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Dichroa Root

Scientific Name(s): Dichroa febrifuga Lour
Common Name(s): Basak, Big golden sword, British Indian, Ch'ang shan, Chi-fen ts'ao, Chi-ku ch'ang-shan, Chi-ku feng, Chicken-bone alum root, Chicken-droppings grass, Chinese quinine, Dichroa root, Huang ch'ang-shan, Native alum root, Pai ch'ang-shan, T'u ch'ang-shan, Ta chin-tao, Thuong son, White alum root, Yellow alum root

Clinical Overview

Use

Dichroa root has been used to treat malaria for centuries in China; however, there are no recent clinical trials to support this use.

Dosing

There are no recent clinical studies of dichroa root to provide dosing recommendations.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Possible adverse effects include nausea, vomiting, and diarrhea. Hepatotoxicity is also a concern.

Toxicology

Limited information concerning toxicity of dichroa root is available.

Botany

Dichroa root comes from a deciduous shrub that prefers damp areas such as wooded valleys or stream edges. The roots and leaves are used medicinally. The plant bears light-blue flowers and blue-colored berries.Doctor's Manual 1977

History

rIn China, dichroa root has been used to treat malaria for many centuries.Hocking 1977, Takaya 1999 One of the earliest records of plants used as medicine includes dichroa root.Taylor 1981 In his book Flora Cochinchinensis (published in 1790), Portuguese Jesuit João de Loureiro described the febrifugal (ie, mitigating fever) and emetic properties of ch’ang shan and provided the scientific name Dichroa febrifuga.Burns 2008 Chinese scholar/emperor Shen Nung (circa 2735 BC) recorded the plant's effectiveness in treating fever caused by malaria parasites.Burger 1999

Chemistry

Alkaloid febrifugine and its isomer isofebrifugine were isolated during World War II in order to study their effects against malaria.Hocking 1977, Takaya 1999 Febrifugine is the main alkaloidal constituent present.Murata 1999 Halofuginone and haloguinol are synthetic derivatives of dichroa root. Halofuginone, along with other febrifugine analogues, was developed in the 1960s for antimalarial evaluation.McLaughlin 2014

Uses and Pharmacology

Antimalarial activity

With drug resistance from medications such as chloroquine and quinine becoming prevalent, researchers have sought other antimalarial sources. Isolates of D. febrifuga, febrifugine and isofebrifugine, were found to be the active components against malaria; however, chemists could not separate adverse effects (eg, nausea, vomiting, diarrhea) from their beneficial actions.Burger 1999, Zeng 1982, Zhao 1986, Zhu 2012 Febrifugine exerts its antimalarial effects by impairing the haemazoin formation needed for parasite maturation at the trophozoite stage. Various analogues have been synthesized in an effort to minimize adverse effects and enhance bioavailability; some of these compounds have therapeutic indices greater than 10 times that of chloroquine.McLaughlin 2014, Zhu 2009 One study suggested that increased lipophilicity of the analogues was associated with improved antimalarial activity.Doctor's Manual 1977, Zhu 2012

Animal and in vitro data

Febrifugine and isofebrifugine in certain preparations (eg, acetone extract) demonstrated high antimalarial activity against Plasmodium falciparum and Plasmodiumberghei.Takaya 1999 In a study evaluating the effects of an aqueous extract of D. febrifuga against P. berghei in mice, a reduction in infection rate and an increase in mean survival time were observed.Gopal 1982.Two reports suggest that dichroa extracts alter nitric oxide (NO) concentrations. In mice infected with P. berghei, febrifugine 1 mg/kg/day orally reduced mortality and parasitemia, and increased NO production and plasma concentration, thus contributing to host defense against malaria infection.Murata 1999 In an in vivo study, febrifugine significantly enhanced NO production in mouse peritoneal macrophages, with dose-dependent activations.Murata 1998 However, another study investigating the effects of an aqueous extract of D. febrifuga root demonstrated a decrease in NO production as well as tumor necrosis factor, which plays a role in endotoxin-mediated shock and inflammation. In mouse macrophages, NO synthase and NO serum levels were decreased, suggesting suppression of inflammatory response and possible use as an anti-inflammatory.Kim 2000

Clinical data

Research reveals no clinical data regarding the use of dichroa root for malaria.

Other uses

Changrolin, a Chinese antiarrhythmic drug derived from dichroa, has been studied for its antiarrhythmic effects in small mammal cardiac cells.Chen 2010, Lu 1995 In a study testing synthetic febrifugine analogues, cytotoxic effects against cancer cells lines (KB, MCF7, LU1, and HepG2) were observed.Mai 2014 In vitro testing demonstrated potential tumoricidal properties associated with dichroa root.Mazzio 2009

In one study, febrifugine analogues exerted activity against Leishmania donovani parasites.Pandey 2017 In a study using rat liver, an aqueous extract of D. febrifuga root regulated inflammation-related proteins, suggesting a potential role in the management of inflammation.Choi 2003 Similarly, in another study in lipopolysaccharide-stimulated macrophages, the aqueous. extract exerted anti-inflammatory effects via inhibition of interleukin (IL)-1beta and IL-6 production in a dose-dependent manner. D. febrifuga did not decrease the viability of the cells.Park 2009

Dosing

There are no recent clinical studies of dichroa root to provide dosing recommendations.

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Nausea, vomiting, and diarrhea have been reported.Burger 1999 Dichroa root may cause hepatotoxicity.Mojab 2012, Zhu 2012, Zhu 2009

Toxicology

Information regarding toxicity with use of dichroa root is lacking.

References

A Barefoot Doctor's Manual: Practical Chinese Medicine and Health. Bethesda, MD: US Department of Health, Education & Welfare; 1977;878.
Burger A. Understanding Medications. What the Label Doesn't Tell You. Washington, DC: American Chemical Society Publication; 1999.
Burns WR. East meets West: how China almost cured malaria. Endeavour. 2008;32(3):101-106.18691761
Chen WH, Yang D, Wang WY, Zhang J, Wang YP. Cellular electrophysiological effects of changrolin in isolated rat cardiac myocytes. Eur J Pharmacol. 2010;647(1-3):139-146.20826150
Choi BT, Lee JH, Ko WS, et al. Anti-inflammatory effects of aqueous extract from Dichroa febrifuga root in rat liver. Acta Pharmacol Sin. 2003;24(2):127-132.12546719
Gopal H, Mohan V, Purushothaman KK. Effect of Dichroa febrifuga on Plasmodium berghei. Indian J Pathol Microbiol. 1982;25(4):269-272.6762348
Hocking, G. A Dictionary of Natural Products. Medford, NJ: Plexus Publishing Inc; 1977;253.
Kim YH, Ko WS, Ha MS, et al. The production of nitric oxide and TNF-alpha in peritoneal macrophages is inhibited by Dichroa febrifuga Lour. J Ethnopharmacol. 2000;69(1):35-43.10661882
Lu LL, Habuchi Y, Tanaka H, Morikawa J. Electrophysiological effects of changrolin, an anti-arrhythmic agent derived from Dichroa febrifuga, on guinea-pig and rabbit heart cells. Clin Exp Pharmacol Physiol. 1995;22(5):337-341.7554424
Mai HD, Thanh GV, Tran VH, et al. Synthesis and biological evaluation of febrifugine analogues. Nat Prod Commun. 2014;9(12):1717-1720.25632466
Mazzio EA, Soliman KF. In vitro screening for the tumoricidal properties of international medicinal herbs. Phytother Res. 2009;23(3):385-398.18844256
McLaughlin NP, Evans P, Pines M. The chemistry and biology of febrifugine and halofuginone. Bioorg Med Chem. 2014;22(7):1993-2004.24650700
Mojab F. Antimalarial natural products: a review. Avicenna J Phytomed. 2012;2(2):52-62.25050231
Murata K, Takano F, Fushiya S, Oshima Y. Enhancement of NO production in activated macrophages in vivo by an antimalarial crude drug, Dichroa febrifuga. J Nat Prod. 1998;61(6):729-733.9644055
Murata K, Takano F, Fushiya S, Oshima Y. Potentiation by febrifugine of host defense in mice against Plasmodium berghei NK65. Biochem Pharmacol. 1999;58(10):1593-1601.10535750
Pandey RK, Kumbhar BV, Srivastava S, et al. Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation. J Biomol Struct Dyn. 2017;35(1):141-158.27043972
Park SY, Park GY, Ko WS, Kim Y. Dichroa febrifuga Lour. inhibits the production of IL-1beta and IL-6 through blocking NF-kappaB, MAPK, and Akt activation in macrophages. J Ethnopharmacol. 2009;125(2):246-251.19607899
Takaya Y, Tasaka H, Chiba T, et al. New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite. J Med Chem. 1999;42(16):3163-3166.10447961
Taylor J. Introductory Medicinal Chemistry. Chichester, UK: Ellis Horwood Ltd; 1981.10447961
Zeng Y. Development of plant derived drugs in China. Pharm Week. 1982;117:1037-1043
Zhao CX. Effect of Dichroa febrifuga L. on chloroquinsensible and chloroquinresistant malaria parasites [in German]. J Tongji Med Univ. 1986;6(2):112-115.3528514
Zhu S, Chandrashekar G, Meng L, Robinson K, Chatterji D. Febrifugine analogue compounds: synthesis and antimalarial evaluation. Bioorg Med Chem. 2012;20(2):927-932.22182577
Zhu S, Zhang Q, Gudise C, Wei L, Smith E, Zeng Y. Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents. Bioorg Med Chem. 2009;17(13):4496-4502.19467876

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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