What Is Valerian Extract and Its Benefit?

Valerian (Valeriana officinalis L.) belongs to the Valerianaceae family and the Valeriana genus. It is a perennial herbaceous plant. There are approximately 250 species in this genus, most of which are distributed in regions with mild and humid climates, spanning Europe, northern Asia, South America, and the United States [1].

In recent years, with the acceleration of the pace of life and the increase in living pressures, insomnia, depression, and tumors have increasingly plagued human health. While some chemically synthesized drugs are effective, they often have significant side effects. Valerian, however, is a natural sedative and analgesic agent that is widely popular due to its significant therapeutic effects and minimal toxic side effects. Valerian is commonly used in Europe and the United States for the treatment of mild to severe insomnia, possessing sedative, anxiolytic, antispasmodic, analgesic, antidepressant, and antitumor properties. It has been used as a mild sedative and hypnotic agent. Valerian extracts and their formulations are highly popular internationally, with sales ranking among the top 10 in the herbal medicine market[2].

The roots and rhizomes of valerian have a long history of use as sedatives. In China, they were first recorded in Li Shizhen's *Compendium of Materia Medica* during the Ming Dynasty [3]. Abroad, the plant was also used during the time of Discorides, and ancient Greeks and Romans recognized its sedative and calming effects [4]. In recent years, scholars both domestically and internationally have conducted extensive research on Valeriana plants, achieving significant progress. This study provides an overview of relevant research on the main medicinal species, chemical components, pharmacological effects, extraction and separation techniques, component detection methods, and tissue culture of Valeriana plants, facilitating future research on this plant.

1 Main medicinal species

Currently, the main medicinal Valerian species used abroad include European Valerian (Valeriana officinalis L.), Indian Valerian (V. wallichii DC), Mexican Valerian (V. edulis Nutt. ex Torr. & Gray), and Japanese Valerian (V. auriei Briq. (Japanese valerian)), among four types.

There are 17 species and 2 varieties of Valerianaceae Valeriana genus plants in China [5], with 9 species documented for medicinal use. Among these, the domestically produced Valerian pseudofficinalis C. Y. Cheng et H. B. Chen, broad-leaved valerian Valerian officinalis L. var. latifolia Miq, black water valerian Valerian amurensis Smir. ex Komarov, spider valerian Valerian jatamansi Jones, and long-spiked valerian Valerian hardwickii Wall, among others.

Chen Lei [6] compiled geographical distribution data for four commonly used Valeriana species based on The Flora of China, various regional floras, relevant books, papers, field surveys, and specimen collection records, and created a distribution map of Valeriana species in China. Sichuan, Chongqing, Yunnan, Guizhou are the main production areas for spider-scented valerian; western Hubei, including Badong, Hefeng, Lichuan, and Wufeng counties, have extensive wild valerian resources; the wild distribution of broad-leaved valerian is similar to that of valerian; and black-water valerian is primarily distributed in the eastern mountainous regions of Northeast China, the Xiao Xing'anling Mountains, the Da Xing'anling Mountains, and the mountainous and hilly areas of Shandong's Jiaodong Peninsula. Additionally, the morphological characteristics and medicinal properties of these four Valeriana species were summarized.

2 Active Components of Valeriana Extracts

2.1 Cycloaromatic Terpenoids

Huang Baokang et al. [7] reported that Valeriana extracts primarily contain Valeriana triolates (valepotriates) and Valeriana acid (valerenic acid). Valepotriates are a mixture of cycloentane ether terpenoids, whose molecules are esters formed by the cyclopentane-pyran ring of polyols and various organic acids. Valepotriates are also the primary components responsible for Valeriana's sedative and antitumor effects. Valerenic acid is the primary component responsible for valerian's anxiety-relieving effects. The content of valerian triolates in Valeriana plants generally ranges from 0.5% to 9.0%. The valerian triolates found in Valeriana roots are primarily valerianate (val-trate), isovalerianate (isovaltrate), followed by acevaltrate and isovaleroxy valtrate [8]. Wang Jixin et al. [9] isolated six compounds from the ethyl acetate fraction of a 95% ethanol extract of broad-leaved valerian, which were identified as the cycloether terpenoid compound valeriridoid P (1), the malic acid-type sesquiterpenoid compound dihydroxymaaliane (2), madolin F (3), a biscyclogymalan-type sesquiterpene compound madolin A (4), volvalerenal B (5), and kissoone A (6). It was concluded that compound 1 is a rare new compound containing two oxygen bridges in the cycloether terpene class, compounds 2–4 are the first isolated compounds of this genus, and compound 6 is the first isolated compound of this plant.

2.2 Volatile oils

Zhou Ting et al. [10] reported that the main components of volatile oils in Valeriana were monoterpenes and sesquiterpenes. Among them, monoterpenes mainly included borneol and its acetate and isovalerate esters; sesquiterpenes exceeded 30 types, with relatively low content, primarily consisting of guaiacol-type sesquiterpenes and valerian-type sesquiterpenes. Other components include 1-cymene, 1-limonene, α-pinene, carvone, α-terpineol, borneol, and α-thujene.

2.3 Alkaloids

Alkaloids are the antibacterial components in valerian extracts, primarily found in the roots and rhizomes, with a content of approximately 1%. Valerian roots contain valerine alkaloids (valerine) A–B, valerianamine, and actinidine (3-acetyl-2,7-naphthyridine), as well as chatinine alkaloids.

Alkaloids (actinidine), 3-acetyl-2,7-diazabicyclo[2.2.1]heptane (3-acetyl-2,7-naphthylidyne), chatinine alkaloids (chatinine), and valerianine alkaloids (valerianine), among which valerine A and B are more important [8].

2.4 Lignans

Zuo Yuming et al. [11] reported 10 bicyclic epoxy lignan compounds, namely: (+)-Pine resin-4,4′-O-β-D-dihydroxyglucoside (1), 3′-demethyl (+)-pine resin-4′-O-β-D-dihydroxyglucoside (2), (+)-Pinusol-4,4′-O-β-D-pyranoglucoside (3), 5′-methoxy-Pinusol-4, 4′-O-β-D-dihydroxyglucopyranoside (4), 8-8′-dihydroxy-pinocembrin-4-O-β-D-glucopyranoside (5), 8-8′-dihydroxy-pinocembrin-8-O-β-D-dihydroxyglucopyranoside glucoside (6), 8-hydroxy-pinocembrin-4-O-β-D-pyranoglucoside (7), 8-hydroxy-pinocembrin-4-O-β-D-pyranoglucoside (8), 8, 8′-dihydroxy-pinocembrin (9), 4,4′-dimethoxy-pinocembrin-3′-demethyl-8-8′-dihydroxy-pinocembrin (10). Among these, compounds 2, 4, 6, and 10 were first isolated from this genus of plants, and compounds 2, 4, 6, 7, 9, and 10 were first isolated from this plant.

2.5 Flavonoids

The extract of Valeriana officinalis contains flavonoids such as quercetin, apigenin, kaempferol, luteolin, and acaenol. The content of flavonoids in the reproductive organs of Valeriana officinalis is often higher than in the leaves.

Zuo Yueming et al. [12] isolated and identified 10 flavonoids from Valeriana, which were identified as: Apigenin-7-O-α-L-pyranosyl-6-glucoside (1), 8-methyl-apigenin-7-O-β-D-pyranosyl-2-glucoside (2), and 6-methyl-apigenin-7-O-β-D-pyranosyl-6-glucoside (3). lactoside (2), 6-Methyl-apigenin-7-O-α-L-pyranosyl (1→6)-[α-L-pyranosyl (1→2)]-β-D-pyranoglucoside (3), Ginkgo biloba extract-7-O-α-L-pyranosyl rhamnose (1→6)-[α-L-pyranosyl rhamnose (1→2)]-β-D-pyranose glucoside (4), Golden acacia-7-O-α-L-pyranosyl rhamnose (1→6)-β-D-pyranoglucoside (5), 5-methoxy-golden acacia-7-O-α-L-pyranosyl rhamnose (1→6)-β-D- pyranoglucoside (6), 5-methoxy-golden acacia-7-O-α-L-pyranosyl (1→6)-[α-L-pyranosyl (1→2)]-β-D-pyranoglucoside (7), 4 '-Methyl-5-methoxyflavone-7-O-α-L-pyranosyl rhamnose (1→6)-β-D-pyranoglucoside (8), L-carnauboside-7-O-α-L-pyranosyl (1→6)-β-D-pyranoglucoside (9), 8-hydroxy-monoterpenoid glycoside (10). These 10 compounds were isolated from this plant for the first time.

2.6 Amino acids

The roots of drynaria contain 18 amino acids, with a total content of 1.73%. The amino acids present in higher amounts include Tyr, Ser, Leu, Cys, Thr, Val, Pro, Ile, Leu, Phe, and Gly, among which Thr, Ile, Leu, Phe, and Lys are essential amino acids for humans [8].

Additionally, Valeriana extract contains caffeic acid, chlorogenic acid, tannins, resins, β-sitosterol, and various other carboxylic acids.

3 Pharmacological effects

3.1 Sedative and hypnotic effects

Valerian extract exhibits strong sedative and hypnotic effects. Zhang Jinpeng et al. [13] found that the water extract of valerian can inhibit spontaneous activity in mice and prolong their sleep duration, demonstrating significant sedative and hypnotic effects. Subsequent studies reported that the water extract of Valeriana officinalis increased the expression levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in peritoneal macrophages and peripheral blood mononuclear cells of mice [14]. This finding is widely recognized as the mechanism by which Valerian water extracts exert their sedative and hypnotic effects [14-15]. However, Ding Fei et al. [16] found that Valeriana officinalis essential oil was more effective than an equivalent dose of Valeriana officinalis water extract in increasing the sleep onset rate and prolonging sleep duration in mice.

3.2 Antidepressant effects

Zhao Lihui et al. [17] observed the time spent on spontaneous activity, tail suspension, and forced swimming immobility in depressed mice and found that the water extract and ethanol extract of Valeriana officinalis, in the form of n-butanol and ethyl acetate, had different degrees of effect on the behavior of mice in a depressed state. Qin Yajing et al. [18] found that chronic stress-induced depression in rats, after being administered Valerian for three weeks, showed improved behavior and weight, reduced serum corticosterone levels to normal levels, and decreased Caspase-3-positive cells in the hippocampus of the brain. It is speculated that Valeriana officinalis may exert its antidepressant effects by promoting the proliferation of neural stem cells and reducing the production of Caspase-3-positive neurons, thereby restoring normal behavior in depressed rats.

3.3 Anxiolytic effects

Murphy et al. [19] found that valerenic acid in valerian is the primary component responsible for reducing anxiety, and the anxiolytic effect of valerenic acid may be enhanced by the response of exogenous γ-aminobutyric acid (GABA) receptors. BENKE et al. [20] also confirmed that two Valeriana extracts, Valerenic acid and Valerenic alcohol, can enhance GABA receptor responses, thereby exerting anxiolytic effects.

3.4 Anticonvulsant and antiepileptic effects

The anticonvulsant and antiepileptic effects of valerian may be closely related to its regulation of GABA levels in the brain. Reports indicate that Valerian water extracts can treat seizures in SD rats induced by electrode stimulation and seizures in mice induced by pentylenetetrazole, which may be due to their inhibition of GABA receptor responses or inhibition of adenosine A(1) receptor responses, thereby achieving anticonvulsant effects [21-22].

3.5 Antitumor effects

Valerian lactones exhibit significant cytotoxic and antitumor effects, with lactones showing particularly pronounced effects [23]. Studies have found that valerianol inhibits liver cancer cells, bone marrow-derived stem cells, Kreb II ascites cancer cells, and human T2 lymphocytes. Pharmacological screening revealed that valerenic acid exhibits cytotoxic effects against cervical squamous cell carcinoma cells, gastric adenocarcinoma cells, and lung adenocarcinoma cells [24]. Ye Jianming et al. [25] found that the extract of Valeriana officinalis, known as “Bochun,” can induce apoptosis in MKN-45 gastric cancer cells.

3.6 Antibacterial and antiviral effects

The total alkaloids in Valeriana extract exhibit good antibacterial activity, with better efficacy against Gram-positive bacteria [26]. Studies have found that Valeriana also has antiviral activity against rotavirus, and the active components responsible for its antiviral effects may be valerian-derived compounds [27].

3.7 Renal Protective Effects

Valerian oil significantly improves kidney damage in type 2 diabetic rats, reduces proteinuria, and delays kidney function damage. Valerian may exert its kidney-protective effects by lowering blood lipids, inhibiting the activation of protein kinase C in the renal cortex, and exerting antioxidant effects [27].

3.8 Other effects

The antioxidant activity of Valeriana officinalis is closely related to its content of flavonoids, polyphenols, and tannins [28]; Valeriana officinalis essential oil has anti-cerebral ischemia effects [29]; and Valeriana officinalis also has preventive effects against vascular stenosis [30].

4 Extraction and separation

4.1 Valeriana triglycerides

Luo Xirong et al. [31] used response surface methodology to establish an accurate and effective regression model for the relationship between the yield of total Valerian triterpenoids and extraction pressure, extraction time, and extraction temperature under conditions of 30 MPa extraction pressure, 45 min extraction time, and 430°C extraction temperature.

Additionally, using supercritical CO₂ extraction, they obtained an average yield of total valerenic esters of 2.46%, with an average content of 49.35% in the extract. This finding is beneficial for subsequent separation, purification, pharmacological, and pharmacodynamic studies.

4.2 Valerenic acid

SAFARALIE et al. [32] employed CO₂ supercritical fluid extraction, achieving optimal conditions with a pressure of 24.3–25.0 MPa, a temperature of 37°C, an extraction time of 19–24 min, with a carrier agent of 100–200 μL, for the extraction of Valerian volatile oil and Valerianic acid. During the experiment, the extraction rate of Valerianic acid increased with increasing pressure, but decreased with increasing temperature. The extraction rate of valerenic acid increases with the amount of ethanol, but when the ethanol reaches 330 μL, the extraction rate decreases, indicating that within a certain range, the amount of ethanol is positively correlated with the extraction rate of valerenic acid. When the extraction time exceeds 30 minutes, the extraction rate of valerenic acid decreases. However, BOY-ADZHIEV et al. [33] found in their study on the extraction conditions of valerenic acid from Valeriana officinalis rhizomes that the extraction rate of valerenic acid increases with temperature, possibly due to the degradation of valerenic acid at high temperatures. Therefore, different extraction conditions can lead to differences in the total extract and valerenic acid content of Valeriana plants.

4.3 Essential Oils

Li Gang et al. [34] used spiderwort as the experimental material and found that extraction pressure of 25 MPa, extraction temperature of 55 °C, and CO₂ flow rate of 20 L·h⁻¹ are the optimal process conditions for extracting valerenic acid volatile oil using supercritical CO₂ extraction. under these conditions, the yield of valerian volatile oil was 5.86%, while the yield using the steam distillation method was 1.27%; under ABTS and FRAP methods, the antioxidant capacity of valerian supercritical CO₂ extracts was not significantly different, but both were stronger than the steam distillation method and the difference was significant, The total valerian triterpenoid content in valerian essential oil obtained by supercritical CO₂ extraction was 3.7%, higher than the 2.8% obtained by the steam distillation method, indicating that the supercritical CO₂ extraction method is more effective than the steam distillation method in preserving the bioactive components and bioactive functions of Valeriana officinalis essential oil. Additionally, Dou Xiaowei et al. [35] used black Valeriana officinalis as the experimental material, and compared three extraction methods—supercritical CO₂ extraction, steam distillation, and water-bath distillation—to determine that steam distillation is the optimal extraction method for black water valerian essential oil. From the above, it can be concluded that the optimal extraction method for valerian essential oil varies depending on the experimental material. Therefore, during experiments, the CO₂ supercritical extraction method and steam distillation method can be used separately to determine the most suitable essential oil extraction method for the current experimental material.

4.4 Flavonoids and Polysaccharides

Gu Zhengwei et al. [36] used extraction and alcohol precipitation techniques to separate flavonoids and polysaccharides. The results showed that under conditions of cellulase concentration 1.9 U·mL^(−1), material-to-liquid ratio 1:28 g·mL^(−1), extraction temperature of 49°C, and ultrasonic assistance for 61 minutes, the flavonoid yield was 7.88%, purity was 28.93%, polysaccharide yield was 1.48%, and purity was 26.56%. Under these optimized conditions, the process is stable and reliable, with high extraction yields, making it suitable for the simultaneous extraction and separation of valerian flavonoids and polysaccharides.

5 Component Analysis

5. 1    Thin-Layer Chromatography

Thymol triterpenes were identified using thin-layer chromatography with silica gel as the support medium, n-hexane-methyl ethyl ketone (4:1) as the developing solvent, and 3% nitrophenylpyridine solution as the developing agent. After spraying the developing agent, the plate was heated at 40°C for 90 minutes. Then, the plate was immersed in a 10% tetramethylamine acetone solution. Based on the different color development, different types of cycloether terpenes, such as monoterpenes, diterpenes, and alcohols, could be distinguished [8].

5.2 High-Performance Liquid Chromatography

Hou Wenhui et al. [37] used the ultrasonic method to determine the components of spider perfume herbal medicine. Chromatography column: Agilent ZORBAX SB-C18 column (4.6 mm × 250 mm, 5 μm, Agilent Technologies, USA); mobile phase: water (A) - acetonitrile (B); gradient elution; flow rate: 1 mL·min⁻¹; column temperature: 25 °C; detection wavelength: 241 nm; injection volume: 10 μL. Under these conditions, the content of valerian triterpenes, acetyl vibur-tinal ester, and the degradation products 11-ethoxy vibur-tinal and baldrinal. This method is not only precise and stable but also has good reproducibility, making it suitable for determining the content of spider incense components. It provides a reliable basis for the quality control and development of spider incense as a medicinal material. Liang Chao-feng et al. [38] used a Diamonsil C18 (250 mm × 4.6 mm, 5 μm) chromatographic column, with methanol (A) and 0.5% phosphoric acid solution (B) as the mobile phase, and performed gradient elution (0–5 min, 60% A → 70% A; 5–22 min, 70% A → 82% A; 22–30 min, 82% A → 82% A; 30–35 min, 82% A → 90% A), flow rate 1 mL·min^(−1), using the wavelength switching method (268 nm for valerenic acid and 255 nm for valerenol), the content of valerenic acid and valerenol in black water valerian was simultaneously determined at a column temperature of 35 °C. This method is simple to operate, provides accurate results, and has good reproducibility, providing a reliable method for evaluating the quality of black water Vaccinium myrtillus herbal materials.

5.3 Gas Chromatography Method

Hu Lixia et al. [39] employed gas chromatography with naphthalene as the internal standard, a DB-17 capillary column, helium as the carrier gas, and an electron impact (EI) ion detector. Under these chromatographic conditions, the concentration of acetyl borneol ester showed a good linear relationship (r = 0.9996) within the injection range of 0.1096 to 1.7536 μg; the recovery rate of acetyl borneol ester was 101.33%, with an RSD of 1.79%. This method can accurately determine the content of borneol acetate in black water valerian essential oil. Huo Jinhai et al. [40] used the following chromatographic conditions: DB-WAX capillary column (0.32 mm × 25 m), a temperature program of 60°C (10°C·min⁻¹) → 120°C (6°C·min⁻¹) → 140°C (10°C·min⁻¹) → 230°C (5 min), a split ratio of 30:1, and a FID detector, with naphthalene as the internal standard. The results showed that acetic acid borneol ester exhibited a linear relationship in the range of 0.016–0.250 mg (r = 0.99999), with an average recovery rate of  104.85%. This study provides a method for determining the volatile oil content of broad-leaved valerian and lays the foundation for the development and utilization of broad-leaved valerian plant resources.

5.4 Gas Chromatography-Mass Spectrometry

Qi Huan Yang et al. [41] utilized gas chromatography-mass spectrometry (GC-MS) with the following conditions: SE-54, 50 m × 250 μm × 0.50 μm capillary column (Chengdu Institute of Chemical Physics, Chinese Academy of Sciences), gasification chamber temperature 260 °C, split ratio 30:1, column pressure 17.8 kPa, using a constant flow mode carrier gas with He flow rate 1.2 mL·min^(−1), injection volume 1 μL, and a temperature program: initial temperature 60 °C, increased at 20 °C/min to 250 °C and held for 7 min. Mass spectrometry conditions: electron impact ionization (EI), electron energy 70 eV; ion source temperature 230 °C; quadrupole temperature 150 °C; transmission rod temperature 280 °C; solvent delay 5 min; scan range 14–400 m/z. Under these chromatographic and mass spectrometry conditions, the chemical components of Valeriana officinalis essential oil were determined, followed by identification of 67 components using the NIST spectral library and manual spectral analysis. The mass fractions of each component were determined using peak area normalization, accounting for 95.36% of the total chromatographic peak area. The aromatic components are mainly monoterpenes and sesquiterpenes, with the main aromatic components being patchouli alcohol (33.23% of the total) and valerianone (11.53% of the total). This study provides a basis for the determination of the chemical composition of Valeriana wallichii essential oil.

6  Tissue culture

In the field of tissue culture research on Valeriana wallichii, BACK et al. [42] analyzed the effects of light and medium composition on cell growth rate and the secondary metabolite yield of V.  wallichi. RUSS- OWSKI et al. [43] found that under various hormone combinations in MS and B5 culture media, changes in total biomass and triterpenoid content were not directly related to light intensity. Cui Lei [44] suggested that MS medium is more suitable as a basal medium for callus induction and subculture.

ZAMINI et al. [45] found that explant type significantly influences callus formation, with intermediate leaves forming callus more easily than basal leaves and petioles. Cui Lei [44] suggested that leaf tissue is more suitable as explants for callus induction. DAS et al. [46] found that rhizomes have the highest callus induction potential, followed by leaves. It can be seen that the callus formation potential is rhizomes > intermediate leaves > basal leaves and petioles.

DAS et al. [46] studied tissue culture and hormone combinations in Valeriana plants and found that MS medium supplemented with different concentrations of 2,4-D, NAA, and IBA could produce large amounts of callus tissue, even under different explant conditions. The 2, 4-D + KT combination of MS medium generally yielded higher callus formation rates than the NAA + KT combination of MS medium [45]. MATHUR et al. [47] found that adding 2,4-D (1.0 mg·L⁻¹) or NAA (3.0 mg·L⁻¹) to MS medium containing KT (0.25 mg·L⁻¹) is the optimal hormone combination for inducing callus formation in V. wallichi. MAURMANN et al. [48] found that adding 2,4-D (1.0 mg/L) and KT (0.25 mg/L) to MS medium resulted in the highest yield of cycloenthrone terpenoids in callus tissue. DAS et al. [46] found that a medium containing 2,4-D (1.0 mg/L) increased the yield of valerenic acid, while adding NAA (1.0 mg/L) to the medium resulted in higher valerenic acid yields. while IBA facilitates the accumulation of valerenic acid and valerenol concentrations.

Additionally, ABDI et al. [49] found through experiments that silver nanoparticles (NS) exhibit good potential for removing bacterial contaminants during Valeriana tissue culture. Cui Lei [44] discovered that the suspended adventitious root culture system is highly suitable as a high-yield cell culture system for Valerenic acid biosynthesis for further research. Li Meiyang et al. [50] found that under conditions where the NO:NH ratio was 1:1, the growth of adventitious roots, as well as the production of valerenic esters and valerenic acid, reached their highest levels.

7 Prospects

Valerian extracts and their formulations are highly popular in Europe and the United States, but in China, they are still in the clinical application and research stages, and the development and utilization of valerian in China remain relatively lagging. Valerian also possesses a distinctive aromatic fragrance, making it suitable for use in the tobacco industry, food and beverage products, and as a flavoring agent. Strengthening the adoption of rapid and large-scale tissue culture techniques for valerian seedling production, variety development, and industrialization is of particular importance.

Pharmacological tests have proven that Chinese valerian also possesses excellent sedative and antispasmodic effects. However, there is still a significant gap between China and other countries in the industrial development and utilization of valerian resources, making it difficult to compete with other valerian products in the international market. Therefore, further research and development of domestically produced valerian have become particularly important.

References

[1] LEATHWOOD, P. D., CHAUFFARD, F., HECK, E., et al. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man [J].  Pharmacology and Biochemistry and Behavior, 1982, 17(1): 65-71.

[2]    Huang Renquan, Zhang Li, Yang Jianli, et al. HPLC analysis and comparison of valerenic acid and valerenic acid derivatives in different species of Valeriana [J]. Chinese Herbal Drugs, 2002, 33(11): 1000-1001.

[3]    Li Shizhen. Compendium of Materia Medica (Herbal Section). Vol. 14 [M]. Beijing: People's Health Publishing House, 1991.

[4] HOUGHTON P J. The biological activity of valerian and related plants [J]. Journal of Ethnopharmacology, 1988, 22(2): 121-142.

[5] Editorial Committee of the Flora of China. Flora of China, Volume 73, Part 1 [M]. Beijing: Science Press, 1986.

[6] Chen Lei. Pharmacognosy and Resource Utilization of Valerian Genus Medicinal Plants in China [D]. Shanghai: Second Military Medical University, 2002.

[7] Huang Baokang, Zheng Hancen, and Qin Leping. Material basis of the sedative and hypnotic effects of Valeriana. Pharmaceutical Services and Research, 2006, 6(3): 165-168.

[8] Deng Jun, Tan Feng. Research Progress on Valerian [J]. Foreign Medicine (Plant Medicine Edition), 2000, 15(2): 53-56.

[9] Wang Jinxin, Han Zhuzhen, Li Hui Liang, et al. A new cycloartenol terpenoid compound from broad-leaved valerian [J]. Chinese Herbal Medicines, 2015, 46(1): 11-14.

[10] Zhou Ting, Huang Baokang. Chemical composition and pharmacological activities of Valeriana officinalis essential oil [J]. Journal of Traditional Chinese Medicine, 2008, 19(11):2663-2664.

[11] Zuo Yueming, Yan Huan, Zhang Zhongli. Study on the chemical components of Valeriana officinalis dioxo-lignans [J]. Chinese Herbal Medicines, 2017, 40(7): 1607-1610.

[12] Zuo Yueming, Xu Yuanli, Zhang Zhongli. Study on Flavonoid Components in Valerian [J]. Chinese Herbal Medicines, 2017, 40(6): 1331-1334.

[13] Zhang Jinpeng, Zhang Enxia. Experimental study on the sedative and hypnotic effects of Valerian [J]. Inner Mongolia Traditional Chinese Medicine, 2010, 29(10): 34

[14] Zhang Jinpeng, Han Guangting, Gong Ying, et al. Effects of Valeriana officinalis on IL-1β and TNF-α gene expression in mouse mononuclear cells [J]. Journal of Liaoning University of Traditional Chinese Medicine, 2010, 12(11): 237-238.

[15] Zhang Jinpeng, Han Guangting, Zhang Jinfeng, et al. Effects of Valeriana officinalis on the expression of IL-1β and TNF-α genes in mouse macrophages [J]. Journal of Liaoning University of Traditional Chinese Medicine, 2010, 12(9): 51-52.

[16] Ding Fei, Fang Ying, Wen Li, et al. Comparative study on the sedative and hypnotic effects of Valeriana officinalis essential oil and water extract [J]. Chinese Pharmacist, 2011, 14(10): 1411-1413.

[17] Zhao Lihui, Zhang Yizhe, Han Deming, et al. Antidepressant effects of valerian alcohol extract and water extract components on mice [J]. Journal of Zhengzhou University (Medical Edition), 2012, 47(1): 47-49.

[18] Qin Yajing, Lin Yukun, Zhou Chunchun, et al. Effects of Valeriana officinalis on serum corticosterone levels and the number of caspase-3-positive cells in the hippocampus of rats with chronic stress-induced depression [J]. Anatomical Research, 2009, 31(2): 88-93.

[19] Murphy K, Kubin ZJ, Shepherd JN, et al. Valeriana officinalis root extracts have potent anxiolytic effects in laboratory rats [J]. Phytomedicine, 2010, 17(8): 674-678.

[20] BENKE D, BARBERIS A, KOPP S, et al. GABA A receptors as an in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts [J]. Neuropharmacology, 2009, 56(1): 174-181.

[21] NOURIM H K, ABADA N A. GABAergic system role in aqueous extract of Valeriana officinalis L. root on PTZ-induced clonic seizure threshold in mice [J]. African Journal of Pharmacology, 2011, 5(9): 1212-1221.

[22] Rezvani ME, Roohbaksh A, Allahtaavakoli M, et al. Anticonvulsant effect of aqueous extract of Valeriana officinalis in amygdalakindled rats: Possible involvement of adenosine[J].  Journal of Ethnopharmacology, 2010, 127(2): 313-318.

[23] Xue C, He X, Zhang S, et al. Experimental study on the antitumor activity of valerian ringene terpenoid[J]. Journal of Modern Chinese Medicine, 2005, 14(15): 1969-1972.

[24] Zhang Renwei. Isolation and identification of terpenoid compounds from Valeriana officinalis[J]. Yunnan Journal of Botany, 1986, 8(1): 107-109.

[25] Ye Jianming, Yi Cuiqiong, Xue Cunkuan. Relationship between Valeriana bohemica extract-induced apoptosis and signal molecule expression in gastric cancer cells [J]. Chinese Journal of Digestive Diseases, 2004, 24(10): 619-620.

[26] Yuan Shanqin. Progress in the chemical and pharmacological research of Valeriana plants [J]. Foreign Medicine and Pharmacy, 1992, 1(6): 346-351.

[27] Guo Jixian. Specialized Research on Valerian. Common Chinese Herbal Medicines: Classification and Quality Research, Vol. 2 [M]. Fujian: Fujian Science and Technology Press, 1997: 490.

[28] PILEROOD S A, PRAKASH J. Evaluation of nutritional composition and antioxidant activity of Borage (Echium ammoenum) and Valerian (Valeriana officinalis) [J]. Food Sci, 2014, 51(5):845-854.

[29] Li Ying, Xue Cunkuan, He Xuebin, et al. Evaluation of the effects of Valerian extract on cerebral blood flow in mice using 99m Tc-ECD tracer [J]. Radiological Practice, 2003, 19(2): 133-134.

[30] Chen, B. Experimental study on the inhibitory effects of broad-leaved valerian on the proliferation and migration of rabbit vascular smooth muscle cells [J]. Journal of Mathematical Medicine, 2004, 17(3):281-282.

[31] Luo Xirong, Yuan Tianhong, Yang Jun, et al. Process study on the extraction of total valerian triterpenoids from spider incense using supercritical CO₂ [J]. Guangdong Agricultural Sciences, 2012, 16(8): 119-121.

[32] SAFARALIE A, FATEMI S, SALIMI A. Experimental design on supercritical extraction of essential oil from valerian roots and study of optimal conditions [J]. Food Bioprocessing, 2010, 88(2):312-318.

[33] BOYADZHIEV L, KANCHEVA D, GOURDON C. et al. Extraction of valerenic acids from Valeriana officinalis L. rhizomes [J]. Pharmazie, 2004, 59(9): 727-728.

[34] Li Gang, Fan Wenlei, Yu Deshun, et al. Study on the extraction and antioxidant activity of Valeriana officinalis essential oil [J]. Shizhen Guo Yi Guo Yao, 2015, 26(11):2647-2650.

[35] Dou Xiaowei, Sun Hui, Wu Jun Kai. Extraction methods and chemical composition of volatile oil from Heishui Valeriana [J]. Chinese Herbal Medicines, 2008, 1(1):32-33.

[36] Gu Zhengwei, Li Jilie, Wang Wei, et al. Simultaneous extraction and separation process of valerian flavonoids and polysaccharides [J]. Journal of Environmental Engineering, 2017, 11(2): 1141-1146.

[37] Hou Wenhui, Liu Yong, Wang Chungen, et al. Simultaneous determination of valerian triterpenoids and their degradation products in spider incense herbs by HPLC [J]. World Science and Technology - Modernization of Traditional Chinese Medicine, 2014, 16(12):2658-2663.

[38] Liang Chao-feng, Du Xiao-wei, Yan Mei. Simultaneous determination of valerenic acid and valerenol in black valerian by RP-HPLC [J]. Journal of Pharmaceutical Analysis, 2011, 31(4):671-673.

[39] Hu Lixia, Wang Xiaoxian, Zhao Ming. Determination of borneol acetate content in volatile oil of broad-leaved valerian by gas chromatography [J]. Chinese Journal of Ethnic and Folk Medicine, 2016, 25(21):23-25.

[40] Huo Jinhai, Dou Xiaowei, Sun Hui, et al. Determination of borneol acetate content in volatile oil of black water valerian by gas chromatography [J]. Shizhen Guo Yi Guo Yao, 2007, 18(10): 2381-2382.

[41] Qi Huanyang, Shi Yanping. Analysis of aromatic components of Valeriana microphylla by gas chromatography-mass spectrometry [C]. Shanghai: 2006 China Conference on Flavors and Fragrances, 2006.

[42] BACH K K, GHIA F, TORSSELL K B. Valtrates and lignans in Valeriana microphylla[J]. Planta Med, 1993, 59 (5): 478-479.

[43] Russowski D, Maurmann N, Rech S B, et al. Role of light and medium composition on growth and valepotriate contents in Valeriana glachomifolia whole plant liquid cultures[J]. Plant Cell, Tissue and Organ Culture, 2006, 86(2):211-218.

[44] Cui Lei. Study on the synthesis of valerenic acid in Valeriana officinalis cell culture [D]. Harbin Institute of Technology, 2013.

[45] ZAMINI A, MOKHTARI A, TANSAZ M, et al. Callus induction and plant regeneration of Valeriana officinalis are affected by different leaf explants and various concentrations of plant growth regulators [J]. Biotechnologia, 2017, 4(4):261-269.

[46] DAS A, MAO AA, HANDIQUE PJ. Callus-mediated organogenesis and effect of growth regulators on production of different valepotriates in Indian valerian [J]. Acta Physiologiae Plantarum, 2013, 35(1):55-63.

[47] MATHUR J, AHUJA P S. Plant regeneration from callus cultures of Valeriana wallichii D. C[J]. Plant Cell Reports, 1991, 9(9):523-526.

[48] MAURMANN N, de CARVALHO CMB, SILVA AIL, et al. Valepotriates accumulation in callus, suspended cells, and untransformed root cultures of Valeriana glechomifolia [J].  In Vitro Cellular & Developmental Biology Plant, 2006, 42(1):50-53.

[49] ABDI G, SALEHI H, KHOSH-KHUI M. Nano silver: A novel nanomaterial for removal of bacterial contaminants in valerian (Valeriana officinalis L.) tissue culture [J]. Acta Physiologiae Plantarum, 2008, 30(5):709-714.

[50] Li, M. Y., & Jin, J. (2016). Study on tissue culture of Valeriana officinalis adventitious roots. Hubei Agricultural Sciences, 55(5), 1304-1306.