(E)-Tonghaosu

Bioactive compounds from Matricaria chamomilla: structure identification, in vitro antiproliferative, antimigratory, antiangiogenic, and antiadenoviral activities.[Pubmed:34463438]

Z Naturforsch C J Biosci. 2021 Jun 22;77(3-4):85-94.

During our exploring the anticancer activity of some medicinal plants and their major metabolites, the aerial parts of the Egyptian Matricaria chamomilla (flowers and stems) were studied. GC-MS analysis of the organic soluble extracts of the flowers and stems fractions revealed the presence of 43 and 45 compounds, respectively. Individual chromatographic purification of the flowers and stems' extracts afforded three major compounds. Structures of these compounds were identified by 1D- and 2D-NMR and HRESI-MS spectroscopic data as bisabolol oxide A (1) and (E)-Tonghaosu (2) (as mixture of ratio 2:1) from the flowers extract, meanwhile apigenin-7-beta-d-glucoside (3) from the stems fraction. Biologically, the chamomile extracts announced significant antiproliferative activities exceeded in potency by approximately 1.5 fold in case of the stem, recording GI(50) 13.16 and 17.04 mug/mL against Caco-2 and MCF-7, respectively. Both fractions were approximately equipotent against the migration of the same cell type down to 10 mug/mL together, compounds 1, 2 but not 3, showed considerable growth inhibition of the same cells at GI(50) 13.36 and 11.83 mug/mL, respectively. Interestingly, they were able to suppress Caco-2 colon cancer cells migration at 5.8 mug/mL and potently inactivate the VEGFR2 angiogenic enzyme (1.5-fold relative to sorafenib. The obtained compounds and corresponding chamomile extracts were evaluated against Adeno-7 virus, revealing that both chamomiles' extracts (flowers and stems) and their corresponding obtained compounds (1-3) were potent in their depletion to the Adeno 7 infectivity titer, however, the flower extract and compounds 1-2 were more effective than those of the stem extract and its end-product (3).

Matricaria chamomilla (Chamomile) Ameliorates Muscle Atrophy in Mice by Targeting Protein Catalytic Pathways, Myogenesis, and Mitochondrial Dysfunction.[Pubmed:34247561]

Am J Chin Med. 2021;49(6):1493-1514.

Muscle atrophy, or loss of skeletal muscle, is caused by aging, malnutrition, immobility through injury, or diseases such as cancer. Chamomile (Matricaria chamomilla L.) contains various active components, including flavonoids, sesquiterpenes, polyacetylenes, and coumarins, and is used in various herbal medicines in the European Pharmacopoeia. In this study, we investigated the effects of ethanol extract of chamomile [Formula: see text](MC) on muscle wasting and its mechanism of action. Mice with dexamethasone (DEX)-induced muscle atrophy were orally administered MC (100, 200, and 300 mg/kg) for 4 weeks. Micro-computed tomography analysis showed that MC (200 and 300 mg/kg) significantly recovered DEX-induced loss of muscle volume, density, and weight and MC-treated DEX-induced mice also showed increased moving distance and grip strength. MC suppressed the mRNA level of muscle RING finger 1 (MuRF1) while increasing the expression of mitochondrial transcription factor A (TFAM), MyoD, and Myogenin-1. We found 25 peaks in MC samples through HPLC analysis and identified 6 peaks by comparison with a profile of standard compounds: chlorogenic acid (CGA), luteolin-7-O-glucoside (L7G), patulitrin, apigenin-7-O-glucoside (A7G), herniarin, and (E)-Tonghaosu. Of these components, the gene expression of MyoD was significantly augmented by patulitrin, herniarin, CGA, and L7G in C2C12 cells, while Myogenin-1 gene expression was increased by A7G, patulitrin, herniarin, CGA, and L7G. Moreover, TFAM gene expression and phosphorylation of AKT were increased by all six ingredients. Based on our results, we suggest MC for use as a supplement or remedy for muscle wasting, including cachexia and sarcopenia.

B-ring-homo-tonghaosu, isolated from Chrysanthemum morifolium capitulum, acts as a peroxisome proliferator-activated receptor-gamma agonist.[Pubmed:30790129]

J Nat Med. 2019 Jun;73(3):497-503.

The capitula of Chrysanthemum morifolium and C. indicum are used to prepare Chrysanthemi Flos in traditional Japanese Kampo medicine. In our previous study, we reported on the agonistic effect of methanol extract of C. indicum capitulum on peroxisome proliferator-activated receptor (PPAR)-gamma. We further isolated (E)-Tonghaosu from C. indicum capitulum as one of the active ingredients. In the present study, we aimed to evaluate the PPAR-gamma agonistic activity of a methanol extract of C. morifolium capitulum (MCM) in which (E)-Tonghaosu could not be detected. MCM exhibited PPAR-gamma agonistic activity in a concentration-dependent manner, and at a dose of 100 microg/ml, it showed similar activity to pioglitazone (30 microM), a standard PPAR-gamma agonist. Through activity-guided fractionation, we isolated two geometric isomers, (E)- (1) and (Z)-B-ring-homo-tonghaosu (2), as the active ingredients of MCM. Both compounds exerted concentration-dependent PPAR-gamma agonistic effects, and 1 had higher activity than 2. At 1.4 microM, 1 had similar activity to pioglitazone (30 microM), which was achieved by 2 at a concentration of 140 microM. Thus, 1 has the potential to become a lead compound for the drug discovery of PPAR-gamma agonists. We compared the activities and the contents of (E)-, (Z)-tonghaosu, 1, and 2 among 13 commercial samples of Chrysanthemi Flos, including those derived from both C. morifolium and C. indicum. Their PPAR-gamma agonistic activities were not related to the contents of these compounds. 1 and 2 were detected in the samples derived from both species but (E)- and (Z)-tonghaosu were not detected in the samples derived from C. morifolium; hence (E)- and (Z)-tonghaosu can serve as marker compounds to identify the capitula of C. indicum in Chrysanthemi Flos samples.