Scientific names: Rehmannia glutinosa.
Family: Scrophulariaceae
Alternate names:
Chinese Foxglove, Chinese Rehmanniae Radix, Chinese RR, Di Huang, Dihuang, Gun-Ji-Whang, Japanese Rehmanniae Radix, Japanese RR, Jio, Juku-Jio, Kan-Jio, R. Glutinosa, Racine de Rehmannia, Radix Rehmanniae, Rehmanniae, Rehmannia Glutinosa Oligosaccharide, Rehmannia Radac, Rehmanniae Radix, Rehmanniae Root, RR, Rhemannia Root, Rehmannia Steamed Root, RGAE, RGX, ROS, Saeng-Ji-Whang, Sheng Dihuang, Sho-Jio, Shu Di Huang, Shu Dihuang, Sook-Ji-Whang, To-Byun, Xian Dihuang.
Background
Rehmannia is a perennial plant that grows up to 30 cm tall. It is primarily cultivated in China where it is used extensively as a component in herbal decoctions of traditional Chinese medicine (TCM). The root of rehmannia, known for its sticky properties, is used in either fresh, dried, or steamed form, with each form valued for different medicinal properties (93668).
Dosage & Administration
Rehmannia roots are classified in traditional Chinese medicine (TCM) based on the way they are processed. Fresh roots are known as “Xian Dihuang,” dried roots are known as “Sheng Dihuang,” and steamed roots are known as “Shu Dihuang” (93660, 93668). The pharmacological activity of rehmannia root products varies depending on the processing method used (93667, 93668).
Adverse Effects
General: Orally, rehmannia seems to be well tolerated.
Toxicology
There is insufficient reliable information available about the presentation or treatment of overdose with rehmannia.
ANTIDIABETES DRUGS
Rating: Moderate
Be cautious with this combination.
Severity:moderate
Occurrence:possible
Level of Evidence:D
Theoretically, rehmannia might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research shows that rehmannia may have hypoglycemic effects (15061, 93668).
ANTIHYPERTENSIVE DRUGS
Rating: Moderate
Be cautious with this combination.
Severity:moderate
Occurrence:possible
Level of Evidence:D
Theoretically, rehmannia might increase the risk of hypotension when taken with antihypertensive drugs.
Animal research shows that rehmannia may have hypotensive effects. Laboratory research shows that formulations of dried and processed rehmannia root inhibit angiotensin-converting enzyme (ACE) (104272).
Herb Interactions
and Supplements with Hypoglycemic Potential
Theoretically, rehmannia might have hypoglycemic effects.
Taking rehmannia with other products with hypoglycemic potential might increase the risk of hypoglycemia. Animal research shows that rehmannia may have hypoglycemic effects (15061, 93668). See other products with hypoglycemic potential here.
AND SUPPLEMENTS WITH HYPOTENSIVE EFFECTS
Theoretically, rehmannia might have hypotensive effects.
Taking rehmannia with other products with hypotensive effects might increase the risk of hypotension. In vitro and animal research shows that rehmannia can lower blood pressure (104272).
Food Interactions
None known.
Lab Interactions
None known.
Disease Interactions
PERIOPERATIVE: Rehmannia might have hypoglycemic and hypotensive effects (15061, 93668, 104272), which might interfere with blood glucose or blood pressure control if used perioperatively. Tell patients to discontinue rehmannia at least 2 weeks before elective surgical procedures.
Mechanisms of Action
General: The applicable parts of rehmannia are the root and above ground parts. Over 70 compounds have been identified in rehmannia. These include iridoid compounds, saccharides, flavonoids, amino acids, organic acids, triterpenes such as ursolic acid and oleanolic acid, furans, monoterpenoids, and micronutrients, including chromium, manganese, and zinc (93668, 104272). Catalpol, an iridoid monosaccharide glycoside, is the primary active constituent of rehmannia root. Glycoside A, an iridoid disaccharide glycoside, is another important constituent within rehmannia root (93668).
Anti-allergy effects: Animal research shows that steamed rehmannia root extract reduces histamine levels and immediate-type allergic skin reactions (15060).
Antidiabetic effects: Rehmannia roots are thought to have hypoglycemic effects (93668). These effects may be due to stachyose and manninotriose, oligosaccharides found in rehmannia root. In animal models of diabetes, these constituents decreases blood glucose by increasing hepatic glycogen content and decreasing glucose-6-phosphatase activity (15061). In another animal model of diabetes, rehmannia inhibits weight loss, reduces fasting blood glucose, improves insulin resistance, and increases glucose uptake in insulin-resistant hepatocytes. Researchers theorize that rehmannia regulates pathways involved in diabetes pathogenesis. Rehmannia upregulates transient receptor potential vanilloid 1, which prevents early apoptosis and is implicated in adipose accumulation, energy expenditure through lipolysis, and oxidative stress induced by hyperglycemia. Rehmannia also downregulates stearoyl-CoA desaturase 1, which is implicated in insulin sensitivity, lipid metabolism, early apoptosis, and oxidative stress (112824).
Antihypertensive effects: Laboratory research shows that rehmannia root extract inhibits angiotensin-converting enzyme (ACE), which correlates with a reduction in blood pressure seen in hypertensive rats. These effects may be due to ursolic acid and oleanolic acid (104272).
Anti-inflammatory effects: In vitro research shows that steamed rehmannia root extract inhibits secretion of interleukin-1 and tumor necrosis factor-alpha, suggesting possible anti-inflammatory activity (15059).
Antitumor properties: Animal and in vitro research show that low molecular weight polysaccharides from rehmannia exhibit antitumor activity, possibly by increasing the expression of p53, a tumor suppressing protein (70702, 93668).
Bone effects: There is interest in using rehmannia for osteoporosis (93668). Animal research shows that rehmannia root extracts can increase markers of osteoblastic bone building activity and decrease markers of osteoclastic activity (15058).
Drug metabolism effects: In vitro research shows that rehmannia has the potential to inhibit CYP1A2, CYP2A6, CYP2C19, CYP2C9, CYP2D6, CYP2E1, and CYP3A4 at very high concentrations. The concentrations required for this activity make clinically significant drug-supplement interactions unlikely (93663, 93666). Additional in vitro research shows that rehmannia might induce CYP1A2 and CYP3A4; however, the concentration at which this induction occurs is unclear (93665).
Endocrine effects: Preliminary clinical evidence shows that rehmannia might improve symptoms in patients with postpartum pituitary gland necrosis, or Sheehan’s syndrome, possibly by stimulating the hypothalamic-pituitary system (70711).
Gastrointestinal effects: Animal research suggests that rehmannia has anti-ulcer effects (93668). In an animal model of ulcerative colitis, pretreatment with rehmannia improves disease-activity index and ameliorates weight loss, colonic mucosal damage, and colon shortening. Rehmannia also strengthens tight junctions between intestinal epithelial cells and increases the expression of tight junction proteins occludin-1 and ZO-1, but not claudin-1. Rehmannia inhibits the nuclear factor kappa B pathway, thereby reducing overexpression of proinflammatory cytokines interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha and increasing anti-inflammatory cytokine interleukin-10, all of which are implicated in the pathogenesis of colitis. Rehmannia also improves the quantity and diversity richness of intestinal microbiota damaged by colitis (112825).
Hematological properties: Animal research shows that rehmannia root improves the viscosity of blood, which might increase tissue perfusion and decrease the risk for cardiovascular disease (70715, 93668). The mechanism of this effect is unclear.
Immune effects: Rehmannia root may have immunomodulatory activity. Some constituents of rehmannia are believed to have immune-stimulating effects, while others are considered immunosuppressive (93668). Constituents believed to have immunosuppressive activity include jionosides A1 and B1, acetoside, isoacteoside, cistanosides A and F, echinacoside, and purpureaside C (15057, 15059).
Neurological effects: Animal and in vitro research shows that rehmannia might have neuroprotective effects (93668, 104273). In laboratory research, rehmannia increases gene expression of glial cell line-derived neurotrophic factor (GDNF), which might have benefit in dementia (70709). Additional animal research shows that rehmannia root extract reduces symptoms of depression and anxiety following ovariectomy in mice by replenishing depleted neurotransmitters, including serotonin, dopamine, gamma-aminobutyric acid (GABA), and glutamate (104273).
Pharmokinetics
Absorption: In animals, rehmannia is rapidly absorbed and reaches a peak concentration 0.75 hours after administration (112822).
Distribution: In animals, rehmannia and its metabolites are widely distributed at the highest concentrations in the stomach, large intestine, bladder, and kidney (112822).
Metabolism: In animals, rehmannia metabolism is mediated by intestinal flora into a hemiacetal hydroxyl structure containing aglycone. This structure is rapidly converted into a dialdehyde, which undergoes condensation reactions to produce 2 metabolites (112822).
Elimination: In animals, rehmannia is mostly excreted as the parent compound in urine 168 hours after ingestion. Two uncharacterized metabolites are excreted in the feces (112822).
References
15057 Sasaki H, Nishimura H, Morota T, et al. Immunosuppressive principles of Rehmannia glutinosa var. hueichingensis. Planta Med 1989;55:458-62. View abstract.
15058 Oh KO, Kim SW, et al. Effect of Rehmannia glutinosa Libosch extracts on bone metabolism. Clin Chim Acta 2003;334:185-95. View abstract.
15059 Kim HM, An CS, Jung KY, et al. Rehmannia glutinosa inhibits tumour necrosis factor-alpha and interleukin-1 secretion from mouse astrocytes. Pharmacol Res 1999;40:171-6. View abstract.
15060 Kim H, Lee E, Lee S, et al. Effect of Rehmannia glutinosa on immediate type allergic reaction. Int J Immunopharmacol 1998;20:231-40. View abstract.
15061 Zhang R, Zhou J, Jia Z, et al. Hypoglycemic effect of Rehmannia glutinosa oligosaccharide in hyperglycemic and alloxan-induced diabetic rats and its mechanism. J Ethnopharmacol 2004;90:39-43. View abstract.
70702 Wei, X. L. and Ru, X. B. [Effects of low-molecular-weight Rehmannia glutinosa polysaccharides on p53 gene expression]. Zhongguo Yao Li Xue.Bao. 1997;18(5):471-474. View abstract.
70704 Yuan, A., Liu, C., and Huang, X. [Treatment of 34 cases of chronic aplastic anemia using prepared Rehmannia polysaccharide associated with stanozolol]. Zhongguo Zhong.Xi.Yi.Jie.He.Za Zhi 1998;18(6):351-353. View abstract.
70709 Yu, H., Oh-Hashi, K., Tanaka, T., Sai, A., Inoue, M., Hirata, Y., and Kiuchi, K. Rehmannia glutinosa induces glial cell line-derived neurotrophic factor gene expression in astroglial cells via cPKC and ERK1/2 pathways independently. Pharmacol.Res 4-3-2006; View abstract.
70711 Lu, C. S. [Effects of Rehmannia glutinosa in the treatment of Sheehan’s syndrome]. Zhong Xi Yi Jie He Za Zhi 1985;5(8):476-8, 451. View abstract.
93660 Han K, Bose S, Kim YM, et al. Rehmannia glutinosa reduced waist circumferences of Korean obese women possibly through modulation of gut microbiota. Food Funct 2015;6(8):2684-92. View abstract.
93662 Qiu H, Fu P, Fan W, et al. Treatment of primary chronic glomerulonephritis with Rehmannia glutinosa acteosides in combination with angiotensin receptor blocker irbestartan: a randomized controlled trial. Phytother Res 2014;28(1):132-6. View abstract.
93665 Wu B, Liu P, Gao Y, Wang Y. Effect of water extract from traditional Chinese medicines Rehmannia glutinosa, Scrophularia ningpoensis, Asparagus cochinchinensis and Ophiopogon japonicas on contents of CYP450 and activities of CYP3A, CYP2E1 and CYP1A2 in rat. Zhongguo Zhong Yao Za Zhi 2011;36(19):2710-4. View abstract.
93668 Zhang RX, Li MX, Jia ZP. Rehmannia glutinosa: review of botany, chemistry and pharmacology. J Ethnopharmacol 2008;117(2):199-214. View abstract.
104272 Chao CH, Hsu JL, Chen MF, et al. Anti-hypertensive effects of Radix Rehmanniae and its active ingredients. Nat Prod Res. 2020;34(11):1547-1552. View abstract.
104273 Zhou XD, Shi DD, Zhang ZJ. Ameliorative effects of Radix rehmanniae extract on the anxiety- and depression-like symptoms in ovariectomized mice: A behavioral and molecular study. Phytomedicine. 2019;63:153012. View abstract.
112821 Chan KW, Kwong ASK, Tan KCB, et al. Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial. Clin J Am Soc Nephrol 2023. View abstract.
112822 Ge X, Zheng Y, He Y, et al. Pharmacokinetics, Mass Balance, Tissue Distribution, and Metabolism of [3H]Catalpol in Rats: the Main Bioactive Component of Rehmannia glutinosa for the Treatment of Ischemic Stroke. Curr Drug Metab 2023. View abstract.
112824 Liu Y, Zhu R, Liu B, et al. Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1. Front Pharmacol 2022;13:875014. View abstract.
112825 Lv H, Jia H, Cai W, Cao R, Xue C, Dong N. Rehmannia glutinosa polysaccharides attenuates colitis via reshaping gut microbiota and short-chain fatty acid production. J Sci Food Agric 2023;103(8):3926-3938. View abstract.
