Chinese Foxglove

Scientific Name(s): Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch & C.A. Mey. Family: Scrophulariaceae

Common Name(s): Chinese foxglove , Di-Huang , Juku-Jio , Jyuku-Jio , Kan-Jiou , Sheng Di Huang , Sho-Jio , Shoudihuang , Shou-Jiou , Shu Di Huang , To-Byun , Xiandihuang , Sook-Ji-Whang (steamed root), Saeng-Ji-Whang (fresh root), Gun-Ji-Whang (dried root)

Uses

Rehmannia rhizome extracts are used extensively in traditional Chinese medicine. Clinical trials to support documented uses are lacking, and because the preparation is often used in combination with other agents, it is difficult to attribute any benefits to the plant. Catalpol, a chemical constituent of the root, is being evaluated for its potential in treating CNS diseases and its effects on aging.

Dosing

None validated by clinical data. Common prescription products range from Rehmannia root 55 to 350 mg extract in polyherbal mixtures.

Contraindications

Chronic liver disease and GI disease, including diarrhea.

Pregnancy/Lactation

Avoid use. Rehmannia has been used traditionally as an emmenagogue.

Interactions

None well documented.

Adverse Reactions

Minor and transient adverse reactions have been reported and include GI discomfort (eg, mild nausea, loose bowels, flatulence), allergy, headache, dizziness, heart palpitations, fatigue, and vertigo.

Toxicology

None well documented.

Botany

R. glutinosa is a perennial herb that grows wild in northern and northeastern China, particularly in Hunan province. It grows to a height of 0.3 to 0.6 m and has large sticky leaves and purple flowers. The seed is sown in autumn and spring; the yellow-brown to blackish brown root is harvested after the plant has flowered in the autumn. The fresh and dried roots and rhizomes have a soft texture with deep longitudinal wrinkles on the external surface and a darker central cortex. 1 , 2

History

R. glutinosa has been considered a panacea in Chinese medicine for more than 2,000 years, primarily in combination with other herbs. Dried Rehmannia rhizome is reputed to “nourish the yin” and remove heat from the blood, and is used as a tonic for the liver.

Documented historical uses include treatment of anemia, cancer, constipation, diabetes, fatigue, bacterial and fungal infections, hypertension, insomnia, tinnitus, inflammatory conditions, burns, impotence, and osteoporosis. 2 , 3

Chemistry

The major chemical constituents of the herb are polysaccharides and iridoid monoterpenes (eg, catalpol, ajugol, aucubin, rehmanniosides, monomelittoside, melittoside, verbascoside, jionosides). Two acidic polysaccharides, rehmannans SA and SB, were isolated from the dried root of R. glutinosa of Chinese origin. These polysaccharides were composed of differing molar ratios of L-arabinose, D-galactose, L-rhamnose, and D-galacturonic acid. Additional polysaccharides have been isolated. Pharmacological activity of the plant species varies depending on processing (dried or steamed) and location of cultivation (eg, Japan versus China). Other sesquiterpenoids and furans have been isolated. 2 , 4 , 5 , 6 , 7 , 8

Uses and Pharmacology

Rehmannia is most commonly used in combination with other herbs, and clinical trials providing evidence for a definitive place in therapy are lacking.

CNS effects

Catalpol is being studied for its neuroprotective effects, with potential applications in Alzheimer and Parkinson diseases, as well as in ischemia and other conditions associated with aging. 2 , 3 Clinical trials are lacking.

In in vitro studies and animal models of aging, catalpol exerts antioxidant effects on glial cell cultures, protects against beta-amyloid–induced apoptosis, increases hippocampal neuroplasticity, and upregulates gene expression of glial cell-line-derived neurotrophic factor, among other suggested mechanisms. 7 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25

Increased sleeping time in mice has been observed in phenobarbital-induced sleep as well as, antagonism of caffeine-induced excitability and antidepressant effect of chronic stress. 2 , 26

Diabetes

Decreased hyperglycemia was demonstrated in several animal studies in which diabetes had been induced. Suggested mechanisms of action for aqueous or methanol R. glutinosa extracts, oligosaccharide, catalpol, rehmannioside D, or other polysaccharide extracts include decreasing glucose-6-phosphatase and fructokinase activity, decreasing plasma C-reactive protein, increasing hepatic glycogen content and pancreatic insulin release, and decreasing insulin resistance. 2 , 3 , 27 , 28 , 29 Additionally, protective effects were documented for diabetic nephropathy and obesity in animal models, 3 , 30 , 31 while others reported no effect on plasma cholesterol or triglycerides. 28 Despite the use of R. glutinosa in traditional Chinese medicine for the treatment of diabetes, clinical trials are lacking.

Hematology

A 50% ethanolic extract of R. glutinosa inhibited decreases in fibrinolytic activity and erythrocyte deformability, decreases in erythrocyte counts, and increases in connective tissue in rodents. The extract was ineffective in reducing edema and acute or chronic inflammation. R. glutinosa prevented decreases in erythrocyte deformability in rats with endotoxin-induced disseminated intravascular coagulation. In normal rats, R. glutinosa enhanced or increased erythrocyte deformability and fibrinolytic activity. Effects on the hemopoietic system have also been described based on in vitro studies. 3 , 32 , 33

Immune system

In animal studies, R. glutinosa has exerted effects on the immune system, including T-lymphocyte activity, histamine release and tumor necrosis factor, and hemolytic plaque-forming cells. The polysaccharide extracts jionoside and acetoside have been evaluated; however, clinical trials are lacking. 2 , 3 , 34 , 35 Studies in animals have demonstrated Rehmannia Six Formula (a combination preparation in which Rehmannia is the majority herb) as a potential oral adjuvant in immunization. A large and sustained rise in immunoglobulin G response occurred with antitetanus and diphtheria toxoid. 36 , 37

Other effects

Antioxidant effects have been described in several experiments, including in auditory cells. 38 , 39 , 40

Atopic eczema

A limited number of clinical trials have been conducted using a combination of 10 herbs, including Rehmannia ( Zemaphyte ). However, findings from these trials cannot be attributed to any single plant.

Cancer

Reductions in apoptosis have been observed in vitro with steamed root extracts in UV-stimulated cells and in hepatocellular carcinoma. 41 , 42 Antitumor effects have also been described for R. glutinosa polysaccharides, as well as increases in T-lymphocyte production. 3 , 43

Gastric ulcer

A reduction in ethanol-induced gastric mucosal damage was demonstrated with an aqueous extract of the root. Inhibition of gastric acid secretion was shown in animal studies. 2 , 3

Inflammation

An anti-inflammatory effect in animal models has been shown for Radix rehmanniae but not for ethanol extracts. In a poorly described clinical study, arthritis symptoms, including reduced joint pain and swelling, improved and joint mobility increased. 2

Osteoporosis

R. glutinosa extracts may enhance bone metabolism in osteoporosis by stimulating the proliferation and activity of bone-forming osteoblasts as well as inhibiting generation and activity of bone-resorbing osteoclasts. The extract may also increase the expression of bone-related genes. In vivo studies using ovariectomy-induced osteoporotic rats showed an alleviation of decreased trabecular bone mineral density and increased cortical bone thickness and trabeculation of bone marrow spaces. 44

Renal

A protective effect of plant ethanol extracts was demonstrated in animal models of renal failure and diabetic nephropathy. 3 , 29 , 45

Wound healing

In animal models of diabetic foot ulcers, enhanced fibroblast cell viability occurred, as well as a trend toward decreased wound area and greater epithelialization. 46 , 47

Dosage

None validated by clinical data. Common nonprescription products range from Rehmannia root 55 to 350 mg extract in polyherbal mixtures.

Pregnancy/Lactation

Avoid use. Rehmannia has been used traditionally as an emmenagogue; however, no teratogenic or abortifacient effects were found in rats following administration of a 70% methanol extract. An anti-implantation effect in female mice has been recorded. 2

Interactions

None well documented. Antiplatelet action has been described based on in vitro studies 2 ; however, antagonism of the effects of aspirin on coagulation time has been reported. 3 Increased sleeping time in mice has been observed in phenobarbital-induced sleep, as well as antagonism of caffeine-induced excitability. 2

Adverse Reactions

Some ingredients in a combination preparation have been suspected to cause liver toxicity, and the Pharmacopoeia of the Republic of Korea lists liver disease as a contraindication to Rehmannia use. Minor and transient adverse reactions have been reported and include GI discomfort (eg, mild nausea, loose bowels, flatulence), allergy, headache, dizziness, heart palpitations, fatigue, and vertigo. 2 , 40

Toxicology

Information is limited. Aqueous extracts of Radix rahmanniae were not mutagenic in Salmonella assay tests; however, intraperitoneal administration of the extract at doses of 10 to 40 times human doses were mutagenic. 2 An anti-implantation effect in female mice has been recorded; no teratogenic or abortifacient effects were found in rats following administration of a 70% methanol extract. 2

Bibliography

1. Chevallier A. The Encyclopedia of Medicinal Plants . DK Publishing: New York, NY; 1996.
2. Radix Rehmanniae. In: WHO monographs on selected medicinal plants . Vol 3. Geneva, Switzerland: World Health Organization; 2007:283-295.
3. Zhang RX, Li MX, Jia ZP. Rehmannia glutinosa : review of botany, chemistry and pharmacology. J Ethnopharmacol . 2008;117(2):199-214.
4. Oshio H, Inouye H. Iridoid glycosides of Rehmannia glutinosa . Phytochemistry . 1982;21:133-138.
5. Kitagawa I, Fukuda Y, Taniyama T, Yoshikawa M. Chemical studies on crude drug processing. VII. On the constituents of Rehmanniae radix . (1): Absolute stereostructures of Rehmaglutins A, B, and D isolated from Chinese Rehmanniae radix , the dried root of Rehmannia glutinosa Libosch. Chem Pharm Bull . 1991;39:1171-1176.
6. Tomoda M, Miyamoto H, Shimizu N, Gonda R, Ohara N. Two acidic polysaccharides having reticuloendothelial system-potentiating activity from the raw root of Rehmannia glutinosa . Biol Pharm Bull . 1994;17(11):1456-1459.
7. Oshima Y, Tanaka K, Hikino H. Sesquiterpenoid from Rehmannia glutinosa roots. Phytochemistry . 1993;33:233-234.
8. Li YS, Chen ZJ, Zhu DY. A novel bis-furan derivative, two new natural furan derivatives from Rehmannia glutinosa and their bioactivity. Nat Prod Res . 2005;19(2):165-170.
9. Hu L, Sun Y, Hu J. Catalpol inhibits apoptosis in hydrogen peroxide-induced endothelium by activating the PI3K/Akt signaling pathway and modulating expression of Bcl-2 and Bax. Eur J Pharmacol . 2010;628(1-3):155-163.
10. Liu J, He QJ, Zou W, et al. Catalpol increases hippocampal neuroplasticity and up-regulates PKC and BDNF in the aged rats. Brain Res . 2006;1123(1):68-79.
11. Li Y, Bao Y, Jiang B, et al. Catalpol protects primary cultured astrocytes from in vitro ischemia-induced damage. Int J Dev Neurosci . 2008;26(3-4):309-317.
12. Liang JH, Du J, Xu LD, et al. Catalpol protects primary cultured cortical neurons induced by Abeta(1-42) through a mitochondrial-dependent caspase pathway. Neurochem Int . 2009;55(8):741-746.
13. Jiang B, Zhang H, Bi J, Zhang XL. Neuroprotective activities of catalpol on MPP+/MPTP-induced neurotoxicity. Neurol Res . 2008;30(6):639-644.
14. Wang Z, Liu Q, Zhang R, et al. Catalpol ameliorates beta amyloid-induced degeneration of cholinergic neurons by elevating brain-derived neurotrophic factors. Neuroscience . 2009;163(4):1363-1372.
15. Zhang X, Zhang A, Jiang B, Bao Y, Wang J, An L. Further pharmacological evidence of the neuroprotective effect of catalpol from Rehmannia glutinosa . Phytomedicine . 2008;15(6-7):484-490.
16. Zhang XL, An LJ, Bao YM, Wang JY, Jiang B. d-galactose administration induces memory loss and energy metabolism disturbance in mice: protective effects of catalpol. Food Chem Toxicol . 2008;46(8):2888-2894.
17. Zhang XL, Jiang B, Li ZB, Hao S, An LJ. Catalpol ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose. Pharmacol Biochem Behav . 2007;88(1):64-72.
18. Tian YY, Jiang B, An LJ, Bao YM. Neuroprotective effect of catalpol against MPP(+)-induced oxidative stress in mesencephalic neurons. Eur J Pharmacol . 2007;568(1-3):142-148.
19. Tian YY, An LJ, Jiang L, Duan YL, Chen J, Jiang B. Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures. Life Sci . 2006;80(3):193-199.
20. Xu G, Xiong Z, Yong Y, et al. Catalpol attenuates MPTP induced neuronal degeneration of nigral-striatal dopaminergic pathway in mice through elevating glial cell derived neurotrophic factor in striatum. Neuroscience . 2010;167(1):174-184.
21. Bi J, Wang XB, Chen L, et al. Catalpol protects mesencephalic neurons against MPTP induced neurotoxicity via attenuation of mitochondrial dysfunction and MAO-B activity. Toxicol In Vitro . 2008;22(8):1883-1889.
22. Yu H, Oh-Hashi K, Tanaka T, et al. Rehmannia glutinosa induces glial cell line-derived neurotrophic factor gene expression in astroglial cells via cPKC and ERK1/2 pathways independently. Pharmacol Res . 2006;54(1):39-45.
23. Bi J, Jiang B, Liu JH, Lei C, Zhang XL, An LJ. Protective effects of catalpol against H2O2-induced oxidative stress in astrocytes primary cultures. Neurosci Lett . 2008;442(3):224-227.
24. Li DO, Li Y, Liu Y, Bao YM, Hu B, An LJ. Catalpol prevents the loss of CA1 hippocampal neurons and reduces working errors in gerbils after ischemia-reperfusion injury. Toxicon . 2005;46(8):845-851.
25. Jiang B, Du J, Liu JH, Bao YM, An LJ. Catalpol attenuates the neurotoxicity-induced by beta-amyloid(1-42) in cortical neuron-glia cultures. Brain Res . 2008;1188:139-147.
26. Zhang D, Wen XS, Wang XY, Shi M, Zhao Y. Antidepressant effect of Shudihuang on mice exposed to unpredictable chronic mild stress. J Ethnopharmacol . 2009;123(1):55-60.
27. Miura T, Kako M, Ishihara E, et al. Antidiabetic effect of seishin-kanro-to in KK-Ay mice. Planta Med . 1997;63(4):320-322.
28. Waisundara VY, Huang M, Hsu A, Huang D, Tan BK. Characterization of the anti-diabetic and antioxidant effects of rehmannia glutinosa in streptozotocin-induced diabetic Wistar rats. Am J Chin Med . 2008;36(6):1083-1104.
29. Zhang R, Zhou J, Jia Z, Zhang Y, Gu G. Hypoglycemic effect of Rehmannia glutinosa oligosaccharide in hyperglycemic and alloxan-induced diabetic rats and its mechanism. J Ethnopharmacol . 2004;90(1):39-43.
30. Liu HR, Tang XY, Dai DZ, Dai Y. Ethanol extracts of Rehmannia complex (Di Huang) containing no Corni fructus improve early diabetic nephropathy by combining suppression on the ET-ROS axis with modulate hypoglycemic effect in rats. J Ethnopharmacol . 2008;118(3):466-472.
31. Jiang L, Zhang NX, Mo W, et al. Rehmannia inhibits adipocyte differentiation and adipogenesis. Biochem Biophys Res Commun . 2008;371(2):185-190.
32. Kubo M, Asano T, Shiomoto H, Matsuda H. Studies on Rehmanniae radix . I. Effect of 50% ethanolic extract from steamed and dried rehmanniae radix on hemorheology in arthritic and thrombosic rats. Biol Pharm Bull. 1994;17(9):1282-1286.
33. Kubo M, Asano T, Matsuda H, Yutani S, Honda S. Studies on Rehmanniae radix . III. The relation between changes of constituents and improvable effects on hemorheology with the processing of roots of Rehmannia glutinosa [in Japanese]. Yakugaku Zasshi . 1996;116:158-168.
34. Sasaki H, Nishimura H, Morota T, et al. Immunosuppressive principles of Rehmannia glutinosa var. hueichingensis. Planta Med . 1989;55(5):458-462.
35. Kim H, Lee E, Lee S, Shin T, Kim Y, Kim J. Effect of Rehmannia glutinosa on immediate type allergic reaction. Int J Immunopharmacol . 1998;20(4-5):231-240.
36. Underwood JR, Chivers M, Dang TT, Licciardi PV. Stimulation of tetanus toxoid-specific immune responses by a traditional Chinese herbal medicine. Vaccine . 2009;27(47):6634-6641.
37. Licciardi PV, Underwood JR. Identification of a novel vaccine adjuvant that stimulates and maintains diphtheria toxoid immunity. Vaccine . 2010;28(22):3865-3873.
38. Yu HH, Seo SJ, Kim YH, et al. Protective effect of Rehmannia glutinosa on the cisplatin-induced damage of HEI-OC1 auditory cells through scavenging free radicals. J Ethnopharmacol . 2006;107(3):383-388.
39. Yu HH, Kim YH, Jung SY, et al. Rehmannia glutinosa activates intracellular antioxidant enzyme systems in mouse auditory cells. Am J Chin Med . 2006;34(6):1083-1093.
40. Zhang W, Leonard T, Bath-Hextall F, et al. Chinese herbal medicine for atopic eczema. Cochrane Database Syst Rev . 2005;(2):CD002291.
41. Shin SW, Park CI, Yang CH, Park JW. Protective effect of Rehmannia glutinosa on the UV-induced apoptosis in U937 cells. Am J Chin Med . 2008;36(6):1159-1170.
42. Chao JC, Chiang SW, Wang CC, Tsai YH, Wu MS. Hot water-extracted Lycium barbarum and Rehmannia glutinosa inhibit proliferation and induce apoptosis of hepatocellular carcinoma cells. World J Gastroenterol . 2006;12(28):4478-4484.
43. Chen LZ, Feng XW, Zhou JH. Effects of Rehmannia glutinosa polysaccharide b on T-lymphocytes in mice bearing sarcoma 180. Zhongguo Yao Li Xue Bao . 1995;16(4):337-340.
44. Oh K, Kim S, Kim JY, et al. Effect of Rehmannia glutinosa Libosch extracts on bone metabolism. Clin Chim Acta . 2003;334(1-2):185-195.
45. Lee BC, Choi JB, Cho HJ, Kim YS. Rehmannia glutinosa ameliorates the progressive renal failure induced by 5/6 nephrectomy. J Ethnopharmacol . 2009;122(1):131-135.
46. Lau TW, Chan YW, Lau CP, et al. Radix Astragali and Radix Rehmanniae , the principal components of two antidiabetic foot ulcer herbal formulae, elicit viability-promoting effects on primary fibroblasts cultured from diabetic foot ulcer tissues. Phytother Res . 2009;23(6):809-815.
47. Lau TW, Lam FF, Lau KM, et al. Pharmacological investigation on the wound healing effects of Radix Rehmanniae in an animal model of diabetic foot ulcer. J Ethnopharmacol . 2009;123(1):155-162.

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