Antimicrobial, antioxidant, and cytotoxic properties of endophytic fungi isolated from Thysanolaena maxima Roxb., Dracaena spicata Roxb. and Aglaonema hookerianum Schott.

BACKGROUND: Endophytic fungi have recently been recognized as an impressive source of natural biomolecules. The primary objective of the research was to isolate fungal endophytes from Thysanolaena maxima Roxb., Dracaena spicata Roxb. and Aglaonema hookerianum Schott. of Bangladesh and assess their pharmacological potentialities focusing on antimicrobial, antioxidant, and cytotoxic properties. METHODS: The fungal isolates were identified up to the genus level by analyzing their macroscopic and microscopic characteristics. Ethyl acetate extracts of all the fungal isolates were screened for different bioactivities, including antimicrobial (disc diffusion method), antioxidant (DPPH scavenging assay), and cytotoxic (brine shrimp lethality bioassay) activities. RESULTS: Among the thirteen isolates, Fusarium sp. was the most recognized genus, while the others belonged to Colletotrichum sp. and Pestalotia sp. Comparing the bioactivity of all the extracts, Fusarium sp. was shown to be the most effective endophyte, followed by Colletotrichum sp. and Pestalotia sp. In the antimicrobial study, two isolates of Fusarium sp. (internal strain nos. DSLE-1 and AHPE-4) showed inhibitory activity against all the tested bacteria and the highest zone of inhibition (15.5 ± 0.4 mm) was exerted by AHPE-4 against Bacillus subtillis. All the fungal isolates produced mild to moderate free radical scavenging activity, where the highest antioxidant activity was revealed by one isolate of Fusarium sp. (internal strain no. AHPE-3) with an IC50 value of 84.94 ± 0.41 µg/mL. The majority of Fusarium sp. isolates exhibited notable cytotoxic activity, where AHPE-4 exhibited the highest cytotoxicity, having the LC50 value of 14.33 ± 4.5 µg/mL. CONCLUSION: The findings of the study endorsed that the fungal endophytes isolated from T. maxima, D. spicata, and A. hookerianum hold potential as valuable origins of bioactive substances. Nevertheless, more comprehensive research is warranted, which could develop novel natural compounds from these endophytes to treat various infectious and cancerous diseases.

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.

CAUSES OF MORTALITY AND COMORBIDITIES IN CAIMAN LIZARDS (DRACAENA GUIANENSIS) AT SIX ZOOLOGICAL INSTITUTIONS.

An understanding of the main causes of mortality in caiman lizards (Dracaena guianensis) under managed care is imperative to promote optimal husbandry, health, and welfare. A retrospective review of morbidity and mortality in caiman lizards from North American zoological institutions between 2005 and 2020 was conducted. Postmortem data, including gross necropsy and histopathology findings, were available for 32 caiman lizards (n = 12 subadults, n = 20 adults) from six zoological institutions. Necropsy reports were evaluated to collect general demographic data, categorize cause of death (accident/trauma, congenital/genetic, degenerative/geriatric, infectious, deposition disease, neoplastic, unknown, and multifactorial), and assess common comorbidities. Infectious disease was the most common cause of mortality in adult lizards (8/20; 40%) with amoebiasis and bacterial etiologies being overrepresented. Demise due to traumatic/accidental injury was the second most common cause of death in adult lizards (3/20;15%) and included blunt force trauma or suspected drowning. Infectious disease (4/12; 33.3%) and trauma/accidental injury (4/12; 33.3%) were also the most common causes of death in subadults. The most common comorbidities or other incidental findings identified during necropsy included trematode parasitism (15/32; 46.9%), arteriosclerosis (11/32; 34.4%), and adrenocortical hyperplasia (6/32; 18.8%). This retrospective review suggests that management practices to prevent and control infectious diseases and mitigate traumatic injury play a pivotal role in the long-term care and survival of caiman lizards in managed care.

Chinese dragon's blood ethyl acetate extract suppresses gastric cancer progression through induction of apoptosis and autophagy mediated by activation of MAPK and downregulation of the mTOR-Beclin1 signalling cascade.

Gastric cancer (GC) is a malignancy with high morbidity and mortality. Chinese dragon's blood is a traditional Chinese medicine derived from the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen. However, the antigastric cancer effect of Chinese dragon's blood has not yet been reported. Herein, we demonstrated that Chinese dragon's blood ethyl acetate extract (CDBEE) suppressed the proliferative and metastatic potential of human gastric cancer MGC-803 and HGC-27 cells. CDBEE suppressed epithelial-mesenchymal transition in MGC-803 and HGC-27 cells. Moreover, CDBEE induced apoptotic and autophagic cell death in MGC-803 and HGC-27 cells. The cytotoxicity of CDBEE in human gastric epithelial GES-1 cells was dramatically weaker than that in human gastric cancer cells. Mechanistically, the activation of the mitogen-activated protein kinase (MAPK) signalling pathway was involved in the growth inhibition of MGC-803 and HGC-27 cells by CDBEE. Additionally, CDBEE-induced autophagic cell death was mediated by downregulation of the mammalian target of rapamycin (mTOR)-Beclin1 signalling cascade and upregulation of the ATG3/ATG7-LC3 signalling cascade. Importantly, CDBEE exhibited potent anti-GC efficacy in vivo without obvious toxicity or side effects. Therefore, CDBEE may be a promising candidate drug for the treatment of gastric cancer, especially for GC patients with aberrant MAPK signalling or mTOR signalling.

Anti-tyrosinase, anti-skin pathogenic bacterial, and antioxidant activities and phytochemical constituents of Dracaena cochinchinensis (Lour.) S.C. Chen extract

Dracaena cochinchinensis (Lour.) S.C. Chen (Chandaeng) is an important traditional medicinal plant used in ancient Thai household remedies. This research focused on investigating the biological properties, including the antibacterial, anti-tyrosinase, antioxidant activities, and phytochemical characteristics of crude Chandaeng extracts. Dried Chandaeng heartwood powder was extracted using ethanol, methanol, and deionized water. The antibacterial activities of the extracts were then tested against skin pathogens, including Cutibacterium acnes (DMST14916), Staphylococcus epidermidis (TISTR518), and Staphylococcus aureus (TISTR321). The ethanolic extract showed antibacterial activity. In a time-kill assay, all bacteria were completely killed after being exposed to it, while the cell membranes were found to have leaked when viewed under a scanning electron microscope. Antioxidant potential was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2¢-azino-bis -3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. According to the findings, the crude ethanolic extract of Chandaeng showed the highest level of antioxidant activity. Furthermore, the potential of the extract to treat skin hyperpigmentation by inhibiting tyrosinase, an important melanin synthesis enzyme, was determined and the ethanolic extract was found to be an anti-tyrosinase agent. Finally, the crude ethanolic extract showed the highest total phenolic compound and flavonoid content. In conclusion, crude Chandaeng extract showed significant potential in activity against skin pathogenic bacteria, antioxidant activity, and tyrosinase inhibition. These properties of the extract could be applied to skincare cosmetics.

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.

Plastid phylogenomics of the Sansevieria Clade of Dracaena (Asparagaceae) resolves a recent radiation.

Best known as low maintenance houseplants, sansevierias are a diverse group of flowering plants native to Africa, Madagascar, the Arabian Peninsula, and the Indian subcontinent. Traditionally recognised as a distinct genus, Sansevieria was recently merged with the larger genus Dracaena based on molecular phylogenetic data. Within the Sansevieria Clade of Dracaena, taxonomic uncertainties remain despite attempts to unravel the relationships between the species. To investigate the evolutionary relationships, morphological evolution and biogeographical history in the group, we aim to reconstruct a robust dated phylogenetic hypothesis. Using genome skimming, a chloroplast genome (cpDNA) dataset and a nuclear ribosomal (nrDNA) dataset were generated. The sampling included representatives of all sections and informal groups previously described in Sansevieria based on morphology. Analysis of the cpDNA dataset using a maximum likelihood approach resulted in a well-supported phylogeny. The time-calibrated phylogeny indicated a recent radiation with five main clades emerging in the Pliocene. Two strongly supported clades align with previously defined groups, i.e., Sansevieria section Dracomima, characterised by the Dracomima-type inflorescence, and the Zeylanica informal group, native to the Indian subcontinent. Other previously defined groups were shown to be polyphyletic; a result of convergent evolution of the identifying characters. Switches between flat and cylindrical leaves occurred multiple times in the evolution of the Sansevieria Clade. Similarly, the Cephalantha-type inflorescence has originated multiple times from an ancestor with a Sansevieria-type inflorescence. Analysis of the nrDNA dataset resulted in a phylogenetic hypothesis with low resolution, yet it supported the same two groups confirmed by the cpDNA dataset. This study furthers our understanding of the evolution of the Sansevieria Clade, which will benefit taxonomic and applied research, and aid conservation efforts.

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.

[Research progress on anti-tumor effect of Chinese dragon's blood].

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.

Structures and Bioactivities of Steroidal Saponins Isolated from the Genera Dracaena and Sansevieria.

The species Dracaena and Sansevieria, that are well-known for different uses in traditional medicines and as indoor ornamental plants with air purifying property, are rich sources of bioactive secondary metabolites. In fact, a wide variety of phytochemical constituents have been isolated so far from about seventeen species. This paper has reviewed the literature of about 180 steroidal saponins, isolated from Dracaena and Sansevieria species, as a basis for further studies. Saponins are among the most characteristic metabolites isolated from the two genera. They show a great variety in structural motifs and a wide range of biological activities, including anti-inflammatory, anti-microbial, anti-proliferative effects and, in most case, remarkable cytotoxic properties.

Inhibition of Proinflammatory Cytokine Release by Flavones and Flavanones from the Leaves of Dracaena steudneri Engl.

The leaves of Dracaena steudneri yielded 6 new flavonoids-3,5,7-trihydroxy-6-methyl-3',4'-methylenedioxyflavone (1: ), 5,7-dihydroxy-3-methoxy-6-methyl-3',4'-methylenedioxyflavone (2: ), 3,5,7-trihydroxy-6-methoxy-3',4'-methylenedioxyflavone (3: ), (2S,3S)-3,7-dihydroxy-6-methoxy-3',4'-methylenedioxyflavanone (4: ), 4',5,7-trihydroxy-3,3',8-trimethoxy-6-methylflavone (5: ), (2R) 7-hydroxy-2',8-dimethoxyflavanone (6: )-together with 13 known congeners. Their structures were established using spectroscopic and spectrometric methods including NMR, CD, and HRMSn measurements. The compounds were evaluated for their anti-inflammatory potential through measurement of the levels of cytokines IL-1ß, IL-2, GM-CSF, and TNF-α in the supernatant of human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Flavones derivatives 1: -4: with a C-3'/4' methylenedioxy substituent led to a substantial increase in the production of IL-1ß and GM-CSF out of 4 pro-inflammatory cytokines relative to LPS control. Quercetin derivatives 5, 11,: and 13: with a hydroxyl group at C-4' inhibited the production of IL-2, GM-CSF, and TNF-α. The presence of a C-2/C-3 double bond in 14: was pivotal to the significantly stronger (0.4 to 27.5% of LPS control) inhibitory effect compared to its dihydro derivative 8: (36.2 to 262.7% of LPS control) against all tested cytokines. It is important to note that the inhibitory activity of 14: was substantially higher than that of the standard drug used, ibuprofen.

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).

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.

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.

Aqueous and ethanol extracts of Dracaena arborea (Wild) Link (Dracaenaceae) alleviate reproductive complications of diabetes mellitus in rats.

Reproductive dysfunction is one of the most prevalent diabetes complications. Draceana arborea is known to enhance sexual function in diabetic rats, but the underlying mechanisms have not been thoroughly elucidated. This study examined the effects of D. arborea on some reproductive complications of diabetes in rats. Aqueous and ethanol (500 and 100 mg/kg respectively) extracts of D. arborea, Sildenafil citrate (1.44 mg/kg), trimethylamine-N-oxide (TMAO, 20 mg/kg) and distilled water (10 ml/kg) were orally administered for 28 days to streptozotocin-induced diabetic rats. Glycaemia, body and reproductive organ masses, fertility parameters, total proteins, antioxidant enzymes activities, serum and testicular testosterone and the histology of the testes and epididymis were determined. Results revealed significant decreases in body and absolute and relative masses of testes, epididymis, seminal vesicles, prostate and vas deferens, fertility parameters, epididymal and testicular total proteins, serum and testicular testosterone levels as well as antioxidant enzymes activities. Interestingly, while having minor anti-hyperglycaemic effects, these abnormalities associated with testicular and epididymal alterations were alleviated by D. arborea especially the aqueous extract (500 mg/kg). These outcomes provided evidence of the androgenic properties of D. arborea in diabetic rats, which could be useful for a better management of sexual dysfunctions in diabetic patients.

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.

[Anti-tumor activity of HIS-4,a biflavonoid from Resina draconis,on human hepatoma HepG2 and SK-HEP-1 cells].

The research of anti-hepatocellular carcinoma(HCC) drug has attracted more and more attention. Natural products are the important source of active compounds for cancer treatment. A biflavonoid HIS-4 was isolated from Resina draconis in our previous study. MTT assay, hoechst staining, and flow cytometry analysis were used to investigate the effects of HIS-4 on the proliferation and apoptosis of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, the effects of HIS-4 on the migration and invasion ability of HepG2 and SK-HEP-1 cells were evaluated by wound healing assay and Transwell assay. In addition, MTT assay, flow cytometry analyses, Hoechst staining, wound healing assay, Transwell assay, and tube formation assay were used to explore the anti-angiogenic activity of HIS-4 in human umbilical vein endothelial cells(HUVECs). Mechanistically, the HIS-4 regulatory of signal pathways in H9 epG2 and SK-HEP-1 cells were analyzed by Western blot. This results showed that HIS-4 suppressed the proliferation of human hepatoma HepG2 and SK-HEP-1 cells. Moreover HIS-4 induced their apoptosis of HepG2 and SK-HEP-1 cells. HIS-4 inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, HIS-4 exhibited angiogenesis effects. Mechanistically, up-regulation of MAPK signaling pathway and down-regulation of mTOR signaling pathway may be responsible for anti-hepatoma activity of HIS-4. Therefore, HIS-4 may be a promising candidate drug for HCC treatment.

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.