Chinese Foxglove
Scientific Name(s): Rehmannia glutinosa Family: Scrophulariaceae 1
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) 1 , 2 , 3 , 4
Clinical Overview
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Uses of Chinese Foxglove
The herb has been used to treat several medical conditions primarily because it is combined with other numerous herbs rather than being available as a single herb. Its anticarcinogenic effects and activity on the immune and circulatory system, and its clinical use in diabetes and atopic dermatitis have been documented.
Chinese Foxglove Dosing
None validated by clinical data. Products are currently labeled to contain Rehmannia root extract 55 to 350 mg in polyherbal mixtures.
Contraindications
Patients with allergies or who are hypersensitive to the plant species should avoid use.
Pregnancy/Lactation
Avoid use. Clinical data regarding safety and efficacy in pregnancy and lactation are lacking.
Chinese Foxglove Interactions
None well documented.
Chinese Foxglove Adverse Reactions
In 4 clinical trials, no major changes were observed in blood, renal, and liver function tests in patients administered Zemaphyte . Minor adverse reactions were reported and included the following: dizziness, GI discomfort (mild nausea, loose bowels, flatulence), lichenoid eruption, headache, urticaria, photosensitivity, exacerbation of eczema, night diuresis, discoloration of teeth, and bilirubin and creatinine values outside normal limits.
Toxicology
None well documented.
Botany
R. glutinosa is a perennial that grows wild in northern and northeastern China, particularly in the Hunan province. It attains 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, and the root is harvested after the plant has flowered in the autumn. 5
History
R. glutinosa is a traditional Chinese medicinal herb and is considered a panacea in Chinese medicine for more than 2,000 years, primarily combined with other herbs rather than used alone. Documented historical uses include treatment of anemia, cancer, constipation, diabetes, fatigue, bacterial infections, hypertension, insomnia, tinnitus, inflammatory conditions, and osteoporosis. The herb has antifungal, cardiotonic, and diuretic activity. Skin conditions such as eczema have been treated both topically and also internally by drinking a tea containing a mixture of Chinese herbs, including R. glutinosa . In traditional Chinese medicine, the dried root of the herb is used to treat chronic conditions similar to disseminated intravascular coagulation. 1 , 2 , 3 , 4 , 6
Chemistry
The major chemical constituents of the herb are betasitosterol and mannitol. Other constituents include stigmasterol, campesterol, catalpol, rehmannin, and vitamin A. Catalpol is an iridoid glycoside, which may have neuroprotective activity in cerebral ischemia. 3 , 7 Other iridoid glycosides, rehmanniosides A-D, and unusual chlorinated iridoid lactones, rehmaglutins A-D, have been found in the root. 8 , 9
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. Rehmannan SA consisted mainly of arabino-3,6-galactan structural subunits. Additional polysaccharides have been isolated. 10 , 11 , 12
The following phenethyl alcohol glycosides with immunosuppressive effects have been isolated: jionosides A1 and B1, acetoside, isoacteoside, purpureaside C, echinacoside, cistanosides A and F. 13 Pharmacological activity of the plant species varies depending on processing (dried or steamed) and where the plant is cultivated (ie, Japan versus China). Other sesquiterpenoids have been isolated. 14 , 15 A bisfuran derivative and 2 natural furan derivatives were isolated from the dried roots of the herb. The bisfuran derivative is capable of promoting immune system activity and inhibiting blood platelet aggregation. One of the natural furan derivatives inhibits immune system activity, while the other is capable of inhibiting or promoting immune system activity. 16
Chinese Foxglove Uses and Pharmacology
Anticarcinogenic effectsAnimal data
Both 10 and 20 mg/kg intraperitoneal injections of a polysaccharide fraction of R. glutinosa (RGP-b) inhibited sarcoma-180 tumor growth in mice. Nine days after administration, RGP-b decreased the cytotoxicity of cytotoxic T-lymphocytes (CTL) caused by excessive tumor growth, and the decline in interleukin-2 production was partially improved. L3T4+ and lyt-2+ T-cell subsets caused by tumor growth were decreased after treatment with RGP-b. 17
Clinical dataNinjin Yoei To (NYT), used to treat lung cancer, is a traditional herbal Chinese medicine that contains R. glutinosa and ginseng, cinnamon bark, Japanese angelica root, astragalus root, peony root, citrus unshiu peel, polygala root, atractylodes rhizome, schisandra fruit, poria sclerotium, and glycyrrhiza. A case report documented improved tumor marker levels and symptoms in an elderly patient diagnosed with lung carcinoma and treated with NYT 15 g/day for 7 weeks. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels decreased after 7 weeks of treatment. The patient also reported improved appetite and decreased coughing. Chinese medicine scores (yin-yang and xu-shi) changed from negative to positive. 18
DiabetesAnimal data
A suggested mechanism of action for R. glutinosa oligosaccharide (ROS) on glucose metabolism involves increasing hepatic glycogen content and decreasing glucose-6-phosphatase activity. ROS may act through an interaction between insulin and glucocorticoids. 4
The antidiabetic effect of ROS was investigated in glucose-induced hyperglycemic and alloxan-induced diabetic rats. Pretreatment with intraperitoneal injections of ROS 100 mg/kg for 3 days in healthy rats caused a partial prevention of hyperglycemia ( P < 0.05) from 2 g/kg of intraperitoneal glucose injections. ROS 100 mg/kg for 15 days given by intraperitoneal injection decreased blood glucose and hepatic glucose-6-phosphatase activity, as well as increasing hepatic glycogen content in alloxan-induced diabetic rats ( P < 0.05). ROS also raised the plasma insulin level and lowered plasma corticosterone level in alloxan-induced diabetic rats. 4
In another animal study, Seishin-kanro-to (SK), a preparation containing several herbs including R. glutinosa and used in Chinese traditional medicine to treat diabetes, decreased blood glucose levels in KK-Ay mice (a noninsulin dependent diabetes mellitus model). A single SK dose of 1,700 mg/kg reduced blood glucose in KK-Ay mice from 557 to 383 mg per 100 mL 7 hours after administration ( P < 0.001). Long-term administration of SK decreased blood glucose levels compared with controls at 5 weeks. 19
Effects on immune system activityAnimal data
R. glutinosa and its phenethyl alcohol glycoside fractions suppressed the induction of hemolytic plaque-forming cells (HPFC). 13
R. glutinosa inhibits mast cell-mediated, immediate-type allergic reactions and may be beneficial in the treatment of human allergic disorders. In mouse studies, aqueous extracts of R. glutinosa steamed root (RGAE) dose-dependently inhibited various types of allergic reactions using different murine models and in vitro. Pretreatment with RGAE significantly inhibited systemic allergic reactions induced by compound 48/80, a mast cell secretagogue, reduced plasma histamine levels in response to compound 48/80, inhibited skin allergic reactions induced by anti-dinitrophenyl (DNP) IgE, and inhibited tumor necrosis factor-alpha (TNF-alpha) production in rat peritoneal mast cells (PRMC) induced by anti-DNP IgE. The experimental group received oral doses of RGAE ranging from 0.0004 to 1 mg/g 1 hour prior to inducing a systemic allergic reaction. Within 1 hour following induction of the reaction by compound 48/80, mortality was significantly reduced by 53% after pretreatment with R. glutinosa compared with 100% in saline-treated controls. Plasma histamine release in response to compound 48/80 also was significantly inhibited following pretreatment with R. glutinosa compared with controls. Passive cutaneous anaphylaxis reactions induced by anti-DNP IgE were inhibited 42%, 66%, 74%, and 87%, for R. glutinosa at doses of 0.001, 0.01, 0.1 and and 1 mg/g body weight compared with controls. Histamine release from PRMC induced by compound 48/80 and anti-DNP IgE also was significantly inhibited compared with controls. TNF-alpha production in PRMC was significantly inhibited compared with controls, and no significant cytotoxicity was observed. 20
RGAE steamed root inhibited the secretion of cytokines and may inhibit TNF-alpha by inhibiting interleukin-1 (IL-1). 2 The immunomodulation of R. glutinosa in mice indicated that the herb improved cell-mediated and nonspecific immune activity. 21
Effects on circulationAnimal data
An iridoid glycoside of R. glutinosa , catalpol, prevented the loss of hippocampal neurons in gerbils subjected to transient global cerebral ischemia. Catalpol was administered 1 mg/kg by intraperitoneal injection, exhibiting neuroprotective efficacy when used immediately after reperfusion and repeatedly at 12, 24, 48, and 72 hours. Its action was more evident at doses of 5 to 10 mg/kg. The neuroprotection of catalpol was evident during both a short (12 days) and long postischemic (35 days) observational period. 7
R. glutinosa may improve hemorheology in peripheral microcirculation in various chronic diseases. In the thoracic artery of rats with adjuvant-induced arthritis, a 50% ethanolic extract of R. glutinosa inhibited decreases in fibrinolytic activity and erythrocyte deformability, decreases in erythrocyte counts, and increases in connective tissue. 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 (DIC). In normal rats, R. glutinosa enhanced or increased erythrocyte deformability and fibrinolytic activity. 6 , 14
Rats administered an intraperitoneal injection of an herbal formula (Liu-Wei-Dihuang) containing R. glutinosa responded with a mild increase in blood flow to the kidney, liver, and spleen as measured by caudate artery pulse pressure analysis. The herbal formula also decreased blood flow to the heart, lung, stomach, gallbladder, and bladder. 22
Atopic eczemaA specific mechanism of action of Chinese foxglove has not been determined, but pharmacological actions in eczema may include: 1) inhibition of IL-4 induced CD23 (low affinity IgE receptor) expression on monocytes; 2) antioxidant activity; 3) radioprotection activity; 4) inhibition of superoxide generation by macrophages; or 5) reduction of hydrogen peroxide-induced lipid peroxidation. 1
Clinical dataFour randomized clinical trials with 159 patients examined the efficacy of Zemaphyte , a standardized mixture of 10 Chinese herbs including R. glutinosa , for treating atopic eczema. Results from primary and secondary outcome measures showed reduction in erythema and surface damage for patients administered Zemaphyte versus placebo. Patients reported improved sleep and decreased itch when administered Zemaphyte . Adverse effects were reported in all 4 trials, but none were regarded as serious. 1 , 23
Other pharmacological effectsR. glutinos a selectively inhibited 12-S-HHTrE production, a surrogate for cyclooxygenase activity. An herbal mixture containing R. glutinosa lowered receptor affinity and peripheral conversion of T 4 to T 3 in a hyperthyroid rat model. 24 , 25
Yukmi, an herbal formula of 6 plants including R. glutinos a, inhibited oxidative damage induced by paraquat in the liver of senescence accelerated mice (SAM-P/8). The extracts were administered by intravenous injection. Increased hepatic antioxidant superoxide dismutase (SOD) and catalase enzyme activity were observed in animals treated with Yukmi. Yukmi also inhibited hepatic mitochondria and cellular membrane damage induced by paraquat in treated animals. 26
R. glutinosa extracts (RGX) may enhance bone metabolism in osteoporosis by stimulating the proliferation and activity of bone-forming osteoblasts and inhibiting generation and activity of bone-resorbing osteoclasts. RGX also increased the expression of bone-related genes. In vivo studies using ovariectomy-induced osteoporotic rats show that RGX alleviated the decrease in trabecular bone mineral density, and increased cortical bone thickness and trabeculation of the bone marrow spaces. 3
Dosage
None validated by clinical data. Common over-the-counter products range from 55 to 350 mg Rehmannia root extract.
Pregnancy/Lactation
There is no clinical data regarding safety and efficacy in pregnancy and lactation.
Interactions
None well documented. R. glutinosa may help reduce the adverse effects of chemotherapy from high-dose methotrexate and vincristine. 27
Adverse Reactions
Some ingredients in Zemaphyte have been suspected to cause liver toxicity. However, in 4 clinical trials, no major changes were observed in blood, renal, and liver function tests in patients administered Zemaphyte . Minor adverse reactions were reported and included the following: dizziness, GI discomfort (mild nausea, loose bowels, flatulence), lichenoid eruption, headache, urticaria, photosensitivity, exacerbation of eczema, night diuresis, discoloration of teeth, and bilirubin and creatinine values outside normal limits. 23
Toxicology
None well documented.
Bibliography
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12. Tomoda M, Miyamoto H, Shimizu N. Structural features and anti-complementary activity of rehmannan SA, a polysaccharide from the root of Rehmannia glutinosa . Chem Pharm Bull (Tokyo). 1994;42:1666-1668.
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14. 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.
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16. 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;19:165-170.
17. 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;16:337-340.
18. Kamei T, Kumano H, Iwata K, Nariai Y, Matsumoto T. The effect of a traditional Chinese prescription for a case of lung carcinoma. J Altern Complement Med . 2000;6:557-559.
19. Miura T, Kako M, Ishihara E, et al. Antidiabetic effect of seishin-kanro-to in KK-Ay mice. Planta Med . 1997;63:320-322.
20. 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;20:231-240.
21. Luo Z. The use of Chinese traditional medicines to improve impaired immune functions in scald mice [in Chinese]. Zhonghua Zheng Xing Shao Shang Wai Ke Za Zhi . 1993;9:56-58, 80.
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24. Prieto JM, Recio MC, Giner RM, Manez S, Giner-Larza EM, Rios JL. Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions. J Pharm Pharmacol . 2003;55:1275-1282.
25. Shan JC. Determination of hepatocyte adrenergic alpha 1 receptor and study on actions of nourishing yin and replenishing qi drugs in experimental hyperthyroid rats [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi . 1994;14:69-70, 96-98.
26. Kim JS, Na CS, Pak SC, Kim YG. Effects of yukmi, an herbal formula, on the liver of senescence accelerated mice (SAM) exposed to oxidative stress. Am J Chin Med . 2000;28:343-350.
27. Liu JQ, Wu DW. 32 cases of postoperative osteogenic sarcoma treated by chemotherapy combined with Chinese medicinal herbs [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi . 1993;13:132, 150-152.
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