<p>Diabetes mellitus (DM) is a chronic metabolic disorder with substantial global health implications. This study investigated the therapeutic potential of <i>Bukiniczia cabulica</i> (Boiss.) Lincz. against hyperglycemia and pain-related conditions. The polyphenolic profile of the crude methanolic extract (Bc.Cme) was characterized using HPLC–DAD. Its inhibitory activity against α-glucosidase and α-amylase, along with the in-silico binding affinity of identified phytochemicals, was assessed through molecular docking. The anti-diabetic effects of Bc.Cme were evaluated in alloxan-induced diabetic mice, while its antinociceptive activity was tested using tonic visceral (acetic acid-induced writhing) and acute thermal nociception (hot-plate) models. Anti-neuropathic efficacy was further examined in vincristine- and streptozotocin (STZ)-induced peripheral neuropathy. Bc.Cme demonstrated strong enzyme inhibition, suppressing α-glucosidase activity by 87.23% at 1&#xa0;mg/ml and showing potent α-amylase inhibition (IC<sub>50</sub> = 29.53&#xa0;µg/ml). Docking analysis supported favorable interactions between major phenolic constituents and these enzymes. In vivo, Bc.Cme (150&#xa0;mg/kg) significantly reduced blood glucose levels over four weeks in alloxan-induced diabetic mice. In pain models, doses of 50–200&#xa0;mg/kg markedly decreased writhing responses and increased nociceptive latency. Additionally, Bc.Cme produced dose-dependent attenuation of static and cold allodynia, as well as heat hyperalgesia, in both vincristine- and STZ-induced neuropathy models. Overall, <i>B. cabulica</i> exhibits notable anti-diabetic, antinociceptive, and anti-neuropathic effects, likely mediated by its polyphenolic constituents through metabolic enzyme inhibition and modulation of pain pathways. The extract shows therapeutic promise for managing DM and its associated neuropathic complications.</p>

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Bukiniczia cabulica (Boiss.) Lincz. ameliorate diabetes-induced neuropathy: analgesic, anti-diabetic and anti-neuropathic using enzyme inhibitory, molecular docking and in-vivo studies

  • Zeeshan Ahmad,
  • Mushtaq Ahmad Mir,
  • Muhammad Shahid,
  • Nasreena Bashir,
  • Alam Zeb,
  • Mehreen Ghufran,
  • Falak Naz,
  • Muhammad Ayaz

摘要

Diabetes mellitus (DM) is a chronic metabolic disorder with substantial global health implications. This study investigated the therapeutic potential of Bukiniczia cabulica (Boiss.) Lincz. against hyperglycemia and pain-related conditions. The polyphenolic profile of the crude methanolic extract (Bc.Cme) was characterized using HPLC–DAD. Its inhibitory activity against α-glucosidase and α-amylase, along with the in-silico binding affinity of identified phytochemicals, was assessed through molecular docking. The anti-diabetic effects of Bc.Cme were evaluated in alloxan-induced diabetic mice, while its antinociceptive activity was tested using tonic visceral (acetic acid-induced writhing) and acute thermal nociception (hot-plate) models. Anti-neuropathic efficacy was further examined in vincristine- and streptozotocin (STZ)-induced peripheral neuropathy. Bc.Cme demonstrated strong enzyme inhibition, suppressing α-glucosidase activity by 87.23% at 1 mg/ml and showing potent α-amylase inhibition (IC50 = 29.53 µg/ml). Docking analysis supported favorable interactions between major phenolic constituents and these enzymes. In vivo, Bc.Cme (150 mg/kg) significantly reduced blood glucose levels over four weeks in alloxan-induced diabetic mice. In pain models, doses of 50–200 mg/kg markedly decreased writhing responses and increased nociceptive latency. Additionally, Bc.Cme produced dose-dependent attenuation of static and cold allodynia, as well as heat hyperalgesia, in both vincristine- and STZ-induced neuropathy models. Overall, B. cabulica exhibits notable anti-diabetic, antinociceptive, and anti-neuropathic effects, likely mediated by its polyphenolic constituents through metabolic enzyme inhibition and modulation of pain pathways. The extract shows therapeutic promise for managing DM and its associated neuropathic complications.