Menolyte
Chuan Xin Lian
HERBA ANDROGRAPHITIS (COMMON ANDROGRAPHIS HERB)
Chuan Xin Lian is the dried aerial part of Andrographis paniculata (Burm. f.) Nees (Acanthaceae). The plant is introduced from the countries in southeast Asia and cultivated in the southern part of China. The herb is collected in the autumn when the plant grows luxuriantly, and is dried in the sun.
CHEMISTRY
The main components of the herb are diterpene lactones. Andrographolide
was the first diterpene lactone identified1'2. Later, four more diterpene
lactones, i.e. neoandrographolide, deoxy-didehydroandrographolide,
deoxy-oxoandrographolide and deoxyandrographolide, were isolated3'4.
Further, new diterpene lactones were isolated from the aerial part
of the plant. These diterpenes include dideoxy-andrographolide (andrograpanin),
andrographiside and its 14-deoxy analogue, deoxymethoxy-andrographolide,
deoxyandrographiside (andropanoside)5-8.
The content of the major component andrographolide depends on the collection
time, from over 2% in the leaf before the plant blooms to less than 0.5% afterwards.
The stem contains 0.1-0.4% of andrographolide9.
In addition to diterpene lactones, flavonones oroxylin and wogonin were also
isolated from the leaf of A. paniculata10. More flavonones, including andrographidines
A-F; were isolated from the root of A. paniculata11.
PHARMACOLOGY
Antibacterial Activity
The decoction of the herb mildly inhibited the growth of Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Shigella dysenteriae and Escherichia coli. Interestingly, the water-soluble fraction of the herb containing flavonones had an inhibitory activity against Shigella dysenteriae in vitro, but clinically it was not effective in dysentery. On the other hand, the water-insoluble diterpene lactones exhibited therapeutic effect in many infectious diseases whereas no antibacterial activity could be detected in vitro12. Neoandrographolide had a better effect in dysentery than chloromycetin and furazolidone. Andrographolide was also effective in the treatment of dysentery. Both neoandrographolide and andrographolide were also effective in upper respiratory infections13.
Effect on Immune Function
The decoction of the herb enhanced leukocytic phagocytosis of Staphylococcus aureus in vitro. This effect was attenuated by leukocytic phagocytosis inhibitors, such as gentamicin, tetracycline and erythromycin.
Antipyretic and Antiinflammatory Effects
Andrographolide, neoandrographolide, deoxyandrographolide and 1 4-deoxy- 11,12-didehydroandrographolide reduced the fever in rabbits caused by typhoid and paratyphoid vaccine, and in rats caused by 2,4-dinitrophenol. 14-Deoxy-11,12-didehydroandrographolide had the highest activity followed by deoxyandrographolide, neoandrographolide and andrographolide. The four diterpene lactones also showed antiinflammatory activity at an oral dose of 1 g/kg, inhibiting hind paw edema induced by egg-white in rats and decreasing the cutaneous or peritoneal capillary permeability increase caused by xylene or acetic acid in mice. The antiinflammatory activity of the four diterpnene lactones was increased after they were made into water-soluble derivatives. Thus, antiinflammatory action was exhibited by 14-deoxy-11,1 2-didehydroandrographolide hemisuccinate (DAS) at subcutaneous and intraperitoneal doses of 125-250 mg/kg. The antiinflammatory potency was in the same order as their antipyretic activities. No antiinflammatory action was observed after adrenalectomy, indicating that the antiinflammatory effect was mediated by the adrenal gland12,14.
Effect on Pituitary-Adrenocortical Function
The four lactones caused thymic atrophy in infant mice at high doses, indicating an adrenocortical enhancing effect. DAS also caused thymic atrophy in infant mice and reduced the vitamin C content in the rat adrenal gland. Five days of medication did not produce tachyphylaxis. The decremental effect of DAS on the vitamin C content of the rat adrenals was completely abolished after hypophysectomy. DAS could not prolong the survival time of adrenalectomized infant rats. These results suggest that DAS does not have an adrenocorticoid-like effect itself but it is able to activate the anterior pituitary function, promoting the synthesis and release of ACTH and, consequently, increasing the adrenocortical function. Other andrographolide derivatives had similar effects on the pituitary-adrenocortical function12.
Antivenin and Muscarinic Effects
Intraperitoneal administration of the ethanolic extract of the herb significantly delayed the occurrence of respiratory failure and death of mice poisoned with cobra venom. This extract reduced the blood pressure in dogs, which was reinforced by physostigmine and blocked by atropine but not affected by antihistamines or b-blockers. Its contraction effect on the guinea pig ileum was also intensified by physostigmine and blocked by atropine but not affected by antihistamines. The extract inhibited the frog heart in situ. This inhibition could be blocked by atropine. Based on these results, it was concluded that the herb did not activate nicotinic receptors, but produce a muscarmnic action, which might account for its antivenin effect12.
Pregnancy-Terminating Effect
A contraceptive effect in mice fed with the herb was reported. Administration of the herb to pregnant rabbits caused abortion. Intraperitoneal administration of the decoction to mice prevented implantation and caused abortion at different gestational periods. Early pregnancy in mice and rabbits was terminated by intramuscular, subcutaneous, intragastric, intravenous and intrauterine administration of the herb, with intraperitoneal and intravenous administration having the best effect. The abortifacient effect of the herb could be antagonized by progesterone or luteinizing hormone-releasing hormone (LHRH), suggesting an anti-progesterone action of the drug12.
Antihepatotoxic and Choleretic Effects
Pretreatment of dogs with 500 mg/kg of the leaf of A. paniculata or 5 mg/kg of andrographolide prevented the rise of serum GOT and GPT levels and drop of these enzymes in the liver caused by oral dose of CCl4. Simultaneous treatment had no effect. The protective effect of CCl4-induced hepatotoxicity of the leaf extract was more significant than that of andrographolide15.
Cardiovascular Effect
The crude water extract (WE), and its o-butanol (FB) and aqueous (FC) fractions produced a significant fall in mean arterial blood pressure (MAP) in a dose-dependent manner without significant decrease in heart rate in anesthetized rats. The ED50 values for WE, FB and FC were 11.4, 5.0 and 8.6 mg/kg, respectively. The hypotensive action of EB was not mediated through effects on the b-adrenoceptor, muscarinic cholinergic receptor and angiotensin-converting enzyme. It seemed to work via a-adrenoceptors, autonomic ganglion and histaminergic receptors16.
FUNCTIONS AND APPLICATIONS
Traditional Description
Chuan Xin Lian has a bitter taste and a cold property, acting on the heart, lung, large intestine and urinary bladder channels. It has the functions:
(i) removing heat and counteracting toxicity, used for influenza
with fever, sore throat, ulcers in the mouth or on the tongue, acute
or chronic cough;
(ii) removing damp-heat in the blood and inducing subsidence of swelling,
used for colitis, dysentery, urinary infection with difficult and
painful urination, carbuncles, sores, and venomous snake bite.
Applications
The applications and efficacy of the herb were summarized in Table 112.
Table 1 Efficacy of Herba Andrographitis for various diseases.
| Diseases | Number of cases | Number of effective cases | Effective rote |
|---|---|---|---|
| Bacillary dysentery | 1611 | 1471 | 91.3% |
| Enteritis |
955 | 872 | 91.3% |
| Typhoid fever |
31 | 29 | 93.6% |
| Respiratory infections |
2717 | 2430 | 89.4% |
| Tuberculosis |
321 | 280 | 87.2% |
| Leptospirosis |
185 | 160 | 86.5% |
| Leprosy |
112 | 105 | 93.7% |
| Skin infections |
359 | 347 | 96.1% |
| Hepatitis |
112 | 93 | 83.0% |
| Fulminant hepatitis |
26 | 20 | |
| Acute pyelonephritis |
64 | 62 | |
| Otitis media |
55 | 51 | 92.6% |
| Pelvic inflammation |
186 | 183 | 98.4% |
| Choriocarcinoma and
malignant hydatidiform mole |
60 | 47 | 78.3% |
| Induction of labour |
331 | 296 | 89.4% |
| Thromboangiitis obliterans | 108 | 101 | 93.5% |
SIDE EFFECTS AND TOXICITY
The herb has few toxic and side effects. Large oral doses may cause gastric discomfort and poor appetite. The extreme bitter taste of andrographolide may cause vomiting. The oral LD50 values of various components of the herb in mice are listed in Table 2.
Table 2 The LD50 values of the lactones of Andrographis pan iculata.
| Components | LD50 (g/kg, oral) |
|---|---|
| Total lactones |
3.4 |
| Andrographolide |
> 40 |
| Neoadrographolide |
> 20 |
| Deoxyandrographolide |
> 20 |
| 14-Deoxy- 11, 12-didehydroandrographolide | > 20 |
In subacute toxicity tests, oral administration of 1 gfkg of andrographolide or deoxyandrographolide to rats and rabbits once daily for 7 days did not produce any significant changes in body weight, blood picture, hepatic and kidney functions and histology of important organs. Intraperitoneal administration of 84 mg/kg of DAS for consecutive 10 days produced no toxic reactions in rats. In patients and healthy volunteers, oral dose of 0.5 g of andrographolide four times a day for four days caused a transient elevation of SGPT in some subjects, which was gradually recovered after discontinuation of the medication. At the dose of 0.3 g nice daily, liver and kidney functions were not affected12.
DOSAGE
6-9g.
REFERENCES
I. Chan, W.R., Willis, C., Cava, M.P., Stein, R.P. (1963) Stereochemistry
of andrographolide. Chemical Industry, 495.
2. Cava, M.P., Chan, W.R., Stein, R.P., Willis, C.R. (1965) Andrographolide,
further transformations and stereochemical evidence: the structure
of isoandrographolide. Tetrahedron, 21, 2617-2632.
3. Chan, W.R., Taylor, DR., Willis, CR., Bodden, R.L. (1971) The
structure and stereochemistry of neoandrographolide, a diterpene
glucoside from Andrographis pan iculota. Tetrahedron, 27, 5081-5091.
4. Balmain, A., Connolly, J.D. (1973) Minor diterpenoid constituents
of Andrographis poniculata Nees. Journal of the Chemical Society,
Perkin Transaction, I, 1247-1251.
5. Hu, C.Q., Zhao, B.N. (1981) Studies on the new diterpenoids of
Chuan Xin Lian (Andrographispaniculata). Chinese Traditional and
Herbal Drugs, 12, 531.
6. Hu, C.Q., Zhao, B.N., Chou, P.N. (1982) Isolation and structure
of two new diterpenoid glucosides from Andrographis pan iculata Nees.
Acta Pharmaceutica Sinica, 17, 435-440.
7. Chen, W., Liang, X.T. (1982) Deoxyandrographolide-19-D-glucoside
from the leaves of Andrographis paniculata. Planta Medica, 45, 245-246.
8. Fujita, T., Fujitani, R., Takeda, Y., Takaishi, Y., Yamada, T.,
Kido, M., et al. (1971) On the diterpenoids ofAndrographispaniculata
X-ray crystalllographic analysis of andrographolide and structure
determination of new minor diterpenoids. Chemical and Pharmaceutical
Bulletin, 19, 33-34.
9. Zbu, PY., Peng, N.H., Jiang, W.J. (1984) TLC-UV spectrophotometric
determination of andrographolide in the leaves and stems of
Andrographis paniculata. Chinese Journal of Pharmaceutical Analysis,
4, 34-36.
10. Zhu, PY., Liu, G.Q. (1984) Separation and identification of flavonoids
in Andrographis paniculata Nees leaves. Chinese Traditional and
Herbal Drugs, 15, 375-376.
11. Kuroyanagi, M., Sato, M., Ueno, A., Nishi, K. (1987) Flavonoids from Andrographis
paniculata. Chemical and Phar,naceutical Bulletin, 35,
4429-4435.
12. Wang, Y.S. (1983) Pharmacology and Applications of Chinese Materia Medico,
pp. 822-836. Beijing: People's Health Publisher.
13. Wo, B.J. (1983) Pharmacology of Chinese Herbal Medicines, pp. 233-234.
Beijing: People's Health Publisher.
14. Deng, W.L., Nie, R.J., Liu, JY. (1982) Comparison of pharmacological effect
of four andrographolides. Chinese Pharmaceutical Bulletin, 17,
195-198.
15. Choudhury, BR., Poddar, M.K. (1984) Andrographolide and kalmegh (Andrographis
paniculata) extract:
effect on rat liver and serum transaminases. IRCS Journal of Medical Science,
12, 466-467.
16. Zhang, C.Y., Tan, B.K.H. (1997) Mechanisms of cardiovascular activity of
Andrographispaniculata in the anesthetized rat. Journal of
Ethnopharmacology, 56, 97-101.