Steroidal saponins with anti-inflammatory activity from Tribulus terrestris L.

Abstract

Objective: Tribulus terrestris L. (T. terrestris) is a highly valuable traditional Chinese medicine used to treat stroke, inflammation, pulmonary fibrosis, liver cancer, and urolithiasis. To identify the basic substance responsible for the anti-inflammatory effect of TST (total saponins of Tribulus), its chemical composition was systematically studied, and its effect of inhibiting nitric oxide generation and the expression of related inflammatory factors were determined.
Methods: To separate chemical constituents from T. terrestris by column chromatography. Spectroscopic methods, including 1D and 2D nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) techniques, were used to elucidate the isolated compounds. The anti-inflammatory activities of TST and several compounds were evaluated in vitro.
Results: Fifteen steroidal saponins, including 9 furostanol steroidal saponins (1, 2, 3, 4, 5, 6, 7, 8, and 15) and 6 isospirostanol steroidal saponins (9, 10, 11, 12, 13, and 14), were isolated from T. terrestris. TST significantly decreased the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in RAW 264.7 cells stimulated by lipopolysaccharides. Compounds 13 and 15 evidently reduced TNF-α expression. Compounds 6, 10, 12, 13, and 15 markedly reduced IL-6 expression.
Conclusions: Compounds 1 was a novel furostanol steroidal saponin, named 26-O-β-D-glucopyranosyl-(25R)-5α-furostan-12-carbonyl-20(22)-en-3β, 26-diol-3-O-{β-D-xylopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-galactopyranoside}. Compounds 2 was isolated from the family Zygophyllaceae for the first time, and 5 and 6 were isolated from the Tribulus genus. TST and compounds 6, 10, 12, 13, and 15 exerts anti-inflammatory activity.

Keywords

Interleukin-6 / Nitric oxide (NO) inhibition / Steroidal saponins / Tribulus terrestris L. / Tumor necrosis factor-α

References

[[1]] NPCPharmacopoeia of Peoples Republic of China, Part 1. Beijing: Chemical Industry Press; 2020.

[[2]] Xu YJ, Xu TH, Zhou HO, et al. Two new furostanol saponins from Tribulus terrestris. J Asian Nat Prod Res 2010; 12 (5):349-354.

[[3]] Xu Y, Liu Y, Xu T, et al. A new furostanol glycoside from Tribulus terrestris. Molecules 2010; 15 (2):613-618.

[[4]] Liu T, Lu X, Wu B, et al. Two new steroidal saponins from Tribulus terrestris L. J Asian Nat Prod Res 2010; 12 (1):30-35.

[[5]] Liu T, Chen G, Yi GQ, et al. New pregnane and steroidal glycosides from Tribulus terrestris L. J Asian Nat Prod Res 2010; 12 (3):209-214.

[[6]] Su L, Chen G, Feng SG, et al. Steroidal saponins from Tribulus terrestris. Steroids 2009; 74 (4-5):399-403.

[[7]] Xu TH, Xu YJ, Xie SX, et al. Two new furostanol saponins from Tribulus terrestris L. J Asian Nat Prod Res 2008; 10 (5-6):419-423.

[[8]] Chauhdary Z, Saleem U, Ahmad B, et al. Neuroprotective evaluation of Tribulus terrestris L. in aluminum chloride induced Alzheimer’s disease. Pak J Pharm Sci 2019; 32 (2):805-816.

[[9]] Qiu M, An M, Bian M, et al. Terrestrosin D from Tribulus terrestris attenuates bleomycin-induced inflammation and suppresses fibrotic changes in the lungs of mice. Pharm Biol 2019; 57 (1):694-700.

[[10]] Han R, Yang H, Lu L, et al. Tiliroside as a CAXII inhibitor suppresses liver cancer development and modulates E2Fs/Caspase- 3 axis. Sci Rep 2021; 11 (1):8626.

[[11]] Parveen R, Wadud A, Shamsi S, et al. Antilithiatic activity of a nonpharmacopoeial Unani formulation in chemically induced urolithiasis in rats. J Complement Integr Med 2021; 18 (4):685-694.

[[12]] Wang Y, Guo W, Xie S, et al. Multi-omics analysis of brain tissue metabolome and proteome reveals the protective effect of gross saponins of Tribulus terrestris L. fruit against ischemic stroke in rat. J Ethnopharmacol 2021; 278:114280.

[[13]] Geovanini GR, Libby P. Atherosclerosis and inflammation: overview and updates. Clin Sci (Lond) 2018; 132 (12):1243-1252.

[[14]] Chen Q, Liu J, Zhuang Y, et al. Identification of an IKKb inhibitor for inhibition of inflammation in vivo and in vitro. Pharmacol Res 2019; 149:104440.

[[15]] Kim HS, Lee JW, Jang H, et al. Phenolic amides from Tribulus terrestris and their inhibitory effects on nitric oxide production in RAW 264.7 cells. Arch Pharm Res 2018; 41 (2):192-195.

[[16]] Subedi L, Lee SE, Madiha S, et al. PhytochemicalsagainstTNFalphamediated neuroinflammatory diseases. Int J Mol Sci 2020; 21 (3):21.

[[17]] Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol 2021; 33 (3):127-148.

[[18]] Gautam M, Ramanathan M. Saponins of Tribulus terrestris attenuated neuropathic pain induced with vincristine through central and peripheral mechanism. Inflammopharmacology 2019; 27 (4):761-772.

[[19]] Ranjithkumar R, Alhadidi Q, Shah ZA, et al. Tribulusterine containing Tribulus terrestris extract exhibited neuroprotection through attenuating stress kinases mediated inflammatory mechanism: in vitro and in vivo studies. Neurochem Res 2019; 44 (5):1228-1242.

[[20]] Ko HJ, Ahn EK, Oh JS. N-trans-r-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide- stimulated RAW 264.7 cells. Int J Mol Med 2015; 36 (4):1042-1048.

[[21]] Agrawal PK. Spectral assignments and reference data. Magn Reson Chem 2004; 42:990-993.

[[22]] Xu YL, Lyu J, Wang WF, et al. New steroidal alkaloid and furostanol glycosides isolated from Solanum lyratum with cytotoxicity. Chin J Nat Medicines 2018; 16(7):499-504.

[[23]] Liang ZZ, Aquino R, De Simone F, et al. Oligofurostanosides from Asparagus cochinchinensis. Planta Med 1988; 54 (4):344-346.

[[24]] Wang J, Zu X, Jiang Y. Five furostanol saponins from fruits of Tribulus terrestris and their cytotoxic activities. Nat Prod Res 2009; 23 (15):1436-1444.

[[25]] Li XJ, Wang L, Xue PF, et al. New steroidal glycosides from Hosta plantaginea (Lam.) Aschers. J Asian Nat Prod Res 2015; 17 (3):224-231.

[[26]] Acharya D, Mitaine-Offer AC, Kaushik N, et al. Furostane-type steroidal saponins from the roots of Chlorophytum borivilianum. Helv Chim Acta 2008; 91 (12):2262-2269.

[[27]] Hu K, Dong A, Yao X, et al. Antineoplastic agents II: four furostanol glycosides from rhizomes of Dioscorea collettii var. hypoglauca. Planta Med 1997; 63 (2):161-165.

[[28]] Xu YJ, Huang XL, Xie SX, et al. Isolation and identification of a new furosteroidal saponin from fruits of Tribulus terrestris L. Chem J Chin Univ-Chin 2007; 28 (3):484-486.

[[29]] Wang YZ, Feng B, Huang HZ, et al. Glucosylation of steroidal saponins by cyclodextrin glucanotransferase. Planta Med 2010; 76 (15):1724-1731.

[[30]] Guo J, Xu C, Xue R, et al. Cytotoxic activities of chemical constituents from rhizomes of Anemarrhena asphodeloides and their analogues. Arch Pharm Res 2015; 38 (5):598-603.

[[31]] Naveed MA, Riaz N, Saleem M, et al. Longipetalosides A-C, new steroidal saponins from Tribulus longipetalus. Steroids 2014; 83: 45-51.

[[32]] Huang JW, Jiang SH, Tan CH, et al. Structural characterization of three new steroidal sapogenins. J Organic Chem 2002; 11:917-921.

[[33]] Wang Y, Lu Y-R. Study on chemical constituents of Tribulus terrestris L. Northwest Pharm J 1990; 5 (4):14-17.

[[34]] Stefanescu R, Tero-Vescan A, Negroiu A, et al. A comprehensive review of the phytochemical, pharmacological, and toxicological properties of Tribulus terrestris L. Biomolecules 2020; 10 (5): 32.

[[35]] Zhao WR, Shi WT, Zhang J, et al. Tribulus terrestris L. extract protects against lipopolysaccharide-induced inflammation in RAW 264.7 macrophage and zebrafish via inhibition of Akt/ MAPKs and NF-kappa B/iNOS-NO signaling pathways. Evidbased Complement Altern Med 2021; 2021:11.

[[36]] Fan G, Jiang X, Wu X, et al. Anti-inflammatory activity of tanshinone IIA in LPS-stimulated RAW264.7 macrophages via miRNAs and TLR4-NF-kB pathway. Inflammation 2016; 39 (1): 375-384.