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Improving health benefits with considering traditional and modern health benefits of Peganum harmala
Clinical Phytoscience volume 7, Article number: 18 (2021)
Medicinal plants are potential source of natural products that play an important role in preventing different human diseases. P. harmala is used traditionally as emmenagogue and an abortifacient agent in the Middle East, North of Africa and West of China. It belongs to the family of Zygophyllaceae and it is a wild growing flowering plant. Its seeds are main medicinal part of the plant.
The current searching was done by the keywords in main indexing systems including PubMed/MEDLINE, Scopus, and Institute for Scientific Information Web of Science as well as the search engine of Google Scholar. The keywords were wild rue, traditional medicine, Harman, health benefits, and pharmaceutical science.
The most important uses of P. harmala in traditional pharmaceutical sciences are in cardiovascular, gasterointestinal, nervous, endocrine, neoplasm and tumors, pain relieving, organisms, diabetes, respiratory, disinfectant, anti-pyretic, skin and hair, rheumatism, arthritis and inflammation, and ulcers. Pharmacological effects of P. harmala are in cardiovascular system, nervous system, antimicrobial effects, antineoplasm, nervous system, endocrine, gastrointestinal effects, osteocytes, endocrine and respiratory system. Phenolic compounds are the main reason of antioxidant capacity.
Due to its pharmacological activities, P. harmala is a high potential medicinal herb and the suggestion is to increases by doing research in efficacy and safety.
Wild rue (P. harmala) occurrence and classification
Medicinal plants have been used for many years as remedies for both human and animal ailments [1,2,3,4,5]. Aromatic and medicinal plants as the key source of complementary and alternative medicine have been recently bring many hopes in alleviating of symptomatology and curing associated with so many diseases [6,7,8,9]. P. harmala, commonly called Esfand, Wild rue, Syrian rue, African rue, is a plant of the family Nitrariaceae . This plant is native from the eastern Iranian region west to India . P. harmala is a traditional medicinal plant which is used for many purposes, the aim of this review is to survey on some health benefits of this traditional medicinal plant. Scientific classification of harmal is shown in Table 1.
It is considered as one of the most important medicinal plant in Iranian traditional medicine, which has various benefits such as anti infection, anti inflammation, anti tumor and anti parasite. This important multipurpose medicinal plant has many phytochemical features, and contains a number of active alkaloids, particularly beta-carbolines such as harmalol, harmaline, and harmine. The plant is perennial which can grow to approximate 0.8 m tall, and the root can reach a depth of up to 6 m . This perennial herbaceous plant, branched into 5–13 stems, the leaves are palmatisected into 3–5 linear lobes which are 3–6 cms long and 1.5-3.0 mm wide. Flowers arise by 1–3 on apexes of branches which bear whitish-yellow petals in color, and the fruits are globular capsule with 3 chambers, 0.9–1.3 cm in diameter and containing 35–45 angular blackish seeds. Various parts of P. harmala (a) Leaves and Flowers, (b) Fruit, (c) Seeds are shown in Fig. 1.
P. harmala Nutritional Composition and Chemical Constituents
The fruits and seeds are digestive, hallucinogenic, diuretic, antipyretic, antispasmodic, emetic, nauseant, narcotic and a uterine stimulant [13, 14]. The leaves used in the treatment of asthma, colic, dysmenorrhea, hiccups, neuralgia, hysteria and rheumatism . Harmine was originally isolated from seeds of P. harmala in 1847 having a core indole structure and a pyridine ring . Faskhutdinov et al.  isolated two alkaloids, namely dipegine and dipeginol. Four new flavonoids of acacetin 7-O-rhamnoside, 7-O-[6-O-glucosyl-2-O-(3-acetylrhamnosyl)glucoside and 7-O-(2-O-rhamnosyl-2-O-glucosylglucoside), and the glycoflavone 2-O-rhanmosyl-2-O-glucosylcytisoside were found in the aerial parts of P. harmala . Massoud et al.  expressed that the principle alkaloids present are harmaline, harmine, harmalol, and peganine. Lamchouri et al.  also indicated that harmaline, the active principle of the seeds of P. harmala and its derivatives cause visual troubles, agitation, delirium, loss of coordination and it can produce paralysis at high doses. Faridi et al.  showed that the major components of P. harmala smoke were α-pinene (60.4 %), limonene (6.4 %0 and styrene (4.2 %) and those of the volatile oil were α-pinene (72.6 %), trans-verbenole (3.9 %) and sabinene (2.6 %). Herraiz et al.  stated that psychopharmacological and toxicological characteristics of P. harmala were attributed to quinazoline and β-carboline alkaloids. They found three major quinazoline alkaloids, namely, peganine which appeared in flowers and leaves in high levels, high amounts of deoxypeganine and peganine which found in immature and green fruits, and high amounts of deoxypeganine and peganine which discovered in immature and green fruits, and also peganine and peganine glycoside accumulated in high amount in dry seeds, while roots and stems contained low amount of quinazolines. Alkaloids of Esfand can form dangerous reaction with antihistamines, antidepressants, decongestants, expectorant and some stimulants [23,24,25]. Phytochemical screening in the leaves of P. harmala showed the presence of flavonoids, alkaloids, saponins, tannins, glycosides, terpenoids and steroids and the absence of anthraquinone. Asgarpanah and Ramezanloo  and Fatma et al.  announced that the major alkaloids detected and quantified from the intensity of the fluorescence of P. harmala were harmine, harmaline, harmalol and harmol. Javzan et al.  determined alkaloids such as 1H-cyclopenta(b)quinoline, 184.108.40.206.7.8-hexahydro-9-amino-; Vasicinone (1H-Pyrrolo[2.1-b]quinazolin-9-one,3-hydroxy-2.3-dihydro) and harmine were isolated from cultivated plant of P. harmala. Farouk et al.  and Khan et al.  detected alkaloids, saponins, tannins, anthraquinones, flavonoids, flavones, terpenoids, phlobatannins, chalcones and cardiac glycosides in P. harmala Chemical structures of harmala alkaloids are shown in Fig. 1.
Saturated fatty acids and their derivatives composition of P. harmala are tetradecanoic acid, 12-Methyl tetradecanoic acid, pentadecanoic acid, 5,9,13-Trimethyl tetradecanoic acid, tridecanoic acid, hexadecanoic acid, 2-methyl-octadecanoic acid, heptadecanoic acid and octadecanoic acid, and unsaturated fatty acids and their derivatives composition are (E)-9-dodecenoic acid, (Z)-9-Hexadecenoic acid, (Z,Z)-9,12-octadecadienoic acid and (Z,Z,Z)-9,12,15-octadecatrienoic acid [31, 32]. Non-fatty acids compounds composition of P. harmala detected by GC/MS are 1-octadecene, 6,10,14-trimethyl-2-pentadecanone, (E)-15-heptadecenal, xxacyclohexadecan-2-one, 1,2,2,6,8-pentamethyl-7-oxabicyclo(4.3.1)dec-8-en-10-one, hexadecane-1,2,-diol, n-heneicosane and eicosan-3-ol . The extract of P. harmala has antibacterial, antifungal, antipruritic and antiprotozoal effects [33, 34]. Prashanth and John  concluded that the methanolic fraction of P. harmala found to be most effective against all tested microorganisms. Wang et al.  discovered that methanol extracts from the seeds of P. harmala, namely, (S)-vasicinone-1-O-β-d-glucopyranoise and (S)-vasicinone exhibited moderate inhibitory activity. Phytochemicals detected in the crude extracts of P. harmala are alkaloids, terpenoids and phenols [37,38,39]. Major metabolites in P. harmala extracts on the basis of H-NMR assignments are isoleucine, valine, threonine, alanine, lysine, acetic acid, proline, 4-hydroxyisoleucine, succinic acid, malic acid, asparagines, choline, phosphorylcholine, betaine, sucrose, β-glucose, vasicine, harmine, harmaline, vasicinone, and formic acid .
Medicinal Uses and Potential Health Benefits in Traditional Medicine and Modern Medicine Industry
The most important therapeutic effects of P. harmala are included candidiasis, anti-inflammatory, anti-cholinesterase, anti-bacterial, anti-microbial, anti-tumor, angiogensis, antiparasitic, antioxidant and cytotoxicity activities, prevent of hepatoprotective, abortifacient potential, and pesticide effects [41, 42]. The most important traditional uses of P. harmala are cardiovascular, gasterointestinal, nervous, endocrine, neoplasm and tumors, pain relieving, diabetes, respiratory diseases, disinfectant, anti-pyretic, skin and hair, ulcers, rheumatism, arthritis and inflammation [43, 44]. Wang et al.  reported P. harmala as a traditional Chinese and Uygur medicine to treat cancer. They have found Osteoarthritis (OA) as a promising leading compound for the development of an anti-lung cancer drug. Mamedov et al.  found that Syrian rue used for centuries in traditional medicine and shows a potential treatment of anxiety and depression. Abolhassanzadeh et al.  demonstrated that topical application of Peganum oil for knee osteoarthritis is an effective pain-reducing treatment. Shatarat et al.  indicated that the root extract of P. harmala possesses antispasmodic activity and justifies its use traditionally in alleviating gastrointestinal disorders. In most parts of Iran, dried capsules mixed with other ingredients are burnt to produce scented smoke that is used to purify the air and the mind and it is also used as a charm against the evil eye . The most popular activities of P. harmala in traditional Iranian medicines are analgesic, intoxicating, abortive, disinfectant, anthelmintic, insect repellant, carminative and its beneficial effect in colic disorder . Shahverdi et al.  described that P. harmala seeds, smoke is traditionally used in Iran as both a disinfectant agent and for all kinds of rituals against evil eye and bad luck. They have reported the antimicrobial activity of dichloromethane condensate prepared from P. harmala seeds (Esphand). Lamchouri et al.  extracted four alkaloids namely, harmalicidine, harmine, peganine (vasicine) and vasicinone and discovered that P. harmala alkaloid inhibited the growth of four tumor cell lines, and proliferation of Jurkat cells with varying potencies, harmine was the most potent in inhibiting cell growth, and vasicinone was the most active as anti-proliferation substance. The analgesic, anti-inflammatory , disinfectant , growth promoting , cholesterol lowering and hepato protective effects  have been reported. Eini et al.  concluded that methanolic extract of P. harmala could be effectively used in rat to optimize serum lipid profile. Rahimi-Moghaddam et al.  showed P. harmala extract showed significant in vitro and in vivo antileishmanial activities. Ataee et al.  discovered that drinking a glass of boiled Esfand seeds may reduce blood sugar, and complaining of nausea, general weakness, abdominal pain, dizziness and several vomiting episodes. High dose of Esfand can reduce spermatogenesis in mice . Aboualigalehdari et al.  revealed that P. harmala as antibiofilm herbal medicine for C. albicans, they have concluded that it seems to be necessary to investigate traditional herbs against pathogenic microorganisms. It has been reported that the seeds contain a red pigment used for coloring wool and carpets and also use as a spice as important aphrodisiac in traditional medicine . Ismahane et al.  indicated that P. harmala essential oils have an ovicidal, adulticidal and larvicidal effects against Ectomyelois ceratoniae and it may be used as an alternative of chemical pesticides. Rezaei et al.  concluded that aqueous extract of P. harmala could prevent symptoms and reduced oxidative stress markers in rats with Parkinson induced by 6-hydroxydopamine. Singh et al.  showed that the ethanolic extract of P. harmala is as effective as metformin in reducing the blood glucose levels of normoglycemic and streptozotocin-induced diabetic rats. Darabpour et al.  noted that P. harmala can be assigned as a source of antibacterial compounds for treatment of infections caused by multi-drug resistant (MDR) bacterial pathogens. Chegeni et al.  noted that ethanolic extracts of P. harmala could be considered a new natural compound against the Acanthamoeba trophozoites and cysts. Tanweer et al.  discovered that methanolic extract of P. harmala could be effectively used in broilers to optimize serum lipid profile to decrease feeding cost and to maximize gross return. Shah and Khan  reported that P. harmala seeds are antiseptic, and used is the treatment of asthma, paralysis, gastrointestinal, urinary problems, epilepsy and also menstrual disorders. Khademalhosseini et al.  confirmed that ethanol extract of P. harmala has appropriate effect on the microorganisms and the healing of skin wounds in comparison with Betadine. Mohsenipour and Hassanshahian  suggested that P. harmala extracts applied as antimicrobial agents testing bacteria particularly in biofilm forms. Shirani-Boroujeni et al.  noted that the application of P. harmala seed can be useful in reducing urinary symptoms in patients with benign prostatic hyperplasia (BPH). Berrougui et al.  suggested that P. harmala compounds could be a major source of compounds that inhibit low density lipoprotein (LDL) oxidative modification induced by copper. The seeds of P. harmala have been widely used for the treatment of nervous, cardiovascular, gastrointestinal, respiratory and endocrine diseases and some human aliments [70, 71]. Harmaline has multiple pharmacological impacts such as antileishmanial, antimicrobial, antiplatelet, antiplasmodial, antitumoral, hypothermic and vasorelaxant activity [72,73,74]. P. harmala alkaloids are capable of disrupting the permeability of the membranes of red blood cells of ruminants . Pharmaceutical benefits of P. harmala are shown in Table 2. The most important health benefits of P. harmala are shown in Fig. 2.
P. harmala is a perennial herbaceous, glabrous plant mainly found in the Middle East, North Africa, and Central Asia. The plant is not usually grazed by animals due to its bitter taste. Its seeds showed that alkaloids belonging to the β-carboline family such as harmine, harmaline, harman, harmol and harmalol are responsible or a wide range of pharmacological effects. The main compounds from P. harmala seeds are dodecane, tetradecane, methyl dodecanoate, hexadecane, 2-octanol benzoate, heptadecane, methyl tetradecanoate, 2,6,10,14-tetramethyl pentadecane, octadecane, 2,6,10,14-tetramethyl hexadecane, nonadecane, methyl hexadecanoate, dibutyl phthalate, eicosane, methyl oleate, henicosane, docosane, harmine and tricosane. The most important properties of P. harmala are anti-cholinesterase, anti-tumor, angiogenesis, antiparasitic effect, anti-inflammatory effect, cytotoxicity effect, antioxidant effect, cerebroprotective effect, cancer effect, hepatoprotective effect, hypoglycemic effect, antibacterial effect, pesticide effect, antitumor effect, antinociceptive effects, haemosporidian infections effect and different unknown beneficial properties. This review article suggests the important potential of P. harmala to be employed in both new western and eastern therapeutic drugs. This review article emphasizes on the need of widespread researches and studies for covering the supplementary information and knowledge on the importance of medicinal crops. This review also suggests more evidences for other researchers to use P. harmala as an ancient efficacious natural drug.
Availability of data and materials
Shahrajabian MH, Sun W, Cheng Q. Clinical aspects and health benefits of ginger (Zingiber officinale) in both traditional Chinese medicine and modern industry. Acta Agr Scand B-S P. 2019;69(6):1–11.
Shahrajabian MH, Sun W, Cheng Q. A review of ginseng species in different regions as a multipurpose herb in traditional Chinese medicine, modern herbology and pharmacological science. J Med Plants Res. 2019;13(10):213–26.
Shahrajabian MH, Sun W, Cheng Q. Modern pharmacological actions of longan fruits and their usages in traditional herbal remedies. J Med Plant Stud. 2019;7(4):179–85.
Sun W, Shahrajabian MH, Khoshkharam M, Cheng Q. Adaptation of acupuncture and traditional Chinese herbal medicines because of climate change. J Stress Physiol Biochem. 2020;16(1):85–90.
Sun W, Shahrajabian MH, Cheng Q. Pyrethrum an organic and natural pesticide. J Biol Environ Sci. 2020;14(40):41–4.
Shahrajabian MH, Sun W, Shen H, Cheng Q. Chinese herbal medicine for SARS and SARS-CoV-2 treatment and prevention, encouraging using herbal medicine for COVID-19 outbreak. Acta Agr Scand B-S P. 2020;70(5):437–43.
Shahrajabian MH, Sun W, Cheng Q. Chinese star anise (Illicum verum) and pyrethrum (Chrysanthemum cinerariifolium) as natural alternatives for organic farming and health care- A review. Aust J Crop Sci. 2020;14(03):517–23.
Shahrajabian MH, Sun W, Cheng Q. Product of natural evolution (SARS, MERS, and SARS-CoV-2); deadly disease, from SARS to SARS-CoV-2. Hum Vaccin Ummunother. 2020. DOI:https://doi.org/10.1080/21645515.2020.1797369.
Shahrajabian MH, Sun W, Chen Q. Traditional herbal medicine for the prevention and treatment of cold and flu in the autumn of 2020, overlapped with COVID-19. Nat Prod Commun. 2020;15(8):1–10.
Ghasemi M, Ghasemi N, Azimi-Amin J. Adsorbent ability of treated Peganum harmala-L. seeds for the removal of Ni (II) from aqueous solutions: kinetic, equilibrium and thermodynamic studies. Indian J Mater Sci. 2014. DOI:https://doi.org/10.1155/2014/459674.
Mashreghi M, Niknia S. The effect of Peganum harmala L. and Teucrium polium alcoholic extracts on growth of Escherichia coli 0157. Jundishapur J Microbiol. 2012;5(3):511–5.
Ababou A, Chouieb M, Bouthiba A, Saidi D, Hamedi Bouzina MM, Mederbal K. Spatial pattern analysis of Peganum harmala L. on the salted lower Chelif plain, Algeria. Turk J Bot. 2013;37:111–21.
Kartal M, Altun ML, Kurucu S. HPLC method for the analysis of harmol, harmalol, harmine and harmaline in the seeds of Peganum harmala L. J Pharm Biomed Anal. 2003;31:263–9.
Goel N, Singh N, Saini R. Efficient in vitro multiplication of Syrian Rue (Peganum harmala L.) using 6-benzylaminopurine preconditioned seedling explants. Nat Sci. 2009;7:129–34.
Ezer N, Mumcu AO. Folk medicines in Merzifon (Amasya, Turkey). Turk J Bot. 2006;30:223–30.
Patel K, Gadewar M, Tripathi R, Prasad SK, Patel DK. A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”. Asian Pac J Trop Biomed. 2012;2(8):660–4.
Faskhutdinov MF, Telezhenestskaya MV, Levkovich MG, Abdullaev ND. Alkaloids of Pganum harmala L. Chem Nat Compd. 2000;36(6). DOI:https://doi.org/10.1023/A:1017524027513.
Sharaf M, El-Ansari MA, Matlin S, Saleh NAM. Four flavonoid glycosides from Peganum harmala L. Phytochemistry. 1997;44(3):533–6.
Massoud M, Jalilpour H, Salehian P. Toxicity of Peganum harmala L.: Review and a Case Report. Iran J Pharmacol Ther. 2002;1:1–4.
Lamchouri F, Settaf A, Cherrah Y, Hamidi MN, Tligui N, Lyoussi B, Hassar M. Experimental toxicity of Peganum harmala L. seeds. Ann Pharm Fr. 2002;60(2):123–9.
Faridi P, Younes G, Mohagheghzadeh A. Chemical composition of Peganum harmala L. smoke and volatile oil. J Essent Oil Bear Pl. 2013;16(6):850–4.
Herraiz T, Guilen H, Aran VJ, Salgado A. Identification, occurrence and activity of quinazoline alkaloids in Peganum harmala L. Food Chem Toxicol. 2017;103:261–9.
Dastagir G, Hussain F, Rehman IU. Essential oil composition of some plants of family Zygophyllaceae and Euphorbiaceae. Pak J Bot. 2014;46(6):2043–9.
Kumar MRP, Joshi SD, Kulkarni VH, Savant C. Phytochemical screening and evaluation of analgesic, anti-inflammatory activities of Peganum harmala L., seeds in rodents. J Appl Pharm Sci. 2015;5(05):052–5.
Ataee Z, Dadpour B, Najari F, Rahimpour M, Najari D. Acute poisoning with Peganum Harmala L., Esfand: a rare case report. Int J Med Toxicol Forensic Med. 2018;8(3):119–21.
Asgarpanah J, Ramezanloo F. Chemistry, pharmacology and medicinal properties of Peganum harmala L. Afr J Pharm Pharmacol. 2012;6(22):1573–80.
Fatma B, Fatiha M, El attafia B, Noureddine D. Phytochemical and antimicrobial study of the seeds and leaves of Peganum harmala L. against urinary tract infection pathogens. Asian Pac J Trop Dis. 2016;6(10):822–6.
Javzan S, Selenge D, Jamyansan Y, Nadmid J, Ouynbileg Y. Alkaloids from cultivated plant of Peganum harmala L. Mong J Chem. 2011;12(38):113–6.
Farouk I, Laroubi A, Aboufatima R, Benharref A, Chait A. Antinociceptive activity of various extracts of Peganum harmala L. and possible mechanism of action. Iranian J Pharmacol Therap. 2009;8:29–35.
Khan AM, Qureshi RA, Ullah F, Gilani SA, Nosheen S, Sahreen MK, Laghari MY, Shafiq-ur-Rehman, Hussain I, Murad W. Phytochemical analysis of selected medicinal plants of Margalla Hills and surroundings. J Med Plants Res. 2011;5(25):6017–23.
Moussa TAA, Almaghrabi OA. Fatty acid constituents of Peganum harmala L. plant using gas chromatography-mass spectroscopy. Saudi J Biol Sci. 2016;23:397–403.
Shi CC, Liao JF, Chen CF. Comparative study on the vasorelaxant effects of three harmala alkaloids in vitro. Jpn J Pharmcol. 2001;85:299–305.
El-Saad El-Rifaie M. Peganum harmala L. Int J Dermatol. 1980;19(4):221–2.
Moloudizargari M, Mikaili P, Aghajanshakeri S, Asghari MH, Shayegh J. Pharmacological and therapeutic effects of Peganum harmala L. and its main alkaloids. Pharmacogn Rev. 2013;7:199–212.
Prashanth D, John S. Antibacterial activity of Peganum harmala L. Fitoterapia. 1999;70(4):438–9.
Wang CH, Zeng H, Wang YH, Li C, Cheng J, Ye ZJ, He XJ. Antitumor quinazoline alkaloids from the seeds of Peganum harmala L. J Asian Nat Prod Res. 2015;17(5):595–600.
Mohammad MH. The role of Peganum harmala L. extract on activity of P53 on some cancerous cell lines. Iraqi J Biotechnol. 2011;10(1):77–88.
Mayad EH, Hassani LMI, Ferji Z, Chebli B, Hadek ME. Quantitative and qualitative analysis by HPLC of major Peganum harmala L. alkaloids at different stages of development. J Nat Sci Res. 2013;3(11):104–11.
Mamedov NA, Pasdaran A, Mamadalieva NZ. Pharmacological studies of Syrian rue (Peganum harmala L., Zygophyllaceae). Int J Second Educ. 2018;5(1):1–6.
Li Y, He Q, Du S, Guo S, Geng Z, Deng Z. Study of methanol extracts from different parts of Peganum harmala L. using 1H-NMR plant metabolomics. J Anal Methods Chem. 2018;4:1–9.
Majid A. A review study of the chemical constituents and therapeutic effects of Peganum harmala L. Global J Pure Appl Chem Res. 2018;6(2):12–9.
Miraj S. A review study of therapeutic effects of Peganum harmala L. Der Pharm Lett. 2016;8(13):161–6.
Lamchouri F, Settaf A, Cherrah Y, Zemzami M, Lyoussi B, Zaid A, Atif N, Hassar M. Antitumor principles from Peganum harmala L. seeds. Therapie. 1999;54(6):753–8.
Wang C, Zhang Z, Wang Y, He X. Cytotoxic constituents and mechanism from Peganum harmala L. Chem Biodivers. 2016;13(7):199–212.
Abolhassanzadeh Z, Yousefi G, Mohagheghzadeh A. Randomized clinical trial of Peganum oil for knee Osteoarthritis. Evid Based Complement Alternat Med. 2015;20(2):126–31.
Shatarat A, Abuhamdah S, Al-Essa M, Mohammed F, Al-Olimat S. Pharmacological effects of Peganum harmala L. root extract on isolated rat small intestine. Pharmacogn Commun. 2014;4(3):56–61.
Frison G, Favretto D, Zancanaro F, Fazzin G, Ferrara SD. A case of b-carboline alkaloid intoxication following ingestion of Peganum harmala L. seed extract. Forensci Sci Int. 2008;179:e37–43.
Cheraghi Niroumand M, Farzaei MH, Amin G. Medicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a review. J Tradit Chin Med. 2015;35(1):104–9.
Shahverdi AR, Ostad SN, Khodaee S, Bitarafan L, Monsef-Esfahani HR, Jamalifar H, Nikavar B, Mohsenin M. Antimicrobial and cytotoxicity potential of Peganum harmala L. smoke. Pharmacogn Mag. 2008;4(15):236–40.
Lamchouri F, Zemzami M, Jossang A, Abdellatif A, Israili Z, Badiaa L. Cytotoxicity of alkaloids isolated from Peganum harmala L. seeds. Pak J Pharm Sci. 2013;26(4):699–706.
Monsef HR, Ghobadi A, Iranshahi M. Antinociceptive effects of Peganum harmala L. alkaid extract on mouse formalin test. J Pharm Sci. 2004;7:65–9.
Shahverdi AR, Monsef-Esfahani HR, Nickavar B, Bitarafan L, Khodaee S, Khoshakhlagh N. Antimicrobial activity and mainchemical composition of two smoke condensates from Peganum harmala L. seeds. Z Naturforsch C. 2005;60:707–10.
Qazan WS. The effect of low levels of dietary Peganum harmala L. and Ballotaundulata or their mixture on chicks. J Anim Vet Adv. 2009;8:1535–8.
Hamdan K, Masmoudi H, Ellouz F, Feki AE, Carreau S. Protective effects of Peganum harmala L. extracts on thiourea induced diseases in adult male rat. J Environ Biol. 2008;29:73–7.
Eini AM, Fazaely H, Fard MM, Meini M, Drab M, Far MA. Effect of Peganum harmala L. on lipid parameters in hypercholesterolemia-induced male Wistar rat. Acad J Med Plants. 2014;2(5):074–8.
Moghadam MS, Maleki S, Darabpour E, Motamedi H, Seyyed Nejad SM. Antibacterial activity of eight Iranian plant extracts against methicillin and cefixime resistant Staphylococcous aureus strains. Asian Pac J Trop Med. 2010;3(4):262–5.
Hemmateenejad B, Abbaspour A, Maghami H, Miri R, Panjehshahin MR. Partial least squares-based multivariate spectral calibration method for simultaneous determination of beta-carboline derivatives in Peganum harmala L. seed extracts. Anal Chim Acta. 2006;575(2):290–9.
Aboualigalehdari E, Sadeghifard N, Taherikalani M, Zargoush Z, Tahmasebi Z, Badakhsh B, Rostamzad A, Ghafourian S, Pakzad I. Anti-biofilm properties of Peganum harmala L. against Candida albicans. Osong Public Health Res Perspect. 2016;7(2):116–8.
Ismahane L, Sghir MM, Ibrahim M, Khadija B, Laid OM. Ovicidal, larvicidal and adulticidal activities of essential oils from Peganum harmala L. (Zygophyllacae) against date moth Ectomyelois ceratoniae Zeller (Lepidoptera: Pyralidae). Int J Biosci. 2016;8(5):146–52.
Rezaei M, Nasri S, Roughani M, Niknami Z, Ziai SA. Peganum harmala L. extract reduces oxidative stress and improves symptoms in 6-hydroxydopamine-induced Parkinson ,s disease in rats. Iran J Pharm Sci. 2016;15(1):275–81.
Singh AB, Chaturvedi JP, Narender T, Srivastava K. Preliminary studies on the hypoglycemic effect of Peganum harmala L. seeds ethanol extract on normal and streptozotocin induced diabetic rats. Indian J Clin Biochem. 2008;23(4):391–3.
Darabpour E, Poshtkouhian Bavi A, Motamedi H, Seyyed Nejad SM. Antibacterial activity of different parts of Peganum Harmala L. growing in Iran against multi-drug resistant bacteria. EXCLI J. 2011;10:252–63.
Chegeni TN, Ghaffarifar F, Khoshzaban F, Dalimi Asl A. Evaluation of anti-amoebic activity of Peganum harmala L. ethanolic extract on acanthamoeba in vitro. Arak Med Uni J. 2018;20(129):74–82.
Tanweer AJ, Chand N, Khan S, Sultan A, Qureshi MS, Akhtar A, Inam M. Rafiullah. Association of Peganum hamala L. supplementation with lipid profile and its economic benefit in broiler production. Pak Vet J. 2013;33(3):313–6.
Shah GM, Khan MA. Common medicinal folk recopies of Siran Valley, Mansehra. Pak J Ethnobot Leaflets. 2006;10:49–62.
Khademalhosseini AA, Tabatabaei A, Akbari P, Fereidouni MS, Akhlaghi M. Comparison of in vivo antiseptic and in vitro antimicrobial effects of Peganum harmala L. seeds ethanolic extract with Betadine. J Coast Life Med. 2015;3(1):70–7.
Mohsenipour Z, Hassanshahian M. Antibacterial of espand (Peganum harmala L.) alcoholic extracts against six pathogenic bacteria in planktonic and biofilk forms. Biol J Microorganism. 2016;4(6):109–20.
Shirani-Boroujeni M, Heidari-Soureshjani S, Hafshejani K. Impact of oral capsule of Peganum harmala L. on alleviating urinary symptoms in men with benign prostatic hyperplasia; a randomized clinical trial. J Renal Inj Prev. 2017;6(2):127–31.
Berrougui H, Isabelle M, Cloutier M, Hmamouchi M, Khalil A. Protective effects of Peganum harmala L. extract, harmine and harmaline against human low-density lipoprotein oxidation. J Pharm Pharmacol. 2006;58:967–74.
Edziri H, Mastouri M, Mahjoub MA, Patrich G, Matieu M, Ammar S, Ali SM, Laurent G, Zine M, Aouni M. Antibacterial, antiviral and antioxidant activities of aerial part extracts of Peganum harmala L. grown in Tunisia. Toxicol Environ Chem. 2010;92(7):1283–92.
Wang Y, Wang H, Zhang L, Zhang Y, Deng G, Li S, Cao N, Guan H, Cheng X, Wang C. Potential mechanisms of tremor tolerance induced in rats by the repeated administration of total alkaloid extracts from the seeds of Peganum harmala L. J Ethnopharmacol. 2020;262. DOI:https://doi.org/10.1016/j.jep.2020.113183.
Herraiz T, Gonzalez D, Ancin-Azpilicueta C, Aran VJ, Guillen H. Β-Carboline alkaloid in Peganum harmala L. and inhibition of human monoamine oxidase (MAO). Food Chem Toxicol. 2010;48(3):839–45.
Khan FA, Maalik A, Iqbal Z, Malik I. Recent pharmacological developments in β-carboline alkaloid harmaline. Eur J Pharmacol. 2013;721(1–3):391–4.
Benarous K, Bombarda I, Iriepa I, Moraleda I, Gaetan H, Linani A, Tahri D, Sebaa M, Yousif M. Harmaline and hispidin from Peganum harmala L. and Inonotus hispidus with binding affinity to Candida rugosa lipase: In silico and in vitro studies. Bioorg Chem. 2015;62:1–7.
Mahdeb N, Mayouf S, Boukhari F, Souilah S, Bouzidi A. Hemolytic effect of total alkaloids from the seeds of Peganum harmala L. in vitro on erythrocytes of ruminants: Sheep, cattle and goats. Asian J Plant Sci Res. 2013;3(6):53–9.
Daoud A, Song J, Xiao F, Shang J. B-9-3, a novel β-carboline derivative exhibits anti-cancer activity via induction of apoptosis and inhibition of cell migration in vitro. Eur J Pharmacol. 2014;724:219–30.
Shabani SHS, Tehrani SSH, Rabiei Z, Enferadi ST, Vannozzi GP. Peganum harmala L. ,s anti-growth effect on a breast cancer cell line. Biotechnol Rep. 2018;8:138–43. DOI:https://doi.org/10.1016/j.btre.2015.08.007.
Bournine L, Bensalem S, Fatmi S, Bedjou F, Mathieu V, Iguer-Uuada M, Kiss R, Duez P. Evaluation of the cytotoxic and cytostatic activities of alkaloid extracts from different parts of Peganum harmala L. (Zygophyllaceae). Eur J Integr Med. 2017;9:91–6.
Kiani SJ, Shamsi Shahrabadi M, Ataei A, Sajjadi N. Peganum harmala L. seed extract can prevent HSV-1 replication in vitro. Iran J Virol. 2007;1(4):11–6.
Benzekri R, Bouslama L, Papetti A, Hammami M, Smaoui A, Limam F. Anti HSV-2 activity of Peganum harmala L. and isolation of the active compound. Microb Pathog. 2018;114:291–98.
Moradi MT, Karimi A, Fotouhi F, Kheiri S, Torabi S. 2017. In vitro and in vivo effects of Peganum harmala L. seeds extract against influenza A virus. Avicenna J Phytomed. 2017;7(6):519 – 30.
Liu X, Li M, Tan S, Wang C, Fan S, Huang C. Harmine is an inflammatory inhibitor through the suppression of NF-κB signaling. Biochem Biophys Res Commun. 2017;489(3):332–38.
Edziri H, Marzouk B, Mabrouk H, Garreb M, Douki W, Mahjoub A, Verschaeve L, Najjar F, Mastouri M. Phytochemical screening butyrylcholinesterase inhibitory activity and anti-inflammatory effect of some Tunisian medicinal plants. A Sfr J Bot. 2018;114:84–8.
Akbary P, Fereidouni MS, Akhlaghi M. In vitro antibacterial activity of Pganum harmala L. extract to some fish pathogenic bacteria. Iran J Aquatic Anim Health. 2015;1(1):7–16.
Alomari AA, Fares KEK, Moustafa NE. Green synthesis of assembled silver nanoparticles in nano capsules of Peganum harmala L. leaf extract, antibacterial activity and conjugate investigation. Cogent Chem. 2018;4(1):1–13.
Azizi M, Sedaghat S, Tahvildari K, Derakhshi P, Ghaemi A. Synthesis silver nanoparticles using Peganum harmala L. extract as a green route. Green Chem Lett Rev. 2017;10(4):420–27.
Nenaah G. Antibacterial and antifungal activities of (beta)-carboline alkaloids of Peganum harmala L. seeds and their combination effects. Fitoterapia. 2010;81(7):779–82.
Javadian F, Bagheri G, Sepehri Z, Anbari M, Shahi Z, Sohil Baigi G, Gholipour N. Activity of Peganum harmala L. extract against antibiotic resistant Staphylococcus aureus. Bull Environ, Pharmacol Life Sci. 2014;3:14 – 6.
Wang K-B, Hu X, Li S-G, Li X-Y, Li D-H, Bai J, Pei Y-H, Li Z-L, Hua H-M. Racemic indole alkaloids from the seeds of Peganum harmala L. Fitoterapia. 2018;125:155–60.
Shaheen HA, Issa MY. In vitro and in vivo activity of Peganum harmala L. alkaloids against phytopathogenic bacteria. Sci Hortic. 2020;264. DOI:https://doi.org/10.1016/j.scienta.2019.108940.
Li H, Wang Z, Wang Y, Xu J, He X. Triterpenoids with anti-proliferative effects from the seeds of Peganum harmala L. Phytochemistry. 2020;174. DOI:https://doi.org/10.1016/j.phytochem.2020.112342.
Hayet E, Maha M, Mata M, Mighri Z, Laurent G, Mahjoub A. Biological activities of Peganum harmala L. leaves. Afr J Biotechnol. 2010;9(48):8199–205.
Soliman AM, Abu-El-Zahab HS, Alswiai GA. Efficacy evaluation of the protein isolated from Peganum harmala L. seeds as an antioxidant in liver of rats. Asian Pac J Trop Med. 2012;285 – 95.
Naresh G, Jaiswal N, Sukanya P, Srivastava AK, Tamrakar AK, Narender T. Glucose uptake stimulatory effect of 4-hydroxypipecolic acid by increased CLUT 4 translocation in skeletal muscle cells. Bioorg Med Chem Lett. 2012;22(17):5648–51.
Bakim B, Sertcelik S, Tankaya O. A case serotonin syndrome with antidepressant treatment and concomitant use of the herbal remedy (Peganum harmala L.). Klin Psikofarmakol B. 2012;22(4):359–61.
Sassoui D, Seridi R, Azin K, Usai M. Evaluation of phytochemical constituents by GC-MS and antidepressant activity of Peganum harmala L. seeds extract. Asian Pac J Trop Dis. 2015;5(12):971–74.
Sodaeizadeh H, Rafieiolhossaini M, Van Damme P. Herbicidal activity of a medicinal plant, Peganum harmala L., and decomposition dynamics of its phytotoxins in the soil. Ind Crops Prod. 2010;31:385–94.
Deng C, Shao H, Pan X, Wang S, Zhang D. Herbicidal effects of harmaline from Peganum harmala L. on photosynthesis of Chlorella pyrenoidosa: Probed by chlorophyll fluorescence and thermoluminescence. Pestic Biochem Physiol. 2014;115:23–31.
Sodaeizadeh H, Rafieiolhossaini M, Havlik J, Van Dammer P. Allelopathic activity of different plant parts of Peganum harmala L. and identification of their growth inhibitors substances. Plant Growth Regul. 2009;59:227–36.
Davoodi H, Ghaemi E, Mazandarani M, Shakeri F, Javid SN, Klishadi M. Anit-mycobacterial and anti-inflammatory activity of Peganum harmala L. J Chem Pharm Res. 2015;7(4):1611–16.
Jahanpour S, Ghazisaidi K, Davoodi H, Mazandarani M, Samet M, Jahanpour N, Ghaemi EA. Antimicrobial effects fold medicinal plants from the north of Iran against Mycobacterium tuberculosis. Arch Pediatr Infect Dis. 2015;3(1 TB):e18098.
Tahraoui A, El-Hilaly J, Israili ZH, Lyoussi B. Ethnopharmacological survey of plants used in the traditional treatment of hypertension and diabetes in south-eastern Morocco (Errachidia province). J Ethnopharmacol. 2007;110(1):105–17.
Poorbarkhordari E, Fooladsaz K, Hosseini SH, Danafar H, Kheiri Manjili H, Ramazani A. The hypoglycemic effects of an ethanol extract of Peganum harmala L. in streptozotocin-induced diabetics rats. Iran J Pharm Sci. 2014;10(3):47–54.
Abd El Baky HH, Abd El Rahman AA, Mekawi EM, Ibrahem EA, Shalapy NM. The anti-diabetic and anti-lipidemic effects of Peganum harmala L. seeds in diabetic rats. Der Pharm Lett. 2016;8(10):1–10.
Abedi Gaballu F, Abedi Gaballu Y, Moazenzade Khyavy O, Mardomi A, Ghahremanzadeh K, Shokouhi B, Mamandy H. Effects of a triplex mixture of Peganum harmala, Rhus coriaria, and Urtica dioica aqueous extracts on metabolic and histological parameters in diabetic rats. Pharm Biol. 2015;53(8):1104–09.
Kajbaf F, Oryan S, Ahmadi R, Eidi A. Harmine, a natural β-carboline alkaloid, ameliorates apoptosis by decreasing the expression of caspase-3 in the kidney of diabetic male Wistar rats. Gene Rep. 2020;21. DOI:https://doi.org/10.1016/j.genrep.2020.100863.
Komeili G, Hashemi M, Bameri-Niafar M. Evaluation of antidiabetic and antihyperlipidemic effects of Peganum harmala L. seeds diabetic rats. Cholesterol. 2016. DOI:https://doi.org/10.1155/2016/7389864.
Soosaraei M, Fakhar M, Teshnizi SH, Hezarjaribi HZ, Sadat E. Medicinal plants with promising antileishmanial activity in Iran: a systematic review and meta-analysis. Ann Med Surg. 2017;21:63–80.
Khaliq T, Misra P, Gupta S, Reddy KP, Kant R, Maulik PR, Dube A, Narender T. Peganine hydrochloride dehydrate an orally active antileishmanial agent. Bioorg Med Chem Lett. 2009;19(9):2585–86.
Liu W, Zhu Y, Wang Y, Qi S, Wang Y, Ma C, Li S, Jiang B, Cheng X, Wang Z, Xuan Z, Wang C. Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala L. on scopolamine-induced memory deficits in mice. J Ethnopharmacol. 2017;204:95–106.
Filali I, Bouajila J, Znati M, Bousejra-El Garah F, Ben Jannet H. Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities. J Enzyme Inhib Med Chem. 2015;30(3):371–76.
Salari E, Ahmadi K, Zamani Dehyaghobi R, Purhematy A, Takalloozadeh HM. Toxic and repellent effect of harmal (Peganum harmala L.) acetonic extract on several aphids and Tribolium castaneum (Herbst). Chil J Agric Res. 2012;72(1):147–51.
Abbasipour H, Mahmoudvand M, Rastegar F, Basij M. Insecticidal activity of Peganum harmala L. seed extract against the diamondback moth, Plutella xylostella. Bull Insectology. 2010;63(2):259–63.
Jbilou R, Amri H, Bouayad N, Ghailani N, Ennabili A, Sayah F. Insecticidal effects of extracts of seven plant species on larval development, α-amylase activity and offspring production of Tribolium castaneum (Herbst) (Insecta: Coleoptera: Tenebrionidae). Bioresour Technol. 2008;99(5):959–64.
This work was supported by the National Key R&D Program of China (Research grant 2019YFA0904700).
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Shahrajabian, M.H., Sun, W. & Cheng, Q. Improving health benefits with considering traditional and modern health benefits of Peganum harmala. Clin Phytosci 7, 18 (2021). https://doi.org/10.1186/s40816-021-00255-7
- Peganum harmala
- Traditional medicine
- Health Benefits
- Pharmaceutical Benefits