Abstract
Background: Antinociceptive effect of fenugreek seeds (Trigonella foenum-graecum L.) has been reported in different animal models in response to various chemical or thermal stimuli. In a recent study, alkaline chloroform fraction (AKC) of this plant has exhibited the greatest analgesic effect.
Objective: In the present study, to isolate the active component(s) from the plant, the subfractions resulting from AKC column chromatography were evaluated in an animal model for anti-nociception effect.
Methods: From the 17 separated fractions, 5 major fractions (F4, F6, F14, F15 and F16) were used for the formalin test at three different doses (2.5, 5 10 mg/kg). Antioxidant activity of the most active subfractions was studied too.
Results: Subfractions F16 and F14 (5, 10 mg/kg) showed the greatest analgesic effect and reduced the pain score which was similar to morphine and even stronger than morphine in some doses. The greatest antioxidant activity was observed by F14 (radical inhibition percentage of 17.34 ± 0.14 in DPPH assay, reduction power percentage of 74.05 ± 4.23 in RPA versus green tea (91.68 ± 3.04 and 97.59 ± 6.24 in DPPH assay and RPA test respectively). The absorbance of F14 was 0.25 ± 0.11 in the FTC method in comparison to ascorbic acid 10 μg/ml and 100 μg/ml (0.72 ± 0.33 and 0.05 ± 0.41 respectively).
Conclusion: Separated subfractions exhibited more antinociceptive effect than AKC fraction, so further separation can lead to the acquisition of antinociceptive compound (s), while AKC fraction was found to be more potent antioxidant than separated sub-fractions in all three experiments. So, most likely, the anti-nociception effect of subfractions might be achieved via other mechanisms than antioxidant activity. Based on phytochemical screening, AKC and all sub-fractions especially F14, F15 and F16 were positive for the presence of alkaloids and only F14 was positive for flavonoids.
[1]
Moore, R.A.; Wiffen, P.J.; Derry, S.; Maguire, T.; Roy, Y.M.; Tyrrell, L. Non-prescription (OTC) oral analgesics for acute pain: An overview of Cochrane reviews. Cochrane Database Syst. Rev., 2013, (11), CD010794.
[2]
Cordell, W.H.; Keene, K.K.; Giles, B.K.; Jones, J.B.; Jones, J.H.; Brizendine, E.J. The high prevalence of pain in emergency medical care. Am. J. Emerg. Med., 2002, 20(3), 165-169.
[http://dx.doi.org/10.1053/ajem.2002.32643] [PMID: 11992334]
[http://dx.doi.org/10.1053/ajem.2002.32643] [PMID: 11992334]
[3]
Kris-Etherton, P.M.; Hecker, K.D.; Bonanome, A.; Coval, S.M.; Binkoski, A.E.; Hilpert, K.F.; Griel, A.E.; Etherton, T.D. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am. J. Med., 2002, 113(9)(9B), 71-88.
[http://dx.doi.org/10.1016/S0002-9343(01)00995-0] [PMID: 12566142]
[http://dx.doi.org/10.1016/S0002-9343(01)00995-0] [PMID: 12566142]
[4]
Dehghan Noudeh, G.; Sharififar, F.; Noodeh, A.D.; Moshafi, M.H.; Afzadi, M.A.; Behravan, E. Antitumor and antibacterial activity of four fractions from Heracleum persicum Desf. and Cinnamomum zeylanicum Blume. J. Med. Plants Res., 2010, 4(21), 2176-2180.
[5]
Sharififar, F.; Moshafi, M.H.; Shafazand, E.; Koohpayeh, A. Acetyl cholinesterase inhibitory, antioxidant and cytotoxic activity of three dietary medicinal plants. Food Chem., 2012, 130(1), 20-23.
[http://dx.doi.org/10.1016/j.foodchem.2011.06.034]
[http://dx.doi.org/10.1016/j.foodchem.2011.06.034]
[6]
Dehghan Noudeh, G.; Sharififar, F.; Khatib, M.; Behravan, E.; Afzadi, M.A. Study of aqueous extract of three medicinal plants on cell membrane–permeabilizing and their surface properties. Afr. J. Biotechnol., 2010, 9(1)
[7]
Jamshidzadeh, A.; Shokri, Y.; Ahmadi, N.; Mohamadi, N.; Sharififar, F. Quercus infectoria and Terminalia chebula decrease melanin content and tyrosinase activity in B16/F10 cell lines. J. Pharm. Pharmacogn. Res., 2017, 5(5), 270-277.
[8]
Mehta, P.; Shah, R.; Lohidasan, S.; Mahadik, K.R. Pharmacokinetic profile of phytoconstituent(s) isolated from medicinal plants—A comprehensive review. J. Tradit. Complement. Med., 2015, 5(4), 207-227.
[http://dx.doi.org/10.1016/j.jtcme.2014.11.041] [PMID: 26587392]
[http://dx.doi.org/10.1016/j.jtcme.2014.11.041] [PMID: 26587392]
[9]
Biswal, S.; Das, M.C.; Nayak, P. Antinociceptive activity of seeds of Trigonella foenum gracecum in rats. Indian J. Physiol. Pharmacol., 2003, 47(4), 479-480.
[PMID: 15266964]
[PMID: 15266964]
[10]
Mandegary, A.; Pournamdari, M.; Sharififar, F.; Pournourmohammadi, S.; Fardiar, R.; Shooli, S. Alkaloid and flavonoid rich fractions of fenugreek seeds (Trigonella foenum-graecum L.) with antinociceptive and anti-inflammatory effects. Food Chem. Toxicol., 2012, 50(7), 2503-2507.
[http://dx.doi.org/10.1016/j.fct.2012.04.020] [PMID: 22542922]
[http://dx.doi.org/10.1016/j.fct.2012.04.020] [PMID: 22542922]
[11]
Vyas, S.; Agrawal, R.P.; Solanki, P.; Trivedi, P. Analgesic and anti-inflammatory activities of Trigonella foenum-graecum (seed) extract. Acta Pol. Pharm., 2008, 65(4), 473-476.
[PMID: 19051589]
[PMID: 19051589]
[14]
Mohamadi, N.; Sharififar, F.; Ansari, M.; Pournamdari, M.; Rezaei, M.; Hassanabadi, N. Pharmacokinetic profile of diosgenin and trigonelline following intravenous and oral administration of fenugreek seed extract and pure compound in rabbit. J. Asian Nat. Prod. Res., 2021, 23(5), 466-477.
[http://dx.doi.org/10.1080/10286020.2020.1769609] [PMID: 32447972]
[http://dx.doi.org/10.1080/10286020.2020.1769609] [PMID: 32447972]
[15]
Mohamadi, N.; Sharififar, F.; Pournamdari, M.; Ansari, M. Determination of trigonelline in human plasma by magnetic solid-phase extraction: A pharmacokinetic study. Nanomedicine, 2021, 16(4), 323-333.
[http://dx.doi.org/10.2217/nnm-2020-0365] [PMID: 33501838]
[http://dx.doi.org/10.2217/nnm-2020-0365] [PMID: 33501838]
[16]
Khazaeli, P.; Goldoozian, R.; Sharififar, F. An evaluation of extracts of five traditional medicinal plants from Iran on the inhibition of mushroom tyrosinase activity and scavenging of free radicals. Int. J. Cosmet. Sci., 2009, 31(5), 375-381.
[http://dx.doi.org/10.1111/j.1468-2494.2009.00503.x] [PMID: 19467035]
[http://dx.doi.org/10.1111/j.1468-2494.2009.00503.x] [PMID: 19467035]
[17]
Mohamadi, N.; Rajaei, P.; Moradalizadeh, M.; Amiri, M.S. Essential oil composition and antioxidant activity of Levisticum officinale Koch. at various phenological stages. J. Med. Plants Res., 2017, 16(61), 45-55.
[18]
Güder, A.; Korkmaz, H. Evaluation of in-vitro antioxidant properties of hydroalcoholic solution extracts urtica dioica l., malva neglecta wallr. and their mixture. Iran. J. Pharm. Res., 2012, 11(3), 913-923.
[PMID: 24250519]
[PMID: 24250519]
[19]
Yassa, N.; Sharififar, F.; Shafiee, A. Otostegia persica. as a source of natural antioxidants. Pharm. Biol., 2005, 43(1), 33-38.
[http://dx.doi.org/10.1080/13880200590903336]
[http://dx.doi.org/10.1080/13880200590903336]
[20]
Shailajan, S.; Sayed, N.; Menon, S.; Singh, A.; Mhatre, M. A validated RP-HPLC method for quantitation of trigonelline from herbal formulations containing Trigonella foenum-graecum (L.) seeds. Pharm. Methods, 2011, 2(3), 157-160.
[http://dx.doi.org/10.4103/2229-4708.90354] [PMID: 23781448]
[http://dx.doi.org/10.4103/2229-4708.90354] [PMID: 23781448]
[21]
Hashjin, M.R.; Zeinalabedini, A.A.M.; Ghaffari, M.R. Comparison of trigonelline content in some species of medicinal plant of fenugreek (Trigonella L.). Iran. J. Med. Arom. Plant. Res., 2019, 35(5), 721-730.
[22]
Arya, P.; Kumar, P. Comparison of ultrasound and microwave assisted extraction of diosgenin from Trigonella foenum graceum seed. Ultrason. Sonochem., 2021, 74, 105572.
[http://dx.doi.org/10.1016/j.ultsonch.2021.105572] [PMID: 33933831]
[http://dx.doi.org/10.1016/j.ultsonch.2021.105572] [PMID: 33933831]
[23]
Tjølsen, A.; Berge, O.G.; Hunskaar, S.; Rosland, J.H.; Hole, K. The formalin test: An evaluation of the method. Pain, 1992, 51(1), 5-17.
[http://dx.doi.org/10.1016/0304-3959(92)90003-T] [PMID: 1454405]
[http://dx.doi.org/10.1016/0304-3959(92)90003-T] [PMID: 1454405]
[24]
Shibata, M.; Ohkubo, T.; Takahashi, H.; Inoki, R. Modified formalin test: Characteristic biphasic pain response. Pain, 1989, 38(3), 347-352.
[http://dx.doi.org/10.1016/0304-3959(89)90222-4] [PMID: 2478947]
[http://dx.doi.org/10.1016/0304-3959(89)90222-4] [PMID: 2478947]
[25]
Hunskaar, S.; Hole, K. The formalin test in mice: Dissociation between inflammatory and non-inflammatory pain. Pain, 1987, 30(1), 103-114.
[http://dx.doi.org/10.1016/0304-3959(87)90088-1] [PMID: 3614974]
[http://dx.doi.org/10.1016/0304-3959(87)90088-1] [PMID: 3614974]
[26]
Hayashida, K.; Takeuchi, T.; Shimizu, H.; Ando, K.; Harada, E. Lactoferrin enhances opioid-mediated analgesia via nitric oxide in the rat spinal cord. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2003, 285(2), R306-R312.
[http://dx.doi.org/10.1152/ajpregu.00760.2002]
[http://dx.doi.org/10.1152/ajpregu.00760.2002]
[27]
Ahmadiani, A.; Javan, M.; Semnanian, S.; Barat, E.; Kamalinejad, M. Anti-inflammatory and antipyretic effects of Trigonella foenum-graecum leaves extract in the rat. J. Ethnopharmacol., 2001, 75(2-3), 283-286.
[http://dx.doi.org/10.1016/S0378-8741(01)00187-8] [PMID: 11297864]
[http://dx.doi.org/10.1016/S0378-8741(01)00187-8] [PMID: 11297864]
[28]
Abbas, N.; Al Rubaish, A.R.; Ali, S. Study of anti-inflammatory analgesic and antipyretic antimicrobial effect of aqueous extract of Trigonella foenum-graecum sprouts and effect of glacial acetic acid on blood cells of mice. Int J Res Pharmacy Pharmaceut Sci., 2016, 1, 67-73.
[29]
Parvizpur, A.; Ahmadiani, A.; Kamalinejad, M. Spinal serotonergic system is partially involved in antinociception induced by Trigonella foenum-graecum (TFG) leaf extract. J. Ethnopharmacol., 2004, 95(1), 13-17.
[http://dx.doi.org/10.1016/j.jep.2004.05.020] [PMID: 15374601]
[http://dx.doi.org/10.1016/j.jep.2004.05.020] [PMID: 15374601]
[30]
Kiplimo, J.J.; Islam, MS; Koorbanally, NA A novel flavonoid and furoquinoline alkaloids from Vepris glomerata and their antioxidant activity. Natural product commun., 2011, 6(12), 1934578X1100601215.
[http://dx.doi.org/10.1177/1934578X1100601215]
[http://dx.doi.org/10.1177/1934578X1100601215]
[31]
Gan, J; Feng, Y; He, Z; Li, X; Zhang, H Correlations between antioxidant activity and alkaloids and phenols of maca (Lepidium meyenii). J. Food. Qual., 2017, 2017
[32]
Yashin, A.; Yashin, Y.; Xia, X.; Nemzer, B. Antioxidant activity of spices and their impact on human health: A review. Antioxidants, 2017, 6(3), 70.
[http://dx.doi.org/10.3390/antiox6030070] [PMID: 28914764]
[http://dx.doi.org/10.3390/antiox6030070] [PMID: 28914764]
[33]
Al-Sultan, S.I.; El-Bahr, S.M. Effect of aqueous extract of fenugreek (Trigonella foenum-graecum L.) on selected biochemical and oxidative stress biomarkers in rats intoxicated with carbon tetrachloride. Int. J. Pharmacol., 2014, 11(1), 43-49.
[http://dx.doi.org/10.3923/ijp.2015.43.49]
[http://dx.doi.org/10.3923/ijp.2015.43.49]
[34]
Fatima, T.; Maqbool, K.; Hussain, S.Z. Potential health benefits of fenugreek. J. Med. Plant. Stud., 2018, 6(2), 166-169.
[35]
Szabó, K.; Gesztelyi, R.; Lampé, N.; Kiss, R.; Remenyik, J.; Pesti-Asbóth, G.; Priksz, D.; Szilvássy, Z.; Juhász, B. Fenugreek (Trigonella foenum-graecum) seed flour and diosgenin preserve endothelium-dependent arterial relaxation in a rat model of early-stage metabolic syndrome. Int. J. Mol. Sci., 2018, 19(3), 798.
[http://dx.doi.org/10.3390/ijms19030798] [PMID: 29534453]
[http://dx.doi.org/10.3390/ijms19030798] [PMID: 29534453]
