Antihyperglycaemic potential of rosmarinic acid attenuates glycoprotein moiety in high-fat diet and streptozotocin-induced diabetic rats

Figures & data

Figure 1. Structure of rosmarinic acid.

Table 1. ¹H and ¹³C- NMR data for isolated compound rosmarinic acid (500 MHz, Acetone).

Position	^1H-NMR	^13C-NMR
1	–	126.60
2	7.44 (1H, s)	114.04
3	8.35 (OH)	143.90
4	8.12 (OH)	145.38
5	6.73 (1H, d, J=8.0 Hz)	115.47
6	6.93 (1H, d, J=2.5 Hz)	116.42
7	7.41(1H, d, J=16 Hz)	148.01
8	6.61(1H, d, J=8 Hz)	115.06
9	–	165.92
1’	–	128.28
2’	7.03 (1H, s)	116.42
3’	8.35 (OH)	145.68
4’	8.12 (OH)	144.81
5’	6.91 (1H, d, J=2.0 Hz)	121.87
6’	6.72 (1H, d, J=2.0 Hz)	120.77
7’	3.00 (2H, d, J=4 Hz)	36.58
8’	5.08 (1H, dd J=8.5, 4.5 Hz)	72.81
9’	–	170.22

Table 2. Effect rosmarinic acid on the changes in plasma glucose, insulin levels and HOMA-IR index in control and experimental animals.

	Blood glucose (mg/dl)		Plasma Insulin (µU/ml)		HOMA IR
Group	Initial	Final	Initial	Final	Initial	Final
Control	90.77 ± 6.75	88.86 ± 7.20	17.10 ± 1.06	16.92 ± 1.57	3.84 ± 0.44	3.70 ± 0.36
Normal + Rosmarinic acid 100 mg/kg b.wt	86.98 ± 6.20	91.24 ± 3.08	16.69 ± 1.58	18.03 ± 1.25	3.59 ± 0.46	4.06 ± 0.30
Diabetes induced	258.61 ± 6.58	295.90 ± 9.95^b	9.76 ± 0.59	9.50 ± 0.87^b	6.23 ± 0.34	6.93 ± 0.47^b
Diabetic + Rosmarinic acid 100 mg/kg b.wt	255.67 ± 5.73	140.57 ± 13.22^c	10.33 ± 0.79	13.72 ± 1.36^c	6.52 ± 0.47	4.74 ± 0.42^c
Diabetic + Metformin (500 mg/kg/b.wt)	253.67 ± 8.04	135.22 ± 11.57	9.59 ± 0.96	15.08 ± 1.00	6.00 ± 0.50	5.02 ± 0.35

Notes: Values are given as mean ± SD for six animals in each group. Values are considered significantly different at P < 0.05 with post hoc LSD test *P < 0.05.

^aControl vs. Rosmarinic acid alone treated control rats.

^bControl rats vs. diabetic rats.

^cDiabetic rats vs. Rosmarinic acid treated diabetic rats.

^dRosmarinic acid treated diabetic rats vs. Metformin treated diabetic rats.

Table 3. Effect of rosmarinic acid on body weight, fluid intake, food intake, liver weight and urine sugar of control and experimental animals.

	Body weight (g)		Food intake (g/rat/day)		Water intake (ml/rat/day)
Group	Initial	Final	Initial	Final	Initial	Final	Liver weight (g)	Urine sugar
Control	188.25 ± 9.90	211.69 ± 4.60	14.59 ± 1.33	15.67 ± 1.42	67.77 ± 5.69	64.96 ± 4.89	13.69 ± 1.21	Nil
Normal + Rosmarinic acid 100 mg/kg b.wt	192.17 ± 9.14	215.28 ± 3.43	15.38 ± 1.19	13.865 ± 1.14	65.45 ± 6.12	61.83 ± 4.69	14.24 ± 1.07	Nil
Diabetes induced	190.83 ± 7.49	157.52 ± 8.53^b	59.17 ± 5.74	68.87 ± 5.87^b	136.14 ± 7.17	175.31 ± 3.34^b	7.83 ± 0.79^b	3+
Diabetic + Rosmarinic acid 100 mg/kg b.wt	193.96 ± 6.63	197.93 ± 8.98^c	39.98 ± 3.15	34.37 ± 3.34^c	131.06 ± 5.07	81.98 ± 6.58^c	11.43 ± 0.99^c	Nil
Diabetic + Metformin (500 mg/kg/b.wt)	191.62 ± 6.77	201.54 ± 5.61	37.88 ± 3.03	31.95 ± 3.13	128.19 ± 5.19	77.06 ± 5.94	12.60 ± 0.89	Nil

Notes: Values are given as mean ± SD for six animals in each group. Values are considered significantly different at P < 0.05 with post hoc LSD test *P < 0.05.

^aControl vs. Rosmarinic acid alone treated control rats.

^bControl rats vs. diabetic rats.

^cDiabetic rats vs. Rosmarinic acid treated diabetic rats.

^dRosmarinic acid treated diabetic rats vs. Metformin treated diabetic rats.

Table 4. Effects of rosmarinic acid on haemoglobin and gycosylated haemoglobin levels in control and experimental animals.

Group	Haemoglobin (g/dl)	HbA1C (%)
Control	15.39 ± 1.54	5.21 ± 0.47
Normal + Rosmarinic acid 100 mg/kg b.wt	16.61 ± 1.30	4.83 ± 0.34
Diabetes induced	10.72 ± 1.02^b	12.62 ± 1.18^b
Diabetic + Rosmarinic acid 100 mg/kg b.wt	13.91 ± 0.87^c	7.76 ± 0.73^c
Diabetic + Metformin (500 mg/kg/b.wt)	14.77 ± 0.76	6.89 ± 0.57

Notes: Values are given as mean ± SD for six animals in each group. Values are considered significantly different at P < 0.05 with post hoc LSD test *P < 0.05.

^aControl vs. Rosmarinic acid alone treated control rats.

^bControl rats vs. diabetic rats.

^cDiabetic rats vs. Rosmarinic acid treated diabetic rats.

^dRosmarinic acid treated diabetic rats vs. Metformin treated diabetic rats.

Table 5. Effects of rosmarinic acid on the levels of glycogen content, glycogen synthase and glycogen phosphorylase in control and experimental animals.

Group	Glycogen content (mg/g tissue)	Glycogen synthase (µ moles of UDP formed/h/mg protein)	Glycogen phospharylase (µ moles Pi liberated/h/mg protein)
Control	59.46 ± 5.27	836.47 ± 13.63	592.57 ± 25.12
Normal + Rosmarinic acid (100 mg/kg b.wt)	61.14 ± 5.19	834.40 ± 13.23	594.03 ± 25.17
Diabetes induced	28.79 ± 2.78^b	485.31 ± 17.90^b	801.27 ± 12.61^b
Diabetic + Rosmarinic acid 100 mg/kg b.wt	45.54 ± 3.47^c	800.54 ± 11.64^c	621.57 ± 35.75^c
Diabetic + Metformin (500 mg/kg/b.wt)	47.05 ± 3.51	802.27 ± 12.16	619.08 ± 36.25

Notes: Values are given as mean ± SD for six animals in each group. Values are considered significantly different at P < 0.05 with post hoc LSD test *P < 0.05.

^aControl vs. Rosmarinic acid alone treated control rats.

^bControl rats vs. diabetic rats.

^cDiabetic rats vs. Rosmarinic acid treated diabetic rats.

^dRosmarinic acid treated diabetic rats vs. Metformin treated diabetic rats.

Figure 2. Changes in the levels of plasma glycoproteins in control and experimental animals. Values are given as mean ± SD for six animals in each group. Values are considered significantly different at P < 0.05 with post hoc LSD test *P < 0.05. (a) Control vs. Rosmarinic acid alone treated control rats. (b) Control rats vs. diabetic rats. (c) Diabetic rats vs. Rosmarinic acid treated diabetic rats. (d) Rosmarinic acid treated diabetic rats vs. Metformin treated diabetic rats.

Figure 3. Changes in the levels of liver glycoproteins in control and experimental animals. Values are given as mean ± SD for six animals in each group. Values are considered significantly different at P < 0.05 with post hoc LSD test *P < 0.05. (a) Control vs. Rosmarinic acid alone treated control rats. (b) Control rats vs. diabetic rats. (c) Diabetic rats vs. Rosmarinic acid treated diabetic rats. (d) Rosmarinic acid treated diabetic rats vs. Metformin treated diabetic rats.

Figure 4. Changes in the levels of kidney glycoproteins in control and experimental animals. Values are given as mean ± SD for six animals in each group. Values are considered significantly different at P < 0.05 with post hoc LSD test *P < 0.05. (a) Control vs. Rosmarinic acid alone treated control rats. (b) Control rats vs. diabetic rats. (c) Diabetic rats vs. Rosmarinic acid treated diabetic rats. (d) Rosmarinic acid treated diabetic rats vs. Metformin treated diabetic rats.