Solanum nigrum in the Treatment of Cancer

By Adam Tate
September, 2019

Introduction

Solanum nigrum is a common herb of the Solanaceae (potato) family and is found worldwide. It is commonly found in gardens, hence its traditional name, Garden Nightshade. It has been used in various medical traditions including the ‘Western’ (Greek/European) Tradition, Unani, Ayurveda, Siddha and TCM.

It is a perennial herb growing to 1.5 meters with dark green leaves, white flowers, the unripe fruit being 5–7mm, round, in small clusters and green, the ripe fruit becoming black.

In both East and West it has been regarded as cold, dry, slightly bitter, slightly sweet and pungent. It is also slightly toxic.

In medicine, usually the whole dried herb is used. In some instances, the root-bark or dried, ripe fruit are used. Occasionally, the juice is also used, in this case the juice being gently boiled to remove the scum.

History

Solanum nigrum was used by Hippocrates (C. 400 BCE) and was listed in the Herbal of Dioscorides (70 CE) as Stychnon manikon. (4)

In China it was first listed in the Tang Materia Medica (659 CE). (5)

The plant has been used as a culinary plant since early times, and has been used as a famine food in China during the 15th century. (6) It has been used as food in various countries, the leaves being well boiled and eaten like spinach. In south India the leaves are cooked with Tamarind, onion and cumin seed. (7) Leaves are likewise eaten in Africa and elsewhere. In Greece, Turkey and Crete the leaves are boiled to form the dish called horta. The ripe berries are eaten raw or cooked to produce a jam and are non-toxic.

Constituents

(1, 2, 3)

The herb contains a range of potent phyto-chemicals:

Glycoproteins (25% protein in the dried leaf)
Steroidal Alkaloids (0.6–2% incl. the toxic solanine, highest in unripe fruit & mature leaf)
Steroidal Saponins (incl. tigogenin, highest in the fruit)
Glycosides (1–2%)
Polysaccharides
Coumarins (incl. scopoletin)
Polyphenols
Tannins (to 10%)
Minerals (10% ash, K, Ca, Fe, S, P, N)
Vitamins (A, B, C, E, Folic acid)
Fruit contains acetylcholine (250mcg/gm)

Five separate classes of phytochemicals within Solanum nigrum have demonstrated anti-cancer effects: steroidal alkaloid saponins, steroidal saponins, polyphenols, glycoproteins, and polysaccharides (8)

Medicinal effects

(1, 2, 10)

Clears Heat and Toxin
Anti-inflammatory
Resolves Swellings and Masses
Used for Wind-Heat spasms and convulsions
Used for urinary dysfunction associated with Heat
Stops Cough and Wheezing
More recently has been used for Heart disease and Angina Pectoris
Used internally and externally for Inflammations, Swellings, Hemorrhoids, Ulcers, Abscesses, Eczema
Used internally and topically for Tumors and Cancers

Mode of Administration

With a pharmacologically potent and diverse herb such as Solanum nigrum, dosage form can have a marked effect on behavior of the herb. This is especially so with the toxic elements such as solanine. When the herb or juice is boiled, solanine is denatured. Levels of Solanine are also decreased when the herb is dried.

Gataker used the infusion of the powdered herb prepared with boiling water (see Case Histories below). TCM sources tend to use a decoction, and the decoction has been studied for anti-cancer effect. (14) It needs to be investigated as to the effect of boiling water added to the powdered herb as an infusion. It may denature some of the solanine however the small dose (approximately 65–100mg) used by Gataker would appear to suggest some toxins present as the dose used by TCM is typically 15–30 grams (2) or more (over 100 times the dose used by Gataker). In these cases, the herb is decocted for up to 1 hour, thereby allowing full degradation of the toxic solanine.

As stated elsewhere, the large amounts of nitrites found in the herb can be implicated in toxicity when such large doses are used as those given in TCM. Further, larger doses also implicate the polysaccharide-content into being of important medicinal effect, especially in the treatment of Cancer.

The fluid extract and hydro-ethanol tinctures are also used and these are likewise given in very small doses and would be expected to contain solanine.

One would expect that when such small doses are used as the infusion or tincture, the toxic alkaloids, notably solanine, would be the most active constituent. When large doses are used such as in TCM, other constituents, especially glycoprotein and polysaccharide content are relatively more active. It also remains to be seen what effects the denatured solanine has. For example, strychnine in Nux Vomica is denatured when prepared according to traditional preparations methods using heat. Denatured chemicals include iso-strychnine and strychnine N-oxide. This makes it far safer, and yet it still shares similar effects to strychnine. (9, 10)

Dosage

(1, 2)

Dose tends to vary greatly with different sources.

Liquid extract (1:1): 5–10 drops 2 or 3 times daily.
Tincture (1:10): 5–10 grams daily.
Leaf powder: 200–500mg
Dried leaf in Infusion: 65–130mg (Gataker)
Leaf juice: 5–10 mls.
Leaf juice (that has been heated until brown): 6–8 oz. (Ayurveda)
Whole dried herb in Decoction: 15–30 grams; up to 60 grams for Cancer (TCM)
Dried Root in Decoction: 10–20 grams (Ayurveda)

Due to the great variation in dosage recommended by different sources, the reported variation in potency, the potential for varying individual sensitivity to the toxic compounds, and the necessity of long-term use in Cancer therapy. several things should be taken into account when using Solanum in Cancer therapy:

It is always recommended to begin with lower doses and increase dose gradually.
As suggested by Gataker, most beneficial effects may be noted when mild side effects are experienced, although this may not be necessary in all cases.
Due to tolerance increased with continued usage, dosage can be expected to be increased with long-term use.
Courses of treatment, rather than continued usage, may be more effectual. For example, 4–6 weeks of treatment, followed by a 7–10 day break, this cycle being continued over months.
Finally, due to the synergistic effect with a number of modern Chemotherapy drugs, using Solanum concurrently with Chemotherapy and following the course of Chemotherapy would be expected to achieve best results.

Toxicity

The plant appears to have a wide variation of toxicity depending on age, location, environment, method of administration, and part used. The main toxic principle is solanine which is toxic in doses of 2.8mg/kg.

Several points to note:

Unripe fruit and mature leaf are most toxic (highest levels of solanine). The young leaf has relatively low levels of solanine and has been cooked and eaten. The ripe fruit is non-toxic and has also been eaten as food.
Drying reduces the toxic alkaloids in the leaf.
Decoction reduces toxicity, and larger does are used in TCM due to decoction being the main form of administration in that system. Toxic dose when decocted has been stated to be 40–60 grams. (2)
The plant contains high levels of nitrates. Nitrate toxicity has been suspected as causing some of the toxic effects. This is implicated in the larger doses used in TCM.
The juice was occasionally used in both Europe and India, but as per standard practice, the juices of herbs were gently simmered to clarify them, thus the toxic alkaloids are greatly reduced due to heat degradation.
The distilled water was commonly recommended during the 17th and 18th centuries where it was used to clear Heat and used as an anti-inflammatory. The distilled water likewise requires boiling in its preparation. Culpeper and others said this was the best form of Nightshade to use internally.
A Hypotensive effect has been noted. (12) This may make it unsuitable for people with low blood pressure.

Traditional use of Solanum nigrum in Cancer treatment

The use of Black Nightshade in Cancer treatment can be noted by Ancient Greeks, and it has been used for toxic swellings, tumors and cancers in various systems since ancient times.

Examples:

Juice of Nightshade was mixed with Galen’s White Cerate to form an ointment for Heat, pain, Inflammation and Tumors. (13)
The Green Plaster of the Surgeons was applied to all old sores and old ulcers.
Various Western sources during the 16th–18th centuries listed Black Nightshade for Breast Cancer, (14, 15)
It was used by various physicians including Culpeper for Uterine and Cervical Cancer, being injected directly into the womb (ie. a douche). (16)
Various authors listed it for Cancer of the Uterus. (17)
Culpeper, for ‘running sores’ and ‘corroding ulcers’. (18)
Topically for Foul and Running Ulcers. (8)
Tang Materia Medica (659 CE) said it expels heat and reduces swellings. (2)

Case Histories from Gataker

One of the earliest texts to talk in detail about the use of Solanum in cancer therapy was from 1757 when a Mr. Gataker, surgeon of the Westminster Hospital detailed a number of case Histories successfully treated with Solanum.

Observations on the Internal Use of the Solanum Or Nightshade.
… a woman about 50 years of Age, a patient in the Westminster Hospital. She had a sore under her Right-eye, which began by a slight Accident upon the part about a year and half before she came under my care. The Sore, which was as broad as a Half-crown, consisted of several indigested, foul Ulcerations, intermixed with callous Eminences, or hard Knots rising in particular parts of it, and the whole was encircled by an unequal jagged Edge. Below the Sore the Cheek was discolored by a deep red Appearance, and was swelled. She had suffered considerable and frequent Pains in the parts many Months. The common methods were tried for her relief ineffectually. Amongst other things the solution of Mercury, and other Mercurials were used so as to produce a slight salivation. The sore however appeared in full as bad a state as has been just represented, when I began to give her the Infusion of Garden Nightshade: In a month after taking it the pains entirely ceased, and in a little more than another month the Ulcerations were healed, and the callosities subsided, leaving only a slight soreness or tenderness of the skin, with two or three scurfy Inequalities in the Upper part of it. No application was used to the sore except common softening dressings to keep it from the Air …

‘The Medicine, in this instance, occasioned at first a sickness in the Night, and a moderate Purging in the morning, with some increase of Urine. It continued to sweat her considerably as long as she took it, preserving also in general a lax state of her Bowels, and acting sometimes as a Diuretic. She never took more than an Infusion of two grains at a time. I have not yet had any account of her since she left the Hospital.

‘The other patient who suffered under this Disease, was a woman above 70 years of Age, and in the same Hospital. She came there about five months ago with a very large and bad-looking sore on her Left-breast, with callous Edges surrounding the Ulcers, the Hardnesses in other Parts. This complaint began above a Year before with a small hard Knot, which increasing, broke into a sore, and for some months had gradually spread broader and corrode deeper. She began to take the Infusion of Garden Nightshade, after a Dose or two of purging Physic, and in less than three Months, the sore was reduced to a very inconsiderable size, without any remaining Hardnesses at the Edges of it, and had the Appearance of healing in a Week or ten days. The hardnesses about the Breast were likewise diminished’.

Another Hospital case: ‘The First of the Patients is a woman of 35 years of Age. She was admitted into the Hospital about seven months ago. She had then a very great Inflammation and Swelling of her Foot, Leg, Knee, attended with a Fever, besides a very large Sore on the lower part of the Leg, which began two years before, and has gradually been growing worse. The sore has the most malignant Appearance, discharged a great deal of a sharp thin Humor, and was extremely painful. The swelling and inflammation were considerably abated after she had been in the Hospital some time, but the Sore continued in a very bad state, having extended itself from the lower part of the Calf to the Heel, and from one ankle backwards to the other. The Fever was sometimes very intense, with violent purgings with other symptoms intervened, which reduced her strength and left very little hopes of her recovery. In this situation she was about a month ago, having been bed-rid five months, unable to feed or help herself, and the last six weeks having never enjoyed one hours sleep at a time, on account of violent Pains which she felt in her Head and Limbs. She complained also of a great weight and heaviness in her Head, and at times was not sensible. The first dose she took of the Infusion of Garden Nightshade affected her in a manner, to use her own words, as if she had drank too much liquor. It then threw her into plentiful sweat, and purged her twice. The second and third doses operated as the first, except that they occasioned no sensation of giddiness. After the third dose her pains were much lessened, and she was able to walk with a very little assistance. In eight days she was perfectly free from Pain, could walk very well about the ward, had an exceeding good appetite, and her strength was remarkably increased, as was soon evident; for on the twelfth day after she had made use of this medicine, she, without my leave, and imprudently in regard to her leg, walked near two miles. The sore however healed incredibly fast, and as it is at present quite easy, and continues mending, it probably will not be long before it is well. It is now a month and some days since she began the Infusion, and except the remaining sore she has not had a complaint from the eighth day after she began the medicine’. (Observations on the Internal Use of the Solanum Or Nightshade, Thomas Gataker, 1757)

The author in this work mentions mild side effects for each case: dizziness, sweating, purging and diuresis. The dose, 1, 1½ or 2 grain doses of the dried leaf given by infusion made with boiling water. If a one-grain dose was not effective on the first night, 1½ or 2 grains would be given the next night. Often a dizziness or drunkenness was experienced when first given, but not after repeated taking. Plentiful sweating seems to be a desired result and dose was usually increased to procure perspiration. The strong pain of advanced Cancer was ameliorated within 3 doses in some subjects. In addition, dose usually continued to be effective without needing to increase, once the correct dose for an individual was achieved.

Topical Preparations

Green Plaster of the Surgeons
Dog Fat, Wax, Rosin, Barrow Grease 1 oz. each
Fresh Nightshade and Mallow 1 handful each
Seethe the herbs to a pap in Goat Milk, stirring until thick, then mix with the other ingredients to form a Plaster. (12)

Nightshade juice mixed with Orpiment applied to open Cancers was said to be very effective. (12)

Of the use for Uterine and Cervical Cancer

Culpeper gives two topical uses of Nightshade for Cancer of the Womb:
1.      Juices of Plantain,
            of Black Nightshade,
            of Purslane                                               2 oz. ea.
       Mucilage of Fleabane                              1 oz.
       Oil of Roses                                                3 oz.
Mix in a leaden mortar.

2.      Black Nightshade juice                           6 oz.
       Tutty (Zinc oxide), burnt Lead                 2 drams ea.
      Camphor                                                    ½ dram
Mix them in a leaden mortar, and add powder of (River) Crayfish.
These were used as topical medicines, the former as a Douche; the latter is to be applied topically as a paste. (19)
These are by no means unique to Culpeper. The juice or water of Black Nightshade was regularly used in this manner in douches and pastes for Uterine and Cervical cancer.
It should be noted that the juices in such instances are gently boiled to clarify them.

A contemporary Chinese use for the same purpose:

Black Nightshade (30–60 grams dry, or 90–150 grams of the fresh) is decocted twice with a gentle fire in 800 mls of water. The 2 decoctions (about 300 mls) are mixed for oral intake. One course of treatment being 15 days. (20)

Recent Research on the Combined use of Solanum and modern Chemotherapeutic Drugs

Recently there has been a number of research articles indicating the synergistic effect of using Solanum nigrum with modern chemotherapy agents including Cisplatin, Doxorubicin, Docetaxel and 5-Fluorouracil. (15, 16, 21, 22)

These effects have been noted in Colorectal cancer (13), Ovarian Cancer (14), Hepatocellular cancer (23), and Endometrial cancer (24).

Researchers showed that the aqueous extract of Solanum nigrum had a potent anti-cancer effect against the tested cells, and that there was a synergistic effect with the above-named Chemotherapeutic agents. Solanum appears to also prevent or reverse chemo-resitance.

Research

Anti-Cancer Research

Anti-cancer activity was demonstrated by Chinese researchers prior to 1991: Solanum nigrum was shown to inhibit Sarcoma-180, WA (carcinosarcoma), Cervical Cancer, Ascites Cancer and Stomach Cancer cells in animals. It inhibited transplanted animal tumors at a rate of 40-50%. It has proven to be clinically useful for cancers of Cervix, Ovary, Esophagus, Breast, Lung, Liver, as well as Chorioepithelioma and Sarcoma in humans helping to reduce signs and symptoms, prolong life, and to promote tumor regression and total remission in some cases. (10)
Three potent anti-neoplastic steroidal glycosides were isolated in 1999: 2-solamargine, solamargine and degalactotigonin. (25)
Solamargine has been isolated as (one of) the main anti-cancer compounds. (11)
Breast Cancer: Potent anti-tumor and apoptosis-inducing effect was noted against several Breast Cancer cell lines. It was demonstrated that some of these effects were due to immune system enhancement rather than direct anti-cancer activity. (26, 27, 28, 29, 30)
Prostate Cancer: Polyphenol extract of mature Fructus Solanum Nigrii promoted cell cycle arrest and apoptosis in several Prostate Cancer cell lines without affecting normal prostate cells. (31)
Liver Cancer: Hydro-alcoholic extracts of Solanum Nigrii were cytotoxic against Liver Cancer cell lines, being more effective than extracts of Taxus baccata. (32) Solamargine was shown to induce apoptosis in human Hepatoma cells. (33)
Cervical Cancer: water extractable polysaccharides from Solanum Nigrii showed significant inhibition on U14 cervical cancer. (34)
Solmargine inhibits growth and induces apoptosis of human Lung cancer cells. (35)
Aqueous extract activates autophagic cell death and increases cytotoxicty of Docetaxel in Endometrial Cancer. (36)
Aqueous extract inhibits metastasis in mouse melanoma cells in vitro and in vivo. (37)

Other research related to Cancer treatment:

Immunomodulatory: due to polysaccharide content. (38)
Potent Anti-inflammatory. (39)
Hepato-protective. (40, 41)
Free Radical Scavenging effect. (42)
Rich source of anti-oxidants. (43)
A potent ant-ulcer effect has been shown. (44)

Non-referenced research has reportedly shown it to stimulate Antibody production, have anti-coagulant effect and a potent Cortisone-like effect.

Other research demonstrated significant CNS depressant activity; Pentobarbitol-induced sleeping time was significantly increased, there was suppression of aggressive behavior and reduced spontaneous motility. (45)

Direct anti-tumor and anti-cancer activity is seen in the alkaloid content including solanine and solmargine. The glycoprotein content also has the ability to induce apoptosis. (46, 47, 48, 49) In addition, the ripe fruit demonstrated apoptosis-inducing effects in Human Breast cancer cells, though the active compounds have not been isolated. However, due to the lack of toxic alkaloids reported in the ripe fruit, one may expect some other compounds to be implicated. (50) The immuno-modulatory effect is due primarily to the polysaccharide content. (30)

A Review of the Effects beneficial in Cancer Therapy

Broad-spectrum Anti-Cancer activity, including common cancers such as Breast and Prostate Cancer, and difficult Cancers such Lung, Liver and Ovarian Cancers.
Broad Spectrum Apoptosis-inducing effect.
Increases Immunity
Demonstrated to inhibit Metastasis
Works synergistically with a number of modern chemotherapeutic agents.
A number of different compounds have been shown to have anticancer effect.
Potent Anti-inflammatory
Rich in anti-oxidants
Long history of use both internally and topically for various Cancers.
Other beneficial effects include Hepato-protective, Anti-ulcer, Sedative, anti-coagulant

Conclusion

Solanum nigrum is one of our most important anti-cancer herbs. It is common and found worldwide so is easy and cheap to administer.

There is a long history of clinical use against various cancers, both internally and topically, and modern research has shown an overwhelming amount of support for its use as an anti-cancer medicinal. Despite research indicating the alkaloids to have direct anti-cancer activity against a number of different human cancer cells lines, its mechanism of action is complicated and not fully understood. The fact that the toxin-free ripe fruit has demonstrated effectiveness against cancer cells suggests other anti-cancer compounds other than the toxic alkaloid content may contribute to anti-cancer effects. Immuno-modulatory effects from the polysaccharide content is another complimentary way in which cancer treatment is assisted.

The fact that it has shown synergistic effects with a number of modern chemotherapeutic drugs makes it all the more relevant in modern anti-cancer therapy.

Despite its reputation as a toxic plant, it tends to be well tolerated. However, individual differences in the herbs toxicity along with individual sensitivity requires the herb to be initiated at a lower dose, increasing as required.

As with any mild-to-moderately toxic herb used in the long-term treatment of a chronic or obstinate disease, it is easy to begin with a low dose, increasing gradually until an optimal dose is achieved. This averts side-effects and toxicity while achieving maximum effect.

Gataker recommends increasing the dose until mild dizziness (which is transient and disappears with continued use), and doses which induce perspiration, diuretic and mild purging were deemed beneficial.

There is also the benefit of it being widely applied in both China and Russia against Cancer, proving its effectiveness and necessary dose.

This is a most useful and important herbal medicine which should be studied more widely and can in general be added to other anti-cancer regimes.

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