Anti-inflammatory effect and metabolic mechanism of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on atopic dermatitis in vivo and in vitro.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing skin disease accompanied by itchy and dry skin. AD is caused by complex interactions between innate and adaptive immune response. AD treatment include glucocorticoids and immunosuppressants. However, long-term treatment can have serious side effects. Thus, an effective AD treatment with fewer side effects is required. Natural materials, including herbal medicines, have potential applications. PURPOSE: This study evaluated the in vivo and in vitro therapeutic effects of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on AD and investigated the underlying metabolic mechanisms. METHODS: The anti-inflammatory effects of BS012 were assessed using a mouse model of AD induced by 1­chloro-2,4-dinitrobenzene (DNCB) and in tumor necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ) stimulated normal human epidermal keratinocytes (NHEKs). In DNCB-induced mice, total dermatitis score, histopathological analysis, and immune cell factors were assessed to evaluate the anti-atopic activity. In TNF-α/IFN-γ-stimulated NHEKs, pro-inflammatory cytokines, chemokines, and related signaling pathways were investigated. Serum and intracellular metabolomics were performed to identify the metabolic mechanism underlying the therapeutic effects of BS012 treatment. RESULTS: In DNCB-induced mice, BS012 showed potent anti-atopic activity, including reducing AD-like skin lesions and inhibiting the expression of Th2 cytokines and thymic stromal lymphopoietin. In TNF-α/IFN-γ-stimulated keratinocytes, BS012 dose-dependently inhibited the expression of pro-inflammatory cytokines and chemokines by blocking nuclear factor-kappa B and signal transducer and activator of transcription signaling pathways. Serum metabolic profiles of mice revealed significant changes in lipid metabolism related to inflammation in AD. Intracellular metabolome analysis revealed that BS012 treatment affected the metabolism associated with inflammation, skin barrier function, and lipid organization of the stratum corneum. CONCLUSION: BS012 exerts anti-atopic activity by reducing the Th2-specific inflammatory response and improving skin barrier function in AD in vivo and in vitro. These effects are mainly related to the inhibition of inflammation and recovery of metabolic imbalance in lipid organization. BS012, a novel combination with strong activity in suppressing the Th2-immune response, could be a potential alternative for AD treatment. Furthermore, the metabolic mechanism in vivo and in vitro using a metabolomics approach will provide crucial information for the development of natural products for AD treatment.

Chemical profiling and identification of anti-osteoporosis chemical-markers of Cinnamomum cassia (L.) presl extracts using GC-MS and spectrum-activity analyses.

Cinnamomum cassia (L.) Presl (cinnamon), an important folk medicine is widely used to prevent osteoporosis for long time in China. Our study aimed to investigate the anti-osteoporosis activity and mechanisms of cinnamon extracts obtained by supercritical CO2 extraction (SFE) and identify activity associated chemical components by gas chromatography-mass spectrometry. The cinnamon SFE exhibited superior anti-osteoporosis efficacy in an ovariectomised mice model to common alcohol extracts. It could induce calcified nodules and ALP activity, upregulate the mRNA expression of ALP, BMP-2, and RUNX2 in MC3T3-E1 cells. The major chemical classes of cinnamon extracts were alcohol esters (28.2%), and terpenes (16.1%). The spectrum-activity analysis indicated that the potential chemical-markers of extracts could be (E)-Cinnamaldehyde, γ-Sitosterol, and (Z, Z)-9,12-Octadecadienoic acid, which could induce the proliferation and ALP activity in MC3T3-E1 cells. Our study revealed the promising applications of the cinnamon SFE in prevention of osteoporosis, and identified its anti-osteoporosis associated compounds.

In vivo antioxidant activity of Cinnamomum cassia leaf residues and their effect on gut microbiota of d-galactose-induced aging model mice.

BACKGROUND: To thoroughly explore the values of Cinnamomum cassia leaf residues (CcLR), their antioxidant activity in vivo and the relationship with gut microbiota were investigated using d-galactose-induced aging mice. RESULTS: Results showed that CcLR extract treatment exerted antioxidant activity by increasing the levels of superoxide dismutase (P < 0.01) and glutathione peroxidase (P < 0.05), as well as inhibiting the formation of malondialdehyde (P < 0.01). Meanwhile, the inflammatory response was also alleviated as the ratio of pro-inflammatory tumor necrosis factor-α (P < 0.01) and interleukin-1ß (P < 0.01))/anti-inflammatory cytokines (interleukin-10; P < 0.05) in serum was decreased and the contents of inflammatory markers (induced nitrogen monoxide synthase and nitric oxide) in brain and liver tissues (P < 0.01) were reduced. Moreover, through inhibiting acetylcholinesterase activity and improving choline acetyltransferase activity, the cholinergic system in aging mice recovered to levels comparable to the normal control group. In addition, 16S rRNA sequencing results demonstrated that CcLR extract promoted the growth of beneficial bacteria. In particular, Spearman correlation analysis revealed that the abundance of Colidextribacter was negatively correlated with serum superoxide dismutase (P < 0.05, R = -0.943), and Helicobacter displayed a positive correlation with the content of brain nitric oxide (P < 0.05, R = 0.899), suggesting that regulating gut microbiota might be one of the mechanisms for reducing oxidative stress, thus postponing the aging process. CONCLUSION: It is suggested that CcLR extract could be used as a novel antioxidant and anti-aging resource in the pharmaceutical and food industries. © 2022 Society of Chemical Industry.

The effect of Cinnamomum cassia extract on oxidative stress in the liver and kidney of STZ-induced diabetic rats.

OBJECTIVES: Many diabetes-related complications are caused by oxidative stress. In the current study, the protective effect of Cinnamomum cassia against diabetes-induced liver and kidney oxidative stress was evaluated. METHODS: The male Wistar rats (n=48) were randomly divided into six groups including; control group received 500 µL normal saline orally for 42 days. Diabetes groups received intraperitoneally (i.p.) streptozotocin (STZ) as single-dose (60 mg/kg, i.p.). Cinnamon extract (100, 200, 400 mg/kg) and metformin (300 mg/kg) were orally administered to diabetic rats for 42 days. After the experiment period, the animals were anesthetized and the liver and kidney tissues were quickly removed and restored for oxidative stress evaluation. The levels of malondialdehyde (MDA), total thiol content, glutathione (GSH), nitric oxide (NO) metabolites, as well as, superoxide dismutase (SOD) and catalase (CAT) activities were measured in kidney and liver tissue. RESULTS: The level of MDA, SOD, and CAT activities increased significantly, while the total thiol content, and NO production were significantly reduced in diabetic animals compared to the control group (from p<0.05 to p<0.001). Treatment with cinnamon extract significantly decreased the MDA level, as well as, SOD and CAT activities in the liver and kidney of diabetic rats (from p<0.05 to p<0.001). In the liver and kidney of cinnamon treated groups, GSH and total thiol contents and NO production were significantly higher than diabetic group (from p<0.05 to p<0.001). CONCLUSIONS: Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications.

Comprehensive feature-based molecular networking and metabolomics approaches to reveal the differences components in Cinnamomum cassia and Cinnamomum verum.

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.

Development of a strategy for a quick process for separation of volatile compounds in counter-current chromatography: purification of cinnamaldehyde from Cinnamomum cassia by high performance counter-current chromatography.

It is a challenge for many researchers to separate volatile compounds. In this study, we introduce a rapid and efficient method of separating target compound from the twigs of Cinnamomum cassia by high performance counter-current chromatography. Under the bioassay guidance, the total extract exhibited a potential activity against NO production in RAW 264.7 macrophages and the total extract was further separated by high performance counter-current chromatography. Cinnamaldehyde (1) was enriched by counter-current chromatography (CCC) with reversed-phase mode using n-hexane-ethyl acetate-methanol-water (1:1:1:1,v/v/v/v) as the solvent system. Further identification was achieved by high performance liquid chromatography (HPLC).

Protective effects of Cinnamomum verum, Cinnamomum cassia and cinnamaldehyde against 6-OHDA-induced apoptosis in PC12 cells.

Cinnamon (Cinnamomum verum and C. cassia) is a medicinal plant, widely-used as a culinary spice. It possesses various therapeutic effects and can slow down the progression of neurological disorders impressively. In this article, the effects of hydro-alcohol extract and essential oil of C. verum and C. cassia and its main bioactive component cinnamaldehyde, has been examined on 6-OHDA-exposed PC12 cells as an in vitro model of Parkinson's disease. The cytotoxicity and cell apoptosis has been induced by 6-OHDA in PC12 cells. The protective effect was determined by measuring cell viability, the amount of reactive oxygen species (ROS), and apoptosis. Cell viability and apoptosis were assessed using resazurin assay, flow cytometry of propidium iodide (PI) stained cells, and western blot analysis. 6-OHDA resulted in the death and apoptosis of cells while, pretreatment with the extract and essential oil of C. verum and C. cassia at 20 µg/ml and cinnamaldehyde at 5 and 10 µM for 24 h could significantly increase the viability (p < 0.001), and decrease ROS content (p < 0.05). Pretreatment with the extracts increased survivin and decreased cyt-c whereas, pretreatment with the essential oil decreased cyt-c, increased survivin, and reduced P-p44/42/p44/42 levels to a level near that of the related control. The extract and essential oil of C. verum and C. cassia can be effective against 6-OHDA cytotoxicity. It is suggested that, the synergistic effects of cinnamaldehyde and other components of extract and essential oil promote cinnamon's medicinal properties.

In Vitro Antiviral Activity of Cinnamomum cassia and Its Nanoparticles Against H7N3 Influenza A Virus.

Nanoparticles have wide-scale applications in various areas, including medicine, chemistry, electronics, and energy generation. Several physical, biological, and chemical methods have been used for synthesis of silver nanoparticles. Green synthesis of silver nanoparticles using plants provide advantages over other methods as it is easy, efficient, and eco-friendly. Nanoparticles have been extensively studied as potential antimicrobials to target pathogenic and multidrug-resistant microorganisms. Their applications recently extended to development of antivirals to inhibit viral infections. In this study, we synthesized silver nanoparticles using Cinnamomum cassia (Cinnamon) and evaluated their activity against highly pathogenic avian influenza virus subtype H7N3. The synthesized nanoparticles were characterized using UVVis absorption spectroscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy. Cinnamon bark extract and its nanoparticles were tested against H7N3 influenza A virus in Vero cells and the viability of cells was determined by tetrazolium dye (MTT) assay. The silver nanoparticles derived from Cinnamon extract enhanced the antiviral activity and were found to be effective in both treatments, when incubated with the virus prior to infection and introduced to cells after infection. In order to establish the safety profile, Cinnamon and its corresponding nanoparticles were tested for their cytotoxic effects in Vero cells. The tested concentrations of extract and nanoparticles (up to 500 µg/ml) were found non-toxic to Vero cells. The biosynthesized nanoparticles may, hence, be a promising approach to provide treatment against influenza virus infections.

Cinnamomum cassia essential oil inhibits α-MSH-induced melanin production and oxidative stress in murine B16 melanoma cells.

Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for the development of aromatherapy for complementary and alternative medicine. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has various functional properties; however, little information is available regarding its anti-tyrosinase and anti-melanogenic activities. In this study, 16 compounds in the CC-EO have been identified; the major components of this oil are cis-2-methoxycinnamic acid (43.06%) and cinnamaldehyde (42.37%). CC-EO and cinnamaldehyde exhibited anti-tyrosinase activities; however, cis-2-methoxycinnamic acid did not demonstrate tyrosinase inhibitory activity. In murine B16 melanoma cells stimulated with α-melanocyte-stimulating hormone (α-MSH), CC-EO and cinnamaldehyde not only reduced the melanin content and tyrosinase activity of the cells but also down-regulated tyrosinase expression without exhibiting cytotoxicity. Moreover, CC-EO and cinnamaldehyde decreased thiobarbituric acid-reactive substance (TBARS) levels and restored glutathione (GSH) and catalase activity in the α-MSH-stimulated B16 cells. These results demonstrate that CC-EO and its major component, cinnamaldehyde, possess potent anti-tyrosinase and anti-melanogenic activities that are coupled with antioxidant properties. Therefore, CC-EO may be a good source of skin-whitening agents and may have potential as an antioxidant in the future development of complementary and alternative medicine-based aromatherapy.