Andrographis and Upper Respiratory Tract Infection

By Mary Scanlon-O’Kelly, MD, and Benjamin Kligler, MD, MPH

Botanical medicines are becoming increasingly popular among the public for the treatment of uncomplicated infection, including upper respiratory tract infections (URTIs) such as the common cold.

Andrographis paniculata is a shrub indigenous to India and other Asiatic countries. Also known as andrographolide and Indian echinacea, it has been used during epidemics, including the Indian flu epidemic of 1919, in which a tincture of andrographis was credited with arresting the spread of disease.1 It also has been employed in the treatment of malaria,2 snake bites,3 fever, toxic hepatic injury, the common cold, and pharyngotonsillitis, among others.4

Over the last two decades, andrographis has been commonly used as an herbal medicinal product in Scandinavia for the treatment of colds. The most widely used product is Kan Jang, a standardized extract from Andrographis paniculata and Eleutherococcus senticosus.5 Kan Jang is manufactured by the Swedish Herbal Institute and is standardized to contain 4-5.6 mg of andrographolide.6 Of note is the fact that isolated andrographolide does not appear to affect the immune system to the same extent as the whole plant extract.

Andrographis is now available in the United States and, as discussed below, there is reasonably good evidence that it can reduce the severity of cold symptoms; in addition, it also may help prevent colds.

Mechanism of Action

Although the mechanism of action of andrographis is unknown, preliminary evidence suggests that it may stimulate immune function, specifically by increasing antibody activity and phagocytosis by macrophages.7 The active ingredients are thought to be lactones, especially andrographolide, dehydroandrographolide, neoandrographolide, and deoxyandrographolide.1

Clinical Applications: Animal Studies

Although the focus of this article is on the use of andrographis for URTI, there are interesting preliminary data from animal research on a number of other potential applications of this herb. For example, animal studies suggest a possible role for andrographis as an agent that may help prevent heart disease.2,3 In addition, preliminary studies suggest that andrographis may help protect the liver from toxic injury.8,9 In rats and guinea pigs, andrographis appears to stimulate gallbladder contraction.10 It is noteworthy that andrographis does not appear to have any antibacterial properties.11

Clinical Studies: Andrographis for URTI

Although andrographis is used for a wide variety of indications in Ayurvedic and herbal medicines, to date clinical effectiveness in humans has been documented only for the common cold. Most of the trials have examined Kan Jang, which contains both andrographis and eleutherococcus; thus, at this point it is difficult to draw definitive conclusions about the efficacy of andrographis as a solitary preparation. Nevertheless, the combination product does appear to be quite effective in reducing both severity and duration of URTI.

Symptom Reduction. When used as an oral preparation for the common cold, andrographis seems to improve symptoms significantly when started within 72 hours of the onset of symptoms. Some improvement can be seen after two days of treatment, but it typically takes 4-5 days before there is maximal symptom relief.1,6,12

Three double-blind, placebo-controlled studies, enrolling about 400 people have evaluated either the combination remedy Kan Jang or andrographis extract alone. For example, a five-day, double-blind, parallel-group, placebo-controlled trial of 185 adults with acute URTIs, including sinusitis, found that treatment with Kan Jang reduced cold symptoms and also relieved the inflammatory symptoms of sinusitis.5

A second trial compared andrographis extract to paracetamol (acetaminophen). In this study, 142 adults with sore throat and fever were randomized to receive low-dose andrographis (3 g daily), high-dose andrographis (6 g daily), or paracetamol (3.9 g daily).13 Symptoms were similar in all three groups at baseline. The higher dose of andrographis (6 g) decreased symptoms of fever and throat pain to about the same extent as paracetamol after three days of treatment, whereas the lower dose of andrographis (3 g) was not as effective. There were no significant side effects in either group.

URTI Prevention. When used orally for prevention of the common cold, there is some evidence that andrographis can decrease the relative risk of developing a cold by approximately 50%. However, this beneficial effect does not seem to occur until after two months of continuous treatment, and it is unclear how long this benefit lasts.

Preventive treatment with Kan Jang in one double-blind, placebo-controlled study of 107 students reduced the risk of catching a cold by a factor of 2 as compared to placebo.6 Fifty-four students took two 100-mg tablets standardized to 5.6% andrographolide daily—considerably less than the 1,200-6,000 mg per day that has been used in studies on treatment of colds. The other 53 students were given placebo tablets with a coating identical to the treatment. Then, once a week through-out the study, a clinician evaluated all the participants for cold symptoms. In the third month of treatment, only 16 people in the group using andrographis had experienced colds, compared to 33 of the placebo-group participants. This difference was statistically significant (P < 0.05).

Safety Issues

Andrographis extract used in Kan Jang was tested in acute, subacute, reproductive, and toxicological studies without encountering toxic effects. In one study, participants were monitored for changes in liver function, blood counts, kidney function, and other laboratory measures of toxicity. No problems were detected.1

Contraindications include hypersensitivity to andrographis and pregnancy.14 Safety in young children, nursing women, or individuals with kidney or liver disease has not been established. Also, because andrographis may stimulate gallbladder contraction, it would be prudent to avoid use in patients with gallbladder disease.

Some animal studies have raised concerns about fertility; however, the results are equivocal and thus no useful conclusions can be drawn.

Finally, based on a single recent study in HIV-positive adults, andrographis may potentially increase viral replication rates.15 In addition, a universal immune booster like andrographis has the potential, theoretically, to exacerbate autoimmune disease.

Dosage

Dosing of herbal preparations varies and is dependent on factors such as growing and harvesting conditions, plant parts, and extraction methods. A typical dosage of andrographis is 400 mg three times a day for the common cold. Doses as high as 1,000-2,000 mg three times daily have been used in studies of pharyngotonsillitis. Andrographis usually is standardized to andrographo-lide content, typically 4-6% as is found in Kan Jang.

Conclusion

Andrographis is used primarily as an overall tonic in Ayurvedic medicine and also has been used as a cold remedy for many years in Sweden. Patients generally tolerate andrographis without ill effects when taken at the recommended doses. The literature supports its use as a safe, effective herb for alleviating symptoms associated with the common cold, and possibly for prevention of URTI as well.

Recommendation

Given its favorable safety profile and reasonable evidence of efficacy, clinicians can consider recommending andrographis at a dose of 400 mg three times daily for patients presenting with URTI. For patients who experience frequent URTI, a three-month trial of andrographis extract for prevention could be considered. This herb should be avoided in pregnancy, and probably also in patients with HIV infection.

Dr. Scanlon-O’Kelly is in Family Practice, Beth Israel Center for Healing and Health; and Dr. Kligler is Assistant Professor of Family Medicine, Albert Einstein College of Medicine, and Co-Director, Beth Israel Fellowship Program in Integrative Medicine, New York, NY.

References

1. Hancke J, et al. A double-blind study with a new monodrug Kan Jang: Decrease of symptoms and improvement in the recovery from common colds. Phytother Res 1995;9:559-562.

2. Najib Nik A, et al. Antimalarial activity of extracts of Malaysian medicinal plants. J Ethnopharmacol 1999;64:249-254.

3. Martz W. Plants with a reputation against snakebite. Toxicon 1992;30:1131-1142.

4. Burgos R, et al. Testicular toxicity assessment of Andrographis paniculata dried extract in rats. J Ethnopharmacol 1997;58:219-224.

5. Gabrielian ES, et al. A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis. Phytomedicine 2002;9:589-597.

6. Caceres DD, et al. Use of visual analog scale measurements (VAS) to assess the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind placebo study. Phytomedicine 1999;6: 217-223.

7. Puri A, et al. Immunostimulant agents from Andrographis paniculata. J Nat Prod 1993;56:995-999.

8. Kapil A, et al. Antihepatotoxic effects of major constituents of Andrographis paniculata. Biochem Pharmacol 1993;46:182-185.

9. Subramoniam A, Pushpangadan P. Development of phytomedicines for liver diseases. Indian J Pharmacol 1999;31:166-175.

10. Shukla B, et al. Choleretic effect of andrographolide in rats and guinea pigs. Planta Med 1992;58:146-149.

11. Leelarasamee A, et al. Undetectable anti-bacterial activity of Andrographis paniculata (Burma) wall. ex Ness. J Med Assoc Thai 1990;73:299-304.

12. Melchoir J, et al. Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection. Phytomedicine 2000;7:341-350.

13. Thamlikitkul V, et al. Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai 1991;74:437-442.

14. McGuffin M, et al. American Herbal Products Association’s Botanical Safety Handbook. Boca Raton, FL: CRC Press; 1997.

15. Calabrese C, et al. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res 2000;14:333-338.