Acorus calamus and osmanthus fragrans smelling traditional Chinese medicine compound essential oil for treating or improving depression

Abstract

The invention provides acorus tatarinowii, cinnamon and cinnamon odor-absorbing traditional Chinese medicine compound essential oil for treating or improving depression, and relates to the technical field of traditional Chinese medicine essential oil, the traditional Chinese medicine compound essential oil is prepared from acorus tatarinowii essential oil, cinnamon essential oil, ginger essential oil, radix curcumae essential oil, pericarpium citri reticulatae essential oil and mint essential oil; the traditional Chinese medicine compound essential oil provided by the invention can obviously or obviously improve apparent symptoms of depression model mice; the sweet water preference rate is remarkably or obviously increased, the movement time of the mouse is prolonged, and the activity of the mouse is improved; according to the traditional Chinese medicine compound essential oil disclosed by the invention, the expression level of IL-1beta and TNF-alpha in serum indexes is reduced, the expression level of DA, 5-HT, NE, BDNF, cAMP and P-CREB in brain tissue homogenate is improved, the traditional Chinese medicine compound essential oil has a remarkable improvement effect on depression, and the traditional Chinese medicine compound essential oil is administered in a sniffing manner, so that the anti-depression effect of the traditional Chinese medicine compound essential oil is equivalent to that of oral fluoxetine hydrochloride and is superior to that of oral capsules for soothing liver and relieving depression. The calamus-osmanthus fragrans odor-absorbing traditional Chinese medicine compound essential oil provided by the invention provides a new treatment thought and method for treating or improving depression.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine essential oils, and in particular to a Chinese medicine compound essential oil for olfactory administration of Acorus cinnamomea for treating or improving depression. Background Art

[0003] In the treatment of depression, most of the antidepressants used in clinical practice are synthetic antidepressants. The first generation of such drugs have been gradually abandoned due to safety issues, and the transition has been made to the second generation of synthetic antidepressants. However, the second generation of drugs still have shortcomings such as slow onset and relatively single target. These factors have prompted scientists to develop new third-generation antidepressants with higher targeting, higher efficiency and higher safety. However, the current third-generation antidepressants still have problems such as insufficient efficacy and many adverse reactions in the long-term and short-term treatment of patients. Therefore, the search for natural antidepressants with less toxicity and higher efficacy has become a new development hotspot.

[0004] Chinese herbal essential oil is a volatile oily liquid extracted from Chinese herbal medicine. It is a secondary metabolite composed of volatile small molecule active compounds and an oily liquid substance with a strong fragrance and smell. Chinese herbal essential oil has obvious advantages in treating depression. For example, the lipophilic small molecule compounds rich in essential oils can easily pass through the blood-brain barrier and quickly enter the brain to play an antidepressant effect; essential oils have a unique aromatic smell, which makes depressed patients feel happy and improves treatment compliance; essential oils can directly stimulate the olfactory nerves, promote the release of brain neurotransmitters and hormones, regulate BDNF and proinflammatory cytokines, etc., and play a multi-target and multi-pathway antidepressant effect. In addition, essential oil-derived aromatherapy covers a variety of administration methods, such as smearing, rubbing, gargling, medicinal bathing, sniffing, etc. Aromatherapy can affect the limbic cerebral cortex and neurotransmitters through the mouth, nose, and skin, and ultimately improve brain depression-like symptoms. Therefore, Chinese herbal essential oils are of great value in the development of new antidepressants. Summary of the invention

[0005] 1. Technical issues to be resolved

[0006] In view of the deficiencies in the prior art, the present invention provides a Chinese medicinal compound essential oil for olfactory use for treating or improving depression.

[0007] (II) Technical solution

[0008] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0009] The invention provides a Chinese medicinal compound essential oil for olfactory use of calamus and osmanthus for treating or improving depression. The Chinese medicinal compound essential oil is prepared from the following raw materials in parts by weight: 5-15 parts of calamus essential oil, 5-15 parts of cinnamon essential oil, 5-15 parts of ginger essential oil, 5-15 parts of curcuma essential oil, 1-10 parts of tangerine peel essential oil and 1-10 parts of peppermint essential oil.

[0010] Furthermore, the Chinese medicine compound essential oil is prepared from the following raw materials in parts by weight: 8-13 parts of calamus essential oil, 8-13 parts of cinnamon essential oil, 8-13 parts of ginger essential oil, 8-13 parts of turmeric essential oil, 3-8 parts of tangerine peel essential oil, and 3-8 parts of peppermint essential oil.

[0011] Furthermore, the Chinese medicine compound essential oil is made from the following raw materials in parts by weight: 10 parts of calamus essential oil, 10 parts of cinnamon essential oil, 8 parts of ginger essential oil, 10 parts of turmeric essential oil, 4 parts of tangerine peel essential oil, and 4 parts of peppermint essential oil.

[0012] The single essential oils of the above ingredients are all commercially available with a purity of more than 99%.

[0013] The osmanthus fragrans olfactory Chinese medicinal compound essential oil provided by the invention is used for preparing a preparation for treating or improving depression, and the preparation is a medically acceptable external preparation for an olfactory treatment method.

[0014] The rhizome of Acorus calamus is pungent and warm in nature, with an aromatic smell and strong dispersing power, and has the effect of promoting qi and opening the orifices; in addition, it also has the effects of removing dampness and stimulating appetite, opening the orifices and resolving phlegm, refreshing the mind and improving intelligence; Acorus calamus volatile oil is the main medicinal ingredient in Acorus calamus, and the content of β-asarone and α-asarone in Acorus calamus volatile oil is the highest. Studies have shown that Acorus calamus volatile oil has multiple effects on the central nervous system, such as anti-epileptic, anti-depressant, anti-Parkinson's disease, and anti-Alzheimer's disease.

[0015] Cinnamon is the dried bark of the cinnamon plant of the Lauraceae family. It is pungent, sweet and hot in nature, and has the effects of replenishing the original yang, warming the spleen and stomach, removing accumulated cold and activating blood circulation. Cinnamon volatile oil is the main active ingredient of cinnamon, which mainly contains four effective active ingredients: coumarin, cinnamyl alcohol, cinnamic acid and cinnamaldehyde. Studies have shown that cinnamon volatile oil has certain effects in antioxidant, anti-tumor and antibacterial aspects, but there has been no research on the anti-depression effect of cinnamon volatile oil.

[0016] Ginger is the fresh rhizome of the ginger plant of the ginger family. It tastes spicy and slightly warm in nature. It has the effects of dispelling cold, warming the middle and stopping vomiting, resolving phlegm and relieving cough, and detoxifying fish and crabs. Studies have shown that ginger volatile oil has certain effects in antioxidant, anti-tumor, antibacterial, and anti-inflammatory aspects.

[0017] Curcuma is the dried tuberous root of the ginger family plants Curcuma longa, Curcuma longa, Curcuma zedoaria or Curcuma zedoaria, also commonly known as "Wen Curcuma"; volatile oil is the main medicinal substance of Wen Curcuma, among which half of the terpenoid components are the main components. Wen Curcuma volatile oil has multiple effects such as anti-tumor, anti-inflammatory, sedative and analgesic, and anti-thrombotic.

[0018] Tangerine peel is the dried mature peel of the citrus plant and its cultivated varieties of the Rutaceae family. It has a slight fragrance, bitter and spicy taste, and is warm in nature. It has the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm. Tangerine peel volatile oil is one of the main active ingredients in tangerine peel. Tangerine peel volatile oil mainly contains active ingredients such as D-limonene, β-myrcene, α-pinene, etc., which have antibacterial, anti-inflammatory, anti-tumor, antitussive and analgesic effects.

[0019] Mint is an aromatic plant that is pungent in taste and cool in nature. It has the effects of dispersing wind-heat, clearing the head, relieving sore throat, clearing rashes, soothing the liver and promoting qi. Its mint volatile oil is the most important effective part. Relevant pharmacological studies have shown that mint volatile oil has anti-inflammatory, antibacterial, antiviral, antioxidant, and anti-anxiety and depression effects.

[0020] (III) Beneficial effects

[0021] The invention provides a Chinese medicinal compound essential oil for olfactory administration of Acorus cinnamomea for treating or improving depression. The present invention is based on the principle of syndrome differentiation and treatment in traditional Chinese medicine, and is modified from Acorus calamus and Curcuma decoction and Wendan decoction to obtain a Chinese medicine formula of Acorus calamus, cinnamon bark, ginger, Curcuma aromatica, tangerine peel and mint. In the formula, Acorus calamus is used as the main medicine for opening the orifices and dispelling phlegm, refreshing the mind and improving intelligence, and removing dampness and turbidity; Curcuma aromatica, cinnamon bark and ginger are used as the assistant medicines. Curcuma aromatica is a blood Qi medicine that can activate blood circulation, dispel blood stasis and relieve pain, and can also soothe the liver, promote qi and relieve depression; cinnamon bark warms yang and dispels cold, harmonizes qi and blood, and ginger warms the middle and dispels cold. The three are together the assistant medicines, and the Acorus calamus is used to make the qi flow smoothly and relieve liver depression, dissolve blood stasis and promote qi and blood, warm the yang and dispel cold and dampness, so that the mind can be clear; finally, tangerine peel and mint are used as adjuvants. Tangerine peel regulates qi and strengthens the spleen, digests food and resolves phlegm, and mint has the functions of soothing wind and dissipating heat, cooling and detoxifying. The two medicines have good effects of soothing emotions and enhancing the refreshing feeling of the formula. The six medicines work together to play the role of clearing the mind and calming the nerves, promoting blood circulation and qi, warming the yang and dispelling cold, regulating qi and digesting food, and are suitable for symptoms such as liver qi stagnation, restlessness, insomnia and dreaminess. On the basis of traditional Chinese medicine theory, we rationally match the volatile oils, i.e. essential oils, of the above-mentioned Chinese herbal medicines to obtain a Chinese herbal compound essential oil with the effect of treating or improving depression, which is prepared from calamus essential oil, cinnamon essential oil, ginger essential oil, turmeric essential oil, tangerine peel essential oil and peppermint essential oil.

[0022] We also used CUMS combined with solitary breeding to prepare depression model mice, and explored the antidepressant effect of the compound essential oil of the Chinese medicine of osmanthus fragrans for sniffing. The results of the study showed that the compound essential oil of the Chinese medicine of the present invention can significantly or significantly improve the apparent symptoms of depression model mice; significantly or significantly increase the preference rate for sugar water, increase the exercise time of mice, and improve the activity of mice; reduce the expression levels of IL-1β and TNF-α in serum indicators, and increase the expression levels of DA, 5-HT, NE, BDNF, cAMP, and P-CREB in brain tissue homogenate, which has a significant improvement effect on depression. The Chinese medicine compound essential oil of the present invention is administered by sniffing, and its antidepressant effect is equivalent to that of oral fluoxetine hydrochloride, and is better than oral Shugan Jieyu Capsules. The compound essential oil of osmanthus fragrans for sniffing provided by the present invention provides a new treatment idea and method for treating or improving depression. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is the establishment of the CUMS combined orphan depression model and drug intervention diagram.

[0024] Figure 2 The effect of the compound essential oil of Acorus cinnamomea on the body weight of mice in the depression model induced by CUMS combined with solitary rearing was compared with the blank group. △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05.

[0025] Figure 3 The effect of the compound essential oil of Acorus cinnamomea on the preference for sugar water in mice with depression model induced by CUMS combined with solitary rearing was compared with the blank group. △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05.

[0026] Figure 4 The effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the open field test of CUMS combined with solitary depression model mice; compared with the blank group, △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05.

[0027] Figure 5 The effect of the compound essential oil of Acorus cinnamomea on the tail suspension test of CUMS combined with solitary depression model mice was compared with the blank group. △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05.

[0028] Figure 6The effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the forced swimming test of CUMS combined with solitary depression model mice; compared with the blank group, △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05.

[0029] Figure 7 The effect of the compound essential oil of Acorus cinnamomea on the serum indexes IL-1β and TNF-α of mice with depression model induced by CUMS combined with solitary rearing was compared with the blank group. △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05.

[0030] Figure 8 The effect of the compound essential oil of Acorus cinnamomea on the expression levels of DA and 5-HT in the brain tissue homogenate of mice with depression model induced by CUMS combined with solitary rearing was compared with the blank group. △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05.

[0031] Fig. 9 The effect of the compound essential oil of Acorus cinnamomea on the expression levels of NE and BDNF in the brain tissue homogenate of mice with depression model induced by CUMS combined with solitary rearing; compared with the blank group, △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05.

[0032] Fig.10 The effect of the compound essential oil of Acorus cinnamomea on the expression levels of cAMP and P-CREB in the brain tissue homogenate of mice with depression model induced by CUMS combined with solitary rearing; compared with the blank group, △△ P<0.01, △ P<0.05; compared with the model group, **P<0.01, *P<0.05. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] Example 1

[0035] A Chinese medicinal compound essential oil for inhalation of calamus and osmanthus for treating or improving depression. The Chinese medicinal compound essential oil is prepared from the following raw materials in parts by weight: 5 parts of calamus essential oil, 5 parts of cinnamon essential oil, 5 parts of ginger essential oil, 5 parts of turmeric essential oil, 1 part of tangerine peel essential oil and 1 part of peppermint essential oil.

[0036] The single essential oils of the above ingredients are all commercially available with a purity of more than 99%.

[0037] The calamus chinensis traditional Chinese medicine compound essential oil provided by the invention is used for preparing a preparation for treating or improving depression, and the preparation is a medically acceptable oral or external preparation.

[0038] Example 2

[0039] The difference between this embodiment and embodiment 1 is that the Chinese medicine compound essential oil is made of the following raw materials in parts by weight: 15 parts of calamus essential oil, 15 parts of cinnamon essential oil, 15 parts of ginger essential oil, 15 parts of turmeric essential oil, 10 parts of tangerine peel essential oil, and 10 parts of peppermint essential oil.

[0040] Example 3

[0041] The difference between this embodiment and embodiment 1 is that the Chinese medicine compound essential oil is made of the following raw materials in parts by weight: 7 parts of calamus essential oil, 8 parts of cinnamon essential oil, 6 parts of ginger essential oil, 8 parts of turmeric essential oil, 2 parts of tangerine peel essential oil, and 3 parts of peppermint essential oil.

[0042] Example 4

[0043] The difference between this embodiment and embodiment 1 is that the Chinese medicine compound essential oil is made of the following raw materials in parts by weight: 14 parts of calamus essential oil, 12 parts of cinnamon essential oil, 11 parts of ginger essential oil, 14 parts of turmeric essential oil, 8 parts of tangerine peel essential oil, and 7 parts of peppermint essential oil.

[0044] Example 5

[0045] The difference between this embodiment and embodiment 1 is that the Chinese medicine compound essential oil is made of the following raw materials in parts by weight: 8 parts of calamus essential oil, 8 parts of cinnamon essential oil, 8 parts of ginger essential oil, 8 parts of curcuma essential oil, 3 parts of tangerine peel essential oil, and 3 parts of peppermint essential oil.

[0046] Example 6

[0047] The difference between this embodiment and embodiment 1 is that the Chinese medicine compound essential oil is made of the following raw materials in parts by weight: 13 parts of calamus essential oil, 13 parts of cinnamon essential oil, 13 parts of ginger essential oil, 13 parts of curcuma essential oil, 8 parts of tangerine peel essential oil, and 8 parts of peppermint essential oil.

[0048] Example 7

[0049] The difference between this example and Example 1 is that the traditional Chinese medicine compound essential oil is made from the following raw materials in parts by weight: 10 parts of Acorus tatarinowii essential oil, 12 parts of Cinnamon essential oil, 9 parts of Ginger essential oil, 12 parts of Curcuma aromatica Salisb. essential oil, 6 parts of Tangerine Peel essential oil, and 4 parts of Mentha haplocalyx Briq. essential oil.

[0050] Example 8

[0051] The difference between this example and Example 1 is that the traditional Chinese medicine compound essential oil is made from the following raw materials in parts by weight: 9 parts of Acorus tatarinowii essential oil, 8 parts of Cinnamon essential oil, 11 parts of Ginger essential oil, 11 parts of Curcuma aromatica Salisb. essential oil, 5 parts of Tangerine Peel essential oil, and 4 parts of Mentha haplocalyx Briq. essential oil.

[0052] Example 9

[0053] The difference between this example and Example 1 is that the traditional Chinese medicine compound essential oil is made from the following raw materials in parts by weight: 10 parts of Acorus tatarinowii essential oil, 10 parts of Cinnamon essential oil, 8 parts of Ginger essential oil, 10 parts of Curcuma aromatica Salisb. essential oil, 4 parts of Tangerine Peel essential oil, and 4 parts of Mentha haplocalyx Briq. essential oil.

[0054] Test Example

[0055] Effect of the Acorus tatarinowii, Curcuma aromatica Salisb., and Cinnamon smelling traditional Chinese medicine compound essential oil of the present invention on CUMS combined with single housing-induced depression model mice

[0056] 1 Experimental materials

[0057] 1.1 Experimental animals

[0058] 120 SPF-grade male C57 mice, weighing 18 - 20 g, were purchased from Jinan Pengyue Experimental Animal Breeding Co., Ltd. The animal certificate number: NO.370726221100428546; The license number of the Animal Experiment Center of Henan University of Chinese Medicine is SYXK(Yu)2021 - 0015. The mouse feed was provided by Jinan Pengyue Experimental Animal Breeding Co., Ltd., with the license number: SCXK(Lu)20190003.

[0059] The animals were raised in an SPF-grade laboratory. After being grouped and caged, the feeding conditions were maintained: temperature (26 ± 2)°C, relative humidity (49 ± 5)%, and they were fed and watered on time at 9:00 every day. The body weight was measured once a week, and the experiment started after one week of adaptive feeding.

[0060] 1.2 Experimental drugs

[0061] The Acorus tatarinowii, Curcuma aromatica Salisb., and Cinnamon smelling traditional Chinese medicine compound essential oil prepared in Example 9;

[0062] Fluoxetine Hydrochloride Tablets (positive drug), Changzhou Siyao Pharmaceutical Co., Ltd., product batch number: 202109102;

[0063] Shugan Jieyu Capsule (positive drug), Sichuan Jishengtang Pharmaceutical Co., Ltd., product batch number: 220103;

[0064] 2 Experimental design and methods

[0065] 2.1 Experimental design

[0066] After all mice were purchased, they were adaptively raised in the animal observation room for one week, and 12 mice were randomly divided into a blank group, and all the other mice were subjected to CUMS combined with solitary raising for 6 weeks to establish the model. After the model was established, neurobehavioral assessment was performed.

[0067] 2.2 Experimental methods

[0068] 2.2.1 Model preparation

[0069] 120 SPF c57 strain male mice were randomly selected as the blank group, and the remaining 108 mice were used to prepare the CUMS combined with single cage single-house depression model. The establishment of the CUMS model includes more than 10 different stress methods, two stresses are randomly arranged every day, and they are different within three days. The stress lasts for 6 weeks. The control group was not given any stimulation. (See Table 1 for details of the stimulation method)

[0070] Table 1 CUMS model making method

[0071]

[0072] 2.2.2 Experimental groups and drug administration

[0073] The body weight of 120 mice was measured once a week from the beginning of modeling. Within one week after the modeling, behavioral experiments were performed on the mice to evaluate depression. According to the results of body weight and behavioral experiments, 60 mice with successful model preparation and good condition were selected from 108 model mice and randomly divided into 5 groups, 12 mice in each group, including model group, Shugan Jieyu capsule group, fluoxetine hydrochloride group, high-dose osmanthus oil group, and low-dose osmanthus oil group for subsequent experiments. See the schematic diagram of the scheme for details. Figure 1 .

[0074] After the model was successfully prepared, medication was started, that is, medication was started from the 43rd day, once a day, for a total of 28 days. The Shugan Jieyu Capsule group (referred to as Caps-SGJY) was gavaged with Shugan Jieyu Capsule at a dose of 360 mg / kg; the fluoxetine hydrochloride group (referred to as Fluoxetine) was gavaged with fluoxetine hydrochloride at a dose of 5 mg / kg; the high-dose group of C. cinnamomea essential oil (referred to as H-CJGVO) was administered by sniffing at a dose of 0.5 mL / kg; the low-dose group of C. cinnamomea essential oil (referred to as L-CJGVO) was administered by sniffing at a dose of 0.25 mL / kg.

[0075] 2.3 Experimental indicators and tests

[0076] 2.3.1 Observation indicators

[0077] After the start of CUMS stimulation, the fur color, spirit, and activity of mice in each group were observed weekly, and the bedding was changed every 7 days. After the end of CUMS stimulation and drug administration, each group of mice was subjected to sugar water preference rate test, open field activity test, tail suspension test, and forced swimming test.

[0078] After 28 days of administration, the mice were fasted but not watered for 12 hours. They were weighed 2 hours after the last administration. Blood was collected from the eye sockets of the mice and centrifuged (3500rpm, 10min). The supernatant was taken to detect the levels of IL-6 and TNF-α in the serum. The brain was dissected and the expression levels of 5-HT, DA, NE, BDNF, cAMP, and p-CREB in the brain tissue homogenate were detected.

[0079] 2.3.2 Detection methods

[0080] 2.3.2.1 General status observation

[0081] a. Observation status: observe the mental state, behavioral changes, hair color, etc. of each group of mice;

[0082] b. Weight changes: Body weight was measured before the experiment and every week to observe the changes in body weight;

[0083] 2.3.2.2 Behavioral index detection

[0084] (1) Sugar Preference Test (SPT)

[0085] The mice were tested for sugar water preference before and after administration. The experimental steps are shown in Table 3:

[0086] Table 3 Experimental design of sugar water preference rate

[0087]

[0088]

[0089]

[0090] (2) Tail suspension test (TST)

[0091] The mice were suspended on the tail suspension device for rats and mice, and the immobility time of the mice was recorded within 6 minutes and the last 4 minutes.

[0092] Behavioral standards: hanging—the tip of the mouse's tail is fixed on a 30 cm high horizontal pole; inverted—a cylindrical plastic tube is placed at the base of the mouse's tail, with the body upright and downward; struggling—the mouse's limbs struggle violently / the forelimbs remain motionless; immobile—the mouse's limbs are spread out in a spread-eagle position and it gives up struggling.

[0093] (3) Forced swim test (FST)

[0094] Place the mouse individually in a glass tank with a length*width*height of 21cm*21cm*50cm, a water depth of about 33cm, and a temperature of about 25℃. Record the immobility time of the mouse in the 3rd to 5th minute within 6 minutes.

[0095] Behavioral standards: Swimming—the mouse swims around in the water; Climbing—the mouse paws paddling the water surface; Struggling—the mouse struggles violently with its limbs / the forelimbs are motionless, while the hind limbs keep paddling; Immobility—the mouse floats on the water surface with its limbs motionless / occasionally slides its limbs, with only the head above the water surface to breathe.

[0096] (4) Open field test (OFT)

[0097] A 50*50*40cm open-field mouse activity experimental system was used to observe the movement distance and movement time of each group of mice within 5 minutes.

[0098] 2.3.2.3 Biochemical index detection method

[0099] Enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β and TNF-α in serum; 5-HT, DA, NE, BDNF, cAMP, and p-CREB ELISA in brain homogenate were detected.

[0100] 2.4 Statistical methods

[0101] SPSS 26.0 software was used for statistical analysis of the data. Indicates. One-way-ANOVA was used for multiple group comparisons. LSD method was used for comparisons between two groups of data when the variances were equal, Games-Howell method was used for comparisons between unequal variances, and T test was used for two independent samples. Pathological results were analyzed using Radit test. P<0.05 was statistically significant, P<0.05 and P<0.01 represented obvious differences and significant differences, respectively. GraphPrism8.0.2 software was used to draw bar graphs. 3 Results

[0102] 3.1 Effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the body weight of mice in the depression model induced by CUMS combined with solitary rearing

[0103] The results are as follows Figure 2As shown in the figure, compared with the blank group, the body weight of the model group was significantly reduced (P<0.01). Compared with the model group, there was no significant change in the body weight growth of each medication group in the first 2 weeks of medication. After the third week of medication, the body weight of the fluoxetine hydrochloride group and the high-dose osmanthus oil group increased significantly (P<0.05), and the body weight of the Shugan Jieyu capsule group and the low-dose osmanthus oil group showed an increasing trend. After the fourth week of medication, the body weight of the fluoxetine hydrochloride group and the low-dose osmanthus oil group increased significantly (P<0.05), and the body weight of the high-dose osmanthus oil group increased significantly (P<0.01).

[0104] 3.2 Effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the neurobehavior of CUMS-induced depression model mice

[0105] 3.2.1 Effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the sugar water preference rate of mice with depression model induced by CUMS combined with solitary care

[0106] The results are as follows Figure 3 As shown in the figure, compared with the blank group, the preference rate of sugar water in the model group mice was significantly reduced (P<0.01). Compared with the model group, each drug-treated group can significantly increase the preference rate of sugar water in depressed mice (P<0.01). Among them, the high-dose group of osmanthus fragrans essential oil increased the preference rate of sugar water in depressed mice more significantly than other drug-treated groups. The results show that after drug intervention, the anhedonia of CUMS combined with solitary-reared depression model mice has significantly improved, and the high-dose osmanthus fragrans essential oil has the best effect.

[0107] 3.2.2 Effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the open field test of CUMS combined with solitary depression model mice

[0108] The mice were subjected to an open field trial test, and their movement status was determined by counting the movement distance and the time they stayed in the central area within 5 minutes.

[0109] The results are as follows Figure 4 As shown in the figure, compared with the blank group, the movement distance and central zone residence time of mice in the model group were significantly reduced (P<0.01). Compared with the model group, the movement distance of mice in the Shugan Jieyu capsule group and the low-dose cinnamon essential oil group was significantly increased (P<0.05), and the central zone residence time showed an increasing trend. The movement distance of mice in the fluoxetine hydrochloride group was significantly increased (P<0.01), and the central zone residence time was significantly increased (P<0.05). The movement distance and central zone residence time of mice in the high-dose cinnamon essential oil group were significantly increased (P<0.01).

[0110] 3.2.3 Effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the tail suspension test of CUMS combined with solitary depression model mice

[0111] The results are as follows Figure 5As shown in the figure, compared with the blank group, the immobility time of the model group mice was significantly prolonged (P<0.01). Compared with the model group, the immobility time of the tail suspension of the mice in the high-dose osmanthus oil group was significantly shortened (P<0.01), the immobility time of the tail suspension of the mice in the fluoxetine hydrochloride group and the low-dose osmanthus oil group was significantly shortened (P<0.05), and the immobility time of the tail suspension of the mice in the Shugan Jieyu capsule group showed a trend of shortening.

[0112] 3.2.4 Effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the forced swimming test of CUMS combined with solitary depression model mice

[0113] The results are as follows Figure 6 As shown in the figure, compared with the blank group, the immobility time of mice in the model group was significantly prolonged (P<0.01). Compared with the model group, the immobility time of mice in the fluoxetine hydrochloride group, the high-dose and low-dose osmanthus essential oil groups were significantly shortened (P<0.01), and the immobility time of mice in the Shugan Jieyu capsule group was significantly shortened (P<0.05).

[0114] 3.3 Effect of the compound essential oil of Acorus cinnamomea on the biochemical indexes of serum and brain tissue homogenate of mice with depression model induced by CUMS combined with solitary care

[0115] 3.3.1 Effect of the compound essential oil of Acorus cinnamomea on serum indicators IL-1β and TNF-α in mice with depression induced by CUMS combined with solitary care

[0116] The results are as follows Figure 7 As shown in the figure, compared with the blank group, the levels of IL-1β and TNF-α in the serum of the mice in the model group were significantly increased (P<0.01). Compared with the model group, the expression levels of IL-1β and TNF-α in the fluoxetine hydrochloride group were significantly decreased (P<0.01), the expression levels of IL-1β and TNF-α in the serum of the mice in the Shugan Jieyu capsule group were significantly decreased (P<0.05), the expression level of IL-1β in the serum of the mice in the high-dose cinnamon essential oil group was significantly decreased (P<0.05), and the expression level of TNF-α in the serum of the mice in the low-dose cinnamon essential oil group was significantly decreased (P<0.01), and the expression level of IL-1β in the serum of the mice in the low-dose cinnamon essential oil group was significantly decreased (P<0.05).

[0117] 3.3.2 Effect of the compound essential oil of Acorus cinnamomea on the expression levels of DA and 5-HT in the brain tissue homogenate of mice with depression model induced by CUMS combined with solitary care

[0118] The results are as follows Figure 8As shown in the figure, compared with the blank group, the expression of DA and 5-HT in the brain tissue homogenate of the model group mice was significantly decreased (P<0.01). Compared with the model group, the expression levels of DA and 5-HT in the brain tissue homogenate of the high and low doses of Acorus cinnamomea essential oil groups were significantly increased (P<0.01), and the expression levels of DA and 5-HT in the brain tissue homogenate of the mice in the fluoxetine hydrochloride group were significantly increased (P<0.05); the expression levels of DA and 5-HT in the brain tissue homogenate of the mice in the Shugan Jieyu capsule group showed an increasing trend.

[0119] 3.3.3 Effect of the compound essential oil of Acorus cinnamomea of ​​the present invention on the expression levels of NE and BDNF in the brain tissue homogenate of mice with depression model induced by CUMS combined with solitary care

[0120] The results are as follows Fig. 9 As shown in the figure, compared with the blank group, the expression levels of NE and BDNF in the brain tissue homogenate of mice in the model group were significantly decreased (P<0.01). Compared with the model group, the expression level of NE in the brain tissue homogenate of mice in the fluoxetine hydrochloride group and the high-dose osmanthus oil group was significantly increased (P<0.05), the expression level of NE in the brain tissue homogenate of mice in the Shugan Jieyu capsule group and the low-dose osmanthus oil group had an increasing trend, the expression level of BDNF in the brain tissue homogenate of mice in the Shugan Jieyu capsule group, the fluoxetine hydrochloride group, and the low-dose osmanthus oil group was significantly increased (P<0.01), and the expression level of BDNF in the brain tissue homogenate of mice in the high-dose osmanthus oil group was significantly increased (P<0.05).

[0121] 3.3.4 Effect of the compound essential oil of Acorus cinnamomea on the expression levels of cAMP and p-CREB in brain tissue homogenate of mice with depression model induced by CUMS combined with solitary care

[0122] The results are as follows Fig.10 As shown in the figure, compared with the blank group, the expression levels of cAMP and p-CREB in the brain tissue homogenate of the mice in the model group were significantly decreased (P<0.01). Compared with the model group, the expression level of cAMP in the brain tissue homogenate of the mice in the fluoxetine hydrochloride group and the high-dose osmanthus oil group was significantly increased (P<0.01), the expression level of cAMP in the brain tissue homogenate of the mice in the low-dose osmanthus oil group was significantly increased (P<0.05), the expression level of cAMP in the brain tissue homogenate of the mice in the Shugan Jieyu capsule group had an increasing trend, the expression level of p-CREB in the brain tissue homogenate of the mice in the Shugan Jieyu capsule group, the fluoxetine hydrochloride group, and the high-dose osmanthus oil group was significantly increased (P<0.05), and the expression level of p-CREB in the brain tissue homogenate of the mice in the low-dose osmanthus oil group had an increasing trend.

[0123] 4 Conclusion

[0124] We used CUMS combined with solitary breeding to prepare depression model mice, and explored the antidepressant effect of the scutellaria baicalensis compound essential oil by sniffing. The above experimental results show that the scutellaria baicalensis compound essential oil can significantly or significantly improve the apparent symptoms of depression model mice; significantly or significantly increase the preference rate for sugar water, increase the exercise time of mice, and improve the activity of mice; reduce the expression levels of IL-1β and TNF-α in serum indicators, and increase the expression levels of DA, 5-HT, NE, BDNF, cAMP, and p-CREB in brain tissue homogenate, which has a significant improvement effect on depression. The scutellaria baicalensis compound essential oil of the present invention is administered by sniffing, and its antidepressant effect is equivalent to that of oral fluoxetine hydrochloride, and is better than oral Shugan Jieyu Capsules. The scutellaria baicalensis compound essential oil provided by the present invention provides a new treatment idea and method for treating or improving depression.

[0125] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A Chinese medicinal compound essential oil of Acorus cinnamomea for treating or improving depression, characterized in that: The traditional Chinese medicine compound essential oil is prepared from the following raw materials in parts by weight: 5-15 parts of calamus essential oil, 5-15 parts of cinnamon essential oil, 5-15 parts of ginger essential oil, 5-15 parts of turmeric essential oil, 1-10 parts of tangerine peel essential oil and 1-10 parts of peppermint essential oil.

2. The Chinese medicinal compound essential oil of Acorus cinnamomea for treating or improving depression according to claim 1, characterized in that: The traditional Chinese medicine compound essential oil is prepared from the following raw materials in parts by weight: 8-13 parts of calamus essential oil, 8-13 parts of cinnamon essential oil, 8-13 parts of ginger essential oil, 8-13 parts of turmeric essential oil, 3-8 parts of tangerine peel essential oil and 3-8 parts of peppermint essential oil.

3. The Chinese medicinal compound essential oil of Acorus cinnamomea for treating or improving depression according to claim 1, characterized in that: The traditional Chinese medicine compound essential oil is prepared from the following raw materials in parts by weight: 10 parts of calamus essential oil, 10 parts of cinnamon essential oil, 8 parts of ginger essential oil, 10 parts of turmeric essential oil, 4 parts of tangerine peel essential oil and 4 parts of peppermint essential oil.

4. Use of the compound essential oil of the Chinese medicine for olfactory absorption of Cnidium monnieri as claimed in any one of claims 1 to 3 in the preparation of a preparation for treating or improving depression, wherein the preparation is a medically acceptable external dosage form for olfactory absorption therapy.

5. The Chinese medicinal compound essential oil of Cinnamomum cassia twig olfactory preparation according to any one of claims 1 to 3, characterized in that: The single essential oils of various components in the compound essential oil of osmanthus fragrans for olfactory Chinese medicine are all commercially available, and the purity is above 99%.

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