Antinociceptive, Anti‐Hyperalgesia and Antiallodynic Activities of Polyphenol Rich Extract fromShorea roxburghiiagainst Cyclophosphamide Induced Peripheral Neuropathy

Abstract

Cyclophosphamide (CYP) is a widely used antineoplastic and immunosuppressive drug, however, despite its efficacy, it has shown extensive multiple organ toxicities, including peripheral neuropathy which significantly affects the quality of life of cancer patients. This study elucidated the protective properties of Shorea roxburghii polyphenol extract (SLPE) in CYP‐induced peripheral neuropathy. Rats were treated with SLPE (100 and 400 mg/kg) for five weeks plus CYP once a week from the second week of SLPE treatment. Using UHPLC‐QTOF‐MS, 54 polyphenolic compounds were identified in SLPE extract. After the treatment period the antinociceptive, anti‐hyperalgesia and antiallodynic effects was evaluated using formalin paw edema, acetic acid abdominal writhing, hot plate, tail immersion and von Frey filament tests. While the locomotive and motor coordination effects were evaluated by open field and rotarod tests. The administration of CYP led to significant increases in mechanical and thermal hyperalgesia, in addition to hyper‐nociceptive responses in the formalin and acetic acid writhing tests. CYP also significantly reduced locomotive activity and motor coordination. SLPE significantly protected against CYP‐induced mechanical and thermal hyperalgesia. Furthermore, SLPE displayed robust antinociceptive effect by counteracting formalin and acetic acid induced hyper‐nociception. In addition, SLPE increased the locomotive activity as well as the grip and motor coordination of the CYP treated rats. In conclusion, these results revealed the protective effects of SLPE against CYP‐induced peripheral neuropathy and could be an effective therapeutic remedy for chemotherapy induced peripheral neuropathy.

Protective Effects of Shorea roxburghii Phenolic Extract on Nephrotoxicity Induced by Cyclophosphamide: Impact on Oxidative Stress, Biochemical and Histopathological Alterations

“…[33 -34] In this study, the antioxidant, anti-inflammatory and renoprotective activities of SRPF may be attributed to the existence of several polyphenolic compounds in SRFR, including phenolic acids such as gallic acid, coumaric acid, fertaric acid; flavonoids such as apigenin, myricetin, luteolin and epicatechin; flavonoid glycosides such as hyperoside, miquelianin and kaempferol-3-rhamnoside; as well as stilbenoids such as resveratrol, viniferin, vitisifuran B and foeniculoside I, among several others, which was previously reported in our earlier study. [13] These compounds have strong antioxidants and anti-inflammatory effects along with other wide range of bioactivities that supported the nephroprotective properties of S. roxburghii. [35 -38] The results obtained from this study corroborated with previous reports obtained from S. roxburghii.…”

“…This result corroborated with earlier reports on the antioxidant efficacy of SRPF. [13,15] In addition to oxidative stress, inflammation and apoptosis characterized by increase in proinflammatory cytokines (IL-6, IL-1β and TNF-α), NF-кB, and caspase 3 levels are prevalent features associated with CTX induced renal damage. [9,25] NF-кB is a vital inflammatory transcription factor that rapidly responds to various stimulus after its phosphorylation and degradation from IкB protein.…”

“…[12,15] Furthermore, S. roxburghii polyphenols was reported to be effective against CTX-induced peripheral neuropathy via modulation of oxidative stress and inflammation. [13] However, the protective role of S. roxburghii against CTX-mediated nephrotoxicity is unknown. As such, this study investigated the nephroprotective effects of the polyphenolic rich fraction of S. roxburghii against CTX-induced nephrotoxicity in rats.…”

“…Earlier studies have highlighted the hepatoprotective and gonado‐protective effects of S. roxburghii [12,15] . Furthermore, S. roxburghii polyphenols was reported to be effective against CTX‐induced peripheral neuropathy via modulation of oxidative stress and inflammation [13] . However, the protective role of S. roxburghii against CTX‐mediated nephrotoxicity is unknown.…”

Unravelling the Protective Effects of Emodin Against Cyclophosphamide Induced Gonadotoxicity in Male Wistar Rats

“…The concentration of CP and EMD used in this study was based on earlier studies. 24–26 At the end of the experiment, the rats were all anesthetised using thiopental sodium and blood were directly taken via cardiac puncture. The serum obtained from the whole blood after centrifugation was used for analysing reproductive hormones levels including testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH).…”