Total alkaloids and anti-inflammatory activity of Glaucium grandiflorum wildly grown in Syria: A study on formalin induced paw edema in rats

Year 2025, Volume: 29 Issue: 5, 2035 - 2044, 01.09.2025

Nivin Alabdullah Alsheikh Thanaa Harami Amina Ibrahim Ahmad Manee

https://doi.org/10.12991/jrespharm.1766199

Abstract

Glaucium grandiflorum, a perennial herb belonging to the Papaveraceae family, exhibits significant biological activities. This study aims to quantitatively determine the alkaloid content in various plant parts and evaluate the anti- inflammatory activity of its hydroethanolic extract from aerial parts during the flowering stage in rats.The total alkaloid content was determined through alkaloid precipitation at pH=10 using concentrated ammonium hydroxide, followed by weighing. The anti-inflammatory activity was assessed by injecting 0.1 mL of 2.5% formalin into the right hind paw to induce acute inflammation. Quantitative analysis revealed the presence of alkaloids in all tested plant parts. The highest alkaloid content was found in fruits (5.07%), followed by aerial parts in the fruiting stage (3.21%) and aerial parts in the flowering stage (1.41%), with the lowest content in the roots (0.66%). The extract exhibited significant inhibition of paw edema (P < 0.05). Both oral and intraperitoneal administration of 200 and 400 mg/kg of the extract reduced edema formation, indicating that G. grandiflorum possesses anti-inflammatory activity. The maximum anti-inflammatory activity was observed at a dose of 400 mg/kg (95.42%), surpassing indomethacin at 10 mg/kg (89.77%) on oral administration. Our study suggests that the hydroethanolic extract of flowering aerial parts is likely safe in rats up to a dose of 2000 mg/kg and possesses anti-inflammatory activity when administered orally or intraperitoneally. In conclusion, the hydroethanolic extract of G. grandiflorum may be a valuable resource for managing disorders associated with inflammation as an anti-inflammatory agent. This activity is likely attributed to the presence of alkaloids, phenols, flavonoids, and saponins.

Keywords

Glaucium grandiflorum , Papaveraceae , total alkaloids , anti-inflammatory activity , formalin , paw edma

References

• [1] Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X , Zhao L. Inflammatory responses and inflammation- associated diseases in organs. Oncotarget. 2018; 9(6): 7204-7218 .https://doi.org/10.18632%2Foncotarget.23208
• [2] Punchard NA, Whelan CJ, Adcock I. The Journal of Inflammation. J Inflamm (Lond). 2004;1(1):1. https://doi.org/10.1186/1476-9255-1-1
• [3] Dzoyem JP, McGaw L J, Kuete V, Bakowsky U. Anti-inflammatory and Anti-nociceptive Activities of African Medicinal Spices and Vegetables (CHAPTER 9). Medicinal Spices and Vegetables from Africa. 2017;239-270, https://doi.org/10.1016/B978-0-12-809286-6.00009-1
• [4] Sherwood ER, Toliver-Kinsky T. Mechanisms of the inflammatory response. Best Pract Res Clin Anaesthesiol. 2004;18(3):385-405. https://doi.org/10.1016/j.bpa.2003.12.002
• [5] Patil KR, Mahajan UB, Unger BS, Goyal SN, Belemkar S, Surana SJ, Ojha S, Patil CR. Animal models of inflammation for screening of anti-inflammatory drugs: implications for the discovery and development of phytopharmaceuticals. Int J Mol Sci. 2019; 20(18):4367. https://doi.org/10.3390%2Fijms20184367
• [6] Nunes CdR , Arantes MB, Pereira SM, Cruz LL, Passos MS, MoraesLP, Vieira IJC, Oliveira DB. Plants as sources of anti-inflammatory agents. Molecules. 2020; 25: 3726. https://doi.org/10.3390%2Fmolecules25163726
• [7] Oguntibeju OO. Medicinal plants with anti-inflammatory activities from selected countries and regions of Africa. J Inflamm Res. 2018; 11: 307-317. https://doi.org/10.2147/JIR.S167789
• [8] Muzamil A, Tahir H, Ali S, Liaqat I, Ali A, Summer M. Inflammatory process and role of cytokines in inflammation: An overview. Punjab Univ J Zool. 2021; 36(2): 237-252. https://dx.doi.org/10.17582/journal.pujz/2021.36.2.237.252
• [9] Tavakkoli Z, Assadi M. A taxonomic revision of the genus Glaucium (Papaveraceae) in Iran, Survey to the genus Glaucium in Iran. Acta Bot Croat. 2019; 78(1). https://doi.org/10.2478/botcro-2019-0003
• [10] Kiliç FM, Yild K, Bat MB, Kiliç M, Büyük İ. Morphological, palynological and phylogenetic relationships of Glaucium Mill. in Turkey. Bangladesh J Plant Taxon. 2019; 26(2): 259‒268. http://dx.doi.org/10.3329/bjpt.v26i2.44585
• [11] Semnani KM, Saeedi M, Mahdavi MR. Antibacterial Studies on extracts of three species of Glaucium from Iran. Pharm Biol. 2005; 43(3): 234–236. https://doi.org/10.1080/13880200590928816
• [12] Semnani K M, Saeedi M, Hamidian M. Anti-inflammatory and analgesic activity of the topical preparation of Glaucium grandiflorum. Fitoterapia. 2004; 75: 123–129. https://doi.org/10.1016/j.fitote.2003.12.007
• [13] Dehkordi NE, Shafaroodi H, Asgarpanah J. Anticonvulsant activity of Glaucium vitellinum Boiss & Buhse. Bio Sci Bio Technol Res Asia. 2014; 11(2): 727-731. https://doi.org/10.13005/bbra/1328.
• [14] Akaberi T, Shourgashtib K, Emami SA, Akaberi M. Phytochemistry and pharmacology of alkaloids from Glaucium spp. Phytochemistry. 2021; 191:112923. https://doi.org/10.1016/j.phytochem.2021.112923
• [15] Ozsoy N, Ozden TY, Sagirli PA, Şahin H, Sarı A. Antioxidant, Anti-acetylcholinesterase, anti-inflammatory and DNA protection activities of Glaucium grandiflorum var. grandiflorum. Iran J Pharm Res. 2018; 17(2): 677-684. https://doi.org/10.22037/ijpr.2018.2195
• [16] Sariyar G, Unsal C. Alkaloids From Glaucium Grandiflorum Var.Grandiflorum. J Fac Pharm Istanbul Univ. 1998; 32:55-58.
• [17] Gözler T. Alkaloids of Turkish Glaucium Species.I. Alkaloids of Glaucium grandiflorum var. torquatum. J Med Plant Res. 1982; 46: 179-180. https://doi.org/10.1055/s-2007-971209
• [18] El-Afifi F, Al-Eisawi D, Al-Khalil S, Schiff PL. Alkaloids Of Glaucium Grandiflorum. J Nat Prod. 1986; 49(6). https://doi.org/10.1021/np50048a055
• [19] Hadjiakhoondi F, Ostad SN, Khanavi M, Hadjiakhoondi A, Farahanikia B, Salarytabar A. Cytotoxicity of two species of Glaucium from Iran. J Med Plants. 2013; 12(45):85-92.
• [20] Semnani KM, Saeedi M, Hamidian M, Vafamehr H, Dehpoura R. Anti-inflammatory, analgesic activity and acute toxicity of Glaucium grandiflorum extract. J Ethnopharmacol. 2002; 80: 181-186. https://doi.org/10.1016/s0378- 8741(02)00027-2
• [21] Liu W, Yin D, Li N, Hou X, Wang D, Li D, Liu J. Influence of environmental factors on the active substance production and antioxidant activity in Potentilla fruticosa L. and its quality assessment. Sci Rep. 2016;6:28591. https://doi.org/10.1038/srep28591
• [22] Damas J, Liégeois JF. The inflammatory reaction induced by formalin in the rat paw. Naunyn-Schmiedeberg’s Arch Pharmacol. 1999; 359: 220–227. https://doi.org/10.1007/pl00005345
• [23] Coderre T, Abbott FV, Sawynok J. Formalin Test. In: Encyclopedia of pain. Springer-Verlag, Berlin, Heidelberg, 2007.
• [24] Liua JY, Leeb KF, Szea CW, Tong Y, Tangc SCW, Ngd TB, Zhanga YB. Intestinal absorption and bioavailability of traditional Chinese medicines: a review of recent experimental progress and implication for quality control. J Pharm Pharmacol. 2013; 65: 621–633. https://doi.org/10.1111/j.2042-7158.2012.01608.x
• [25] Alsheikh NA, Harami T, Ibrahim A, Manee A. Morphological, anatomical study and phytochemical screening of Glaucium grandiflorum wildly grown in Syria. Res J Aleppo University- Med Sci. 2023; 173: accepted on 5/2/2023.
• [26] Alsheikh NA, Harami T, Ibrahim A, Manee A. Determination of total phenolic and total flavonoid content of Glaucium grandiflorum and evaluation of antioxidant activity in vitro. Res J Aleppo University- Med Sci. 2023; 173: (- accepted on 2/2/2023.
• [27] Pérez DLA, López NL, Grijalva EpG, Heredia JB. Phenolic compounds: Natural alternative in inflammation treatment. A Review. Cogent Food & Agric. 2016; 2(1): 1131412. https://doi.org/10.1080/23311932.2015.1131412
• [28] Serafini M, Peluso I, Raguzzini A. Flavonoids as anti-inflammatory agent. Proceedings of the Nutrition Society. 2010; 69: 273–278. https://doi.org/10.1017/s002966511000162x
• [29] Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chem. 2019;299:125124.https://doi.org/10.1016/j.foodchem.2019.125124
• [30] Pinto L, Borrelli F, Ardelli EB, Cristoni A, Capasso F. Anti-inflammatory, analgesic and antipyretic effects of glaucine in rats and mice. Pharm Pharmacol Commun. 1998; 4:502-505. https://doi.org/10.1111/j.2042- 7158.1998.tb00663.x
• [31] Li S, Liu X, Chen X, Bi L. Research progress on anti-inflammatory effects and mechanisms of alkaloids from Chinese medical herbs. Evid-Based Complement Altern Med. 2020; 2020:1303524.https://doi.org/10.1155/2020/1303524
• [32] Dong Z, Wang YH, Tang ZS, Li CH, Jiang T, Yang ZH, Zeng JG. Exploring the anti-inflammatory effects of protopine total alkaloids of Macleaya Cordata (Willd.) R.Br. Front Vet Sci. 2022;9:935201. https://doi.org/10.3389/fvets.2022.935201
• [33] Hassan HS, Sule MI, Musa AM, Musa KY, Abubakar MS, Hassan AS. Anti-Inflammatory activity of crude saponin extracts from five Nigerian medicinal plants. Afr J Tradit Complement Altern Med. 2012; 9(2): 250-255. https://doi.org/10.4314%2Fajtcam.v9i2.10
• [34] Santiago LAM, Neto RNM, Ataíde ACS, Fonseca DCSC, Soares EFA, de Sa Sousa JC, Mondego-Oliveira R, Ribeiro RM, Cartágenes M, Neto L, Carvalho R, de Sousa Cartágenes MdS, Lima-Neto LG, Carvalho RC, de Sousa EM. Flavonoids, alkaloids and saponins: Are these plant-derived compounds an alternative to the treatment of rheumatoid arthritis? A literature review. Clin Phytosci. 2021; 7:58. https://doi.org/10.1186/s40816-021-00291-3
• [35] Arafa AM, Mohamed M S, Eldahmy SI. The aerial parts of yellow horn poppy (Glaucium flavum Cr.) growing in Egypt: Isoquinoline alkaloids and biological activities. J Pharm Sci Res 2016; 8(5):323-332.
• [36] Hamamcioglu B, Kocanci FG, Aslim B. Phytochemical screening and evaluation of neuroprotective, anti-mutagenic and anti-genotoxic effects of Turkish endemic Glaucium acutidentatum. S Afr J Bot. 2018; 117:232-239. https://doi.org/10.1016/j.sajb.2018.05.027
• [37] Ajiboye B, Ibukun E, Edobor G, Ojo AO, Onikanni S. Qualitative and quantitative analysis of phytochemicals in Senecio Biafrae leaf. Int J Inv Pharm Sci. 2013; 1(5):428-432.
• [38] Ezeonu CS, Ejikeme CM. Qualitative and quantitative determination of phytochemical contents of indigenous Nigerian softwoods. New J Sci. 2016; 5601327. http://dx.doi.org/10.1155/2016/5601327.
• [39] Ghafoor K, Choi YH, Jeon J Y, Jo IH. Optimization of ultrasound-assisted extraction of phenolic compounds, antioxidants, and anthocyanins from grape (Vitis vinifera) seeds. J Agric Food Chem. 2009; 57:4988–4994. https://doi.org/10.1021/jf9001439.
• [40] Eltom SEM, Abdellatif AA H, Maswadeh H, Al-Omar MS, Abdel-Hafez AA, Mohammed HA, Agabein EME, Alqasoomi I, Alrashidi SA, Sajid MSM, Mobark MA. The anti-inflammatory effect of a γ-Lactone isolated from ostrich oil of Struthio camelus (Ratite) and its formulated nano-emulsion in formalin-induced paw edema. Molecules. 2021; 26:3701. https://doi.org/10.3390/molecules26123701
• [41] Dutta S, Hossain S, Islam E, Haque U, Parvin S. Assessment of Antioxidant and anti-inflammatory activities of stem bark of Bauhinia acuminata L. Biomed J Sci Tech Res. 2020; 24(5):18519-18527. http://dx.doi.org/10.26717/BJSTR.2020.24.004101.
• [42] Chi S C, Jun HW. Anti-inflammatory activity of ketoprofen gel on carrageenan-induced paw edema in rats. J Pharm Sci. 1990; 79(11): 974-977. https://doi.org/10.1002/jps.2600791106