Kend de aktive stoffer i andrographis paniculata – engelsk artikel

Kend de aktive indholdsstoffer i Andrographis paniculata

Michael Thomsen, N.D., M.H.

Commonly known in the United States simply as Andrographis, Andrographis paniculata is an important ingredient in various Ayurvedic preparations for fever and liver diseases. It is a major constituent of an Ayurvedic formulation for the treatment of vitiligo. The macerated leaves and juice, together with certain spices such as cardamom, clove, and cinnamon, are made into pills and prescribed for relief from stomach ailments in infants. A decoction or infusion of the leaves is used to treat general debility and dyspepsia. The leaves and roots are also used for their tonic, stomachic, and anthelmintic activity. The tincture prepared from the root is tonic, stimulant, and aperient. Besides being well known as an Ayurvedic herb, Andrographis is used traditionally in China and Thailand. In Traditional Chinese Medicine (TCM) Andrographis is indicated for conditions of “heat,” particularly in the lungs, throat, and urinary tract, as well as for manifestations of “Fire Poison” on the skin, such as sores and carbuncles.(1) According to TCM, the “channels” through which Andrographis exerts its effects are the lung, stomach, large intestine and bladder meridians; through which it acts to dispel heat and remove toxins. In Western herbal medicine, Andrographis is used as an adaptogen and as an anti-inflammatory, antioxidant, antipyretic, bitter tonic, cholagogue, hepatoprotective, and immunostimulatory agent.

Habitat and Nomenclature
A. paniculata is a member of the family Acanthaceae. It is an annual shrub growing to 1 m high, with sharply quadrangular branches, and bears small and solitary flowers that grow in panicles. The fruit of the plant is approximately 2 cm long, and its seeds are numerous and yellow-brown. Andrographis is distributed across tropical Asia in India, Sri Lanka, Indonesia, Malaysia, and Thailand, frequently growing in isolated patches, and can be found in a variety of habitats such as plains, hill slopes, wastelands, farms, dry or wetlands, and seashores, and even on roadsides. It is common in India, where it favors moist tropical, deciduous forests, in which it grows as an understorey plant. The parts of Andrographis that are used medicinally are the parts that grow above ground, and especially the leaves. Among common regional names for Andrographis are bhavprakash, madanpal, and rajnighantu, in India; kalmegh, in Bengali; chiretta and King of Bitters in English; and chuan xin lian in Chinese.

Active Components
The key active constituents of Andrographis (2,3) are bitter diterpenoid lactones, especially andrographolides consisting of aglycones and glucosides; diterpene dimmers; and flavonoids. The marker compounds for quality control of Andrographis are the andrographolides that are its chief active constituents, and extracts of Andrographis are often standardized to these compounds. Unfortunately, not all powdered Andrographis extracts used in the manufacturing of tablets are of adequate quality.

Laboratory Analysis
Table 1 lists the level of andrographolides in the various powdered extracts of andrographis as supplied by different manufacturers as opposed to the levels actually detected by high-pressure liquid chromatography (HPLC). Significant differences are seen between the claimed levels of andrographolides and the levels actually detected. Apart from direct fraud, it is possible that the discrepancies are due to the use of different test methods. Analysis by gravimetric methods, although described in 1966 in the Indian Pharmacopoeia as an acceptable method for quantitating these active constituents of the plant, is in fact notoriously unreliable, as shown by the table. The accurate qualitative and quantitative analysis of andrographolides in Andrographis requires the use of HPLC with photodiode array detection (PDA).

Main Indications
The main indications for use of Andrographis as an herbal medicament are acute and chronic infections, including the common cold and other respiratory tract infections, and poor general immunity. It is also used for dyspepsia, flatulence, parasitic infestation of the gastrointestinal tract, diarrhea, poor digestion, hepatitis, liver insufficiency, and liver toxicity.

Clinical Studies
A number of clinical studies have investigated the use of Andrographis in various settings. A randomized, double-blind study determined that 1200 mg/day of anA. paniculata extract given for 5 days reduced the prevalence and intensity of symptoms of the common cold. The efficacy of the A. paniculata extract in this study was determined by patients subjective evaluations made on days 0, 2, and 4 of the study on a visual analogue scale for severity of headache, tiredness, earache, sleeplessness, sore throat, nasal secretion, phlegm, frequency and intensity of cough as parameters. A significant decrease in intensity of tiredness, sleeplessness, sore throat, and nasal secretion was observed in the Andrographis group on day 2 of treatment, as compared with the placebo group. By day 4 the Andrographis group showed a significant decrease in the intensity of all symptoms. The investigators who conducted the study concluded that from day 2 of treatment onward,A. paniculata had a high degree of efficacy in reducing the prevalence and intensity of the symptoms of uncomplicated common colds, No adverse effects were observed or reported.(4). The effect of a standardized extract of A. paniculata fixed combination (In Scandianavi known as Kan jang in treating uncomplicated upper-respiratory tract infections was examined in a randomized, double-blind, placebo-controlled parallel-group pilot study and ensuing phase III trial in Sweden. In the pilot study, which involved 46 patients, the Andrographis preparation was taken three times daily for a minimum of 3 days and a maximum of 8 days, while in the phase III trial, which involved 179 patients, it was taken for 3 days. The primary outcome measures, again evaluated by patient self-evaluation, were related to muscle ache, cough, throat symptoms, headache, nasal symptoms, eye symptoms, and temperature. A fixed- score physician’s diagnosis was primarily based on signs and symptoms related to the ears, nose, oral cavity, lymph glands, tonsils, and eyes. Total symptom score in the pilot study showed a tendency toward improvement (p = 0.08) with use of the Andrographis preparation, but in the phase III trial both the total symptom score and total diagnosis score showed highly significant improvement (p <0.0006 and p<0.003 respectively). The most significant improvement in both studies occurred in signs and symptoms of throat-related illness.(5)

Cautions and Contraindications
Andrographis has not been associated with any side effects in human studies, although animal studies have raised concerns about its effects on fertility. In one study, human participants given an Andrographis extract were monitored for changes in liver function, blood-cell counts, kidney function, and other laboratory measures of toxicity. No adverse effects were found.(6) In a study with rats in which a combination product containing standardized extracts of Andrographis and Siberian Ginseng was given for the first 19 days of pregnancy in doses of 200, 600, and 2000 mg/kg—equivalent to 30-, 90-, and 300-fold higher doses than its daily therapeutic dose in humans—no effects were found in pregnancy-related increased plasma levels of progesterone. It was concluded on this basis that therapeutic doses of the two extracts could not induce progesterone-mediated termination of pregnancy.(7) Animal studies have found that very high doses (20 times the recommended dose) of Andrographis extract may reduce fertility.(3,8) .However, a subsequent study showed no effect in male rats, and this issue therefore remains unclear.(9) In view of these studies however, Andrographis should still be used with caution in pregnancy, and should not be used by persons with reduced fertility.

Dosage
The dose of A. paniculata as the dry herb ranges from 1.5 to 6 g/day; this would equate to 3 to 12 mL/day of a 1:2 liquid extract. The clinically effective dosage of andrographolides for treating acute respiratory tract infections, such as in the studies described above, is 60mg/day.

References
1. Bensky D, Gamble A. Andrographis paniculata. Chinese Herbal Medicine Materia Medica. Seattle: Eastland Press, 1986, p. 136. 2. Matsuda T, Kuroyanagi M, Sugiyama S, et al. Cell differentiation-inducing diterpenes from Andrographis paniculata Nees. Chem Pharm Bull 42(6):1216-1225, 1994 3. Zhu PY, Liu GQ. Chin Trad Herb Drugs 15:373-376, 1984. 4. Caceres DD, Hancke JL, Burgos RA, et al. Use of visual analogue scale measurements (VAS) to asses the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study.Phytomedicine 6(4):217-223, 1999. 5. Melchior J, Spasov AA, Ostrovskij OV, et al. Double-blind, placebo-controlled pilot and phase III study of activity of standardizedAndrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection. Phytomedicine 7(5):341-350, 2000. 6. Hancke J, Burgos R, Caceres D, et al. A double-blind study with a new monodrug Kan Jang: Decrease of symptoms and improvements in the recovery from common colds.Phytotherapy Res 9: 559-562, 1995. 7. Zoha MS, Hussain AHM, Choudhury SAR Antifertility effect of Andrographis paniculata in mice. Bangladesh Med Res Counc Bull 15(1): 34-37, 1989. 8. Akbarsha MA, Manivannan B, Shahul Hamid K, et al. Antifertility effect of Andrographis paniculata (Nees) in male albino rat. Indian J Exp Biol 28(5): 421-426, 1990. 9. Panossian A, Kochikian A, Gabrielian E, et al. Effect of Andrographis paniculata extract on progesterone in blood plasma of pregnant rats. Phytomedicine 6(3):157-161, 1999.

________________________________________________________________________ Michael Thomsen, N.D., M.H., is a consultant to the herbal medicine industry. He lectures on herbal medicine and has published the Phytotherapy Desk Reference, 2nd Ed. He is also technical information manager for Phytomedicine, Pty., Ltd