Iridoid glycosides fraction from Picrorhiza kurroa attenuates cyclophosphamide-induced renal toxicity and peripheral neuropathy via PPAR-γ mediated inhibition of inflammation and apoptosis

Phytomedicine ◽  
2017 ◽  
Vol 36 ◽  
pp. 108-117 ◽  
Author(s):  
Supriya Sharma ◽  
Pallavi Sharma ◽  
Pankaj Kulurkar ◽  
Damanpreet Singh ◽  
Dinesh Kumar ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Renal Toxicity ◽  
Iridoid Glycosides ◽  
Picrorhiza Kurroa ◽  
Ppar Γ

scholarly journals Gentiopicroside Ameliorates Diabetic Peripheral Neuropathy by Modulating PPAR- Γ/AMPK/ACC Signaling Pathway

2018 ◽  
Vol 50 (2) ◽  
pp. 585-596 ◽  
Author(s):  
Yi Lu ◽  
Jiayin Yao ◽  
Chulian Gong ◽  
Bao Wang ◽  
Piao Zhou ◽  
...  
Keyword(s):  
Blood Flow ◽  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
Conduction Velocity ◽  
Nerve Conduction ◽  
Diabetic Peripheral Neuropathy ◽  
Nerve Conduction Velocity ◽  
Nerve Blood Flow ◽  
Ppar Γ ◽  
Compound C

Background/Aims: Gentiopicroside is promising as an important secoiridoid compound against pain. The present study aimed to investigate the analgesic effect and the probable mechanism of Gentiopicroside on Diabetic Peripheral Neuropathy (DPN), and to figure out the association among Gentiopicroside, dyslipidemia and PPAR- γ/AMPK/ACC signaling pathway. Methods: DPN rat models were established by streptozotocin and RSC96 cells were cultured. Hot, cold and mechanical tactile allodynia were conducted. Blood lipids, nerve blood flow, Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity (SNCV) were detected. Gene and protein expression of PPAR- γ/AMPK/ACC pathway was analyzed by reverse transcription-quan titative polymerase chain reaction (RT-qPCR) and Westernblot. Besides, PPAR-γ antagonist GW9662 and agonist rosiglitazone, AMPK antagonist compound C and activator AICAR as well as ACC inhibitor TOFA were used to further confirm the relationship between PPAR-γ and AMPK. Results: The results demonstrated that Gentiopicroside markedly ameliorated hyperalgesia with prolonged paw withdrawal latency to heat and cold stimuli and fewer responses to mechanical allodynia compared with DPN model group. Gentiopicroside regulated dyslipidemia, enhanced nerve blood flow and improved MNCV as well as SNCV. Gentiopicroside suppressed ACC expression through the activation of AMPK and PPAR-γ mediated the activation of AMPK and subsequent inhibition of ACC expression. Conclusion: In conclusion, the present study demon strated that Gentiopicroside exerted nerve-protective effect and attenuated experimental DPN by restoring dyslipidmia and improved nerve blood flow through regulating PPAR-γ/AMPK/ACC signal pathway. These results provided a promising potential treatment of DPN.

Acylated iridoid glycosides with hyaluronidase inhibitory activity from the rhizomes of Picrorhiza kurroa Royle ex Benth

2020 ◽  
Vol 169 ◽  
pp. 112185 ◽  
Author(s):  
Toshio Morikawa ◽  
Yusuke Nakanishi ◽  
Naoki Inoue ◽  
Yoshiaki Manse ◽  
Hideyuki Matsuura ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Iridoid Glycosides ◽  
Picrorhiza Kurroa

Bis-iridoid and iridoid glycosides: Viral protein R inhibitors from Picrorhiza kurroa collected in Myanmar

Fitoterapia ◽  
2019 ◽  
Vol 134 ◽  
pp. 101-107 ◽  
Author(s):  
Nwet Nwet Win ◽  
Takeshi Kodama ◽  
Khine Zar Wynn Lae ◽  
Yi Yi Win ◽  
Hla Ngwe ◽  
...  
Keyword(s):  
Viral Protein ◽  
Iridoid Glycosides ◽  
Picrorhiza Kurroa ◽  
Viral Protein R

scholarly journals Nuclear PPAR-γ Activation Modulates Inflammation and Oxidative Stress in Attenuating Chemotherapy-Induced Neuropathic Pain in Vivo

2021 ◽  
pp. 167-179
Author(s):  
Haritha Pasupulati ◽  
Satyanarayana S. V. Padi ◽  
Sujatha Dodoala ◽  
Prasad V. S. R. G. Koganti
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Mechanical Allodynia ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Ppar Γ ◽  
Markers Of Inflammation ◽  
And Oxidative Stress

Background: Paclitaxel-induced painful neuropathy is a major dose-limiting side effect and can persist for up to two years after completing treatment that greatly affects both the course of chemotherapy and quality of life in cancer patients. Peroxisome proliferator-activated receptor (PPAR)-γ belongs to a family of nuclear receptors known for their transcriptional and regulatory roles in metabolism, inflammation, and oxidative stress. However, the role of PPAR-γ activation on paclitaxel-induced neuropathic pain is not yet known. Objective: To investigate whether pioglitazone, a PPAR-γ agonist reduce paclitaxel-induced neuropathic pain and to elucidate underlying mechanisms. Methodology: Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and nitroso-oxidative stress were estimated. Results: Pioglitazone did not induce hypoalgesia and had no effect on locomotor activity. Repeated oral administration of pioglitazone (10 and 20 mg/kg,) for 2 weeks started 14 days after paclitaxel injection markedly attenuated paw withdrawal responses to thermal (hyperalgesia) and mechanical (allodynia) stimuli. Further, pioglitazone administration significantly reduced elevated level of pro-inflammatory cytokine, TNF-α, in both the dorsal root ganglia and the spinal cord accompanied by marked decrease in oxidative stress parameters as well as increase in activity of antioxidant defense enzyme, superoxide dismutase, in the spinal cord after paclitaxel injection. Conclusion: The results of the present study demonstrate that pioglitazone, a PPAR-γ agonist exerted antinociceptive effect in paclitaxel-induced neuropathic pain through inhibiting neuroimmune inflammation in both the periphery and spinal cord and by reducing nitroso-oxidative stress in spinal cord. Our findings strongly suggest pharmacological activation of PPAR-g as a promising therapeutic target in paclitaxel-induced peripheral neuropathy and provide rationale for the clinical evaluation.

scholarly journals Ameliorative Effect of Berberine on Neonatally Induced Type 2 Diabetic Neuropathy via Modulation of BDNF, IGF-1, PPAR-γ, and AMPK Expressions

Dose-Response ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 155932581986244 ◽  
Author(s):  
Guangju Zhou ◽  
Mingzhu Yan ◽  
Gang Guo ◽  
Nanwei Tong
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Peripheral Neuropathy ◽  
Sciatic Nerve ◽  
Nitrosative Stress ◽  
Ppar Γ ◽  
Tnf Α ◽  
Protein Expressions

Neonatal-streptozotocin (n-STZ)-induced diabetes mimics most of the clinicopathological symptoms of type 2 diabetes mellitus (T2DM) peripheral neuropathy. Berberine, a plant alkaloid, is reported to have antidiabetic, antioxidant, anti-inflammatory, and neuroprotective potential. The aim of the present study was to investigate the potential of berberine against n-STZ-induced painful diabetic peripheral polyneuropathy by assessing various biochemical, electrophysiological, morphological, and ultrastructural studies. Type 2 diabetes mellitus was produced neonatal at the age of 2 days (10-12 g) by STZ (90 mg/kg intraperitoneal). After confirmation of neuropathy at 6 weeks, rats were treated with berberine (10, 20, and 40 mg/kg). Administration of n-STZ resulted in T2DM-induced neuropathic pain reflected by a significant alterations ( P < .05) in hyperalgesia, allodynia, and motor as well as sensory nerve conduction velocities whereas berberine (20 and 40 mg/kg) treatment significantly attenuated ( P < .05) these alterations. Berberine treatment significantly inhibited ( P < .05) STZ-induced alterations in aldose reductase, glycated hemoglobin, serum insulin, hepatic cholesterol, and triglyceride levels. The elevated oxido-nitrosative stress and decreased Na-K-ATPase and pulse Ox levels were significantly attenuated ( P < .05) by berberine. It also significantly downregulated ( P < .05) neural tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 messenger RNA (mRNA), and protein expressions both. Streptozotocin-induced downregulated mRNA expressions of brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), and peroxisome proliferator-activated receptors-γ (PPAR-γ) in sciatic nerve were significantly upregulated ( P < .05) by berberine. Western blot analysis revealed that STZ-induced alterations in adenosine monophosphate protein kinase (AMPK; Thr-172) and protein phosphatase 2C-α protein expressions in dorsal root ganglia were inhibited by berberine. It also attenuated histological and ultrastructural alterations induced in sciatic nerve by STZ. In conclusion, berberine exerts its neuroprotective effect against n-STZ-induced diabetic peripheral neuropathy via modulation of pro-inflammatory cytokines (TNF α, IL-1β, and IL-6), oxido-nitrosative stress, BDNF, IGF-1, PPAR-γ, and AMPK expression to ameliorate impaired allodynia, hyperalgesia, and nerve conduction velocity during T2DM.

Advances in Ethnobotany, Synthetic Phytochemistry and Pharmacology of Endangered Herb Picrorhiza kurroa (Kutki): A comprehensive review (2010-2020)

2021 ◽  
Vol 21 ◽  
Author(s):  
Sharuti Mehta ◽  
Anil Kumar Sharma ◽  
Rajesh K. Singh
Keyword(s):  
Iridoid Glycosides ◽  
Review Article ◽  
Bioactive Metabolites ◽  
Future Research ◽  
Picrorhiza Kurroa ◽  
Bioactive Constituents ◽  
Active Metabolites ◽  
Natural Habitats ◽  
Picroside Ii ◽  
Endangered Status

: Picrorhiza kurroa Royle ex Benth. (Family: Plantaginaceae) is a well-recognized an Ayurvedic herb. It is commonly called “Kutki” or “Kurro” and ‘Indian gentian’. Iridoid glycosides are the plant’s bioactive constituents and accountable for the bitter taste and medicinal properties of the plant. The iridoid glycosides such as picrosides and other active metabolites of the plant exhibited many pharmacological activities like hepatoprotective, antioxidant, anti-inflammatory, anticancer, immunomodulator, anti-ulcerative colitis, antimicrobial etc. This review aims to provide updated information on the ethnobotany, synthetic phytochemistry, pharmacological potential, safety and toxicology of P. kurroa and its active metabolites. Indiscriminate exploitation, ecological destruction of natural habitats, slower plant growth and unawareness regarding cultivation and uprooting of plants has brought kutki as an endangered status. So, various techniques used for the conservation and production of bioactive metabolites from P. kurroa have also been reported. Information on the plant has been collected from Science Direct, Google Scholar, PubMed, Scopus by using ‘Picrorhiza kurroa’, ‘Picroside-‘, ‘Picroside-II’, ‘Picroliv’, ‘Immunomodulator’ keywords. All studies on ethnobotany, phytochemistry and pharmacology of plant from 2010- 2020 were comprised in this review article. The possible directions for the future research have also been outlined in brief in review article.

scholarly journals Cisplatin-induced renal toxicity: possible reversal by N-acetylcysteine treatment.

1997 ◽  
Vol 8 (10) ◽  
pp. 1640-1644 ◽  
Author(s):  
D Sheikh-Hamad ◽  
K Timmins ◽  
Z Jalali
Keyword(s):  
Renal Failure ◽  
Peripheral Neuropathy ◽  
Renal Insufficiency ◽  
Renal Toxicity ◽  
Therapeutic Trial ◽  
Tubular Dysfunction ◽  
Cisplatin Nephrotoxicity ◽  
Oliguric Renal Failure

Cisplatin administration is frequently associated with renal insufficiency and tubular dysfunction. In this article, a case of massive cisplatin overdose as a result of an accidental substitution for carboplatin is reported. The patient developed oliguric renal failure, hepatotoxicity, ototoxicity, peripheral neuropathy, blindness, and severe myelosuppression. A therapeutic trial with N-acetylcysteine to reverse renal toxicity was attempted. This article reviews the literature on cisplatin nephrotoxicity, with an emphasis on possible mechanisms involved, and suggests therapy for its modification.

A Pilot Study on the Effect of Acetyl-L-Carnitine in Paclitaxel-And Cisplatin-Induced Peripheral Neuropathy

2005 ◽  
Vol 91 (2) ◽  
pp. 135-138 ◽  
Author(s):  
Antonio Maestri ◽  
Adolfo De Pasquale Ceratti ◽  
Sante Cundari ◽  
Claudio Zanna ◽  
Enrico Cortesi ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Exploratory Study ◽  
Renal Toxicity ◽  
Chemotherapeutic Agents ◽  
Bone Marrow Suppression ◽  
Antitumor Therapy ◽  
Therapy Discontinuation ◽  
Double Blind ◽  
Who Grade ◽  
Regimen Modification

Aims and background In addition to bone marrow suppression and renal toxicity, neurotoxicity is a commonly occurring side effect of widely used chemotherapeutic agents like taxanes, cisplatin and vinca alkaloids. Neurotoxicity can cause antitumor therapy discontinuation or dose regimen modification. The aim of the present exploratory study was to investigate the activity of acetyl-L-carnitine in reversing peripheral neuropathy in patients with chemotherapy-induced peripheral neuropathy. Methods and study design Twenty-seven patients (16 males and 11 females) with paclitaxel and/or cisplatin-induced neuropathy (according to WHO recommendations for the grading of acute and subacute toxic effects) were enrolled. Patients received at least one cisplatin- (n = 5) or one paclitaxel- (n = 11) based regimen, or a combination of both (n = 11). Patients with chemotherapy-induced peripheral neuropathy were treated with acetyl-L-carnitine 1 g/die iv infusion over 1-2 h for at least 10 days. Results Twenty-six patients were evaluated for response having completed at least 10 days of acetyl-L-carnitine therapy (median, 14 days; range, 10-20). At least one WHO grade improvement in the peripheral neuropathy severity was shown in 73% of the patients. A case of insomnia related to ALC treatment was reported in one patient. Acetyl-L-carnitine seems to be an effective and well-tolerated agent for the treatment of chemotherapy-induced peripheral neuropathy. Conclusions Our preliminary results should be confirmed in double-blind, placebo controlled studies.

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