Hepato-, neuroprotective effects and QSAR studies on flavoalkaloids and flavonoids from Astragalus monspessulanus

Figures & data

Figure 1. Structures of the studied flavoalkaloids (2–3), flavonoids from A. monspessulanus ssp. monspessulanus (6–13) and A. monspessulanus ssp. illyricus (4–5). Silybin was used as a reference compound.

Table 1. Effects of compounds 1–13 and Silybin (S) (at concentrations 1, 10 and 100 µmol/L) administered alone on isolated rat hepatocytes.

Condition	Concentration	LDH activity (%)	GSH level (%)	MDA production (%)
Control	(µmol/L)	100	100	100
1	1	102	90*	164**
	10	107*	80*	189**
	100	188**	75*	221***
2	1	101	90*	172**
	10	109*	85*	193***
	100	189**	80*	231***
3	1	102	90*	177**
	10	110*	80*	198***
	100	187**	75*	228***
4	1	100	90*	180**
	10	108*	85*	205***
	100	190**	75*	230***
5	1	118*	80*	205***
	10	124**	70*	236***
	100	206***	60**	258***
6	1	119**	80*	211***
	10	121**	70*	228***
	100	204***	65**	261***
7	1	100	95	184***
	10	105	90*	210***
	100	186**	80*	230***
8	1	116*	70*	205***
	10	125**	65**	233***
	100	206***	60**	264***
9	1	120**	75*	210***
	10	128**	70*	239***
	100	209***	65**	272***
10	1	121**	75*	215***
	10	130**	65**	233***
	100	211***	60**	267***
11	1	116*	80*	221***
	10	133**	70*	238***
	100	214***	65**	270***
12	1	120**	80*	218***
	10	136**	70*	248***
	100	218***	65**	280***
13	1	122**	75*	225***
	10	139**	70*	241***
	100	217***	65**	274***
Silybin	1	123**	70*	230***
	10	140**	65**	250***
	100	220***	60**	280***

Note: Values are the mean ± SEM of six experiments. Values are expressed as a present relative to the control condition.

* p < 0.05;

** p < 0.01;

*** p < 0.001

vs. control (non-treated hepatocytes).

Table 2. Hepatotoxic activities* and relevant descriptors of the studied compounds.

Compound	pEC50 LDH	pEC50 MDA	% GSH at 100 μmol/L	SaasC_acnt	phia	Log p	SaasC
1	4.729	6.082	75	7	14.964	−0.543	−3.820
2	4.739	6.124	80	8	14.037	−1.677	−4.288
3	4.753	6.451	75	7	13.826	−1.578	−2.642
4	4.726	6.600	75	7	12.415	0.893	−3.544
5	4.917	7.037	60	6	12.209	1.181	−2.001
6	4.906	7.114	65	6	14.754	−0.473	−2.227
7	4.728	6.870	80	7	11.767	0.440	−3.394
8	4.911	6.763	60	6	11.556	0.672	−1.871
9	4.951	6.752	65	7	9.079	0.623	−3.006
10	4.967	7.109	60	6	5.991	0.865	−0.057
11	4.946	7.368	65	6	5.991	0.986	0.049
12	4.980	6.893	65	6	6.202	0.379	−1.267
13	5.018	7.434	65	7	9.079	0.628	−3.006
Silybin	5.021	7.533	60	–	–	–	–

* Note: Activities are given as –logEC₅₀ (pEC₅₀) for LDH release and MDA production and as percent (%) for the GSH levels at a concentration of 100 μmol/L of the tested compound.

Figure 2. Effects of compounds 1–13 (at concentration 100 µmol/L), on LDH leakage, in t-BuOOH-induced oxidative stress (at concentration 75 µmol/L) in isolated rat hepatocytes. Each symbol indicates the mean ± SEM of six experiments. Statistically significant differences: ***p < 0.001 vs. control (non-treated hepatocytes); ⁺⁺p < 0.01; ⁺⁺⁺p < 0.001 vs. t-BuOOH.

Figure 3. Effects of compounds 1–13 (at concentration 100 µmol/L), on GSH level, in t-BuOOH-induced oxidative stress (at concentration 75 µmol/L) in isolated rat hepatocytes. Each symbol indicates the mean ± SEM of six experiments. Statistically significant differences: ***p < 0.001 vs. control (non-treated hepatocytes); ⁺⁺p < 0.01; ⁺⁺⁺p < 0.001 vs. t-BuOOH.

Figure 4. Effects of compounds 1–13 (at concentration 100 µmol/L), on MDA production, in t-BuOOH-induced oxidative stress (at concentration 75 µmol/L) in isolated rat hepatocytes. Each symbol indicates the mean ± SEM of six experiments. Statistically significant differences: ***p < 0.001 vs. control (non-treated hepatocytes); ⁺p < 0.05; ⁺⁺ p < 0.01; ⁺⁺⁺ p < 0.001 vs. t-BuOOH.

Figure 5. Effects of compounds 1–13 (at concentration 100 µmol/L), on synaptosomal viability, in 6-OHDA-induced oxidative stress (at concentration 150 µmol/L) in isolated rat synaptosomes. Each symbol indicates the mean ± SEM of six experiments. Statistically significant differences: ***p < 0.001 vs. control (non-treated synaptosomes); ⁺⁺p < 0.01; ⁺⁺⁺p < 0.001 vs. 6-OHDA.

Figure 6. Effects of compounds 1–13 (at concentration 100 µmol/L), on GSH level, in 6-OHDA-induced oxidative stress (at concentration 150 µmol/L) in isolated rat synaptosomes. Each symbol indicates the mean ± SEM of six experiments. Statistically significant differences: *** p < 0.001 vs. control (non-treated synaptosomes); ⁺ p < 0.05; ⁺⁺ p < 0.01; ⁺⁺⁺ p < 0.001 vs. 6-OHDA.