Preparation and Evaluation of Curcumin Derivatives Nanoemulsion Based on Turmeric Extract and Its Antidepressant Effect

Figures & data

Table 1 The Independent Variables with the Actual Values of Their Experimental Level Codes

Independent Variables	Level
	−1	0	+1
Tween 80 (X1)	200	275	350
Absolute ethanol (X2)	150	200	250
MCT (X3)	300	350	400
Lecithin (X4)	100	150	200

Figure 1 The experimental timeline.

Figure 2 (A) Degradation curves of CU in mixtures of CU, DMC and BDMC with different ratios and in TUR. (B) The effect of Vit C, CU and TUR solution on scavenging ability of ABTS•+ radicals. (C) The protective effects of CU, TUR and fluoxetine hydrochloride on H₂O₂-induced cell injury model. Compared with control group: **P < 0.05, compared with H₂O₂ group: ^#P < 0.05. (D) The inhibition rate of fluoxetine hydrochloride on different concentrations of ASP+. (E) The inhibition rate of CU and TUR on ASP+. The line: the inhibition rate of fluoxetine hydrochloride on 100 μM ASP+. Compared with fluoxetine hydrochloride on ASP+: *P < 0.05, **P< 0.01.

Table 2 Single Factor Analysis of the TUR-NE Preparation Process

		EE (%)	Size (nm)	PDI
Emulsification temperature (°C)	50	80.61 ± 3.78	865.3 ± 1.62	0.406 ± 0.03
	60	87.53 ± 3.75	125.4 ± 0.56	0.319 ± 0.02
	70	91.81 ± 1.42	137.1 ± 0.32	0.231 ± 0.01
Emulsification time (min)	5	93.83 ± 0.62	240.1 ± 0.69	0.083 ± 0.02
	10	95.52 ± 0.93	101.2 ± 0.52	0.234 ± 0.02
	20	90.38 ± 1.38	104.1 ± 1.16	0.262 ± 0.01
Speed (rpm)	250	94.43 ± 2.09	118.6 ± 0.76	0.240 ± 0.06
	500	95.95 ± 0.93	103.2 ± 0.13	0.213 ± 0.06
	800	77.68 ± 1.85	133.3 ± 0.88	0.155 ± 0.02

Table 3 Single Factor Analysis of the TUR-NE Prescription

		EE (%)	Size (nm)	PDI
PEG-400 (mg)	300	92.20 ± 0.41	163.1 ± 0.23	0.294 ± 0.02
	350	98.14 ± 0.31	101.9 ± 0.74	0.229 ± 0.05
	400	97.95 ± 1.30	117.2 ± 0.74	0.266 ± 0.02
	450	96.52 ± 0.93	123.3 ± 0.52	0.269 ± 0.06
	500	96.07 ± 1.12	136.5 ± 0.13	0.275 ± 0.06
Lecithin (mg)	75	97.29 ± 0.40	279.0 ± 14.00	0.654 ± 0.25
	100	98.23 ± 0.40	240.0 ± 2.06	0.518 ± 0.21
	150	98.98 ± 0.45	105.3 ± 0.56	0.204 ± 0.12
	200	95.56 ± 1.20	120.2 ± 0.46	0.823 ± 0.32
	250	92.03 ± 1.87	141.0 ± 5.78	1.000 ± 0.85
MCT (mg)	250	96.33 ± 1.90	110.4 ± 0.32	0.624 ± 0 0.23
	300	97.05 ± 0.81	112.7 ± 1.00	0.495 ± 0.11
	350	98.74 ± 0.49	103.5 ± 0.79	0.203 ± 0.01
	400	93.78 ± 1.02	313.2 ± 0.46	0.246 ± 0.02
	450	92.70 ± 0.25	376.2 ± 1.07	0.254 ± 0.06
Tween 80 (mg)	100	77.97 ± 2.09	391.4 ± 0.82	0.584 ± 0.12
	150	87.05 ± 2.06	147.1 ± 0.57	0.482 ± 0.09
	200	91.03 ± 1.86	140.4 ± 0.14	0.451 ± 0.02
	250	94.52 ± 0.85	116.8 ± 0.68	0.322 ± 0.04
	300	96.52 ± 0.93	92.52 ± 0.13	0.269 ± 0.02
TUR (mg)	15	96.19 ± 0.42	101.9 ± 0.737	0.244 ± 0.01
	20	97.95 ± 0.75	108.0 ± 0.615	0.229 ± 0.01
	25	97.20 ± 1.01	122.7 ± 0.519	0.156 ± 0.03
	30	98.18 ± 0.89	138.0 ± 0.191	0.179 ± 0.04
	40	90.80 ± 0.73	259.5 ± 0.76	0.234 ± 0.06
Absolute ethanol (µL)	25	86.56 ± 1.63	40.05 ± 3.70	0.542 ± 0.23
	50	89.19 ± 1.15	57.37 ± 0.44	0.524 ± 0.12
	100	90.95 ± 0.83	71.42 ± 0.77	0.439 ± 0.02
	150	95.66 ± 0.54	86.39 ± 2.45	0.356 ± 0.03
	200	97.89 ± 0.94	103.2 ± 0.74	0.236 ± 0.05
Ultrapure water (mL)	0.5	89.92 ± 0.60	816.3 ± 0.17	0.588 ± 0.26
	1.5	94.20 ± 0.04	756.0 ± 1.50	0.402 ± 0.12
	2.0	96.24 ± 0.31	120.1 ± 0.85	0.230 ± 0.01
	3.0	95.20 ± 0.56	942.0 ± 6.52	0.595 ± 0.23
	4.0	91.33 ± 0.11	992.0 ± 2.71	0.608 ± 0.32

Table 4 Experimental Design and the Experimental Values of Response Variables

Number	X1 (mg)	X2 (mg)	X3 (mg)	X4 (mg)	Y1 (%)	Y2
1	200.00	150.00	350.00	150.00	82.03	0.438
2	350.00	150.00	350.00	150.00	92.03	0.195
3	200.00	250.00	350.00	150.00	80.01	0.471
4	350.00	250.00	350.00	150.00	92.62	0.101
5	275.00	200.00	300.00	100.00	97.52	0.113
6	275.00	200.00	400.00	100.00	95.22	0.201
7	275.00	200.00	300.00	200.00	71.20	0.982
8	275.00	200.00	400.00	200.00	75.03	0.524
9	200.00	200.00	350.00	100.00	82.99	0.247
10	350.00	200.00	350.00	100.00	94.09	0.200
11	200.00	200.00	350.00	200.00	60.23	0.775
12	350.00	200.00	350.00	200.00	77.02	0.467
13	275.00	150.00	300.00	150.00	82.20	0.352
14	275.00	250.00	300.00	150.00	98.87	0.242
15	275.00	150.00	400.00	150.00	96.44	0.266
16	275.00	250.00	400.00	150.00	96.87	0.080
17	200.00	200.00	300.00	150.00	79.36	0.368
18	350.00	200.00	300.00	150.00	97.46	0.187
19	200.00	200.00	400.00	150.00	98.23	0.179
20	350.00	200.00	400.00	150.00	98.19	0.085
21	275.00	150.00	350.00	100.00	86.02	0.169
22	275.00	250.00	350.00	100.00	96.42	0.278
23	275.00	150.00	350.00	200.00	65.20	0.681
24	275.00	250.00	350.00	200.00	80.20	0.367
25	275.00	200.00	350.00	150.00	98.56	0.117
26	275.00	200.00	350.00	150.00	97.10	0.130
27	275.00	200.00	350.00	150.00	97.77	0.148
28	275.00	200.00	350.00	150.00	97.64	0.141
29	275.00	200.00	350.00	150.00	96.73	0.152

Table 5 Analysis of Variance (ANOVA) for the Quadratic Model

Quadratic Model	R^2 value	Adjusted R^2	F-value	P-value
Y1	0.9447	0.8894	22.14	< 0.0001
Y2	0.9246	0.8492	11.30	0.0003

Figure 3 The response surface plots of the effect for the independent variable on EE (A-F) and PDI (G-L).

Figure 4 (A) Size and (B) Zeta potential of TUR-NE. (C) TEM image of TUR-NE (12,000 × magnification). (D) Accumulative release rate for TUR and TUR-NE in HCl (PH 1.2) and PBS (PH 7.4). The variation in (E) size, (F) PDI, (G) EE, and (H) LE of TUR-NE during stability study.

Table 6 The Main Pharmacokinetic Parameters of CU, TUR, and TUR-NE

	Unit	CU	TUR	TUR-NE
AUC(0-t)	mg/L^−1·min	63.341	118.879	534.363
MRT(0-t)	min	290.448	314.971	235.029
T1/2	min	352.539	456.397	300.181
Tmax	min	30.000	120.000	60.000
CL	L·min^−1·kg^−1	1.208	0.554	0.160
Cmax	mg/L	0.170	0.281	1.532

Abbreviations: AUC_(0-t), area under the curve; MRT_(0-t), the mean residence time; T_1/2, the half-life period; T_max, the time to peak concentration; CL, the clearance rate; C_max, the peak concentration.

Figure 5 (A) The plasma concentration-time curves of CU after given CU, TUR, and TUR-NE by oral administration. (B) The sucrose preference value of the CUMS model mice in SPT. (C) The immobility time of the CUMS model mice in FST. (D-F) The depression-like and anxiety-like behaviors were improved after administration. (D) The sucrose preference value of the mice in SPT, (E) the immobility time of the mice in FST, (F) the latency time to feed of the mice in NSFT. (G-J) The levels of 5-HT and MAO in plasma and brain of the mice. Compared with control group: **P < 0.01, compared with CUMS model group: ^#P < 0.05, ^##P < 0.01.

Figure 6 Pathological section images of heart, liver, and kidney in mice (400 × magnification). The green arrow: slight degeneration of the tissue organs.