Herbal Research

Zhi Zi

FRUCTUS GARDENIAE (CAPE JASMINE FRUIT)

Zhi Zi is the dried ripe fruit of Gardenia jasmino ides Ellis (Rubiaceae). The herb is mainly produced in the provinces of Hunan, Jiangxi, Fujian, Zhejiang, Sichuan and Hubei. It is collected from September to November when the fruit becomes reddish yellow. It is then removed from pedicels and steamed thoroughly or blanched briefly in boiling water before being dried.

CHEMISTRY

The fruit contains a number of iridoid glycosides, including gardenoside, geniposide (genipin-1-glucoside), genipin gentiobioside, gardoside, scandoside methyl ester and shanzhisidelA. It also yields pigment crocetin and its glycoside crocin5. In addition, two lipoxygenase inhibitors were isolated and structurally determined as 3,4-dicaffeoyl-5-(3-hydroxy-3-methylglutaroyl) quinic acid and 3-caffeoyl-4-sinapoylquinic acid6'7.

PHARMACOLOGY

Effects on Digestive System
On liver functions

The hepatotoxicity of a-naphthylisothiocyanate, increasing serum bilirubin, glutamic pyruvic transaminase and glutamic oxalacetic transaminase activities in rats, was significantly decreased by oral administration of geniposide. Histopathological observations of the liver gave good agreement with the serological data. However, geniposide appeared unable to reduce the toxic effect of a large dose of CCl4 or D-galactosamlne8.

On bile secretion, excretion and metabolism

The bile secretion in rats and rabbits was increased by administration of the ethanolic extract of the fruit, crocin, crocetin or gempin, and plasma bilirubin level decreased by gardenoside. Genipin increased rat bile secretion given either orally, intravenously or intraduodenally at a dose of 25 mg/kg. The most prominent effect was achieved via duodenum, whereby the activity obtained was close to that of sodium dehydrocholate. Cholecystography performed in man after oral administration of the decoction of the fruit revealed significant gallbladder contraction, indicating a cholagogic effect. Sodium crocin and sodium crocetin as well as the aqueous and ethanolic extracts of the fruit were shown to decrease the serum bilirubin in rabbits with ligated common bile duct. Apparently, the herb promoted the metabolism of bilirubin5.

On gastric secretion and motiliiy

Intraduodenal administration of 25 mg/kg of genipin to rats with ligated pylorus decreased the gastric secretion and total acidity and increased the pH value; its strength was 1/10-1/5 that of atropine sulphate. Intravenous injection of 100 mg/kg of geniposide or 25 mg/ kg of genipin to rats inhibited spontaneous gastric peristalsis and pilocarpine-induced gastric contraction; but the effects were short-lived5.

Effect on the CNS

The ethanolic extract of the fruit, when given intraperitoneally, decreased spontaneous activity of mice. It also synergises with hexobarbital in prolonging sleep by almost 12 times. However, the extract could not antagonize amphetamine-induced activity and convulsion induced by pentylenetetrazole, strychnine nitrate and electric shock.
Body temperature of mice dropped by a mean of 30C one hour after intraperitoneal administration of the ethanolic extract; in rats after intraperitoneal dose of 200 mg/kg, the effect was sustained for more than 7 h5.

Hypotensive Effect

A hypotensive effect was exhibited by the decoction and ethanolic extract of the fruit in anesthetized and non-anesthetized cats, rabbits and rats whether administered orally, intraperitoneally or intravenously. The intravenous route produced a rapid but transient effect. The fruit was devoid of any influence on the pressor effect of epinephrine and the pressor reflex of blocked carotid arterial blood flow, and had no potentiating effect on the hypotensive action of acetyleholine. The hypotensive action was not affected by administration of antihistaminic drugs such as diphenhydramine; hence, it was not related to histamine release. Likewise, intravenous injection of procaine failed to alter the hypotensive effect of this herb, indicating no involvement of the afferent nerves. However, its hypotensive action was greatly attenuated or completely abolished by bilateral vagotomy. Atropine also cancelled its effect. Thus, the site of action is inferred to be in the CNS and the hypotensive effect is attributed to increased excitability of the medullary parasympathetic centers5.

Antimicrobial Activity

In the well diffusion method, the fruit showed inhibition against Staphylococcus aureus, Diplococcus meningitidis and Neisseria catarrhalis. It also inhibited some skin fungi in vitro5.

FUNCTIONS AND APPLICATIONS

Traditional Description

Zhi Zi has a bitter taste and a cold property, acting on the heart, lung and three-jiao channels. It has the functions of:

(i) reducing fire and easing the mind, thus used for febrile diseases with restlessness;
(ii) eliminating damp-heat, used for jaundice with dark urine, hematuria with difficult painful urination; and
(iii) removing heat from blood and counteracting toxicity, used for hemoptysis and epistaxis caused by heat
in the blood.

Applications
Acute icteric hepatitis

The decoction of the herb was used in treating 19 acute icteric hepatitis patients, of whom 7 were cured, 10 nearly cured and the average duration of hospitalization was 30.3 days. The herb has also been used in the treatment of acute bacterial cystitis and infections of skin and mucous membrane, sprain and contusion.

Sprain and contusion

A dressing of the powdered herb and alcohol employed in 104 cases of sprain of the extremities improved local blood stasis, swelling and pain. These symptoms disappeared in 30 h and limb functions recovered in an average of 5.1 days.

Hemostasis

The sterilized powders of the herb can be used as a hemostatic agent for upper gastrointestinal tract bleeding and also in local bleeding at oral doses of 3-6 g, trice daily.

DOSAGE

6-9g.

SIDE EFFECTS AND TOXICITY

The acute subcutaneous LD50 of the aqueous extract of the fruit was 31.79 g/kg in mice. Another report claimed that geniposide and the aqueous extract had a very low toxicity; no death occurred in animals after administration of 3 g/kg of geniposide orally, intraperitoneally or intravenously, and after intraperitoneal injection of 5 g/kg of the aqueous extract. The LD50 values of a single dose of genipin were 237 mg/kg by oral administration, 190 mg/kg by intraperitoneal administration and 158 mg/kg by intravenous administration, respectively. The subcutaneous lethal dose of crocin and sodium crocetin in mice were 15 g/kg and 5 g/kg, respectively5.

REFERENCES

1. Lnouye, H., Saito, S., Taguchi, H., Endo, T. (1969) Zwei neue iridoidgiucoside aus Gardenia jasminaides: gardenoside and geniposide. Tetrahedron Letters, 2347-2350.
2. Endo, T., Taguchi, H. (1970) New iridoid glycoside from Gardenia jasminoides: genipin l-13-gentiobioside. Chemical and Pharmaceutical Bulletin, 18, 1066-1067.
3. Inouye, H., Takeda, Y., Nishimura, H. (1974) Monoterpene glucosides and related natural products. XXVI. Two new iridoid glucosides from Gardenia jasminoides fruits. Phytachemistry, 13, 2219-2224.
4. Inouye, H., Saito, S., Shingu, T. (1970) Fin weiteres neues iridoidglucoside aus Gardenia jasminoides: shanahiside. Tetrahedron Letters, 3581-3584.
5. Wang, Y.S. (1983) Pharmacology and Applications of Chinese Materia Medico, pp. 933-937. Beijing: People's Health Publisher.
6. Nishizawa, M., Fujimoto, Y. (1986) Isolation and structural elucidation of a new lipoxygenase inhibitor from gardeniae fructus. Chemical and Pharmaceutical Bulletin, 34, 1419-1421.
7. Nishizawa, M., Izuhara, R., Kaneko, K., Fujimoto, Y. (1987) 3-Caffeoyl-4-sinapoylquinic acid, a novel lipoxygenase inhibitor from Gardenia fructus. Chemical and Pharmaceutical Bulletin, 35, 2133-2135.
8. Chang, H.M., Cheng, Y.Y., Chan, Y.S., Choang, K.F. (1985) Active component from a Chinese composite prescription for the treatment of liver diseases. In Advances in Chinese Medicinal Materials Research, edited by H.M. Chang, H.W. Yeung, W.W. Tso, A. Koo, pp. 221-137. Singapore: World Scientific.