Estudio sobre la valeriana y la depresión

Valeriana (Valeriana officinalis L.)is a perennial herbaceous plant belonging to the Valerianaceae family and Valeriana genus. Valerian is primarily distributed in regions with mild temperatures and high humidity. It is associated with the heart and liver meridians, calms the mind, and has therapeutic effects for insomnia, depression, and anxiety [1].

1 efectos contra el cáncer

Modern pharmacological studies suggest that Valeriana may possess anticancer activity. Xue Cunkuan et al. [2] employed an in vivo mouse tumor transplantation experiment and an in vitro MTT assay using thiazole blue staining to investigate the antitumor activity of total cycloentran, cycloentran glycosides, and cycloentran esters in Valeriana. The results showed that the cycloartenol terpenoids in Valeriana officinalis exhibited significant cytotoxic effects against monocyte leukemia (U937) and cervical cancer (Hale), with a half-maximal inhibitory concentration (IC50) of 20–30 mg/L. In vivo experiments in mice demonstrated a marked antitumor effect, with an IC₅₀ of 46.38% to 68.71%. Zhang Shuqin et al. [3] reported that valerianolide can significantly prolong the survival time of Ehrlich ascites carcinoma (EAC) mice, with a prolongation rate ranging from 62% to 66%, comparable to 5-FU, and it can increase the formation of red blood cell clusters, indicating that it may have immune-enhancing effects.

Ye Jianmin et al. [4] encontraron esoExtracto de Valeriana officinalisPuede inducir apoptosis en las células de cáncer gástrico MKN-45, que se asocia con la activación de la caspasa, logrado a través de la activación de la vía intrínseca de la apoptosis, sin relación con la vía extrínseca de la apoptosis, y presenta efectos dependientes de la concentración y dependientes del tiempo. Su mecanismo de acción se asocia con la regulación de la expresión de la proteína P53, mejorando el efecto pro-apoptótico de Bax e inhibide la expresión de la survivina y Bcl-2. Sin embargo, el mecanismo específico subyacente a la alta expresión de la proteína P53 y la baja expresión de la proteína de supervivencia requiere una mayor investigación.

Chen et al. [5] used the MTT assay, quantitative polymerase chain reaction (qPCR), and Western blot (WB) to investigate the effects of Valeriana officinalis on pancreatic cancer (PC) cells, and conducted a preliminary discussion on the underlying mechanisms. The results indicated that Valeriana officinalis significantly inhibited the growth of PC cells but did not affect the growth of normal pancreatic epithelial cells. The mechanism of action was associated with increasing Bax expression levels, inhibiting Bcl-2, c-Myc, and cell cycle protein B1, and suppressing Stat3 transcriptional activity. Valeriana officinalis induced apoptosis and cell cycle arrest, thereby exerting anticancer effects.

Lu et al. [6] used a xenograft mouse model to confirm that valerian acid inhibits the growth of glioblastoma multiforme (GBM) by enhancing intrinsic signaling, increasing ROS levels, and activating the AMPK pathway, thereby inducing GBM cell apoptosis. In summary, Valeriana officinalis exerts its antitumor effects by regulating factors or pathways such as P53, Bax, survivin, Bcl-2, c-Myc, B1, Stat3, ROS, and AMPK, which holds significant implications for the development of anticancer drugs in the future.

2. Mejora de la calidad del sueño

Zhang Zhongli et al. [7] administered Extracto de valeriana to D-galactose-induced and sleep-deprived Alzheimer&#Enfermedad de las ratas (SDAD) Y encontraron que en comparación con el grupo modelo, el grupo de extracto de alcohol desfatado de valeriana, el grupo de extracto lavado con etanol al 20% y el grupo de extracto lavado con etanol al 70% aumentaron los niveles de catalasa (CAT) y la capacidad antioxidante total (T-AOC) en suero de rata, disminuyeron la actividad de la acetilcolinesterasa (AChE) e incrementaron la actividad de la superóxido dismutasa (SOD), glutatión peroxid(GSH-Px), aumentaron la actividad de GSH-Px y disminuyeron los niveles de peroxidlipíde malondialdehído (MDA) (P < 0,05, P < 0.01). Los resultados indican que el extracto de Valeriana puede mejorar la capacidad de aprendizaje y memoria, la calidad del sueño y la capacidad antioxidante en ratas modelo SDAD. El mecanismo puede estar relacionado con la mejora de la actividad T-AOC, la reducción de los niveles de ACh E, y la mejora de la capacidad antioxidante en ratas SDAD. Ab-dellah [8] et al. informaron que la combinación de hierba en forma de flor y valeriana aumentó significativamente la duración del sueño en adultos insomnes, la eficiencia del sueño de 78,4% ± 12,5% a 84,6% ± 10,2% (P = 0,002), y el número de despertaros y la duración total disminuyó, pero la latencia del sueño no mejoró. Esto sugiere que los extractos de Polygonum cuspidatum y Valeriana podrían tener un efecto beneficioso sobre el sueño en adultos con insom.

Sichardt et al. [9] compared the effects of methanol (M-E), ethanol (E-E), and ethyl acetate (EA-E) extracts on postsynaptic potentials (PSP) of cortical neurons at concentrations ranging from 0.1 to 15 mg/mL. M-E induced strong inhibition, while E-E (1–10 mg/mL) had no significant effect on PSP. The adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 μmol/L) completely antagonized the maximum inhibitory effect induced by M-E. In contrast to M-E, EA-E (10 mg/mL) increased PSP, GABA_A receptor antagonist picrotoxin (100 μmol/L) completely blocked PSP. Therefore, it was found that the mechanism of action is related to adenosine A1 receptors and GABA_A receptors, and the activation of these two receptors is mediated by different components in Valeriana extractEjerciendo así su efecto inducdel sueño.

Tokunaga et al. [10] investigated the effects of valerian extract preparations (BIM) on the sleep-wake cycle in a rat sleep disorder model, comparing them with the valerian extract group. Both significantly shortened the sleep latency period but had no significant effect on the total duration of wakefulness, non-rapid eye movement (non-REM) sleep, and REM sleep. However, the specific mechanism of BIM&#Los efectos antiinsom39;s siguen siendo poco claros y requieren más investigación. Sudati et al. [11] demostraron que en el homogendel cerebro, la valeriana exhibiefectos inhibitdependientes de la concentración en sustancias activas del ácido tiobarbitúrico inducidos por oxidantes, inhibisignificativamente la peroxidlipí(LPO) en la corteza cerebral y redujo la degradación de la desoxitribosa. Y también redujo significativamente la producción de especies reactivas de oxígeno inducida por el ácido quinolínico en las rodajas cortic, lo que indica que el extracto de valeriana tiene un cierto efecto regulador sobre la LPO inducida por diferentes pro-oxidantes, y puede servir como un antioxidante para reducir el insomasociado con el estrés oxidativo.

Zhang Jinpeng et al. [12] used reverse transcription PCR (RT-PCR) to detect changes in the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in peripheral blood mononuclear cells induced by Valeriana. The results showed that Valeriana administration significantly increased the expression of IL-1β and TNF-α, with significant differences compared to the blank control group (P < 0.05), thereby improving sleep quality. The mechanism of action may be related to the increased levels of IL-1β and TNF-α in mice [13]. Valerian/cascade mixture significantly increased NREM and total sleep time in the pentobarbital-induced sleep model, reduced sleep latency and wakefulness time, and its sleep-promoting mechanism is due to upregulation of GABAAR [14].

Por lo tanto, la valeriana puede mejorar el insommediante la activación de los receptores GABAA y los receptores de adenosina A1, mejorando la capacidad antioxidante, e influen los neurotransmien el cerebro.

3 efectos antidepresiy ansiolíticos

Benke et al. [15] informaron que el efecto ansiolítico devalerian extract valerianic acid targets the β3 subunit of GABAA receptors. Experimental results showed that point mutations in the β2 or β3 subunits (N265M) of GABAA receptors significantly reduced drug response. In in vivo experiments, valerian acid and valerianol exhibited high-efficiency anxiolytic activity in the elevated plus maze test and light/dark choice test in wild-type mice. However, in β3 (N265M) point mutation mice, the anxiolytic activity of valerenic acid was absent. Therefore, the GABAA receptor containing the β3 subunit was identified as the target of valerenic acid's efectos ansiolíticos.

Neamati et al. [16] found that valerenol extracts could prevent depressive behavior in ovalbumin-sensitized rats, and oxidative stress plays a role in depression and anxiety [17], and oxidative stress was also increased in ovalbumin-sensitized animals [18]. Therefore, this study suggests that the antidepressant effects of valeren extracts may be related to oxidative stress responses, but the specific mechanisms require further investigation. Mojica et al. [19] used a light/dark preference test in zebrafish to demonstrate that valerian and valerenic acid exhibit anxiolytic activity in zebrafish, The anxiolytic effects disappeared after administration of LAP3 (mGluR I antagonist) and EGLU (mGluR II antagonist), suggesting that the mechanism may be related to metabotropic glutamate receptors (mGluR). Murphy et al. [20] employed the elevated plus maze test and behavioral tests, and found that valerenic acid is the primary anxiolytic component, and its anxiolytic effect is enhanced due to the presence of GABAB receptors.

Gonulalan et al. [21] reported that valerian extract (VO), valerenic acid (VA), acetoxy valerenic acid (AVA), valerenic acid-free (VAF), and acetoxy valerenic acid-free (AVAF) on the expression of brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells, GABAA receptors are regulated by BDNF and modulate depressive behavior. The results showed that VO and VA extracts significantly increased BDNF expression in SH-SY5Y cells (P < 0.001). When cells were treated with VAF extract, this effect was completely abolished. AVA alone did not cause any significant changes in BDNF levels. The effect of the extracts on cells was concentration-dependent with increasing VA content. Therefore, Valerian extract can increase BDNF levels in SH-SY5Y cells. 

Valerian extract can improve stress responses in mice induced by physical shock and psychological stress, reduce plasma corticosterone, serotonin (5-HT), and norepinephrine (NE) levels in the hippocampus and amygdala of mice, thereby alleviating the negative effects of stress on mice [22]. Farah et al. [23] conducted a randomized, crossover experiment, selected 20 anxious patients with bilateral extraction of the third molars in the mandible, assessed their physiological parameters, and found that valerian provided a comforting and relaxing effect, demonstrating anxiolytic effects, with fewer adverse reactions compared to midazolam. However, further clinical studies are needed for clinical application. The above studies indicate that valerian can improve depression and anxiety through mechanisms such as regulating GABA receptors and reducing oxidative stress.

4 efectos neuroprotectores

As lifespan increases, a better understanding of the physiological and pathological mechanisms associated with brain aging can help prevent neurological diseases, thereby improving the quality of life in the elderly. Brito et al. [24] conducted in vitro experiments on C6 glioma cells in rats using the MTT method and found that valerian had a protective effect against rotenone-induced cytotoxicity. In vivo experiments investigated the interaction between valerian and rotenone in cortical spreading depolarization (CSD), showing that valerian had a certain inhibitory effect on the proliferation rate of CSD. The specific mechanism remains a subject of debate and requires further investigation.

Cornara et al. [25] investigaron el biological effects of valerian on the nervous system using acetylcholinesterase (AChE) inhibitory activity and microelectrode array (MEA) analysis. The AChE results indicated that the IC50 of valerian was 127.30 μg/mL, MEA analysis was conducted by recording the mean firing rate (MFR) and mean burst rate (MBR), with results of 16.5 and 22.5 μg/mL, suggesting its potential therapeutic effects on neurological disorders. Sudati et al. [26] investigated the protective effects of Valeriana against the harmful effects of rotenone on black-bellied fruit flies. The results indicated that Valerian extract significantly reduced the toxic effects of rotenone on black-bellied fruit flies. After Valerian treatment, the content of total thiols, as well as the mRNA expression of SOD and CAT, were reduced. This confirmed the potential of this model in exploring treatments for neurodegenerative diseases; however, the specific neural pathways involved require further investigation.

Un estudio estableció un Parkinson& indupor MPTP#Modelo de ratón con enfermedad de 39;s. A través de pruebas de fuerza muscular, pruebas de haz de equilibrio, pruebas de capacidad de actividad de campo, y pruebas de soporte de peso de las extremidades posteriores, y la detección ELISA de las citocinas inflamil-1 -, IL-6, TNF- -, y IFN- -, los resultados mostraron que el ácido Valeriano puede regular la neuroinflamación en Parkinson#39;s, reduciendo los niveles de citocinas proinflamatorias y GFAP en la región mesencéfalo. El mecanismo de acción puede implicar la inhibición de la activación de los receptores NF- − B y 5-HT5A en astrocitos [27]. Sin embargo, otro estudio utilizó un enfoque genómico para evaluar los mecanismos potenciales de Valeriana officinalis en el tratamiento de la EP. Los resultados indicaron que la hesperidina y el ácido linoleico pueden reducir el estrés oxidativo durante el consumo de ATP al unirse a SUR1Ácido valerénico y apigeninaPuede desempeñar un papel clave en la inducde la liberación de GABA de las neuronde la sustancia nigra (SN) en el tronco cerebral, evitando así la exciexcicortical excesiva [28].

Sharifzadeh et al. [29]induced morphine withdrawal syndrome in mice by injecting naloxone and found that animals treated with Valeriana officinalis water extracts and methanol extracts significantly reduced naloxone-induced jumping. The mechanism of action may involve interacting with inhibitory neurotransmitters in the nervous system to influence morphine withdrawal syndrome. A study involving healthy volunteers in a double-blind, randomized, crossover, placebo-controlled experiment found that a single oral dose of Valerian extract can influence human excitatory cortico-spinal pathways [30]. Fachi-netto et al. [31] administered Valerian to animals with oromotor dysfunction (OD) induced by long-term haloperidol administration, to assess empty chewing movements (VCMs), motor activity, maze performance, and oxidative stress parameters. The results indicated that valerian did not cause any oxidative damage to the central nervous system (CNS) and did not prevent VCMs.

Additionally, another study found that valerian had a preventive effect on VCMs induced by reserpine in rats, which significantly increased VCMs in rats. However, co-treatment with valerian reduced the intensity of VCMs. In the cerebral cortex, VCMs were significantly positively correlated with DCF-oxidized levels (P < 0.05), while Na+ K+ -ATPase was negatively correlated in the substantia nigra of the midbrain, indicating that valerian has a behavioral protective effect against reserpine-induced VCMs in rats. However, the exact mechanism remains to be further investigated [32]. Circosta et al. [33] reported that valerian alcohol extracts and water extracts protect guinea pig coronary artery spasm and blood pressure induced by pituitary vasopressin, with the mechanism possibly mediated by interfering with calcium overload capacity. In summary, Valerian has therapeutic potential for neurological disorders characterized by oxidative stress imbalance and astrocyte dysfunction, as well as degenerative neurological diseases.

5 efectos antiepilépticos

La epilepsia es una enfermedad actualmente incurable, y sus episodios recurrentes causan sufrimiento y algunas secuelas en los pacientes#39; Vidas. Por lo tanto, encontrar fármacos clínicamente eficaces con efectos secundarios mínimos se ha convertido en una prioridad urgente. Rezvani et al. [34] informaron eso Valeriana officinalis water extracts exhibit significant anticonvulsant effects in a temporal lobe epilepsy animal model, whereas petroleum ether extracts show no significant anticonvulsant effects. Selective adenosine A1 receptor antagonists can reduce the anticonvulsant effects of Valerian water extract, suggesting that Valerian's los efectos anticonvulpueden mediarse a través de la activación del sistema de adenosina.

Bianca et al. [35] induced seizures in adult zebrafish using pentylenetetrazole (PTZ) and found that ethanol valerian extract significantly enhanced the anticonvulsant effects of clonazepam and phenytoin, increased the seizure latency period, and improved survival rates, with a concentration-dependent increase in seizure latency. However, the specific mechanism of action remains unclear and requires further investigation. Additionally, studies have shown that valerian extract can improve PTZ-induced epileptic seizure behavior in rats, increase plasma SOD antioxidant enzyme activity, and correct the QT interval (QTc), which may serve as a predictive factor for recurrent epileptic seizures and epilepsy onset [36]. Therefore, valerian holds significant potential as an adjunctive therapeutic agent for anticonvulsant therapy.

Otros 6

La investigación ha informado por primera vez que la valeriana puede convertirse en una nueva dirección para el futuroTratamiento de la diabetes tipo 2. Mediante el estudio de los efectos del extracto de valeriana en los adipocitos 3T3-L1, se encontró que la valeriana puede promover la diferenciación de adipocitos, aumentar significativamente los niveles de ARNm del peroxisoma proliferactiv-receptor gamma (PPARγ), CCAAT-element-binding protein α, y adipoadipoproteína 2, y también aumentar significativamente el ARNm y los niveles de proteínas de adiponectina. Adicionalmente, se encontró que la diferenciación de adipocitos y el aumento de los niveles de adiponectina están asociados con la Unión de PPAR − [37].

Occhiuto et al. [38] reported that Valeriana extract inhibits uterine contractions in a concentration-dependent manner and reduces the maximum contraction response induced by acetylcholine, norepinephrine, and histamine without requiring stimulation. The mechanism of action may be mediated by interfering with calcium overload. Studies have indicated that valerian has the strongest toxicity against red flour beetles (LD₅₀ = 10.0 μg/adult) and exhibits additive effects, suggesting that valerian can serve as a plant-based insecticide, providing reference for the development of insecticides [39]. Jenabi et al. [40] conducted a three-month clinical trial involving 60 postmenopausal women using a triple-blind, randomized, controlled design. The severity and frequency of hot flashes were assessed using the Kupperman indEx exat different intervention periods. The results indicated that valerian alleviated the severity and frequency of hot flashes, thus being effective for hot flashes in postmenopausal women; however, the results remain non-generalizable.

Meanwhile, Nam et al. [41] found that Valerian root extract enhanced cognitive function in aged mice induced by d-galactose, promoted cell proliferation and neural progenitor cell differentiation, and reduced serum corticosterone and lipid peroxidation. Its mechanism of action may be related to the antioxidant function of valerian extract on the hippocampus and GABA. Dugaheh et al. [42] evaluated the antioxidant effects of valerian using the diphenylpyridine (DPPH) inhibition method and β-carotene bleaching method. Valerian exhibited strong inhibitory effects on DPPH, with an IC50 value of 38 mg/mL, indicating significant antioxidant activity. Liang Qun et al. [43] found that valerian terpenoids A, B, and C have inhibitory effects on liver fibrosis formation, with mechanisms potentially related to inhibiting hepatic stellate cell (HSC) proliferation and antioxidant activity. Additionally, Xing Jinmei [44] demonstrated that valerian terpenoid lactones A and C exhibit a dose-dependent inhibitory effect on HSC proliferation.

Xu Shali et al. [45] used an enzymatic method to detect total cholesterol (TC) and total bile acid (TBA) levels in rabbits fed a high-cholesterol, high-fat, and high-sugar diet. The results indicated that Valeriana extract increased TBA content in bile, improved TBA/TC ratio, reduced serum TBA concentration, and significantly alleviated liver damage. Valerian extract has certain preventive and therapeutic effects on bleomycin-induced alveolitis and pulmonary fibrosis in rats, and its mechanism may be related to downregulating the expression of transforming growth factor β1 (TGF-β1) [46,47]. Research has found that Valeriana officinalis may exert its pharmacological effects in treating irritable bowel syndrome (IBS) visceral hypersensitivity by acting on the parahippocampal gyrus and inhibiting gastrointestinal motility. This is achieved by increasing GABABR expression, enhancing its expression in the myenteric plexus of the colon, thereby strengthening the inhibitory effect on Ca²⁺ channels and reducing Ca²⁺ influx, inhibiting colonic contractions, alleviating IBS symptoms, and reducing gastrointestinal sensitivity by suppressing gastrointestinal smooth muscle movement [48-50].

7 conclusión

Valeriana, como aMedicina tradicional a base de hierbasCon una larga historia, juega un papel importante en el mantenimiento de la salud humana. La revisión de la literatura revela que la valeriana posee varias actividades biológicas, con sus efectos en el tratamiento de la depresión y la ansiedad convirtiéndose en un foco de investigación tanto a nivel nacional como internacional. Además, presenta actividad antitumoral, promueve el sueño, protege el sistema nervioso, y tiene efectos antiepilépticos, ofreciendo amplias perspectivas de desarrollo. En los últimos años, expertos nacionales e internacionales han realizado estudios cada vez más exhaussobre los efectos farmacológicos de la Valeriana officinalis; Sin embargo, sus complejos mecanismos multi-objetivo siguen siendo poco claros y requieren una mayor exploración. Según las revisiones de la literatura, la investigación actual sobre la valeriana se centra principalmente en la validación funcional, con aplicaciones clínicas aún en sus primeras etapas. Por lo tanto, los autores recomiendan más investigaciones sobre los mecanismos de regulación molecular subyacentes a Valerian&#Los efectos farmacológicos, así como su potencial para aplicaciones clínicas más amplias, sentarán las bases para su uso más generalizado.

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