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The comprehensive quantitative analysis of the flavonoid chemistry of Artemisia vulgaris L., a plant used as an emmenagogue in traditional medicine, is presented in conjunction with an evaluation of its estrogenic activity. Twenty known flavonoids were isolated and identified as tricine, jaceosidine, eupafolin, chrysoeriol, diosmetin, homoeriodictyol, isorhamnetin, apigenin, eriodictyol, luteolin, luteolin 7-glucoside, kaempferol 3-glucoside, kaempferol 7-glucoside, kaempferol 3-rhamnoside, kaempferol 3-rutinoside, quercetin 3-glucoside, quercetin 3-galactoside, quercetrin, rutin, and vitexin. The most abundant compounds were eriodictyol and luteolin. The estrogenic activity of all flavonoids was assayed by employing a reconstituted estrogen transcription unit in Saccharomyces cerevisiae transformed with both a human estrogen receptor expression plasmid and a reporter plasmid. Two flavonoids, eriodictyol and apigenin, were able to induce the transcription of the reporter gene in transgenic yeast. The transcriptional activity increased proportionally with increased amounts of purified eriodictyol or apigenin added to the yeast cells. Keywords: Artemisia vulgaris; estrogenic activity; estrogen transcriptional system in yeast; flavonoids; apigenin; eriodictyol; luteolin

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Lesion or disease of the somatosensory system leads to the development of neuropathic pain. Peripheral neuropathic pain encompasses damage or injury of the peripheral nervous system. On the other hand, 10–15% of individuals suffer from acute postoperative pain followed by persistent pain after undergoing surgeries. Antidepressants, anticonvulsants, baclofen, and clonidine are used to treat peripheral neuropathy, whereas opioids are used to treat postoperative pain. The negative effects associated with these drugs emphasize the search for alternative therapeutics with better efficacy and fewer side effects. Curcumin, a polyphenol isolated from the roots of Curcuma longa, possesses antibacterial, antioxidant, and anti-inflammatory properties. Furthermore, the low bioavailability and fast metabolism of curcumin have led to the advent of various curcumin formulations. The present review provides a comprehensive analysis on the effects of curcumin and its formulations in preclinical and clinical studies of neuropathic and postoperative pain. Based on the positive outcomes from both preclinical and clinical studies, curcumin holds the promise of mitigating or preventing neuropathic and postoperative pain conditions. However, more clinical studies with improved curcumin formulations are required to involve its use as adjuvant to neuropathic and postoperative drugs.

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Oxidative stress, resulting from an imbalance between the formation of damaging free radicals and availability of protective antioxidants, can contribute to peripheral neuropathic pain conditions. Reactive oxygen and nitrogen species, as well as products of the mitochondrial metabolism such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, are common free radicals. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is a transcription factor encoded by the NFE2L2 gene and is a member of the cap ‘n’ collar subfamily of basic region leucine zipper transcription factors. Under normal physiological conditions, Nrf2 remains bound to Kelch-like ECH-associated protein 1 in the cytoplasm that ultimately leads to proteasomal degradation. During peripheral neuropathy, Nrf2 can translocate to the nucleus, where it heterodimerizes with muscle aponeurosis fibromatosis proteins and binds to antioxidant response elements (AREs). It is becoming increasingly clear that the Nrf2 interaction with ARE leads to the transcription of several antioxidative enzymes that can ameliorate neuropathy and neuropathic pain in rodent models. Current evidence indicates that the antinociceptive effects of Nrf2 occur via reducing oxidative stress, neuroinflammation, and mitochondrial dysfunction. Here, we will summarize the preclinical evidence supporting the role of Nrf2 signaling pathways and Nrf2 inducers in alleviating peripheral neuropathic pain.

Background:Fruits are considered one of the richest sources of natural antioxidants. Their consumption has been linked to the prevention of oxidative stress-induced diseases.Objective:In this study, in vitro antioxidant activities of blueberry, jackfruit, blackberry, black raspberry, red raspberry, strawberry, and California table grape extracts were evaluated.Materials and Methods:Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), nitric oxide (NO), superoxide anion (O2−) scavenging assays, and ferric reducing power.Results:Black raspberry extract had the highest phenolic (965.6 ± 2.9 mg gallic acid equivalents [GAE]/g), flavonoid (186.4 ± 1.7 mg quercetin equivalents/g), and proanthocyanidin (2677 ± 71.1 mg GAE/g) contents. All fruit extracts exhibited increasing radical scavenging activities with increased concentrations. At 100 μg/ml, red raspberry extract showed the highest ferric reducing power (A700 =0.3 ± 0.0052) and FRAP activity (A593 =11.43 mM Fe2+/g). Black raspberry extract (100 μg/ml) exhibited the highest DPPH activity (A517 =89.03 ± 0.0471). Jackfruit extract (100 μg/ml) had the highest ABTS (A734 =35.6 ± 0.613), NO (A540 =81.7 ± 0.2), and O2− radical scavenging (A230 =55.5 ± 0.2) activities. Positive correlations were observed between IC50 values for different radical scavenging activities and different polyphenolics. Red raspberry extract had the highest Pearson's coefficient values (0.952–1) between total phenolics, flavonoids, and proanthocyanidins and DPPH and superoxide radical scavenging activities.Conclusions:The antioxidant rich fruits in this study are good source of functional food and nutraceuticals that have the potential to improve human health.SUMMARY All fruit extracts exhibited increasing radical scavenging activities with increased concentrationsBlack raspberry extract is enriched in total phenols, flavonoids, and proanthocyanidins and showed the highest 2,2-diphenyl-1-picrylhydrazyl scavenging activity and red raspberry extract showed the highest ferric reducing power and ferric reducing antioxidant potential activityJackfruit extract exhibited the highest 2,2′azino-bis (3-ethylbenzothiazoline-6-sulfonicacid) diammonium salt, nitric oxide, O2- scavenging activitiesPositive correlations were observed between IC50 values for different radical scavenging activities and different polyphenolics. Abbreviations Used: Abs: Absorbance, ABTS: 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, BHT: Butylated hydroxytoluene, DPPH: 2,2-diphenyl-1-picrylhydrazyl, DW: Dry weight, FRAP: Ferric reducing antioxidant potential, FW: Fresh weight, GAE: Gallic acid equivalents, NADH: β-nicotinamide adenine dinucleotide hydrate, NFL: The National Food Laboratories, NO: Nitric oxide, ONPG: ortho-nitrophenyl-β-galactoside, PBS: Phosphate buffered saline, PMS: Phenazine methosulfate, QE: Quercetin equivalents, ROS: Reactive oxygen ...