Andrographis paniculata

 

Andrographis paniculata 

Synonyms

No documentation

Vernacular Name

King of bitters, kalmegh

Description

Andrographis paniculata, also known as “King of Bitters”, is a plant found in China, India and Southeast Asia and is commonly used in Traditional Chinese Medicine and Ayurvedic Medicine. A. paniculata is traditionally used to support digestion and healthy cardiovascular and urinary systems. The major interest in A. paniculata currently is for immune support, especially in colds and influenza (upper respiratory tract infections).  

The most widely tested supplement containing A. paniculata is called Kan Jang® (Swedish Herbal Institute). This product is available with A. paniculata alone and also in combination with Eleuthero, formerly known as Siberian ginseng (Eleutherococcus senticosus).

A. paniculata is a flowering herbaceous plant of the family Acanthaceae.  Slender and upright, A. paniculata can reach a height of little more than 100cm.  The stems are square, furrowed and support glabrous, lanceolate leaves.  The leaves, usually no longer than 8cm, grow in a pinnate pattern from the stem.  The flowers of A. paniculata are white with lavender or purple spots and grow from a pubescent stem.  The flowers are lobed, typically with three of its four petals erect, while the fourth is prostrate.  The stamen is white, covered in long pubescence and red or gold at the tip.

Origin / Habitat

A. paniculata originated in India and now is propagated in Southern India and throughout China. It can also grow in Thailand and Pakistan. The plant grows in the plains and wastelands of India preferring moist soil and partial shade, although A. paniculata can grow in direct sunlight.

Chemical Constituents

Diterpenes, including andrographolide, 14-deoxy-11,12-didehydroandrographolide, bisandrographolide A, andrographic acid, andrographiside and neoandrographolide Arabinogalactan proteins

Andrograpanin

Flavonoid glycosides including 5-hydroxy-7,8-dimethoxy (2R)-flavanone-5-O-beta-D-glucopyranoside and 5-hydroxy-7,8,2',5'-tetramethoxy-flavone-5-O-beta-D-glucopyranoside [1],[2],[3],[4],[5],[6],[7]

Plant Part Used

Leaf

Medicinal Uses

General

Immune Support
Colds/influenza Prevention and Treatment
Antiviral/Antibacterial
Anti-inflammatory
Antioxidant
Cancer
Liver support
Blood Sugar Regulation

Most Frequently Reported Uses

Immune Support
Colds/influenza Prevention and Treatment
Antiviral/Antibacterial
Anti-inflammatory

Dosage

Dosage Range

Therapeutic dosages range from 400mg to 2000mg and depend upon the specific application. Doses as high as 1,000-2,000mg, 3 times daily standardized to 5% andrographolide have been used in some studies. For preventative measures, 3 weeks on and 2 weeks off is recommended.

Most Common Dosage

Doses of 200-400mg, 3 times daily standardized to 5-30% andrographolide

Standardization Dosage

A. paniculata products are standardized to 5-30% andrographolide.

Pharmacology

Pre-clinical

Laboratory studies have found that constituents contained in A. paniculata have antioxidant properties, including neuroprotection, nephroprotection and also hepatic protection by decreasing lipid peroxidation and increasing glutathione levels similar to the popular hepatoprotective herb milk thistle (Silymarin).[8],[9],[10],[11]

The constituent andrographolide is reported to have anti-viral activity against Epstein Barr virus and also HIV.[12],[13]

A. paniculata has been reported to have blood sugar regulating properties. Studies have reported that A. paniculata is a strong, dose dependent insulinotropic agent, glucose dependent and independent insulin secreting agent.[14] Part of the pharmacology behind blood sugar regulation is the antioxidant potential of androphophis. In laboratory studies, A. paniculata has been reported to increase the activity of superoxide dismutase (SOD) and catalase (CAT), leading to a decrease in oxidative stress.[15],[16],[17]

 

The constituent andrographolide is reported in laboratory studies to have anti-tumor activity in gastric cancer, liver cancer, lung cancer and breast cancer.[18] Andrographolide has been reported to induce the apoptosis of cancer cell, inhibit the cell cycle, and increase the antitumor activity of lymphocytes.[19],[20]

Andrographolide is reported to cause cell-cycle arrest at G0/G1 phase through induction of cell-cycle inhibitory protein p27 and decreased expression of cyclin-dependent kinase 4 (CDK4).[21] Andrographolide also is reported to increase tumor necrosis factor-alpha (TNF-alpha) production and CD marker expression, resulting in increased cytotoxic activity of lymphocytes against cancer cells.[22]

In laboratory studies, the addition of A. paniculata to 5-FU (5-fluorouricil), a commonly used chemotherapeutic agent, was found to produce synergistic apoptosis in cancer cells.[23] The compound increased caspase-8, p53 activity and significantly changed  Bax conformation in these cells, resulting in increased losses of mitochondrial membrane potential, increased release of cytochrome c, and activation of caspase-9 and caspase-3.[24]

A. paniculata has been found in laboratory studies to increase lymphocyte production and proliferation, along with increasing key cytokines such as tumor necrosis factor alpha (TNF-alpha), natural killer cell (NK) function and interleukin-2 (IL-2).[25],[26]

 

Andrographolide may be useful in the treatment of inflammatory conditions, such as asthma, by inhibiting the NF-kappaB pathway at the level of inhibitory kappaB kinase-beta activation. [27],[28],[29] A laboratory study found that andrographolide’s anti-inflammatory effect was also in part due to prevention of oxygen radical production by human neutrophils through modulation of PKC-dependent pathway.[30]

Clinical

A small study found that andrographolide may inhibit HIV-induced cell cycle dysregulation, leading to a rise in CD4+ lymphocyte levels in HIV-1 infected individuals.[31] However, dosages used in this study caused side effects, including headache, fatigue, a bitter/metallic taste in the mouth, and elevated liver enzymes (which returned to normal after the medication was stopped).

 

In clinical studies, A. paniculata supplements (sometimes combined with eleuthero) have been found to decrease severity and duration of upper respiratory tract infections.[32],[33],[34] Improvements in muscle pain, cough, throat symptoms, headache, nasal symptoms, eye symptoms and temperature have been reported.[35] Also, A. paniculata has been reported to relieve the inflammatory symptoms of sinusitis, such as stuffy nose and sinus pressure.

A review of the literature and meta-analysis of randomized controlled trials to assess the efficacy of A. paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection was performed. [36] A total of 433 patients reported in three trials were included in the statistical analysis. A. paniculata in combination with Eleutherococcus senticosus (Kan JangÔ) was more effective than placebo.

A small clinical study in 60 patients with rheumatoid arthritis found that an extract of A. paniculata (standardized to 30% andrographolide) reduced rheumatoid factor, IgA, and C4 while improving joint pain.[37]

Interaction and Depletions

Interaction with other Herbs

No documentation

Interaction with Drugs

Based on pharmacology, use with caution in individuals taking anticoagulant medications, such as aspirin or warfarin (Coumadin).[40],[41]

Precautions and Contraindications

Side effects

A. paniculata has been reported safe in recommended doses.[38]

High doses may lead to side effects such as headache, fatigue, a bitter/metallic taste in the mouth, and elevated liver enzymes.

Use with caution in pre-existing liver conditions.

Pregnancy

Do not use A. paniculata in pregnancy, as laboratory studies report uterine smooth muscle relaxation when using A. paniculata in rats.[39]

Age limitation

No documentation

Adverse reaction

No documentation

Read more

  1) Botanical Info

  2) Cultivation

  3) Malaysian Herbal Plants

  4) Ayuverda

References

  1. Kapil A, Koul IB, Banerjee SK, Gupta BD. Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. Biochem Pharmacol. 6Jul1993;46(1):182-185.
  2. Suebsasana S, Pongnaratorn P, Sattayasai J, et al. Analgesic, antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals. Arch Pharm Res. Sep2009;32(9):1191-1200.
  3. Smith PL, Maloney KN, Pothen RG, Clardy J, Clapham DE. Bisandrographolide from Andrographis paniculata activates TRPV4 channels. J Biol Chem. 6Oct2006;281(40):29897-29904.
  4. Kleipool, RJC. Constituents of Andrographis paniculata Nees. Nature. 1952;169:33-34.
  5. Singha PK, Roy S, Dey S. Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. J Ethnopharmacol. 20Apr2007;111(1):13-21.
  6. Ji LL, Wang Z, Dong F, Zhang WB, Wang ZT. Andrograpanin, a compound isolated from anti-inflammatory traditional Chinese medicine Andrographis paniculata, enhances chemokine SDF-1alpha-induced leukocytes chemotaxis. J Cell Biochem. 1Aug2005;95(5):970-978.
  7. Li W, Xu X, Zhang H, Ma C, Fong H, van Breemen R, Fitzloff J. Secondary metabolites from Andrographis paniculata. Chem Pharm Bull (Tokyo). Mar2007;55(3):455-458.
  8. Das S, Gautam N, Dey SK, Maiti T, Roy S. Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E. Appl Physiol Nutr Metab. Apr2009;34(2):124-135.
  9. Singh P, Srivastava MM, Khemani LD. Renoprotective effects of Andrographis paniculata (Burm. f.) Nees in rats. Ups J Med Sci. 2009;114(3):136-139.
  10. Kapil A, Koul IB, Banerjee SK, Gupta BD. Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. Biochem Pharmacol. 6Jul1993;46(1):182-185.
  11. Li W, Xu X, Zhang H, Ma C, Fong H, van Breemen R, Fitzloff J. Secondary metabolites from Andrographis paniculata. Chem Pharm Bull (Tokyo). Mar2007;55(3):455-458.
  12. Lin TP, Chen SY, Duh PD, Chang LK, Liu YN. Inhibition of the epstein-barr virus lytic cycle by andrographolide. Biol Pharm Bull. Nov2008;31(11):2018-2023.
  13. Reddy VL, Reddy SM, Ravikanth V, et al. A new bis-andrographolide ether from Andrographis paniculata nees and evaluation of anti-HIV activity.Nat Prod Res. Apr2005;19(3):223-230.
  14. Wibudi A, Kiranadi B, Manalu W, winarto A, Suyono S. The traditional plant, Andrographis paniculata (Sambiloto), exhibits insulin-releasing actions in vitro. Acta Med Indones. Apr2008;40(2):63-68.
  15. Verma N, Vinayak M. Antioxidant action of Andrographis paniculata on lymphoma. Mol Biol Rep. Dec 2008;35(4):535-540.
  16. Zhang XF, Tan BK. Anti-diabetic property of ethanolic extract of Andrographis paniculata in streptozotocin-diabetic rats. Acta Pharmacol Sin. Dec2000;21(12):1157-1164.
  17. Dandu AM, Inamdar NM. Evaluation of beneficial effects of antioxidant properties of aqueous leaf extract of Andrographis paniculata in STZ-induced diabetes. Pak J Pharm Sci. Jan2009;22(1):49-52.
  18. Trivedi NP, Rawal UM, Patel BP. Potency of andrographolide as an antitumor compound in BHC-induced liver damage. Integr Cancer Ther. Jun2009;8(2):177-189.
  19. Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R. Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. J Exp Ther Oncol. May-Jun2003;3(3):147-158.
  20. Varma A, Padh H, Shrivastava N. Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon.Evid Based Complement Alternat Med. 14Sep2009.
  21. Chen JH, Hsiao G, Lee AR, Wu CC, Yen MH. Andrographolide suppresses endothelial cell apoptosis via activation of phosphatidyl inositol-3-kinase/Akt pathway. Biochem Pharmacol. 1Apr2004;67(7):1337-1345.
  22. Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S. Anticancer and immunostimulatory compounds from Andrographis paniculata. J Ethnopharmacol. Jun2004;92(2-3):291-295.
  23. Han Y, Bu LM, Ji X, Liu CY, Wang ZH. Modulation of multidrug resistance by andrographolid in a HCT-8/5-FU multidrug-resistant colorectal cancer cell line. Chin J Dig Dis. 2005;6(2):82-86.
  24. Yang L, Wu D, Luo K, Wu S, Wu P. Andrographolide enhances 5-fluorouracil-induced apoptosis via caspase-8-dependent mitochondrial pathway involving p53 participation in hepatocellular carcinoma (SMMC-7721) cells. Cancer Lett. 18Apr2009;276(2):180-188.
  25. Sheeja K, Kuttan G. Activation of cytotoxic T lymphocyte responses and attenuation of tumor growth in vivo by Andrographis paniculata extract and andrographolide. Immunopharmacol Immunotoxicol. 2007;29(1):81-93.
  26. Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S. Anticancer and immunostimulatory compounds from Andrographis paniculata. J Ethnopharmacol. Jun2004;92(2-3):291-295.
  27. Ji LL, Wang Z, Dong F, Zhang WB, Wang ZT. Andrograpanin, a compound isolated from anti-inflammatory traditional Chinese medicine Andrographis paniculata, enhances chemokine SDF-1alpha-induced leukocytes chemotaxis. J Cell Biochem. 1Aug2005;95(5):970-978.
  28. Bao Z, Guan S, Cheng C, Wu S, et al. A novel antiinflammatory role for andrographolide in asthma via inhibition of the nuclear factor-kappaB pathway. Am J Respir Crit Care Med. 15Apr2009;179(8):657-665.
  29. Xia YF, Ye BQ, Li YD, et al. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. J Immunol. 15Sep2004;173(6):4207-4217.
  30. Shen YC, Chen CF, Chiou WF. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect. Br J Pharmacol. Jan2002;135(2):399-406.
  31. Calabrese C, Berman SH, Babish JG, et al. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res. 2000;14(5):333-338.
  32. Gabrielian ES, Shukarian AK, Goukasova GI, 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. Oct2002;9(7):589-597.
  33. Shakhova EG, Spasov AA, Ostrovskiĭ OV, et al. [Effectiveness of using the drug Kan-Yang in children with acute respiratory viral infection (clinico-functional data)] Vestn Otorinolaringol. 2003;(3):48-50.
  34. Cáceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK. 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. Oct 1999;6(4):217-223.
  35. Melchior J, Spasov AA, Ostrovskij OV, Bulanov AE, Wikman G. 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. Oct2000;7(5):341-350.
  36. Poolsup N, Suthisisang C, Prathanturarug S, Asawamekin A, Chanchareon U. Andrographis paniculata in the symptomatic treatment of uncomplicated upper respiratory tract infection: systematic review of randomized controlled trials. J Clin Pharm Ther. Feb2004;29(1):37-45.
  37. Burgos RA, Hancke JL, Bertoglio JC,et al. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol. Aug 2009;28(8):931-946.
  38. Coon JT, Ernst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med. Apr2004;70(4):293-298.
  39. Burgos RA, Aguila MJ, Santiesteban ET, Sánchez NS, Hancke JL. Andrographis paniculata (Ness) induces relaxation of uterus by blocking voltage operated calcium channels and inhibits Ca2+ influx. Phytother Res. May2001;15(3):235-239.
  40. Zhang YZ, Tang JZ, Zhang YJ. [Study of Andrographis paniculata extracts on antiplatelet aggregation and release reaction and its mechanism] Zhongguo Zhong Xi Yi Jie He Za Zhi. Jan1994;14(1):28-30, 34, 35.
  41. Amroyan E, Gabrielian E, Panossian A, Wikman G, Wagner H. Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation. Phytomedicine. Mar1999;6(1):27-31.