Objective To determine whether Corosolic acid (CA) targeting nuclear protein expression of Nrf2 activation can be used to attenuate renal damage and preserve renal function in alloxan diabetic mice. Methods A mouse model with diabetic nephropathy was established to examine the Nrf2 expression. Mice were randomly divided into control, diabetic control, and CA groups treated at 0.4 mg/kg, 2 mg/kg and 10 mg/kg p.o. for 8 weeks. Diabetes was induced in mice by single intraperitoneal injection of alloxan 200 mg/kg in all groups except the control. The mice with fasting blood glucose level over 200 mg/dL were considered as diabetic and were employed in the study. After 4th and 8th weeks, urine samples were collected (using metabolic cages) to measure protein and urea. Animals were euthanized, and serum samples were collected to estimate the glucose, creatinine, total protein, urea and blood urea nitrogen. Kidney was isolated at the end of experiment for histology to evaluate anti-oxidant parameters. Immunohistochemistry was performed to examine the Nrf2 expression. Results CA treatment showed dose dependent reduction in level of biochemical parameters in serum and urine. CA group (10 mg/kg) showed significantly higher body weight and reduced kidney weight. Histopathological examination revealed reduced inflammation, collagen deposition and glomerulosclerosis in renal tissue. CA attenuated renal dysfunction, oxidative stress and inflammatory pro-cytokine levels. Conclusions CA treatment exhibited ameliorative effect on kidney in mice with its enhanced Nrf2 expression.

Objective: To compare the cardioprotective efficacy of equimolar doses (50 mM/kg, p.o.) of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats. Methods: Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg. This study included four treatment groups of rats (n=6): the control group (0.5% carboxymethyl cellulose solution-treated), the doxorubicin- treated group (0.5% carboxymethyl cellulose solution along with doxorubicin), the genistein-treated group (50 mM/kg/day; p.o. along with doxorubicin) and phloretin-treated group (50 mM/kg/day; p.o. along with doxorubicin). On the 10th day of dosing, rats were anesthetized for recording ECG, mean arterial pressure, and left ventricular function. Oxidative stress, nitric oxide levels, and inflammatory cytokines were estimated in the cardiac tissue. Cardiac function parameters (creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase) were estimated in the serum samples. Results: Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats. Phloretin administration attenuated doxorubicin- induced alterations in hemodynamic parameters (heart rate, mean arterial blood pressure, and left ventricular function) and suppressed the expression of pro-inflammatory cytokines. The cardiac injury markers like creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase were reduced by both genistein and phloretin. All these effects of phloretin were more prominent than genistein. Conclusions: Phloretin offers cardioprotection that is comparable to genistein, a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity. Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

Objective: To investigate the effect of aloin against chronic constriction injury (CCI)-induced neuropathic pain in rats. Methods: Rats were randomly divided into 7 groups: Group I (normal control), Group II (sham-operated), Group III (CCI control) and Group IV, V, VI, and VII, which underwent CCI surgery and then were administered with aloin (5 mg/kg, p.o.; 25 mg/kg, p.o.; 125 mg/kg, p.o.) and gabapentin (50 mg/kg, p.o.), respectively for 14 days. Peripheral neuropathy was induced by silk ligatures (4-0) loosely placed around the sciatic nerve. Nociceptive thresholds against mechanical stimuli (Von-Frey filaments) and thermal stimuli (12 °C and 40 °C) were measured at mid-plantar paw region ipsilateral to the compressed nerve on day-3, 7, 11, and 14. The concentration of cytokines including tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β was estimated at day-7. At day 14, motor nerve conduction velocity was determined under urethane anesthesia (1.25 g/kg). Oxidative stress parameters (malondiadehyde, glutathione, catalase, and superoxide dismutase) were estimated in sciatic nerve homogenates at day 14. Representative nerve samples were processed for histological investigations. Results: Aloin significantly reduced CCI-induced mechanical and thermal allodynia. It also improved motor nerve conduction velocity and decreased oxidative stress in nerve tissues. In addition, it decreased pro-inflammatory cytokine levels and restored the histoarchitecture of compressed sciatic nerve. Conclusions: Aloin mitigates CCI-induced neuropathic pain in rats by inhibiting oxidative stress and pro-inflammatory cytokines in the afflicted sciatic nerve.