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Antinociceptive effect of Valeriana fauriei regulates BDNF signaling in an animal model of fibromyalgia
Abstract
The genus Valeriana has been widely used in popular medicine for centuries, to treat sleep disorders, anxiety, epilepsy and insomnia. Recent studies have focused on the novel pharmacological effects of Valeriana fauriei Briq. (VF) species. Previous studies have attempted to determine the pharmacological functions of Valeriana in various human diseases, particularly with regards to its neuroprotective effects, and its ability to reduce pain and stress. The present study constructed an animal model of fibromyalgia (FM), which was induced by intermittent cold stress with slight modification. Subsequently, the study aimed to determine whether VF exerts antinociceptive effects on the FM‑like model following oral administration of VF extracts. The effects of VF extracts on the FM model were investigated by analyzing behavioral activity, including pain, and detecting protein expression. In the behavioral analysis, the results of a nociception assay indicated that the pain threshold was significantly decreased in the FM group. Subsequently, western blotting and immunohistochemical analyses of the hippocampus demonstrated that the protein expression levels of brain‑derived neurotrophic factor (BDNF) and phosphorylated‑cAMP response element‑binding protein were downregulated in the FM group. Conversely, VF restored these levels. These results suggested that the effects of VF extract on a model of FM may be associated with its modulatory effects on the BDNF signaling pathway in the hippocampus and medial prefrontal cortex. In conclusion, the mechanism underlying the protective effects of VF as a therapeutic agent against FM may involve the BDNF signaling pathway.
... 21 We have recently reported that ethanol extract of VF exerts antinociceptive effect by regulating BDNF signaling in an animal model of fibromyalgia. 22 The ethanol extract of VF can also downregulate several proteins (Lasp1, Dpysl2, Dlg4, and Nefm) in the prefrontal cortex of the offspring of prenatally stressed rats, suggesting that VF might be able to decrease the incidence of prenatal stress-related psychiatric disorders such as depression and schizophrenia. 23 However, the role of VF extract's antioxidant and anti-inflammatory activities in depression-like behaviors or its molecular mechanisms is not well understood yet. ...
... 36 VF extract can increase BDNF expression in an animal model of fibromyalgia. 22 Therefore, we evaluated whether VF extract might exert beneficial effects on BDNF expression in brain of CRS-induced mouse. Based on western blot analysis, protein levels of BDNF were significantly decreased in the prefrontal cortex (60.1% -13.8%), hippocampus (62.0% ...
... 38 VF extract regulates BDNF signaling in an animal model of fibromyalgia. 22 Thus, we further evaluated whether VF extract might have antidepressant effect by regulating the antioxidant system. Results of western blot analysis showed that protein expression levels of Nrf2 were increased (by 28.6% -11.5% in the prefrontal cortex, by 53.2% -3.3% in the hippocampus, and by 41.1% -12.8% in the amygdala) in the CRS group compared with those in the sham group (38.5% -9.7%, 21.9% -2.6%, and 20.4% -7.3% in the prefrontal cortex, hippocampus, and amygdala, respectively). ...
Although depression is the most common psychiatric disorder, its pharmacological properties are not well known yet. It has been reported that Valeriana fauriei (VF) extract is beneficial for several neurological diseases. However, little information is available regarding its antidepressant activity. Therefore, the objective of this study was to determine antidepressant activity of VF and the underlying mechanism involved in its effect on chronic restraint stress (CRS)-induced depression using a mouse model. Oral treatment of VF extract for 14 days significantly ameliorated depression-like behavior (immobility time) in forced swimming and tail suspension tests following CRS induction, in accordance with decreased levels of serum corticosterone. VF extract ameliorated c-Fos expression, microglial activation, phosphorylated p38 expression, and inflammatory response (protein expression levels of cyclooxygenase-2 and inducible nitric oxide) in the prefrontal cortex, hippocampus, and amygdala of mice after CRS induction. However, VF extract enhanced the stimulation of nuclear factor erythroid 2-related factor 2 pathways, in accordance with upregulation in protein expression of brain-derived neurotrophic factor (BDNF). Collectively, our findings demonstrate that VF extract has antidepressant-like activity against CRS-induced depression through its anti-inflammatory and antioxidant effects by inhibiting BDNF expression. Further studies are warranted to investigate VF extract's fraction and components to develop possible antidepressants.
... We have previously reported that VF alleviates hepatic steatosis in obese mice by inducing autophagy [22]. VF also exerts neuroprotective effects and reduces pain and stress [23]. However, the effect of VF on myotube differentiation and muscle atrophy has not been investigated. ...
Skeletal muscle atrophy is defined as wasting or loss of muscle. Although glucocorticoids (GCs) are well-known anti-inflammatory drugs, their long-term or high-dose use induces skeletal muscle atrophy. Valeriana fauriei (VF) is used to treat restlessness, anxiety, and sleep disorders; however, its effects on skeletal muscle health have not been investigated. This study investigated whether Valeriana fauriei could ameliorate muscle atrophy. We induced muscle atrophy in vitro and in vivo, by treatment with dexamethasone (DEX), a synthetic GC. In DEX-induced myotube atrophy, Valeriana fauriei treatment increased the fusion index and decreased the expression of muscle atrophic genes such as muscle atrophy F-box (MAFbx/Atrogin-1) and muscle RING-finger protein 1 (MuRF1). In DEX-treated mice with muscle atrophy, Valeriana fauriei supplementation increased the ability to exercise, muscle weight, and cross-sectional area, whereas it inhibited myosin heavy chain isoform transition and the expression of muscle atrophy biomarkers. Valeriana fauriei treatment led to via the downregulation of muscle atrophic genes via inhibition of GC receptor translocation. Valeriana fauriei was also found to act as a reactive oxygen species (ROS) scavenger. Didrovaltrate (DI), an iridoid compound from Valeriana fauriei, was found to downregulate atrophic genes and decrease ROS in the DEX-induced myotube atrophy. Consolidated, our results indicate that Valeriana fauriei prevents DEX-induced muscle atrophy by inhibiting GC receptor translocation. Further, Valeriana fauriei acts as a ROS scavenger, and its functional compound is didrovaltrate. We suggest that Valeriana fauriei and its functional compound didrovaltrate possess therapeutic potentials against muscle atrophy.
... The effects of V. adscendens extracts on the central nervous system have been associated with the interaction with serotoninergic, dopaminergic, and noradrenergic receptors [95]. On the other hand, studies from Lee et al. [39] suggest that the antinociceptive effects of V. fauriei can be related to modulatory effects on the BDNF signaling pathway in the hippocampus and medial prefrontal cortex. Recently, Choi et al. [96] demonstrated that this species exerts antidepressant effects through its anti-inflammatory and antioxidant effects by inhibiting BDNF expression. ...
Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispas-modic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valeriana officinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed,
... Received 10 September 2019; Received in revised form 15 December 2019; Accepted 18 December 2019 characterized by strong resin fragrance or off-flavor. Some species of Valerianaceae family have been confirmed to possess therapeutic activities (Chen et al., 2015;Lee et al., 2018a;Zhang et al., 2018;Jugran et al., 2019). Therefore, Valerianaceae plants have extensive applications in perfumery and pharmaceutical industry. ...
In this work, the essential oil (EO) and supercritical CO2 fluid extract (SF extract) of four Valerianaceae plants (Valeriana officinalis L., Valeriana officinalis L. var. latifolia Miq., Valeriana jatamansi Jones and Nardostachys chinensis Bat.) were chemically characterized. GC-MS analysis identified 74 compounds, representing 35.2%-82.4% of the total EOs and SF extracts. The EO was dominated by low-molecular-weight components while the SF extract was rich in fatty acids. Bornyl acetate and camphene were the characteristic compounds in EO and SF extracts. The efficacy of six extracts against three stored-product insects was investigated. In contact assays, V. officinalis exhibited strongest toxicity to red flour beetle (LD50 = 10.0 μg/adult), and V. jatamansi EO was the most active one against the cigarette beetle (LD50 = 17.6 μg/adult), while V. officinalis var. latifolia EO showed outstanding efficacy against the booklouse (LD50 = 40.2 μg/cm2). Binary mixtures of two major compounds (camphene and bornyl acetate) were assessed for the contact toxicity to the red flour beetle. Additive effect existed in the natural proportion of V. officinalis, and synergism was observed in that of V. officinalis var. latifolia. This work confirmed the insecticidal efficacy of the species of the Valerianaceae family, and it would offer some information for the development of botanical insecticide.
... Valeriana officinalis L. is a perennial herbaceous plant belonging to the Valerianaceae family, inherently possessing characteristic off-flavor and being used as medicines worldwide. This kind of plant has been widely investigated; however, nearly 40% published works focused on the therapeutic and pharmaceutical properties of Valeriana owing to its antiepileptic (Torres-Hernandez et al. 2015), anodyne (Lee et al. 2018a), especially hypnotic (Fernandez et al. 2004;Hattesohl et al. 2008;Choi et al. 2018), and anxiolytic (Hattesohl et al. 2008;Zhang et al. 2018) functions in modern days (Aabid et al. 2012;Kakehashi et al. 2014;Chen et al. 2015). Only a few investigations reported its insecticidal properties. ...
The essential oil was extracted from the roots of Valeriana officinalis L. by hydrodistillation. The qualitative and quantitative analysis of its chemical constituents was conducted on GC-MS and GC-FID in this study. Seventeen compounds were detected and the major constituents included bornyl acetate (48.2%) and camphene (13.8%). The toxic and repellent effects of the essential oil and its two major constituents were evaluated on Liposcelis bostrychophila and Tribolium castaneum. The results of bioassays indicated that the essential oil showed the promising fumigant and contact toxicity against L. bostrychophila (LC50 = 2.8 mg/L air and LD50 = 50.9 μg/cm², respectively) and the notable contact effect on T. castaneum (LD50 = 10.0 μg/adult). Meanwhile, the essential oil showed comparable repellent effect on T. castaneum at all testing concentrations. Bornyl acetate and camphene also exhibited strong fumigant and contact toxicity against both species of pests (LC50 = 1.1, 10.1 mg/L air and LD50 = 32.9, 701.3 μg/cm² for L. bostrychophila; > 126.3, 4.1 mg/L air, and 66.0, 21.6 μg/adult for T. castaneum). Bornyl acetate and camphene showed moderate repellent effect on T. castaneum and conversely showed attractant effect on L. bostrychophila. This work highlights the insecticidal potential of V. officinalis, which has been noted as a traditional medicinal plant.
... To date, attempts to develop a specific treatment for FMS have proven far from successful. The ICS animal model is able to induce mechanical and thermal hyperalgesia, and thermal allodynia, and it has also been demonstrated that causes a decrease in exploratory behaviour and muscular strength, and increases the generation of an inflammatory response in mice [19,30]. ...
Improving the health and quality of life in patients with fibromyalgia syndrome (FMS) is currently of crucial relevance. In this study, the effect of the consumption of Annona muricata L. (Annonaceae) leaves (AM) was investigated on a model for intermittent cold stress (ICS)-induced fibromyalgia in mice. An aqueous extract of AM was investigated in experiments involving 60 five-week-old female mice C57BL/6J.
The animals were allocated into six groups (n = 10). Groups (I) Healthy control, (II) ICS control, and (III) ICS + acetaminophen (0.5%), were all fed a standard diet, while groups (IV) and (V) received standard diets supplemented with 15% (AM15) and 30% (AM30) aqueous extract of AM leaves, respectively. Group (VI) received a standard diet supplemented with 30% of aqueous extract of AM leaves and 0.5% of acetaminophen over a period of 4 weeks.
After having been subjected to the ICS model, the mice of the (II–VI) groups were tested for their nociception and behaviour. The results indicate that daily consumption of the leaves of AM confers protection not only against chronic pain of fibromyalgia, but also against other associated symptoms, such as anxiety and depression.
Fibromyalgia (FM) is a complex syndrome, with an indefinite aetiology and intricate pathophysiology that affects 2 – 3% of the world population. From the beginning of the 2000s, experimental animal models have been developed to mimic clinical FM and help obtain a better understanding of the relevant neurobiology. These animal models have enabled a broad study of FM symptoms and mechanisms, as well as new treatment strategies. Current experimental FM models include the reserpine-induced systemic depletion of biogenic amines, muscle application of acid saline, and stress-based (cold, sound, or swim) approaches, among other emerging models. FM models should: (i) mimic the cardinal symptoms and complaints reported by FM patients (e.g., spontaneous nociception, muscle pain, hypersensitivity); (ii) mimic primary comorbidities that can aggravate quality of life and lead to worse outcomes (e.g., fatigue, sleep disturbance, depression, anxiety); (iii) mimic the prevalent pathological mechanisms (e.g., peripheral and central sensitization, inflammation/neuroinflammation, change in the levels of the excitatory and inhibitory neurotransmitters); and (iv) demonstrate a pharmacological profile similar to the clinical treatment of FM. However, it is difficult for any one of these models to include the entire spectrum of clinical FM features once even FM patients are highly heterogeneous. In the past six years (2015 – 2020), a wide range of experimental FM studies has amounted to the literature reinforcing the need for an updated review. Here we have described, in detail, several approaches used to experimentally study FM, with a focus on recent studies in the field and in previously less discussed mechanisms. We highlight each model’s challenges, limitations, and future directions, intending to help preclinical researchers establish the correct experimental FM model to use depending on their goals.
Cartilage stem/progenitor cells (CSPCs) are a novel stem cell population and function as promising therapeutic candidates for cell‑based cartilage repair. Until now, numerous existing research materials have been obtained from humans, horses, cows and other mammals, but rarely from sheep. In the present study, CSPCs with potential applications in repairing tissue damage and cell‑based therapy were isolated from 45‑day‑old Small‑tailed Han Sheep embryos, and examined at the cellular and molecular level. The expression level of characteristic surface markers of the fetal sheep CSPCs were also evaluated by immunofluorescence, reverse transcription‑polymerase chain reaction analysis and flow cytometric assays. Biological growth curves were drawn in accordance with cell numbers. Additionally, karyotype analysis showed no marked differences in the in vitro cultured CSPCs and they were genetically stable among different passages. The CSPCs were also capable of adipogenic, osteogenic and chondrogenic lineage progression under the appropriate induction medium in vitro. Together, these findings provide a theoretical basis and experimental evidence for cellular transplant therapy in tissue engineering.
Exposing a pregnant female to stress is a risk factor for the development of psychiatric disorders in the offspring. In the present study, we examined the effects of an extract of Valeriana fauriei (VF) root (100 mg/kg/day, administered on postnatal days 35-56) on behavioral patterns as well as protein expression in the prefrontal cortex of the offspring of prenatally-stressed rats. Modified behavioral tests, including the forced swim test, the open field test, a social interaction test and the prepulse inhibition test were performed and many of the parameters were found to decrease in the offspring of the rats exposed to PNS compared with the offspring of the non-stressed rats. Western blot and immunohistochemical analyses of the prefrontal cortex revealed that the downregulation of several neurodevelopmental proteins in the offspring of rats dams exposed to PNS was reversed after treatment with VF extract. These findings demonstrate that the downregulation of several proteins in the prefrontal cortex of the offspring of prenatally‑stressed rats may be associated with subsequent behavioral changes, and that these phenomena recovered following VF treatment. Our results suggest that VF decreases the incidence of prenatal stress related-psychiatric disorders, such as depression and schizophrenia.
Background:
Brain-derived neurotrophic factor (BDNF) from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold.
Methods:
Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression.
Results:
Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period.
Conclusion:
These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.
The prevalence and comorbidity of psychiatric disorders such as depression, anxiety and insomnia are very common. These well-known forms of psychiatric disorders have been affecting many people from all around the world. Herb alone, as well as herbal formula, is commonly prescribed for the therapies of mental illnesses. Since various adverse events of western medication exist, the number of people who use herbs to benefit their health is increasing. Over the past decades, the exploration in the area of herbal psychopharmacology has received much attention. Literatures showed a variety of herbal mechanisms of action used for the therapy of depression, anxiety and insomnia, involving reuptake of monoamines, affecting neuroreceptor binding and channel transporter activity, modulating neuronal communication or hypothalamic-pituitary adrenal axis (HPA) etc. Nonetheless, a systematic review on herbal pharmacology in depression, anxiety and insomnia is still lacking. This review has been performed to further identify modes of action of different herbal medicine, and thus provides useful information for the application of herbal medicine.
To investigate health anxiety and depressive symptoms in patients with fibromyalgia syndrome (FMS).
Patients with FMS and healthy control subjects were recruited. All participants completed the Health Anxiety Inventory Short Form (HAI-SF) and Beck Depression Inventory (BDI). Pain was assessed in patients with FMS using the Fibromyalgia Impact Questionnaire (FIQ) and Visual Analogue Scale (VAS).
This study involved 95 patients with FMS (15 male) and 95 healthy controls (17 male). Mean ± SD HAI-SF and BDI scores were significantly higher in patients with FMS = than in controls=. HAI-SF scores were 23.50 ± 10.78 and 9.38 ± 4.24 respectively; BDI scores were 18.64 ± 10.11 and 6.21 ± 4.05 respectively. There were highly significant correlations between FIQ and HAI-SF, FIQ and BDI, and HAI-SF and BDI.
Patients with FMS had significantly higher HAI-SF and BDI scores than healthy controls. Psychiatric support is essential for patients with FMS. Treatment should include biological, psychological and social approaches.
© The Author(s) 2015.
A novel test procedure for antidepressants was designed in which a mouse is suspended by the tail from a lever, the movements of the animal being recorded. The total duration of the test (6 min) can be divided into periods of agitation and immobility. Several psychotropic drugs were studied: amphetamine, amitriptyline, atropine, desipramine, mianserin, nomifensine and viloxazine. Antidepressant drugs decrease the duration of immobility, as do psychostimulants and atropine. If coupled with measurement of locomotor activity in different conditions, the test can separate the locomotor stimulant doses from antidepressant doses. Diazepam increases the duration of immobility. The main advantages of this procedure are (1) the use of a simple, objective test situation, (2) the concordance of the results with the validated "behavioral despair" test from Porsolt and, (3) the sensitivity to a wide range of drug doses.
Recent studies in vivo and vitro have shown that Fuzi polysaccharide has an antidepressant-like effect. Polysaccharide and total alkaloid are the two most important components of Fuzi. However, little is known about the antidepressant-like effect of Fuzi total alkaloid. To investigate the antidepressant-like effect of Fuzi total alkaloid, behavioral studies were performed in the open field test and forced swimming test. Repeated intragastric administration of Fuzi total alkaloid for 7 days (10 mg/kg) to normal mice decreased immobility time compared to the vehicle group. Furthermore, repeated administration of Fuzi total alkaloid (10 or 30 mg/kg) to ovariectomized mice also decreased immobility time in a dose-dependent manner. However, these antidepressant-like behavioral effects were not simply due to locomotor hyperactivity. Further experiments showed that Fuzi total alkaloid enhanced the ratio of phospho-CREB/CREB (cAMP response element-binding) and BDNF (brain-derived neurotrophic factor) protein level in the frontal cortex and hippocampus in ovariectomized mice but not in normal mice. These results indicate that the CREB-BDNF pathway may be involved in the antidepressant-like effect of Fuzi total alkaloid in ovariectomized mice.
Objectives:
In the current study, we have evaluated the intermittent cold stress (ICS) induction in mice, in order to validate and optimize its utility as a fibromyalgia-like model.
Methods:
Twenty-four mice of 5-week old, female Swiss, weighing 18-22 g were used for the experiments. These mice were divided into three groups of eight animals per group [health control group (control), ICS group (ICS), and Gabapentin group (GBP)]. When in-vivo tests were completed, we proceeded to isolation and culture of peritoneal macrophages in order to determine the effects of the ICS on the release of proinflammatory mediators.
Results:
The results showed that this model is suitable to induce mechanical allodynia, thermal allodynia, and hyperalgesia. It is also able to reproduce behavioral changes related to cognitive disturbances, anxiety, and depression. Besides, ICS model might increase the inflammatory response in LPS-macrophages stimulated from stressed mice.
Conclusions:
Our results show that ICS is a useful animal model to assess hypothesis about underlying mechanisms involved in the development of fibromyalgia as well as to evaluate possible future therapies.
In this study, we investigated the potential protective effects of Valeriana officinalis (V. officinalis) against the toxicity induced by rotenone in Drosophila melanogaster (D. melanogaster). Adult wild-type flies were concomitantly exposed to rotenone (500μM) and V. officinalis aqueous extract (10mg/mL) in the food during 7 days. Rotenone-fed flies had a worse performance in the negative geotaxis assay (i.e. climbing capability) and open-field test (i.e. mobility time) as well as a higher incidence of mortality when compared to control group. V. officinalis treatment offered protection against these detrimental effects of rotenone. In contrast, the decreased number of crossings observed in the flies exposed to rotenone was not modified by V. officinalis. Rotenone toxicity was also associated with a marked decrease on the total-thiol content in the homogenates and cell viability of flies, which were reduced by V. officinalis treatment. Indeed, rotenone exposure caused a significant increase in the mRNA expression of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and also in the tyrosine hydroxylase gene (TH). The expression of SOD and CAT mRNAs were normalized by V. officinalis treatment. Our results suggest that V. officinalis extract was effective in reducing the toxicity induced by rotenone in D. melonogaster as well as confirm the utility of this model to investigate potential therapeutic strategies on movement disorders, including Parkinson disease (PD).