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Rehmannia

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Background & General Info

Rehmannia glutinosa is considered among the earliest recognized edible crude herbs used medicinally in East Asia and can be categorized into two types based on processing method, namely, Gun-Ji-Whang, which is the unprocessed dried root, and Sook-Ji-Whang, which on the other hand is the processed steamed root. [1] Belonging to the Scrophulariaceae family, it is a commonly prescribed traditional Chinese herb with a very high medicinal value. [2]



Botany

Rehmannia glutinosa is a hardy herbaceous perennial plant whose entire length is covered with long soft hairs and can achieve heights of around 25 to 40 cm. It has a thick, fleshy, tuberous rhizome that is either cylindrical or spindle-shaped and thrives in well-drained sandy and loamy soils along roadsides, mountain slopes, woods, and trails. [3]

History & Traditional Use

Rehmannia glutinosa possesses a long history of efficacious and safe use in traditional folk medicine, especially in East Asia, and several chemical and pharmacological studies concerning this herb have been published in the recent decades. [2] In Chinese herbal medicine, Rehmannia glutinosa is an extensively used traditional treatment of diabetes and its complications. [4] Earliest records on the medicinal use of dried roots of Rehmannia glutinosa date back to nearly 200 BC–AD 100, while the cured roots had been documented since AD 1061. [3] Its dried roots are valued as a kidney-tonifying herbal medicine and used as remedies of joint diseases. [1]

General Herbal Uses

The dried or steamed roots of Rehmannia glutinosa are medicinally employed to reduce fever, activate blood circulation, and tonify the kidney. According to traditional Chinese medicine, they can also be recommended for Yin deficiency syndrome and be used in various therapeutic applications. Studies have indicated that the roots of Rehmannia glutinosa exert antitumor, anti-stress, anti-thrombic, and hypoglycemic effects. [1] Rehmannia glutinosa and its active principles have been scientifically confirmed to possess a wide array of pharmacological actions on the circulatory, immune, endocrine, cardiovascular, and nervous systems. [2]

The roots of cultivated Rehmannia glutinosa can be consumed fresh, raw or dried, and cured or cooked and are termed xian dihuang, sheng dihuang, and shu dihuang, respectively, in Chinese medicine. The dried and cured roots seem to taste rather sweet. [3] The former is considered “cold,” can lower the body’s heat, and can be employed for diseases characterized by “hot” symptoms, including fever, deep-red tongue, fidgets, and thirst, whereas the latter is “slightly warming,” making it an excellent tonic that can replenish the blood and reinforce the body’s essence and marrow. [5] According to Chinese medicine, both are capable of nourishing the Yin. [3]



Constituents/Active Components

To date, over 70 compounds have been detected in Rehmannia glutinosa, including iridoids, saccharides, amino acid, inorganic ions, and other trace elements. [2] 5-Hydroxymethyl-pyrrole-2-carbaldehyde, tyrosol, and isomartynoside had been isolated by Li et al. (2011) from Rehmannia glutinosa for the first time through chromatographic methods, as well as 5-hydroxymethyl furfural, 5,6-dihydroxy-beta-ionone, 6-O-E-feruloyl ajugol, acteoside, leucosceptoside A, martynoside, purpureaside C, jionoside A1, and jionoside B1. [6] As analyzed by gas chromatography–mass spectrometry (GC–MS), a total of 46 components were identified in Rehmannia glutinosa essential oil, including methyl palmitate, ethyl oleate, furfural, and methyl linoleate. [7]

Medicinal/Scientific Research

Antidiabetic

Zhang et al. (2004) demonstrated the hypoglycemic and antidiabetic property of an oligosaccharide from Rehmannia glutinosa in glucose-induced hyperglycemic and alloxan-induced diabetic rats. Intraperitoneal injection of Rehmannia glutinosa oligosaccharide during pretreatment in normal rats at a dose of 100 mg/kg for 3 days prevented hyperglycemia caused by intraperitoneally injected 2 g/kg glucose. Similarly, this oligosaccharide at the same dose for 15 days significantly reduced the level of blood glucose level and activity of hepatic glucose-6-phosphatase in alloxan-induced diabetic rats, along with an increase in hepatic glycogen content. In addition, the Rehmannia glutinosa oligosaccharide increased the level of plasma insulin but reduced the plasma corticosterone level in alloxan-induced diabetic rats. The oligosaccharide’s adrenal-dependent regulatory mechanism on glucose metabolism appears to be closely associated with the neuroendocrine system. [8]

The intraperitoneally administered polysaccharide fraction of Rehmannia glutinosa has likewise been put forward to display hypoglycemic effect. In the study of Zhou et al. (2015), orally administered Rehmannia glutinosa polysaccharide fraction was found to effectively ameliorate hyperglycemia, hyperlipidemia, vascular inflammation, and oxidative stress in streptozotocin-induced diabetic mice. The polysaccharide fraction, comprising rhamnose, arabinose, mannose, glucose, and galactose, was orally administered daily to mice at doses of 20, 40, and 80 mg/kg for 4 weeks. This treatment resulted in a significant reduction in blood levels of glucose, total cholesterol, triglycerides, and low-density lipoprotein-cholesterol and an elevation in blood levels of high-density lipoprotein-cholesterol and insulin in diabetic mice, along with increases in body weights and pancreatic insulin contents. Furthermore, it considerably improved both basal and glucose-stimulated insulin secretions and islet insulin contents in the pancreatic islets of diabetic mice and reversed the increase in mRNA expression of PEPCK and the decrease in glycogen contents in the liver of diabetic mice. Not only did the Rehmannia glutinosa polysaccharide fraction display antidiabetic effect, but also it exhibited potent anti-inflammatory and anti-oxidative activities, as supported by the observed reduction in blood levels of TNF-α, IL-6, monocyte chemoattractant protein-1, and MDA and an elevation in blood levels of SOD and GPx activities in diabetic mice. [4]

Antidepressant

The steamed roots of Rehmannia glutinosa, termed Shu dihuang in traditional Chinese medicine, had been evidenced in the study of Zhang et al. (2009) to exert an antidepressant effect in mice exposed to unpredictable chronic mild stress and thus to be potentially therapeutically helpful as treatment for depression-like disorders. Findings from the study pointed out that steamed roots of Rehmannia glutinosa administered at low dose (2.5 g/kg body weight) restored the locomotion reduced by unpredictable chronic mild stress and dose-dependently ameliorated alterations caused by unpredictable chronic mild stress such as aggravated gastric ulceration, increased levels of liver malondialdehyde, and decreased total antioxidant capability, glutathione content, and superoxide dismutase and catalase activities. [9]

Anticancer

Chao et al. (2006) had demonstrated that hot water-extracted Rehmannia glutinosa at a dose of 2–5 g/L inhibits cell proliferation, as measured by a colorimetric method, and induces p53-mediated apoptosis in rat and/or human hepatocellular carcinoma cells. Specifically, after 6–24 hours, crude Rehmannia glutinosa dose-dependently prevented rat H-4-II-E cells from proliferating by 11% (p < 0.05) to 85% (p < 0.01) and, after 24 hours, human HA22T/VGH cells by 14–43% (p < 0.01). Additionally, H-4-II-E cells underwent significantly increased apoptosis after 24 hours of treatment using higher doses of crude Rehmannia glutinosa (5–10 g/L) (p < 0.01). [10]

Antioxidant

Study results of Guo, Nam, and Kim (2016) verified the antioxidant activities of Rehmannia glutinosa ethanol extract on metal-chelating, reducing power, and total antioxidant activity assays. In terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, the antioxidant activity reached IC50 values of 469.87 ± 12.42 μg/g. [11] In the study of Chun-Ping et al. (2015), the essential oil from the roots of Rehmannia glutinosa obtained through steam distillation after ultrasound method exhibited higher antioxidant properties than Rehmannia glutinosa essential oil without ultrasound-assisted isolation. Antioxidant activity of the essential oil samples was examined through hydroxyl radical scavenging activity assay and DPPH radical scavenging activity assay. [7]

Anti-osteoporotic

Extracts from Rehmannia glutinosa have been demonstrated in a 2003 study to stimulate the proliferation and activities of osteoblasts while concurrently suppressing the generation and resorptive activities of osteoclasts. In in vivo studies, the extracts also prevented osteoporotic bone loss induced by ovariectomy in osteoporotic rats, as evidenced by reduced trabecular bone mineral density and increased cortical bone thickness and trabeculation of the bone marrow spaces. A significant increase in both proliferation and alkaline phosphatase activity of osteoblasts and an increased expression of bone-related genes resulted from Rehmannia glutinosa extract treatment. Additionally, the Rehmannia glutinosa extract treatment considerably augmented the secretion of osteoprotegerin and lowered the number of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells and resorption areas. [12]

Lim et al. (2013) similarly revealed the ability of extracts from standardized dried roots of Rehmannia glutinosa to avert ovariectomy-induced bone loss without adversely affecting hormones such as estrogen in rat models of osteoporosis. Treatment included for 8-week oral administration of the dried root extracts at doses of 30, 100, and 300 mg/kg two times a day. At a dose of 300 mg/kg, this Rehmannia glutinosa treatment significantly warded off any decrease in bone mineral density in the femur and lumbar (17.5% and 16.4%, p < 0.05, respectively) due to ovariectomy without influencing the body, organs, and uterus weights. In the treated rats, the level of serum alkaline phosphatase was notably lowered, but the estradiol level did not change. [1]

Hepatoprotective

In a 2012 study published in Journal of Natural Products, iridoid glycosides from the air-dried roots of Rehmannia glutinosa at a concentration of 10 μM have been found to display moderate hepatoprotective activities against HL-7702 cell damage elicited by D-galactosamine in in vitro assays. [13]

Contraindications, Interactions, and Safety

Toxicology studies indicate a relative safety of the use of the herb, with the decoction and alcoholic extract orally administered to mice at a dose of 60 g/kg for 3 days having been observed to produce zero mortality and absence of adverse events. [3]

References:

[1] D. Lim and Y. Kim, "Dried root of Rehmannia glutinosa prevents bone loss in ovariectomized rats," Molecules, vol. 18, no. 5, p. 5804–5813, 2013. https://www.ncbi.nlm.nih.gov/pubmed/23685937

[2] R. Zhang, M. Li and Z. Jia, "Rehmannia glutinosa: review of botany, chemistry and pharmacology," Journal of Ethnopharmacology, vol. 117, no. 2, p. 199–214, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18407446

[3] I. A. Khan and E. A. Abourashed, "Rehmannia," in Leung's Encyclopedia of Common Natural Ingredients: Used in Food, Drugs and Cosmetics, 3rd ed., Hoboken, New Jersey: John Wiley & Sons, Inc., 2009, p. 195–198. http://naturalingredient.org/wp/wp-content/uploads/leungs-encyclopedia-of-common-natural-ingredients-3rd-edition.pdf

[4] J. Zhou, G. Xu, J. Yan, et al., "Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice," Journal of Ethnopharmacology, vol. 164, p. 229–238, 2015. https://www.ncbi.nlm.nih.gov/pubmed/25698243

[5] Q. Liang, J. Ma, Z. Ma, et al., "Chemical comparison of dried rehmannia root and prepared rehmannia root by UPLC-TOF MS and HPLC-ELSD with multivariate statistical analysis," Acta Pharmaceutica Sinica B, vol. 3, no. 1, p. 55–64, 2013. https://www.researchgate.net/publication/257742126

[6] X. Li, M. Zhou, P. Shen, J. Zhang, C. Chu, Z. Ge and J. Yan, "Chemical constituents from Rehmannia glutinosa," Zhongguo Zhong Yao Za Zhi, vol. 36, no. 22, p. 3125–3129, 2011. https://www.ncbi.nlm.nih.gov/pubmed/26790295

[7] X. Chun-Ping, L. Yuanshang, Z. Shanshan, Z. Ying and L. Shaohua, "Chemical composition and in vitro antioxidant activity of the essential oil of Rehmannia glutinosa Libosch using ultrasound as a pretreatment," Journal of Biologically Active Products from Nature, vol. 5, no. 4, p. 276–282, 2015. https://www.researchgate.net/publication/284224342

[8] R. Zhang, J. Zhou, Z. Jia, Y. Zhang and G. Gu, "Hypoglycemic effect of Rehmannia glutinosa oligosaccharide in hyperglycemic and alloxan-induced diabetic rats and its mechanism," Journal of Ethnopharmacology, vol. 90, no. 1, p. 39–43, 2004. https://www.ncbi.nlm.nih.gov/pubmed/14698506

[9] D. Zhang, X. Wen, X. Wang, M. Shi and Y. Zhao, "Antidepressant effect of Shudihuang on mice exposed to unpredictable chronic mild stress," Journal of Ethnopharmacology, vol. 123, no. 1, p. 55–60, 2009. https://www.ncbi.nlm.nih.gov/pubmed/19429340

[10] J. C.-J. Chao, S.-W. Chiang, C.-C. Wang, Y.-H. Tsai and M.-S. Wu, "Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells," World Journal of Gastroenterology, vol. 12, no. 28, p. 4478–4484, 2006. https://www.ncbi.nlm.nih.gov/pubmed/16874858

[11] H. Guo, S.-H. Nam and H.-Y. Kim, "A study on the free radical scavenging activity of the Rehmannia glutinosa extracts," Indian Journal of Science and Technology, vol. 9, no. 14, 2016. https://www.researchgate.net/publication/303127589

[12] K. Oh, S. Kim, J. Kim, et al., "Effect of Rehmannia glutinosa Libosch extracts on bone metabolism," Clinica Chimica Acta, vol. 334, no. 1–2, p. 185–195, 2003. https://www.ncbi.nlm.nih.gov/pubmed/12867291

[13] Y.-F. Liu, D. Liang, H. Luo, et al., "Hepatoprotective iridoid glycosides from the roots of Rehmannia glutinosa," Journal of Natural Products, vol. 75, no. 9, p. 1625–1631, 2012. https://www.ncbi.nlm.nih.gov/pubmed/22916954

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

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