The herb decoction inhibited the motility of the isolated small intestines of mice and rabbits; the intravenous injection of the decoction demonstrated an inhibitory effect on the gastrointestinal musculature of anesthetized dogs, small intestine of anesthetized rabbits, and stomach of unanesthetized rabbits. The action was weaker than that of epinephrine but more prolonged. This was probably due to the relative stability of the active component of the herb. In experiments on the isolated rabbit intestine, various kinds of Chinese medicines including this herb, which are reputed to "regulate the vital energy", antagonized the effect of acetylcholine. But the inhibitory action of the herb on the isolated rabbit intestine was antagonised by acetylcholine.

Further relaxation of the intestines could be elicited by the herb if the intestinal muscular tone was already reduced by pretreatment with atropine.

The herb also antagonized intestinal spastic contraction due to pilocarpine or barium chlorite. All these results suggest that the mode of action mainly involves direct inhibition of the intestinal smooth muscles.

Hesperitin had a biphasic action on the isolated intestinal muscles, i.e., an initial transient stimulant action followed by inhibition.

In conclusion, the various actions of the herb on the digestive tract are not only due to its various constituents, but also subject to the functional states of the digestive tract itself. Hence, it exhibits aromatic, stomachic, carminative and antiflatulent actions, and relieves stagnation of vital energy in the "spleen" and stomach.

The volatile oil of the herb had stimulant and expectorant actions; the principal active component was limonene. Perfusion of the fresh herb into rabbit bronchi produced a slight acceleration of the fluid flow, indicating the presence of a bronchodilatory action.

Preliminary screening of 11 kinds of Chinese herbs derived from the Citrus plants, which are thought to "regulate the vital energy", indicated that the peel of C. reticulata was one of those with a potent antiasthmatic effect. Its alcohol extract at the concentration of 0.02 g(crude drug)/ml abolished histamine-induced spastic contraction of the isolated bronchi of guinea pigs. Preliminary clinical observations also indicated that it was therapeutically effective in bronchial asthma. Nobiletin showed a bronchodilatory action on isolated bronchi of guinea pigs and in anesthetized cats given the intravenous injection; its action was slightly inferior to that of aminophylline.

Nobiletin markedly antagonized the allergic contraction of isolated ilea and bronchi in egg white-sensitized guinea pigs at the effective concentrations of 5 x 10-5 ant 1 x 10-4 , respectively.

Experimental rat models of gastric ulcer were produced by ligating the pylorus of the animals. Medication was given before and during the experiments. The results were as follows: daily subcutaneous injection of methylhesperitin at 100 mg/kg for 6 days markedly reduced the incidence of ulcers. It also inhibited gastric secretion. The antiulcer action was greatly enhanced when this agent was used concomitantly with vitamin C and vitamin K4.

Action on the heart. The decoction and the alcohol extract of the herb as well as hesperidin stimulated isolated and in situ frog hearts . Intravenous injection of hesperidin increased the contractility of the in situ rabbit heart and, at the same time, increased cardiac output, but it had an insignificant effect on heart rate. Perfusion experiments in the isolated rabbit heart also showed that the decoction dilated the coronary vessels.

Reports on the actions of methylhesperidin on the heart are numerous. Perfusion of methylhesperidin into the isolated rabbit heart markedly increased the coronary flow.

Its strength was one-fourth to one-half that of theophylline, but it hardly affected heart rate and cardiac contractility. The larger dose decreased the atrial beat and contractility of the isolated heart of guinea pigs. Intravenous infusion of methylhesperidin into dogs at the dose of 40 mg/kg lowered coronary resistance, increased coronary flow and lowered blood pressure and heart rate for more than 30 minutes. However, it did not significantly alter the oxygen consumption and oxygen utilisation of the myocardium, nor did it affect heart rate and myocartial contractility. A comparative study of the action of a few methylated derivatives of hesperidin and hesperidin chalcone on the isolated rabbit hearts proved that all dilated the coronary vessels to various degrees. Other experimental data indicated that methylhesperidin had a more potent dilatory action on the coronary vessels than hesperidin methylchalcone, but neither significantly affected myocardial contractility.

Perfusion of the alcohol extract of the herb into the systemic blood vessels of the toad produced a mild vasoconstrictive effect. Intravenous injection of the decoction or of the alcohol extract to anesthetized dogs or rabbits rapidly increased blood pressure, and sometimes caused a transient hypotensive reaction after normalization of blood pressure.

Nobiletin injected intravenously to anesthetized cats at 10-22 mg/kg also produced a significant pressor action.

Intravenous injection of methylhesperidin at 5-25 mg/kg to anesthetized cats, rabbits or dogs gradually lowered blood pressure; recovery was slow and there was no rapid development of tolerance. The hypotensive action was shown to be due to direct vasodilation.

Both hesperidin and methylhesperitin had vitamin P-like actions. Intraperitoneal injection of hesperitin to mice at the dose of 175-250 mg/kg antagonised the incremental effect of the pit viper venom (Agkistrodron halys) or of the hemolytic lecithin on vascular permeability. Increased vascular permeability induced by histamine in mice was also antagonised by intraperitoneal injection of hesperidin at 10 mg/animal. Likewise, hesperidin inhibited the inflammatory reaction of croton oil granulation in rats as well as markedly reducing the intracystic exudates. Oral administration of hesperidin to rabbits at the daily dose of 20-25 mg/kg, whether given for seven days before experiment or seven days before and after experiment, reduced the symptoms of ear chilblain due to chloroethane. Both in vitro and in vivo experiments proved that hesperidin failed to inhibit the activity of hyaluronidase, whereas its derivative, phosphoryl hesperidin succeeded. Hence, the reducing effect of hesperidin on vascular permeability could not be attributed to the inhibition of hyaluronidase.

Daily subcutaneous injection of methylhesperidin to rabbits at 50 mg or 100 mg/kg for 2 days inhibited the increase in cutaneous vascular permeability elicited by chloroform. Intraperitoneal injection of 0.5 or 1.0 g/kg inhibited the increase of vascular permeability in mice due to pit viper venom. Its effect was even more marked if it was used together with vitamin C and vitamin K4. Intraperitoneal injection of methylhesperidin at 40 mg/kg to rabbits also antagonised the histamine-induced increase in vascular permeability.

The decoction inhibited the isolated uteri of mice and, at high concentration, caused complete relaxation of the organ. Intravenous injection of the decoction to anesthetized rabbits produced tonic contraction of the in situ uteri; the condition was reversed after 15 minutes. The resting uteri were also very sensitive to the above injection. Methylhesperidin at the concentration of 5 x 10-3 completely inhibited the motility of isolated rat uteri and also antagonised uterine spasm caused by acetylcholine.

The herb inhibited the growth of staphylococci in vitro. The powder preparation given to mice and rabbits by intragastric route shortened the bleeding time and clotting time of the animals.

In cases of abdominal distention, tightness of the chest, anorexia, nausea and vomiting, the herb may be used "to regulate the vital energy" and stimulate the appetite. With more severe abdominal distention and pain, the herb may be used together with the rhizome of Atractylodes lancea and the bark and root bark of Magnolia officinalis. When vomiting and hiccups are prominent, the herb is usually combined with Phyllostachys nigra and the root of Codonopsis pilosula.

In cases with thick viscous white sputum and chest discomfort, the herb can be used to "regulate the vital energy" and to reduce expectoration. Most anti-tussive and expectorant herbal mixtures contain a tincture or syrup of this herb. It is especially suitable for young children. ln 59 cases of whooping cough treated with the powder for 4-16 days, 42 cases were cured, 14 cases markedly improved, and 3 cases remained unchanged.

There were no toxic manifestations after intragastric administration of the 50% decoction of the fresh herb to dogs at 3 ml/kg, or intravenous injection of the decoction of the dried herb to animals, in various experiments using multiple and large doses (each dose: 1 ml/kg of 50% decoction).

Except those noted, all references come from Weng Weiliang, et al., Clinical Chinese materia medica, Henan Science & Technology Press, 1998