Patchoulol is an important sesquiterpenoid in the volatile oil of Pogostemon cablin, and is also considered to be the main contributing component to the pharmacological efficacy and fragrance of P. cablin oil, which has antibacterial, antitumor, antioxidant, and other biological activities. Currently, patchoulol and its essential oil blends are in high demand worldwide, but the traditional plant extraction method has many problems such as wasting land and polluting the environment. Therefore, there is an urgent need for a new method to produce patchoulol efficiently and at low cost. To broaden the production method of patchouli and achieve the heterologous production of patchoulol in Saccharomyces cerevisiae, the patchoulol synthase(PS) gene from P. cablin was codon optimized and placed under the inducible strong promoter GAL1 to transfer into the yeast platform strain YTT-T5, thereby obtaining strain PS00 with the production of(4.0±0.3) mg·L~(-1) patchoulol. To improve the conversion rate, this study used protein fusion method to fuse SmFPS gene from Salvia miltiorrhiza with PS gene, leading to increase the yield of patchoulol to(100.9±7.4) mg·L~(-1) by 25-folds. By further optimizing the copy number of the fusion gene, the yield of patchoulol was increased by 90% to(191.1±32.7) mg·L~(-1). By optimizing the fermentation process, the strain was able to achieve a patchouli yield of 2.1 g·L~(-1) in a high-density fermentation system, which was the highest yield so far. This study provides an important basis for the green production of patchoulol.
Saccharomyces cerevisiae/metabolism* ; Sesquiterpenes/metabolism* ; Pogostemon ; Oils, Volatile/metabolism*

OBJECTIVE: Anxiety is one of the most common symptoms associated with autistic spectrum disorder. The essential oil of Cananga odorata (Lam.) Hook. f. & Thomson, usually known as ylang-ylang oil (YYO), is often used in aromatherapy as a mood-regulating agent, sedative, or hypotensive agent. In the present study, the effects and mechanisms of YYO in alleviating anxiety, social and cognitive behaviors in autism-like rats were investigated. METHODS: The prenatal valproic acid (VPA) model was used to induce autism-like behaviors in offspring rats. The effectiveness of prenatal sodium valproate treatment (600 mg/kg) on offspring was shown by postnatal growth observation, and negative geotaxis, olfactory discrimination and Morris water maze (MWM) tests. Then three treatment groups were formed with varying exposure to atomized YYO to explore the effects of YYO on the anxiety, social and cognitive behaviors of the autistic-like offspring through the elevated plus-maze test, three-chamber social test, and MWM test. Finally, the monoamine neurotransmitters, including serotonin, dopamine and their metabolites, in the hippocampus and prefrontal cortex (PFC) of the rats were measured using a high-performance liquid chromatography. RESULTS: Offspring of VPA exposure rats showed autism-like behaviors. In the VPA offspring, medium-dose YYO exposure significantly elevated the time and entries into the open arms in the elevated plus-maze test, while low-dose YYO exposure significantly enhanced the social interaction time with the stranger rat in session 1 of the three-chamber social test. VPA offspring treated with YYO exposure used less time to reach the platform in the navigation test of the MWM test. YYO exposure significantly elevated the metabolism of serotonin and dopamine in the PFC of VPA offspring. CONCLUSION YYO exposure showed the effects in alleviating anxiety and improving cognitive and social abilities in the offspring of VPA exposure rats. The role of YYO was related to the regulation of the metabolism of serotonin and dopamine. Please cite this article as: Zhang N, Wang ST, Yao L. Inhalation of Cananga odorata essential oil relieves anxiety behaviors in autism-like rats via regulation of serotonin and dopamine metabolism. J Integr Med. 2023; 21(2): 205-214.
Pregnancy ; Female ; Rats ; Animals ; Autistic Disorder/drug therapy* ; Oils, Volatile/therapeutic use* ; Serotonin/metabolism* ; Cananga/metabolism* ; Dopamine ; Anxiety/drug therapy* ; Valproic Acid/pharmacology* ; Plant Oils ; Disease Models, Animal

Objective To observe the role of tumor necrosis factor-α (TNF-α) and platelet-derived growth factor-B (PDGF-B) in kiwi fruit essence-mediated protection of radiation-induced lung injury (RILI) in rats. Methods 96 male healthy Sprague-Dawley rats were divided into normal control group, model group, and kiwi fruit essence treatment group(60 and 240 mg/kg) by the random number table method, with 24 animals in each group. The whole lungs underwent 6 MV X-ray irradiation (18 Gy) to induce RILI animal models in rats of the latter three groups. On the next day after irradiation, rats in the latter two groups were intragastrically administrated with 60 or 240 mg/kg kiwi fruit essence, once a day. The rats in the normal control and model groups were treated with 9 g/L sodium chloride solution. Eight rats in the latter three groups were randomly sacrificed on days 14, 28, and 56, while normal control rats were sacrificed on day 56 as the overall control. Blood samples were collected and separated. Serum concentrations of TNF-α and PDGF-B were detected using ELISA. The lung tissues were isolated for HE and Masson staining to evaluate alveolitis and pulmonary fibrosis (PF). The hydroxyproline (HYP) content in lung tissues was detected. The mRNA and protein expression of pulmonary TNF-α and PDGF-B were determined by quantitative real-time PCR and immunohistochemistry. Results Compared with the model group, treatment with 60 and 240 mg/kg kiwi fruit essence group significantly reduced alveolitis on days 14 and 28 as well as PF lesions on days 28 and 56. Compared with the normal control group, HYP content in the lung tissue of the model group increased on day 28 and day 56, while TNF-α and PDGF-B levels in the serum and lung tissues increased at each time point. Compared with the model group during the same period, 60 and 240 mg/kg kiwi fruit essence element treatment group reported the diminished levels of serum and pulmonary TNF-α on day 14 and day 28. Consistently, the lung tissue HYP content and serum and pulmonary PDGF-B levels on day 28 and day 56 were reduced. In addition, the above indicators in the 240 mg/kg kiwi fruit essence treatment group were lower than those for the 60 mg/kg kiwi fruit essence treatment group. Conclusion Kiwi fruit essence can alleviate RILI in rats, which is related to the down-regulation of TNF-α expression at the early stage and decreased PDGF-B level at the middle and late stages.
Animals ; Male ; Rats ; Fruit/metabolism* ; Lung/radiation effects* ; Lung Injury/prevention & control* ; Oils, Volatile ; Proto-Oncogene Proteins c-sis/metabolism* ; Pulmonary Fibrosis ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/metabolism* ; Actinidia/chemistry*

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.
Humans ; Monoterpenes/metabolism* ; Oils, Volatile/toxicity* ; Sesquiterpenes/metabolism* ; Skin/metabolism* ; Skin Absorption

To investigate the effects of essential oil from three kinds of pungent herbs,namely Menthae Haplocalycis Herba,Atractylodis Rhizoma and Cnidii Fructus,on the transdermal absorption in vitro of alkaloids from Sophorae Flavescentis Radix. The modified vertical Franz diffusion cell was used to conduct a transdermal experiment in vitro with the isolated abdominal skin of the SD rats as the transdermal absorption barrier. The effects of such three kinds of pungent essential oil on percutaneous absorption of alkaloids from Sophorae Flavescentis Radix were investigated by determining the content of 6 alkaloids( oxymatrine,oxysophocarpine,N-methylcytisine,sophoridine,matrine,and sophocarpidine) in the transdermal acceptor with ultra-performance liquid chromatography-triple quadruple mass spectrometry( UPLC-TQ-MS) technique simultaneously. With enhancement ratio( ER) as the index,their effects on promoting penetration was as follows: 1% Atractylodis Rhizoma oil > 1% Cnidii Fructus oil > 3% Azone ≈ 3% Atractylodis Rhizoma oil > 5%Atractylodis Rhizoma oil > 3% Cnidii Fructus oil ≈ 5% Cnidii Fructus oil > 3% Menthae Haplocalycis Herba oil > 5% Menthae Haplocalycis Herba oil > 1% Menthae Haplocalycis Herba oil > Blank. The results showed that these three kinds of pungent essential oil could be used as enhancers for alkaloids of Sophorae Flavescentis Radix,providing scientific guidance for improving percutaneous absorption of alkaloids from Sophorae Flavescentis Radix.
Alkaloids ; metabolism ; Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; metabolism ; Oils, Volatile ; pharmacology ; Plant Roots ; chemistry ; Rats ; Rats, Sprague-Dawley ; Skin Absorption ; Sophora ; chemistry

To study the antidepressant effect of Shugan Hewei Tang on chronic stress depression model rats, and select the effective substance fractions. Several male SD rats were randomly divided into 17 groups: blank control group, model group, positive control group(fluoxetine), Shugan Hewei Tang high and low dose groups, 6 high and low dose groups of different substance fractions. After modeling for 3 weeks and administration for 1 week, the effective substance fractions were selected according to the body mass and behavioral performance of SD rats in each group; several neurotransmitters in hippocampus of rats were determined by LC-MS/MS method, including norepinephrine(NE), serotonin(5-HT), 5-indoleacetic acid(5-HIAA), r-aminobutyric acid(GABA), and glutamic acid(Glu). Behavioral results after modeling showed that as compared with the blank group, the body mass growth of the model group was significantly reduced(P<0.01); the sugar water consumption was reduced(P<0.01); the distance between the open field and the number of crossing the central area were also significantly reduced(P<0.01, P<0.01); the resting time was increased significantly(P<0.01); and the forced swimming time was significantly prolonged(P<0.01), indicating that the depression model was effective. After intragastric administration, as compared with the model group, the above detection indicators of volatile oils, total polysaccharides and terpenoid in Fluoxetine, Shugan Hewei Tang groups were all changed(P<0.05 or P<0.01). The levels of NE, 5-HT and GABA in the hippocampus of the model group were significantly lower than those in the blank group(P<0.01), and the levels of 5-HIAA and Glu were significantly increased(P<0.01). As compared with the model group, neurotransmitters of the treatment groups were changed obviously or significantly(P<0.05 or P<0.01). Shugan Hewei Tang showed obvious anti-depressant effects, and the volatile oils, total polysaccharides and terpenoids acted as the main active substances. The mechanism of anti-depression may be related to its regulation of various neurotransmitter levels in the hippocampus.
Animals ; Chromatography, Liquid ; Depression ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; metabolism ; Male ; Neurotransmitter Agents ; metabolism ; Oils, Volatile ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stress, Psychological ; Tandem Mass Spectrometry

This study aims to compare the internal chemical composition and appearance indifferent growth patterns and years of Saposhnikovia divaricata decoction pieces,which was applied to explore the effect of growth patterns and years on its quality. The appearance characteristic data of 55 batches of different growth patterns and years of S. divaricata were collected using PANTONE color card.High performance liquid chromatography( HPLC) was used to determine the contents of prim-O-glucosyl-cinmifugin,cimifugin,4-O-β-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudol. The content of alcohol soluble extract and water-soluble extract were determined by hot-dip method. The content of volatile oil was determined by steam distillation. The correlation between growth patterns and years and the contents of 4 chromones,extracts and volatile oil were analyzed by modern statistical methods. Also,the method of comprehensively evaluating the quality of Chinese herbal pieces was developed by combining the growth patterns and years,appearance and chemical indexes. MTT assay was used to evaluate the effects on the survival rate of RAW264. 7 cells at four different concentrations of chromones and LPS was used to stimulate well-growing RAW264. 7 cells to establish an inflammatory model. The contents of NO and TNF-α in cell supernatant were detected by NO test kit and ELISA method. The contents of alcohol soluble extracts and water-soluble extracts in different growth patterns and years are: wild productsvolatile oil are: wild products>perennial cultivation>annual cultivation; the contents of four chromones are: wild products>perennial cultivation and annual cultivation. There was no significant difference between the sum of the two indexes in the Pharmacopoeia of perennial cultivation and wild products. 4 chromones showed no toxicity to RAW264. 7 cells at 5 mg·L-1. The release of NO and TNF-α was inhibited by 4 chromones and the anti-inflammatory effect of cimifugin was the best. In summary,there are obvious differences in appearance characteristics,internal quality and effects between different growth patterns and years. It showed that the wild products were superior to the perennial cultivation and the perennial cultivation was superior to the annual cultivation. In order to alleviate the shortage of wild S. divaricata resources,it is suggested that the Chinese Pharmacopoeia standard should increase the character of decoction pieces of perennial cultivation,and properly raise the limit requirement of the sum of the two indexes in the Chinese Pharmacopoeia to ensure the clinical demands and effect.
Animals ; Apiaceae/growth & development* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Mice ; Nitric Oxide/metabolism* ; Oils, Volatile/analysis* ; RAW 264.7 Cells ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVETo study the chemical composition, anticancer, anti-neuroinflflammatory, and antioxidant activities of the essential oil of Patrinia scabiosaefolia (EO-PS).

METHODSPatrinia scabiosaefolia was analyzed by gas chromatography-mass spectrometry. Eight human carcinoma cell lines, including SGC-7901, AGS, HepG2, HT-29, HCT-8, 5-FU/HCT-8, HeLa, and MDA-MB-231, were assessed by methylthiazolyldiphenyltetrazolium bromide (MTT) assay. Anti-neuroinflflammatory activity was assessed by production of interleukin (IL)-1β and IL-6 induced by lipopolysaccharide in BV-2 cells (microglia from mice). The antioxidant activity was evaluated with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay.

RESULTSForty-four components, representing 83.919% of the total oil, were identifified in the EO-PS. The major constituents were caryophyllene oxide (12.802%), caryophyllene (6.909%), α-caryophyllene (2.927%), β-damascenone (3.435%), calarene (5.621%), and phenol (3.044%). The MTT assay showed that the EO-PS exhibited significant dose-dependent growth inhibition in the 50-200 μg/mL dilution range. The EO-PS exhibited a dose-dependent scavenging activity against the DPPH radical, with an half of maximal inhibitory concentration 1.455 mg/mL.

CONCLUSIONSThe EO-PS possesses a wide range of antitumor, anti-neuroinflflammatory and antioxidant activities, suggesting that it may be a good candidate for further investigations of new bioactive substances.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antioxidants ; pharmacology ; Cell Death ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cytokines ; metabolism ; Free Radical Scavengers ; pharmacology ; Humans ; Inflammation Mediators ; metabolism ; Mice ; Oils, Volatile ; chemistry ; pharmacology ; Patrinia ; chemistry

OBJECTIVEThis study was conducted to determine the histopathological and biochemical effects of Thymus algeriensis essential oil (TEO) on hydrogen peroxide (H2O2)-induced oxidative stress in liver and kidney tissues of rats.

METHODSRats were treated in six groups and were exposed for 2 weeks to low (LD; 100 μmol/L) and high doses (HD; 1 mmol/L) of H2O2 in the presence or absence of TEO (180 mg/kg). Liver and kidney atrophy was measured by using biochemical and histopathological assays.

RESULTSOur study demonstrated that H2O2 induced liver and kidney atrophy, as evidenced by the significant elevation of serum aminotransferase, urea, and creatinine levels compared with those in the control rats. Urea levels were estimated by evaluating the activity of serum urease that hydrolyzes urea into CO2 and ammonia. However, TEO treatment significantly alleviated oxidative stress in the H2O2-induced liver and kidney toxicity model by reducing the levels of malondialdehyde concomitantly with marked elevations in superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase, as well as decrease in glutathione activity.

CONCLUSIONOur data demonstrated that TEO protected against H2O2 toxicity by decreasing oxidant levels and DNA damage, as well as increasing antioxidant levels, indicating that TEO has a spectrum of antioxidant and DNA-protective properties.

Animals ; Antioxidants ; pharmacology ; Hydrogen Peroxide ; metabolism ; toxicity ; Kidney ; drug effects ; physiology ; Lipid Metabolism ; drug effects ; Liver ; drug effects ; physiology ; Male ; Malondialdehyde ; metabolism ; Oils, Volatile ; pharmacology ; Oxidative Stress ; drug effects ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Regeneration ; drug effects ; Thymus Plant ; chemistry

PURPOSE: The purpose of this study was to evaluate the effects of essential oil on oxidative stress, immunity, and skin condition in atopic dermatitis (AD) induced mice. METHODS: This study was a 3x3 factorial design. Factors were oil type (Lavender, Thyme, and 2:1 mixture of lavender and thyme oil [blending oil]) and treatment period (0 day, 7 days, and 21 days). The samples were 45 mice with AD and randomly assigned to nine groups of five mice per group. The dependent variables such as superoxide radical, IgE, degranulated mast cells, and epidermal thickness were measured. Data were collected from February to April in 2014. Descriptive statistics, One-way ANOVA, Two-way ANOVA, and Tukey's HSD test were performed using the SPSS WIN 20.0 program. RESULTS: Dependent variables were not statistically significantly different by the three oil types (p >.05). Essential oils such as lavender, thyme, and blending oil were all effective in reducing AD symptoms and especially 2:1 blending oil were most effective. There were statistically significant differences by the three treatment periods in all dependent variables (p <.001). There were statistically significant interactions between oil types and treatment periods in all dependent variables (p <.01). For decreasing superoxide radical, degranulated mast cells, and epidermal thickness, 2:1 mixed oil should be applied for at least 21 days. Otherwise to reduce IgE, 2:1 mixed oil should be used for at least 7 days. CONCLUSION: These findings provide bases for developing effective interventions for AD patients to manage their AD symptoms.
Animals ; Dermatitis, Atopic/chemically induced/*drug therapy/pathology ; Disease Models, Animal ; *Immunity/drug effects ; Immunoglobulin E/blood ; Lavandula/*chemistry/metabolism ; Mast Cells/cytology/metabolism ; Mice ; Oils, Volatile/chemistry/pharmacology/therapeutic use ; *Oxidative Stress/drug effects ; Picryl Chloride/toxicity ; Plant Oils/chemistry/pharmacology/*therapeutic use ; Singlet Oxygen/metabolism ; Skin/drug effects/pathology ; Thymus Plant/*chemistry/metabolism