An Evaluation of 3-Rhamnosylquercetin, a Glycosylated Form of Quercetin, against the Myotoxic and Edematogenic Effects of sPLA₂fromCrotalus durissus terrificus

Abstract

This paper shows the results of quercitrin effects on the structure and biological activity of secretory phospholipase (sPLA2) from Crotalus durissus terrificus, which is the main toxin involved in the pharmacological effects of this snake venom. According to our mass spectrometry and circular dichroism results, quercetin was able to promote a chemical modification of some amino acid residues and modify the secondary structure of C. d. terrificus sPLA2. Moreover, molecular docking studies showed that quercitrin can establish chemical interactions with some of the crucial amino acid residues involved in the enzymatic activity of the sPLA2, indicating that this flavonoid could also physically impair substrate molecule access to the catalytic site of the toxin. Additionally, in vitro and in vivo assays showed that the quercitrin strongly diminished the catalytic activity of the protein, altered its Vmax and Km values, and presented a more potent inhibition of essential pharmacological activities in the C. d. terrificus sPLA2, such as its myotoxicity and edematogenic effect, in comparison to quercetin. Thus, we concluded that the rhamnose group found in quercitrin is most likely essential to the antivenom activities of this flavonoid against C. d. terrificus sPLA2.

Evaluation of Rhamnetin as an Inhibitor of the Pharmacological Effect of Secretory Phospholipase A2

“…There are studies that have evaluated the effect of flavonoids and glycosylated flavonoids on the course of the enzymatic and pharmacological activity of secretory phospholipases A2 [ 5 , 6 ]. Moreover, these studies deserve further efforts to elucidate the mechanism of action of these types of flavonoids on sPLA2, including studies of the conformational changes of flavonoids that modify their antioxidant properties to pro-oxidants, and these mechanisms should be better understood.…”

“…In particular, sPLA2 in snake venom is an attractive therapeutic target due to its accessibility, ease of purification and, in the case of sPLA2 in humans, high levels of systemic enzymatic activity, which characterize and contribute to most of the inflammatory disorders, including neurodegenerative diseases. Therefore, the discovery of new inhibitors of sPLA2 is essential to produce new safe and effective drugs with fewer side effects compared to the current therapy [ 5 , 6 ].…”

Edema Induced by sPLA2 from Crotalus durissus terrificus Involves PLC and PKC Signaling, Activation of cPLA2, and Oxidative Stress

“…The edematogenic assay performed with Edema Induced by sPLA2 from Crotalus durissus terrificus Involves PLC and PKC Signaling… DOI: http://dx.doi.org/10.5772/intechopen.80848 native sPLA2 and 5CQA incubated with sPLA2 clearly showed that edema induced by sPLA2:5CQA was not abolished, but significantly diminished ( Figure 4A). Thus, in part, the anti-inflammatory effect of 5CQA probably involves the downregulation of pharmacological and enzymatic activity of sPLA2 [57,58]. In Figure 3B, we show the effect of p-bromophenacyl bromide (p-BPB) and umbelliferone (7-HOC) on edema induced by sPLA2.…”

Evaluation of Potential Thrombin Inhibitors from the White Mangrove (Laguncularia racemosa (L.) C.F. Gaertn.)

“…Quercetin-3- O -arabinoside: 1 H-NMR (300 MHz, CD 3 OD) δ 6.41 (d, J = 2.1 Hz, H-6), δ 6.23 (d, J = 2.1 Hz, H-8), δ 7.51 (d, J = 2.0 Hz, H-2′), δ 6.85 (d, J = 8.3 Hz, H-5′), δ 7.25 (dd, J = 8.3 Hz and 2.0 Hz, H-6′), δ 5.27 (d, J = 5.1 Hz, H-1″), δ 3.23–3.62 (H-2″–H-5″); 13 C NMR (75 MHz, CD 3 OD) 156.1 (C-2), 133.5 (C-3), 177.3 (C-4), 161.1 (C-5), 98.5 (C-6), 164.3 (C-7), 93.4 (C-8), 155.9 (C-9), 103.5 (C-10), 120.3 (C-1′), 115.3 (C-2′), 145.3 (C-3′), 148.7 (C-4′), 115.7 (C-5′), 123.0 (C-6′), 100.9 (C-1″), 70.5 (C-2″), 71.4 (C-3″), 65.5 (C-4″), 63.6 (C-5″) [ 27 , 28 ].…”

“…Quercetin-3- O -rhamnoside (Quercitrin): 1 H-NMR (300 MHz, CD 3 OD) δ 6.37 (d, J = 2.1 Hz, H-6), δ 6.19 (d, J = 2.1 Hz, H-8), δ 7.34 (d, J = 2.1 Hz, H-2′), δ 6.94 (d, J = 8.7 Hz, H-5′), δ 7.30 (dd, J = 8.4 Hz and 2.1 Hz, H-6′), δ 5.34 (d, J = 1.5 Hz, H-1″), δ 4.23 (dd, J = 3.0 Hz and 1.8 Hz, H-2″), δ 3.75 (dd, J = 9.0 Hz and 3.3 Hz, H-3″), δ 3.32 (dd, J = 9.3 Hz and 3.3 Hz, H-4″), δ 3.41 (d, J = 6.0 Hz, H-5″), δ 0.94 (d, J = 6.0 Hz, H-6″); 13 C NMR (75 MHz, CD 3 OD) 159.2 (C-2), 136.5 (C-3), 179.7 (C-4), 163.1 (C-5), 99.8 (C-6), 165.8 (C-7), 94.9 (C-8), 158.8 (C-9), 106.2 (C-10), 123.1 (C-1′), 117.3 (C-2′), 146.7 (C-3′), 149.8 (C-4′), 116.7 (C-5′), 123.3 (C-6′), 103.5 (C-1″), 72.2 (C-2″), 72.1 (C-3″), 73.4 (C-4″), 72.0 (C-5″), 17.7 (C-6″) [ 27 , 28 ].…”