Cinnamtannin B1

[Condensed tannins from roots of Indigofera stachyodes].[Pubmed:34467724]

Zhongguo Zhong Yao Za Zhi. 2021 Aug;46(16):4131-4138.

Eleven condensed tannins were isolated from the roots of Indigofera stachyodes by various column chromatography techniques including silica gel, octadecyl silica(ODS), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC). These compounds were identified on the basis of physicochemical properties, nuclear magnetic resonance(NMR) and mass spectrometry(MS) data as stachyotannin A(1), epicatechin-(2beta-->O-->7,4beta-->8)-epiafzelechin-(4beta-->8)-catechin(2), cinnamtannin D1(3), Cinnamtannin B1(4), epicatechin-(2beta-->O-->7,4beta-->8)-epiafzelechin-(4alpha-->8)-epicatechin(5), gambiriin C(6), proanthocyanidin A1(7), proanthocyanidin A2(8), aesculitannin B(9), proanthocyanidin A4(10), and procyanidin B5(11). Compound 1 is a new compound. Compounds 2-11 were isolated from Indigofera for the first time. Furthermore, compounds 1, 2, and 4-11 showed inhibitory effects on thrombin-induced ATP release in platelets.

Comprehensive feature-based molecular networking and metabolomics approaches to reveal the differences components in Cinnamomum cassia and Cinnamomum verum.[Pubmed:34415684]

J Sep Sci. 2021 Oct;44(20):3810-3821.

Cinnamon was been a widely used plant in medicinal and spices for a long time and has spread all over the world. However, the differences in the components of the bark from Cinnamomum cassia and Cinnamomum verum, the two most common types of cinnamon, have not been thoroughly investigated. In the present experiment, ultra-high-performance liquid chromatography LTQ-Orbitrap Velos Pro hybrid mass spectrometer-based metabolomics coupled with chemometrics and feature-based molecular networking were employed to dramatically distinguish and annotate Cinnamomum cassia Bark and Cinnamomum verum bark. As a consequence, principal component analysis, orthogonal projection to latent structures discriminates analysis, and heat map analysis demonstrated clear discrimination between the profiles of metabolites in cinnamon. Besides, as the known compounds, proanthocyanidins (Cinnamtannin B1 and procyanidin B2) and alkaloids (norboldine, norisoboldine) with variable importance in the projection scores >6, and an unknown alkaloid (formula C24 H33 NO6 ) were selected as the best markers to discriminate cinnamon. Furthermore, large numbers of proanthocyanidins and alkaloids components were identified through feature-based molecular networking for the first time. Our investigation provides new ideas for the discovery of quality markers and identification of unknown components in natural products.

Inhibition of lytic polysaccharide monooxygenase by natural plant extracts.[Pubmed:34389999]

New Phytol. 2021 Nov;232(3):1337-1349.

Lytic polysaccharide monooxygenases (LPMOs) are monocopper enzymes of industrial and biological importance. In particular, LPMOs play important roles in fungal lifestyle. No inhibitors of LPMOs have yet been reported. In this study, a diverse library of 100 plant extracts was screened for LPMO activity-modulating effects. By employing protein crystallography and LC-MS, we successfully identified a natural LPMO inhibitor. Extract screening revealed a significant LPMO inhibition by methanolic extract of Cinnamomum cassia (cinnamon), which inhibited LsAA9A LPMO from Lentinus similis in a concentration-dependent manner. With a notable exception, other microbial LPMOs from families AA9 and AA10 were also inhibited by this cinnamon extract. The polyphenol Cinnamtannin B1 was identified as the inhibitory component by crystallography. Cinnamtannin B1 was bound to the surface of LsAA9A at two distinct binding sites: one close to the active site and another at a pocket on the opposite side of the protein. Independent characterization of cinnamon extract by LC-MS and subsequent activity measurements confirmed that the compound inhibiting LsAA9A was Cinnamtannin B1. The results of this study show that specific natural LPMO inhibitors of plant origin exist in nature, providing the opportunity for future exploitation of such compounds within various biotechnological contexts.

Cinnamtannin B1 attenuates rosacea-like signs via inhibition of pro-inflammatory cytokine production and down-regulation of the MAPK pathway.[Pubmed:33391878]

PeerJ. 2020 Dec 21;8:e10548.

BACKGROUND: Rosacea is a common inflammatory disease of facial skin. Dysregulation of innate immunity with enhanced inflammation and increased abundance of LL-37 at the epidermal site is a characteristic feature of rosacea. Cinnamtannin B1 (CB1) is a condensed tannin with anti-inflammatory and anti-microbial activities. The aims of the study were to evaluate the potential of CB1 as a therapy for rosacea and to characterize the potential mechanisms of action. METHODS: We intraperitoneally administered 20 mg/kg CB1 once daily for 2 days into the LL-37-induced mouse model of rosacea. The effects of CB1 in vivo were evaluated by the observations of lesions, histology, immunohistochemistry, and the transcription and translation of pro-inflammatory cytokines and chemokines. Human keratinocyte HaCaT and monocyte THP-1 were used to characterize the effects of CB1 on LL-37-induced inflammation in vitro. The changes in pro-inflammatory chemokine interleukin-8 (IL-8) were quantitated by enzyme-linked immunosorbent assay (ELISA), and the expressions of genes involved were determined by Western blotting. RESULTS: CB1 attenuated local redness, inflammation, and neutrophil recruitment in the mouse model of rosacea in vivo. CB1 suppressed myeloperoxidase (MPO) and macrophage inflammatory protein 2 (MIP-2) production, a functional homolog of interleukin-8 (IL-8), at the lesions. In vitro experiments confirmed that CB1 reversed the LL-37-induced IL-8 production in human keratinocytes HaCaT and monocyte THP-1 cells. CB1 inhibited IL-8 production through downregulating the phosphorylation of extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinase (MAPK) pathway. CONCLUSION: CB1 attenuated LL-37-induced inflammation, specifically IL-8 production, through inhibiting the phosphorylation of ERK. CB1 has potential as a treatment for rosacea.

Targeting Trimeric and Tetrameric Proanthocyanidins of Cinnamomum verum Bark as Bioactives for Dental Therapies.[Pubmed:33151073]

J Nat Prod. 2020 Nov 25;83(11):3287-3297.

The present study elucidated the structures of three A-type tri- and tetrameric proanthocyanidins (PACs) isolated from Cinnamomum verum bark to the level of absolute configuration and determined their dental bioactivity using two therapeutically relevant bioassays. After selecting a PAC oligomer fraction via a biologically diverse bioassay-guided process, in tandem with centrifugal partition chromatography, phytochemical studies led to the isolation of PAC oligomers that represent the main bioactive principles of C. verum: two A-type tetrameric PACs, epicatechin-(2beta-->O-->7,4beta-->8)-epicatechin-(4beta-->6)-epicatechin-(2beta- ->O-->7,4beta-->8)-catechin (1) and parameritannin A1 (2), together with a trimer, Cinnamtannin B1 (3). Structure determination of the underivatized proanthocyanidins utilized a combination of HRESIMS, ECD, 1D/2D NMR, and (1)H iterative full spin analysis data and led to NMR-based evidence for the deduction of absolute configuration in constituent catechin and epicatechin monomeric units.

Anti-Inflammatory and Antibacterial Activity Constituents from the Stem of Cinnamomum validinerve.[Pubmed:32722482]

Molecules. 2020 Jul 25;25(15). pii: molecules25153382.

One new dibenzocycloheptene, validinol (1), and one butanolide firstly isolated from the natural source, validinolide (2), together with 17 known compounds were isolated from the stem of Cinnamomum validinerve. Among the isolates, lincomolide A (3), secosubamolide (7), and Cinnamtannin B1 (19) exhibited potent inhibition on both superoxide anion generation (IC50 values of 2.98 +/- 0.3 microM, 4.37 +/- 0.38 microM, and 2.20 +/- 0.3 microM, respectively) and elastase release (IC50 values of 3.96 +/- 0.31 microM, 3.04 +/- 0.23 microM, and 4.64 +/- 0.71 microM, respectively) by human neutrophils. In addition, isophilippinolide A (6), secosubamolide (7), and Cinnamtannin B1 (19) showed bacteriostatic effects against Propionibacterium acnes in in vitro study, with minimal inhibitory concentration (MIC) values at 16 mug/mL, 16 mug/mL, and 500 mug/mL, respectively. Further investigations using the in vivo ear P. acnes infection model showed that the intraperitoneal administration of the major component Cinnamtannin B1 (19) reduced immune cell infiltration and pro-inflammatory cytokines TNF-alpha and IL-6 at the infection sites. The results demonstrated the potential of Cinnamtannin B1 (19) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan C. validinerve during bacterial infections.

Evaluation of the Anti-Diabetic Activity of Some Common Herbs and Spices: Providing New Insights with Inverse Virtual Screening.[Pubmed:31703341]

Molecules. 2019 Nov 7;24(22). pii: molecules24224030.

Culinary herbs and spices are widely used as a traditional medicine in the treatment of diabetes and its complications, and there are several scientific studies in the literature supporting the use of these medicinal plants. However, there is often a lack of knowledge on the bioactive compounds of these herbs and spices and their mechanisms of action. The aim of this study was to use inverse virtual screening to provide insights into the bioactive compounds of common herbs and spices, and their potential molecular mechanisms of action in the treatment of diabetes. In this study, a library of over 2300 compounds derived from 30 common herbs and spices were screened in silico with the DIA-DB web server against 18 known diabetes drug targets. Over 900 compounds from the herbs and spices library were observed to have potential anti-diabetic activity and liquorice, hops, fennel, rosemary, and fenugreek were observed to be particularly enriched with potential anti-diabetic compounds. A large percentage of the compounds were observed to be potential polypharmacological agents regulating three or more anti-diabetic drug targets and included compounds such as achillin B from yarrow, asparasaponin I from fenugreek, bisdemethoxycurcumin from turmeric, carlinoside from lemongrass, Cinnamtannin B1 from cinnamon, crocin from saffron and glabridin from liquorice. The major targets identified for the herbs and spices compounds were dipeptidyl peptidase-4 (DPP4), intestinal maltase-glucoamylase (MGAM), liver receptor homolog-1 (NR5A2), pancreatic alpha-amylase (AM2A), peroxisome proliferator-activated receptor alpha (PPARA), protein tyrosine phosphatase non-receptor type 9 (PTPN9), and retinol binding protein-4 (RBP4) with over 250 compounds observed to be potential inhibitors of these particular protein targets. Only bay leaves, liquorice and thyme were found to contain compounds that could potentially regulate all 18 protein targets followed by black pepper, cumin, dill, hops and marjoram with 17 protein targets. In most cases more than one compound within a given plant could potentially regulate a particular protein target. It was observed that through this multi-compound-multi target regulation of these specific protein targets that the major anti-diabetic effects of reduced hyperglycemia and hyperlipidemia of the herbs and spices could be explained. The results of this study, taken together with the known scientific literature, indicated that the anti-diabetic potential of common culinary herbs and spices was the result of the collective action of more than one bioactive compound regulating and restoring several dysregulated and interconnected diabetic biological processes.

Swarming Inhibitory Potential of Cinnamtannin B1 from Cinnamomum tamala T. Nees and Eberm on Pseudomonas aeruginosa.[Pubmed:31646246]

ACS Omega. 2019 Oct 3;4(16):16994-16998.

In a preliminary screening, the methanol extract of Cinnamomum tamala leaves was found to inhibit the swarming motility of Pseudomonas aeruginosa. Bioassay-guided fractionation by silica gel column chromatography led to the identification of Cinnamtannin B1 (1) as one of the active components of the extract. It inhibited the swarming motility (at 12.5 mug/mL) and biofilm formation (at 25 mug/mL) ofP. aeruginosa. Comparative gene expression analysis revealed downregulation of rhlA and fliC genes upon treatment with the tannin. The tannin may be affecting rhamnolipid and flagellin production. Thus, Cinnamtannin B1 is an active component of C. tamala responsible for inhibiting the swarming motility of P. aeruginosa.

Trimer procyanidin oligomers contribute to the protective effects of cinnamon extracts on pancreatic beta-cells in vitro.[Pubmed:27238208]

Acta Pharmacol Sin. 2016 Aug;37(8):1083-90.

AIM: Cinnamon extracts rich in procyanidin oligomers have shown to improve pancreatic beta-cell function in diabetic db/db mice. The aim of this study was to identify the active compounds in extracts from two species of cinnamon responsible for the pancreatic beta-cell protection in vitro. METHODS: Cinnamon extracts were prepared from Cinnamomum tamala (CT-E) and Cinnamomum cassia (CC-E). Six compounds procyanidin B2 (cpd1), (-)-epicatechin (cpd2), Cinnamtannin B1 (cpd3), procyanidin C1 (cpd4), parameritannin A1 (cpd5) and cinnamtannin D1 (cpd6) were isolated from the extracts. INS-1 pancreatic beta-cells were exposed to palmitic acid (PA) or H2O2 to induce lipotoxicity and oxidative stress. Cell viability and apoptosis as well as ROS levels were assessed. Glucose-stimulated insulin secretion was examined in PA-treated beta-cells and murine islets. RESULTS: CT-E, CC-E as well as the compounds, except cpd5, did not cause cytotoxicity in the beta-cells up to the maximum dosage using in this experiment. CT-E and CC-E (12.5-50 mug/mL) dose-dependently increased cell viability in both PA- and H2O2-treated beta-cells, and decreased ROS accumulation in H2O2-treated beta-cells. CT-E caused more prominent beta-cell protection than CC-E. Furthermore, CT-E (25 and 50 mug/mL) dose-dependently increased glucose-stimulated insulin secretion in PA-treated beta-cells and murine islets, but CC-E had little effect. Among the 6 compounds, trimer procyanidins cpd3, cpd4 and cpd6 (12.5-50 mumol/L) dose-dependently increased the cell viability and decreased ROS accumulation in H2O2-treated beta-cells. The trimer procyanidins also increased glucose-stimulated insulin secretion in PA-treated beta-cells. CONCLUSION: Trimer procyanidins in the cinnamon extracts contribute to the pancreatic beta-cell protection, thus to the anti-diabetic activity.

Structural characterization and bioactivity of proanthocyanidins from indigenous cinnamon (Cinnamomum osmophloeum).[Pubmed:27185335]

J Sci Food Agric. 2016 Nov;96(14):4749-4759.

BACKGROUND: Barks and twigs of common species of cinnamon with abundant proanthocyanidins are used as a spice, fold medicine or supplement. Cinnamomum osmophloeum is an endemic species in Taiwan and coumarin was not detected in the oil of the C. osmophloeum twig. The present study aimed to evaluate the relationship between the bioactivities and proanthocyanidins of C. osmophloeum twig extracts (CoTE). The n-butanol soluble fraction from CoTE was divided into 10 subfractions (F1-F10) by Sephadex LH-20 gel chromatography. The antihyperglycemic activities were examined by alpha-glucosidase, alpha-amylase and protein tyrosine phosphatase 1B inhibitory assays. Total antioxidant activities were examined by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging and ferrous ion-chelating assays. RESULTS: The results revealed that subfractions F6-F10, with high proanthocyanidin contents, showed excellent antihyperglycemic and antioxidant activities. Subfractions F6-F10 were analyzed further by matrix-assisted laser desorption/ionization-time of flight/mass spectrometry and thiolysis-reversed-phase high-performance liquid chromatography/tandem mass spectrometry methods. The results showed that the mean degrees of polymerization of proanthocyanidins in subfractions F6-F10 ranged from 3.5 to 5.1, with the highest degrees of polymerization of proanthocyanidins reaching 8 in subfractions F8-F10. Two compounds in F6 were identified as Cinnamtannin B1 and parameritannin A1. These proanthocyanidins contained at least one A-type and major B-type linkages. CONCLUSION: These results demonstrate that proanthocyanidins are associated with their antihyperglycemic and antioxidant activities in CoTE. (c) 2016 Society of Chemical Industry.

Identification of phenolics in litchi and evaluation of anticancer cell proliferation activity and intracellular antioxidant activity.[Pubmed:25857215]

Free Radic Biol Med. 2015 Jul;84:171-184.

Litchi leaf is a good resource for phenolics, which are good candidates for medicines. In this work, three phenolics were isolated from litchi leaf by column chromatography. Their structures were identified by electrospray ionization-mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy as secoisolariciresinol 9'-O-beta-D-xyloside (1), 4,7,7',8',9,9'-hexahydroxy-3,3'-dimethoxy-8,4'-oxyneolignan (2), and Cinnamtannin B1 (3). Cinnamtannin B1 showed better extra- and intracellular antioxidant activities than Compounds 1 and 2. The intracellular antioxidant activity of Cinnamtannin B1 was related to the upregulation of endogenous antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), and inhibition of ROS generation. Furthermore, Cinnamtannin B1 exhibited strong antiproliferative effects against HepG2 and Siha cell lines with no significant cytotoxicities. In the case of the HepG2 cell line, cell cycle arrest and apoptosis induction were the underlying anticancer mechanisms of Cinnamtannin B1. The results indicated that Cinnamtannin B1 was a potent cancer cell proliferation inhibitor and a good intracellular antioxidant.

Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala.[Pubmed:25530780]

Evid Based Complement Alternat Med. 2014;2014:365258.

Cinnamon barks extracts have been reported to regulate immune function; however, the component(s) in cinnamon barks responsible for this effect is/are not yet clear. The aim of this study is to find out the possible component(s) that can be used as therapeutic agents for immune-related diseases from cinnamon bark. In this study, the immunosuppressive effects of fraction (named CT-F) and five procyanidin oligomers compounds, Cinnamtannin B1, cinnamtannin D1 (CTD-1), parameritannin A1, procyanidin B2, and procyanidin C1, from Cinnamomum tamala or Cinnamomum cassia bark were examined on splenocytes proliferation model induced by ConA or LPS. Then, the effects of activated compound CTD-1 on cytokine production and 2,4-dinitrofluorobenzene (DNFB) induced delayed-type hypersensitivity (DTH) response were detected to evaluate the immunosuppressive activity of CTD-1. It was found that CT-F and CTD-1 significantly inhibited the splenocyte proliferation induced by ConA or LPS. CTD-1 dose-dependently reduced the level of IFN-gamma and IL-2 and intensively suppressed DNFB-induced DTH responses. These findings suggest that the immunosuppressive activities of cinnamon bark are in part due to procyanidin oligomers. CTD-1 may be a potential therapeutic agent for immune-related diseases.