What Active Ingredient Is in Valerian Extract?

Currently, there are few reviews or summaries of research on the chemical composition and physiological activities of Valeriana officinalis. This paper aims to organize and analyze recent domestic and international research progress on Valeriana officinalis, providing a reference basis for future studies on its chemical composition, physiological activities, and comprehensive development. Valerian (Valeriana officinalis L.) is the dried root and rhizome of the plant Valeriana officinalis L., belonging to the Valerianaceae family [1]. It has a cold nature, a pungent and bitter taste, and enters the heart and liver meridians. This herb has sedative, anxiolytic, and antispasmodic effects. Clinically, it is primarily used to treat insomnia, palpitations, anxiety, and other conditions associated with nervous system disorders, as well as for anxiety relief and the treatment of gastrointestinal pain [2-3]. It is widely distributed in northwestern and southwestern regions of China, including Chang'an, Ningxian, Lantian, and Huanglong in Shaanxi Province.

1  Morphology and identification

Valerian is a perennial herbaceous plant belonging to the Valerianaceae family. It has a thick and short rhizome, fleshy, with numerous fibrous roots that are elongated and branched, and emits a strong aromatic odor. The stem is erect, 50–100 cm tall, cylindrical with multiple purple longitudinal ridges, the nodes slightly protruding, and covered with white hairs. The basal leaves are pinnately deeply lobed. They have long petioles, which wither early or remain as remnants; stem leaves are opposite, odd-pinnately lobed, with 3–15 lobes, the margins having irregular coarse teeth or entire, both surfaces sparsely covered with white short hairs, the veins sunken and convex, the leaf bases flattened and broad, slightly clasping the stem. Flowers bloom in spring and summer, forming dense corymbose inflorescences; bracts are linear, opposite at the base of the flower axis, covered with white short hairs; calyx inconspicuous; corolla tubular, 5-lobed at the apex, white with a red halo, the red halo particularly prominent on the corolla tube; 3 stamens; 1 pistil, stigma extending beyond the corolla. Achenes narrow, elongated, and flattened, with a feathery crown at the apex.

V. officinalis L. (V. officinalis L.) is a medicinal herb first recorded in *Scientific Folk Herbs*, also known as “small rescue,” “large rescue,” “ground-clinging tiger,” and “seven-mile fragrance” (*Shaanxi Herbal Medicine*). In *Natural Medicinal Plants of the Qinling and Ba Mountains*, its authentic name is “small rescue,” and its commonly used parts are the root and rhizome [4]. Based on the source of the medicinal plant, it is also recorded in *Chinese Materia Medica* and *Comprehensive Dictionary of Chinese Herbal Medicines*. Due to its primary distribution in Shaanxi Province and its extensive coverage, “V. officinalis” serves as the original plant source for medicinal V. officinalis in Shaanxi, making it the primary medicinal variety.

2 Active Components of V. officinalis Extract

Valerian extract primarily contains volatile oil components (monoterpenes and sesquiterpenes), with the roots containing higher levels of cycloartenol and sesquiterpenes, and the roots having a higher content of volatile oils [5].

2.1 Monoterpenes and Sesquiterpenes

Volatile oils are important compounds in the roots and rhizomes of medicinal Valeriana, with specified minimum content requirements in the European Pharmacopoeia. Michael et al. [6] confirmed the presence of oil droplets in both the external and internal regions of Valeriana roots through histological techniques, optical microscopy, and Fourier transform infrared spectroscopy in preliminary experiments. Based on this, fluorescence microscopy was subsequently used to analyze images of the entire root cross-section, revealing a large number of oil droplets (averaging 43% of total oil droplets) located near the root surface. The remaining oil droplets were found in the internal regions (parenchymatous tissue), and their density showed a gradient from the internal to external regions depending on genotype, root thickness, and harvest depth.

Pharmacological activity is primarily concentrated in monoterpenes, whose chemical components mainly include borneol, isoborneol acetate, and borneol acetate; sesquiterpenes are present in relatively lower amounts, primarily belonging to the valerianane and guaiacolane types [7].

Wang et al. [8-9] isolated two new guaiane-type sesquiterpenoids from the roots of Valeriana: valerol A (1) and kessyl 3-acetate (2); and five known compounds: valer-acetate (3), anismol A (4), orientalol C (5), spatulenol (6), and 4α,10α-epoxyaromade-ndrane (7). Additionally, Volvalerenone A (8) was first isolated from Valeriana officinalis, marking the first discovery of a novel tricyclic terpenoid compound with a 5/6/6 ring system. The structural formulas of the components are shown in Figure 1. A total of 34 cycloaromatic terpenoids have been isolated from Valeriana officinalis, including 26 aglycones and 8 glycosides. Most of the triterpenoid glycoside aglycones are triterpenoid triterpenoids (also known as valerian triterpenoids or valerian glycosides), with most glycosides formed by the condensation of the hydroxyl group at the C-11 position with the hydroxyl group at the glucose terminal. The molecular structure contains Δ3(4), Δ5(6) [not Δ7(8)], and a three-membered oxygen-containing ring between C-8 and C-10. Substituents are primarily located at the C-1, C-7, and C-11 positions. The triterpenoids in Valeriana can be further classified into four categories: mono-ene closed-ring, polyene, diene closed-ring, and diene open-ring [10], with their parent nuclei shown in Figure 2.

2.2 Triterpenoids

Jiang Xia et al. [11] isolated tetrahydro-triterpenoids from Valeriana: β-sitosterol, and ursolic acid, a triterpenoid of the ursolic acid type.

2.3 Phenylpropanoids

In recent years, phenylpropanoid compounds isolated from Valeriana include phenylpropanoids and lignans, mostly of the monoxepane and dioxepane types. Zuo Yue-ming et al. purified six phenylpropanoid compounds using various column chromatography methods. Britta et al. studied the lignan content in the methanol extract of Valeriana root and isolated eight lignan compounds. See Tables 1 and 2.

Table 1  Phenylpropane compounds

Table 2  Lignin compounds

2.4 Flavonoids

Valerian also contains flavonoid chemical components, which are primarily found in the aboveground parts of the plant. The flavonoid content in flowers and fruits generally exceeds that in leaves. Zuo et al. isolated and purified flavonoids from valerian using various chromatographic methods, identifying the following flavonoid compounds. See Table 3.

Table 3  Flavonoid compounds

2.5 Alkaloids

The alkaloids present in Valeriana plants are primarily found in the underground parts of the plant, with a content of approximately 1%. Approximately 19 alkaloids have been isolated from Valeriana, primarily classified into two types: monoterpenoid and apioid. Monoterpenoids include pyridine-type (valeroline, valeranine) and quaternary ammonium-type. Alkaloids in Valeriana are present in low concentrations, and recent reports on the isolation of alkaloids from Valeriana are limited. It is currently believed that the total alkaloids have antibacterial activity, and the roots contain alkaloids such as β-valerine, 8-methoxyactinidine, chatinine, actinidine, isovaleramide, valeriamine, and valeriane [19].

3  Physiological activity

3.1 Effects on the nervous system

3.1.1 Sedative

Sung et al. [20] reported that Valeriana contains valerian diol and valerian triterpenes. Among these, valerian diol can reduce the excitability of reflexes and smooth muscle spasms, thereby effectively inhibiting the cerebral cortex, making it the active component responsible for Valeriana's sedative effect. Valerian triterpenes exhibit stronger sedative activity. Hyeon et al. [21] investigated the beneficial effects of Valeriana/Cascade mixtures on sleep in a mammalian animal model. In a pentobarbital-induced sleep model, Valeriana, Cascade, and Valeriana/Cascade mixtures significantly shortened the latency to sleep and effectively increased total sleep time compared to the control group. Taavoni et al. [22] selected women aged 50–60 as subjects. Comparisons between the experimental group and the placebo group indicated that Valerian effectively improved sleep disorder symptoms in perimenopausal women. Huang Huabin et al. [23] reported that valerian can effectively treat primary insomnia. This study investigated the effects of valerian on plasma melatonin (MT) levels and primary insomnia, finding that its therapeutic effects were approximately associated with an increase in plasma melatonin levels.

3.1.2 Antispasmodic and Analgesic Effects

Parvaneh et al. [24] selected 100 female students as subjects to investigate whether valerian could effectively treat dysmenorrhea. The experiment was conducted using a double-blind design at baseline and during the intervention period, with assessments based on observed simulated scoring criteria. By recording the severity of pain and physical manifestations of the subjects, it was concluded that valerian may have antispasmodic effects. Since it effectively inhibited uterine contractions in the subjects, this further demonstrated that valerian has a therapeutic effect on dysmenorrhea in women.

3.1.3 Antidepressant

The volatile oil components in Valerian, including Valerianol and Valerianic acid ester, exhibit significant antidepressant activity. Pakseresht et al. [25] found that Valerian has certain antidepressant and anxiolytic effects. Zhao Lihui et al. [26] found that valerian water extracts and alcohol extracts exhibit antidepressant effects. Yan Shuo [27] synthesized a valerian compound formulation with antidepressant properties. By observing the specific manifestations of experimental animals during the experiment, it was found that the valerian compound formulation significantly alleviated depression in experimental animals with few adverse reactions.

3.1.4 Anti-anxiety and anti-epileptic effects

Valerian root extract exhibits anti-anxiety effects. Wang Yanli et al. [28] found that valerian root extract exerts anti-anxiety effects by regulating the function of the hypothalamic-pituitary-adrenal (HPA) axis. Del et al. [29] used zebrafish as experimental subjects and concluded that valerian acid possesses anti-anxiety effects. The mechanism lies in valerian's selective interaction with metabolic glutamate receptors I and II. Murphy et al. [30] found that valerian's anxiolytic effects may be enhanced through exogenous GABA receptors, and valerenic acid is the primary component responsible for valerian's significant reduction in anxiety behavior in mice. Wu Bo et al. [31] found that the volatile oil components in valerian act on the balance between excitatory and inhibitory amino acids in the brains of model rats, thereby exerting an antiepileptic effect.

3.1.5 Anticonvulsant, cardiovascular protective, and antitumor effects

Mohammad et al. [32] evaluated the effects of Valeriana extract on temporal lobe epilepsy in rats and concluded that it exhibits anticonvulsant effects. Yang Shuhong et al. [33] reported that Valerian extract, when administered as a pretreatment, can protect rat myocardial cells from ischemia-reperfusion injury. Liu Junfeng et al. [34] reported that the volatile components in Valerian have antiarrhythmic effects. The mechanism may involve an unknown component entering the serum in its original form and acting as a serum drug component with antiarrhythmic properties. In vivo experiments using S180 or EAC tumor models in mice, valerian cycloartane terpenoid esters exhibited significant antitumor effects against S180 (solid type) and significantly prolonged the survival time of EAC-induced ascites cancer mice [35].

3.2 Antimicrobial and antiviral effects

Wang et al. [36] found that Valerian essential oil exhibits broad-spectrum antimicrobial activity, with minimum inhibitory concentration (MIC) values ranging widely from 62.5 μg/mL to 400 μg/mL, and the IC₅₀ values ranged from 36.93 μg/mL to 374.72 μg/mL. It also exhibited moderate antifungal activity against Candida albicans growth and inhibited the germination of Magnaporthe oryzae spores. In vitro experiments indicated that valerian components may be the active components responsible for its antiviral activity, thereby conferring valerian with anti-rotavirus activity.

3.3 Hepatoprotective and nephroprotective effects

Xu Shali et al. [37] found in a Wistar rat model of liver damage induced by a high-cholesterol, high-fat, and high-sugar diet that Valeriana extract increased total bile acid (TBA) content in bile, improved the TBA/total cholesterol (TC) ratio, reduced serum TBA concentration, and significantly alleviated liver damage. Chen Ling et al. [38] found that Valerian oil effectively improved kidney damage in type 2 diabetic rats, reduced proteinuria, and delayed kidney function damage. Their effects were associated with lipid-lowering, antioxidant properties, and inhibition of protein kinase C (PKC) activation in the renal cortex.

3.4 Other Effects

Valerian has antioxidant properties, In a study comparing the free radical scavenging activity, reducing capacity, and total antioxidant activity of its extracts, the highest and lowest activities were observed in water and acetone extracts. The 80% methanol extract exhibited the highest activity in reducing capacity and free radical scavenging activity measurements [39]. Sung et al. [20] reported that Valeriana root extract and Valerian acid enhance cognitive function in aged mice. Dorian et al. [40] aimed to assess whether the standardized extract (SE) of Valeriana officinalis has muscle relaxant effects by reducing skeletal muscle strength and/or neuromuscular tension in mice. This study provided evidence supporting the muscle relaxant effects of Valeriana officinalis extract on skeletal muscle.

4 Applications as a spice

Valerian has also found widespread application in daily life, primarily in tobacco and food products. Valerian essential oil, derived from its roots and rhizomes, is a key ingredient in the formulation of high-quality tobacco flavorings and is widely used in the tobacco industry as an important spice. Valerian serves as an excellent raw material for essential oil production and is extensively utilized in food products, as well as a valuable perfume and fragrance ingredient in the perfume industry. Valerian essential oil, prepared through processing, is easy to manufacture with simple equipment, a straightforward production process, and is easy to operate and process [41].

5 Conclusion

Valerian contains a large number of active components and exhibits diverse pharmacological effects, which has attracted increasing attention from researchers studying its pharmacological activities. These studies are primarily divided into two aspects: first, as a traditional medicinal plant, valerian contains a wealth of chemical components. By summarizing and organizing relevant literature from recent years, the latest isolated single compounds have been identified, with volatile oil components and cycloartenol derivatives being the most frequently reported. while reports on alkaloids are relatively scarce. In the isolation of single compounds, research has primarily focused on specific extraction sites rather than systematic isolation from all parts. The omission of certain extraction sites may result in an incomplete characterization of their components. The other aspect is the study of physiological activities, with recent years seeing more in-depth research on pharmacological mechanisms, primarily concentrated on the nervous system, antibacterial effects, and liver protection. However, studies on the activity and mechanisms of single compounds isolated from Valeriana are limited, primarily focusing on crude extracts. The physiological activities of some single compounds remain unclear, and the material basis for their pharmacological activities has not been clearly elucidated. Further research is needed to strengthen the study of single active components and their mechanisms.

Additionally, Valeriana officinalis is commonly used as a spice in the tobacco and food industries, primarily as a health supplement and flavoring agent. However, there are few research-based formulations developed from Valeriana officinalis. Therefore, it is essential to conduct comprehensive research on the active components and pharmacological effects of Valeriana officinalis, and based on this, develop effective formulations to uncover its potential market value. The medicinal value and special applications of Valeriana officinalis require further investigation.

References

[1] Du Tongfang, Huang Zhaosheng. Illustrated Dictionary of Chinese Herbal Medicine [M]. Guangzhou: Guangdong Science and Technology Press, 2011: 603.

[2] Liu Chunseng, Zhou Jianzhong, Xie Yu. Color Atlas of Medicinal Plants from the Compendium of Materia Medica [M]. Taiyuan: Shanxi Science and Technology Press, 2016: 911.

[3] Zhao Zhongzhen, Chen Hubiao. Illustrated Dictionary of Microscopic Identification of Chinese Medicinal Materials [M]. Fuzhou: Fujian Science and Technology Press, 2016: 488.

[4] Shaanxi Provincial Food and Drug Administration. Explanatory Notes on the Draft Standards for Medicinal Materials in Shaanxi Province [M]. Xi'an: Shaanxi Science and Technology Press, 2015: 353.

[5] Zhao Ting. Biological activity of Valeriana extract and Valeriana from Shaanxi Province [D]. Xi'an: Northwest University, 2012.

[6] Penzkofer M, Baron A, Naumann A, et al. Characterization of essential oil distribution in the root cross-section of Valeriana officinalis L.s.l. using histological imaging techniques [J]. Plant Methods, 2018, 14 (1): 41.

[7] Shi Jinli, Liu Yong, Xiao Peigen, et al. Chemical constituents and pharmacological effects of Valeriana plants [J]. Foreign Medicine · Plant Medicine, 2003, 18 (6): 231-239.

[8] Wang PC, Ran XH, Chen R, et al. Sesquiterpenoids and lignans from the roots of Valeriana officinalis L [J]. Chem. Biodivers, 2011, 8 (10): 1908-1913.

[ 9 ] Wang PC, Ran XH, Chen R, et al. Volvalerenone A, a new type of mononorsesquiterpenoid with an unprecedented 3,12-oxo bridge from Valeriana officinalis [J]. Tetrahedron Letters, 2010, 51 (41): 5451-5453.

[10] Zhang Zhenxue, Yao Xinsheng. Progress in the chemical research of Valeriana officinalis[J]. Chinese Journal of Medicinal Chemistry, 2000 (3): 226.

[11] Jiang Xia, Zhang Jianchao, Liu Yanwen. Chemical constituents of Valeriana officinalis[J]. Chinese Herbal Medicines, 2007, 30 (11): 1391-1393.

[12] Zuo Yueming, Yan Huan, Zhang Zhongli. Study on the Phenylpropanoid Chemical Constituents of Valerian [J]. Shizhen Guoji Guoyao, 2017, 28 (7): 1545-1546.

[13] Zuo Yueming, Zhang Zhongli, and Zeng Jixiang. Chemical Constituents of Valerian [J]. Chinese Herbal Medicines, 2012, 43 (7): 1091-1092.

[14] Zuo Yueming, Yan Huan, and Zhang Zhongli. Chemical Constituents of Valerian with Dihydroxy-2,3-Dihydro-2H-1-benzopyran-3-carboxylic Acid Esters [J]. Chinese Herbal Medicines, 2017, 40 (7): 1607-1608.

[15] Zuo Yueming, Wang Yafang, Zhang Zhongli, et al. Study on lignan chemical components in Valeriana. Chinese Herbal Medicines, 2018, 41 (5): 1091-1094.

[16] Britta S, Silke S, Josef H, et al. Lignans Isolated from Valerian: Identification and Characterization of a New Olivil Derivative with Partial Agonistic Activity at A(1) Adenosine Receptors [J]. Journal of Natural Products, 2002, 65 (10): 1479-1485.

[17] Zuo Yueming, Xu Yuanli, Zhang Zhongli. Study on flavonoid chemical components in Valeriana officinalis [J]. Chinese Herbal Medicines, 2017 (6): 1331-1332.

[18] Ding Fei. Study on the Sedative and Anxiolytic Active Compounds and Quality Standards of Valerian [D]. Wuhan: Hubei University of Traditional Chinese Medicine, 2012.

[19] Hou Mianzhang. Extracts of Chinese Herbal Medicines [M]. Beijing: China Pharmaceutical Science and Technology Press, 2004: 254-255.

[20] Nam SM, Choi JH, Yoo DY, et al. Valeriana officinalis extract and its main component, valerenic acid, ameliorate D-galactose-induced reductions in memory, cell proliferation, and neuroblast differentiation by reducing corticosterone levels and lipid peroxidation [J]. Exp Gerontol, 2013, 48 (11): 1369-1377.

[21] Choi HS, Hong KB, Han SH, et al. Valerian/Cascade mixture promotes sleep by increasing non-rapid eye movement (NREM) in a rodent model [J]. Biomed Pharmacother, 2018 (99): 912-920.

[22] Taavoni S, Haghani H. Valerian/Lemon balm use for sleep disorders during menopause [J]. Complement Ther Clin Pract, 2013, 19 (4): 193-196.

[23] Huang Huabin, Sha Rong, Wan Zhongxian. Effects of valerian on the efficacy of primary insomnia and endogenous plasma melatonin levels [J]. Asia-Pacific Traditional Medicine, 2013, 9 (3): 4-6.

[24] Mirabi P, Dolatian M, Mojab F. Effects of valerian on the severity and systemic manifestations of dysmenorrhea [J]. Int J Gynecol Obstet, 2011, 115 (3): 285-288.

[25] Pakseresht S, Boostani H, Sayyah M. Extract of valerian root (Valeriana officinalis L.) vs placebo in treatment of obsessive-

compulsive disorder: a randomized double-blind study [J]. Journal of Complementary and Integrative Medicine, 2011, 8 (1): 1553-3840.

[26] 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.

[27] Yan Shuo. Study on the Antidepressant Effects of a Compound Preparation of Ginseng, Valerian, and Omega-3 [D]. Chengdu: University of Electronic Science and Technology of China, 2012.

[28] Wang Yanli, Liu Yong, Shi Puli, et al. Preliminary investigation of the anxiolytic effects of valerenic acid and its mechanisms [J]. Chinese Journal of Pharmacology, 2011, 27 (4): 501-504.

[29] Del VM, Lisa M, Ortíz J. Anxiolytic properties of Valeriana officinalis in the zebrafish: a possible role for metabotropic glutamate receptors [J]. Planta Med, 2012, 78 (16): 1719-1724.

[30] 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.

[ 31 ] Wu Bo, Fu Yumei, Huang Aihua, et al. Effects of Valeriana officinalis essential oil on C-aminobutyric acid and glutamic acid levels in the hippocampus of pentylenetetrazole-induced epileptic rats[ J ] . Chinese Journal of Traditional and Western Medicine, 2008, 26 ( 11 ): 2476-2477.

[32] Rezvani ME, Roohbakhsh A, Allahtaavakoli M, et al. Anticonvulsant effect of aqueous extract of Valeriana officinalis in amygdala-kindled rats: possible involvement of adenosine [J]. Journal of Ethnopharmacology, 2010, 127 (2): 313-318.

[33] Yang Shuhong, Chen Fang, Ma Hongmei, et al. Protective effect of Valeriana officinalis extract pretreatment on myocardial ischemia-reperfusion injury in rats [J]. Journal of Wuhan University, 2012, 33(5): 639-643.

[34] Liu Junfeng, Fang Ying, Gong Zhanfeng, et al. Preliminary study on the serum pharmacochemistry of the active components of Valerian against arrhythmia [J]. Journal of Hubei Traditional Chinese Medicine, 2013, 35 (12): 72-73.

[35] Zhang Shuqin, Xue Cunkuan, He Xuebin, et al. The anti-tumor effect of valerian ringene terpene ester on mouse transplanted tumors [J]. Chinese Journal of Hospital Pharmacy, 2010 (12): 1008.

[36] Wang J, Zhao J, Liu H, et al. Chemical analysis and biological activity of the essential oils of two Valerianaceae species from China: Nardostachys chinensis and Valeriana officinalis [J]. Molecules, 2010, 15 (9): 6411.

[ 37 ] Xu Shali, Li Zhongming, Li Hanni, et al. Experimental study on the effects of Valeriana extract on bile acid metabolism and liver injury [ J ] . Pharmaceutical Guide, 2011, 30 ( 3 ): 298-301.

[38] Chen Ling, Jia Ruhan, Ding Guohua, et al. Protective effects of valerian oil on the kidneys of type 2 diabetic rats and a discussion of its mechanisms [J]. Chinese Journal of Nephrology, 2003, 19 (3): 168-169.

[39] Adel Pilerood S, Prakash J. Evaluation of nutritional composition and antioxidant activity of Borage (Echium amoenum) and Valerian (Valerian officinalis) [J]. Journal of Food Science and Technology, 2014, 51 (5): 845-846.

[40] Dorian C, Isabelle G, Aude L, et al. Skeletal muscle relaxant effect of a standardized extract of Valeriana officinalis L. after acute administration in mice [J]. Journal of Traditional and Complementary Medicine, 2018, 8 (2): 335-340.

[41] Wei Guimin, Li Dewen, Wang Shaoming. Research progress on Valeriana officinalis [J]. Agricultural Technology Services, 2016 (12): 19-20.