Fig 1.
Schematic representation of experimental protocol.
Behavioral analysis was monitored by using Kondziela inverted screen test (KIST), pole test (PT), beam walking test (BWT), open field test (OFT), inclined plane test (IPT), social interaction test (SIT), sucrose preference test (SPT), Morris water maze test (MWM), novel object recognition task (NOR), footprint (FP) test.
Table 1.
Drug dose and route of administration of groups.
Fig 2.
Effects of rotenone and pre-and post-administration of quercetin on food intake (A) and growth rate (B).Values are mean±SD (n = 8). Non-significant difference was obtained by one-way ANOVA following Tukey’s test. Growth rate in % was calculated by (Present weight/Initial weight) × 100).
Fig 3.
Effects of pre- and post-supplementation of quercetin on Kondziela inverted screen test in rotenone-injected rats.
Significant differences were obtained by one-way ANOVA followed by Tukey’s test. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group.
Fig 4.
Effects of pre- and post-supplementation of quercetin on pole test in rotenone-injected rats.
Significant differences were obtained by one-way ANOVA followed by Tukey’s test. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group. Values are mean±SD (n = 8).
Fig 5.
Effects of pre- and post-supplementation of quercetin on beam walking test in rotenone-injected rats.
Significant differences were obtained by one-way ANOVA followed by Tukey’s test. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; #p<0.05 as compared to Pre-Que+Rot group. Values are mean±SD (n = 8).
Fig 6.
Effect of quercetin pre- and post-supplementation on exploratory activity by open field test in terms of (A) latency to move (s) and (B) number of square crossed. Values are represented as mean±SD (n = 8). **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group.
Fig 7.
Effect of quercetin pre- and post-supplementation on rotenone-induced cataleptic condition in rotenone-injected rats.
Values are represented as mean±SD (n = 8). Data was analyzed by Tukey’s test following one-way ANOVA. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group.
Fig 8.
Walking pattern was attained by footprint test following pre-and post-supplementation of quercetin in rotenone-induced PD model (A) forepaws and hindpaws were coated with red and green ink. The dotted lines indicate stride length. The irregular distance between the fore- and hind paws in control and test rats is encircled. The quantification of (B) strides, (C) base width, and (D) paw overlap in all groups. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group.
Fig 9.
Depressive-like symptom following pre- and post-quercetin supplementation in rotenone-induced PD model were monitored by social interaction test.
Values are represented as mean±SD (n = 8). Data was analyzed by Tukey’s test following one-way ANOVA. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01, #p<0.05 as compared to Pre-Que+Rot group.
Fig 10.
Depressive-like symptom following pre- and post-quercetin supplementation in rotenone-induced PD model were monitored by sucrose preference test.
Values are represented as mean±SD (n = 8). Data was analyzed by Tukey’s test following one-way ANOVA. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group.
Fig 11.
Effect of pre- and post-administration of quercetin (50 mg/kg) in rotenone-induced memory impairment was monitored by novel object recognition test.
Values are mean±SD (n = 8). Data was analyzed by one-way ANOVA followed by Tukey’s post-hoc test. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group.
Fig 12.
Effect of pre- and post-administration of quercetin in rotenone-induced memory impairment was monitored by Morris water maze test.
Values are mean±SD (n = 8). Data was analyzed by one-way ANOVA followed by Tukey’s post-hoc test. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01, #p<0.05 as compared to Pre-Que+Rot group.
Fig 13.
Neurotransmitter levels following pre- and post- supplementation of quercetin in rotenone-injected rats were estimated by HPLC in (A,B) striatum, (C,D) hippocampus. Values are mean±SD (n = 8). Significant differences were obtained by one-way ANOVA following Tukey’s test. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group.
Fig 14.
Effect of pre- and post-supplementation of quercetin on striatal acetylcholinesterase (mmol/g/min) activity, acetylcholine (μmol/g) levels in rotenone-injected rats.
Values are mean±SD (n = 8) Significant differences were obtained by one-way ANOVA following Tukey’s test. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group.
Fig 15.
Effect of pre- and post-supplementation of quercetin on brain (A) malondialdehyde (μmol/g of brain tissue), reduced glutathione (nmol/g of brain tissue) levels and (B) antioxidant enzymes activity such as superoxide dismutase (U/g), catalase (μmol/min/g), and glutathione peroxidase (μmol/min/g) were also estimated. Values are mean±SD (n = 8). Significant differences were obtained by one-way ANOVA following Tukey’s test. **p<0.01 as compared to the control group; ++p<0.01 as compared to rotenone group; ##p<0.01 as compared to Pre-Que+Rot group.
Fig 16.
Summarized experimental findings showing inhibition of mitochondrial complex-I by rotenone causing the generation of reactive species and neuronal disruption.
Rotenone is also found to inhibit the activity of acetylcholinesterase (AChE) enzyme. Oxidative stress and reduced activity of AChE lead to imbalance DA-ACh and reduced serotonin levels resulting in motor and non-motor PD-like symptoms. Availability of quercetin, on the other hand, reduces the oxidative stress, and regulates AChE activity and thus helps in attenuation of rotenone-induced motor and non-motor symptoms of PD.