experiments on zebrafish and evaluated the protective effect of the Cistanche extract on the central nervous system of zebrafish based on the statistical analysis results of the fluorescence intensity of apoptotic cells. Wang and others found through research that the total glycosides of Cistanche can induce neurovascular regeneration in MCAO/R rats through the nuclear factor E2 - related factor 2 (Nrf - 2)/Kelch - like ECH - associated protein 1 (Keap - 1) pathway, promoting the recovery of nerve function. Huang Huilian and others used the random number method to divide 198 patients with vascular dementia into groups for treatment. After the two groups received basic treatment, they were treated with piracetam and the total glycosides of Cistanche respectively. After the treatment, by comparing the treatment effects, cognitive functions, and serum p - tau protein expression levels of the two groups, it was concluded that the total glycosides of Cistanche can effectively improve the cognitive function of patients with vascular dementia, is conducive to shortening the hospital stay, and improving the ability of daily living. Ju Bowei and others randomly divided 60 6 - month - old APP/PS1 double - transgenic AD model mice into groups and gave them distilled water, donepezil, the total phenylethanol glycosides of Cistanche, and verbascoside of Cistanche for 3 months. At the age of 9 months, the behavioral changes of the mice were detected by the Morris water maze method, the lesions of the hippocampus in the mouse brain were observed by HE staining, and the expression of Aβ1 - 42 and Aβ1 - 40 proteins in the hippocampus was examined by immunohistochemistry and Western - blot methods. The experimental results showed that the phenylethanoid glycosides of Cistanche can significantly reduce the damage of hippocampal neurons in the mouse brain, improve the learning and memory ability of the mice, reduce the number of Aβ1 - 42 and Aβ1 - 40 positive cells, and down - regulate the protein expression. Wang Jingkang and others sub - cultured PC12 cells, then constructed a damage model, and then used the MTT method to detect the cell survival rate, and carried out various staining analyses and Western blotting analyses. It was found that the alcohol extract of Tubular Cistanche has a good protective effect on PC12 nerve cell damage caused by hypoxia/glucose deprivation and reperfusion.
Zeng Kewu and others used the suture method to construct a rat middle cerebral artery occlusion model, detected the expression level of superoxide dismutase in the rat brain by immunohistochemistry, used agarose solid - phase microspheres surface - bonded with the chemical components of phenylethanoid glycosides of Cistanche to enrich the target group of phenylethanoid glycosides, captured the relevant brain - protecting target proteins, and identified them by high - resolution mass spectrometry technology. The experiment showed that the phenylethanoid glycosides of Cistanche can effectively improve the cerebral ischemia - reperfusion injury in rats.

Immune Effect
Cistanche polysaccharide is the material basis for the immunomodulatory effect of Cistanche. It can promote the proliferation of lymphocytes, improve the body's immune function, activate immune cells, and at the same time, can significantly improve the phagocytic and secretory functions of macrophages, thereby activating macrophages and playing a role in regulating immune activity. Wang Xiangyan detected the spleen lymphocytes of mice and measured the phagocytic activity of mouse peritoneal macrophages, indicating that Cistanche polysaccharide can significantly improve the activity of macrophages and promote the proliferation of lymphocytes, and concluding that Cistanche polysaccharide is the main material basis for the immunomodulation of Cistanche. The phenylethanoid glycoside extract of Cistanche can also regulate the immune system. Luo Ziyan and others proved through mouse animal experiments that the phenylethanoid glycoside extract of Tubular Cistanche can induce the expression of inducible nitric oxide synthase (iNOS), thereby stimulating macrophages to synthesize NO. At the same time, it also stimulates macrophages to release tumor necrosis factor - α (TNF - α) and interleukin - 6 (IL - 6), activating the immunomodulatory function of macrophages. The extracts of Angelica sinensis and Astragalus membranaceus can enhance the effect of the phenylethanoid glycoside extract in activating macrophages. Making the extracts of Angelica sinensis, Astragalus membranaceus, and phenylethanoid glycosides into compound tablets can enhance the immune effect by regulating the cellular immunity and mononuclear - macrophage functions of normal mice.

Anti - aging Effect

Antioxidation: Ailadan Maimaitiali and others optimized the extraction process of polysaccharides from Cistanche residues through orthogonal experiments based on single - factor experiments and conducted a preliminary study on their in - vitro antioxidant activity. The results showed that Cistanche polysaccharides have high antioxidant activity, with the ability to scavenge DPPH free radicals and hydroxyl free radicals and a strong reducing ability for copper ions. Yang Ting and others used the water - extraction and alcohol - precipitation method to extract the polysaccharide components from Cistanche residues, determined their content by the anthrone - sulfuric acid method, and studied the antioxidant activity of the polysaccharide components in Cistanche residues using 3 antioxidant models. It was concluded that the polysaccharide extract from Cistanche residues contains a high content of α - polysaccharide and has antioxidant activity.

Anti - fatigue: Luan Zhaoxia first prepared a polyphenol extract, then selected the appropriate resin type through resin pretreatment, static adsorption and elution experiments, and obtained the optimal purification process conditions through dynamic adsorption and elution experiments. The experimental results showed that high, medium, and low doses of the purified Cistanche polyphenol products can significantly prolong the swimming time of mice, significantly increase the content of liver glycogen and muscle glycogen in the body, increase the activity of lactate dehydrogenase, and effectively inhibit the level of lactate production, enhancing the body's endurance and thus being able to better relieve the body's fatigue. Yan Cuimin and others randomly divided 160 male mice into 4 groups. After administration, compared with the negative control group, the low, medium, and high - dose groups showed that the compound Cistanche tablets can significantly increase the weight - bearing swimming exhaustion time of mice, delay the onset of fatigue, increase the level of liver glycogen, and accelerate the clearance of blood lactate. Yan Lei and others compared the weight - bearing swimming time, lactate (LA), serum urea nitrogen (BUN) levels, activities of superoxide dismutase, malondialdehyde, and glutathione peroxidase in liver tissue, and the contents of liver glycogen and muscle glycogen in 4 groups of mice: the normal control group, the model group, the low - dose Cistanche polysaccharide group, and the high - dose Cistanche polysaccharide group. The results showed that Cistanche polysaccharide has an anti - fatigue effect on D - galactose - induced aging mice, and this effect may be related to reducing the content of serum BUN and LA, increasing the content of liver glycogen and muscle glycogen, and enhancing the anti - free radical damage.

Anti - osteoporosis
Zhang and others, based on the theory of "the kidney governing the bones", used an ovariectomized rat model of postmenopausal osteoporosis to observe the therapeutic effect of the Cistanche extract (CDE) on osteoporosis. All the data showed that CDE has potential anti - osteoporosis effects.
Wu Yang and others randomly divided 70 patients with primary osteoporosis diagnosed and treated in the outpatient departments of traditional Chinese medicine internal medicine and orthopedics of Wenzhou Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Zhejiang Chinese Medical University from June 2015 to June 2017 into a treatment group and a control group. The two groups were given Cistanche and Caltrate D tablets respectively. After 6 months of treatment, the treatment group achieved significant curative effects. The results showed that the traditional Chinese medicine Cistanche has a two - way regulatory effect on bone resorption and bone formation, can increase bone density, and thus plays an anti - osteoporosis role.

Yu Lixin and others randomly divided 52 SPF - grade SD female rats into a model group of 18 rats, a treatment group of 18 rats, and a control group of 16 rats. They established osteoporosis and fracture models, then administered drugs and collected samples. Finally, they detected bone density. After the samples were fixed, they were scanned by Micro - CT, and the levels of interleukin - 1β and transforming growth factor - β1 were measured. The analysis showed that the water extract of Cistanche can promote the healing of osteoporotic fractures.

Liver Protection
Zhang Shilei and others prepared the total phenylethanol glycoside (CPhGs) liposome of Cistanche by the thin - film dispersion method, observed the particle shape, detected its particle size distribution, determined the encapsulation efficiency and drug - loading amount by high - performance liquid chromatography. They randomly divided 65 SD rats into groups and gave them the corresponding test substances. They compared the serum biochemical indexes of the normal control group and the BSA - sensitized model group rats, observed the fiber distribution of the liver tissue of each group of rats by Masson staining, detected the expression of Collagen I and Collagen III mRNA in the liver tissue of rats by real - time fluorescence quantitative PCR, and detected the expression levels of α - smooth muscle actin and Collagen I proteins in the liver tissue of rats by Western blot method. It was found that the liver protection of the Cistanche total phenylethanol glycoside liposome on the model rats is better than that of the un - liposomalized raw material of the total phenylethanol glycoside of Cistanche and the blank liposome. Guo and others also confirmed that a polysaccharide component isolated from Cistanche polysaccharides can reduce the contents of malondialdehyde (MDA) and triglyceride and regulate the activities of related enzymes, thus playing a protective role against alcoholic liver injury.

Cistanche and Constipation: A Gentle and Effective Remedy
One of the most common concerns among patients is constipation. In modern medicine, constipation is often caused by a combination of factors. An unbalanced diet lacking in dietary fiber, a sedentary lifestyle, stress, and certain medications can all lead to this uncomfortable condition. The discomfort of constipation, including abdominal pain, bloating, and a feeling of incomplete evacuation, can significantly affect one's quality of life. It can also have a negative impact on overall health, affecting digestion, nutrient absorption, and even mental well - being.

Cistanche offers a natural and gentle solution for constipation. Liu Xianhong and others randomly divided 61 constipation patients admitted from 2017 to 2018 into two groups and gave them Cistanche decoction and domperidone tablets for treatment respectively. By comparing the curative effects of the two groups, it was shown that Cistanche decoction is suitable for the clinical treatment of constipation and can address both the symptoms and root causes. Gao Yunjia and others randomly divided 67 mice into a model group, various extract groups, and a blank control group. The model group and various extract groups were modeled by intragastric administration of compound diphenoxylate, and then the extracts of different parts of Cistanche were given respectively. By observing the feces, it was found that the effective substances for the laxative effect of Cistanche are total oligosaccharides and galactitol.

Cistanche contains dietary fiber and other substances that play a crucial role in promoting healthy digestion. The dietary fiber in Cistanche can absorb water in the intestines, increasing the volume of feces and making them softer. This is especially important for those who struggle with hard and dry stools. When feces become softer, they are easier to pass through the intestines, reducing the pain and discomfort associated with constipation.

Moreover, Cistanche can stimulate intestinal peristalsis. It promotes the rhythmic contractions of the intestinal muscles, which helps move feces along the digestive tract. This gentle stimulation is different from the harsh effects of some chemical laxatives. Chemical laxatives may cause sudden and strong bowel movements, often accompanied by abdominal cramps and potential electrolyte imbalances. In contrast, Cistanche acts gently, providing a more comfortable and sustainable way to relieve constipation without the risk of these harsh side effects. It is especially suitable for the elderly, those with sensitive digestive systems, or those who have had long - term problems with constipation.

Clinical studies have shown that Cistanche can effectively improve the symptoms of constipation. In a research involving a group of patients with chronic constipation, those who took Cistanche - based supplements for a certain period experienced a significant increase in the frequency of bowel movements and a decrease in the difficulty of defecation. Their overall quality of life was also improved as the discomfort of constipation was alleviated.
7. Other Pharmacological Effects
Liu Tao and others found through research that Cistanche can regulate the levels of follicle - stimulating hormone, estrogen, and anti - Müllerian hormone, inhibit the expression of tumor necrosis factor - α (TNF - α) and interferon - γ (IFN - γ) genes, and it may affect premature ovarian failure by regulating sex hormone