Research – World Wide

Syrian Rue has carved its name into the chronicles of time.  Michelangelo used Syrian Rue (known also by its Latin name – Peganum harmala).  Leonardo da Vinci said Syrian Rue is “miracle smart nutrient”.  In the Middle East it is known as Esfand where its use dates back to pre-Zoroastrian ancient times .  Most references to Syrian Rue in Persian history involve the use of magick.  Greeks refer to it as Persaia botane.  Shakespeare referred to it in his writings, although his personal use of it is unknown.  Traces have been found in the hair of Egyptian mummified bodies.

When whole seeds are placed on hot charcoals the seeds releasing a fragrant smoke.  It is very likely that the ancient “Soma Plant” is Syrian Rue by another name for the somatic science that surrounds it.   Pedanius Dioscorides documented that Syrian Rue not only antidotes snake poisons but all deadly poisons, including poison mushrooms, scorpions, spiders, and mistletoe.  Syrian Rue is also recommended for fevers with rigors(chills).  Serapio calls it ‘the ultimate medicine against the evil of poisons’.  Syrian Rue was used by thieves who robbed the houses of plague victims under the protection of their aromatic repellent.  It is also known as the “anti-plague” plant.  After the assignation of his father by poison, Mithridates King of Pontus studied poisons and used Syrian Rue to protect himself.

In addition to all the ancient documentation about Syrian Rue, more recent scientific observations from research teams around the world (fully referenced below) prove that the fluorescent harmala beta-carboline alkaloid combined with all the other alkaloids in Syrian Rue is arguably magical or contains a synergy of alkaloids which is responsible for the unusual combination of it being antibacterial, antiviral, and antiparasitic, as well as antimutagenic and antigenotoxic.

In 2007 it was first proposed that Syrian Rue might help with diabetes, by 2015 independent studies are reporting success with Rue, in 2017 now we know Type 2 diabetics might be able to achieve a reversal of their condition and Type 1 diabetes patients are able to produce healthy new pancreatic beta cells.  Researchers all around the world are finding , documenting, and sharing the details of their discovery surrounding the healing powers of Syrian Rue, therefore we are not forced to blindly trust ancient knowledge as we consider the following modern science:

Growth Inhibitory Impact of Peganum harmala L. on Two Breast Cancer Cell Lines

The P. harmala extract exposure against two cancer cell lines, MDA-MB-231 and Mcf-7.  In conclusion, the results of the current research address the anti-cancer effect of P. harmala L. to its alkaloid components mainly hamine and harmaline.  It is suggested to perform further studies to elucidate the mechanism of action of both harmine and harmaline on more human cancer cell lines and eventual use of these herbal active principle compounds in future anti-cancer pharmaceutical is considerable.

Article 2, Volume 12, Issue 1, Winter 2014, Page 8-14 XML PDF (655 K)
Document Type: Research Paper
DOI: 10.5812/ijb.18562
Sahar Seyed Hassan Tehrani; Somayeh Hashemi Sheikh Shabani; Sattar Tahmasebi Enferadi ; Zohreh Rabiei

Vaginitis still remains as a health issue in women. It is notable that Candida albicans producing biofilm is considered a microorganism responsible for vaginitis is hard to treat.   Peganum harmala was applied as an anti fungal in treatment for many infections in Iran. Therefore, this study goal to investigate the role of P. harmala in inhibition of biofilm formation in C. albicans.  Results demonstrated that P. harmala in concentration of 12 μg/ml easily inhibited strong biofilm formation.

Osong Public Health and Research Perspectives Volume 7, Issue 2, April 2016, P 116-118
Elham Aboualigalehdari, Nourkhoda Sadeghifard, Morovat Taherikalani, Zaynab Zargoush, Zahra Tahmasebi, Behzad Badakhsh, Arman Rostamzad, Sobhan Ghafourian, Iraj Pakzad

The cytotoxic effects of peganum harmala were evaluated on six malignant cancer cells. Total alkaloids of the different parts were cytotoxic towards practically all cancer cell lines with IC50 ranging 1–52 µg/mL after 72 h of treatment. These data indicate that P. harmala alkaloids extract may support the traditional claims regarding its anticancer uses which could be helpful in providing of new cytotoxic agents against chemo-resistant cancer cells.

European Journal of Integrative Medicine Volume 9, January 2017, Pages 91-96
Lamine Bournine, Sihem Bensalem, Sofiane Fatmi, Fatiha Bedjou, Véronique Mathieue, Mokrane Iguer-Ouada, Robert Kisse, Pierre Duez

Peganum harmala has been shown to have antibacterial and anti-protozoal activity (cures protozoan infections also), including antibacterial activity against drug-resistant bacteria.

J. Nat. Prod. 44 (6): 745. PMID 7334386. doi:10.1021/np50018a025
Al-Shamma A, Drake S, Flynn DL

P harmala seeds extract showed significant in vitro and in vivo antileishmanial activities. Cutaneous leishmaniasis (CL), an endemic disease in many tropical and subtropical areas, including central and southern parts of Iran, continues to present serious treatment problems. The disease, although usually self-limiting, can cause considerable morbidity and may result in severe disfigurement.  P. harmala, vasicine (peganine), has been found to kill the protozoan parasite Leishmania donovani.

Journal of Research in Medical Sciences. 2011 Aug; 16(8): 1032–1039.
Parvaneh Rahimi-Moghaddam, Soltan Ahmed Ebrahimi, Hourmazd Ourmazdi, Monawar Selseleh, Maryam Karjalian, Giti Haj-Hassani, Mohammad Hossein Alimohammadian, Massoud Mahmoudian, and Massoumeh Shafiei

P. harmala has appreciable efficacy in destroying intracellular parasites in the vesicular forms.   Because of its appreciable efficacy in destroying intracellular parasites as well as non-hepatotoxic and non-nephrotoxic nature, harmine, in the vesicular forms, may be considered for clinical application in humans.

Journal of Drug Targeting,
2004 Apr;12(3):165-75.
Lala S, Pramanick S, Mukhopadhyay S, Bandyopadhyay S, Basu M

In this study, we investigated the protective effects of Peganum harmala seeds extract (CPH) against chronic ethanol treatment. Hepatotoxicity was induced in male Wistar rats by administrating ethanol 35% (4?g/kg/day) for 6 weeks. CPH was co-administered with ethanol, by intraperitonial (IP) injection, at a dose of 10?mg/kg bw/day. Control rats were injected by saline solution (NaCl 9‰). Chronic ethanol administration intensified lipid peroxidation monitored by an increase of TBARS level in liver. Ethanol treatment caused also a drastic alteration in antioxidant defence system; hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. A co-administration of CPH during ethanol treatment inhibited lipid peroxidation and improved antioxidants activities. However, treatment with P. harmala extract protects efficiently the hepatic function of alcoholic rats by the considerable decrease of aminotransferase contents in serum of ethanol-treated rats.

Archives of Physiology and Biochemistry – The Journal of Metabolic Diseases
Volume 121, Issue 2  Published online: 14 May 2015
Ezzeddine Bourogaa, Raoudha Mezghani Jarraya, Mohamed Damak & Abdelfattah Elfeki

From mice to men.

Peganum harmala seed extracts also show effectiveness against various tumor cell lines, both in vitro and in vivo.  Results obtained indicate that alkaloids of Peganum have a high cell toxicity in vitro. The active principle at a dose of 50 mg/kg given orally to mice for 40 days was found to have significant antitumoural activity. Peganum harmala alkaloids thus possess significant antitumour potential, which could prove useful as a novel anticancer therapy.

1999 Nov-Dec;54(6):753-8.
Lamchouri F, Settaf A, Cherrah Y

Plant derived agents may exert a new approach to the treatment of leukaemia. The present study was an evaluation of proliferation, cytotoxicity and differentiation of harmine and harmaline on HL60 cells, alone or in combination with ATRA and G-CSF. Counting of cells, viability, MTT assay, morphology, NBT reduction and flow cytometry analysis were performed using CD11b and CD 14 monoclonal antibodies. The data showed that harmine and harmaline reduced proliferation in dose and time dependent manner.  This shows that the direction of differentiation is dominantly determined by ATRA. These preliminary data implies a new approach in treatment of leukemia.

Archives of Pharmacal Research  July 2007, Volume 30, Issue 7, pp 844
Farhad Zaker, Arezo Oody, Alireza Arjmand

Twelve indole alkaloids, including two novels, were purified and identified from P. harmala. The chemical structures were determined by spectroscopic and chemical methods.  The cytotoxicities against five human leukemia cell lines were assayed for the alkaloids.  Some alkaloids showed potent cytotoxicity against human leukemia cells. Harmalacidine (HMC) showed the highest cytotoxicity against U-937, which could induce cell apoptosis. The results suggest that the alkaloids have perfect selectivity for human leukemia cells.

Toxins (Basel). 2017 May; 9(5): 150.
Published online 2017 Apr 28. doi: 10.3390/toxins9050150
Yuan Li, Yunli Zhao, Xia Zhou, Wei Ni, Zhi Dai,Dong Yang, Junjun Hao, Lin Luo, Yaping Liu,Xiaodong Luo, and Xudong Zhao

The beta-carboline alkaloids present in medicinal plants, such as Peganum harmala and Eurycoma longifolia, have recently drawn attention due to their antitumor activities. Further mechanistic studies indicate that beta-carboline derivatives inhibit DNA topoisomerases and interfere with DNA synthesis. Moreover, some beta-carboline compounds are specific inhibitors of cyclin dependent kinases (CDKs). In this study we used budding yeast as a model system to investigate the antitumor mechanism of beta-carboline drugs. We found that DH334, a beta-carboline derivative, inhibits the growth of budding yeast.

Cancer and Biological Therapy,  2007 Aug;6(8):1193-9. Epub 2007 May 4.Li Y, Liang F, Jiang W, Yu F, Cao R, Ma Q, Dai X, Jiang J, Wang Y, Si S.

We report the in vivo antioxidative properties of the aromatic (harmane, harmine, harmol) and dihydro-beta-carbolines (harmaline and harmalol) studied by using Saccharomyces cerevisiae strains proficient and deficient in antioxidant defenses. Their antimutagenic activity was also assayed in S. cerevisiae and the antigenotoxicity was tested by the comet assay in V79 cell line, when both eukaryotic systems were exposed to H(2)O(2). We show that the alkaloids have a significant protective effect against H(2)O(2) and paraquat oxidative agents in yeast cells, and that their ability to scavenge hydroxyl radicals contributes to their antimutagenic and antigenotoxic effects.

Mutagenesis. 2007 Jul;22(4):293-302. Epub 2007 Jun 1.
Moura DJ, Richter MF, Boeira JM, Pêgas Henriques JA, Saffi J

Gamma-harmine exhibited relatively good radioprotective effect.   Gamma-harmine is the first alkaloid isolated from a plant having protective effects against whole-body lethal irradiation in mice

Yao Xue Xue Bao. 1995;30(9):715-7..

A 2016 study investigated the antimicrobial activity of Harmal ( Peganum harmala) aqueous extracts against two fungi (Aspergillusniger and Peniciliumitalicum) and two Gram negative bacteria (Escerichia coli and Salmonellatyphi). The Harmal methanolic extracts were found to inhibit mycelial radial growth of both fungi. This effect was found to be significant at first day of the experiment as well as the last days. Mycelial fresh and dry weights of both fungi were also greatly reduced with harmal extracts. The higher concentration of Harmal gave the maximum effect which decreased with dilution. The effect on mycelial growth was more pronounced on P.italicum than on A.niger. The effect of Harmal leaves extract on the two bacteria (E.coli and S.typhi) was evaluated by the inhibition zone and dilution methods. A clear zone of inhibition was shown by the extracts against both bacteria, although the inhibition was less against E.coli. The results of the dilution plate method showed that the log number of colonies of both bacteria was highly decreased with Harmal extract; however, S.typhi was more susceptible and greatly affected by the extract.

Journal of Microbiology Research,   p-ISSN: 2166-5885 e-ISSN: 2166-5931,   2016
Abdel Moneim E. Sulieman, Ahmed A. Alghamdi, Vajid N. Veettil, Nasir A. Ibrahim

According to test results, P. harmala seeds extract showed potent antioxidant activity with IC50 values ranging between 40-129 µg/ml. In case of antibacterial assay, P. harmala seeds showed better inhibitory activity than leaves against both strains i.e. Staphylococcus aureus and Pseudomonas aeruginosa with values ranging between 70 to 100% while in case of antifungal assay water-acetone extract of seeds showed significant antifungal effect against Aspergillus niger. In terms of cytotoxic assay, hexane extract of seeds of were more cytotoxic against shrimp larvae (LD50 = 57.07 µg/ml). Aqueous extract of leaves of and acetone extract of seeds showed < 80% mortality in antileishmanial assay. GC-MS analysis revealed that leaves and seeds contain some important biological metabolites. It is concluded that selected plants could be a potential source of antileishmanial, antibacterial, antifungal and anticancer lead compound. Hence it is indicated to further investigate this plant in vitro as well as in vivo for new drug discovery.

International Journal of Biosciences, 9(1), 45-58, July 2016.
Zainab Gul Kanwal, Abdul Hafeez, Ihsan Ul Haq, Tofeeq-Ur-Rehman, Syed Aun Muhammad, Irum Shazadi, Nighat Fatima, Nisar Ur Rehman

Introduction: Benign prostatic hyperplasia (BPH) is considered as a major cause of lower urinary tract symptoms (LUTS) in older men and its most common sign is nocturia. Objectives: This study aimed to determine the effect of the seeds of Peganum harmala compared with tamsulosin on alleviating urinary symptoms in patients with BPH. Patients and Methods: In this single blind clinical trial study, 90 patients diagnosed with BPH and LUTS, based on international prostate standard survey (IPSS) were divided into three groups. The first group was received oral capsule of P. harmala, the second group was administered tamsulosin with oral P. harmala seed and the third group was received tamsulosin drug and they were evaluated after 4 weeks. Results: The results showed that the difference between mean scores of IPSS was significant after the intervention (P=0.001). Besides, the mean of IPSS in the three groups was significantly different (P=0.001) (the first group 41.9±5.3, the second group 21.0±4.4 ,the third group 16.5±3.7 respectively). However, after the intervention, patients in the second group had the lowest average on most indicators of IPSS but the difference was only significant about urinary frequency, nocturia and intermittency(P<0.05). Conclusion: Application of Peganum harmala seed can be useful in reducing urinary symptoms in patients with BPH.

Journal of Renal Injury Prevention  2017 ;6(2):127-131.  PMID: 28497089
Majid Shirani-Boroujeni, Saeed Heidari-Soureshjani, Zahra Keivani Hafshejani

Syrian Rue exhibits antisecretory and cytoprotective properties and is successfully treating gastric ulcers.
Phytomedicine Volume 20, Issue 13, 15 October 2013, Pages 1180-1185
Biochem Biophys Res Commun. 2011 Jun 3; 409(2):260-5

Two different studies showed bone anabolic effects of harmine.  These findings suggest that harmine, as the main alkaloid of P. harmala, may be useful for treatment of some bone diseases.  Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling.

Yonezawa T, Lee JW, Hibino A, Asai M, Hojo H, Cha BY, Teruya T, Nagai K, Chung UI, Yagasaki K, Woo JT
European Journal of Pharmacology 2011 Jan 15; 650(2-3):511-8.

Using X-ray crystallographic analysis, Ten new alkaloids (peganumine B-I and two enantiomers), containing five β-carbolines, three quinazolones were isolated from the ethanol extract of Peganum harmala seeds testing their measured potential cytotoxicity and cholinesterase inhibitory activities.

DOI: 10.1039/C6RA00086J (Paper) RSC Adv., 2016, 6, 15976-15987
a-di Yang, Xue-mei Cheng, Wei Liu, Zhu-zhen Han, Gui-xin Chou, Ying Wang, Du-xin Sun, Zheng-tao Wang and Chang-hong Wang

Rats?  Diabetic humans has been done already….

In 2016, a  study indicated that hydroalcoholic extract of Peganum harmala seeds possesses antidiabetic and hypolipidemic activities in streptozotocin-induced diabetic male rats.

Cholesterol,   Volume 2016 (2016), Article ID 7389864, 6 pages
Gholamreza Komeili, Mohammad Hashemi, and Mohsen Bameri-Niafar

Rats again…  I have never heard of a human Parkinson’s Disease study with Syrian Rue, I expect to see one in 2018 if not by the close of 2017…..

Another 2016 study finds Peganum Harmala L. Extract Reduces Oxidative Stress and Improves Symptoms in 6-Hydroxydopamine-Induced Parkinson’s Disease in Rats.

Iran J Pharm Res. 2016 Winter;15(1):275-81.  PMID:27610168   PMCID:PMC4986102
Rezaei M, Nasri S, Roughani M, Niknami Z, Ziai SA.

A 2016 study found that Syrian Rue fights dental plaque.  An ethanolic extract of P. harmala can inhibit the growth of S. mutans. Despite the higher inhibitory effect of 0.2% chlorhexidine compared to 50 mg/mL of this extract, other studies indicate that higher concentrations of P. harmala extract can have similar or greater inhibitory effect against microorganisms. However, high cell toxicity of this extract on cells limits the use of this plant as an antimicrobial agent (like mouthwash) in oral cavity. Even if limited to low concentrations, either lonely or in combined preparations, its application might be more useful for resistant bacteria compared to the routine available mouthwashes. Further antimicrobial and cytotoxicity studies on animals or human subjects are needed to obtain more accurate and applicable results.

Journal of dentistry (Shiraz),  2016 Sep; 17(3): 213–218.  PMCID: PMC5006831
Mohammad Motamedifar, Hengameh Khosropanah, and Shima Dabiri

The extract of Peganum harmala was used topically to treat certain dermatoses of inflammatory nature. Results were encouraging and proved the antibacterial, antifungal, antipruritic and probably antiprotozoal effects of the extract.

International Journal of Dermatology,  May 1980,  DOI:10.1111/j.1365-4362.1980.tb00305.x
El-Saad El-Rifaie M

In very very extremely large doses, Syrian Rue is an abortifacient in humans.

In a study on cattle, the curative effect of P. harmala was better than that of diminazene aceturate and produced minimal side effects proven safe for pregnant animals. It was concluded that the total alkaloid of P. harmale showed a marked effect as a treatment for haemosporidican infections in cattle.

Trop Anim Health Prod. 1997 Nov;29(4 Suppl):72S-76S.
Hu T, Fan B, Liang J, Zhao S, Dang P, Gao F, Dong M