Phytochemical, Pharmacological, and Toxicological Studies on Peganum harmala L.: An Overview of the Last Decade

Yıl 2023, Cilt: 13 Sayı: 3, 664 - 678, 11.09.2023

İçim Gökkaya Gülin Renda Tuğba Subaş Ufuk Özgen

https://doi.org/10.33808/clinexphealthsci.1125345

Öz

Objective: Plants have been used to treat ailments since the dawn of humanity. The use of medicinal plants for various purposes such as preventing diseases, treating diseases and supporting medical treatment is increasing day by day. On the other hand, medicinal plants are important sources of raw materials for the pharmaceutical industry. It has been demonstrated that Peganum harmala L. and the phytochemicals it contains have a wide variety of pharmacological activities. P. harmala and its active ingredients can be an important resource for the pharmaceutical industry. In this review, the phytochemistry, pharmacological effects, clinical studies, and toxicity of P. harmala are discussed under the current information.
Methods: Studies on P. harmala were searched using Pubmed, Scopus, Science Direct databases, and Google Scholar search engine. As a result of the searches, 96 articles were included in the study.
Results: The main group of secondary metabolites responsible for the biological activities of P. harmala is alkaloids. The plant and its isolated secondary plant compounds have been shown to have many pharmacological actions, counting antiamnestic, anticancer, antidepressant, antiinflammatory, cardiovascular, gastroprotective, hepatoprotective, nephroprotective, and vasodilator activities. Studies evaluating the plant's clinical effects have been carried out in recent years. However, it has been recorded in the literature that the use of P. harmala causes poisoning with symptoms such as neurosensory symptoms, visual hallucination, bradycardia, hypotension, agitation, tremor, ataxia, and vomiting. Conclusion: Considering the pharmacological effects, the number of studies on the efficacy and safety of P. harmala and its secondary metabolites should be increased.

Anahtar Kelimeler

Peganum harmala, alkaloid, β-carboline, antidepressant, anticancer, toxicity

Kaynakça

• Sharifi-Rad J, Quispe C, Herrera-Bravo J, Semwal P, Painuli S, Özçelik B, Hacıhasanoğlu FE, Shaheen S, Sen S, Acharya K, Amirian M, Castillo CMS, López MD, Schoebitz M, Martorell M, Goloshvili T, Al-Harrasi A, Al-Rawahi A, Kumar M, Suleria HAR, Cho WC. Peganum spp.: A comprehensive review on bioactivities and health-enhancing effects and their potential for the formulation of functional foods and pharmaceutical drugs. Oxid Med Cell Longev. 2021;2021:5900422. DOI: 10.1155/2021/5900422
• Hürkul M, Köroğlu A. Investigation of Peganum harmala L. (üzerlik) fruits sold in the market from the view of pharmaceutical botany. Biodivers Conserv. 2019;12(2):65-77. DOI: 10.5505/biodicon.2019.52724
• Ullah M, Khan MU, Mahmood A, Malik RN, Hussain M, Wazir SM, Daud M, Shinwari ZK. An ethnobotanical survey of indigenous medicinal plants in Wana district south Waziristan agency, Pakistan. J Ethnopharmacol. 2013;150(3):918-924. DOI: 10.1016/j.jep.2013.09.032
• Upadhyay B, Parveen, Dhaker AK, Kumar A. Ethnomedicinal and ethnopharmaco-statistical studies of Eastern Rajasthan, India. J Ethnopharmacol. 2010;129(1):64-86. DOI: 10.1016/j.jep.2010.02.026
• Özdemir E, Alpınar E. An ethnobotanical survey of medicinal plants in western part of central Taurus Mountains: Aladaglar (Nigde-Turkey). J Ethnopharmacol. 2015;166:53-65. DOI: 10.1016/j.jep.2015.02.052
• Korkmaz M, Karakuş S, Özçelik H, Selvi S. An ethnobotanical study on medicinal plants in Erzincan, Turkey. Indian J Tradit Knowl. 2016;15(2):192-202.
• Güler B, Manav E, Uğurlu E. Medicinal plants used by traditional healers in Bozüyük (Bilecik-Turkey). J Ethnopharmacol. 2015;173:39-47. DOI: 10.1016/j.jep.2015.07.007
• Boudjelal A, Henchiri C, Sari M, Sarri D, Hendel N, Benkhaled A, Ruberto G. Herbalists and wild medicinal plants in M'Sila (NorthAlgeria): an ethnopharmacology survey. J Ethnopharmacol. 2013; 148(2):395-402. DOI: 10.1016/j.jep.2013.03.082
• Pawera L, Verner V, Termote C, Sodombekov I, Kandakov A, Karabaev N, Skalicky M, Polesny Z. Medical ethnobotany of herbal practitioners in the Turkestan Range, southwestern Kyrgyzstan. Acta Soc Bot Pol. 2016;85(1):3483. DOI: 10.5586/asbp.3483
• Mosaddegh M, Naghibi F, Moazzeni H, Pirani A, Esmaeili S. Ethnobotanical survey of herbal remedies traditionally used in Kohghiluyeh va Boyer Ahmad province of Iran. J Ethnopharmacol. 2012;141(1): 80-95. DOI: 10.1016/j.jep.2012.02.004
• Sher H, Bussmann RW, Hart R, de Boer HJ. Traditional use of medicinal plants among Kalasha, Ismaeli and Sunni groups in Chitral District, Khyber Pakhtunkhwa province, Pakistan. J Ethnopharmacol. 2016;188:57-69. DOI: 10.1016/j.jep.2016.04.059
• Herraiz T, González D, Ancín-Azpilicueta C, Arán VJ, Guillén H. beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food Chem Toxicol. 2010;48(3):839-845. DOI: 10.1016/j.fct.2009.12.019
• Li S, Cheng X, Wang C. A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum. J Ethnopharmacol. 2017;203:127-162. DOI: 10.1016/j.jep.2017.03.049
• Mina CN, Farzaei MH, Gholamreza A. Medicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a review. J Tradit Chin Med. 2015;35(1):104-9. DOI: 10.1016/s0254-6272(15)30016-9
• Wen F, Cheng X, Liu W, Xuan M, Zhang L, Zhao X, Shan M, Li Y, Teng L, Wang Z, Wang C. Chemical fingerprint and simultaneous determination of alkaloids and flavonoids in aerial parts of genus Peganum indigenous to China based on HPLC-UV: application of analysis on secondary metabolites accumulation. Biomed Chromatogr. 2014;28(12):1763-73. DOI: 10.1002/bmc.3218
• Yang Y, Cheng X, Liu W, Chou G, Wang Z, Wang C. Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a bioassay-guided fractionation. J Ethnopharmacol. 2015;168:279-286. DOI: 10.1016/j.jep.2015.03.070
• Wang KB, Yuan CM, Xue CM, Li DH, Jing YK, He HP, Hao XJ, Di YT, Li ZL, Hua HM. Pegaharmalines A and B, two novel β-carboline alkaloids with unprecedented carbon skeletons from Peganum harmala. RSC Adv. 2014;4:53725-53729.
• Wang KB, Di YT, Bao Y, Yuan CM, Chen G, Li DH, Bai J, He HP, Hao XJ, Pei YH, Jing YK, Li ZL, Hua HM. Peganumine A, a β-carboline dimer with a new octacyclic scaffold from Peganum harmala. Org Lett. 2014;16(15):4028-31. DOI: 10.1021/ol501856v
• Yang YD, Cheng XM, Liu W, Han ZZ, Chou GX, Wang Y, Sun DX, Wang ZT, Wang CH. Peganumine BI and two enantiomers: new alkaloids from the seeds of Peganum harmala Linn. and its their potential cytotoxicity and cholinesterase inhibitory activities. RSC Adv. 2016;6:15976-15987. DOI: 10.1039/C6RA00086J
• Wang KB, Li DH, Hu P, Wang WJ, Lin C, Wang J, Lin B, Bai J, Pei YH, Jing YK, Li ZL, Yang D, Hua HM. A series of β-carboline alkaloids from the seeds of Peganum harmala show G-quadruplex interactions. Org Lett. 2016;18(14):3398-3401. DOI: 10.1021/acs.orglett.6b01560
• Wang KB, Li DH, Bao Y, Cao F, Wang WJ, Lin C, Bin W, Bai J, Pei YH, Jing YK, Yang D, Li ZL, Hua HM. Structurally diverse alkaloids from the seeds of Peganum harmala. J Nat Prod. 2017;80(2):551-559. DOI: 10.1021/acs.jnatprod.6b01146
• Wu ZN, Chen NH, Tang Q, Chen S, Zhan ZC, Zhang YB, Wang GC, Li YL, Ye WC. β-Carboline alkaloids from the seeds of Peganum harmala and their anti-HSV-2 virus activities. Org Lett. 2020; 22(18):7310-7314. DOI: 10.1021/acs.orglett.0c02650
• Herraiz T, Guillén H, Arán VJ, Salgado A. Identification, occurrence and activity of quinazoline alkaloids in Peganum harmala. Food Chem Toxicol. 2017;103:261-269. DOI: 10.1016/j.fct.2017.03.010
• Li SG, Wang KB, Gong C, Bao Y, Qin NB, Li DH, Li ZL, Bai J, Hua HM. Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala. Bioorganic Med Chem Lett. 2018;28:103-106. DOI: 10.1016/j.bmcl.2017.12.003
• Wang CH, Zeng H, Wang YH, Li C, Cheng J, Ye ZJ, He XJ. Antitumor quinazoline alkaloids from the seeds of Peganum harmala. J Asian Nat Prod Res. 2015;17(5):595-600. DOI: 10.1080/10286020.2015.1042373
• Li SG, Wang YT, Zhang Q, Wang KB, Xue JJ, Li DH, Jing YK, Lin B, Hua HM. Pegaharmols A-B, Axially chiral β-carboline-quinazoline dimers from the roots of Peganum harmala. Org Lett. 2020;22(19):7522-7525. DOI: 10.1021/acs.orglett.0c02709
• Wang C, Zhang Z, Wang Y, He X. Cytotoxic indole alkaloids against human leukemia cell lines from the toxic plant Peganum harmala. Toxins. 2015;7(11):4507-4518. DOI: 10.3390/toxins7114507
• Wang KB, Hu X, Li SG, Li XY, Li DH, Bai J, Pei YH, Li ZL, Hua HM. Racemic indole alkaloids from the seeds of Peganum harmala. Fitoterapia. 2018;125:155-160. DOI: 10.1016/j.fitote.2018.01.008
• Moussa TAA, Almaghrabi OA. Fatty acid constituents of Peganum harmala plant using Gas Chromatography Mass Spectroscopy. Saudi J Biol Sci. 2016;23(3):397-403. DOI: 10.1016/j.sjbs.2015.04.013
• Khadhr M, Bousta D, Hanane EH, El Mansouri L, Boukhira S, Lachkar M, Jamoussi B, Boukhchina S. HPLC and GC–MS analysis of Tunisian Peganum harmala seeds oil and evaluation of some biological activities. Am J Ther. 2017;24(6):706–712. DOI: 10.1097/MJT.0000000000000402
• Hajji A, Bnejdi F, Saadoun M, Ben Salem I, Nehdi I, Sbihi H, Alharthi FA, El Bok S, Boughalleb-M'Hamdi N. High reserve in δ-tocopherol of Peganum harmala seeds oil and antifungal activity of oil against ten plant pathogenic fungi. Molecules. 2020;25(19):4569. DOI: 10.3390/molekül25194569
• 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: 112342. DOI: 10.1016/j.phytochem.2020.112342
• Elansary HO, Szopa A, Kubica P, Ekiert H, Al-Mana FA, El-Shafei AA. Polyphenols of Frangula alnus and Peganum harmala leaves and associated biological activities. Plants (Basel). 2020;9(9):1086. DOI: 10.3390/plants9091086
• Moazeni M, Saadaty Ardakani ZS, Saharkhiz MJ, Jalaei J, Khademolhoseini AA, Shams Esfand Abad S, Mootabi Alavi A. In vitro ovicidal activity of Peganum harmala seeds extract on the eggs of Fasciola hepatica. J Parasit Dis. 2017;41(2):467–472. DOI: 10.1007/s12639-016-0830-1
• Selim SA, Aziz MHA, Mashait MS, Warrad MF. Antibacterial activities, chemical constitutes and acute toxicity of Egyptian Origanum majorana L., Peganum harmala L. and Salvia officinalis L. essential oils. Afr J Pharm Pharmacol. 2013;7(13):725-735. DOI: 10.5897/AJPP2013.3518
• Dastagır G, Hussaın F, Rehman IU. Essential oil composition of some plants of family Zygophyllaceae and Euphorbiaceae. Pak J Bot. 2014;46(6):2043-2049.
• Yang S, Bai M, Yang J, Yuan Y, Zhang Y, Qin J, Kuang Y, Sampietro DA. Chemical composition and larvicidal activity of essential oils from Peganum harmala, Nepeta cataria and Phellodendron amurense against Aedes aegypti (Diptera: Culicidae). Saudi Pharm J. 2020;28(5):560-564. DOI: 10.1016/j.jsps.2020.03.007
• Faridi P, Ghasemi Y, Mohagheghzadeh A. Chemical composition of Peganum harmala smoke and volatile oil. J Essent Oil-Bear Plants. 2013;16(4):850-854. DOI: 10.1080/0972060X.2013.861993
• Apostolico I, Aliberti L, Caputo L, De Feo V, Fratianni F, Nazzaro F, Souza LF, Khadhr M. Chemical composition, antibacterial and phytotoxic activities of Peganum harmala seed essential oils from five different localities in Northern Africa. Molecules. 2016;21(9):1235. DOI: 10.3390/molecules21091235
• Asadzadeh R, Abbasi N, Bahmani M. Extraction and identification of chemical compounds of Peganum harmala L. seed essential oil by HS-SPME and GC-MS methods. Trad Integr Med. 2021;6(3):229-235. DOI: 10.18502/tim.v6i3.7310
• 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 on scopolamine-induced memory deficits in mice. J Ethnopharmacol. 2017;204:95-106. DOI: 10.1016/j.jep.2017.04.019
• Deng G, Wu C, Rong X, Li S, Ju Z, Wang Y, Ma C, Ding W, Guan H, Cheng X, Liu W, Wang C. Ameliorative effect of deoxyvasicine on scopolamine-induced cognitive dysfunction by restoration of cholinergic function in mice. Phytomedicine. 2019;63:153007. DOI: 10.1016/j.phymed.2019.153007
• Saleh RA, Eissa TF, Abdallah DM, Saad MA, El-Abhar HS. Peganum harmala enhanced GLP-1 and restored insulin signaling to alleviate AlCl3-induced alzheimer-like pathology model. Sci Rep. 2021;11(1):12040. DOI: 10.1038/s41598-021-90545-4
• Azzazy H, Fahmy SA, Mahdy NK, Meselhy MR, Bakowsky U. Chitosan-Coated PLGA nanoparticles loaded with Peganum harmala alkaloids with promising antibacterial and wound healing activities. Nanomaterials (Basel). 2021;11(9):2438. DOI: 10.3390/nano11092438
• 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):971-974. DOI: 10.1016/S2222-1808(15)60967-7
• Bensalem S, Soubhye J, Aldib I, Bournine L, Nguyen AT, Vanhaeverbeek M, Rousseau A, Boudjeltia KZ, Sarakbi A, Kauffmann JM, Nève J, Prévost M, Stévigny C, Maiza-Benabdesselam F, Bedjou F, Van Antwerpen P, Duez P. Inhibition of myeloperoxidase activity by the alkaloids of Peganum harmala L. (Zygophyllaceae). J Ethnopharmacol. 2014;154(2):361-369. DOI: 10.1016/j.jep.2014.03.070
• Abbas MW, Hussain M, Qamar M, Ali S, Shafiq Z, Wilairatana P, Mubarak MS. Antioxidant and anti-inflammatory effects of Peganum harmala extracts: an in vitro and in vivo study. Molecules. 2021;26(19):6084. DOI: 10.3390/molecules26196084
• Akhtar MF, Raza SA, Saleem A, Hamid I, Ashraf Baig MMF, Sharif A, Sohail K, Javaid Z, Saleem U, Rasul A. Appraisal of anti-arthritic and anti-inflammatory potential of folkloric medicinal plant Peganum harmala. Endocr Metab Immune Disord Drug Targets. 2022;22(1):49-63. DOI: 10.2174/1871530321666210208211310
• Wang L, Wang Q, Wang W, Ge G, Xu N, Zheng D, Jiang S, Zhao G, Xu Y, Wang Y, Zhu R, Geng D. Harmine alleviates titanium particle-induced inflammatory bone destruction by immunomodulatory effect on the macrophage polarization and subsequent osteogenic differentiation. Front Immunol. 2021;12:657687. DOI: 10.3389/fimmu.2021.657687
• Liu W, Cheng X, Wang Y, Li S, Zheng T, Gao Y, Wang G, Qi S, Wang J, Ni J, Wang Z, Wang C. In vivo evaluation of the antitussive, expectorant and bronchodilating effects of extract and fractions from aerial parts of Peganum harmala Linn. J Ethnopharmacol. 2015;162:79-86. DOI: 10.1016/j.jep.2014.12.046
• 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;114:291-298. DOI: 10.1016/j.micpath.2017.12.017
• Moradi MT, Karimi A, Rafieian-Kopaei M, Fotouhi F. In vitro antiviral effects of Peganum harmala seed extract and its total alkaloids against Influenza virus. Microb Pathog. 2017;110:42-49. DOI: 10.1016/j.micpath.2017.06.014
• Keihanian F, Moohebati M, Saeidinia A, Mohajeri SA, Madaeni S. Therapeutic effects of medicinal plants on isoproterenol-induced heart failure in rats. Biomed Pharmacother. 2021;134:111101. DOI: 10.1016/j.biopha.2020.111101
• Huang J, Liu Y, Chen JX, Lu XY, Zhu WJ, Qin L, Xun ZX, Zheng QY, Li EM, Sun N, Xu C, Chen HY. Harmine is an effective therapeutic small molecule for the treatment of cardiac hypertrophy. Acta Pharmacol Sin. 2022;43(1):50–63. DOI: 10.1038/s41401-021-00639-y
• Yavari N, Emamian F, Yarani R, Reza Mohammadi-Motlagh H, Mansouri K, Mostafaie A. 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. Pharm Biol. 2015;53(6):855-861. DOI: 10.3109/13880209.2014.946057
• Ruan S, Jia F, Li J. Potential antitumor effect of harmine in the treatment of thyroid cancer. Evid Based Complement Alternat Med. 2017; 2017(4):1-7. DOI: 10.1155/2017/9402615
• Hamsa T, Kuttan G. Studies on anti-metastatic and anti-invasive effects of harmine using highly metastatic murine B16F-10 melanoma cells. J Environ Pathol Toxicol Oncol. 2011;30(2):123-37. DOI: 10.1615/jenvironpatholtoxicoloncol.v30.i2.40
• Yalçın D, Bayraktar O. Inhibition of catechol-O-methyltransferase (COMT) by some plant-derived alkaloids and phenolics. J Mol Catal B Enzym. 2010;64(3):162-166. DOI: 10.1016/j.molcatb.2009.04.014
• 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. Iranian J Pharm Res. 2016;15(1):275-281.
• Singh VK, Mishra V, Tiwari S, Khaliq T, Barthwal MK, Pandey HP, Palit G, Narender T. Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ülcers. Phytomedicine. 2013; 20(13):1180-1185. DOI: 10.1016/j.phymed.2013.06.017
• Niu X, Yao Q, Li W, Zang L, Li W, Zhao J, Liu F, Zhi W. Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-κB/NLRP3 inflammasome signalling pathway in mice. Eur J Pharmacol. 2019;849:160-169. DOI: 10.1016/j.ejphar.2019.01.062
• Singh AB, Chaturvedi JP, Narender T, Srivastava AK. 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):391-393. DOI: 10.1007/s12291-008-0086-3
• Singh AB, Khaliq T, Chaturvedi JP, Narender T, Srivastava AK. Anti-diabetic and anti-oxidative effects of 4-hydroxypipecolic acid in C57BL/KsJ-db/db mice. Hum Exp Toxicol. 2012;31(1):57-65. DOI: 10.1177/0960327111407227
• Al-Saikhan FI, Ansari MN. Evaluation of the diuretic and urinary electrolyte effects of methanolic extract of Peganum harmala L. in Wistar albino rats. Saudi J Biol Sci. 2016;23(6):749-75. DOI: 10.1016/j.sjbs.2016.01.025
• Berrougui H, Marhuenda E, Haddad W, Hmamouchi M, Khalil A, El-Bouadili A, Herrera MD. Comparative study on the vasorelaxant effects of three alkaloids-rich extracts from seeds of Peganum harmala L. J Nat Remedies. 2012;12(1):87-91. DOI: 10.18311/jnr/2012/42
• Khoshzaban F, Ghaffarifar F, Koohsari HRJ. Peganum harmala aqueous and ethanol extracts effects on lesions caused by Leishmania major (MRHO/IR/75/ER) in BALB/c mice. Jundishapur J Microbiol. 2014;7(7):e10992. DOI: 10.5812/jjm.10992
• Shang XF, Guo X, Li B, Pan H, Zhang J, Zhang Y, Miao X. Microwave-assisted extraction of three bioactive alkaloids from Peganum harmala L. and their acaricidal activity against Psoroptes cuniculi in vitro. J Ethnopharmacol. 2016;192:350-361. DOI: 10.1016/j.jep.2016.07.057
• Bourogaa E, Jarraya RM, Damak M, Elfeki A. Hepatoprotective activity of Peganum harmala against ethanol-induced liver damages in rats. Arch Physiol Biochem. 2015;121(2):62-67. DOI: 10.3109/13813455.2015.1016974
• Derakhshanfar A, Oloumi MM, Mirzaie M. Study on the effect of Peganum harmala extract on experimental skin wound healing in rat: pathological and biomechanical findings. Comp Clin Pathol. 2010;19:169-172. DOI: 10.1007/s00580-009-0848-1
• Abolhassanzadeh Z, Aflaki E, Yousefi G, Mohagheghzadeh A. Randomized clinical trial of Peganum oil for knee osteoarthritis. Evid Based Complement Alternat Med. 2015;20(2):126-131. DOI: 10.1177/2156587214566867
• Hafshejani ZK, Lorigooini Z, Deris F, Akbari N, Farahbod F, Fazelian S, Moradi F, Dehghan M. Effect of oral capsule of Peganum harmala seeds on bone density in menopausal women prone to osteoporosis. J Shahrekord Univ Med Sci. 2021;23(3):139-145. DOI: 10.34172/jsums.2021.23
• Boroujeni MS, Soureshjani SH, Hafshejani ZK. Impact of oral capsule of Peganum harmala on alleviating urinary symptoms in men with benign prostatic hyperplasia: a randomized clinical trial. J Ren Inj Prev. 2017;6(2):127-131. DOI: 10.15171/jrip.2017.25
• Shakeri N, Mehrabi S, Mehrabi A, Jahanabad HM. Comparison efficacy of oral Peganum harmala seed versus tamsulosin on pain relief and expulsion of renal and ureteral stones; a randomized clinical trial. J Nephropathol. 2020;9(4):e40. DOI: 10.34172/jnp.2020.40
• Panahi Y, Saadat A, Seifi M, Rajaee M, Butler AE, Sahebkar A. Effects of spinal-Z in patients with gastroesophageal cancer. J Pharmacopuncture. 2018;21(1):026-034. DOI: 10.3831/KPI.2018.21.004
• Tabrizizadeh M, Kazemipoor M, Hakimian M, Maleksabet M, Kazemipoor M, Zandi H, Poorrajab F, Che C, Cordell GA. Effects of Peganum harmala (Zygophyllaceae) preparation for root canal disinfection. Phytotherapy Research. 2018;32(4):672-77. DOI: 10.1002/ptr.6015
• Boeira JM, da Silva J, Erdtmann B, Henriques JA. Genotoxic effects of the alkaloids harman and harmine assessed by comet assay and chromosome aberration test in mammalian cells in vitro. Pharmacol Toxicol. 2001;89(6):287-94. DOI: 10.1034/j.1600-0773.2001.d01-162.x
• Boeira JM, Viana AF, Picada JN, Henriques JA. Genotoxic and recombinogenic activities of the two beta-carboline alkaloids harman and harmine in Saccharomyces cerevisiae. Mutat Res. 2002;500(1-2):39-48. DOI: 10.1016/s0027-5107(01)00294-9
• Benbott A, Bahri L, Boubendir A, Yahia A. Study of the chemical components of Peganum harmala and evaluation of acute toxicity of alkaloids extracted in the Wistar albino mice. J Mater Environ Sci. 2013;4(4):558-565.
• Muhi-eldeen Z, Al-Shamma KJ, Al-Hussainy TM, Al- Kaissi EN, Al-Daraji AM, Ibrahim H. Acute toxicological studies on the extract of Iraqi Peganum harmala in rats. Eur J Sci Res. 2008;22(4):494-500.
• Lamchouri F, Settaf A, Cherrah Y, El Hamidi M, Tligui N, Lyoussi B, Hassar B. Experimental toxicity of Peganum harmala seeds. Ann. Pharm. Fr. 2002; 60: 123-129.
• Wang Y, Wang H, Zhang L, Zhang Y, Sheng Y, Deng G, Li S, Cao N, Guan H, Cheng X, Wang C. 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. J Ethnopharmacol. 2019;238:111866. DOI: 10.1016/j.jep.2019.111866
• Abderrahman SM, Soliman S, Mohammad MG. Genotoxic effects of Peganum harmala L. in relation to traditional use. JPP. 2018;10(9):167-173. DOI: 10.5897/JPP2018.0493
• Shapira Z, Terkel J, Egozi Y, Nyska A, Friedman J. Abortifacient potential for the epigeal parts of Peganum harmala. J Ethnopharmacol. 1989;27:319-325. DOI: 10.1016/0378-8741(89)90006-8
• Fathiazad F, Azarmi Y, Khodaie L. Pharmacological effects of Peganum harmala seeds extract on ısolated rat uterus. Iran. J. Pharm. Sci. 2006;2(2):81-86.
• El-Dwairi QA, Banihani SM. Histo-functional effects of Peganum harmala on male rat's spermatogenesis and fertility. Neuro Endocrinol Lett. 2007; 28(3):305-10.
• Bakim B, Sertcelik S, Tankaya O. A case of serotonin syndrome with antidepressant treatment and concomitant use of the herbal remedy (Peganum harmala). Klin Psikofarmakol B. 2012;22(4):359-36. DOI: 10.5455/bcp.20120729095402
• Liu CH, Chu WL, Liao SC, Yang CC, Lin CC. Syrian rue seeds interacted with Acacia tree bark in an herbal stew resulted in N,N-dimethyltryptamine poisoning. Clin Toxicol. 2019;57(10):867-869. DOI: 10.1080/15563650.2019.1576877
• Durmaz Çelik N, Ger Akarsu F, Ozkan S, Özdemir AÖ, Aykac Ö, Memmedova F. Herbal teas can be harmful: a case of Peganum harmala induced coma in a patient with Parkinson's disease. Neurocase. 2021;27(2):117-119. DOI: 10.1080/13554794.2021.1876092
• Ghizlane EA, Manal M, Ines HA, Soufiane D, Moussa L, Houssam B, Brahim H. Fatal poisoning of pregnant women by Peganum harmala L.: A case reports. Ann Med Surg (Lond). 2021;68:102649. DOI: 10.1016/j.amsu.2021.102649
• Vahabzadeh M, Mohammadi AB, Delirrad M. Abortion induced by Peganum harmala ingestion in a pregnant woman; a case report and literature review. Int J Med Toxicol. 2019;9(3):165-170. DOI: 10.32598/ijmtfm.v9i3.25910
• Ataee Z, Dadpour B, Najari F, Rahimpour M, Najari D. Case report: acute poisoning with Peganum harmala, esfand: a rare case report. Int J Med Toxicol Forensic Med. 2018;8(3):119-121. DOI: 10.22037/ijmtfm.v8i3(Summer).22342
• Mohammadi RS, Bidaki R, Mirdrikvand F, Yazdi SNM, Anari PY. Peganum harmala (Aspand) intoxication; a case report. Emergency. 2016;4(2):106-107.
• Berdai MA, Labib S, Harando M. Peganum harmala L. intoxication in a pregnant woman. Case Reports in Emergency Medicine. 2014;2014:783236. DOI: 10.1155/2014/783236
• Moshiri M, Etemad L, Javidi S, Alizadeh A. Peganum harmala intoxication, a case report. Avicenna J. Phytomedicine. 2013;3(3):288-292.
• Yuruktumen A, Karaduman S, Bengi F, Fowler J. Syrian rue tea: a recipe for disaster. Clin Toxicol. 2008;46:749-752. DOI: 10.1080/15563650701323205
• Mahmoudian M, Jalipour H, Dardashti PS. Toxicity of Peganum harmala: review and a case report. IJPT. 2002;1: 1-4.