Supriya Sharma1, Pallavi Sharma1, Pankaj Kulurkar2, Damanpreet Singh1, Dinesh Kumar3, Vikram Patial4. 1. Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India. 2. Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India. 3. Natural Products Chemistry and Process Development Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India. Electronic address: dineshkumar@ihbt.res.in. 4. Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India. Electronic address: vikrampatial@ihbt.res.in.
Abstract
BACKGROUND: Picrorhiza kurroa Royle (Scrophulariaceae) is an important medicinal herb being widely used in variety of ailments. PURPOSE: The present study was envisaged to evaluate the effects of iridoid glycosides enriched fraction (IGs) from Picrorhiza kurroa rhizome against cyclophosphamide (CP) -induced renal toxicity and peripheral neuropathy. METHODS: Mice in different groups were pretreated with 25, 50 and 100 mg/kg; p.o. doses of IGs for 21 days, followed by cyclophosphamide intoxication for consecutive two days. Further, to identify the putative role of PPAR-γ receptors for the protective effect of IGs, an additional group of mice were pretreated with PPAR-γ antagonist BADGE (5 mg/kg; i.p.) followed by IGs (100 mg/kg; p.o.) for 21 days before CP intoxication. RESULTS: IGs pretreatment decreased the hyperalgesic responses toward acetone and heat in acetone drop and tail immersion tests. The abolition of intramyelin odema, cytoplasmic vacuolization and axonal degeneration of sciatic nerve were observed in IGs pretreated mice in a dose-dependent manner. IGs treatment also attenuated the altered serum biochemical markers for renal injury. Furthermore, the treatment prevented renal tubular swelling, granular degeneration and glomerular damage. The levels of IL-1β and TNFα in different group revealed the anti-inflammatory effect of IGs, which was further confirmed by improvement in altered expressions of NF-kB in kidney and sciatic serve. Bax/Bcl-2 expressions and caspase 3/9 activity in renal tissues showed the anti-apoptotic effect of IGs. IGs pretreatment also improved the PPAR-γ expression in the kidney tissues. All the observed protective effects of IGs were suppressed after pretreatment with BADGE. CONCLUSION: Present study concludes that IGs from Picrorhiza kurroa attenuates CP-induced renal toxicity and peripheral neuropathy via PPAR-γ -mediated pathways.
BACKGROUND: Picrorhiza kurroa Royle (Scrophulariaceae) is an important medicinal herb being widely used in variety of ailments. PURPOSE: The present study was envisaged to evaluate the effects of iridoid glycosides enriched fraction (IGs) from Picrorhiza kurroa rhizome against cyclophosphamide (CP) -induced renal toxicity and peripheral neuropathy. METHODS:Mice in different groups were pretreated with 25, 50 and 100 mg/kg; p.o. doses of IGs for 21 days, followed by cyclophosphamide intoxication for consecutive two days. Further, to identify the putative role of PPAR-γ receptors for the protective effect of IGs, an additional group of mice were pretreated with PPAR-γ antagonist BADGE (5 mg/kg; i.p.) followed by IGs (100 mg/kg; p.o.) for 21 days before CP intoxication. RESULTS: IGs pretreatment decreased the hyperalgesic responses toward acetone and heat in acetone drop and tail immersion tests. The abolition of intramyelin odema, cytoplasmic vacuolization and axonal degeneration of sciatic nerve were observed in IGs pretreated mice in a dose-dependent manner. IGs treatment also attenuated the altered serum biochemical markers for renal injury. Furthermore, the treatment prevented renal tubular swelling, granular degeneration and glomerular damage. The levels of IL-1β and TNFα in different group revealed the anti-inflammatory effect of IGs, which was further confirmed by improvement in altered expressions of NF-kB in kidney and sciatic serve. Bax/Bcl-2 expressions and caspase 3/9 activity in renal tissues showed the anti-apoptotic effect of IGs. IGs pretreatment also improved the PPAR-γ expression in the kidney tissues. All the observed protective effects of IGs were suppressed after pretreatment with BADGE. CONCLUSION: Present study concludes that IGs from Picrorhiza kurroa attenuates CP-induced renal toxicity and peripheral neuropathy via PPAR-γ -mediated pathways.
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