Cantharides seu Mylabris, Ban Mao 斑蝥

Blister Beetle, Spanish Fly
Ban Mao (TCM)
Zarawih, Telni-Makkhi, Telni-Pokh (Unani)
Byang Pa བྱང་པ་ (Mylabris spp., Tibet)

Gart der Gesundheit, Cuba, 1485

Cantharides & Buprestes
(Dioscorides Materia Medica, Mathias, 1563)

A. Cantharis vesicatoria; B. Mylabris cichorii; C. Cantharis vitatta
(Scientific and Applied Pharmacognosy, Kraemer, 1915)

Mylabris phalerata at the Chengdu Market (Adam, 2012)

Mylbaris phalerata, one of the official Chinese species.
(Photo by Len Worthington) (Wikimedia)

A Selection of Mylabris species:

7. Mylabris pustulata
(Photos by Udo Schmidt) (Wikimedia 1, 2, 3, 4, 5, 6, 7)

Other Species used similarly:

Blister Fly, Lytta vesicatoria
(Photo by Franco christophe) (Wikimedia)

Epicauta vittata
(Photo by Robert Webster) (Wikimedia)

Entomological name:

Several species are used, the two primary species are:

Mylabris spp. is the Cantharide: M phalerata, M. cichorrii
Cantharis spp., C. vesicatoria, C. vitatta

Other species used similarly or synonymously include:

Blister Fly (Lytta vesicatoria)
Blister Beetle (Epicauta sp.)
Oil Beetle (Meloe spp.) are all used similarly, and can be substituted.

In Tibetan Medicine, 3 varieties are recognised:

Black-striped; superior quality
Black and Red striped; medium quality
Golden-striped; inferior quality

Some said the Black is too strong for use, and regarded the Black and Red striped (Mylabris) as best for medicine. In their strength, 3 Black-striped insects were said to be equal to 7 Black and Red-striped, and 11 Golden-striped insects. (Tibetan text)
There are over 7500 species of Blister Bettle worldwide.

Parts used:

Dried Beetle with head, legs, tail and wings removed, and roasted.
“The most effective spanish flies are those which are multi-coloured having longitudinal yellow lines on their wings and also having some resemblance with cockroach in size. The varieties with one uniform colour are considered weak in action”. (Avicenna)

Temperature & Taste:

Hot, dry (Cold in TCM). Pungent. Toxic
‘Hot in taste, Cold and Toxic in nature”.
“According to some physicians the spanish flies are excessively Hot but some other physicians opine them to be Hot and Dry in the Second degree. The latter statement appears to be correct … The flies are intensely pungent, putrefactive and burning“. (Avicenna)

Classifications:

2M. DRAWING
3E. DIURETIC , 3I. APHRODISIAC
C. Clear Damp, Promote Urine
TCM:
T. External Medicines

Uses:

1. Clears Damp, Promotes Urine, Clears Stones (TCM, West):

-difficulty urinating, urinary Retention, urinary Stones
-Gout, Arthritis, Rheumatism.
-Leukorrhea

2. Moves the Blood, Resolves Phlegm, Clears Masses:

-Scrofula, swollen Lymph nodes and immobile masses.
-Amenorrhea from obstruction of the circulation; forcefully promotes Menstruation
-Uterine growths.
-Cancer (TCM, West)
-internally for “obstinate Ulcers”.
-Promotes Labor, also as an Abortifacient (Salmon); TCM uses it for retention of a Dead Fetus.
-used in Tibetan Medicine to clear and “scrape” the Channels
-“They are also included in Diuretic, Emmenagogue and Ecbolic medicines without causing any harm”. (Avicenna)

3. Clears Wind-Phlegm, Stops Spasms:

-some forms of Paralysis, Epilepsy etc. (Ayurveda)

4. Warms the Kidneys (TCM, West):

-Aphrodisiac for both sexes; its action is via irritation

5. Resists Poison:

-various insect Venoms and other Poisons
-“used in a number of Antidotes”. (Galen)
-Poison of Rabid Dogs and Calomel. (Li Shi Zhen)
-Traditionally used for possession. (TCM)

6. Externally:

-applied to sores, ulcers, scrofula, swollen lymph glands, and necrotic tissue leukoderma, vitiligo, psoriasis and neuro-dermatitis
-“It removes Pityriasis and Leukoderma if used as a paint with vinegar”. (Avicenna)
-“If it is painted on the cancerous swellings it dissolves them”. (Avicenna)
-applied to Alopecia; it is used in hair oils to stimulate hair growth.
-applied to joint pains including Gout, Sciatica and Rheumatism. Often it may be used over the spinal nerves as a counter-irritant with good effect.
-similarly applied to various type of Neuralgia.
-used to draw blisters in acute inflammations
-used in external preparations to be rubbed onto the penis to stimulate erection, and as a stimulant aphrodisiac
-applied as a plaster to the nape of the neck for Fever (old TCM)
-“They are used as a paint to remove Warts”. (Avicenna)

Dose:

1. If used internally, always begin with lesser dose, increasing as required.
2. Different species vary greatly in strength. Individual tolerances can also vary widely.
Prepared Beetle in Powder (head, legs, tail and wings removed): 30–60mg (daily maximum 150mg); traditionally dose was one-quarter to 1 grain.
Tincture (2 drams in a pint of spirit): 5–20 drops, well dilute
Cantharidin (isolated active compound): 0.25–0.5 mg three times a day for Cancers, especially Liver Cancer.

Corrective:

1. Mung bean; Mung bean tea (TCM)
2. Licorice and Mung Bean tea correct its function.
3. Ghee, Almond oil, animal fats
4. Gum Arabic, Tragacanth
5. Talc acts an adjuvant to its cleansing action, stopping the painful urine that can easily accompany its use. (TCM)

Substitutes:

1. As stated above Blister Fly (Lytta spp.), Blister Beetle (Epicauta sp.), Oil Beetle (Meloe spp.) are all used similarly, and can be substituted.
2. Winged Ants were used similarly.
3. Glow Worms “act similar to Cantharides, except that they are stronger and sharper”. (Simun)
4. The potato-bug (Doryphora decemlineata) contains cantharidin; a strong tincture was proposed as a substitute for topical use.
5. Copper sulphate can be used externally. (Unani)

Preparation:

1. Stir-Fried Cantharides:
i. Stir fry with glutinous rice until yellow, then separate from the rice, remove the legs and wings.
ii. A similar method recommends stir-frying with glutinous rice and Hemp seed.
iii. Yet another method says to stir-fry with Bran, then boil in vinegar. (Li Shi Zhen).
iv. Some sources recommended frying “until no more smoke rises”. This is effectively carbonised.
Any of these medicines reduce toxicity.
3. Vinegar prepared Cantharides:
“It is better to store the flies in an earthen pot, the mouth of which is tied with a piece of neat and clean linen cloth. Afterwards the mouth of the pot should be made upside down and then the vapours of a mixture of refined and boiled “wine-vinegar” should be made to pass through it till the flies die. The dead flies should now be collected in a piece of linen and kept”. (Avicenna)
Preparing with Vinegar will moderate their harshness, and is stronger to move the Blood.

Main Combinations:

1. Strongly promote Urine in Edema:
i. Cantharide powder (5 grains), Extract of Squill (1 scruple), Licorice juice sufficient to form 30 pills. Dose: 1 pill, up to three times daily. (Sobernheim, 1840)
ii. calcined Egg shells (½ dram), Camphor (1 scruple), Cantharide prepared (½ scruple), Venice Turpentine sufficient to make 9 pills. (Fuller)
iii. Cantharide with Celery seed, Saltpeter, Madder, Juniper berry, Asarabacca, Bitter Almond, Melon seed (as in Pills for Retention of Urine)
2. For Stones:
i. Cantharide, Burnt Scorpion
ii. Cantharide with Pill Millipedes and Bees
3. Aphrodisiac:
i. Cantharide with Borax, Ash tree keys, Skink, Long Pepper, Cinnamon
ii. Cantharide with Saffron, Cinnamon, Nutmeg, Clove
iii. Cantharide with Cinnamon, Mace, Clove, Long Pepper, Rocket seed, Parsnip seed, Deer/Bull Pizzle (as in Powder to Stimulate Venery)
4. Impotence, Debility, Cantharide with Camphor
5. To strongly promote Menstruation, Hippocrates recommended a pessary of Cantharide, Myrrh and Frankincense, applied topically (this would, of course, not be repeated today). The same combination may be of use internally to treat Uterine tumors, for example.
6. To expel a Dead Fetus, one Cantharide is burned and ground to powder. Take some with water and the fetus will be expelled. (Ben Cao Gang Mu)
7. Acute Asthma, Tincture of Cantharide (1 dram), Spirit of Angelica, Compound Camphorated Spirit (2 oz. each)
8. When an abscess fails to form a head, make a paste with Cantharide and fresh Garlic, apply topically.
9. Warts, Moles, black Spots, stir-fry Cantharide and a little Arsenic with glutinous rice until it yellows. Discard the rice, and Garlic and form a paste to apply. (Ben Cao Gang Mu)
10. Scrofula:
i. Cantharide, prepared and taken daily for 7 days cures inveterate Scrofula.
ii. Cantharide roasted (1 part), Mint (4 parts), powder and form pills the size of Mung Beans with Egg White. Take 3 pills on the first day, increasing by one pill per day until 5 pills are taken. Then decrease by 1 pill per day until 1 pill is taken. Then take 5 pills daily until cured. (Ben Cao Gang Mu)
iii. Cantharide with Millipedes.
11. Fibroid tumors and Cancer, Cantharide with Millipedes, Bee and Toad
12. Bite of a Mad (Rabid) Dog:
i. fry 7 Cantharides with glutinous rice until it yellows, separate the rice and powder the beetles. Boil in 1 cup of wine down to half and take warm on an empty stomach. If “30–40 small pieces of meat shaped like dogs are discharged, all the Poison has left the body. If the number is smaller, have the patient ingest again after a few days”. (NOTE: this seems an excessivly large dose. Perhaps a milder variety was used) (Ben Cao Gang Mu)
ii. lightly fry 7 Cantharides with glutinous rice; remove them and add another 7 Catharides and fry until the rice is yello. Remove and add a third lot of 7 Cantharides and fry until green smoke rises. Remove the Cantharides and take only the rice, which powder. Mix with water to which a little oil is added and give to drink. (Ben Cao Gang Mu)
13. To promote hair growth:
i. “When painted, after being powdered with mustard, it helps in hair growth. Similar action is produced if the flies are cooked with olive oil till it becomes thick”. (Avicenna)
ii. Cantharides (1 oz.), Bay Rum (half oz.), Musk (2 drams), Rosemary (2 drams), Water (4 oz.). Shake the bottle and apply to the hair roots once daily. (Valuable Herbal Prescriptions, late 1800’s)
iii. Vaseline (2 oz.), Cantharide powder (1 dram), Oil of Rosemary, Oil of Lavender (15 drops each). Mix well. Apply once daily to promote hair growth. It was applied to the eyebrows to help them grow thick and full.
14. Deafness: 2 fried Cantharides and 2 Croton seeds (skin and heart removed) are powdered and formed into pills the size of a Chinese Date kernel. Wrap in silk and insert in the ear. (Ben Cao Gang Mu)

Major Formulas:

Pills for Retention of Urine (Wirtzung)
Powder for Urinary Retention
Powder to Stimulate Venery (Wecker)
Confection of Ashes
Cantharide 37 (Tibetan Meidicine)

Cautions:

1. Highly toxic and irritant. Avoid overdose.
“If taken in a dose of three tasasij (80 mg) orally, it causes ulceration in the bladder”. (Avicenna)
2. Not used in Pregnancy, the very weak, the very young or the very old.
3. Not used in women with heavy menstrual bleeding.
4. When used to promote blisters, care must be taken over sensitive skin, and to avoid secondary infection after bursting of the blister.

Toxicity:

1. Overdose can cause burning urine, excruciating pain, blood in the urine, bloody diarrhea.
2. Toxic effects may be caused with doses of 125–500mg but usually occurs with doses over 600mg. Fatality has been reported with doses of 1300mg.

Antidotes:

Do not induce vomiting.
1. Take 5–10 Egg Whites immediately.
2. Sheep milk with oil of Almonds. (De venenis, Petrus, 1487)
3. Take 10 Winter Cherries. (De venenis, Petrus, 1487)
4. Goat Milk or fresh Butter taken
5. “Almond milk is also highly recommended”. (De venenis, Ramesey, 1663)
6. Rice cooked with Milk
7. Emulsion of Pine nuts, White Poppy seed, Winter Cherries made with Water of Violets. (De venenis, Ramesey, 1663)
8. Pennyroyal repels the force of Cantharides “with special force”. (De venenis, Ramesey, 1663)
9. Hematuria from an excess dose, take Acorn powder with wine (Brunschwig, 1561)
10. Earth of Lemons (2 drams)
11. Troches of Earth of Lemons with Troches of Winter Cherries taken with Milk.
12. “To treat cantharide poisoning let them drink milk, and melted fresh butter or clarified butter; administer mild enemas; feed him fatty broths of lamb meat; inject an enema containing milk towards the bladder and, once he urinates, repeat, for this spares him from ulcers of the bladder”. (Rhazes)

From TCM:
13. Halloysite (Red Earth, Chi Shi Zhi) 30 grams
14. Decoction of 60 grams of Green Tea
15. Licorice (30 grams), Isatis folium Da Qing Ye (15 grams) as a decoction
16. Decoction of Mung Bean (30 grams), Licorice (10 grams), Coptis Huang Lian (3 grams)
17. The poison of the various species of Blister Beetle is resolved by Indigo, Coptis Huang Lian, Black Beans, Onions and Tea. (Li Shi Zhen)
18. To settle strong irritation of topical application, Coptis Huang Lian or Borneo Camphor (Bing Pian) can be applied. Honey can be applied for mild irritation.

Main Preparations used:

Tincture of Cantharides, Volatile Salt of Cantharides, Blister Plaster

1. Tincture of Cantharides:
i. Cantharide powder (2 drams), Proof Spirit (1 pint). Form a tincture and strain.
Dose: 5–20 drops, well diluted.
2. Tincture of Capsicum and Cantharides:
i. Cantharides (10 drams), Capsicum (1 dram), Proof Spirit (1 pound). Digest 10 days, filter.
This tincture is highly irritant. It was used in Gangrene. Dose: 10 drops in gum water or Decoction of Marshmallow. (Niemann)
3. Salt of Cantharides
Burn Cantharides then powder. Extract their salt with vinegar, then evaporate and keep the salt.
This is powerfully Diuretic and also dissolves Scrofula. Dose: 12–15 or 16 grains. (780mg–975mg) (Lemery)
4. Blister Plaster:
i. White Pitch (8 oz.), Venice Turpentine, Cantharides finely powdered (2 ½ oz. each), mix. (Fuller)

Extra Info
History
Research
Comment

GENERAL / REVIEW
–A Comprehensive Review on Ethnopharmacology, Phytochemistry of Mylabris, and Pharmacology of Cantharidin.
–Medical uses of mylabris in ancient China and recent studies
–Norcantharidin: research advances in pharmaceutical activities and derivatives in recent years
ALLERGIC RHINITIS
–Vesiculation therapy of Cantharides extract for perennial allergic rhinitis and its effect on serum total IgE
APHRODISIAC
–Potent natural aphrodisiacs for the management of erectile dysfunction and male sexual debilities
FIBRINOLYTIC
–[Fibrinolytic activity in cantharide blisters of urticaria patients].
–Five New Cantharidin Derivatives from the Insect Mylabris cichorii L. and Their Potential against Kidney Fibrosis In Vitro.
CANCER:
–[Chemical constituents from Mylabris phalerata and their cytotoxic activity in vitro].
–[Comparative study of antitumor activity of cantharidin and cantharis peptides].
–Norcantharidin, derivative of cantharidin, for cancer stem cells.
–The effects of cantharidin and cantharidin derivates on tumour cells.
BLADDER:
–Cantharidin alters the expression of genes associated with the NKG2D-associated immune response in TSGH-8301 human bladder carcinoma cells.
–Cantharidin induces DNA damage and inhibits DNA repair-associated protein expressions in TSGH8301 human bladder cancer cell
BREAST:
–Application of digital holographic tomography in antitumor effect of cantharides complex on 4T1 breast cancer cells
–Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing Autophagy and Inducing Apoptosis in Vitro and in Vivo.
–Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway.
COLORECTAL:
–Norcantharidin promotes M1 macrophage polarization and suppresses colorectal cancer growth.
–[Molecular mechanism of Mylabris for colorectal cancer based on integrative pharmacology].
EHRLICH ASCITES:
–Bioactive component, cantharidin from Mylabris cichorii and its antitumor activity against Ehrlich ascites carcinoma.
GASTRIC:
–Norcantharidin-induced Apoptosis of AGS Human Gastric Cancer Cells Through Reactive Oxygen Species Production, and Caspase- and Mitochondria-dependent Signaling Pathways.
LEUKEMIA:
–Pharmacological mechanism of mylabris in the treatment of leukemia based on bioinformatics and systematic pharmacology.
–Cantharidin Induces Apoptosis and Promotes Differentiation of AML Cells Through Nuclear Receptor Nur77-Mediated Signaling Pathway.
LIVER:
–Cantharidin suppresses hepatocellular carcinoma development by regulating EZH2/H3K27me3-dependent cell cycle progression and antitumour immune response.
–Identification of the molecular targets and mechanisms of compound mylabris capsules for hepatocellular carcinoma treatment through network pharmacology and bioinformatics analysis.
–Unique Responses of Hepatocellular Carcinoma and Cholangiocarcinoma Cell Lines toward Cantharidin and Norcantharidin.
LUNG:
–Inhibitory effect of Cantharidin on proliferation of A549 cells
–Cantharidin suppresses cell growth and migration, and activates autophagy in human non-small cell lung cancer cells.
–Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways.
–Cantharidin induces apoptosis of H460 human lung cancer cells through mitochondria-dependent pathways.
–Cantharidin induces DNA damage and inhibits DNA repair-associated protein levels in NCI-H460 human lung cancer cells.
–Norcantharidin suppresses cell growth and migration with enhanced anticancer activity of gefitinib and cisplatin in human non-small cell lung cancer cells.
LYMPHOMA:
–Multi-omics and experimental validation reveal mechanism of compound mylabris capsules in treating diffuse large B-cell lymphoma.
MELANOMA:
–Cantharidin impairs cell migration and invasion of A375.S2 human melanoma cells by suppressing MMP-2 and -9 through PI3K/NF-κB signaling pathways.
–Cantharidin induces G2/M phase arrest by inhibition of Cdc25c and Cyclin A and triggers apoptosis through reactive oxygen species and the mitochondria‑dependent pathways of A375.S2 human melanoma cells
NEUROBLASTOMA:
–Norcantharidin Inhibits SK-N-SH Neuroblastoma Cell Growth by Induction of Autophagy and Apoptosis.
PANCREATIC:
–The combination of cantharidin and antiangiogenic therapeutics presents additive antitumor effects against pancreatic cancer.
–Cantharidin and norcantharidin impair stemness of pancreatic cancer cells by repressing the β-catenin pathway and strengthen the cytotoxicity of gemcitabine and erlotinib.
–Cantharidin represses invasion of pancreatic cancer cells through accelerated degradation of MMP2 mRNA.
–Tamoxifen enhances the anticancer effect of cantharidin and norcantharidin in pancreatic cancer cell lines through inhibition of the protein kinase C signaling pathway.
–Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stress-independent growth inhibition of pancreatic cancer cells through G2/M cell-cycle arrest and apoptosis.
PROSTATE:
–Downregulation of c‑FLIP and upregulation of DR‑5 by cantharidin sensitizes TRAIL‑mediated apoptosis in prostate cancer cells via autophagy flux.
SYNERGISTIC WITH CHEMOTHERAPY:
–Tamoxifen enhances the anticancer effect of cantharidin and norcantharidin in pancreatic cancer cell lines through inhibition of the protein kinase C signaling pathway.
–Norcantharidin suppresses cell growth and migration with enhanced anticancer activity of gefitinib and cisplatin in human non-small cell lung cancer cells.