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Background & General Info
Polygala tenuifolia is a perennial herbaceous plant vastly distributed in the prairies, grasslands, shrub forests, and thickets of China, Mongolia, the Russian Federation, and South Korea.
Polygala tenuifolia is a 15–50-cm-tall perennial herb with a stout, fleshy principal root and branched, pubescent stems that are ridged and sulcate. The subsessile papery leaves have linear to linear-lanceolate blades and are glabrous or very sparsely puberulent. The flowers are characterized by five sepals and three purple petals that are connate in the lower third portion. The ovoid black seeds are roughly 2 mm in diameter, with two-lobed decurrent strophiole. 
History & Traditional Use
Along with other Chinese medicinal herbs, Polygala tenuifolia (yuan zhi in Chinese) possesses a long history of traditional use in China and other Asian countries. Its conventional use in traditional Chinese medicine includes treating dementia, insomnia, depression, and amnesia, and the roots from this historically used herbal plant are believed to exhibit nootropic activity.  The plant is officially listed in the Chinese Pharmacopoeia as a mucolytic in cough treatment, a sedative, and an anti-swelling agent. 
General Herbal Uses
In Chinese medicinal practice, the dried roots of Polygala tenuifolia are employed in Asia as alternative expectorant, tonic, tranquilizer, and antipsychotic agents and are recommended for amnesia, neurasthenia, anxiety-related palpitations, restlessness, nocturnal emission, disorientation, and insomnia.  Polygala tenuifolia roots, according to the Chinese Materia Medica, are believed to also specially influence the will and mental powers and enhance comprehension and memory and have been suggested to boost memory. 
Tenuifoside A, a new triterpenoid saponin, was isolated by Xu et al. (2008) from the roots of Polygala tenuifolia Willd.  Shi et al. (2012) isolated for the first time ten flavonoids from this plant, namely, isorhamnetin-3-O-β-D-glucopyranoside, isorhamnetin-3-O-β-D-galactopyranoside, quercetin-3-O-β-D-glucopyranosyl (1→2)-β-D-galactopyranoside, quercetin-3-O-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside, linarin, quercetin-3-O-β-D-glucopyranoside, 5,7-dihydroxy-8-methxoyflavone-7-O-β-D-glucuronoside, isorhamnetin, kaempferol, and quercetin. Evaluation in DPPH free radical scavenging assay indicated that quercetin-3-O-β-D-glucopyranosyl (1→2)-β-D-galactopyranoside, quercetin-3-O-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside, quercetin-3-O-β-D-glucopyranoside, isorhamnetin, and kaempferol exhibited potent antioxidant activities. 
Antidepressant activity was found for 3,6'-disinapoyl sucrose, an active oligosaccharide ester existing in the roots of Polygala tenuifolia, based on results from forced swimming test and tail suspension test. Employing a chronic unpredictable mild stress model in rats, Hu et al. (2009) associated the antidepressant effects of 3,6'-disinapoyl sucrose in chronically stressed rodents with its modulating activity on the hypothalamus–pituitary–adrenal axis. In this study, rats exposed to chronic stress for 28 days manifested decreased sensitivity to reward and abnormality in the hypothalamus–pituitary–adrenal axis, but intragastric administration of 3,6'-disinapoyl sucrose at a concentration of 10 or 20 mg/kg enhanced the reward reaction of these rats, as evidenced by their improved sucrose consumption and remarkably reduced levels of serum corticosterone, adrenocorticotropic hormone, and corticotropin-releasing hormone. Moreover, the expression of glucocorticoid receptor and mineralocorticoid receptor mRNA appeared to have been improved by 3,6'-disinapoyl sucrose.  Anxiolytic and sedative–hypnotic activities of polygalasaponins extracted from Polygala tenuifolia had also been demonstrated in mice using various tests such as hole-board, elevated plus maze, open field, and sodium pentobarbital-induced hypnosis tests. An hour following oral administration of polygalasaponins from Polygala tenuifolia at doses of 40, 80, and 160 mg/kg in mice, a significant increase in central crossing counts and percentage of central/total ambulation had been observed, with rearings and defecations having been inhibited in the open field test. 
A 2010 Chinese study published in Pharmaceutical Biology ascertained the ability of YZ-50 to reverse the injurious effects induced by chronic mild stress on mood and behaviors in rats and, more importantly, its antidepressant effect that is at least partly mediated by the neuroendocrine systems. YZ-50, which is an active fraction extracted from the roots of Polygala tenuifolia Willd., has been earlier revealed to improve mental health of depressed patients. Findings indicated that repeated 28-day administration of YZ-50 at doses of 140 and 280 mg/kg in chronic mild stress models of depression in Sprague-Dawley rats led to a reversal of injurious alterations in sucrose consumption, plasma corticosterone levels, and open field activity elicited by chronic mild stress. Additionally, YZ-50 was able to effectively hinder any decrease in levels of hippocampal brain-derived neurotrophic factor mRNA caused by chronic mild stress. 
Recently, extract from Polygala tenuifolia had been validated to display antipsychotic property and, in the study of Shin et al. (2004), to hinder cocaine-induced behavioral effects such as hyperlocomotion and conditioned place preference by activating the adenosine A2A receptor. Daily intraperitoneal injection of Polygala tenuifolia extract at a concentration of 25 mg or 50 mg/kg attenuated cocaine-induced behavioral responses, which took place in parallel with increases in fos-related antigen-immunoreactivity and activator protein-1 DNA binding activity in the nucleus accumbens. 
Tenuifoliside B is an acylated oligosaccharide that has been isolated from the roots of Polygala tenuifolia. In the study of Ikeya et al. (2004), tenuifoliside B has been demonstrated to exert cerebral protective effect against anoxia experimentally induced by potassium cyanide in mice, which has been used as an animal model for cerebrovascular disease. Furthermore, tenuifoliside B has also been shown to ameliorate scopolamine-induced performance impairment in passive avoidance task in rats and to significantly improve tremors elicited by oxotremorine in mice, suggesting enhancement of the cholinergic system. 
Aβ deposition and cognitive degeneration are among the hallmarks of Alzheimer’s disease; hence, several disease- and symptom-modifying therapeutic strategies have been developed that focus on decreasing the production of Aβ while improving cognitive function. Li et al. (2016) have shown that onjisaponin B obtained from “radix polygalae” (i.e., Polygala tenuifolia roots) inhibits the production of Aβ without directly suppressing the activities of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase and also encourages the degradation of amyloid precursor protein (APP). Its oral administration had been observed to improve Aβ pathology and behavioral defects in APP/PS1 mice and to ameliorate cognitive impairments, making it a potential new therapeutic agent for Alzheimer’s disease. 
Park et al. (2008) demonstrated the beneficial effects of extract from Polygala tenuifolia roots on the proliferation of stem cell populations in the rat hippocampus. At a dose of 2 mg/kg, intraperitoneally injected root extract of Polygala tenuifolia improved the incorporation of bromodeoxyuridine into the cells in the hippocampal CA1 region, which was enriched in the saponin-containing fraction. As has been mentioned, Polygala tenuifolia root extract had been suggested in this study to promote the proliferation of neural stem cells, as validated by majority of bromodeoxyuridine-labeled cells being immunoreactive to nestin or Tuj1 and increased percentages of nestin/bromodeoxyuridine- and Tuj1/bromodeoxyuridine-double positive cells. The root extract had additionally encouraged the neurite outgrowth of rat neuronal precursor cells, HiB5. 
Results from the study of Sun et al. (2007) suggested that Polygala tenuifolia precipitate fraction and saponin-rich fraction beneficially reversed memory impairment triggered by dysfunction of the cholinergic system in the brain, with such memory improvement in the radial maze performance test attributed to an improvement in short-term memory. To determine the effect of the aforementioned Polygala tenuifolia root fractions on the retrieval process of spatial cognition in rat models in an eight-arm radial maze task, a precipitate fraction acquired from the extract of Polygala tenuifolia roots, at concentrations of 100 mg/kg and 200 mg/kg, was orally administered in rats and, as indicated by the findings, significantly decreased the number of total errors and working memory errors. Likewise, the saponin-rich fraction markedly reduced the number of total errors and working memory errors at a dose of 100 mg/kg.  In the study of Egashira et al. (2003), the water extract from 100 mg/kg Polygala tenuifolia roots considerably enhanced scopolamine-induced impairment of passive avoidance response and improved oxotremorine-induced tremors in mice. 
Spermicidal agents are effective in barrier methods of birth control. Out of more than 300 Chinese medicinal herbs screened, Qiu et al. (2011) demonstrated the strong sperm-immobilizing activity in vitro of crude extracts from Polygala tenuifolia roots. Semen samples were collected from 42 healthy fertile men. It was found that the Polygala tenuifolia crude extract, at concentrations of 20.0 and 10.0 mg/mL, could immobilize and kill all human spermatozoa within 20 seconds in vitro; at a lower extract concentration (5.0 mg/mL), spermatozoa were immobilized in 39.5 ± 3.2 seconds. It appears the integrity of sperm membrane is disrupted and accounts for the rapid spermicidal activity of this crude extract. Furthermore, the rate of normal hypo-osmotic swelling (tails swollen) and white head (unstained) was 0%, whereas that of abnormal hypo-osmotic swelling (tails unswollen) and red head (stained) was 100%, with the sperm revival test not showing any spermatozoa that recovered their motilities.
Contraindications, Interactions, And Safety
In a 2014 animal study evaluating the preclinical safety of Polygala tenuifolia root extract in rats and beagle dogs, the root extract of Polygala tenuifolia had been concluded to be likely not toxic to the tested animals in terms of acute oral toxicity and subchronic toxicity. In the test for acute oral toxicity, there was a noted absence of treatment-related death or clinical and gross findings after extract administration, as well as toxicological changes. The subchronic toxicity test indicated no abnormal findings and adverse effects associated with Polygala tenuifolia root extract based on clinical signs, body weight, and hematological and biochemical findings. 
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 X. Li, J. Cui, Y. Yu, W. Li, et al., "Traditional Chinese nootropic medicine Radix Polygalae and its active constituent onjisaponin B reduce β-Amyloid production and improve cognitive impairments," PLOS One, vol. 11, no. 3, p. e0151147, 2016. https://www.ncbi.nlm.nih.gov/pubmed/26954017
 W. Tang and G. Eisenbrand, "Polygala tenuifolia Willd.," in Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine, Berlin, Springer-Verlag, 1992, p. 781–786. http://link.springer.com/chapter/10.1007%2F978-3-642-73739-8_99#page-1
 Y. Hu, P. Liu, D. Guo, K. Rahman, D. Wang and T. Xie, "Antidepressant effects of the extract YZ-50 from Polygala tenuifolia in chronic mild stress treated rats and its possible mechanisms," Pharmaceutical Biology, vol. 48, no. 7, p. 794–800, 2010. https://www.ncbi.nlm.nih.gov/pubmed/20645779
 Y. Ikeya, S. Takeda, M. Tunakawa, et al., "Cognitive improving and cerebral protective effects of acylated oligosaccharides in Polygala tenuifolia," Biological and Pharmaceutical Bulletin, vol. 27, no. 7, p. 1081–1085, 2004. https://www.ncbi.nlm.nih.gov/pubmed/15256744
 X.-L. Sun, H. Ito, et al., "Effect of Polygala tenuifolia root extract on scopolamine-induced impairment of rat spatial cognition in an eight-arm radial maze task," Biological and Pharmaceutical Bulletin, vol. 30, no. 9, p. 1727–1731, 2007. https://www.ncbi.nlm.nih.gov/pubmed/17827729
 T.-H. Xu, et al., "A novel triterpenoid saponin from Polygala tenuifolia Willd.," Journal of Asian Natural Products Research, vol. 10, no. 8, p. 803–806, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18696336
 T. Shi, Y. Li, Y. Jiang and P. Tu, "Isolation of flavonoids from the aerial parts of Polygala tenuifolia Willd. and their antioxidant activities," Journal of Chinese Pharmaceutical Sciences, vol. 22, no. 1, p. 36–39, 2013. http://220.127.116.11/Jwk_zgyxen/EN/abstract/abstract1205.shtml
 Y. Hu, H. Liao, P. Liu, D. Guo and K. Rahman, "A bioactive compound from Polygala tenuifolia regulates efficiency of chronic stress on hypothalamic-pituitary-adrenal axis," Pharmazie, vol. 64, no. 9, p. 605–608, 2009. https://www.ncbi.nlm.nih.gov/pubmed/19827305
 Y. Yao, M. Jia, J.-G. Wu, et al., "Anxiolytic and sedative-hypnotic activities of polygalasaponins from Polygala tenuifolia in mice," Pharmaceutical Biology, vol. 48, no. 7, p. 801–807, 2010. https://www.ncbi.nlm.nih.gov/pubmed/20645780
 E. Shin, K. Oh, K. Kim, et al., "Attenuation of cocaine-induced conditioned place preference by Polygala tenuifolia root extract," Life Sciences, vol. 75, no. 23, p. 2751–2764, 2004. https://www.ncbi.nlm.nih.gov/pubmed/15464827
 H. Park, K. Lee, H. Heo, M. Lee, et al., "Effects of Polygala tenuifolia root extract on proliferation of neural stem cells in the hippocampal CA1 region," Phytotherapy Research, vol. 22, no. 10, p. 1324–1329, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18693285
 N. Egashira, M. Yuzurihara, N. Hattori, I. Sakakibara and A. Ishige, "Ninjin-yoei-to (Ren-Shen-Yang-Rong-Tang) and Polygalae radix improves scopolamine-induced impairment of passive avoidance response in mice," International Journal of Phytotherapy and Phytopharmacology, vol. 10, no. 6–7, p. 467–473, 2003. https://www.ncbi.nlm.nih.gov/pubmed/13678229
 K. Y. Shin, B. Y. Won, H. J. Ha, et al., "Preclinical safety of the root extract of Polygala tenuifolia Willdenow in Sprague-Dawley rats and beagle dogs," Evidence-Based Complementary and Alternative Medicine, vol. 2014, p. 15, 2014. https://www.researchgate.net/publication/268879274
Article researched and created by Dan Albir for herbs-info.com. © herbs-info.com 2018
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