Peganum, Wild Rue Syrian Rue, African Rue Harmal, Armala; Ispand, Safand asfand (Unani) Haramal, Isband, Ispand Lahouri (Ayurveda) Luo Tuo Peng Zi (TCM)

New Kreuterbuch, Matthiolus, 1563

Kreutterbuch, Matthiolus, 1586

Sibthrop, Smith, Flora Graeca, vol. 5: 1825

Peganum harmala seed
(Photo by Roger Culos) (Wikimedia)

Botanical name:

Peganum harmala

Parts used:

Herb; Seeds

Temperature & Taste:

Warm, dry. Pungent, Bitter
“Syrian Rue is Hot and Dry in the Third degree”. (Avicenna)

Classifications:

3I. APHRODISIACS
3P. ANTHELMINTIC
TCM:
J. Regulate Qi
S. Worms and Parasites

Constituents:

Seeds contain highest amounts of harmaline, harmine, and vasicine
Root contains highest amounts of acetic acid, proline, lysine, and sucrose

Uses:

1. Opens Obstructions:
-Swelling of the Spleen
-Intermittent Fever, Malaria
-Jaundice
-Stones of the Bladder or Gall Bladder

2. Warms the Kidneys, Promotes Urine:
-retention of Urine; Edema
-excess Sex drive; quells Lust; conversely, has been used as an Aphrodisiac
-promotes retention of Semen (for Premature Ejaculation)

3. Clears Wind and Damp, Eases Pain:
-Rheumatism, Lumbago, Sciatica
-Neuralgia, Paralysis, Hemiplegia, Parkinsonism
-itchy skin

4. Calms the Mind, Settles Wind, Stops Spasms:
-Epilepsy; Insanity; Hysteria
-various forms of Neuralgia (internally and topically)
-Parkinson’s Disease, Amnesia
–‘They help the Melancholicis, who are in a state of heavy fantasy’ (Matthiolus)
-seeds are Narcotic, and Euphoric

5. Stops Cough and Wheezing:
-Cough, Asthma (TCM, Unani)

6. Moves the Blood, Clears Stasis, Promotes Menstruation:
-Amenorrhea; Dysmenorrhea
-induces abortion
-traditionally for diseases of the Heart
-Tumor, Cancer

7. Promotes Milk.

8. Kills Worms:
-particularly useful for Tapeworm

9. Resists Poison:
-“useful against all kinds of Poisons”. (Avicenna)

10. Externally:
-ointment for baldness
-applied to Hemorrhoids
-topically for Herpes
-seeds are heated in Olive oil and dropped into the ear to relieve Tinnitus and hearing problems.
-Dental cavities are fumigated with the smoke to relieve pain.
-leaves are applied topically to Rheumatism.
-“good for Arthralgia and Sciatica if used as a paint”. (Avicenna)
-strong wash or vinegar tincture are used for Lice
-seeds were used in fumigations to purify the air during epidemics
-topically for Opthalmia
-seeds are burned after childbirth in Middle East to repel Evil forces and protect the infant

Dose:

Powder: 1–4 grams
Infusion or decoction: 2–5 grams, up to 9 grams

Correctives:

1. Vinegar; Oxymel
2. Pear Jam
3. Lemon juice; Citrus fruits (Unani)

Substitutes:

1. “Common Rue is substitute for Syrian Rue”. (Avicenna)
2. Rue seed; Carum copticum seed; Radish seed (Unani)
3. White Dittany root

Main Combinations:

1. Swelling of the Spleen, Wild Rue seed with Pennyroyal
2. Amenorrhea, Wild Rue seed with Fennel seed and Wormwood
3. Diabetes, Wild Rue seed, Sumac, Nettle
4. Arthritic diseases, Wild Rue seed with Withania, Galangal and Colchicum (Unani)
5. Premature Ejaculation, Wild Rue seed, Poppy seed, Sesame seed (as in Habb e Hindi Mumsik)
6. Heart diseases, Wild Rue, Nigella, Camphor, Pyrethrum, Spikenard, Saffron, Cassia, Costus, Sagapen, made into an Electuary with Honey (Syrian ‘Book of Medicine‘, Budge, 1913)
7. For Sadness and Worry, Wild Rue seed with Saffron, Aloeswood and Peony
8. Cancer, Wild Rue, Arum palaestinum and Curcuma longa (this has been studied for head and neck cancers; see below)
9. Dim-sightedness, triturate Wild Rue seed with Wine, Honey, Chicken Bile, Fennel juice and Saffron for topical use (Dioscorides)

Major Formulas:

Expert Electuary of Catilinae
Pills for Asthma and Shortness of Breath (Unani)
Pills of Opopanax (De morbus internis curandis)
Pills to Aggregate Greater (Mesue)
Pills to Crumble Kidney Stones (Unani)
Habb e Hindi Mumsik

Cautions:

1. Not used during Pregnancy (induces abortion)
2. Avoid overdose; large doses are toxic, narcotic, hallucinogenic and may cause depression.
3. “It is an intoxicant like wine”. (Avicenna)

Intoxicant:
–Peganum Harmala (Aspand) Intoxication; a Case Report.
–Peganum harmala intoxication, a case report.
–Peganum harmala L. Intoxication in a Pregnant Woman.
–A case of beta-carboline alkaloid intoxication following ingestion of Peganum harmala seed extract.

Toxicity:

–Subchronic toxicity and concomitant toxicokinetics of long-term oral administration of total alkaloid extracts from seeds of Peganum harmala Linn: A 28-day study in rats.
–[Peganum harmala L. poisoning and pregnancy: two cases in Morocco].
–[Peganum harmala L. poisoning in Morocco: about 200 cases].
–Syrian rue tea: a recipe for disaster.
–Experimental toxicity of Peganum harmala seeds.
–Abortifacient potential for the epigeal parts of Peganum harmala.

Drug Interaction:
Inhibits P450 enzyme
–Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives.
–Peganum harmala L. differentially modulates cytochrome P450 gene expression in human hepatoma HepG2 cells.

Reduces Male Rat Spermatogenesis & Fertility:
–Histo-functional effects of Peganum harmala on male rat’s spermatogenesis and fertility.

Main Preparations used:

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‘In native works on Materia Medica, Hurmul is described as an alterative and purifying medicine in atrabilis, and also in diseases supposed to arise from cold humors, such as palsy, lumbago, &c.; it is also said to stimulate the sexual system both in the male and female, increasing the flow of milk and menses in the latter. For administration a concentrated decoction is mixed with sweet oil and honey, or the crushed seeds are boiled in wine down to one-fourth of the original bulk of the latter, and the mixture strained (vide Makhzan-el-Adwiya, article Hurmal). Recently, Dr. P. Gopal, a medical graduate of the Bombay University, has experimented with this drug. He informs me that the infusion or tincture acts as a stimulant emmenagogue, and produces slight intoxication like Cannabis Indica. He gave the tincture

in 1 drachm doses to a female suffering from amenorrhoea, and it had the effect of producing a free menstrual discharge; he further says that it is sometimes used by the native midwives to procure abortion. Dr. P. Gopal believes that it has properties in common with Ergot, Savin, and Rue. The equal activity of watery and spirituous preparations may be explained by the fact that the red resinous colouring matter is a secondary product formed by the oxidation of the alkaloid Harmaline; it is only produced after digestion of the seeds in spirit. In Persia P. Harmala is called Sipand; when sprinkled upon burning coals it is supposed to avert the malignant influence of the evil eye. Popular allusions to it in Persian books are frequently met with.’ (Vegetable Materia Medica of Western India, Dymock, 1885)

GENERAL: –Analysis of alkaloids from Peganum harmala L. sequential extracts by liquid chromatography coupled to ion mobility spectrometry. –A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum. –Identification, occurrence and activity of quinazoline alkaloids in Peganum harmala. –A rapid and simple method for the determination of psychoactive alkaloids by CE-UV: application to Peganum Harmala seed infusions. –[ALKALOIDS OF PEGANUM HARMALA L. AND THEIR BIOLOGICAL ACTIVITY]. –Medicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a review. –Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids. ANTI-BACTERIAL: –Chemical composition and antibacterial properties of Peganum harmala L. –Chemical Composition, Antibacterial and Phytotoxic Activities of Peganum harmala Seed Essential Oils from Five Different Localities in Northern Africa. –Antimicrobial Activity of Peganum Harmala L. on Streptococcus mutans Compared to 0.2% Chlorhexidine. –Antibacterial Activity of Some Plant Extracts Against Extended- Spectrum Beta-Lactamase Producing Escherichia coli Isolates. –Phenol content, antioxidant capacity and antibacterial activity of methanolic extracts derived from four Jordanian medicinal plants. –Antibacterial activity of different parts of Peganum harmala L. growing in Iran against multi-drug resistant bacteria. –Antibacterial activity in spices and local medicinal plants against clinical isolates of Karachi, Pakistan. –Antibacterial and antifungal activities of (beta)-carboline alkaloids of Peganum harmala (L) seeds and their combination effects. ANTI-VIRAL: COMMON COLD-Determination of elements by atomic absorption spectrometry in medicinal plants employed to alleviate common cold symptoms. ENTEROVIRUS-Harmine, a small molecule derived from natural sources, inhibits enterovirus 71 replication by targeting NF-κB pathway. INFLUENZA-In vitro and in vivo effects of Peganum harmala L. seeds extract against influenza A virus. –In vitro antiviral effects of Peganum harmala seed extract and its total alkaloids against Influenza virus. HERPES-Anti HSV-2 activity of Peganum harmala (L.) and isolation of the active compound. HIV-Purification and characterization of a novel antifungal protein with antiproliferation and anti-HIV-1 reverse transcriptase activities from Peganum harmala seeds. ANTI-MALARIAL: –Seeds of Peganum Harmala L. chemical analysis, antimalarial and antioxidant activities, and cytotoxicity against human breast cancer cells. ANTI-FUNGAL: –Anti-biofilm Properties of Peganum harmala against Candida albicans. –Purification and characterization of a novel antifungal protein with antiproliferation and anti-HIV-1 reverse transcriptase activities from Peganum harmala seeds. –Antifungal properties of crude extracts of five Egyptian medicinal plants against dermatophytes and emerging fungi. –Antibacterial and antifungal activities of (beta)-carboline alkaloids of Peganum harmala (L) seeds and their combination effects. ANTI-INFLAMMATORY: –Harmine is an inflammatory inhibitor through the suppression of NF-κB signaling. HYPOTHERMIC: –Hypothermic effect of harmala alkaloid in rats: involvement of serotonergic mechanism. ANALGESIC: –Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: possible mechanisms involved. SKIN DISEASES: –Peganum harmala: its use in certain dermatoses. GASTRIC ULCER: –Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ulcers. HEPATOPROTECTIVE: –Hepatoprotective activity of Peganum harmala against ethanol-induced liver damages in rats. RADIOPROTECTIVE: –[Radioprotective effect of gamma-harmine and its carboline analogues]. ANTI-TUSSIVE, BRONCHODILATING: –Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids (±)-vasicine, deoxyvasicine, and (±)-vasicinone from aerial parts of Peganum harmala L. –In vivo evaluation of the antitussive, expectorant and bronchodilating effects of extract and fractions from aerial parts of Peganum harmala linn. ANTI-AGEING: –Anti-aging effects of some selected Iranian folk medicinal herbs-biochemical evidences. VASORELAXANT: –Vasorelaxant effects of harmine and harmaline extracted from Peganum harmala L. seeds in isolated rat aorta. –Relaxant activity of methanolic extract from seeds of Peganum harmala on isolated rat aorta. –Comparative study on the vasorelaxant effects of three harmala alkaloids in vitro. –Vasorelaxant effect of harman. CEREBROPROTECTIVE: –Cerebroprotective effect of isolated harmine alkaloids extracts of seeds of Peganum harmala L. on sodium nitrite-induced hypoxia and ethanol-induced neurodegeneration in young mice. AMNESIA, COGNITIVE DYSFUNCTION: –Ameliorative effect of deoxyvasicine on scopolamine-induced cognitive dysfunction by restoration of cholinergic function in mice. –Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice. –Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice. –Suggesting a possible role of CA1 histaminergic system in harmane-induced amnesia. –Involvement of nitrergic system of CA1in harmane induced learning and memory deficits.

SENILE DEMENTIA / PARKINSONISM: –In vivo and in vitro metabolism and pharmacokinetics of cholinesterase inhibitor deoxyvasicine from aerial parts of Peganum harmala Linn in rats via UPLC-ESI-QTOF-MS and UPLC-ESI-MS/MS. –Peganum Harmala L. Extract Reduces Oxidative Stress and Improves Symptoms in 6-Hydroxydopamine-Induced Parkinson’s Disease in Rats. –Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities. ANTI-PSYCHOTIC: –High-Performance Thin-Layer Chromatography Method for Simultaneous Determination of Antipsychotic and Medicinally Important Five β-Carboline Alkaloids. DEPRESSION: –Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions. ANTI-CANCER, ANTI-TUMOR, CYTOTOXIC: –Potent Antitumor Effects of a Combination of Three Nutraceutical Compounds. –Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala. –Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells. –Cytotoxic Constituents and Mechanism from Peganum harmala. –Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities. –Antitumor quinazoline alkaloids from the seeds of Peganum harmala. –B-9-3, a novel β-carboline derivative exhibits anti-cancer activity via induction of apoptosis and inhibition of cell migration in vitro. –Cytotoxicity of alkaloids isolated from Peganum harmala seeds. –Harmaline and harmalol inhibit the carcinogen-activating enzyme CYP1A1 via transcriptional and posttranslational mechanisms. –Alkaloids derived from genus Veratrum and Peganum of Mongolian origin as multidrug resistance inhibitors of cancer cells. –Harmine inhibits tumour specific neo-vessel formation by regulating VEGF, MMP, TIMP and pro-inflammatory mediators both in vivo and in vitro. –DH334, a beta-carboline anti-cancer drug, inhibits the CDK activity of budding yeast. –Antitumor and neurotoxic effects of novel harmine derivatives and structure-activity relationship analysis. –In vitro cell-toxicity of Peganum harmala alkaloids on cancerous cell-lines. –Antitumour principles from Peganum harmala seeds. BREAST: –Peganum harmala L.’s anti-growth effect on a breast cancer cell line. –Seeds of Peganum Harmala L. chemical analysis, antimalarial and antioxidant activities, and cytotoxicity against human breast cancer cells. COLORECTAL: –Harmine induces cell cycle arrest and mitochondrial pathway-mediated cellular apoptosis in SW620 cells via inhibition of the Akt and ERK signaling pathways. GASTRIC: –Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells. –Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer. –[Harmine induces apoptosis in human SGC-7901 cells]. LUNG: –Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK. LEUKEMIA: –Harmine, a Novel DNA Methyltransferase 1 Inhibitor in the Leukemia Cell Line. –Cytotoxic indole alkaloids against human leukemia cell lines from the toxic plant Peganum harmala. MELANOMA: –Studies on anti-metastatic and anti-invasive effects of harmine using highly metastatic murine B16F-10 melanoma cells. –Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma. ANTI-ANGEOGENESIS: –In vitro inhibition of angiogenesis by heat and low pH stable hydroalcoholic extract of Peganum harmala seeds via inhibition of cell proliferation and suppression of VEGF secretion. OSTEOARTHRITIS: –Randomized clinical trial of peganum oil for knee osteoarthritis. ANTI-DIABETIC: –Evaluation of Antidiabetic and Antihyperlipidemic Effects of Peganum harmala Seeds in Diabetic Rats. –Effects of a triplex mixture of Peganum harmala, Rhus coriaria, and Urtica dioica aqueous extracts on metabolic and histological parameters in diabetic rats. –Improvement in The Function of Isolated Rat Pancreatic Islets through Reduction of Oxidative Stress Using Traditional Iranian Medicine. –Anti-diabetic and anti-oxidative effects of 4-hydroxypipecolic acid in C57BL/KsJ-db/db mice. –Preliminary studies on the hypoglycemic effect of Peganum harmala L. Seeds ethanol extract on normal and streptozotocin induced diabetic rats. –The effect of medicinal plants of Islamabad and Murree region of Pakistan on insulin secretion from INS-1 cells. URINARY SYMPTOMS OF PROSTATIC HYPERPLASIA: –Impact of oral capsule of Peganum harmala on alleviating urinary symptoms in men with benign prostatic hyperplasia; a randomized clinical trial. ACUTE KIDNEY INJURY: –Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-κB/NLRP3 inflammasome signalling pathway in mice. INSECTICIDAL: –Design, synthesis, anti-TMV, fungicidal, and insecticidal activity evaluation of 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid derivatives based on virus inhibitors of plant sources. –Cytotoxic and insecticidal activities of derivatives of harmine, a natural insecticidal component isolated from Peganum harmala. ANTI-PARASITIC: –Antiparasitic effect of wild rue (Peganum harmala L.) against experimentally induced coccidiosis in broiler chicks. LEISHMANIA –In vitro and in vivo activities of Peganum harmala extract against Leishmania major. –Peganine hydrochloride dihydrate an orally active antileishmanial agent. –Antileishmanial activity mediated by apoptosis and structure-based target study of peganine hydrochloride dihydrate: an approach for rational drug design.