Traditional Medicinal Uses, Phytochemicals, and Pharmacological Activities of Genus Rhamnus: A review

Year 2021, Volume: 8 Issue: 3, 899 - 932, 31.08.2021

Gashaw Nigussie , Haregua Melak Milkyas Endale Annisa

https://doi.org/10.18596/jotcsa.929188

Cited By: 6

Abstract

The genus Rhamnus belongs to the Rhamnaceae family, which contains approximately 137 species, traditionally used as folk medicine in East Asia, North and South America, and subtropical regions of Africa. The genus is used traditionally to treat diseases such as cancer, wound, jaundice, hepatitis, gonorrhea, laxative, hypertension, malaria, stomach ache, snake bite and diarrhea. Anthraquinones and flavonoids are the most cited compounds from the genus of which polyphenols were abundant with tremendous antioxidant, wound healing and antiinflammatory activities. Pharmacological activity evaluation of the extracts and isolated compounds revealed anti-inflammatory, antioxidant, antimalarial, antibacterial, anti-mutagenic, anti-genotoxic, hepatoprotective, anticancer, and anti-proliferative activity. The genus afforded drug leads such as 6-methoxysorigenin (12) and prinoidin (23) with anti-tyrosinase and cytotoxicity, respectively, as well as antioxidant drug leads such as Kaempferol-3-O-β-rhamninoside (31) rhamnetin-3-O-β-isorhamninoside (37) and isotorachrysone (55). The present review endeavors to provide a comprehensive and up to date compilation of documented traditional medicinal uses, phytochemicals and pharmacological activities of the genus and provided valuable information in support of its uses as an alternative medicine for future healthcare practice.

Keywords

Rhamnus, anthraquinones, flavonoids, pharmacological activities

Thanks

Authors express their gratitude to Adama Science and Technology University for providing access to various journal databases.

References

• 1. Nigussie G. A review on traditionally used medicinal plants for scabies therapy in Ethiopia. ADV TRADIT MED (ADTM). 2021 Jun;21(2):199–208. .
• 2. Nigussie G, Ibrahim F, Neway S. A Phytopharmacological Review on a Medicinal Plant: Cordia africana Lam. J Trop Pharm Chem. 2021 Jan 18;5(3):254–63. .
• 3. Anonymous. Plants of the World online [Internet]. 2021. .
• 4. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants [Internet]. CRC Press; 2014 [cited 2021 Jul 29]. .
• 5. Dafni A, Yaniv Z, Palevitch D. Ethnobotanical survey of medicinal plants in northern Israel. Journal of Ethnopharmacology. 1984 May;10(3):295–310. .
• 6. Watson RR, Preedy VR, editors. Arab herbal medicine. In: Botanical medicine in clinical practice. Wallingford, UK ; Cambridge, MA: CABI; 2008. p. 31–9. ISBN: 978-1-84593-413-2.
• 7. Moerman DE. Native American ethnobotany. Portland, Or: Timber Press; 1998. 927 p. ISBN: 978-0-88192-453-4.
• 8. Zevin IV, Altman N, Zevin LV. A Russian herbal: traditional remedies for health and healing [Internet]. Rochester, Vt.: Healing Arts Press; 1997 [cited 2021 Jul 29]. ISBN: 978-0-89281-549-4.
• 9. Watson RR, Preedy VR, editors. Botanical medicine in clinical practice. Wallingford, UK ; Cambridge, MA: CABI; 2008. 915 p. ISBN: 978-1-84593-413-2.
• 10. Page L. Detoxification: all you need to know to recharge, renew and rejuvenate your body, mind and spirit! Carmel Valley, CA: Traditional Wisdom, Inc.; 2002. ISBN: 978-1-884334-54-2.
• 11. Xutian S. Handbook of traditional chinese medicine. Singapore: World Scientific; 2014. ISBN: 978-981-4571-34-0.
• 12. Tucakov J. [Ethnophytotherapy of diabetes. Critical view on the use of medicinal plant extracts in our national medicine in the treatment of diabetes mellitus]. Srp Arh Celok Lek. 1978 Feb;106(2):159–73.
• 13. Chhabra S, Uiso F. Antibacterial activity of some Tanzanian plants used in traditional medicine. Fitoterapia. 1991;62(6):499–503.
• 14. Abdelkrim B, Khaled K, Miloud S, Imane D, Kheira A. Hepatoprotective effects of the decoction and macerated leaves of Rhamnus alaternus L. on rats exposed to carbon tetrachloride. J Pharmacognosy Phytother. 2015 Oct 31;7(10):253–62. .
• 15. Amabye TG. Evaluation of Phytochemical, Chemical Composition, Antioxidant and Antimicrobial Screening Parameters of Rhamnus prinoides (Gesho) Available in the Market of Mekelle, Tigray, Ethiopia. Nat Prod Chem Res [Internet]. 2016;04(01):1000198, 1-6. .
• 16. Montalvo A, Riordan E, Beyers J. Plant profile for Rhamnus crocea and Rhamnus ilicifolia. Native Plant Recommendations for Southern California Ecoregions. 2020;
• 17. Evans WC, Evans D. Trease and Evans pharmacognosy. Edinburgh; London; New York: Saunders Elsevier; 2009. ISBN: 978-0-7020-2933-2.
• 18. Kubitzki K. Flowering plants - Dicotyledons: Celastrales, oxalidales, rosales, cornales, ericales [Internet]. 2004 [cited 2021 Jul 29]. ISBN: 978-3-662-07257-8.
• 19. Boukef K. Rhamnus alaternus. Essaydali. 2001;81:34–5.
• 20. Benarba B. Medicinal plants used by traditional healers from South-west Algeria: an ethnobotanical study. J Intercult Ethnopharmacol. 2016;5(4):320. .
• 21. Nazim B, Houari T, Ismail B. Ethnobotanical Survey of Some Plants Used in Tessala Region, Algeria. Current Perspectives on Medicinal and Aromatic Plants (CUPMAP). 2020 Apr 1;3(1):18–24. .
• 22. Miara MD, Bendif H, Rebbas K, Rabah B, Hammou MA, Maggi F. Medicinal plants and their traditional uses in the highland region of Bordj Bou Arreridj (Northeast Algeria). Journal of Herbal Medicine. 2019 Jun;16:100262. .
• 23. Calvo MI, Cavero RY. Medicinal plants used for cardiovascular diseases in Navarra and their validation from Official sources. Journal of Ethnopharmacology. 2014 Nov;157:268–73. .
• 24. Menendez-Baceta G, Aceituno-Mata L, Molina M, Reyes-García V, Tardío J, Pardo-de-Santayana M. Medicinal plants traditionally used in the northwest of the Basque Country (Biscay and Alava), Iberian Peninsula. Journal of Ethnopharmacology. 2014 Feb;152(1):113–34. .
• 25. Leto C, Tuttolomondo T, La Bella S, Licata M. Ethnobotanical study in the Madonie Regional Park (Central Sicily, Italy)—Medicinal use of wild shrub and herbaceous plant species. Journal of Ethnopharmacology. 2013 Mar;146(1):90–112. .
• 26. Akerreta S, Cavero RY, López V, Calvo MI. Analyzing factors that influence the folk use and phytonomy of 18 medicinal plants in Navarra. J Ethnobiology Ethnomedicine. 2007 Dec;3(1):16. .
• 27. Fortini P, Di Marzio P, Guarrera PM, Iorizzi M. Ethnobotanical study on the medicinal plants in the Mainarde Mountains (central-southern Apennine, Italy). Journal of Ethnopharmacology. 2016 May;184:208–18. .
• 28. Redzic S. Wild medicinal plants and their usage in traditional human therapy (Southern Bosnia and Herzegovina, W. Balkan). Journal of Medicinal Plants Research. 2010;4(11):1003–27. .
• 29. Altundag E, Ozturk M. Ethnomedicinal studies on the plant resources of east Anatolia, Turkey. Procedia - Social and Behavioral Sciences. 2011;19:756–77. .
• 30. Jarić S, Kostić O, Mataruga Z, Pavlović D, Pavlović M, Mitrović M, et al. Traditional wound-healing plants used in the Balkan region (Southeast Europe). Journal of Ethnopharmacology. 2018 Jan;211:311–28. .
• 31. Jarić S, Popović Z, Mačukanović-Jocić M, Djurdjević L, Mijatović M, Karadžić B, et al. An ethnobotanical study on the usage of wild medicinal herbs from Kopaonik Mountain (Central Serbia). Journal of Ethnopharmacology. 2007 Apr;111(1):160–75. .
• 32. Šamec D, Kremer D, Grúz J, Jurišić Grubešić R, Piljac-Žegarac J. Rhamnus intermedia Steud. et Hochst.–a new source of bioactive phytochemicals. Croatica Chemica Acta. 2012;85(2):125–9. .
• 33. Šarić-Kundalić B, Dobeš C, Klatte-Asselmeyer V, Saukel J. Ethnobotanical survey of traditionally used plants in human therapy of east, north and north-east Bosnia and Herzegovina. Journal of Ethnopharmacology. 2011 Feb;133(3):1051–76. .
• 34. Menković N, Šavikin K, Tasić S, Zdunić G, Stešević D, Milosavljević S, et al. Ethnobotanical study on traditional uses of wild medicinal plants in Prokletije Mountains (Montenegro). Journal of Ethnopharmacology. 2011 Jan;133(1):97–107. .
• 35. Mohagheghzadeh A, Faridi P, Shams-Ardakani M, Ghasemi Y. Medicinal smokes. Journal of Ethnopharmacology. 2006 Nov;108(2):161–84. .
• 36. Bozyel ME, Merdamert Bozyel E, Canli K, Altuner EM. Türk Geleneksel Tıbbında Tıbbi Bitkilerin Antikanser Kullanımları. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi. 2019 Dec 31;22(Suppl2):465–84. .
• 37. Purkayastha J, Nath SC, Islam M. Ethnobotany of medicinal plants from Dibru-Saikhowa Biosphere Reserve of Northeast India. Fitoterapia. 2005 Jan;76(1):121–7.
• 38. Fakir H, Korkmaz M, Güller B. Medicinal Plant Diversity of Western Mediterrenean Region in Turkey. Journal of Applied Biological Sciences. 2019;3(2):33–43.
• 39. Maleki T, Akhani H. Ethnobotanical and ethnomedicinal studies in Baluchi tribes: A case study in Mt. Taftan, southeastern Iran. Journal of Ethnopharmacology. 2018 May;217:163–77.
• 40. Nankaya J, Nampushi J, Petenya S, Balslev H. Ethnomedicinal plants of the Loita Maasai of Kenya. Environ Dev Sustain. 2020 Mar;22(3):2569–89.
• 41. Muthee JK, Gakuya DW, Mbaria JM, Kareru PG, Mulei CM, Njonge FK. Ethnobotanical study of anthelmintic and other medicinal plants traditionally used in Loitoktok district of Kenya. Journal of Ethnopharmacology. 2011 Apr;135(1):15–21.
• 42. Nankaya J, Gichuki N, Lukhoba C, Balslev H. Medicinal Plants of the Maasai of Kenya: A Review. Plants. 2019 Dec 27;9(1):44. . .
• 43. Mesfin F, Seta T, Assefa A. An ethnobotanical study of medicinal plants in Amaro Woreda, Ethiopia. Ethnobotany Research and Applications. 2014;12:341–54.
• 44. Elgorashi E. Screening of medicinal plants used in South African traditional medicine for genotoxic effects. Toxicology Letters. 2003 Jul 20;143(2):195–207.
• 45. Seleteng Kose L, Moteetee A, Van Vuuren S. Ethnobotanical survey of medicinal plants used in the Maseru district of Lesotho. Journal of Ethnopharmacology. 2015 Jul;170:184–200.
• 46. Njoroge GN, Bussmann RW. Traditional management of ear, nose and throat (ENT) diseases in Central Kenya. J Ethnobiology Ethnomedicine. 2006 Dec;2(1):54.
• 47. Kidane B, van Andel T, van der Maesen L, Asfaw Z. Use and management of traditional medicinal plants by Maale and Ari ethnic communities in southern Ethiopia. J Ethnobiology Ethnomedicine. 2014;10(1):46.
• 48. Teka A, Asfaw Z, Demissew S, Van Damme P. Traditional uses of medicinal plants practiced by the indigenous communities in Gurage Zone, south central Ethiopia. Ethnobotany Research and Applications. 2020;19:1–31.
• 49. Tamene S. Ethnobotanical study of indigenous knowledge on medicinal plant uses and threatening factors around the Malga District, Southern Ethiopia. International Journal of Biodiversity and Conservation. 2020;12(3):215–26.
• 50. Bitew H, Gebregergs H, Tuem KB, Yeshak MY. Ethiopian medicinal plants traditionally used for wound treatment: a systematic review. Ethiopian Journal of Health Development. 2019;33(2).
• 51. Araya S, Abera B, Giday M. Study of plants traditionally used in public and animal health management in Seharti Samre District, Southern Tigray, Ethiopia. J Ethnobiology Ethnomedicine. 2015 Dec;11(1):22.
• 52. Teklehaymanot T, Giday M. Ethnobotanical study of medicinal plants used by people in Zegie Peninsula, Northwestern Ethiopia. J Ethnobiology Ethnomedicine. 2007 Dec;3(1):12.
• 53. Asmare T, Yilkal B, Mekuannint T, Yibeltal A. Traditional medicinal plants used to treat maternal and child health illnesses in Ethiopia: an ethno-botanical approach. J Tradit Med Clin Natur. 2018;7(277):2.
• 54. Tabuti JRS, Kukunda CB, Waako PJ. Medicinal plants used by traditional medicine practitioners in the treatment of tuberculosis and related ailments in Uganda. Journal of Ethnopharmacology. 2010 Jan;127(1):130–6.
• 55. Mesfin K, Tekle G, Tesfay T. Ethnobotanical study of traditional medicinal plants used by indigenous people of Gemad District, Northern Ethiopia. Journal of Medicinal Plants Studies. 2013;1(4):32–7.
• 56. Siyum D, Woyessa D. Assessment of bacteriological quality and traditional treatment methods of water-borne diseases among well water users in Jimma Town, South West Ethiopia. ARPN J Ag & Bio Sci. 2013;8:477–86.
• 57. Abdeta D, Amante M, Tamiru Y. Survey on Ethno Botany and Medicinal Animals at Sayo and Hawa Gelan Districts of Kelem Wollega Zone, Western Ethiopia. preventive medicine. 2020;28(2):21408–20.
• 58. Kamanja I, Mbaria J, Gathumbi P, Mbaabu M, Lanyasunya A, Gakuya D, et al. Medicinal plants used in the management of sexually transmitted infections by the Samburu Community Kenya. Int J Pharm Res. 2015;7:44–52.
• 59. Amuka O, Mbugua PK, Okemo PO. Ethnobotanical survey of selected medicinal plants used by the Ogiek communities in Kenya against microbial infections. Ethnobotany Research and Applications. 2014;12:627–41.
• 60. Garedew B, Bizuayehu B. A Review on Ethnobotanical Study of Traditional Medicinal Plants Used for Treatment of Liver Problems in Ethiopia. EJMP. 2018 Dec 1;26(1):1–18.
• 61. Malik ZA, Bhat JA, Ballabha R, Bussmann RW, Bhatt AB. Ethnomedicinal plants traditionally used in health care practices by inhabitants of Western Himalaya. Journal of Ethnopharmacology. 2015 Aug;172:133–44.
• 62. Sharma P, Samant S. Diversity, distribution and indigenous uses of medicinal plants in Parbati Valley of Kullu district in Himachal Pradesh, Northwestern Himalaya. Asian J Adv Basic Sci. 2014;2:77–98.
• 63. Josabad Alonso-Castro A, Jose Maldonado-Miranda J, Zarate-Martinez A, Jacobo-Salcedo M del R, Fernández-Galicia C, Alejandro Figueroa-Zuñiga L, et al. Medicinal plants used in the Huasteca Potosina, México. Journal of Ethnopharmacology. 2012 Aug;143(1):292–8.
• 64. Kiringe JW. A survey of traditional health remedies used by the Maasai of Southern Kaijiado District, Kenya. Ethnobotany Research and Applications. 2006;4:061–74.
• 65. Ajaib M, Khan Z, Khan N, Wahab M. Ethnobotanical studies on useful shrubs of district Kotli, Azad Jammu & Kashmir, Pakistan. Pak J Bot. 2010;42(3):1407–15.
• 66. Phondani P, Maikhuri R, Bisht N. Medicinal plants used in the health care system practiced by traditional Vaidyas in Alaknanda catchment of Uttarakhand, India. Ethnobotanical Leaflets. 2009;2009(12):4.
• 67. Rokaya MB, Münzbergová Z, Timsina B. Ethnobotanical study of medicinal plants from the Humla district of western Nepal. Journal of Ethnopharmacology. 2010 Aug;130(3):485–504.
• 68. Rana TS, Datt B. E THNOBOTANICAL O BSERVATION AMONG J AUNSARIS OF J AUNSAR -B AWAR , D EHRA D UN (U.P.), I NDIA. International Journal of Pharmacognosy. 1997 Jan;35(5):371–4.
• 69. Mai LP, Guéritte F, Dumontet V, Tri MV, Hill B, Thoison O, et al. Cytotoxicity of Rhamnosylanthraquinones and Rhamnosylanthrones from Rhamnus nepalensis. J Nat Prod. 2001 Sep;64(9):1162–8.
• 70. Lu T-M, Ko H-H. A new anthraquinone glycoside from Rhamnus nakaharai and anti-tyrosinase effect of 6-methoxysorigenin. Natural Product Research. 2016 Dec 1;30(23):2655–61.
• 71. Liao J-C, Deng J-S, Chiu C-S, Huang S-S, Hou W-C, Lin W-C, et al. Chemical Compositions, Anti-Inflammatory, Antiproliferative and Radical-Scavenging Activities of Actinidia callosa var. ephippioides. Am J Chin Med. 2012 Jan;40(05):1047–62.
• 72. Ammar RB, Bhouri W, Sghaier MB, Boubaker J, Skandrani I, Neffati A, et al. Antioxidant and free radical-scavenging properties of three flavonoids isolated from the leaves of Rhamnus alaternus L. (Rhamnaceae) : A structure-activity relationship study. Food Chemistry. 2009 Sep;116(1):258–64.
• 73. Bhouri W, Sghaier MB, Kilani S, Bouhlel I, Dijoux-Franca M-G, Ghedira K, et al. Evaluation of antioxidant and antigenotoxic activity of two flavonoids from Rhamnus alaternus L. (Rhamnaceae): Kaempferol 3-O-β-isorhamninoside and rhamnocitrin 3-O-β-isorhamninoside. Food and Chemical Toxicology. 2011 May;49(5):1167–73.
• 74. Chen G, Wu J, Li N, Guo M. Screening for anti-proliferative and anti-inflammatory components from Rhamnus davurica Pall. using bio-affinity ultrafiltration with multiple drug targets. Anal Bioanal Chem. 2018 Jun;410(15):3587–95.
• 75. Bhouri W, Bouhlel I, Boubaker J, Kilani S, Ghedira K, Ghedira LC. Induction of apoptosis in human lymphoblastoid cells by kaempferol 3-O-β-isorhamninoside and rhamnocitrin 3-O-β-isorhamninoside from Rhamnus alaternus L. (Rhamnaceae): Induction of apoptosis in human lymphoblastoid cells. Cell Proliferation. 2011 Jun;44(3):283–90.
• 76. Raja WRT, Antony S, Entomology Research Institute, Loyola College, Chennai - 600034, India, Pachaiyappan SK, Entomology Research Institute, Loyola College, Chennai - 600034, India, Amalraj J, et al. Antibacterial Activity study of Musizin isolated from Rhamnus wightii Wight & Arn. Bioinformation. 2018 Dec 31;14(9):511–20.
• 77. Carranza MG, Sevigny MB, Banerjee D, Fox-Cubley L. Antibacterial activity of native California medicinal plant extracts isolated from Rhamnus californica and Umbellularia californica. Ann Clin Microbiol Antimicrob. 2015 Dec;14(1):29.
• 78. Bribi N. Pharmacological activity of alkaloids: a review. Asian Journal of Botany. 2018;1:1–6.
• 79. Lin C-N, Chung M-I, Lu C-M. Anthraquinones from Rhamnus formosana. Phytochemistry. 1990;29(12):3903–5.
• 80. Ben Ammar R, Miyamoto T, Chekir-Ghedira L, Ghedira K, Lacaille-Dubois M-A. Isolation and identification of new anthraquinones from Rhamnus alaternus L and evaluation of their free radical scavenging activity. Natural Product Research. 2019 Jan 17;33(2):280–6.
• 81. Hernández-Carlos B, Fernández R, Delgado F, Tamariz J, Zepeda LG, Joseph-nathan P. The Chemical Constituents of Rhamnus serrata var. serrata. Natural Product Letters. 1996 Feb;8(1):39–42.
• 82. Moussi K, Nayak B, Perkins LB, Dahmoune F, Madani K, Chibane M. HPLC-DAD profile of phenolic compounds and antioxidant activity of leaves extract of Rhamnus alaternus L. Industrial Crops and Products. 2015 Nov;74:858–66.
• 83. Wang L, Fan S, Wang X, Wang X, Yan X, Shan D, et al. Physicochemical Aspects and Sensory Profiles as Various Potential Factors for Comprehensive Quality Assessment of Nü-Er-Cha Produced from Rhamnus heterophylla Oliv. Molecules. 2019 Sep 4;24(18):3211.
• 84. Chen G, Li X, Saleri F, Guo M. Analysis of Flavonoids in Rhamnus davurica and Its Antiproliferative Activities. Molecules. 2016 Sep 23;21(10):1275.
• 85. Abegaz BM, Kebede T. Geshoidin: A bitter principle of Rhamnus prinoides and other constituents of the leaves. Bulletin of the Chemical Society of Ethiopia. 1995;9(2):107–14.
• 86. Kosalec I, Kremer D, Locatelli M, Epifano F, Genovese S, Carlucci G, et al. Anthraquinone profile, antioxidant and antimicrobial activity of bark extracts of Rhamnus alaternus, R. fallax, R. intermedia and R. pumila. Food Chemistry. 2013 Jan;136(2):335–41.
• 87. Gonçalves RS, Silva EL, Hioka N, Nakamura CV, Bruschi ML, Caetano W. An optimized protocol for anthraquinones isolation from Rhamnus frangula L. Natural Product Research. 2018 Feb 1;32(3):366–9.
• 88. Moreira TF, Sorbo JM, Souza F de O, Fernandes BC, Ocampos FMM, de Oliveira DMS, et al. Emodin, Physcion, and Crude Extract of Rhamnus sphaerosperma var. pubescens Induce Mixed Cell Death, Increase in Oxidative Stress, DNA Damage, and Inhibition of AKT in Cervical and Oral Squamous Carcinoma Cell Lines. Oxidative Medicine and Cellular Longevity. 2018 Jul 3;2018:1–18.
• 89. Genovese S, Tammaro F, Menghini L, Carlucci G, Epifano F, Locatelli M. Comparison of three different extraction methods and HPLC determination of the anthraquinones aloe-emodine, emodine, rheine, chrysophanol and physcione in the bark of Rhamnus alpinus L. (Rhamnaceae): Determination of Anthraquinones in Rhamnus Alpinus. Phytochem Anal. 2010 May;21(3):261–7.
• 90. Locatelli M, Genovese S, Carlucci G, Kremer D, Randic M, Epifano F. Development and application of high-performance liquid chromatography for the study of two new oxyprenylated anthraquinones produced by Rhamnus species. Journal of Chromatography A. 2012 Feb;1225:113–20.
• 91. Locatelli M, Tammaro F, Menghini L, Carlucci G, Epifano F, Genovese S. Anthraquinone profile and chemical fingerprint of Rhamnus saxatilis L. from Italy. Phytochemistry Letters. 2009 Nov;2(4):223–6.
• 92. Abegaz B, Dagne E. Anthracene derivatives of Rhamnus prinoides. Bulletin of the Chemical Society of Ethiopia. 1988;2(1):15–20.
• 93. Abegaz BM, Peter MG. Emodin and emodinanthrone rhamnoside acetates from fruits of Rhamnus prinoides. Phytochemistry. 1995 Aug;39(6):1411–4.
• 94. Hamed MM, Refahy LA, Abdel-Aziz MS. Evaluation of antimicrobial activity of some compounds isolated from Rhamnus cathartica L. Orient J Chem. 2015;31(2):1133–40.
• 95. Sharp H, Latif Z, Bartholomew B, Thomas D, Thomas B, Sarker SD, et al. Emodin and syringaldehyde from Rhamnus pubescens (Rhamnaceae). Biochemical systematics and ecology. 2001;29(1):113–5.
• 96. Zeouk I, Ouedrhiri W, Jiménez IA, Lorenzo-Morales J, Bazzocchi IL, Bekhti K. Intra-combined antioxidant activity and chemical characterization of three fractions from Rhamnus alaternus extract: Mixture design. Industrial Crops and Products. 2020 Feb;144:112054.
• 97. Dwivedi SPD, Pandey VB, Shah AH, Rao YB. Chemical constituents ofRhamnus procumbens and pharmacological actions of emodin. Phytother Res. 1988 Mar;2(1):51–3.
• 98. Ben Ghezala H, Chaouali N, Gana I, Snouda S, Nouioui A, Belwaer I, et al. Toxic Effects of Rhamnus alaternus : A Rare Case Report. Case Reports in Emergency Medicine. 2015;2015:1–5.
• 99. Epifano F, Genovese S, Kremer D, Randic M, Carlucci G, Locatelli M. Re-investigation of the Anthraquinone Pool of Rhamnus spp.: Madagascin from the Fruits of Rhamnus cathartica and R. intermedia. Natural Product Communications. 2012 Aug;7(8):1934578X1200700.
• 100. Cuoco G, Mathe C, Vieillescazes C. New emodin arabinoside acetates from fruits of Rhamnus alaternus. Current Topics in Phytochemistry, Volume 10. 2011;61–6.
• 101. Coskun M, Toshiko S, Hori K, Saiki Y, Tanker M. Anthraquinone glycosides from Rhamnus libanoticus☆. Phytochemistry. 1990;29(6):2018–20.
• 102. Coskun M, Tanker N, Sakushima A, Kitagawa S, Nishibe S. An anthraquinone glycoside from Rhamnus pallasii. Phytochemistry. 1984 Jan;23(7):1485–7.
• 103. Bezabih M, Abegaz BM. Glucofrangulin A diacetate from the fruits of Rhamnus prinoids. Bulletin of the Chemical Society of Ethiopia. 1998;12(1):45–8.
• 104. Lin C-N, Chung M-I, Gan K-H, Lu C-M. Flavonol and anthraquinone glycosides from Rhamnus formosana. Phytochemistry. 1991 Jan;30(9):3103–6.
• 105. Özi̇pek M, Çaliş İ, Ertan M, Rüedi P. Rhamnetin 3-p-coumaroylrhamninoside from Rhamnus petiolaris. Phytochemistry. 1994 Jan;37(1):249–53.
• 106. Cuoco G, Mathe C, Vieillescazes C. Liquid chromatographic analysis of flavonol compounds in green fruits of three Rhamnus species used in Stil de grain. Microchemical Journal. 2014 Jul;115:130–7.
• 107. Payá M, Máñez S, Villar A. Flavonoid Constituents of Rhamnus lycioides L. Zeitschrift für Naturforschung C. 1986 Dec 1;41(11–12):976–8. 108. Sakushima A, Coşkun M, Hisada S, Nishibe S. Flavonoids from Rhamnus pallasii. Phytochemistry. 1983 Jan;22(7):1677–8.
• 109. Marzouk MS, El-Toumy SAA, Merfort I, Nawwar MAM. Polyphenolic metabolites of Rhamnus disperma. Phytochemistry. 1999 Nov;52(5):943–6.
• 110. Máñez S, Payá M, Terencìo C, Villar A. Flavonoids of Rhamnus lycioides ; Part 2. Planta Med. 1988 Apr;54(02):187–8.
• 111. Hsiao G, Ko F-N, Lin C-N, Teng C-M. Antioxidant properties of isotorachrysone isolated from Rhamnus nakaharai. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1996 Nov;1298(1):119–30.
• 112. Sut S, Dall’Acqua S, Ibrahime Sinan K, Bene K, Kumar G, Fawzi Mahomoodally M, et al. Cola caricifolia (G.Don) K. Schum and Crotalaria retusa L. from Ivory Coast as sources of bioactive constituents. Industrial Crops and Products. 2020 May;147:112246.
• 113. Campbell M, Zhao W, Fathi R, Mihreteab M, Gilbert ES. Rhamnus prinoides (gesho): A source of diverse anti-biofilm activity. Journal of Ethnopharmacology. 2019 Sep;241:111955.
• 114. Chouitah O, Meddah B, Aoues A. Analysis of the Chemical Composition and Antimicrobial Activity of the Essential Oil from Rhamnus alaternus. Journal of Biologically Active Products from Nature. 2012 Jan;2(5):302–6.
• 115. Thakur C, Prasad B. Antiinflammatory Activity of Stem Bark of Rhamnus purpureus. Int J Adv Microbiol Health Res. 2019;3(1):21–8.
• 116. Chen G-L, Munyao Mutie F, Xu Y-B, Saleri FD, Hu G-W, Guo M-Q. Antioxidant, Anti-inflammatory Activities and Polyphenol Profile of Rhamnus prinoides. Pharmaceuticals. 2020 Mar 26;13(4):55.
• 117. Molla Y, Nedi T, Tadesse G, Alemayehu H, Shibeshi W. Evaluation of the in vitro antibacterial activity of the solvent fractions of the leaves of Rhamnus prinoides L’Herit (Rhamnaceae) against pathogenic bacteria. BMC Complement Altern Med. 2016 Dec;16(1):287.
• 118. Ben Ammar R, Kilani S, Bouhlel I, Skandrani I, Naffeti A, Boubaker J, et al. Antibacterial and cytotoxic activities of extracts from (Tunisian)Rhamnus alaternus (Rhamnaceae). Ann Microbiol. 2007 Sep;57(3):453–60.
• 119. Koch A, Tamez P, Pezzuto J, Soejarto D. Evaluation of plants used for antimalarial treatment by the Maasai of Kenya. Journal of Ethnopharmacology. 2005 Oct;101(1–3):95–9.
• 120. Bosire K. An investigation of a traditional herbal therapy used to treat malaria in Kisii [Internet] [Master of Science Thesis]. [Nairobi, Kenya]: University of Nairobi; 2003.
• 121. Gebru M. Phytochemical and antiplasmodial investigation of rhamnus prinoides and kniphofia foliosa [Internet] [Master of Science Thesis]. [Nairobi, Kenya]: University of Nairobi; 2010.
• 122. Muregi FW, Ishih A, Suzuki T, Kino H, Amano T, Mkoji GM, et al. In Vivo antimalarial activity of aqueous extracts from Kenyan medicinal plants and their Chloroquine (CQ) potentiation effects against a blood-induced CQ-resistant rodent parasite in mice. Phytother Res. 2007 Apr;21(4):337–43.
• 123. Rocchetti G, Miras-Moreno MB, Zengin G, Senkardes I, Sadeer NB, Mahomoodally MF, et al. UHPLC-QTOF-MS phytochemical profiling and in vitro biological properties of Rhamnus petiolaris (Rhamnaceae). Industrial Crops and Products. 2019 Dec;142:111856.
• 124. Ammar RB, Sghaier MB, Boubaker J, Bhouri W, Naffeti A, Skandrani I, et al. Antioxidant activity and inhibition of aflatoxin B1-, nifuroxazide-, and sodium azide-induced mutagenicity by extracts from Rhamnus alaternus L. Chemico-Biological Interactions. 2008 Jul;174(1):1–10.
• 125. Ben Ammar R, Kilani S, Bouhlel I, Ezzi L, Skandrani I, Boubaker J, et al. Antiproliferative, Antioxidant, and Antimutagenic Activities of Flavonoid-Enriched Extracts from (Tunisian) Rhamnus alaternus L.: Combination with the Phytochemical Composition. Drug and Chemical Toxicology. 2008 Jan;31(1):61–80.
• 126. Bhouri W, Boubaker J, Kilani S, Ghedira K, Chekir-Ghedira L. Flavonoids from Rhamnus alaternus L. (Rhamnaceae): Kaempferol 3-O-β-isorhamninoside and rhamnocitrin 3-O-β-isorhamninoside protect against DNA damage in human lymphoblastoid cell and enhance antioxidant activity. South African Journal of Botany. 2012 May;80:57–62.
• 127. Chaouche TM, Haddouchi F, Boudjemai O, Ghellai I. Antioxidant and hemolytic activity of Ziziphus jujuba Mill and Rhamnus alaternus L (Rhamnaceae) extracts from Algeria. Activité antioxydante et hémolytique des extraits de Ziziphus jujuba Mill et Rhamnus alaternus (Rhamnaceae) d’Algérie. Bulletin de la Société Royale des Sciences de Liège [Internet]. 2020; . .
• 128. Mazhar F, Jahangir M, Abbasi MA, Ilyas SA, Khalid F, Khanum R, et al. Rhamnus triquetra: A Valuable Source of Natural Antioxidants to Shield from Oxidative Stress. Asian Journal of Chemistry. 2013;25(15):8569–73.
• 129. Boussahel S, Dahamna S, Ruberto G, Siracusa L, Harzallah D. Phytochemical Study and Antioxidant Activities of Leaves Extracts from Rhamnus alaternus L. Pharmacognosy Communications. 2013;3(1):46–53.
• 130. Speciale A, Ferlazzo G, Harzallah D, Boussahel S, Dahamna S, Amar Y, et al. Flavonoid profile, antioxidant and cytotoxic activity of different extracts from Algerian Rhamnus alaternus L. bark. Phcog Mag. 2015;11(42):102.
• 131. Tessema Z, Molla Y. Evaluation of the wound healing activity of the crude extract of root bark of Brucea antidysentrica, the leaves of Dodonaea angustifolia and Rhamnus prinoides in mice. Heliyon. 2021 Jan;7(1):e05901.
• 132. Ahmadi R, Hatami F, Molseghi M. The Effects of Co-administration of Frangula alnus and Rhamnus frangula Extract on Breast Cancer Cells in Cell Culture. In: BIOES-16 [Internet]. 2016. p. 78–80.
• 133. Tacherfiout M, Petrov PD, Mattonai M, Ribechini E, Ribot J, Bonet ML, et al. Antihyperlipidemic effect of a Rhamnus alaternus leaf extract in Triton-induced hyperlipidemic rats and human HepG2 cells. Biomedicine & Pharmacotherapy. 2018 May;101:501–9.