Hasan S. Yusufoglu

Diabetic polyneuropathy is characterized by structural abnormalities, oxidative stress, and neuroinflammation. The current study aimed to determine the antinociceptive effects of isoeugenol and eugenol and their combinations in neuropathic pain resulting from streptozotocin (STZ)-induced diabetes and neuroinflammation. Female SD rats were categorized into normal control, diabetic control, and treatment groups. On the 28th day and 45th day, behavioral studies (allodynia and hyperalgesia) were performed to analyze the development and protection of diabetic polyneuropathy. The levels of inflammatory and oxidative mediators, such as superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), catalase, reduced glutathione, and thiobarbituric acid reactive substances (TBARS), were estimated. In addition, the level of nerve growth factor (NGF) was estimated at the end of the study in different groups. The anti-NGF treatment decreased its upregulation in the dorsal root ganglion significantly. The results showed that isoeugenol, eugenol, and their combination have therapeutic potential against neuronal and oxidative damage induced by diabetes. In particular, both compounds significantly affected behavioral function in treated rats and showed neuroprotection against diabetic neuropathy, and their combination had synergistic effects.

Neuropathic pain, a prevalent concern associated with various pathological conditions, poses a significant public health risk due to its poorly understood pathophysiology and treatment complexities. Multimodal therapy is often the most efficacious approach to managing neuropathic pain, yet it is also highly labour intensive. The exact underlying causes of neuropathic pain are unclear; evidence suggests that cytokines, neuropeptides, and neurotrophic factors may play a role in its pathogenesis. The current study aimed to investigate the anti-neuropathic pain activity of caraway oil and the molecular mechanisms underlying its actions in rats with CCI, a model of neuropathic pain. Behavioural evaluations of cold allodynia, heat hyperalgesia, mechanical allodynia, and mechanical hyperalgesia were conducted using the acetone spray test, hot plate test, Von Frey hair test, and pinprick test, respectively. Additionally, the level of TNF-α in the sciatic nerve was examined as an indicator of inflammation, and NGF and substance P levels were determined in the DRG to identify mechanistic processes. Rats were administered caraway oil orally at doses of 25 and 50 mg/kg for 21 days. Results indicated that caraway oil administration significantly reduced behaviour associated with injury-related pain and elevated TNF levels. After an anti-NGF injection on the 21st day, significant attenuated behavioural effects were observed. Furthermore, caraway oil administration was able to inhibit the upregulation of NGF in DRG caused by CCI and minimize the increase in substance P in DRG. These findings suggest that caraway oil has promising therapeutic potential for managing neuropathic pain by targeting peripheral and secondary sensitization mechanisms.

Nine xanthone derivatives ( 1 – 9 ) were isolated from the roots of Polygala azizsancarii , which is a narrow endemic species for the flora of Türkiye. Based on all of the evidence, the structures of 1 – 9 were established as two previously undescribed xanthone O ‐glucosides, 3‐ O ‐ β ‐D‐glucopyranosyloxy‐1,6‐dihydroxy‐2,5,7‐trimethoxyxanthone ( 1 ), 3‐ O ‐ β ‐D‐glucopyranosyloxy‐1,6‐dihydroxy‐2,7‐dimethoxyxanthone ( 2 ), and seven previously described xanthones, 1,3,6‐trihydroxy‐2,5,7‐trimethoxyxanthone ( 3 ), 1,3,6‐trihydroxy‐2,7‐dimethoxyxanthone ( 4 ), 1,2,3,4,7‐pentamethoxyxanthone ( 5 ), 1,3‐dihydroxy‐2,5,6,7‐tetramethoxyxanthone ( 6 ), 1,3‐dihydroxy‐4,7‐dimethoxyxanthone ( 7 ), 1,7‐dihydroxy‐3‐methoxyxanthone ( 8 ), and 1,7‐dihydroxy‐2,3‐methylenedioxyxanthone ( 9 ). The structures of the compounds were determined by spectroscopic methods, including 1D‐NMR ( 1 H‐NMR, 13 C‐NMR, DEPT‐135), 2D‐NMR (COSY, NOESY, HSQC, HMBC, INADEQUATE), and HR‐MS. The solid‐state structures of 1 – 4 , including the absolute configurations of the stereogenic carbons of the sugar moiety in 1 and 2 , were established by X‐ray crystal‐structure analyses. For the newly described compounds, the trivial names sancarosides A ( 1 ) and B ( 2 ) are proposed.