Baptisia – a somewhat mysterious phytomedicine

Herbal medicine is full of plants where our historical records of their applications to treat disease and illness are somewhat lacking in content or accuracy. Its also somewhat concerning but also hardly surprising, just how little we really understand about the therapeutic potential and best ways of using, some of the many plants we are taught about or have been made aware of. The fact that much of the knowledge around use of plants as medicines was traditionally transmitted through an oral rather than written form, and that diseases of concern and our understanding of them in the past were different to now, is contributory to this. I remember for example being surprised at how little written information on Echinacea’s traditional use I could find in books on Native Indian Medicine I looked at when travelling in the U.S. many years ago, although we now know it is a brilliant medicine for numerous infectious and inflammatory conditions, for which it was of course also traditionally used.

Wild Indigo

Another North American herb that has always held some mystery to me, is Wild Indigo root (Baptisia tinctoria).  Native to eastern parts of the U.S. and Canada, Baptisia is a Leguminosae family member, and its young shoots were sometimes eaten for greens and used in soups(1) Its root has a somewhat bitter and acrid taste and was a treasured medicine to some native American Indians(2,3).  While having yellow flowers, all parts of Wild Indigo when dried yield a blue dye.  Another species, Baptisia australis, which grew well in my garden years ago, has blue rather than yellow flowers and has been said to be able to be used interchangeably(4), although this claim has not been validated.

Antimicrobial

These indications are reflective of a good antimicrobial phytomedicine. Moderate in vitro activity has been reported for extracts against Staphylococcus aureus(6), and yet surprisingly few other studies into antimicrobial activity or clinical studies appear to have been published on the use of Wild Indigo alone.  Clinical trials involving combinations of Baptisia tinctoria root, Echinacea purpurea root, Echinacea pallida root and Thuja occidentalis reported an improvement in cold symptoms earlier than placebo(7, 8, 9). Enhanced phagocytic activity by leukocytes was also reported for a combination of Baptisia tinctoria, Eupatorium cannabinum and Arnica with Echinacea angustifolia, than that measured for Echinacea alone(10).

The fact that large doses can be emetic, may account for some of this relative paucity of scientific studies into the Wild Indigo’s antimicrobial potential. However, early investigations into its use as a fresh tincture by the Eclectic physicians for typhoid, spurred by the fact that excessive doses can produce fever and other symptoms similar to those of typhoid, appear also to have clouded our view of this phytomedicine.

Large polysaccharide fractions were reported by German researchers in 1985 to show significant immunostimulant activities(11) and enhance production of antibodies against sheep red blood cells(12). A contribution of arabinogalactan proteins extracted from polysaccharides found in Wild Indigo root to its claimed immune-stimulant properties has also been reported(13, 14). These are said to be mediated through a specific antigen-antibody reaction rather than non-specific immune system activation. These effects and reported efficacy using low doses of Wild Indigo root for the treatment of typhoid, has attracted the interest of homoeopathic researchers and product manufacturers(15). However, little published evidence of such effects from low doses in human studies appears to exist, and it would seem this impression of Wild Indigo’s therapeutic properties has perhaps contributed to a blurred understanding of how best to use it, and in what dose.

Typhoid (Salmonella typhi) used to be a serious bacterial infection in much of the world until the development of a vaccine 120 years ago, and still remains a serious infectious bacterial disease in third world countries. Successful management of typhoid fever using antibiotics is also becoming increasingly difficult due to emerging and spreading drug resistance(16). As such, and given the strong historical reputation of Wild Indigo, further research into its relevant activities in the management of this and other infectious diseases seems warranted.

Other applications

Wild Indigo was also sometimes taken in large doses as a purgative. In the 1870’s two chemists Weaver and Greene characterised certain alkaloids including baptisine (baptotoxine), said to be poisonous and likely to contribute to these effects(1). Baptisine was however subsequently shown to be identical with another quinolizidine alkaloid cytisine(17). This is a well-known constituent of various medicinal and somewhat poisonous plants such as the unripe seeds of Laburnum (Cytisus laburnum) and species of Sophora, including those used in traditional Chinese medicine as well as the New Zealand native Kowhai (various Sophora species)(18, 19).

All medicines including plant-derived ones can produce adverse effects, particularly in sensitive individuals or when excessive doses are taken. However, one person’s poison can be another person’s medicine, and while probably contributory to nausea and vomiting when excessive doses of Wild Indigo are taken, cytisine is also used as a medicine. As an alkaloid with nicotinic acetylcholine receptor-agonist properties, it is being increasingly used in small doses for smoking cessation(20). Various clinical trials in New Zealand have in fact found cytisine to have promising potential as an aid to smoking cessation(21, 22, 23, 24).

Case reports of poisoning following ingestion of Wild Indigo mistaken for asparagus have been made, although doses taken were much higher than recommended when used as a medicine (Anderson). As with Wild Indigo poisoning in North America, poisoning due to ingestion of too high a dose of Kowhai (particularly of the high cytisine-containing seeds or aerial parts rather than bark)i, is  not uncommon here in New Zealand(25).  Notably, the effects of such poisoning or overdose are similar to the most frequently reported adverse reactions of cytisine when used as a drug, and include gastrointestinal symptoms that are mostly reported as either mild or moderate in severity(20).

While its content of cytisine and thus tolerance to different doses will vary between individuals, the use of Wild Indigo bark in smoking cessation treatment is potentially indicated.  Analogies to the use of Lobelia inflata, which contains another nicotinic receptor-agonist lobeline, for smoking cessation treatment but invokes emesis in excessive doses (hence its common name ‘Pukeweed’), also spring to mind.  Novel nicotinic partial agonists including cytisine also show potential protective effects in animal studies, against Parkinson’s disease(26), depression and anxiety (27).

True Indigo (Indigofera tinctoria)

Native to southern Asia and now naturalised in many countries, the botanically related True Indigo (Indigofera tinctoria) was one of the original sources of indigo dye. It is also used in traditional medicine, and was used in India to control epileptic seizures. Dose dependent anticonvulsant effects in animal studies have been shown for an ethanolic extract of the whole plant, effects accompanied by increased brain levels of the inhibitory neurotransmitter GABA (gamma amino butyric acid)(28). Protection against the negative immunological effects of noise stress, and stimulation of both adaptive and innate immunity, has also been reported in rats(29).

Anthelmintic activity including inhibition of egg hatching has also been reported against gastrointestinal nematodes in sheep (30). Planting of Indigofera tinctoria has also been shown to help control nematode infestations in the soil(31).

References:

  1. Felter HW, Lloyd JR. 1898. King’s American Dispensatory. Sandy, Oregon: Eclectic Medical Publications.
  2. Hutchens AR. 1973. Indian Herbalogy of North America. Boston, Massachusetts: Shambhala Publications Inc.
  3. Millspaugh CF, American Medicinal Plants, Dover Publications Inc, New York, 1974.
  4. Milton Welch J. The Medical Flora of Kansas. Transactions of the National Eclectic Association. 1882-83, Vol. X. Accessed 18 September 2008.
    <http://www.henriettesherbal.com/eclectic/journals/net1882/net-1882-kansas1.html&gt;
  5. Felter HW. 1922. The Eclectic Materia Medica, Pharmacology and Therapeutics. Sandy, Oregon: Eclectic Medical Publications.
  6. Snowden R, Harrington H, Morrill K, Jeane L, Garrity J, Orian M, Lopez E, Rezaie S, Hassberger K, Familoni D, Moore J, Virdee K, Albornoz-Sanchez L, Walker M, Cavins J, Russell T, Guse E, Reker M, Tschudy O, Wolf J, True T, Ukaegbu O, Ahaghotu E, Jones A, Polanco S, Rochon Y, Waters R, Langland J. A comparison of the anti-Staphylococcus aureus activity of extracts from commonly used medicinal plants. J Altern Complement Med. 2014 May;20(5):375-82. doi: 10.1089/acm.2013.0036. Epub 2014 Mar 17. PMID: 24635487.
  7. Henneicke-von Zepelin H, Hentschel C, Schnitker J, Kohnen R, Köhler G, Wüstenberg P. Efficacy and safety of a fixed combination phytomedicine in the treatment of the common cold (acute viral respiratory tract infection): results of a randomised, double blind, placebo controlled, multicentre study. Curr Med Res Opin. 1999;15(3):214-27. doi: 10.1185/03007999909114094. PMID: 10621929.
  8. Naser B, Lund B, Henneicke-von Zepelin HH, Köhler G, Lehmacher W, Scaglione F. A randomized, double-blind, placebo-controlled, clinical dose-response trial of an extract of Baptisia, Echinacea and Thuja for the treatment of patients with common cold. Phytomedicine. 2005 Nov;12(10):715-22. doi: 10.1016/j.phymed.2005.03.002. PMID: 16323289.
  9. Henneicke-von Zepelin HH, Nicken P, Naser B, Kuchernig JC, Brien N, Holtdirk A, Schnitker J, Nolte KU. Non-interventional observational study broadens positive benefit-risk assessment of an immunomodulating herbal remedy in the common cold. Curr Med Res Opin. 2019 Oct;35(10):1711-1719. doi: 10.1080/03007995.2019.1618252. Epub 2019 Jun 17. PMID: 31074674.Anderson MJ, Kurtycz DF, Cline JR. Baptisia poisoning: a new and toxic look-alike in the neighborhood. J Emerg Med. 2015 Jan;48(1):39-42. doi: 10.1016/j.jemermed.2014.09.037. Epub 2014 Nov 6. PMID: 25453859.
  10. Wagner H, Jurcic K. Immunologische Untersuchungen von pflanzlichen Kombinationspräparaten. In-vitro- und In-vivo-Studien zur Stimulierung der Phagozytosefähigkeit [Immunologic studies of plant combination preparations. In-vitro and in-vivo studies on the stimulation of phagocytosis]. Arzneimittelforschung. 1991 Oct;41(10):1072-6. German. PMID: 1799388.
  11. Wagner H, Proksch A, Riess-Maurer I, Vollmar A, Odenthal S, Stuppner H, Jurcic K, Le Turdu M, Fang JN. Immunstimulierend wirkende Polysaccharide (Heteroglykane) aus höheren Pflanzen [Immunostimulating action of polysaccharides (heteroglycans) from higher plants]. Arzneimittelforschung. 1985;35(7):1069-75. German. PMID: 4052142.Mineur YS, Eibl C, Young G, Kochevar C, Papke RL, Gündisch D, Picciotto MR. Cytisine-based nicotinic partial agonists as novel antidepressant compounds. J Pharmacol Exp Ther. 2009 Apr;329(1):377-86. doi: 10.1124/jpet.108.149609. Epub 2009 Jan 22. PMID: 19164465; PMCID: PMC2670591.
  12. Beuscher N, Kopanski L. Stimulation der Immunantwort durch Inhaltsstoffe aus Baptisia tinctoria. (Stimulation of immunity by the contents of Baptisia tinctoria]. Planta Med. 1985 Oct;51(5):381-4. doi: 10.1055/s-2007-969525. PMID: 17342588.
  13. Egert D, Beuscher N. Studies on antigen specifity of immunoreactive arabinogalactan proteins extracted from Baptisia tinctoria and Echinacea purpurea. Planta Med. 1992 Apr;58(2):163-5. doi: 10.1055/s-2006-961420. PMID: 1382301.
  14. Classen B, Thude S, Blaschek W, Wack M, Bodinet C. Immunomodulatory effects of arabinogalactan-proteins from Baptisia and Echinacea. Phytomedicine. 2006 Nov;13(9-10):688-94. doi: 10.1016/j.phymed.2005.10.004. Epub 2005 Nov 14. PMID: 17085292.
  15. Banerji P, Banerji P, Das GC, Islam A, Mishra SK, Mukhopadhyay S. Efficacy of Baptisia tinctoria in the treatment of typhoid: its possible role in inducing antibody formation. J Complement Integr Med. 2012 Jul 2;9:Article 15. doi: 10.1515/1553-3840.1622. PMID: 22850071.
  16. Masuet-Aumatell C, Atouguia J. Typhoid fever infection – Antibiotic resistance and vaccination strategies: A narrative review. Travel Med Infect Dis. 2021 Mar-Apr;40:101946. doi: 10.1016/j.tmaid.2020.101946. Epub 2020 Dec 8. PMID: 33301931.
  17. Plugge PC, Arch. der Pharm. (1891), 229, p. 48.
  18. McDougal OM, Heenan PB, Jaksons P, Sansom CE, Smallfield BM, Perry NB, van Klink JW. Alkaloid variation in New Zealand kōwhai, Sophora species. Phytochemistry. 2015 Oct;118:9-16. doi: 10.1016/j.phytochem.2015.07.019. Epub 2015 Aug 6. PMID: 26253652.
  19. Wang H, Xia C, Chen L, Zhao J, Tao W, Zhang X, Wang J, Gao X, Yong J, Duan JA. Phytochemical Information and Biological Activities of Quinolizidine Alkaloids in Sophora: A Comprehensive Review. Curr Drug Targets. 2019;20(15):1572-1586. doi: 10.2174/1389450120666190618125816. PMID: 31215388.
  20. Tutka P, Vinnikov D, Courtney RJ, Benowitz NL. Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation. Addiction. 2019 Nov;114(11):1951-1969. doi: 10.1111/add.14721. Epub 2019 Jul 19. PMID: 31240783.
  21. Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C. Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014 Dec 18;371(25):2353-62. doi: 10.1056/NEJMoa1407764. PMID: 25517706.
  22. Walker N, Smith B, Barnes J, Verbiest M, Parag V, Pokhrel S, Wharakura MK, Lees T, Cubillos Gutierrez H, Jones B, Bullen C. Cytisine versus varenicline for smoking cessation in New Zealand indigenous Māori: a randomized controlled trial. Addiction. 2021 Mar 24. doi: 10.1111/add.15489. Epub ahead of print. PMID: 33761149.
  23. Thompson-Evans TP, Glover MP, Walker N. Cytisine’s potential to be used as a traditional healing method to help indigenous people stop smoking: a qualitative study with Māori. Nicotine Tob Res. 2011 May;13(5):353-60. doi: 10.1093/ntr/ntr002. Epub 2011 Mar 8. PMID: 21385905.
  24. Cahill K, Lindson-Hawley N, Thomas KH, Fanshawe TR, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2016 May 9;2016(5):CD006103. doi: 10.1002/14651858.CD006103.pub7. PMID: 27158893; PMCID: PMC6464943.
  25. Slaughter RJ, Beasley DM, Lambie BS, Wilkins GT, Schep LJ. Poisonous plants in New Zealand: a review of those that are most commonly enquired about to the National Poisons Centre. N Z Med J. 2012 Dec 14;125(1367):87-118. PMID: 23321887.
  26. Henderson BJ, Lester HA. Inside-out neuropharmacology of nicotinic drugs. Neuropharmacology. 2015;96(Pt B):178-193. doi:10.1016/j.neuropharm.2015.01.022.
  27. Mineur YS, Cahuzac EL, Mose TN, Bentham MP, Plantenga ME, Thompson DC, Picciotto MR. Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology. 2018 Sep;43(10):2118-2125. doi: 10.1038/s41386-018-0024-x. Epub 2018 Feb 22. PMID: 29472646; PMCID: PMC6098039.
  28. Garbhapu A, Yalavarthi P, Koganti P. Effect of Ethanolic Extract of Indigofera tinctoria on Chemically-Induced Seizures and Brain GABA Levels in Albino Rats. Iran J Basic Med Sci. 2011 Jul;14(4):318-26. PMID: 23493444; PMCID: PMC3586835.
  29. Madakkannu B, Ravichandran R. In vivo immunoprotective role of Indigofera tinctoria and Scoparia dulcis aqueous extracts against chronic noise stress induced immune abnormalities in Wistar albino rats. Toxicol Rep. 2017;4:484-493. Published 2017 Sep 6. doi:10.1016/j.toxrep.2017.09.001.
  30. Meenakshisundaram A, Harikrishnan TJ, Anna T. Anthelmintic activity of Indigofera tinctoria against gastrointestinal nematodes of sheep. Vet World. 2016 Jan;9(1):101-6. doi: 10.14202/vetworld.2016.101-106. Epub 2016 Jan 31. PMID: 27051192; PMCID: PMC4819.
  31. Morris JB, Walker JT. Non-traditional legumes as potential soil amendments for nematode control. J Nematol. 2002 Dec;34(4):358-61. PMID: 19265956; PMCID: PMC2620579.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s