Herbal Research

Chen Pi

PERICARPIUM CITRI RETICULATAE (TANGERINE PEEL)

Chen Pi is the dried pericarp of the ripe fruit of Citrus reticulata Blanco and its cultivated varieties (Rutaceae). The herb is peeled off from the ripe fruit and dried in the sun or at a lower temperature. It is mainly produced in the provinces of Sichuan, Zhejiang and Fujian.

CHEMISTRY

The herb contains 1.52% of essential oil, with d-limonene and citrol as the major constituents of the oil1. Other monoterpenes of the oil include a-pinene, b-pinene, camphene, myrcene, 3-carene, a-phellandrene, b-phellandrene, a-terpinene, b-terpinene, and aromatic hydrocarbon q-cymene2. Two ketones cis- and trans-4,7-dimethyl-bicyclo[3 .2.1 ]oct-3-en-6-one were also found in the oil3.
The herb also contains flavones hesperidine, neohesperidin, tangeretin, nobiletin, citroniitin, 5-O-demethyl citromitin1, 5-demethylnobiletin, and 5,7,8,4'-tetramethoxyflavone4'5.

About 7-10% of hesperidin was detected in different variants of C. reticulata6'7. Besides, alkaloids synephrine and N-methyltyramine were isolated from the herb8'9.

PHARMACOLOGY

Effects on Gastrointestinal Smooth Muscles

The decoction of the herb inhibited the movement of isolated small intestine of mice and rabbits. Intravenous injection was also inhibitory on the movement of the stomach and the intestines of anesthetized dogs, the small intestine of anesthetized rabbits and the stomach of conscious rabbits.
In experiments with isolated intestines of rabbits, the herb produced antagonistic activity against acetyicholine. On the other hand, its inhibition on isolated rabbit intestine could be antagonized by acetyicholine. It also antagonized the spasmodic contraction of intestines induced by pilocarpine or barium chloride1.

Antiulcerative Effect

Intragastric administration of 100 and 150 mg/kg of hesperidine to rats showed a marked capacity to reduce the ulcer index in cold-restraint induced ulcer in a clear dose-related manner. The amount of gastric mucus and total protein were not modified, but there was a significant increase in hexosamine content. When the acute ulcer was induced by absolute ethanol hesperidine was inactive. These results suggest that mucus is not involved in the antiulcer activity10.

Expectorant and Anticough Effects

The essential oil of the herb has irritant expectorant effect and limonene is the major active principle. The ethanolic extract (0.02 g/ml of crude drug) completely inhibited histamine-induced spasmodic contraction of isolated bronchus of guinea pigs. Nobiletin showed bronchus dilation activity on isolated tracheas of guinea pigs and in anesthetized cats when given intravenously, but oral or intramuscular administration did not antagonize the bronchus spasm induced by histamine1.

Antiinflammatory and Antiallergic Effects

Intraperitoneal administration of 175-250 mg/kg of hesperidin antagonized the vascular permeability-increasing effect of snake venom or lysolecithin in mice. Intraperitoneal dose of 10 mg/kg of hesperidin also inhibited increased permeability caused by histamine in mice. Hesperidin inhibited croton oil-induced granuloma in rats, significantly reducing intracapsular exudates.
Nobiletin at concentrations of 5 x 1O-5 to 1 x l0-4 M significantly inhibited the allergic contraction of isolated ileum and bronchus of guinea pigs due to egg white1.

Cardiovascular Effects

The decoction or ethanolic extract of the herb, or hesperidin produced stimulant action on frog heart, both in situ and isolated. Intravenous administration of hesperidin strengthened contraction of rabbit heart in situ and increased cardiac output. The decoction also dilated the coronary artery as tested in isolated perfused rabbit hearts.
The ethanolic extract of the herb showed a slight contracting effect on vessels as tested in perfused frogs. The blood pressure increased rapidly after intravenous administration of the decoction or the ethanolic extract to anesthetized dogs or rabbits. Repeated dosage produced no tolerance. Intravenous dose of 10-22 mg/kg of nobiletin also resulted in increase of blood pressure in anesthetized cats. Oral administration of the decoction or nobiletin, however, did not increase blood pressure even at higher doses1.
Continuous intravenous infusion of 4 mg/mm synephrine into healthy volunteers significantly increased the systolic and mean arterial blood pressure, but did not affect the diastolic pressure and heart rate. The cardiac index increased and the peripheral vascular resistance decreased significantly11.
In mice and rats, synephrine increased plasma and myocardial cGMP levels, whereas N-methyltyramine increased plasma and myocardial cGMP as well as cAMP levels'2. Increase of cGMP in plasma and myocardium after administration of N-methyltyramine was also observed in rabbits13. Injection of N-methyltyramine increased renal and cerebral vascular resistance in dogs, resulting from a-receptor stimulation14.

Effect on the Uterus

The decoction of the herb showed inhibition effect on isolated uterus of mice, and at higher concentrations caused a complete relaxation. Intravenous injection, however, caused tetanic contraction of the in situ uterus of anesthetized rabbits, which returned to normal in 15 mm1.

FUNCTIONS AND APPLICATIONS

Chen Pi has pungent and bitter tastes and a warm property, acting on the spleen and lung channels. It has the following functions:

(i) regulating the flow of Qi and invigorating the spleen functions, used in distension and fullness sensation in the chest and epigastrium with anorexia, vomiting and diarrhea; and
(ii) eliminating damp and resolving phlegm, used in cough with copious phlegm.

DOSAGE

3-9g.

SIDE EFFECTS AND TOXICITY

No acute toxicity was observed in animals for the decoction given orally or intravenously. The oral LD50 of nobiletin was 780±9 mg/kg1.

REFERENCES

1. Wang, Y.S. (1983) Pharmacology and Applications of Chinese Mate na Medica, pp. 567-575, Beijing: People's Health Publisher.
2. Ashoor, S.H.M., Bernhard, R.A. (1967) Isolation and characterization of terpenes from Citrus reticulata Blanco and their comparative distribution among other Citrus species. Journal of Agricultural and Food Chemistry, 15, 1044-1047.
3. Koepsel, M., Surhurg, H. (1988) Two new naturally occurring ketones from the essential oil of orange peel. Flavour and Flagrance Journal, 3, 135-136.
4. linuma, M., Matsura, S., Kurogochi, K., Tanaka, T. (1980) Studies on the constituents of useful plants.V. Multisubstituted flavones in the fruit peel of Citrus reticulata and their examination by gas-liquid chromatography. Chemical and Pharmaceutical Bulletin, 28, 717-722.
5. Lu, ST., Wo, T.S., Chang, SI. (1977) Studies on the constituents of the peels of Citrus reticulata Blanco. Journal of Taiwan Pharmaceutical Association, 29, 1-6.
6. Huang, HY., He, ZY. (1982) Assay of hesperidin in Chen Pi (peels of some Chinese citrus fruit). Chinese Traditional and Herbal Drugs, 13, 21-24.
7. Xu, LX., Liu, AR. (1983) Analysis of active principles in Chinese herbal drugs. VII. Determination of hersperidin in Citrus reticulata Blanco. Chinese Journal of Pharmaceutical Analysis, 3, 203-206.
8. Chen, F.Q., Hou, L. (1984) Determination of synephrine in citrus plants. Chinese Journal of Pharmaceutical Analysis, 4, 169-171.
9. Fang, X.D., Qian, L.J., She, B.Z., Shi. ZY. (1985) Chemical constituents in the fruits of Citrus reticulata Blanco. Bulletin of Chinese Materia Medico, 10, 77-78.
10. Su~rez, J., Herrera, M.D., Marhuenda, E. (1996) Hesperidine and neohesperidine dihydrochalcone on different experimental models of induced gastric ulcer. Phytatherapy Research, 10, 6 16-618.
11. Hofstetter, R., K..reuder, J., von Bemuth, G. (1985) Effect of oxedrine on the left ventricle and peripheral vascular resistance. Arzneimittelforschung, 35, 1844-1846.
12. Yen,YF.,Chung,W.P., Liu,Z.S.,Ye,Y.W. (1983) Mechanism of the antishock effect of the active principles of the Chinese medicine Zhi Shi. Effect of N-meshyltyramine and synephrine on plasma and myocardial cyclic nucleotide levels. Bulletin of Hunan Medical College, 8, 145-147.
13. Yen, Y.F., Chung, H.P. (1981) Effect of N-methyltyramine, the active principle of Citrus aurantium on cardiac a-receptor and cUMP content. Chinese Pharmaceutical Bulletin, 16, 51.
14. Chen, X., Lin, LY., Deng, H.W., Fang, Y.X., Ye, Y.W. (1981) Effects of Cirrus aurantium and its active principle N-methyltyramine on the cardiovascular receptors. Acta Pharmaceutica Sinica, 16, 253-259.