Anti-Inflammatory and Anti-Melanogenic Steroidal Saponin Glycosides from Fenugreek (Trigonella foenum-graecum L.) Seeds

Abstract

Fenugreek seed (Trigonella foenum-graecum L.) is used as an herbal medicine for treating metabolic and nutritive dysfunctions. To determine if this plant has other beneficial effects, we tested the inhibitory activities of a methanol (MeOH) extract of fenugreek seed on the production of inflammatory cytokines and melanin synthesis in cultured cell lines in vitro. The MeOH extract inhibited the production of phorbol-12-myristate-13-acetate-induced inflammatory cytokines such as tumor necrosis factor (TNF)-α in cultured THP-1 cells, and also restrained the intracellular synthesis of melanin in murine melanoma B16F1 cells. We isolated three active constituents from fenugreek seed extracts. These were identified as the steroidal saponins 26-O-β-D-glucopyranosyl-(25R)-furost-5(6)-en-3β,22β,26-triol-3-O-α-L-rhamno-pyranosyl-(1′′→ 2′)-O-[β-D-glucopyranosyl-(1′′′ → 6′)-O]-β-D-glucopyranoside 1, minutoside B 2, and pseudoprotodioscin 3. Compounds 1 and 2 strongly suppressed the production of inflammatory cytokines, whereas 3 showed a weaker suppressing effect. Melanogenesis in B16F1 cells was significantly suppressed by 1 and 3, and weakly suppressed by 2. All three compounds showed moderate cytotoxicities. These results indicate that fenugreek extract and its active constituents could protect against skin damage.

Key words

Trigonella foenum‐graecum - Fabaceae - anti‐inflammatory - melanogenesis - steroidal saponin

References

• 1 Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek.  Altern Med Rev. 2003;  8 20-27
• 2 Yoshikawa M, Murakami T, Komatsu H, Murakami N, Yamahara J, Matsuda H. Medicinal foodstuffs. IV. Fenugreek seed. (1): structures of trigoneosides Ia, Ib, II a, II b, III a, and III b, new furostanol saponins from the seeds of Indian Trigonella foenum-graecum L.  Chem Pharm Bull (Tokyo). 1997;  45 81-87
• 3 Patil S P, Niphadkar P V, Bapat M M. Allergy to fenugreek (Trigonella foenum graecum).  Ann Allergy Asthma Immunol. 1997;  78 297-300
• 4 Srinivasan K. Plant foods in the management of diabetes mellitus: spices as beneficial antidiabetic food adjuncts.  Int J Food Sci Nutr. 2005;  56 399-414
• 5 Sur P, Das M, Gomes A, Vedasiromoni J R, Sahu N P, Banerjee S, Sharma R M, Ganguly D K. Trigonella foenum graecum (fenugreek) seed extract as an antineoplastic agent.  Phytother Res. 2001;  15 257-259
• 6 Hibasami H, Moteki H, Ishikawa K, Katsuzaki H, Imai K, Yoshioka K, Ishii Y, Komiya T. Protodioscin isolated from fenugreek (Trigonella foenum graecum L.) induces cell death and morphological change indicative of apoptosis in leukemic cell line H-60, but not in gastric cancer cell line KATO III.  Int J Mol Med. 2003;  11 23-26
• 7 Dini I, Tenore G C, Trimarco E, Dini A. Furostanol saponins in Allium caepa L. Var. tropeana seeds.  Food Chem. 2005;  93 205-214
• 8 Barile E, Bonanomi G, Antignani V, Zolfaghari B, Sajjadi S E, Scala F, Lanzotti V. Saponins from Allium minutiflorum with antifungal activity.  Phytochemistry. 2007;  68 596-603
• 9 Dong M, Feng X-Z, Wang B-X, Wu L-J, Ikejima T. Two novel furostanol saponins from the rhizomes of Dioscorea panthaica Prain et Burkill and their cytotoxic activity.  Tetrahedron. 2001;  57 501-506
• 10 Hasegawa T, Takano F, Takata T, Niiyama M, Ohta T. Bioactive monoterpene glycosides conjugated with gallic acid from the leaves of Eucalyptus globulus.  Phytochemistry. 2008;  69 747-753
• 11 Bhatnagar V, Srirangam A, Abburi R. In vitro modulation of proliferation and melanization of melanoma cells by citrate.  Mol Cell Biochem. 1998;  187 57-65
• 12 Matsuda H, Kawaguchi Y, Yamazaki M, Hirata N, Naruto S, Asanuma Y, Kaihatsu T, Kubo M. Melanogenesis stimulation in murine B16 melanoma cells by Piper nigrum leaf extract and its lignan constituents.  Biol Pharm Bull. 2004;  27 1611-1616
• 13 Hill S E, Bleehen S S, MacNeil S. I alpha-25-dihydroxyvitamin D3 increases intracellular free calcium in murine B16 melanoma.  Br J Dermatol. 1989;  120 21-30
• 14 Bornstein S R, Rutkowski H, Vrezas I. Cytokines and steroidogenesis.  Mol Cell Endocrinol. 2004;  215 135-141
• 15 Nehmé A, Edelman J. Dexamethasone inhibits high glucose-, TNF-alpha-, and IL-1beta-induced secretion of inflammatory and angiogenic mediators from retinal microvascular pericytes.  Invest Ophthalmol Vis Sci. 2008;  49 2030-2038
• 16 Maeda K, Fukuda M. Arbutin: mechanism of its depigmenting action in human melanocyte culture.  J Pharmacol Exp Ther. 1996;  276 765-769
• 17 Raju J, Bird R P. Alleviation of hepatic steatosis accompanied by modulation of plasma and liver TNF-α levels by Trigonella foenum graecum (fenugreek) seeds in Zucker obese (fa/fa) rats.  Int J Obes (Lond). 2006;  30 1298-1307
• 18 Raju J, Patlolla J M, Swamy M V, Rao C V. Diosgenin, a steroid saponin of Trigonella foenum-graecum (fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells.  Cancer Epidemiol Biomarkers Prev. 2004;  13 1392-1398
• 19 Ali L, Azad Khan A K, Hassan Z, Mosihuzzaman M, Nahar N, Nasreen T, Nur-e-Alam M, Rokeya B. Characterization of the hypoglycemic effects of Trigonella foenum graecum seed.  Planta Med. 1995;  61 358-360
• 20 Aggarwal B B, Kunnumakkara A B, Harikumar K B, Tharakan S T, Sung B, Anand P. Potential of spice-derived phytochemicals for cancer prevention.  Planta Med. 2008;  74 1560-1569
• 21 Shim S H, Lee E J, Kim J S, Kang S S, Ha H, Lee H Y, Kim C, Lee J H, Son K H. Rat growth-hormone release stimulators from fenugreek seeds.  Chem Biodivers. 2008;  5 1753-1761
• 22 Gupta R K, Jain D C, Thakur R S. Two furostanol saponins from Trigonella foenum-graecum.  Phytochemistry. 1986;  25 2205-2207