acteoside and Neuralgia

Verbascoside, a representative phenylethanoid glycoside, is widely distributed in plants and has various activities beneficial for human health. Although systemically administered verbascoside has an antinociceptive effect, little is known about the site and mechanism of its activity. The aim of the present study was to determine whether verbascoside attenuates neuropathic pain in the spinal cord and which pain regulatory systems are involved.. Chronic constriction injury of the sciatic nerve was introduced to male Sprague Dawley rats. The effects of intrathecal administration of verbascoside and its components (caffeic acid and hydroxytyrosol) on mechanical hyperalgesia and cold hyperalgesia were examined using the electronic von Frey test and cold-plate test, respectively. Several antagonists of spinal pain processing receptors were administered intrathecally to evaluate their effects on the antihyperalgesic action of verbascoside. A rotarod test was performed to assess the effects on motor coordination.. Verbascoside attenuated mechanical and cold hyperalgesia and affected motor performance in a dose-dependent manner. Caffeic acid suppressed hyperalgesia only at high doses, whereas hydroxytyrosol did not affect hyperalgesia. The inhibitory effects of verbascoside on hyperalgesia and motor coordination were reversed by naloxone, a µ-opioid receptor antagonist.. These findings imply that verbascoside exerts an antihyperalgesic effect by activating µ-opioid receptors in the spinal cord, and that neither caffeic acid nor hydroxytyrosol alone mediates its activity. Verbascoside shows promise for the treatment of neuropathic pain.. Currently available treatments for neuropathic pain have limited efficacy in most patients. Some natural products have favourable biological activities for long-term administration such as antioxidative and neuroprotective effects. Verbascoside inhibits spinal nociceptive transmission without serious side effects to the same degree as gabapentin, a first-line remedy for neuropathic pain. Natural products may be promising candidates for novel treatments of neuropathic pain.

Topics: Analgesics; Animals; Biological Products; Constriction; Disease Models, Animal; Glucosides; Humans; Hyperalgesia; Male; Neuralgia; Phenols; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Receptors, Opioid, mu

Chronic hyperalgesia and allodynia associated with progressive damage of peripheral neurons are the most prevalent complications of diabetes mellitus. Plants belonging to the family of Oleaceae were traditionally used in folk medicine for the management of diabetes.. The aim of this study was to investigate whether an aqueous extract from the leaves of Ligustrum vulgare (common privet) could be useful to target neuropathic pain in a rat streptozotocin (STZ) model of diabetes.. The chemical composition of the aqueous extract from privet leaf was characterized with the UHPLC-DAD-MS method and the analytical quantification of its constituents was performed with HPLC-DAD. Mechanical hyperalgesia and allodynia were evaluated with the Randall-Selitto and von Frey tests.. Our investigation revealed the presence of secoiridoids: oleacein (23.48 ± 0.87 mg/g), oleocanthal (8.44 ± 0.08 mg/g), oleuropein (1.50 ± 0.01 mg/g), as well as phenylpropanoids: echinacoside (6.46 ± 0.07 mg/g), verbascoside (4.03 ± 0.04 mg/g) and p-coumaroyl glucarates in the dried aqueous extract of privet leaves. Behavioral data indicated that chronic intraperitoneal administration of the extract (50-200 mg/kg) for 21 days resulted in a decrease in diabetes-induced hyperalgesia and allodynia. Blood glucose levels remained unaltered, while body weight and water intake decreased significantly.. The aqueous privet leaf extract could serve useful in facilitating treatment of painful diabetic neuropathy. Additionally, the study showed that the antihyperalgesic activity of Ligustrum vulgare leaf extract is not likely related to its antihyperglycemic properties.

Topics: Aldehydes; Animals; Chromatography, High Pressure Liquid; Cyclopentane Monoterpenes; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Glucosides; Glycosides; Hyperalgesia; Iridoid Glucosides; Iridoids; Ligustrum; Male; Neuralgia; Phenols; Plant Extracts; Plant Leaves; Rats; Streptozocin

Verbascoside (acteoside) possesses various pharmacological properties for human health, including antioxidant, anti-inflammatory, and antineoplastic properties in addition to numerous wound healing and neuroprotective properties, with an excellent and well-known safety profile. However, its poor chemical stability, due to hydrolysis, limits its use in the clinic. To overcome these limitations, we prepared unilamellar liposomal formulations of verbascoside for parenteral administration.Two formulations were prepared: V-L1 and V-L2, where V-L2 contains phospholipid and cholesterol about 4 times higher than the V-L1 sample, and about 2 times higher than verbascoside. The mean particle size of the liposomes prepared was found to be around 120 nm with a polydispersity index < 0.2. Encapsulation efficacy resulted in 30 %. A total of 82.28 ± 1.79 % of verbascoside was released from the liposomes within 24 hours. Liposomes ameliorate the stability of verbascoside by preventing its hydrolysis.The optimized drug delivery formulation was tested in the paw pressure test in two animal models of neuropathic pain: a peripheral mononeuropathy was produced either by a chronic constriction injury of the sciatic nerve or by an intra-articular injection of sodium monoiodoacetate. The performance of the liposomal formulation was compared with that of the free drug.For evaluating the paw pressure test in chronic constriction injury rats, a liposomal formulation administered i. p. at the dosage of 100 mg/kg showed a longer lasting antihyperalgesic effect in comparison with a 100-mg/kg verbascoside saline solution, as well as in the sodium monoiodoacetate models. The effect appeared 15 min after administration and persisted for up to 60 min.

Topics: Analgesics; Animals; Drug Delivery Systems; Drug Stability; Glucosides; Hyperalgesia; Liposomes; Mice; Neuralgia; Phenols; Rats; Rats, Sprague-Dawley

We examined the effects of verbascoside in rats subjected to chronic constriction injury (CCI). Verbascoside (50, 100, and 200 mg/kg, i.p.), was administered from the day of surgery for 14 days. Spinal cord levels of apoptotic factors and glia markers were quantified on days 3, 7, and 14 post-CCI. Oxidative stress markers were assessed on days 7 and 14. CCI rats exhibited a marked mechanical allodynia, cold allodynia, and thermal hyperalgesia on days 3, 5, 7, 10, and 14 post-CCI. A significant increase in the levels of Iba (a marker of microglia activation) and Bax (a proapoptotic factor) was observed on day 3. Iba remained high on day 7. In contrast, there were no differences in glial fibrillary acidic protein contents between sham and CCI animals. Malondialdehyde increased and reduced glutathione decreased on day 14. Verbascoside significantly attenuated behavioral changes associated with neuropathy. Bax decreased, while Bcl-2 was increased by verbascoside on day 3. Verbascoside also reduced Iba protein on days 3 and 7. The results support evidence that microglial activation, apoptotic factors, and oxidative stress may have a pivotal role in the neuropathic pain pathogenesis. It is suggested that antinociceptive effects elicited by verbascoside might be through the inhibition of microglia activation, apoptotic pathways, and antioxidant properties.

Topics: Analgesics; Animals; Apoptosis; bcl-2-Associated X Protein; Calcium-Binding Proteins; Constriction; Glial Fibrillary Acidic Protein; Glucosides; Glutathione; Hyperalgesia; Male; Malondialdehyde; Microfilament Proteins; Neuralgia; Neuroglia; Oxidative Stress; Phenols; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Spinal Cord

This study reports on the rapid isolation of verbascoside from Lippia citriodora H.B.K. (Verbenaceae), an inexpensive and widespread source, and the evaluation of its antihyperalgesic activity.. Isolation of verbascoside was achieved by size exclusion chromatography with Sephadex LH-20 eluting with 50% EtOH, which is proposed as a fast and efficient method of separation.. The antihyperalgesic activity of verbascoside was tested by in-vivo assay using the paw-pressure test in two animal models of neuropathic pain: a peripheral mononeuropathy produced either by a chronic constriction injury of the sciatic nerve (CCI) or by an intra-articular injection of sodium monoiodoacetate (MIA).. Verbascoside administered intraperitoneally at a dose of 100 mg/kg reverted the mechanical hyperalgesia in both CCI and MIA treated rats, as evaluated in the paw-pressure test. Verbascoside was also effective against mechanical hyperalgesia after oral administration at doses of 300 and 600 mg/kg.

Topics: Administration, Oral; Analgesics; Animals; Disease Models, Animal; Drugs, Chinese Herbal; Glucosides; Hyperalgesia; Injections, Intraperitoneal; Iodoacetates; Lippia; Male; Neuralgia; Phenols; Phytotherapy; Rats; Rats, Sprague-Dawley; Rotarod Performance Test; Sciatic Nerve