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Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala.

ABSTRACT: 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-? 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.

SUBMITTER: Chen L

PROVIDER: S-EPMC4230008 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala.

Chen Liang L Yang Yang Y Yuan Pulong P Yang Yifu Y Chen Kaixian K Jia Qi Q Li Yiming Y

Evidence-based complementary and alternative medicine : eCAM 20141030

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 ...[more]

PMID: 25530780

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Project description:BACKGROUND:A proprietary composition GMCT contains extracts of two popular Asian herbs viz., Garcinia mangostana (GM) fruit rind and Cinnamomum tamala (CT) leaf. We systematically evaluated physical performance and muscle strength enhancing ability of GMCT in a preclinical mouse model followed by a 42-days double-blind placebo controlled human trial in resistance trained adult males. METHODS:Four groups of Swiss albino mice (20-30 g body weight) (n?=?6) were fed a standard laboratory diet and given Carboxymethylcellulose sodium (CMC), 150 mg/kg GMCT (GMCT-150), 300 mg/kg GMCT (GMCT-300) or 50 mg/kg Oxymetholone (OXY) via oral gavage for 21 days. On day 22, the animals' physical performance and muscle strength were assessed in a forced swimming test (FST) and forelimb grip strength experiment, respectively. In the human trial, thirty-eight resistance-trained young adults (mean age 26.32?±?4.39 years, body weight 67.79?±?12.84 kg, BMI 22.92?±?3.54 kg/m2) completed the trial. The participants received either GMCT (n?=?19; 800 mg daily) or matched placebo (n?=?19) for 42 days. As primary variables, 1-RM bench press, 1-RM leg press, and leg extension repetitions were measured at baseline and on days 14, 28 and 42 of the intervention. Anthropometric parameters and serum markers such as free testosterone, insulin-like growth factor 1 (IGF-1), insulin and lactate were also measured before and after the intervention. RESULTS:GMCT-300 mice showed significant improvement in swimming time (GMCT: 395.3?±?81.70 s vs. CMC: 271.6?±?56.86 s; p?=?0.0166), distance (GMCT: 341.22?±?65.88 m vs. CMC: 260.84?±?49.15 m; p?=?0.0461) and grip strength (GMCT: 43.92?±?6.97 N vs. CMC: 35.0?±?6.92 N; p?=?0.0490), compared with the CMC group. At the end of the 42-day human trial, the per protocol analyses reveal that mean changes from baseline 1-RM bench press (GMCT: 23.47?±?10.07 kg vs. PL: 3.42?±?2.06 kg; p?<?0.0001), leg press (GMCT: 29.32?±?16.17 kg vs. PL: 5.21?±?1.72 kg; p?<?0.0001), number of leg extension repetitions (GMCT: 6.58?±?2.57 vs. PL: 2.05?±?1.22; p?<?0.0001) in GMCT group were significantly improved, compared with placebo. Intergroup difference analyses show that the changes from baseline left arm (GMCT: 1.09?±?0.36 cm vs. PL: 0.68?±?0.42 cm; p?=?0.0023), right arm (GMCT: 1.50?±?0.44 cm vs. PL: 1.11?±?0.43 cm; p?=?0.0088) circumference and lean mass (GMCT: 2.29?±?2.09 kg vs. PL: 0.52?±?2.58 kg; p?=?0.0404) in GMCT group were also significantly improved, compared with placebo. In comparison to placebo, GMCT supplementation did not improve free testosterone, IGF-1, insulin or lactate levels. Parameters of clinical biochemistry, hematology, urine and vital signs of the participants were within the normal range. CONCLUSION:GMCT supplementation is effective in increasing muscle strength, muscle size and, total lean mass, as well as endurance performance. TRIAL REGISTRATION:Clinical Trial Registry of India (CTRI/2015/01/005374), Registered on Jan 07, 2015; CTRI Website URL - http://ctri.nic.in.

Project description:Cinnamomum tamala (Buch.-Ham.) T.Nees & Eberm., or Indian Bay Leaf, is a well-known traditional ayurvedic medicine used to treat various ailments. However, the molecular mechanism of action of Cinnamomum tamala essential oil (CTEO) against non-small cell lung cancer (NSCLC) remains elusive. The present study aims to decipher the molecular targets and mechanism of CTEO in treating NSCLC. GC-MS analysis detected 49 constituents; 44 successfully passed the drug-likeness screening and were identified as active compounds. A total of 3961 CTEO targets and 4588 anti-NSCLC-related targets were acquired. JUN, P53, IL6, MAPK3, HIF1A, and CASP3 were determined as hub genes, while cinnamaldehyde, ethyl cinnamate and acetophenone were identified as core compounds. Enrichment analysis revealed that targets were mainly involved in apoptosis, TNF, IL17, pathways in cancer and MAPK signalling pathways. mRNA expression, pathological stage, survival analysis, immune infiltrate correlation and genetic alteration analysis of the core hub genes were carried out. Kaplan-Meier overall survival (OS) curve revealed that HIF1A and CASP3 are linked to worse overall survival in Lung Adenocarcinoma (LUAD) cancer patients compared to normal patients. Ethyl cinnamate and cinnamaldehyde showed high binding energy with the MAPK3 and formed stable interactions with MAPK3 during the molecular dynamic simulations for 100 ns. The MM/PBSA analysis revealed that van der Waals (VdW) contributions predominantly account for a significant portion of the compound interactions within the binding pocket of MAPK3. Density functional theory analysis showed cinnamaldehyde as the most reactive and least stable compound. CTEO exhibited selective cytotoxicity by inhibiting the proliferation of A549 cells while sparing normal HEK293 cells. CTEO triggered apoptosis by arresting the cell cycle, increasing ROS accumulation, causing mitochondrial depolarisation, and elevating caspase-3, caspase-8 and caspase-9 levels in A549 cells. The above study provides insights into the pharmacological mechanisms of action of Cinnamomum tamala essential oil against non-small cell lung cancer treatment, suggesting its potential as an adjuvant therapy.

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Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala.

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Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala.

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