Cryptolepis

Across West Africa the root is taken for fever and malaria, and for hepatitis, high blood pressure, urinary and upper respiratory tract infections, colic and stomach complaints, amoebic dysentery and diarrhoea ^{35Reference 35FernFern, K. (n.d.). Cryptolepis sanguinolenta (Lindl.) Schltr. — habit, range, habitat, uses and hazards, drawing on PROTA (Plant Resources of Tropical Africa) — species database. Useful Tropical Plants Database. https://tropical.theferns.info/viewtropical.php?id=Cryptolepis+sanguinolentaView study →}.

It is also used for wounds, measles, hernia, snakebite, rheumatism and insomnia ^{35Reference 35FernFern, K. (n.d.). Cryptolepis sanguinolenta (Lindl.) Schltr. — habit, range, habitat, uses and hazards, drawing on PROTA (Plant Resources of Tropical Africa) — species database. Useful Tropical Plants Database. https://tropical.theferns.info/viewtropical.php?id=Cryptolepis+sanguinolentaView study →}. The root is chewed, or the root bark or an extract of the root is taken as a tea ^{35Reference 35FernFern, K. (n.d.). Cryptolepis sanguinolenta (Lindl.) Schltr. — habit, range, habitat, uses and hazards, drawing on PROTA (Plant Resources of Tropical Africa) — species database. Useful Tropical Plants Database. https://tropical.theferns.info/viewtropical.php?id=Cryptolepis+sanguinolentaView study →}.

The roots are collected from the wild and sold in local markets, both as medicine and as a source of yellow dye ^{35Reference 35FernFern, K. (n.d.). Cryptolepis sanguinolenta (Lindl.) Schltr. — habit, range, habitat, uses and hazards, drawing on PROTA (Plant Resources of Tropical Africa) — species database. Useful Tropical Plants Database. https://tropical.theferns.info/viewtropical.php?id=Cryptolepis+sanguinolentaView study →}.

A related species, Cryptolepis buchananii, grows through Indonesia, Thailand, China, India and Nepal. Its alkaloid profile differs from that of the West African plant.

In Thailand it was used for systemic inflammation, arthritis and muscle pain.

In India it was used for diarrhoea, bacterial infections and ulcers, and for rickets in children.

This is the herb’s traditional core use. In vitro, cryptolepine and related root-bark alkaloids strongly inhibit chloroquine-resistant strains of Plasmodium falciparum, and cryptolepine hydrochloride suppressed P. berghei infection in mice ^{2Reference 2Cimanga et al. · 1997In vitroIn vitro and in vivo antiplasmodial activity of cryptolepine and related alkaloids from Cryptolepis sanguinolenta — in vitro and animal in vivoView study →}.

Aqueous and ethanolic extracts of both the leaves and the roots gave 90% inhibition of a multidrug-resistant P. falciparum strain at concentrations below 23 μg/mL. Cryptolepine was the most active alkaloid, with potency comparable to chloroquine ^{3Reference 3Paulo et al. · 2000In vitroAntiplasmodial activity of Cryptolepis sanguinolenta alkaloids from leaves and roots — in vitroView study →}.

Cryptolepine also acts synergistically with artemisinin derivatives against P. falciparum in vitro and with artesunate in infected mice ^{4Reference 4Forkuo et al. · 2016In vitroSynergistic anti-malarial action of cryptolepine and artemisinins — in vitro and animal modelView study →}.

The one human study was an open, uncontrolled trial in 44 people with acute uncomplicated falciparum malaria ^{1Reference 1Bugyei et al. · 2010Clinical trialClinical efficacy of a tea-bag formulation of Cryptolepis sanguinolenta root in the treatment of acute uncomplicated falciparum malaria — clinical trialView study →}. Each took a tea bag holding 2.5 g of root powder three times a day for five days. Half had cleared the parasites by 72 hours and all by day 7, and fever, chills, nausea and vomiting had resolved by day 3. The overall cure rate was 93.5%, with two recurrences on days 21 and 28, and laboratory tests showed no toxicity ^{1Reference 1Bugyei et al. · 2010Clinical trialClinical efficacy of a tea-bag formulation of Cryptolepis sanguinolenta root in the treatment of acute uncomplicated falciparum malaria — clinical trialView study →}.

Gap: one small open-label trial, no comparator, and no randomised controlled trial. Efficacy against severe or non-falciparum malaria is untested — and severe malaria kills quickly, so this is not a substitute for established antimalarial treatment.

The in vitro record is broad. In one fractionation study of an ethanolic root extract, the chloroform fraction inhibited every organism tested and was the only fraction that killed bacteria rather than just stopping their growth. The water fraction inhibited 75–88% of strains ^{7Reference 7Mills-Robertson et al. · 2012In vitroIn vitro antimicrobial activity of ethanolic fractions of Cryptolepis sanguinolenta — in vitroView study →}.

In a screen against seven reference strains, the ethanol root extract and the alkaloids cryptolepine and cryptoheptine inhibited every strain except Pseudomonas aeruginosa ^{8Reference 8Paulo et al. · 1994In vitroIn vitro antibacterial screening of Cryptolepis sanguinolenta alkaloids — in vitroView study →}. Cryptolepine and the ethanol extract are active against Campylobacter strains from gastroenteritis, and more weakly against Vibrio cholerae ^{9Reference 9Paulo et al. · 1994In vitroCryptolepis sanguinolenta activity against diarrhoeal bacteria — in vitroView study →}.

Cryptolepine kills Staphylococcus aureus, and electron microscopy shows the bacterial cells breaking apart ^{10Reference 10Sawer et al. · 2005In vitroThe killing effect of cryptolepine on Staphylococcus aureus — in vitroView study →}.

Neocryptolepine inhibits Gram-positive bacteria and is less active against Gram-negative ones. Biscryptolepine is active against some Gram-positive bacteria, and both slow growth rather than kill. Cryptoquindoline showed no activity ^{11Reference 11Cimanga et al. · 1998In vitroAntibacterial and antifungal activities of neocryptolepine, biscryptolepine and cryptoquindoline, alkaloids isolated from Cryptolepis sanguinolenta — in vitroView study →}.

Gap: no clinical trial has tested cryptolepis against any bacterial infection. The most bactericidal fraction is a chloroform extract, not the water decoction the tradition uses.

Cryptolepine intercalates into DNA and inhibits topoisomerase II, and it blocks DNA synthesis in melanoma cells ^{34Reference 34Bonjean et al. · 1998In vitroThe DNA intercalating alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in B16 melanoma cells — in vitroView study →}. Most of the anticancer work is in cell lines, with a few mouse xenografts.

In colorectal cancer cells it suppresses proliferation, stemness and migration by inhibiting WNT/β-catenin signalling, and it reduced cell viability more potently than the reference WNT inhibitor XAV 939 ^{15Reference 15Quarshie et al. · 2023In vitroCryptolepine suppresses colorectal cancer cell proliferation, stemness, and metastatic processes by inhibiting WNT/β-catenin signaling — in vitroView study →}.

In liver cancer (HepG2) cells it downregulates IL-6/STAT3 signalling ^{16Reference 16Domfeh et al. · 2021In vitroCryptolepine inhibits hepatocellular carcinoma growth through inhibiting interleukin-6/STAT3 signalling — in vitroView study →}.

In breast cancer models it blocks HIF-1-mediated glycolysis and slowed tumour growth in a 4T1 xenograft ^{17Reference 17Zheng et al. · 2022In vitroCryptolepine suppresses breast adenocarcinoma via inhibition of HIF-1 mediated glycolysis — in vitro and mouse xenograftView study →}.

In triple-negative breast cancer cells it acts on mutant p53 to trigger cell-cycle arrest and apoptosis, and it was more toxic to these cells than to other breast cancer lines ^{19Reference 19Qayoom et al. · 2024In vitroMutant p53 modulation by cryptolepine through cell cycle arrest and apoptosis in triple negative breast cancer — in vitroView study →}.

In melanoma it inhibited human melanoma cells but not normal melanocytes, and 10 mg/kg injected into the abdomen slowed A375 xenograft growth in nude mice. The effect involved AMPK-LKB1 activation and disrupted mitochondrial dynamics ^{18Reference 18Pal et al. · 2017In vitroCryptolepine inhibits melanoma cell growth through coordinated changes in mitochondrial biogenesis, dynamics and the metabolic tumor suppressor AMPKα1/2-LKB1 — in vitro and mouse xenograftView study →}.

A review frames cryptolepine as a lead compound for cancer drugs ^{14Reference 14Ansah et al. · 2013ReviewA review of the anticancer potential of the antimalarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine — reviewView study →}.

The work is preclinical and centred on isolated cryptolepine. Its DNA-intercalating cytotoxicity also affects healthy cells, and no data establish a safe therapeutic dose in humans.

Cryptolepine injected into the abdomen at 10–40 mg/kg produced dose-dependent inhibition of carrageenan-induced paw oedema and pleurisy in rats, compared against indomethacin. It also reduced LPS-induced leakage from small blood vessels in mice and relieved pain in the writhing test. Four days of oral dosing up to 40 mg/kg caused no stomach lesions ^{20Reference 20Olajide et al. · 2009AnimalAnti-inflammatory properties of cryptolepine — animal modelView study →}.

In LPS-activated rat microglia, cryptolepine lowered TNF-α, IL-6, IL-1β, nitric oxide and PGE2 and reduced COX-2 and iNOS, acting partly through NF-κB and p38 MAPK ^{21Reference 21Olajide et al. · 2013In vitroInhibition of neuroinflammation in LPS-activated microglia by cryptolepine — in vitroView study →}. In IL-1β-stimulated human neuroblastoma cells it lowered TNF-α, IL-6 and PGE2 ^{22Reference 22Olajide et al. · 2013In vitroAnti-neuroinflammatory properties of synthetic cryptolepine in human neuroblastoma cells: possible involvement of NF-κB and p38 MAPK inhibition — in vitroView study →}.

The animal data use injected cryptolepine at doses far above anything a root decoction reaches, with no human data and no oral dose-response for the whole herb.

In a controlled screen of botanical medicines against Borrelia burgdorferi, cryptolepis was one of the two most active herbs. It was strongly active against both growing (MIC 0.03–0.06%) and non-growing stationary-phase spirochetes. A 1% cryptolepis extract was the only treatment that caused complete eradication in subculture, whereas the antibiotics doxycycline and cefuroxime did not ^{5Reference 5Feng et al. · 2020In vitroEvaluation of natural and botanical medicines for activity against growing and non-growing forms of B. burgdorferi — in vitroView study →}.

Gap: killing spirochetes in a dish is not treating Lyme disease. This is in-vitro work from a single group, with no animal or human study behind it.

In a companion Johns Hopkins screen, cryptolepis had good in vitro activity against Babesia duncani in hamster red blood cells. Its alkaloid cryptolepine had an IC50 of 3.4 μM, lower than the clinical drugs quinine (10 μM) and clindamycin (37 μM). Parasites treated with cryptolepine at 1× IC50 or more did not regrow in subculture, and neither did those treated with the 90% ethanol extract at 2–8× IC50 ^{6Reference 6Zhang et al. · 2021In vitroBotanical medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia demonstrate inhibitory activity against Babesia duncani — in vitroView study →}.

Gap: one in-vitro study, no animal or human data, and the favourable IC50 belongs to isolated cryptolepine rather than the decoction. Babesiosis is a serious infection requiring diagnosis and antimicrobial treatment.

Cryptolepine was identified as the blood-sugar-lowering component of the root by fractionation guided by its traditional use. It stimulates glucose uptake in 3T3-L1 fat cells and lowers blood glucose in rodent models of type II diabetes ^{23Reference 23Bierer et al. · 1998In vitroEthnobotanical-directed discovery of the antihyperglycemic properties of cryptolepine: its isolation from Cryptolepis sanguinolenta, synthesis, and in vitro and in vivo activities — in vitro and animal in vivoView study →}.

In normal rats, an ethanol extract of the stem given by mouth for 21 days lowered blood glucose and blood lipids and reduced glucose absorption from the gut ^{24Reference 24Ajayi et al. · 2012In vitroEffect of ethanolic extract of Cryptolepis sanguinolenta stem on in vivo and in vitro glucose absorption and transport — animal and in vitroView study →}. A review collates the mechanism and rodent data ^{25Reference 25Osafo et al. · 2017ReviewPhytochemical and pharmacological review of Cryptolepis sanguinolenta — reviewView study →}.

The evidence is rodent and in-vitro work, with no human trial.

Cryptolepis has consistent in vitro activity against mycobacteria. Cryptolepine hydrochloride inhibits several fast-growing Mycobacterium species, with MICs of 2–32 μg/mL ^{12Reference 12Gibbons et al. · 2003In vitroCryptolepine hydrochloride: a potent antimycobacterial alkaloid derived from Cryptolepis sanguinolenta — in vitroView study →}.

Among seven Ghanaian plants tested against M. ulcerans, the cause of Buruli ulcer, the root aqueous extract of cryptolepis was the most active (MIC 64 μg/mL), and pure cryptolepine had an MIC of 32 μg/mL ^{13Reference 13Amponsah et al. · 2021In vitroIn vitro anti-Mycobacterium ulcerans and cytotoxic activities of some selected medicinal plants and an indoloquinoline alkaloid — in vitroView study →}.

A methanolic root extract was active against M. smegmatis and against both a drug-sensitive and a rifampicin-resistant strain of M. tuberculosis, most strongly against the resistant strain (MIC 97 μg/mL) ^{32Reference 32Tuyiringire et al. · 2022In vitroIn vitro antimycobacterial activity of medicinal plants Lantana camara, Cryptolepis sanguinolenta, and Zanthoxylum leprieurii — in vitroView study →}.

The work is in vitro only, with no animal or clinical data, and cryptolepine’s general cytotoxicity complicates any systemic use against tuberculosis.

In one study of three minor root-bark alkaloids, neocryptolepine inhibited the yeast Candida albicans. Biscryptolepine and cryptoquindoline showed no antifungal activity, and none of the three was active against the other fungi tested at up to 100 μg/mL ^{11Reference 11Cimanga et al. · 1998In vitroAntibacterial and antifungal activities of neocryptolepine, biscryptolepine and cryptoquindoline, alkaloids isolated from Cryptolepis sanguinolenta — in vitroView study →}.

The data are in vitro and alkaloid-based, and no clinical antifungal use is documented.

Cryptolepine is active against Leishmania donovani, and its semi-synthetic analogue 2,7-dibromocryptolepine is about three times more potent and less toxic to mouse macrophages. The analogue killed the parasites by an apoptosis-like process ^{26Reference 26Hazra et al. · 2012In vitroAntileishmanial activity of cryptolepine analogues and apoptotic effects of 2,7-dibromocryptolepine against Leishmania donovani promastigotes — in vitroView study →}.

Four other semi-synthetic halogenated analogues of cryptolepine inhibited Trypanosoma brucei, the parasite behind African sleeping sickness, at nanomolar concentrations in vitro ^{33Reference 33Abacha et al. · 2022In vitroSemi-synthetic analogues of cryptolepine as a potential source of sustainable drugs for the treatment of malaria, human African trypanosomiasis, and cancer — in vitro and mouse toxicityView study →}.

The useful activity here belongs largely to semi-synthetic analogues rather than to the natural alkaloid or the herb, and all of it is in vitro.

Acute toxicity. The whole-root decoction has a rodent LD50 above 5000 mg/kg. In the open malaria trial, five days of root tea caused no clinical or laboratory toxicity ^{1Reference 1Bugyei et al. · 2010Clinical trialClinical efficacy of a tea-bag formulation of Cryptolepis sanguinolenta root in the treatment of acute uncomplicated falciparum malaria — clinical trialView study →}.

Cytotoxicity. The aqueous root extract and cryptolepine are both strongly toxic to mammalian cells in vitro, including hamster lung cells and most human cancer cell lines tested ^{27Reference 27Ansah et al. · 2002In vitroThe popular herbal antimalarial, extract of Cryptolepis sanguinolenta, is potently cytotoxic — in vitroView study →}.

Genotoxicity. In hamster cells, both the root extract and cryptolepine increased micronuclei, a marker of chromosome damage ^{28Reference 28Ansah et al. · 2005In vitroIn vitro genotoxicity of the West African antimalarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine — in vitroView study →}. The extract caused gene mutations only at a concentration that killed most of the cells, and cryptolepine did not cause gene mutations at the doses tested ^{27,28Reference 27Ansah et al. · 2002In vitroThe popular herbal antimalarial, extract of Cryptolepis sanguinolenta, is potently cytotoxic — in vitroView study →Reference 28Ansah et al. · 2005In vitroIn vitro genotoxicity of the West African antimalarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine — in vitroView study →}. The authors conclude that routine use of the root extract could carry a genotoxic risk ^{28Reference 28Ansah et al. · 2005In vitroIn vitro genotoxicity of the West African antimalarial herbal Cryptolepis sanguinolenta and its major alkaloid cryptolepine — in vitroView study →}.

Blood sugar. Cryptolepine lowers blood glucose in rodent models of diabetes ^{23Reference 23Bierer et al. · 1998In vitroEthnobotanical-directed discovery of the antihyperglycemic properties of cryptolepine: its isolation from Cryptolepis sanguinolenta, synthesis, and in vitro and in vivo activities — in vitro and animal in vivoView study →}, so cryptolepis may add to the effect of diabetes medicines.

Sedatives. The extract reduced activity in mice and lengthened barbiturate-induced sleep in rats ^{25Reference 25Osafo et al. · 2017ReviewPhytochemical and pharmacological review of Cryptolepis sanguinolenta — reviewView study →}. Take care alongside sedatives and other central nervous system depressants.

Long courses. Lyme and Babesia protocols often use cryptolepis at high doses for months. The anti-Borrelia and anti-Babesia data are in vitro only ^{5,6Reference 5Feng et al. · 2020In vitroEvaluation of natural and botanical medicines for activity against growing and non-growing forms of B. burgdorferi — in vitroView study →Reference 6Zhang et al. · 2021In vitroBotanical medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia demonstrate inhibitory activity against Babesia duncani — in vitroView study →}, and long high-dose use has not been studied in people.

Male fertility. A leaf extract lowered testosterone and sperm count in male rats ^{30Reference 30Ajayi et al. · 2012AnimalAntifertility activity of Cryptolepis sanguinolenta leaf ethanolic extract in male rats — animal modelView study →}.

Interactions. No human drug-interaction or CYP450 study has been done. The cautions above follow from the plant’s pharmacology.