JP-7856962-B2 - Methods for evaluating antidepressant effects

Inventors

• 太田 美里
• 大岩 優貴
• 牧野 利明
• 牧 靖人
• 関口 光広

Assignees

• 九鬼産業株式会社
• 公立大学法人名古屋市立大学
• 石川県公立大学法人

Dates

Publication Date

20260512

Application Date

20240927

Claims (7)

1. A method for evaluating antidepressant effects, comprising quantitatively analyzing one or more components contained in at least a part of a plant of the genus Valerian or a processed product thereof, and evaluating the antidepressant effect of the test substance by referring to the results of the quantitative analysis and criteria for antidepressant effect , A method comprising calculating a predicted value of relative serotonin uptake from the concentrations of one or more components, kesyl glycol diacetate and canoconyl acetate, using the following formula 1, obtained by quantitative analysis. (Formula 1) Relative serotonin uptake (%) = -440 × log [concentration of canoconyl acetate (μM)] - 327 × log [concentration of kesyl glycol diacetate (μM)] + 122 × log [concentration of canoconyl acetate (μM)] × log [concentration of kesyl glycol diacetate (μM)] + 1259 .
2. The method according to claim 1, wherein the plant of the genus Valeriana is one or more species selected from Valeriana fauriei, Valeriana verna, Valeriana japonica, Valeriana sylvestris, and Valeriana lisianthus.
3. The method according to claim 1 or 2, wherein one or more components include at least one component that is involved in serotonin reuptake inhibition.
4. The method according to claim 1 or 2, wherein one or more components are selected from the group consisting of kesyl glycol diacetate, canoconyl acetate, α-kesyl acetate, and canocol.
5. The method according to claim 1 or 2, wherein quantitative analysis is performed using liquid chromatography-mass spectrometry (LC-MS/MS) and/or high-performance liquid chromatography (HPLC).
6. The method according to claim 1 or 2 , wherein the antidepressant effect is determined to be high if the predicted value of the relative serotonin uptake calculated by formula 1 is 130% or less.
7. A method for selecting candidate active ingredients for an antidepressant or antidepressant food composition, comprising evaluating one or more components contained in at least a part of a plant of the genus Valerian, which is a test substance, or a processed product thereof, by the method described in claim 1 or 2.

Description

This invention relates to a method for evaluating antidepressant effects. Valeriana fauriei (Briq.) has traditionally been used in Japan as an ingredient in women's medicines. It is included in pharmaceuticals for menopausal symptoms, menstrual cramps, blood-related disorders, menstrual irregularities, and cold sensitivity, due to its expected anti-anxiety effects. It is also used as a flavoring agent in confectionery and other foods. Valeriana officinalis has long been used in Europe as a folk remedy for its sedative properties, and is relatively well-known in Japan as well. For this reason, it is included in herbal teas, bath products, cosmetics, and health supplements. Patent Document 1 describes that a composition containing an NSAID and valerian extract significantly improves relief from pain and muscle tension caused by stress and trauma. Patent Document 2 describes that combining a valerian extract with acetaminophen, ethenzamide, and allyl isopropylacetylurea exhibits an effect in improving pain-induced insomnia (sleep maintenance disorder). Patent Document 3 describes that a combination of valerian extract with ascorbic acid, glutamic acid, or Polygala extract can exert an analgesic effect and enhance the sedative effect. Japanese Patent Publication No. 2002-505296, NPS Pharmaceuticals, "Composition containing valerian extract, isovaleric acid or its derivatives together with an NSAID."Japanese Patent Publication No. 2015-189733, Kobayashi Pharmaceutical Co., Ltd., "Medicinal Composition for Pain and Insomnia"Japanese Patent Publication No. 2013-053144, Daiichi Sankyo Healthcare Co., Ltd., "Sedative Composition" Figure 1 shows the amount of serotonin uptake from valerian ethanol extract.Figure 2 shows the amount of serotonin uptake when (a) kesyl glycol diacetate (KGD) is added alone, or (b) a mixture of KGD and a fraction of valerian ethanol extract is added.Figure 3 shows the serotonin uptake levels of (a) canoconyl acetate (KNA), (b) canocol, or (c) α-kessyl acetate (α-KA).Figure 4 shows the correlation between serotonin uptake levels measured by cell experiments and predicted values for samples 1-13 containing KNA, canokol, α-KA, and KGD in various proportions. The numbers in the graph indicate the sample numbers (Table 1).Figure 5 shows the serotonin reuptake inhibitory effects when KNA, KGD, canocol, and α-KA are mixed.Figure 6 is a graph showing the correlation between serotonin uptake calculated from a model equation using KNA and KGD concentrations of valerian extract obtained by various extraction methods, and serotonin uptake measured by cell experiments. The numbers in the graph indicate the sample numbers (Table 2).Figure 7 shows the correlation between serotonin uptake calculated from a model equation using the KNA and KGD concentrations of various marketed valerian extracts and serotonin uptake measured by cell experiments. The numbers in the graph indicate the sample numbers (Table 4). [1. Methods for evaluating antidepressant effects] [Test substance] In the evaluation method of the present invention, the test substance is at least a part of a plant of the genus Valerian, or a processed product thereof. Examples of plants in the genus Valeriana include Valeriana fauriei. Examples include Briq., European valerian (V. officinalis), Indian valerian (V. jatamansi (V. wallichii), climbing valerian (V. flaccidissima), and lisianthus (V. phu (V. edulis)). The plant body of a Valerian genus plant may be only a part of it, for example, a part including the roots, rhizomes, or leaves, preferably a part including the roots and/or rhizomes. Examples of processed products include those obtained by subjecting the plant body or a part thereof of a Valerian genus plant to processing treatments such as crushing, drying, heat treatment, extraction, solid-liquid separation, concentration, granulation and/or powdering (preferably including drying, crushing, and extraction). More specifically, for example, a processed product (V. phu) obtained by drying and pulverizing the raw plant body (whole or part) of Valerian. Valerian powder: may be coarse powder or fine powder. Examples include processed products (chopped) obtained by drying and chopping the raw plant body or a part thereof of a plant of the genus Valerian, and Valerian plant extract. Examples of Valerian plant extract include extract obtained by extracting the raw plant body or a part thereof, dried product, or dried crushed product of a plant of the genus Valerian with a solvent, the dried product thereof (dried extract), and further, powdered dried extract obtained by powdering the same. Preferably, processed products of the roots and rhizomes of Valerian plants are used, and more preferably, a dried extract obtained by drying and crushing a part including the roots and rhizomes of a plant of the genus Valerian and extracting it with a solvent. Examples of extraction solvents include alcohol such as ethanol, a mixed solvent of alcohol and wa