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Cistanche

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Background & General Info

Cistanche is a genus comprising 22 endangered plant species inhabiting the arid lands and warm deserts of northwestern China, Iran, India, and Mongolia under harsh environmental conditions such as intensive sunshine and less than 250 mm of annual precipitation. [1][2] Member species of this genus belong to the Orobanchaceae family, or the broomrapes, and are actually perennial parasitic herbs that affix themselves onto the roots of sand-fixing plants, such as the black saxaul and white saxaul. [2] Traditional Chinese medicine celebrates Cistanche herbs as the “ginseng of the deserts” and deems them as widely accepted superior tonics. [1][2]

Notable Cistanche herbs include Cistanche tubulosa and Cistanche deserticola, which both have more or less comparable chemical components and pharmacological properties and are indexed in the Chinese Pharmacopoeia. [2] Cistanche salsa and Cistanche sinensis are other species of the genus used as herbal alternatives in some regions. [2]



Botany

Species belonging to Cistanche genus are mostly perennial herbs with fleshy, typically unbranched stems and spicate inflorescences. Their corollas are tubular-campanulate or funnelform in shape, with an apex consisting of five subequal lobes. The flowers’ stamens are inserted in corolla tube, and the style is slender, whereas the stigma comprises two lobes. The plants’ ovoid-globose or globose capsule, dehiscing by two or three valves, encloses subglobose seeds. [3]

History & Traditional Use

Plants belonging to the genus Cistanche are widely used as ethnomedicine in East Asian countries. [4] In Chinese medicinal system, Cistanche plants are referred to as “rou cong-rong” and are employed as a warm tonic prescribed for chronic renal disease, impotence and female infertility, morbid whitish or yellowish vaginal discharge, profuse abnormal uterine bleeding, and senile constipation. [1][2] The dried succulent stems of rou cong-rong and their medicinal benefits were first mentioned in Shen Nong’s Chinese Materia Medica.

Cistanche deserticola has long been utilized as a tonic of reproductive function, whereas Cistanche tubulosa is often prescribed by traditional Chinese physicians to treat forgetfulness and its nanopowder form is said to be therapeutic in cases of Parkinson’s disease. [5][6][7] In addition, traditional Chinese medicine indicates Cistanche tubulosa as a chief therapeutic alternative for kidney deficiency syndrome related to androgens. [7]

General Herbal Uses

Several studies had demonstrated the biological activities of Cistanche herbs, including their antioxidant, neuroprotective, and anti aging properties. [1][2] Pharmacology studies have also pointed out the androgen-like activity of Cistanche plants, signifying its utility in reproductive health. [4] Based on traditional Chinese medicine, Cistanche deserticola in particular has been specified to tonify the kidney, to revitalize the “yang,” and to treat conditions related to reproduction, development, and fertility function. [1] There have been numerous clinical and basic studies on Cistanche tubulosa and its activities on neurodegenerative diseases. [7]



Constituents/Active Components

Cistanche herbs contain a number of active constituents, including volatile oils, nonvolatile phenylethanoid glycosides, iridoids, lignans, alditols, oligosaccharides, and polysaccharides. [1][2] Based on data from pharmacological studies, the antioxidant and neuroprotective activities of these herbs are attributable to their phenylethanoid glycoside components, whereas galactitol and oligosaccharides appear to be responsible for their benefits against senile constipation. [1] Nan et al. (2016) isolated and identified nine iridoids in their study, namely, cistadesertoside A, cistanin, cistachlorin, 6-deoxycatalpol, gluroside, kankanoside A, ajugol, bartsioside, and 8-epi-loganic acid. [8]

Medicinal/Scientific Research

Antioxidant

A 2010 study published in Shanghai Journal of Traditional Chinese Medicine demonstrated the total antioxidant capacity of methanol and ethanol extracts from Cistanche tubulosa. Although both extracts were shown to have similar values for total phenolic (32.65 ± 6.22 mg GA/g and 31.45 ±3.54 mg GA/g, respectively) and flavonoid (65.33 ± 6.71 mg RE/g and 62.70 ± 8.56 mg RE/g, respectively) contents, the ethanol extract possessed significantly higher Trolox equivalent antioxidant capacity (TEAC) value than the methanol extract (137.18 ± 2.47 μmol TE/g and 114.42 ± 1.42 μmol TE/g, respectively). Both extracts had comparable DPPH radical scavenging activity and ORAC values and were revealed to have overall high total antioxidant capacities. [9]

Anti-inflammatory

Kyung et al. (2012) demonstrated the anti-inflammatory property of Cistanche tubulosa extract both in vitro in a macrophage culture system and in vivo in a carrageenan-induced air pouch inflammation model. The extract was observed to suppress the production of nitric oxide from activated RAW 264.7 macrophage cells and to considerably lessen tissue inflammation when coadministered with fuciodan, inhibiting vascular exudation and blocking an increase in concentrations of nitric oxide and prostaglandin E2. It also evidently decreased the number of inflammatory cells and inhibited their activation. [10] On the other hand, stems of Cistanche deserticola had also been found by a 2016 phytochemical investigation to contain anti-inflammatory iridoids. The anti-inflammatory activities of these chemical constituents were tested, and among the isolated iridoids, 8-epi-loganic acid was proven to potently inhibit the production of nitric oxide induced by lipopolysaccharide in BV-2 mouse microglial cells, obtaining an IC50 value of 5.2 μmol/L. [8]

Antiallergic

Acteoside, a component of Cistanche tubulosa, had been determined by Yamada et al. (2010) to possess antiallergic property and to inhibit immediate-type and delayed-type allergic reactions mediated by basophilic cells. At a concentration of 0.1–10.0 µg/mL, it prevented the release of histamine and β-hexosaminidase, as well as Ca(2+) I influx from IgE-mediated RBL-2H3 cells. It also dose-dependently inhibited the production of tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4), as evaluated using ELISA in human basophilic (KU812) cells. [11]

Antifatigue

Oral administration of a phenylethanoid-rich extract of Cistanche deserticola at doses of 0.5 and 1 g/kg for 3 weeks resulted in longer swimming time to exhaustion in treated mice, a significant reduction in levels of serum creatine kinase, lactate dehydrogenase, and lactic acid, and a marked increase in hemoglobin and glucose contents. This suggested antifatigue action for the extract, which can be likely attributed to its ability to decrease muscle damage, defer lactic acid accumulation, and improve energy storage. [12]

Antitoxicity

Gu et al. (2013) validated the counteracting and alleviating effect of Cistanche deserticola aqueous extract against testicular toxicity induced by hydroxyurea, an anticancer drug notorious for its cytotoxic effects and potential reproductive toxicity. Daily intragastric administration of Cistanche deserticola decoctions at doses of 1.5, 3.0, and 6.0 g/kg for 4 weeks in male mice resulted in the amelioration of hydroxyurea-induced spermatogenetic cell degeneration and modulated the levels of serum sex hormones. [13]

Hypocholesterolemic

Aqueous ethanol extract obtained from the roots of Cistanche tubulosa had been shown in a 2009 study to display hypocholesterolemic activity in mice and to affect mRNA expressions of molecules associated with cholesterol transport and metabolism. Administration of the extract at a concentration of 400 mg/kg for 14 days led to an upregulation of mRNA expression of apolipoprotein B, very low density lipoprotein (VLDL) receptor, cytochrome P450 side chain cleave (SCC), and steroid 5alpha-reductase 2 in the livers of mice and blocked any increase in serum cholesterol levels in mice fed with a high-cholesterol diet. [14]

Neuroprotective

Cistanche tubulosa had been observed in a 2016 Chinese study to protect dopaminergic neurons by regulating apoptosis and glial cell-derived neurotrophic factor in mice with experimentally elicited Parkinson’s disease. In nanopowder form, it improved the viability of cells treated with MPP+, augmented the expression of tyrosine hydroxylase and Bcl2 protein, and lessened the number of apoptotic cells. More importantly, treatment of Cistanche tubulosa nanopowder at different doses improved the behavioral deficits in mice, decreased the stationary duration of their swimming, and boosted their ability for spontaneous activity. [7]

Sedative

Findings of Lu (1998) demonstrated the sedative activity of ethanol extract of Cistanche deserticola and its water fraction. In this study, a prolonged hexobarbital-induced sleeping time in mice resulted from administration of crude extract of Cistanche deserticola, especially its water fraction. As assessed using the automated activity meter, the spontaneous motor activity of rats, including horizontal activity, ambulatory time, and total distance, also decreased due to the sedative effect of the extract. [15]

Male Fertility

Gu et al. (2016) determined that Cistanche deserticola extract aids in penis erectile response and slightly modulates the serum hormone level. Intragastric treatment of castrated rats with Cistanche deserticola extract at doses of 0.45, 0.90, and 1.8 g/kg daily for 4 weeks led to shortened erectile latency and significantly prolonged erectile duration compared to operated controls, signifying diminution of the negative effects of castration. At a dose of 0.9 g/kg, the extract appeared to regulate the concentration of serum luteinizing hormone in castrated rats to normal levels. [5] A 2016 study on the other hand demonstrated the ability of ethanol extract derived from Cistanche tubulosa stems to increase levels of male sex hormones by stimulating testicular steroidogenic enzymes. Intragastric administration of Cistanche tubulosa ethanol extract to rats at doses of 0.4 and 0.8 g/kg for 20 days increased their sperm count by 2.3- and 2.7-fold and sperm motility by 1.3- and 1.4-fold while decreasing abnormal sperm by 0.76- and 0.6-fold. As quantified in radioimmunoassay, a significant increase in serum level of progesterone and testosterone was also noted in rats treated with the extract, as well as enhanced expression of CYP11A1, CYP17A1, and CYP3A4 per results of immunohistochemistry and western blot analysis. [4]

Alzheimer’s Disease

Cistanche tubulosa water extract has been shown to ameliorate cognitive deficits in a rat model of Alzheimer’s disease. The extract, which contains sufficient amounts of echinacoside and acteoside, prevented the deposition of amyloid β peptide 1-42 (Aβ 1-42) in the brains of rats and reversed the cholinergic and hippocampal dopaminergic neuronal dysfunction caused by Aβ 1-42. Specifically, continual infusion of Aβ 1-42 significantly reduced the levels of acetylcholine and dopamine in the cortex and hippocampus of experimental rats and levels of choline in the hippocampus only, and the extract effectively overturned such decrease. [6]

Another study in 2006 indicated the ability of Cistanche glycosides to distinctly enhance learning and memory in mouse models of Alzheimer’s disease induced by ntracerebroventricular injection of β-amyloid peptide. Assessment of glycoside-treated mice with Alzheimer’s disease also revealed an increase in activity of superoxidase dismutase and glutathione peroxidase and a decrease in contents of malondialdehyde in the brain. As observed through electronic microscopy, the glycosides from Cistanche also ameliorated some pathological features of Alzheimer’s disease. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay detected a significantly decreased cell apoptosis in the brains of mice administered with glycosides from Cistanche, and the use of immunohistochemical SABC method determined a decrease in Bax expression but an increase in Bcl-2 expression. [16] A more recent 2015 study on the glycosides of Cistanche similarly supported the claim that they improve learning and memory in rat models of vascular dementia. Using Morris Water Maze test to evaluate cognitive performance, Chen et al. (2015) concluded that Cistanche glycosides protect neurons in the hippocampus via mechanisms that include a reduction of P-tau phosphorylation and an increase in expression levels of dihydropyrimidinase-related protein 2 (CRMP-2). Treated rats manifested significantly lower escape latency and different expression levels in 21 protein spots in their hippocampus. [17]

Hair Loss

Because of Cistanche tubulosa’s anti-oxidative and anti-inflammatory properties, it has been purported to encourage hair growth and address dandruff and inflammation of the scalp. A 2015 double-blinded, placebo-controlled clinical trial confirmed the ability of Cistanche tubulosa extract and Laminaria japonica extract complex (MK-R7) to promote scalp and hair health in individuals suffering from mild to moderate patterned hair loss and to significantly increase their hair density and diameter following 16 weeks of consumption of the said extract complex. The test group also presented favorable outcomes in terms of visual assessment and patient’s subjective score of dandruff and scalp inflammation. [18]

Contraindications, Interactions, And Safety

The second edition of the American Herbal Products Association’s Botanical Safety Handbook categorized Cistanche species to class 1; that is, these herbs can be safely consumed when used appropriately. Contraindications, drug interactions, and adverse events for these herbs have not yet been decisively established by clinical trials and toxicity studies, although texts on traditional Chinese medicine have not indicated any cautions on their use during pregnancy and lactation. [19] Administration of Cistanche tubulosa ethanol extract to rats at high dose had been shown in the study of Wang et al. (2016) to cause mild hepatic edema. [4]

References:

[1] Y. Jiang and P. Tu, "Analysis of chemical constituents in Cistanche species," Journal of Chromatography A, vol. 1216, no. 11, p. 1970–1979, 2009. https://www.ncbi.nlm.nih.gov/pubmed/18691718

[2] L. Zhiming, L. Huinuan, G. Long, et al., "Herba cistanche (rou cong-rong): one of the best pharmaceutical gifts of traditional Chinese medicine," Frontiers in Pharmacology, vol. 7, p. 41, 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771771/

[3] "Cistanche Hoffmannsegg & Link," Flora of China. http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=107147

[4] T. Wang, C. Chen, M. Yang, et al., "Cistanche tubulosa ethanol extract mediates rat sex hormone levels by induction of testicular steroidgenic enzymes," Pharmaceutical Biology, vol. 54, no. 3, p. 481–487, 2016. https://www.ncbi.nlm.nih.gov/pubmed/26004585

[5] L. Gu, W. Xiong, et al., "Effects of Cistanche deserticola extract on penis erectile response in castrated rats," Pakistan Journal of Pharmaceutical Sciences, vol. 29, no. 2, p. 557–562, 2016. https://www.ncbi.nlm.nih.gov/pubmed/27087079

[6] C. Wu, H. Lin and M. Su, "Reversal by aqueous extracts of Cistanche tubulosa from behavioral deficits in Alzheimer's disease-like rat model: relevance for amyloid deposition and central neurotransmitter function," BMC Complementary and Alternative Medicine, vol. 14, p. 202, 2014. https://www.ncbi.nlm.nih.gov/pubmed/24968859

[7] Q. Xu, W. Fan, S.-F. Ye, et al., "Cistanche tubulosa protects dopaminergic neurons through regulation of apoptosis and glial cell-derived neurotrophic factor: in vivo and in vitro," Frontiers in Aging Neuroscience, vol. 8, p. 295, 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159610/

[8] Z. Nan, M. Zhao, et al., "Anti-inflammatory iridoids from the stems of Cistanche deserticola cultured in Tarim Desert," Chinese Journal of Natural Medicines, vol. 14, no. 1, p. 61–65, 2016. https://www.ncbi.nlm.nih.gov/pubmed/26850348

[9] B. Bao, X. Tang, H. Tian, et al., "Antioxidant activity of extracts from desert living Cistanche tubulosa (Schrenk) R. Wright," Shanghai Journal of Traditional Chinese Medicine, vol. 44, p. 68–71, 2010. http://en.cnki.com.cn/Article_en/CJFDTOTAL-SHZZ201002033.htm

[10] J. Kyung, D. Kim, D. Park, et al., "Synergistic anti-inflammatory effects of Laminaria japonica fucoidan and Cistanche tubulosa extract," Laboratory Animal Research, vol. 28, no. 2, p. 91–97, 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389844/

[11] P. Yamada, R. Iijima, et al., "Inhibitory effect of acteoside isolated from Cistanche tubulosa on chemical mediator release and inflammatory cytokine production by RBL-2H3 and KU812 cells," Planta Medica, vol. 76, no. 14, p. 1512–1518, 2010. https://www.ncbi.nlm.nih.gov/pubmed/20354949

[12] R. Cai, M. Yang, et al., "Antifatigue activity of phenylethanoid-rich extract from Cistanche deserticola," Phytotherapy Research, vol. 24, no. 2, p. 313–315, 2010. https://www.ncbi.nlm.nih.gov/pubmed/19610039

[13] L. Gu, W.-T. Xiong, et al., "Cistanche deserticola decoction alleviates the testicular toxicity induced by hydroxyurea in male mice," Asian Journal of Andrology, vol. 15, no. 6, p. 838–840, 2013. https://www.ncbi.nlm.nih.gov/pubmed/23817499

[14] H. Shimoda, J. Tanaka, Y. Takahara, et al., "The hypocholesterolemic effects of Cistanche tubulosa extract, a Chinese traditional crude medicine, in mice," The American Journal of Chinese Medicine, vol. 37, no. 6, p. 1125–1138, 2009. https://www.ncbi.nlm.nih.gov/pubmed/19938221

[15] M. Lu, "Studies on the sedative effect of Cistanche deserticola," Journal of Ethnopharmacology, vol. 59, no. 3, p. 161–165, 1998. https://www.ncbi.nlm.nih.gov/pubmed/9507899

[16] F. Liu, X. Wang, et al., "The effects of glycosides of cistanche on learning and memory in β-amyloid peptide induced Alzheimers disease in mice and its possible mechanism," Chinese Pharmacological Bulletin, vol. 22, p. 599–601, 2006. https://www.researchgate.net/publication/292545314_The_effects_of_glycosides_of_cistanche

[17] J. Chen, S. Zhou, et al., "Glycosides of cistanche improve learning and memory in the rat model of vascular dementia," European Review for Medical and Pharmacological Sciences, vol. 19, no. 7, p. 1234–1240, 2015. https://www.ncbi.nlm.nih.gov/pubmed/25912583

[18] J. Seok, T. S. Kim, H. J. Kwon, et al., "Efficacy of Cistanche tubulosa and Laminaria japonica extracts (Mk-R7) supplement in preventing patterned hair loss and promoting scalp health," Clinical Nutrition Research, vol. 4, no. 2, p. 124–131, 2015. https://www.ncbi.nlm.nih.gov/pubmed/25954733

[19] Z. Gardner and M. McGuffin, American Herbal Products Association’s Botanical Safety Handbook, 2nd ed., Boca Raton, Florida: CRC Press, 2013.

Article researched and created by Dan Albir for herbs-info.com. © herbs-info.com 2018

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