Dragon's Blood-Loaded Mesoporous Silica Nanoparticles for Rapid Hemostasis and Antibacterial Activity.

Dragon's blood (DB) is a traditional Chinese medicine (TCM) with hemostatic effects and antibacterial properties. However, it is still challenging to use for rapid hemostasis because of its insolubility. In this study, different amounts of DB were loaded on mesoporous silica nanoparticles (MSNs) to prepare a series of DB-MSN composites (5DB-MSN, 10DB-MSN, and 20DB-MSN). DB-MSN could quickly release DB and activate the intrinsic blood coagulation cascade simultaneously by DB and MSN. Hemostasis tests demonstrated that DB-MSN showed superior hemostatic effects than either DB or MSNs alone, and 10DB-MSN exhibited the best hemostatic effect. In addition, the antibacterial activities of DB-MSN against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) improved with the increase in DB. Furthermore, the hemolysis assay and cytocompatibility assay demonstrated that all DB-MSNs exhibited excellent biocompatibility. Based on these results, 10DB-MSN is expected to have potential applications for emergency hemostatic and antibacterial treatment in pre-hospital trauma.

Loureirin C, from Chinese Dragon's Blood (Dracaena cochinchinensis S.C. Chen), is a novel selective estrogen receptor α modulator with anti-Alzheimer's disease effects.

As the incidence of Alzheimer's disease (AD) continues to rise in recent years, there are few therapeutic drugs for AD treatment with limited efficacy. AD occurs twice as often in women as that in men, partially due to the low estrogen level in women after menopause. Phytoestrogens (PEs), similar to endogenous estrogens in chemical structure with neuroprotection and fewer side effects, have good development and application prospects in AD-treatment. Loureirin C is an active ingredient isolated from Chinese Dragon's Blood (CDB) with a similar structure to 17ß-E2. In our study, we found that loureirin C targeted to ERα and had partial-agonistic activity using molecular docking prediction and dual-luciferase reporter assay. However, it is still unclear whether loureirin C has estrogenic effects in body, and whether exerts anti-AD effect through ERα. In this paper, the ERα selective inhibitor MPP or ERα specific small interfering RNA (siERα) mediated gene silencing technology were used. Besides,E-SCREEN method were used to evaluate the estrogen effects of loureirin C in vivo and in vitro. MTT assay, Western blot, real-time PCR technology and behaver tests was used to investigate the neuroprotective effect, cognitive function and the underlying mechanism. We found that loureirin C possessed estrogenic activity, had neuroprotective effects in AD cells and improved cognitive impairment in AD mice via ERα. Loureirin C may be a potential candidate for AD.

Structure and histochemistry of the stem of Dracaena cambodiana Pierre ex Gagnep.

Dracaena cambodiana Pierre ex Gagnep is an important plant resource for producing dragon's blood and one of most popular ornamental trees in China. For a better understanding of the physiological function of the stem, the structural characteristics and main substance histological location of the stems of D. cambodiana were studied. The structural characteristics of the different developmental stages of stems of D. cambodiana were observed and described detailly. And then a schematic diagram of the mature stem was created. Histochemical staining showed that two kinds of polysaccharides distributed in parenchymal cells. Saponins distributed mainly in ground tissue and phenolic compounds distributed mainly in the thick cell walls. An abundant of calcium oxalate raphide bundles were identified in cortex and primary tissue. Finally, the role of the above results in the taxonomy of Dracaena species and in their strong adaptability was discussed.

Synthesis and Structure Revision of Naturally Occurring Homoisoflavane (+)-Dracaeconolide B.

Dracaeconolide B (1), a naturally occurring homoisoflavane, was isolated from the red resin of Dracaena cochinchinensis. Efforts have been made to elucidate the exact structure of compound 1 since it was confirmed that dracaeconolide B did not contain a 7-hydroxy-5,8-dimethoxy moiety. The structure of dracaeconolide B was revised by synthesis of three homoisoflavanes containing a 5,6,7-trioxygenated moiety each and analysis by NMR spectroscopy. The revised structure of dracaeconolide B was proposed as 3-(4-hydroxybenzyl)-7-hydroxy-5,6-dimethoxychromane. Noyori's Ru-catalyzed asymmetric transfer hydrogenation was used to synthesize (+)-dracaeconolide B. The absolute configuration of the compound was revised to S based on the results obtained by the electronic circular dichroism calculation. We examined the antiangiogenic activity of (S)- and (R)-dracaeconolide B and of synthetic 5,6,7- and 5,7,8-trioxygenated homoisoflavanes. The results can potentially help in the synthesis of related natural products and support drug discovery to treat neovascular eye diseases.

Isolated compounds from Dracaena angustifolia Roxb and acarbose synergistically/additively inhibit α-glucosidase and α-amylase: an in vitro study.

BACKGROUND: As a traditional herbal medicine, Dracaena angustifolia Roxb has been used as an anti-inflammatory agent by the Li people in Hainan, China. In preliminary phytochemical studies conducted in our lab, its fractions were found to inhibit α-glucosidase in vitro, indicating a potential for alleviating glucose dysregulation. METHODS: Through in vitro enzymatic assays, the abilities of the separated components to affect α-glucosidase and α-amylase were evaluated. By establishing concentration gradients and generating Lineweaver-Burk plots, the corresponding inhibition modes together with kinetic parameters were assessed. Following the evaluation of the outcomes of their combination with acarbose, computational docking and molecular dynamic simulations were carried out to analyse the interaction mechanisms and perform virtual screening against human enzymes. RESULTS: Compared with acarbose, 7 compounds, including flavonoid derivatives, amides and aromatic derivatives, with higher α-glucosidase inhibitory efficiencies were confirmed. It was found that those competitive/mixed candidates and acarbose interacted synergistically or additively on α-glucosidase. Moreover, 3 of them were able to inhibit α-amylase in mixed mode, and additive effects were observed in combination with acarbose. Through in silico docking, it was found that the active site residues as well as adjacent residues were involved in α-glucosidase and α-amylase binding, which were mainly achieved through hydrogen bonding. Among those dual-function flavonoids, Compound 9 was predicted to be a considerable inhibitor of human enzymes, as the formation of ligand-enzyme complexes was mediated by the residues responsible for substrate recognition and catalysis, the stabilities of which were reiterated by molecular dynamics simulations. CONCLUSION: Despite their mild effects on α-amylase, considerable α-glucosidase inhibitory efficiencies and potential synergy with acarbose were exhibited by these natural candidates. Furthermore, a stable ligand, human α-glucosidase, was predicted by the performed simulations, which provided useful information for the application of Dracaena angustifolia Roxb in diabetes treatment.

Phytochemical Profiling, In Vitro Biological Activities, and In Silico Molecular Docking Studies of Dracaena reflexa.

Dracaena reflexa, a traditionally significant medicinal plant, has not been extensively explored before for its phytochemical and biological potential. The present study was conducted to evaluate the bioactive phytochemicals and in vitro biological activities of D. reflexa, and perform in silico molecular docking validation of D. reflexa. The bioactive phytochemicals were assessed by preliminary phytochemical testing, total bioactive contents, and GC-MS analysis. For biological evaluation, the antioxidant (DPPH, ABTS, CUPRAC, and ABTS), antibacterial, thrombolytic, and enzyme inhibition (tyrosinase and cholinesterase enzymes) potential were determined. The highest level of total phenolic contents (92.72 ± 0.79 mg GAE/g extract) was found in the n-butanol fraction while the maximum total flavonoid content (110 ± 0.83 mg QE/g extract) was observed in methanolic extract. The results showed that n-butanol fraction exhibited very significant tyrosinase inhibition activity (73.46 ± 0.80) and acetylcholinesterase inhibition activity (64.06 ± 2.65%) as compared to other fractions and comparable to the standard compounds (kojic acid and galantamine). The methanolic extract was considered to have moderate butyrylcholinesterase inhibition activity (50.97 ± 063) as compared to the standard compound galantamine (53.671 ± 0.97%). The GC-MS analysis of the n-hexane fraction resulted in the tentative identification of 120 bioactive phytochemicals. Furthermore, the major compounds as identified by GC-MS were analyzed using in silico molecular docking studies to determine the binding affinity between the ligands and the enzymes (tyrosinase, acetylcholinesterase, and butyrylcholinesterase enzymes). The results of this study suggest that Dracaena reflexa has unquestionable pharmaceutical importance and it should be further explored for the isolation of secondary metabolites that can be employed for the treatment of different diseases.

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.

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.

Trimeric chalchonoids from the total phenolic extract of Chinese dragon's blood (the red resin of Dracaena cochinchinensis).

Four new chalchonoid trimers, named cochinchinenins N-Q (1-4), along with a pair of known enantiomers (5-6), were isolated from the total phenolic extract of Chinese dragon's blood (the red resin of Dracaena cochinchinensis). The planar structures of 1-4 were elucidated by extensive spectroscopic analysis including HRESIMS and 1D/2D NMR. The absolute configurations of new compounds were established by ECD data. Compound 1 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 value of 11.5 ± 1.7 µM.

Phytochemistry and Pharmacological Activities of Dracaena cinnabari Resin.

Dracaena cinnabari (D. cinnabari) is an endemic plant located in Socotra Island, Yemen. Deep red resin attained from different plant species including D. cinnabari is commonly known as dragon's blood. In folk medicine, it is prescribed for the treatment of traumatic dermal, dental, and eye injuries as well as blood stasis, pain, and gastrointestinal diseases in humans. Numerous studies have investigated that this resinous medicine has antidiarrheal, antiulcer, antimicrobial, antiviral, antitumor, anti-inflammatory, analgesic, wound healing, and antioxidant activity. Several phytochemicals have been isolated from D. cinnabari, including the biflavonoid cinnabarone, triflavonoids, metacyclophanes, chalcones, chalcanes, dihydrochalcones, sterols, and terpenoids. The present review highlights the structures and bioactivities of main phytochemicals isolated from D. cinnabari regarding the botany and pharmacological effects of the resin derived from this plant.

Dragon's Blood from Dracaena Worldwide: Species, Traditional Uses, Phytochemistry and Pharmacology.

Dragon's blood (DB) refers mainly to the crimson resin of many Dracaena spp. DB has been used by different traditional medicine systems worldwide, including Arabic medicine, African medicine, traditional Chinese medicine, Thai medicine, etc. DB are mainly used to heal wounds, kill pain, stop bleeding, and cure various diseases such as diarrhea, dysentery and ulcers for over 1000 years. 11 Dracaena spp. and 3 subspecies are reported to be able to produce red resin. However, the resources are extremely deficient. Several Dracaena spp. are in threatened status. Over 300 compounds have been isolated from Dracaena spp., mainly including flavonoids, steroids, and phenolics. DB exhibits anti-inflammatory, analgesic, antithrombotic, anti-oxidant, antimicrobial, antidiabetic, and anticancer properties, which explain its wound healing effects, preventive effects on cardiovascular and cerebrovascular diseases, dual-directional regulation of blood flow, neuroprotection and radioprotective effects. No apparent side effects or toxicity have been reported. DB are restricted from being exploited due to limited resources and unclear resin formation mechanism. It is necessary to expand the cultivation of Dracaena spp. and fully understand the mechanism underlying the resin formation process to develop an effective induction method for the sustainable utilization of DB.

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.

Antifungal and wound healing promotive compounds from the resins of Dracaena cochinchinensis.

Five new compounds (xuejieins A-E), including three new phenolic glycosides (1, 2, and 5) and two new flavonoids (10 and 11), together with six known compounds were isolated from the resins of Dracaena cochinchinensis (Chinese dragon's blood). The structures of the new compounds were confirmed by extensive spectroscopic methods and electronic circular dichroism (ECD) data analysis. Especially, the absolute configurations of the sugar moieties in compounds 1, 2, and 5 were clarified by GC analysis after acid hydrolysis. All isolated compounds have been tested for antifungal and wound healing promoting activities, The results showed that compound 9 shows significant antifungal activities against Botrytis cinerea, Magnaporthe grisea, Penicillium digitatum, and Sclerotinia sclerotiorum. In addition, compound 4 could significantly stimulate human keratinocytes (HaCAT) proliferation, mobility, and human umbilical vein vascular endothelial cells (HUVECs) tube formation at 40 µM.

Transcriptome profiling reveals candidate flavonoid-related genes during formation of dragon's blood from Dracaena cochinchinensis (Lour.) S.C.Chen under conditions of wounding stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Dragon's Blood (Resina Draconis) is a red resin that has been used in traditional medicine to promote blood circulation, regenerate muscles, reduce swelling and pain, stop bleeding, etc., and its main chemical constituents are flavonoids. Dracaena cochinchinensis (Lour.) S.C.Chen is the only plant defined by the Pharmacopoeia of the People's Republic of China as a source of dragon's blood. AIM OF THE STUDY: We aimed to reveal genes involved in the biosynthesis and accumulation of flavonoids of D. cochinchinensis which is under wounding stress by performing a de novo transcriptome analysis. MATERIALS AND METHODS: D. cochinchinensis samples were collected for transcriptome sequencing and bioinformatics analysis at 0 days (0 d), 3 days (3 d), 6 days (6 d), and 10 days (10 d) after induction wounding stress, and tissues were microscopically observed after wounding stress. RESULTS: A total of 63,244 unigenes were obtained through bioinformatics analysis, and genes associated with the biosynthesis of flavonoids were identified. Through the analysis of DEGs after wounding stress in D. cochinchinensis, based on gene expression consistent with flavonoid accumulation levels, 20 genes in connection with the flavonoid synthesis pathway and 56 genes that may be responsible for flavonoid modification and transport, and also revealed TFs (MYB, bHLH) that may be responsible for flavonoid biosynthesis. Analysis of DEGs between the four periods revealed that after wounding stress, the greatest number of significant DEGs were enriched during the first 3 days, while fewer DEGs were enriched after day 3, which corresponding to only about 1/10 (353/3883) the number of DEGs during the first 3 days. In addition, putative unigenes involved in lignin biosynthesis, such as CSE, HCT, CCR, F5H, and CAD, were significantly down-regulation after D. cochinchinensis wounding stress, but the putative unigenes responsible for flavonoid biosynthesis, such as CHS, CHI, DFR, F3'5'H, F3H, ANR, FLS, and ANS were significantly up-regulation. CONCLUSION: We performed de novo transcriptome analysis of D.cochinchinensis under wounding stress, candidate genes and TFs involved in the biosynthesis and accumulation of flavonoids were identified, which is the first report on the transcript variants in flavonoid form accumulation in D. cochinchinensis under wounding stress. According to the results of DEGs analysis, wounding stress attenuated lignin biosynthesis meanwhile promoted flavonoid biosynthesis. In addition, we also compared the transcriptomics of the two different original plants (D.cochinchinensis and D.cambodiana) that form dragon's blood in order to provide further understanding of the formation of dragon's blood.

Synthesis and biological activity of (±)-7,3',4'-trihydroxyhomoisoflavan and its analogs.

Acetylcholinesterase (AChE) inhibitors and neurite outgrowth promoters are thought to alleviate the symptoms of degenerative brain disorders, such as Alzheimer's disease. We designed and synthesized a series of homoisoflavonoids based on the structure of natural homoisoflavan isolated from Dracaena cambodiana dragon's blood. The homoisoflavonoids were then evaluated as AChE inhibitors and neurite outgrowth promoters. The catechol structure of the homoisoflavan B rings was important for AChE inhibition, and some of the homoisoflavonoids significantly promoted neurite outgrowth induced by nerve growth factor (NGF).

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.

Anti-inflammatory steroidal sapogenins and a conjugated chalcone-stilbene from Dracaena usambarensis Engl.

Four new steroidal sapogenins, dracaenogenins CF (1-4), a new conjugated chalcone-stilbene, 3''-methoxycochinchinenene H (5) together with eight known compounds namely, (25S)-spirosta-1,4-dien-3-one (6), trans-resveratrol (7), 4,4'-dihydroxy-3'-methoxychalcone (8), N-trans-coumaroyltyramine (9), N-trans-p-coumaroyloctopamine (10), N-trans-feruloyloctopamine (11), 7-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-N2,N3-bis(4-hydroxyphenethyl)-6-methoxy-1,2-dihydronaphthalene-2,3-dicarboxamide (12) and grossamide (13) were isolated from the stems of Dracaena usambarensis Engl. from Kenya. It is important to note that compounds 12 and 13 are being reported from this genus for the first time. Structural elucidation of the isolated compounds was done using spectroscopic (NMR, UV, IR, optical rotation) and spectrometric (HRESIMS) techniques. The absolute and relative configurations of the isolated compounds were determined by employing single crystal X-ray crystallography analysis, NOESY correlations and coupling constants. The anti-inflammatory potencies of the isolated compounds were evaluated by measuring the levels of four cytokines (IL-1ß, IL-2, GM-CSF and TNF-α) in the supernatant media of human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS). At the tested concentration of 100 µM, the new conjugated chalcone-stilbene 5, the dihydrochalcone, 8 and the lignanamide, 13 were substantially more potent than the standard drug, ibuprofen, inhibiting the release of all the cytokines, IL-1ß, IL-2, GM-CSF and TNF-α from 0.06-58.04% compared to LPS control. These compounds should therefore be considered for development into anti-inflammatory drug candidates. Compound 7 significantly decreased the release of GM-CSF (6.11% of LPS control) and TNF-α (18.35% of LPS control). The cytokine TNF-α was sensitive to all the tested compounds 1-13.

Flavonoids and Stilbenoids of the Genera Dracaena and Sansevieria: Structures and Bioactivities.

The genera Dracaena and Sansevieria (Asparagaceae, Nolinoideae) are still poorly resolved phylogenetically. Plants of these genera are commonly distributed in Africa, China, Southeast Asia, and America. Most of them are cultivated for ornamental and medicinal purposes and are used in various traditional medicines due to the wide range of ethnopharmacological properties. Extensive in vivo and in vitro tests have been carried out to prove the ethnopharmacological claims and other bioactivities. These investigations have been accompanied by the isolation and identification of hundreds of phytochemical constituents. The most characteristic metabolites are steroids, flavonoids, stilbenes, and saponins; many of them exhibit potent analgesic, anti-inflammatory, antimicrobial, antioxidant, antiproliferative, and cytotoxic activities. This review highlights the structures and bioactivities of flavonoids and stilbenoids isolated from Dracaena and Sansevieria.

Eight new flavonoids from the fruits of Daemonorops draco.

Eight new flavonoids daemoflavans A-H, including two dimeric proanthocyanidins (1 and 2), four flavans (3-6), two 2-arylbenzofurans (7 and 8), along with nine known compounds (9-17), were isolated from the fruit of Daemonorops draco. Their structures, including the absolute configurations, were elucidated by extensive spectroscopic data, ECD analysis, and X-ray crystal diffraction. Besides, the X-ray crystal data of a known compound dracoflavan B1 (9) was firstly reported. Daemoflavan G (7) represents a rare example of C-5 methylated 2-arylbenzofuran in natural products. Among the known compounds, 15, 16, 17 were reported from this species for the first time. All the compounds were evaluated for their cytotoxicity against HepG2 cell line. Among them, compounds 1, 9 and 10 exhibited modest cytotoxic activity with IC50 values of 12.4, 12.0 and 13.2 µM, respectively.

Bioactive flavonoid dimers from Chinese dragon's blood, the red resin of Dracaena cochinchinensis.

Seven flavonoid dimers, biflavocochins A-G, together with six known compounds were isolated from the red resins of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were elucidated based on extensive spectroscopic analysis. The absolute configurations of 1-7 was assigned by experimental and quantum chemical calculated ECD spectra, and that of 4 was further established by X-ray diffraction analysis using Cu Kα radiation. Compounds 1-3 are novel dimers of homoisoflavonoid and dihydrochalcone with a unique dibenzopyran ring. Compounds 2, 6, 7 exhibited moderate PTP1B inhibitory activities in an enzyme assay. Compound 1 showed neuroprotective effect on serum deficiency-induced cellular damage in PC12 cells.