Atractylodinol

Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-beta receptor 1 recycling by stabilizing vimentin.[Pubmed:37641404]

Mol Ther. 2023 Oct 4;31(10):3015-3033.

Pirfenidone and nintedanib are only anti-pulmonary fibrosis (PF) drugs approved by the FDA. However, they are not target specific, and unable to modify the disease status. Therefore, it is still desirable to discover more effective agents against PF. Vimentin (VIM) plays key roles in tissue regeneration and wound healing, but its molecular mechanism remains unknown. In this work, we demonstrated that Atractylodinol (ATD) significantly inhibits TGF-beta1-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transition in vitro. ATD also reduces bleomycin-induced lung injury and fibrosis in mice models. Mechanistically, ATD inhibited TGF-beta receptor I recycling by binding to VIM (K(D) = 454 nM) and inducing the formation of filamentous aggregates. In conclusion, we proved that ATD (derived from Atractylodes lancea) modified PF by targeting VIM and inhibiting the TGF-beta/Smad signaling pathway. Therefore, VIM is a druggable target and ATD is a proper drug candidate against PF. We prove a novel VIM function that TGF-beta receptor I recycling. These findings paved the way to develop new targeted therapeutics against PF.

Identification and characterization of small molecule inhibitors of porcine reproductive and respiratory syndrome virus.[Pubmed:28811186]

Antiviral Res. 2017 Oct;146:28-35.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiological agent of PRRS, an economically significant disease of swine worldwide. PRRSV is poorly controlled by the currently available vaccines, and alternative control strategies are needed to help prevent the continual circulation of the virus. Previously, we developed a synthetic route for the natural compound Atractylodinol and demonstrated anti-PRRSV activity in vitro. However, the synthetic route was inefficient and the yield was poor. To identify PRRSV inhibitors that could be synthesized easily and cost-effectively, we synthesized a series of Atractylodinol analogs and characterized their anti-PRRSV activity in vitro. A furan-substituted bis-enyne subunit was found to be critical for PRRSV inhibition. Six analogs had potent inhibitory activity against PRRSV with 50% inhibition concentration (IC(50)) of 0.4-1.4 muM and 50% cytotoxic concentration (CC(50)) of 209-1537 muM in MARC-145 cells. Three of the most promising compounds also demonstrated significant antiviral activity and low cytotoxicity in porcine macrophages. Inhibition of PRRSV in MARC-145 cells occurred primarily at a post-entry step during PRRSV replication, between 4 and 12 h post-entry. These results suggest that Atractylodinol analogs are promising antiviral candidates that could augment current PRRSV control strategies.

Insecticidal and repellant activities of polyacetylenes and lactones derived from Atractylodes lancea rhizomes.[Pubmed:25879503]

Chem Biodivers. 2015 Apr;12(4):593-8.

During a screening program for new agrochemicals from Chinese medicinal herbs and local wild plants, the petroleum ether (PE) extract of Atractylodes lancea (Thunb.) rhizomes was found to possess repellent and contact activities against Tribolium castaneum adults. Bioactivity-directed chromatographic separation of PE extract on repeated silica-gel columns led to the isolation of two polyacetylenes, atractylodin and Atractylodinol (1 and 2, resp.), and two lactones, atractylenolides II and III (3 and 4, resp.). The structures of the compounds were elucidated based on NMR spectra. The four isolated compounds were evaluated for their insecticidal and repellent activities against T. castaneum. Atractylodin exhibited strong contact activity against T. castaneum adults with a LD50 value of 1.83 mug/adult. Atractylodin and atractylenolide II also possessed strong repellenct activities against T. castaneum adults. After 4-h exposure, >90% repellency was achieved with atractylodin at a low concentration of 0.63 mug/cm(2) . The results indicated that atractylodin (1) and atractylenolide II (3) have a good potential as a source for natural repellents, and 1 has the potential to be developed as natural insecticide.

Species classification and quality assessment of cangzhu (atractylodis rhizoma) by high-performance liquid chromatography and chemometric methods.[Pubmed:23984190]

J Anal Methods Chem. 2013;2013:497532.

Fast and sensitive high-performance liquid chromatography (HPLC) coupled with chemometric methods was utilized to assist in the quality assessment of Cangzhu (Atractylodis Rhizoma). By comparative analysis of chromatographic profiles, twelve common peaks were selected for multivariate analysis. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of the chromatographic data demonstrated that 16 batches of Cangzhu samples could be welldifferentiated and categorized into two groups, which were closely related to their species (Atractylodes chinensis and A. lancea). By loading plots of PCA and OPLS-DA, the "common peaks" 2, 10, and 12 were defined as "marker peaks," which were identified as Atractylodinol, (4E,6E,12E)-tetradecatriene-8,10-diyne-1,3-diyl diacetate, and atractylodin, respectively. These three "marker peaks" were then simultaneously quantified for further controlling the quality of Cangzhu, which showed acceptable linearity, both intraday and interday precisions (RSD

Identification of porcine reproductive and respiratory syndrome virus inhibitors through an oriented screening on natural products.[Pubmed:32226262]

Chem Res Chin Univ. 2013;29(2):290-293.

Porcine reproductive and respiratory syndrome(PRRS) caused by porcine reproductive and respiratory syndrome virus(PRRSV) is one of the most infectious diseases in the swine industry worldwide, causing big economic losses. Vaccines are major weapons against PRRSV, however, current available vaccines have several limitations. Developing chemical drugs as alternatives is required. On the basis of traditional medical knowledge, we purposely selected 15 natural products originated from Chinese herbs with anti-infectious effects. Their antiviral activities were evaluated by PRRSV-induced cytopathic effect(CPE) on MARC-145 cells and reverse transcription polymerase chain reaction(RT-PCR) assay. Compounds ethoxysanguinarine(EOSG) and Atractylodinol were found to be the hits which could significantly reduce PRRSV-associated CPE with 50% inhibited concentration(IC(50)) values of 7.9 and 39.4 mumol/L, respectively. Meanwhile, compounds ethoxysanguinarine and Atractylodinol significantly decreased mRNA expression of ORF7 gene in a dose-dependent manner. Study results suggest that compounds ethoxysanguinarine and Atractylodinol may be useful anti-PRRSV drugs for swine industry or the hits for further lead optimization.

[Determination of tractylodinol in different populations of Atractylodes lancea].[Pubmed:20575380]

Zhongguo Zhong Yao Za Zhi. 2010 Apr;35(7):834-6.

OBJECTIVE: To establish an RP-HPLC method for determination of Atractylodinol in Ateractylodes lancea and compare the contents of Atractylodinol in the herbs of different origins. METHOD: The samples were separated on an Agilent TC-C18 (4.6 mm x 250 mm, 5 microm) column with the mobile phase of acetonitrile-water (49:51). Flow rate was 1.0 mL x min(-1). The detection wave length was set at 337 nm. Column temperature was 30 degrees C. RESULT: The linear range of Atractylodinol was 9.12 x 10(-2) -9.12 mg x L(-1) (r = 0.999 9), the average recovery was 97.15%, RSD was 1.5% (n = 5). The contents of Atractylodinol were in the range of 0.268-1.213 mg x g(-1) in the samples from different orgins. The contents of Atractylodinol in samples growing in Dabieshan mountain were higher than those in Jiangsu province (P < 0.001). CONCLUSION: The established method for determination of Atractylodinol is accurate and reliable, which can be used to evaluate the quality of A. lancea, the contents of Atractylodinol in the sample was related with its morphological characteristic and geographic orgin.

[Simultaneous determination of polyacetylene components in Cangzhu by reversed-phase high performance liquid chromatography].[Pubmed:17432582]

Se Pu. 2007 Jan;25(1):84-7.

In traditional Chinese medicines, atractylodes rhizome ("Cangzhu" in Chinese) is used for the treatment of rheumatic diseases, digestive disorders, mild diarrhea, night-blindness. According to the Pharmacopoeia of China (2005 Edition), Rhizoma Atractylodis is the dried root of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz. Polyacetylenes is one group of the most important active components in Cangzhu. A reversed-phase high performance liquid chromatographic method was developed for the simultaneous determination of two main polyacetylene components including atractylodin and Atractylodinol in Cangzhu. The chromatographic analysis was carried out using a Polaris-C18 column and the mobile phase of acetonitrile-water with the flow rate of 1.0 mL/min. The detection wavelength was set at 340 nm, and column temperature was set at 25 degrees C. The detection limits (S/N = 3) were 0.069 and 0.016 microg for atractylodin and Atractylodinol, respectively. The recoveries of the two polyacetylene components were found in the range of 97.4% - 104.6%. Thirteen samples collected were determined which includes three species of atractylodes rhizome, A. lancea, A. chinensis, and A. japonica. This rapid and accurate method has been successfully applied to the simultaneous determination of the two polyacetylene components in Cangzhu.

Effect of the rhizomes of Atractylodes lancea and its constituents on the delay of gastric emptying.[Pubmed:12499077]

J Ethnopharmacol. 2003 Jan;84(1):51-5.

The effect of rhizomes of Atractylodes lancea on gastric disorders, in particular, the delay in gastric emptying induced by N(G)-nitro-L-arginine in rats, was investigated. Intragastric treatment with an aqueous extract (250 mg/kg) and its lipophilic fractions (4 mg/kg) significantly improved delayed gastric emptying. The major constituents of the lipophilic fraction were two sesquiterpens, hinesol and beta-eudesmol, and four known polyacetylenic compounds, atractylodin, Atractylodinol, acetylAtractylodinol and 4,6,12-tetradecatriene-8,10-diyne-1,3,14-triol. The activity was found in the four polyacetylenic compounds at a similar potency, but not in the two sesquiterpens. To clarify the effect of the four polyacetylenic compounds in this extract, we attempted to evaluate the activity of atractylodin, as representative, at a dose of 0.2 mg/kg based on the total amounts (0.2 mg/250 mg aqueous extract) of the four polyacetylenic compounds. In addition, atractylodin improved the delay in gastric emptying at between 0.1 and 0.3 mg/kg in a dose-dependent manner. These results suggest that the aqueous extract improved the delayed gastric emptying, and polyacetylenic compounds contributed to its activity.

Further phenols and polyacetylenes from the rhizomes of Atractylodes lancea and their anti-inflammatory activity.[Pubmed:11488458]

Planta Med. 2001 Jul;67(5):437-42.

From the rhizomes of Atractylodes lancea, 2-[(2'E)-3',7'-dimethyl-2',6'-octadienyl]-4-methoxy-6-methylphenol (1) was isolated as a new natural product. The compound showed strong inhibitory effects on 5-lipoxygenase (5-LOX) and cyclooxygenase-1 (COX-1), but exhibited only weak antioxidative activities [IC50 = 0.1 microM (5-LOX), 2 microM (COX-1), 9 microM (PMN/FMLP), 28 microM (PMNIOZ)]. Moreover, five new acetylenes were isolated and elucidated as (3Z,5E,11E)-tridecatriene-7,9-diynyl-1-O-(E)-ferulate (2), erythro-(1,3Z,11E)-tridecatriene-7,9-diyne-5,6-diyl diacetate (3), (1Z)-atractylodin (4), (1Z)-Atractylodinol (5), (1Z)-acetylAtractylodinol (6) plus the known (4E,6E,12E)-tetradecatriene-8,10-diyne-1,3-diyl diacetate (7). Among the acetylenes, only 2 showed strong inhibition of 5-LOX and COX-1 activity (IC50 (5-LOX) = 3 microM, IC50 (COX-1) = 1 microM). In addition, the fatty acids linoleic acid, oleic acid and palmitic acid with previously established 5-LOX-/COX-1 inhibitory actions were identified as major constituents of the n-hexane extract and thus seem to contribute to the plant's in vitro activity.

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