Evidence-Based Comparison of Physical Therapists and Traditional Healers: Distinguishing Science from Quackery.

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Use of kersetin and fisetin flavonoids in combination with pregabalin and gabapentin in the treatment of neuropathic pain.

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.

Examination of the effects of vitexin and vitexin-loaded solid lipid nanoparticles on neuropathic pain and possible mechanisms of action.

This research aims to investigate the possible antiallodynic and antihyperalgesic effects of pure vitexin and vitexin-loaded solid lipid nanoparticles (SLN) on neuropathic pain and the pathways mediating these effects. Chronic constriction nerve injury was induced in female rats, and the effects of vitexin at the doses of 5, 10, 20, 40 mg/kg were evaluated. Ketanserin, ondansetron, WAY-100635, yohimbine and bicuculin, which are antagonists of receptors on pain pathways. were used to examine the mechanisms of the effects of vitexin. Pure vitexin exhibited antiallodynic activity at all administered doses, whereas antihyperalgesic activity was not observed at 5 mg/kg vitexin dose. SLN formulation was prepared with 5 mg/kg vitexin, the lowest dose. Vitexin-loaded formulation significantly increased antiallodynic and antihyperalgesic effects. Ondansetron, WAY-100635, yohimbine, and bicuculine antagonized the antiallodynic and antihyperalgesic effects of vitexin. So, it was concluded that serotonin (5-hydroxtryptamine, 5-HT) receptor subtypes 5-HT3 and 5-HT1A, alpha-2 adrenergic, and γ-Aminobutyric acid type A (GABA-A) receptors are involved in the antiallodynic and antihyperalgesic activity of vitexin. In conclusion, vitexin and vitexin-loaded formulation have the potential for clinical use in neuropathic pain management, and different pain pathways contributed to this effect. And also, it is thought that vitexin-loaded SLN formulation is more effective than pure vitexin, which will provide an advantage in treatment.

Design, Synthesis, and In Vivo Evaluation of a New Series of Indole-Chalcone Hybrids as Analgesic and Anti-Inflammatory Agents.

Indole-chalcone hybrids have burst into prominence as potent weapons in the battle against pain and inflammation due to their unique features, allowing these ligands to form pivotal interactions with biological targets. In this context, the base-catalyzed Claisen-Schmidt condensation of 3',4'-(methylenedioxy)acetophenone with heteroaromatic aldehydes carrying an indole scaffold yielded new chalcones (1-7). The central and peripheral antinociceptive activities of all chalcones (compounds 1-7) at the dose of 10 mg/kg (i.p.) were evaluated by hot plate (supraspinal response), tail immersion (spinal response), and acetic acid-induced writhing tests in mice. The anti-inflammatory activities of compounds 1-7 were also investigated by means of a carrageenan-induced mouse paw edema model. The results revealed that compounds 1-7 extended the latency of response to thermal stimulus significantly in a hot-plate test similar to dipyrone (300 mg/kg; i.p.), the positive control drug. However, only compounds 2-7 were found to be significantly effective in the tail-immersion test. Compounds 1-7 also significantly showed analgesic effect by reducing the number of writhes and anti-inflammatory activity by inhibiting edema formation at different time intervals and levels. 1-(1,3-Benzodioxol-5-yl)-3-(1-methyl-1H-indol-2-yl)prop-2-en-1-one (4) drew attention by providing the highest efficacy results in both acute analgesia and inflammation models. Based on the in silico data acquired from the QikProp module, compound 4 was predicted to possess favorable oral bioavailability and drug-like properties. Taken together, it can be concluded that chalcones (1-7), especially compound 4, are outstanding candidates for further research to investigate their potential use in the management of pain and inflammation.

Antinociception Induced by Moringa Stenopetela (Baker f.) Cufod. Leaves Extract and Possible Mechanisms of Action

Moringa stenopetala (Baker f.) Cufod., is an endemic species growing in the south of Ethiopia. M. stenopetala is often consumed as food and used in traditional medicine and it has also been traditionally used for relieving of pain in Ethiopia. This study aimed to investigate the antinociceptive effect and mechanisms of action of M. stenopetala leaves methanol extract in mice. The per-oral doses of 50, 100, and 200 mg/kg of M. stenopetala extract were tested for antinociceptive action by using hot-plate, tail-immersion, and writhing tests. The possible mechanisms of in the antinociceptive action were investigated by pre-treatment with 5 mg/kg naloxone (non-selective opioid antagonist), 1 mg/kg ketanserin (5-HT2A/2C receptor antagonist), and 1 mg/kg yohimbine (α2 adrenoceptor antagonist). The methanol extract of M. stenopetala showed antinociceptive effect in all tests. The significant involvement of 5-HT2A/2C receptors and α2 adrenoceptors in antinociception induced by M. stenopetala extract in the hot-plate and tail-immersion tests, as well as significant contribution of opioid receptors and α2 adrenoceptors in writhing test, were identified. In conclusion, these findings demonstrate that the methanol extract of M. stenopetala has potential in pain management. Thisstudywillcontributetonewtherapeuticapproachesandprovideguidancefornewdrug development studies.

Hypoglycemic activity of Capparis ovata desf. var. palaestina zoh. methanol extract

Caper (Capparis ovata Desf. and Capparis spinosa L.) is naturally widespread in Turkey. Traditionally, buds, fruits, seeds and roots of this plant are used as tonic, diuretic, anti-rheumatic, expectorant, antidiabetic, and antifungal. The aim of this study is to evaluate potential hypoglycemic effect of C. ovata var. palaestina extracts in alloxan-induced diabetic mice. For this purpose; diabetic mice were administered with 100, 300, 500 mg/kg (i.p.) doses of methanol extract of bud and fruit. Blood glucose levels were screened 60, 120, 240 and 360 min. after treatment. Furthermore, high resolution mass spectrometry (HRMS) analysis, ABTS and DPPH free radical scavenging activity test, and phenolic and flavonoid compounds analysis of extracts were carried out. The data obtained from in vivo study revealed that fruit-methanol 500 mg/kg (FM3), bud-methanol 300 mg/kg (BM2), bud-methanol 500 mg/kg (BM3) extracts showed significant hypoglycemic activity. All extracts indicated significant antioxidant activity, however bud-methanol (BM) extract demonstrated the most potent antioxidant activity. Moreover high levels of phenolic substances and flavonoids were involved in all extracts, but the highest levels were found in FM extract. HRMS study showed that rutin, quercetin 3-O-glucoside (isoquercitrin) and stachydrine substances had seen in BM extract. The results of this study showed that the C. ovata var. palaestina extracts which, indicate hypoglycemic, antioxidant activities, might provide additional support in diabetes.