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Antitumor, Antiviral, and Anti-Inflammatory Efficacy of Essential Oils from Atractylodes Macrocephala Koidz. Produced with Diffe

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Antitumor, Antiviral, and Anti-Inflammatory Efficacy of Essential Oils from Atractylodes Macrocephala Koidz. Produced with Diffe molecules Article Antitumor, Antiviral, and Anti-Inflammatory Efficacy of Essential Oils from Atractylodes macrocephala Koidz. Produced with Different Processing Methods 1, 1, 2 1,3, 1, Sihao Gu y, Ling Li y, Hai Huang , Bing Wang * and Tong Zhang * 1 School of Pharmacy, Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, 1200 Cai-lun Rd, Shanghai 201203, China 2 Experimental Teaching Center of Pharmaceutical Sciences, School of Pharmacy, Fudan University, 826 Zhang-heng Rd, Shanghai 201203, China 3 Center for Pharmaceutics Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai 201203, China * Correspondence: [email protected] (B.W.); [email protected] (T.Z.); Tel.: +86-021-51323068 (B.W.); +86-021-51322318 (T.Z.); Fax: +86-021-51322315 (B.W. & T.Z.) These authors contributed equally to this work. y Academic Editors: Valtcho Jeliazkov, Murray B Isman, Farid Chemat, Vassya Bankova and Niko Radulovi´c Received: 20 July 2019; Accepted: 13 August 2019; Published: 15 August 2019 Abstract: Atractylodes macrocephala Koidz. has been used as an invigorating spleen drug for eliminating dampness and phlegm in China. According to recent researches, different processing methods may affect the drug efficacy, so we collected A. macrocephala from the Zhejiang Province, produced with different processing methods, crude A. macrocephala (CA) and bran-processed A. macrocephala (BA), then analyzed its essential oils (EOs) by GC/MS. The results showed 34 components representing 98.44% of the total EOs of CA were identified, and 46 components representing 98.02% of the total EOs of BA were identified. Atractylone is the main component in A. macrocephala. Compared with CA, BA has 46 detected compounds, 28 of which were identical, and 6 undetected compounds. Pharmacodynamic results revealed that the EOs of CA and atractylone exhibited more effective anticancer activity in HepG2, MCG803, and HCT-116 cells than the EOs of BA; while the EOs of BA exhibited simple antiviral effect on viruses H3N2, both the EOs and atractylone show anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in ANA-1 cells. Keywords: Atractylodes macrocephala Koidz.; essential oils; atractylone; processing methods; GC/MS; pharmacodynamic effect 1. Introduction Atractylodes macrocephala Koidz. (Baizhu in Chinese), a perennial herb from the Compositae family, is a drug commonly used in traditional Chinese medicine. It has been used as a food and medicinal herb in China for thousand years [1]. In China, A. macrocephala is mainly distributed in Zhejiang Province which is known as one of authentic medicinal herbs “Zhebawei” [2]. Many components, such as essential oils (EOs), sesquiterpenoids, polysaccharides, amino acids, vitamins, resins, and other ingredients have been found in A. macrocephala up till recently [3,4]. A. macrocephala has many effects, such as strengthening the spleen, benefiting vital energy, eliminating dampness, hidroschesis, and soothing fetuses [5]. Molecules 2019, 24, 2956; doi:10.3390/molecules24162956 www.mdpi.com/journal/molecules Molecules 2019,, 24,, 2956x FOR PEER REVIEW 22 of of 14 In China, the methods of Chinese medicine processing became more and more common after the SongIn China, Dynasty. the methods The crude of ChineseA. macrocephala medicine (CA) processing and bran-processed became more A. and macrocephala more common (BA) after are the Songtwo drugs Dynasty. that Theare prepared crude A. macrocephalain pieces which(CA) have and b bran-processedeen widely usedA. as macrocephala a tonic in China.(BA) are Clinically, the two drugsthe CA that is aremainly prepared used in for pieces spleen which dampness have been and widely diuresis used aswhile a tonic after in China.bran-processed, Clinically, theit can CA issignificantly mainly used relieve for spleen dryness dampness and to andnify diuresisQi and spleen. while after It is bran-processed, because after processing, it can significantly the content relieve of drynessEOs with and sputum tonify effect Qi and decreased, spleen. It isand because the conten aftert processing, of lactones the which content inhibited of EOs uterine with sputum contraction effect decreased,increased; hence and the the content famous of doctor lactones Zhu which Danxi inhibited in the uterineYuan Dynasty contraction regarded increased; BA as hence the miscarriage the famous doctorprevention Zhu Danximedicine in the for Yuan the Dynastyfirst time regarded in the “D BAanxi as the Heart miscarriage Law” [6]. prevention The main medicine components for the of first A. timemacrocephala in the “Danxi are EOs Heart that Law” are made [6]. The up of main atractylone, components orange of A. linoleum, macrocephala elemene,are EOs and that isoeugenol are made [7]. up ofSo atractylone,after bran processing, orange linoleum, what changes elemene, in and the isoeugenol chemical [composition7]. So after bran of A. processing, macrocephala what have changes caused in thesuch chemical changes composition in its pharmacological of A. macrocephala effects?have caused such changes in its pharmacological effects? In recent years, years, the the research research on on the the active active ingredients ingredients of of A.A. macrocephala macrocephala hashas been been focused focused on onits itspolysaccharides polysaccharides and andlactones. lactones. The research The research on EOs on of EOsA. macrocephala of A. macrocephala focuses onfocuses component on component analysis, analysis,and rarely and involved rarely involved medicinal medicinal ingredients. ingredients. Pharmacological Pharmacological studies studiesand clinical and clinical practice practice have havedemonstrated demonstrated that thatA. macrocephalaA. macrocephala possessespossesses various various bioactivities, bioactivities, including including diarrhea, diarrhea, abdominal pain, and insuinsufficiencyfficiency of the stomach, intestine, liver, kidney, or insuinsufficiencyfficiency of the spleen with abundance of of dampness dampness [8,9]. [8,9]. A.A. macrocephala macrocephala hashas a regulating a regulating effect eff ecton the on thegastrointestinal gastrointestinal tracttract and andis commonly is commonly used used in the in the treatment treatment of ofdigestive digestive tr tractact diseases diseases [9,10]. [9,10]. Atra Atractylodesctylodes lactones lactones have antitumor effects effects [[11–13],11–13], but no study hashas been reported on whether the EOs of A. macrocephala has inhibitory eeffectffect on the digestive tract tumors; the previous research of the research group found that the EOsEOs of ofCinnamomi Cinnamomi ramulus ramulushas has antiviral antiviral and anti-inflammatoryand anti-inflammatory effects effects [14]. So, [14]. it suddenly So, it suddenly occurred tooccurred us that to since us thatA. macrocephalasince A. macrocephalaextract has extract many has pharmacological many pharmacological activities, activities, and the and EOs the are EOs one are of theone mainof the active main components active components of A. macrocephala of A. macrocephala, so the EOs, so oftheA. EOs macrocephala of A. macrocephalamight have might antitumor, have antiviral,antitumor, and antiviral, anti-inflammatory and anti-inflammatory effects. effects. Here, we collected A. macrocephala from the Pan’an District, Ji Jinhuanhua City, City, Zhejiang Province, China and analyzed its EOs constituents by GC/MS. GC/MS. In addition, for further exploitation of this plant, plant, the possible bioactivitiesbioactivities ofof thethe EOsEOs of CAof CA and and BA BA were were examined, examined, including including antitumor, antitumor, antiviral, antiviral, and anti-inflammatoryand anti-inflammatory activities, activities, to investigate to investigate the chemicalthe chemical compositions compositions and and biological biological activities activities of the of EOsthe EOs in the in e fftheective effective part, and part, find and the find material the basismate forrial its basis function. for its Here, function. our schematic Here, our illustration schematic of theillustration work is of revealed the work in Figureis revealed1. in Figure 1. Figure 1. TheThe relevance of chemical compositions in the EOs produced from A. macrocephala and biological activities. 2. Results 2.1. Chemical Composition of Essential Oils Molecules 2019, 24, 2956 3 of 14 2. Results Molecules 2019, 24, x FOR PEER REVIEW 3 of 14 2.1. Chemical Composition of Essential Oils Hydrodistillation of of CA CA yields yields 1.33% 1.33% (v/w) (v/w) and BA yields 1.07% (v/w) (v/w) of the yellow EOs using the Chinese Pharmacopoeia appendix method (Part IV General rule 2202). We We used the National Institute of of Standards and Technology (NIST) database to match and select the material with the highest matching degree and reference to determin determinee the compounds which are described in Figure 22 and TableTable1 .1. A A total total of 34of components34 components representing representing 98.44% 98.44% of the totalof the peak total areas peak of CAareas were of identified.CA were identified.The highest The content highest component content component of the EOs ofof CAthe wasEOs atractyloneof CA was (41.92%).atractylone For (41.92%). BA, 46 components For BA, 46 componentsrepresenting representing 98.02% of the 98.02% total peak of the areas total were peak identified areas were and identified the highest and content the highest component content of componentEOs of BA wasof EOs atractylone of
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