Zhi Shi

Fructus Aurantii Immaturus, Immature Bitter Orange

Dosage

Internal administration: decocted, 3 to 10g, or made into bolus and powder. 5:1 concentrated extract: 0.6 to 2 grams/day.

Toxicity

LD50 (mice/herb solution): 267 ± 37g/kg (peritoneal injection), and 71.8 ± 6.5g/kg (IV injection). No severe adverse effects were observed when as much as 21g/kg of Zhi Shi was administered to anesthetized dogs within half an hour. One time IV administration of Zhi Shi in overdose dosages, however, would cause a steep rise in blood pressure (over 180-200mm Hg), resulting in temporary ectopic rhythm and anuria. (1)

Chemical Composition

Hesperidin; Neohesperidin; Naringin; Synephrine; N-methyltyramine; Umbeliferone; Auraptene; D-limonene; Citric acid; Vitamin C; Vitamin P; Pectin. (2) , (3)

Precautions

Exercise caution when prescribing Zhi Shi to pregnant women.

Pharmacology

Anti-shock effects

Synephrine and N-methyltyramine, two effective components of Zhi Shi, have anti-shock effects on anesthetized dogs. (4) Experiments show that when administered at 06.mg/kg by an IV injection, synephrine is effective in raising the blood pressure of rabbits in severe hemorrhagic shock. (5)

Effects on the electrogastrographic readings of rabbits

Using the electrogastrographic readings of healthy rabbits as the basis for comparison, experiments show that Zhi Shi can significantly increase the amplitude and frequency of rabbits’ electrogastrographic readings. The incubation period of this effect is 30 minutes, and the duration is two hours. (6)

Effects on smooth muscles

Zhi Shi can enhance the myoelectric activity in the smooth muscles of sheep jejunum and ileum, and shorten the cycle of migrating synthetic myoelectricity. (7) The flavone glycosides of Zhi Shi inhibit the contraction of isolated smooth muscles of rats. (8)

Effects on the blood system

In-vitro experiments in rabbits show that Zhi Shi can significantly inhibit platelet aggregation, and enhance erythrocytes’ deformation capacity. (9)

Analgesic effects

Zhi Shi volatile oil can significantly reduce the number of times mice twist their bodies as a reaction to acetic acid stimulation, indicating that the herb has an analgesic effect. (10)

Ant-inflammation effects

Hesperidin and neohesperidin, two active components of Zhi Shi, can significantly suppress carrageenin-induced foot swelling in rats. (11)

Effects on the uterus

Zhi Shi extracts can strengthen the contractility of isolated rabbit uteruses. (12)

Effects on the cardiovascular system

Experiments show that 24mg/ml of N-methyltyramine, an active component of Zhi Shi, can significantly enhance the contractility of isolated guinea pig cardiac atria. At 0.125, 0.25, or 1.0mg, N-methyltyramine can strengthen the myocardial contraction of isolated guinea pig hearts. Administered to rabbits at 20mg/kg by IV injection, N-methyltyramine can significantly increase the level of cGMP in the subjects’ serum. (13)

References

  1. Internal Medicine Group, Hunan Medical College No. 2 Hospital. A pharmacological study of Zhi Shi’s hemopiesic action. Journal of Science. 1978;23(1):58.
  2. Lu Ye Mei Hong, et al. The chemistry and pharmacology of Zhi Shi, Shan Jiao, and Gua Lou Ren. Foreign Medicine (vol. of TCM). 1986;8(6):17-20.
  3. Hunan Medical Industry Institute, et al. A briefing on Zhi Shi’s hemopiesic components. Bulletin of Chinese Materia Medica. 1976;(5):6-9.
  4. Hunan Medical Industry Institute, et al. A briefing on Zhi Shi’s hemopiesic components. Bulletin of Chinese Materia Medica. 1976;(5):6-9.
  5. Wang Tian Shan, et al. Zhi Shi’s effect on rabbits in severe hemorrhagic shock. Journal of Nanjing University of TCM. 1999;15(6):345-346.
  6. Xu Guan Sun, et al. The effects of Zhi Shi, Wu Yao on rabbits’ electrogastrographic readings. Journal of Anhui College of TCM. 1989;8(3):74-76.
  7. Kuang Ling. The effect of Zhi Shi on the myoelectric activity of sheep ileum. Journal of Chinese Medicine Reseach. 1997;13(3):49-50.
  8. Hu Sheng Shan, et al. The pharmacological activity of active components of Zhi Shi. Journal of Chinese Materia Madica. 1994;25(8):419-421.
  9. Feng Ya, et al. A preliminary study on the effects of qi-regulating, phlegm-dispelling herb on blood platelet aggregation, red blood cell deformation, and blood viscosity. Journal of Fujian College of TCM. 1998;8(1):24-26, 36.
  10. Hu Sheng Shan, et al. The pharmacological activity of active components of Zhi Shi. Journal of Chinese Materia Madica. 1994;25(8):419-421.
  11. Lu Ye Mei Hong, et al. The chemistry and pharmacology of Zhi Shi, Shan Jiao, and Gua Lou Ren. Foreign Medicine (vol. of TCM). 1986;8(6):17-20.
  12. Lu Ye Mei Hong, et al. The chemistry and pharmacology of Zhi Shi, Shan Jiao, and Gua Lou Ren. Foreign Medicine (vol. of TCM). 1986;8(6):17-20.
  13. Internal Medicine Group, Hunan Medical College No. 2 Hospital. Then effect of Zhi Shi on the cardiovascular system. Hunan Journal of Medicine. 1974;(3):36.