Herbal Research

Sheng Di Huang

RADIX REHMANNIAE (CHINESE FOXGLOVE ROOT)

Sheng Di Huang is dried root tuber of Rehamannia glutinosa Libosch. (Scrophulariaceae). The herb is collected in autumn, removed from crowns and fibrous roots and then baked to nearly dry. It is mainly produced from cultivated plant in the provinces of Henan and Zhejiang.

CHEMISTRY

The major constituents of the root of R. glutinosa are iridoid glycosides. The first iridoid glycoside isolated from fresh root was catalpol1. Further studies led to the isolation of several other iridoid glycosides: ajugol, leonuride, aucubin, melittoside, and rehmanniosides A-D2. Six ajugol esters, i.e. E-feruloylajugol, Z-feruloylajugol, q-coumaroylajugol, q-hydroxybenzoylajugol, vanilloylajugol and 4-(a-L-rhamnopyranosyloxy)-3-methoxy-benzoylajugol, were identified in the root of R. glutinosa var. purpurea and two new iridoid glycosides named jioglutoside A and jioglutoside B, as well as eight phenolic glycosides jionosides A and B, acetoside, isoacetoside, purpureaside C, echinacoside and castanosides A and F were isolated from the root of R. glutinosa var. hueichingensis3-5. Furthermore, iridoids named rehmaglutins A-D and a chlorine-containing iridoid glycoside, glutinoside were isolated6'7. Three ionone glucosides, rehmaionosides A, B, and C, and a monoterpene glucoside rehmapicroside were found in the root of R. glutinosa5. It also contains b-sitosterol and mannitol, and small amounts of campesterol9.

PHARMACOLOGY

Effects on Adrenocortical Function and Cortisol Metabolism

The herb was able to stop the decrease of plasma corticosterone concentration due to administration of dexamethasone and prevent the adrenal cortex from atrophy. The corticosterone level in rabbits receiving dexamethasone was increased at week 4 and week 6 when the herb was concurrently applied. No morphological changes were observed in the pituitary gland and adrenal cortex of rabbits receiving concurrent treatment of dexamethasone and the herb10. A single large dose (3 g/kg) of the root or together with two other herbs Zhi Mu (Rhizoma Anemarrhenae) and licorice (0.9 g/kg each) given orally antagonized the inhibitory effect of dexamethasone on the pituitary-adrenal system of rabbits, thereby increasing plasma corticosterone level. This mixture also antagonized the inhibitory action of dexamethason on the early morning cortisol secretion peak in 12 normal subjects as tested in diurnal dexamethason suppression test. The crude extract (8 mg) of the root, when incubated with the liver sections of rabbits, protected cortisol from being reduced on the double bond between C4 and C5, and the ketone at C3 and being degraded of the hydroxy groups at C17 and C21, and the ketone at C20, thus delaying the metabolism of cortisol in the liver. When the herb was used simultaneously with exogenous adrenocortical hormones, plasma cortisol could still be kept at a nearly normal level. The mechanism is believed to be a kind of competitive effect which influenced the binding of cortical hormone to the receptors and affected the uptake of corticosteroid hormone by the liver cells, thereby slowing down the catabolism of cortisol9.

Cardiovascular and Diuretic Effects

The effects of the herb on the heart were largely dependent on doses. There was no obvious cordial activity at 0.1 or 0.5% concentration. At 1% concentration, cordial effect was observed in the isolated perfused frog heart. This action was more obvious in weak heart. When concentrations were increased to 2-5%, the heart was inhibited. Its effects on blood pressure was also dose-dependent. In an experiment with perfused vessels, 1-3% of the extract caused vasoconstriction while at 5% vasodilation9.
Intravenous injection of 2.5 ml of the root extract produced a diuretic effect in anesthetized dogs. This action may be related to the cordial and renal vasodilation activities11.

Effect on Blood Glucose

Results in animal experiments have been inconsistent on the effect of the herb on blood glucose. Hypoglycemic effects of alcoholic extract of the root at a subcutaneous dose of 2 g/kg or an oral dose of 4 g/kg in rabbits were reported by early researchers. The result obtained from the subcutaneous injection was more significant; the blood sugar was decreased to the lowest level 4 h after medication. Subcutaneous administration of the alcoholic extract to rabbits also inhibited the prolonged hyperglycemic effect elicited by carbohydrates from the root of Codonopsis pilosula (Dang Shen). Intramuscular administration of 20 g of the same extract also suppressed and prevented epinephrine-induced hyperglycemia in rabbits. Other studies, however, reported that the aqueous or alcoholic extract could only reduced the blood glucose of normal rabbits and was not effective in hyperglycemia due to epinephrine. But there were also reports that the herb had no effect on the normal blood glucose level of rabbits. The decoction or the ethanolic extract at 6 g/kg had no effect on the normal blood glucose measurements of rabbits within 6 h of medication. Subcutaneous administration of 20 g/kg of the same agents also failed to antagonize epinephrine-induced hyperglycemia in rats9. More recently, a weak hypoglycemic activity of rehmannioside D in spontaneous diabetic mice was reported2.

Antiinflammatory and Immunosuppressive Effects

Formaldehyde-induced edema of rat paws subsided after oral administration of the decoction or alcoholic extract at the daily dose of 10 g/kg for 5 days. However, another report claimed that oniy the decoction and not the alcoholic extract had a significant antiinflammatory activity9. At the oral dose of 100 mg/kg, jionoside B and acetoside produced 36% and 18% suppression of hemolytic plaque forming cells in the spleens of mice. In the same test conditions, intraperitoneal dose of 30 mg/kg of cyclophosphamide had a 52.5% suppression5.

Hemostatic Effect

The coagulation time in rabbits was reduced after giving the yellow needle crystal obtained from the ethanolic extract of the root. Intraperitoneal administration of 10 g/kg of the decoction or ethanolic extract, or oral administration of the charred herb shortened the bleeding time in mice with tail wounds9.

Effect on Hemorheology

The effects of the herb on the hemorheology of inflammatory, thrombosic and intact animals were examined. Oral administration of 200 mg/kg of the 50% ethanolic extract of the herb inhibited the reduction of fibrinolytic activity and erythrocyte deformability, the decrease in erythrocyte counts and the increase in connective tissue of the thoracic artery in a chronic inflammatory model, adjuvant-induced arthritis. However, it was ineffective on the development of edema in the arthritic rats and on acute and chronic inflammation. In addition, the extract inhibited the reduction of erythrocyte deformability but not the decrease of coagulative factors in a thrombosic model, endotoxin-induced disseminated intravascular coagulation (DIC). It also exhibited a promoting effect on erythrocyte deformability and fibrinolytic activity in intact rats. These results suggest that oral administration of the extract can prevent an inducement of impediment in the peripheral microcirculation of various chronic diseases through the improvement of hemorheology12.

Other Effects

Antiradiation, antifungal and antihepatotoxic activities have also been observed with extracts of the root in animals. The 100% injection solution of the root given intraperitoneally at 1 ml daily for 6 days mitigated platelet damage in rats caused by 600 rad of c-irradiation. The aqueous extract of the root inhibited in vitro fungi mentagrophyton, Microsporum gypseum and M. audouini. The decoction of the root showed protective effect in mice against CCl4-caused liver intoxication. Oral or intraperitoneal administration of 10 g/kg of the decoction or the alcoholic extract potentiated the hypnotic effect of pentobarbital sodium. Intraperitoneal dose of 20 g/kg of the decoction or the alcoholic extract protected mice from hypobaric hypoxia9.

FUNCTIONS AND APPLICATIONS

Traditional Description

Sheng Di Huang has sweet and bitter tastes and a cold property, acting on the heart, liver and kidney channels. It has the functions of:

(i) removing heat from the blood and stopping bleeding, used in febrile diseases with deep red tongue and thirst, and bleeding due to blood heat, such as hematemesis, epistaxis, hematuria, metrorrhagia and metrostaxis; and
(ii) nourishing Yin and promoting the production of body fluid, used in febrile diseases with lingering fever, deficiency of Yin with internal heat, diabetes caused by internal heat. It is also indicated for skin eruption and maculation.

Applications9
Immunological disorders

Intermittent treatment of 12 cases of rheumatic arthritis and 11 cases of rheumatoid arthritis with the decoction of the herb produced significant effects in most patients, evidenced by abatement of joint pain, subsidence of swelling, improvement of joint movement and normalization of erythrocyte sedimentation rate. The herb also improved the general symptoms of bronchial asthma and urticaria. In a few patients, mild edema, a reaction similar to that induced by adrenocortical hormones, developed following the medication.

Infectious hepatitis

Daily intramuscular administration of 2 ampoules of the injection solution of the herb and licorice (each ampoule contained 12 g of the herb and 6 g of licorice) was given to 50 patients for 10 days. Improvement in symptoms and signs was achieved in 41 cases. Oral administration of the decoction of the mixture was also effective.

Skin disorders

Intermittent treatment of eczema and neurodermatitis with the decoction of the root by oral administration achieved optimal effects. The dosage was 90 g per day.

SIDE EFFECTS AND TOXICITY

A few patients complained of diarrhea, abdominal pain, vertigo, fatigue or palpitation after taking the herb. These side effects, however, disappeared automatically within several days. No toxic effects were observed in mice receiving a daily oral dose of 60 g/kg of the decoction for 3 days during one week of observation. At 18 glkg to rats it did not produce any significant changes in the animal's behaviour, body weight, serum nonprotein nitrogen and SGPT, or any significant lesions in the hepatic and renal tissues during 15 days of observation9.

DOSAGE

9-15-(30) g.

REFERENCES

1. Kitagawa, 1., Nishimura, T., Furubayashi, A., Yosioka, I. (1971) Constituents of rhizome of Rebmannia glutinosa f. hueichingensis. Yakugaku Zasshi, 91, 593-596.
2. Oshio, H., Inouye, H. (1981) Iridoid glycosides of Rehmannia gluconosa. Phytochemistry, 21, 133-138.
3. Nishimura, H., Sasaki, H., Morota, T., Chin, M., Mitsuhashi, H. (1989) Six iridoid glycosides from Rehmannia glutinosa. Phytochemistrv, 28, 2705-2709.
4. Morota, T., Sasaki, H., Nishimura, H., Sugama, K., Chin, M., Mitsuhashi. H. (1989) Two iridoid glycosides from Rehinannia glurinosa. Phytochemi.stry, 28, 2149-2153.
5. Sasaki, H., Nishimura, H., Morota,T., Chin. M., Mitsuhashi, H., Komatsu,Y., etal. (1989) Immunosuppressive principles of Rehmannia glutinosa var. hueichingen.sis. Planta Medico, 55, 458-461.
6. Kitagawa, I., Fukuda, Y., Taniyama, T., Yoshikawa. M. (1986) Ahsolute stereostmctures of rehmaglutins A, B, and D, three new iridoids isolated from Chinese rehmanniae radix. Chemical and Pharmaceutical Bulletin, 34, 1399-1402.
7. Yoshikawa, M., Fukud, Y., Taniyama, T., Kitagawa, 1. (1986) Ahsolute stereostructures of rehmaglutin C and glutinoside, a new iridoid glucoside from Chinese rehmanniae radix. Chemical and Pharmaceutical Bulletin, 34, 1403-1406.
8. Yoshikawa, M., Fukuda, Y., Taniyama, T., Cha, B.C., Kitagawa, I. (1986) Ahsolute configurations of rehmaionosides A, B, and C and rehmapicroside, three new ionone glucosides and a new monoterpene glucoside from Rehmanniae radix. Chemical and Pharmaceutical Bulletin, 34, 2294-2297.
9. Wang, Y.S. (1983) Pharmacology and Applications of Chinese Materia Medico, pp. 400-406. Beijing: People's Health Puhlisher.
10. Yin, 1., Guo, L.G. (1993) Modern Research and Clinical Applications of Chinese Materia Medico (1), pp. 272-279. Beijing: Academic Puhlisher.
11. Wu, B.J. (1983) Pharmacology of Chinese Herbal Medicines, pp. 222. Beijing: People's Health Puhlisher.
12. Buho, M., Asano, T., Shiomoto, H., Matsuda, H. (1994) Studies on Rehmanniae Radix. I. Effect of 50% ethanolic extract from steamed and dried Rehmanniae Radix on hemorheology in arthritic and thromhosic rats. Biological and Pharmaceutical Bulletin, 17, 1282-1286.