Isolation and Characterization of Two Chalcone Derivatives with Anti-Hepatitis B Virus Activity from the Endemic Socotraen Dracaena cinnabari (Dragon's Blood Tree).

Hepatitis B virus (HBV) infection is prevalent and continues to be a global health concern. In this study, we determined the anti-hepatitis B virus (HBV) potential of the Socotra-endemic medicinal plant Dracaena cinnabari and isolated and characterized the responsible constituents. A bioassay-guided fractionation using different chromatographic techniques of the methanolic extract of D. cinnabari led to the isolation of two chalcone derivatives. Using a variety of spectroscopic techniques, including 1H-, 13C-, and 2D-NMR, these derivatives were identified as 2,4'-dihydroxy-4-methoxydihydrochalcone (compound 1) and 2,4'-dihydroxy-4-methoxyhydrochalcone (compound 2). Both compounds were isolated for the first time from the red resin (dragon's blood) of D. cinnabari. The compounds were first evaluated for cytotoxicity on HepG2.2.15 cells and 50% cytotoxicity concentration (CC50) values were determined. They were then evaluated for anti-HBV activity against HepG2.2.15 cells by assessing the suppression of HBsAg and HBeAg production in the culture supernatants and their half maximum inhibitory concentration (IC50) and therapeutic index (TI) values were determined. Compounds 1 and 2 indicated inhibition of HBsAg production in a dose- and time-dependent manner with IC50 values of 20.56 and 6.36 µg/mL, respectively.

ß-Caryophyllene: A Single Volatile Component of n-Hexane Extract of Dracaena cinnabari Resin.

The pure Soqotri resin of Dracaena cinnabari Balf.f. (Dracaenaceae) has no volatile smell due to its low content of volatile constituents. Although it is insoluble in n-Hexane, we found that the resin, when suspended in n-Hexane within five days at 5 °C, led to the extraction of a small portion of a single volatile liquid constituent, which was identified by GC-MS as sesquiterpene ß-caryophyllene. This method of extracting the volatile constituents using hexane under cooling is very suitable for resins of the Dracaena species because these resins usually contain very few volatile terpenes and/or non-terpenes, and they may contain only one volatile terpene per resin as this study result. ß-Caryophyllene was identified and separated for the first time from the Soqotri standard resin of Dracaena cinnabari. Therefore, ß-caryophyllene, as a new chemical property, can support to evaluate the purity of the Soqotri resin. Moreover, a big mass of D. cinnabari resin can yield concentrated ß-caryophyllene as a liquid extract for further pharmaceutical and nutraceutical applications.

Prevention of oral carcinogenesis in rats by Dracaena cinnabari resin extracts.

OBJECTIVES: In vivo study was performed to determine the chemopreventive efficacy of the DC resin methanol extract on a 4-nitroquinoline-1-oxide (4NQO) oral cancer animal model. MATERIALS AND METHODS: This study involves administration of 4NQO solution for 8 weeks alone (cancer induction) or with Dracaena cinnabari (DC) extract at 100, 500, and 1000 mg/kg. DC extract administration started 1 week before exposure until 1 week after the carcinogen exposure was stopped. All rats were sacrificed after 22 weeks, and histological analysis was performed to assess any incidence of pathological changes. Immunohistochemical expressions of selected tumor marker antibodies were analyzed using an image analyzer computer system, and the expression of selected genes involved in apoptosis and proliferative mechanism related to oral cancer were evaluated using RT2-PCR. RESULTS: The incidence of OSCC decreased with the administration of DC extract at 100, 500, and 1000 mg/kg compared to the induced cancer group. The developed tumor was also observed to be smaller when compared to the induced cancer group. The DC 1000 mg/kg group inhibits the expression of Cyclin D1, Ki-67, Bcl-2, and p53 proteins. It was observed that DC 1000 mg/kg induced apoptosis by upregulation of Bax and Casp3 genes and downregulation of Tp53, Bcl-2, Cox-2, Cyclin D1, and EGFR genes when compared to the induced cancer group. CONCLUSIONS: The data indicated that systemic administration of the DC resin methanol extract has anticarcinogenic potency on oral carcinogenesis. CLINICAL RELEVANCE: Chemoprevention with DC resin methanol extract may significantly reduce morbidity and possibly mortality from OSCC.

A new homoisoflavan from Dracaena cinnabari Balf. f. resin: α-glucosidase and COX-II inhibitory activity.

A new homoisoflavan, identified as (3 R)-7-hydroxy-3',4'-methylenedioxyhomoisoflavan, was isolated from Dracaena cinnabari Balf. f. resin. The structure was elucidated by one- and two-dimensional NMR spectroscopy as well as high resolution mass spectrometry. In addition, a diverse group of flavonoids were isolated, representing homoisoflavans, flavans, flavanones, chalcones and dihydrochalcones. The compounds were evaluated for their α-glucosidase and COX-II inhibition activity. The obtained IC50 values of the tested flavonoids gave an insight about some key structural features to their α-glucosidase and COX-II inhibitory activity. For α-glucosidase inhibitory activity, a flavanone skeleton was favorable over a flavan. For COX-II inhibition, the introduction of a fused heterocyclic ring at the homoisoflavan skeleton enhanced the activity.

A unique C-linked chalcone-dihydrochalcone dimer from Dracaena cinnabari resin.

A new C-linked chalcone-dihydrochalcone dimer, named dracidione, was isolated from the ethyl acetate extract of dragon's blood resin of Dracaena cinnabari Balf. f. Structure elucidation of the new compound was carried out by means of one- and two-dimensional NMR spectroscopy in addition to high resolution mass spectrometry. The unique structure incorporated a chalcone and a dihydrochalcone, which is reported for the first time from nature. Furthermore, dracidione showed moderate α-glucosidase inhibitory activity with IC50= 40.27 µg/ml.

A competitive nature-derived multilayered scaffold based on chitosan and alginate, for full-thickness wound healing.

The aim of this study was to evaluate a bioactive multilayer wound dressing, based on chitosan and alginate. To enhance healing potential, Dracaena Cinnabari and Aloe Vera were loaded as separate layers into the scaffold. The bare and bioactive multilayered scaffolds were fabricated by an iterative layering freeze-drying technique. Following of topographical, chemical, and physical assessment, the performance of the scaffolds was evaluated in vitro and in vivo. The results revealed adequate attachment, and proliferation of human foreskin fibroblasts, indicating excellent biocompatibility of the bioactive scaffold. In vivo, the performance of the multi-layered scaffold loaded with the bioactive materials was comparable with Comfeel plus®. The wounds treated with the bioactive scaffold exhibited superior hypergranulation, fibroblast maturation, epithelization, and collagen deposition, with minimal inflammation, and crust formation. It is concluded that the synergism of extracellular matrix-mimicking multi-layered scaffolding with Aloe Vera and Dracaena Cinnabari could be considered as a supportive wound dressing.

Terpenoid profiles of resin in the genus Dracaena are species specific.

Dragon's blood is the colloquial name for the red resin produced by tree species in the genus Dracaena (Asparagaceae), and the resin is directly involved in plant defensive mechanisms against pathogen and herbivore attack. It is also widely used in traditional folk medicine due to its antiviral, antimicrobial and antitumor activities. In the present work, a method using solid phase microextraction combined with two-dimensional gas chromatography with time-of-flight mass spectrometric detection was developed for the analysis of resin from five Dracaena species, namely Dracaena cinnabari Balf. f., D. serrulata Baker, D. ombet Heuglin ex Kotschy & Peyr., D. draco subsp. draco, and D. draco subsp. ajgal. Twenty terpenoid components in the resins of the five species were identified after comparative study of the volatile metabolite profiles. Monoterpenes were found to be species specific, and the observed differences might be further investigated as a possible means of identifying chemotaxonomic markers. In addition, for the first time, we describe the terpenoid volatile profiles of D. ombet and D. serrulata resins.

The in vitro and in vivo antitumor effects of Dracaena cinnabari resin extract on oral cancer.

OBJECTIVE: To study the potential for apoptosis induction of Dracaena cinnabari Balf. f methanolic extract (DCBME) on tongue squamous cell carcinoma cell line, H103. We evaluated the chemopreventive activity of DCBME against 4-nitroquinolone-1-oxide (4NQO)-induced tongue carcinogenesis in rat. DESIGN: Phase contrast microscope, acridine orange/propidium iodide (AO/PI) analysis of cells under fluorescence microscope, annexin-V flow-cytometry, DNA fragmentation, mitochondrial membrane potential, and caspase 3/7, 8 and 9 assays were performed. In vivo study, the rats were given 4NQO in their drinking water. The tongue was subjected to histopathological study to evaluate the incidence of squamous cell carcinoma (SCC). RESULTS: DCBME showed cytotoxic effect on H103 cells in a dose- and time-dependent manner. Furthermore, DCBME showed low cytotoxic effect on a normal cell line. In H103 cells, it caused cell morphology changes, S and G2/M-phase cell cycle arrest, significant reduction of cell migration and induced apoptosis through the intrinsic (mitochondrial) pathway. The incidence of SCC was 85.7% in the induced cancer and vehicle groups while in rats treated with DCBME at 100, 500 and 1000 mg/kg was 57.1%, 28.6% and 14.3%, respectively. CONCLUSIONS: (DCBME)-apoptosis induction reported in this work can be exploited as a potential antitumor agent with applications in medicinal treatments of tongue SCC.

Ethnobotanical Survey of Dracaena cinnabari and Investigation of the Pharmacognostical Properties, Antifungal and Antioxidant Activity of Its Resin.

Dracaena cinnabari Balf. f. (Dracaenaceae) is an important plant endemic to Soqotra Island, Yemen. Dragon's blood (Dam Alakhwin) is the resin that exudes from the plant stem. The ethnobotanical survey was carried out by semi-structured questionnaires and open interviews to document the ethnobotanical data of the plant. According to the collected ethnobotanical data, the resin of D. cinnabari is widely used in the traditional folk medicine in Soqotra for treatment of dermal, dental, eye and gastrointestinal diseases in humans. The resin samples found on the local Yemeni markets were partly or totally substituted by different adulterants. Organoleptic properties, solubility and extractive value were demonstrated as preliminary methods to identify the authentic pure Soqotri resin as well as the adulterants. In addition, the resin extracts and its solution in methanol were investigated for their in vitro antifungal activities against six human pathogenic fungal strains by the agar diffusion method, for antioxidant activities using the DPPH assay and for cytotoxic activity using the neutral red uptake assay. The crude authentic resin dissolves completely in methanol. In comparison with different resin extracts, the methanolic solution of the whole resin showed the strongest biological activities. It showed strong antifungal activity, especially against Microsporum gypseum and Trichophyton mentagrophytes besides antioxidant activities and toxicity against FL-cells. These findings confirm and explain the traditional uses of the resin for the treatment of skin diseases and mouth fungal infections.