Mangosteen for malignancy prevention and intervention: Current evidence, molecular mechanisms, and future perspectives.

Mangosteen (Garcinia mangostana L.), also known as the "queen of fruits", is a tropical fruit of the Clusiacea family. While native to Southeast Asian countries, such as Thailand, Indonesia, Malaysia, Myanmar, Sri Lanka, India, and the Philippines, the fruit has gained popularity in the United States due to its health-promoting attributes. In traditional medicine, mangosteen has been used to treat a variety of illnesses, ranging from dysentery to wound healing. Mangosteen has been shown to exhibit numerous biological and pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, antifungal, antimalarial, antidiabetic, and anticancer properties. Disease-preventative and therapeutic properties of mangosteen have been ascribed to secondary metabolites called xanthones, present in several parts of the tree, including the pericarp, fruit rind, peel, stem bark, root bark, and leaf. Of the 68 mangosteen xanthones identified so far, the most widely-studied are α-mangostin and γ-mangostin. Emerging studies have found that mangosteen constituents and phytochemicals exert encouraging antineoplastic effects against a myriad of human malignancies. While there are a growing number of individual research papers on the anticancer properties of mangosteen, a complete and critical evaluation of published experimental findings has not been accomplished. Accordingly, the objective of this work is to present an in-depth analysis of the cancer preventive and anticancer potential of mangosteen constituents, with a special emphasis on the associated cellular and molecular mechanisms. Moreover, the bioavailability, pharmacokinetics, and safety of mangosteen-derived agents together with current challenges and future research avenues are also discussed.

13-Butoxyberberine Bromide Inhibits Migration and Invasion in Skin Cancer A431 Cells.

Cancer metastasis is the primary cause of cancer morbidity and mortality. Anti-metastasis mechanism of skin cancer by 13-butoxyberberine bromide, a novel berberine derivative, has not yet been reported. This study investigated the effects of 13-butoxyberberine bromide on migration and invasion of skin cancer A431 cells. The cytotoxicity of 13-butoxyberberine bromide was determined by MTT assay. The effect of 13-butoxyberberine bromide on cell migration and invasion were examined using a wound-healing assay, transwell migration assay, and transwell invasion assay, respectively. The cell adhesion ability was determined by an adhesion assay. Protein expressions that play important roles in cancer migration and invasion were evaluated by Western blot analysis. The results showed that 13-butoxyberberine bromide effectively inhibited cell migration, invasion, and adhesion in A431 cells. Interestingly, 13-butoxyberberine bromide was more effective for cell migration inhibition than berberine. In addition, 13-butoxyberberine bromide showed anti-migration and anti-invasion effects by down-regulated MMP-2 and MMP-9 expression and up-regulated TIMP-1 and TIMP-2 expression in A431 cells. Moreover, pretreatment with 13-butoxyberberine bromide significantly inhibited EGF-induced cell migration and p-EGFR, ERK, p-ERK, STAT3, and p-STAT3 expressions in A431 cells at lower concentrations when compared with the berberine. These findings indicated that 13-butoxyberberine bromide could be further developed as an anticancer agent.

Apoptosis Induction through MAPK Signaling Pathway in LoVo Cells by Fatty Acid Fraction from Rice Bran Oil.

Colorectal cancer is one of the five leading cancer incidents and mortality in Thailand and worldwide. Fatty acids (FA) are bioactive molecules which have potential as adjunctive chemotherapeutic agents. To study the effect of fatty acid fraction (FAs) extracted from organic rice bran oil on apoptosis induction and growth inhibition in human colorectal cancer cell line, LoVo cells. The results demonstrated that FAs inhibited cell viability and induced cell death via apoptosis associated with MAPKs pathway. The EC50 of FAs in LoVo was 172.80 ± 1.05 µg/ml. FAs treatment significantly increased nuclear condensation and decreased mitochondrial membrane potential. Moreover, FAs activated Bax, Caspase-9, -7 and PARP cleavage, while inhibited Bcl-2 expression. Furthermore, FAs increased p53 expression and phosphorylation of ERK and p38. FAs extracted from organic rice bran oil inhibited LoVo cell viability and induced apoptosis via MAPKs pathway. These data suggest the potential use of FAs extracted from organic rice bran oil to prevent or treat colon cancer in the future.

Enhancing Anticancer Potency of a 13-Substituted Berberine Derivative with Cationic Liposomes.

Cationic liposomal formulations of the telomeric G-quadruplex stabilizing ligand, 13-(2-naphthylmethoxy)berberine bromide (1), have been developed with the purpose of delivering 1 into the nucleus of cancer cells for potential telomere targeting. Berberine derivative 1 was encapsulated in various cationic lipids 2-4 by the thin film evaporation method; these lipids are cationic after amine protonation. The most appropriate liposomal berberine formulation was that of 1 and the cholesterol derived cationic lipid 4 in a weight ratio of 1 : 20 with 76.5% encapsulation efficiency of 1. Cellular uptake studies in the HeLa and HT-29 cancer cells lines showed that the liposomal berberine derivative uptake in the cells was higher and more stable than for berberine derivative 1 alone while free 1 was completely decomposed in the cells within 60 min exposure to the cells. Anticancer activity of the liposomal berberine derivative 1 based on 4 was greater than that for the free berberine derivative 1 in the MCF-7, HeLa and HT-29 cell line by 2.3-, 4.9- and 5.3-fold, respectively, and also, interestingly, superior to the anticancer drug doxorubicin against the HT29 cancer cell line.

Effects of Artonin E on Cell Growth Inhibition and Apoptosis Induction in Colon Cancer LoVo and HCT116 Cells.

Today, colon cancer is the leading cause of cancer death. In Thailand, colon cancer is the third most common cancer in men and the second in women. Currently, the treatments for colon cancer include surgery, chemotherapy, radiation therapy, immunotherapy, hormone therapy, targeted drug therapy, and stem cell therapy. However, some treatments have side effects for cancer patients, causing unwanted symptoms. In addition, targeted therapy comes with a high cost for patients. Therefore, bioactive compounds might be a good choice for colon cancer treatment. In this study, we investigated the effect of artonin E on apoptosis induction in colon cancer LoVo and HCT116 cells. The concentration ranges of artonin E at 3, 5, 10, and 30 µg/mL in LoVo cells and 1, 1.5, 2, and 3 µg/mL in HCT116 cells were examined. The results implied that artonin E decreased cell viability and increased apoptotic cells in a dose-dependent manner. In addition, artonin E stimulated mitochondrial membrane potential (ΔΨm) changes associated with apoptosis by increasing the sub-G1 population analyzed by flow cytometry. Western blotting showed that artonin E increased the proapoptotic protein, Bax, and decreased anti-apoptotic proteins' (Bcl-2 and Bcl-x) expression. Moreover, artonin E also increased cleaved caspase-7 and cleaved-PARP expression in both LoVo and HCT116 cells. Interestingly, artonin E induced apoptosis through p-ERK1/2, p-p38/p38, and p-c-Jun expression in both cells. Our results suggested that artonin E induced apoptosis via caspase activation associated with the MAPKs signaling pathway. Therefore, artonin E might be used as a potential anticancer drug for colon cancer in the future.

Etlingera elatior Extract promotes cell death in B16 melanoma cells via down-regulation of ERK and Akt signaling pathways.

BACKGROUND: Torch ginger (Etlingera elatior, EE) is a ginger plant that found in Southeast Asia. Previous study showed its flowers and leaves composed of several flavonoids with anti-cancer activity. This study aims to investigate the mechanism of EE extract on cell death induction in melanoma cells. METHODS: To carry out this study, the cytotoxic effect of EE extract was performed using MTT assay. Nuclear morphological change and loss of mitochondrial membrane potential were observed using Hoechst 33,342 and JC-1 staining. Flow cytometry using Annexin V/PI double staining assessed apoptosis, necrosis and viability. Caspase activity was detected by caspase activity kits. The expression of Bcl-2 family proteins, ERK and Akt signaling pathways were examined by Western blot analysis. RESULTS: The treatment of EE extract resulted in a dose- and time-dependent reduction in cell viability in B16 cells. It also induced nuclear condensation, phosphatidylserine exposure, and loss of mitochondrial membrane potential, which are markers of apoptosis. Furthermore, the expression of Bim was increased instead of Bax and Bcl-2. The results also showed caspase-independent activity and the down-regulation of ERK and Akt signaling pathway. CONCLUSION: The results suggest that EE extract induced caspase-independent cell death via down-regulation of ERK and Akt pathways in B16 cells. This may be beneficial as a chemopreventive or chemotherapeutic agent in melanoma treatment.

Secondary Metabolites from the Marine-Derived Fungus Dichotomomyces sp. L-8 and Their Cytotoxic Activity.

Bioassay-guided isolation of the secondary metabolites from the fungus Dichotomomyces sp. L-8 associated with the soft coral Lobophytum crassum led to the discovery of two new compounds, dichotones A and B (1 and 2), together with four known compounds including dichotocejpin C (3), bis-N-norgliovictin (4), bassiatin (5) and (3R,6R)-bassiatin (6). The structures of these compounds were determined by 1D, 2D NMR and mass spectrometry. (3R,6R)-bassiatin (6) displayed significant cytotoxic activities against the human breast cancer cell line MDA-MB-435 and the human lung cancer cell line Calu3 with IC50 values of 7.34 ± 0.20 and 14.54 ± 0.01 µM, respectively, while bassiatin (5), the diastereomer of compound 6, was not cytotoxic.

Anti-Proliferation and Apoptosis Induction in Breast Cancer Cells by Cratoxylum cochinchinense Extract.

Background: Breast cancer is the most common invasive cancer in females worldwide. It was found about 37.5% in Thai females and is one of the leading causes of death-related cancers in women. Therefore, new finding of anti-cancer compound as a therapeutic candidate in breast cancer is necessary. Objective: To investigate the effect of Cratoxylum cochinchinense extract on anti-proliferation and apoptosis induction in breast cancer cells. Material and Method: Cell proliferation and cell viability assay were determined by MTT assay. Hoechst 33342 and JC-1 staining were used to determined nuclear morphological changes and mitochondrial membrane potential, respectively. Resu;ts: C. cochinchinense extract showed anti-proliferation in MDA-MB-468 treated cells in a time- and dose-dependent manner with IC50 value of 19.19+0.8 µg/ml. In addition, C. cochinchinense extract induced nuclear condensation and apoptotic bodies in MDA-MB-468 treated cells. JC-1 staining revealed that C. cochinchinense extract induced mitochondrial membrane dysfunction. Conclusion: C. cochinchinense extract showed anti-proliferation and apoptosis induction properties in MDA-MB-468 treated cells. These results suggested that C. cochinchinense extract may be a potential candidate for anti-cancer drug developing. The underlying mechanisms of apoptosis induction should be further studied.

Apoptosis induction associated with the ER stress response through up-regulation of JNK in HeLa cells by gambogic acid.

BACKGROUND: Gambogic acid (GA) was extracted from the dried yellow resin of gamboge (Garcinia hanburyi) which is traditionally used as a coloring material for painting and cloth dying. Gamboge has been also used as a folk medicine for an internal purgative and externally infected wound. We focused on the mechanisms of apoptosis induction by GA through the unfold protein response (ER stress) in HeLa cells. METHODS: The cytotoxic effect of GA against HeLa cells was determined by trypan blue exclusion assay. Markers of ER stress such as XBP-1, GRP78, CHOP, GADD34 and ERdj4 were analyzed by RT-PCR and Real-time RT-PCR. Cell morphological changes and apoptotic proteins were performed by Hoechst33342 staining and Western blotting technique. RESULTS: Our results indicated a time- and dose-dependent decrease of cell viability by GA. The ER stress induction is determined by the up-regulation of spliced XBP1 mRNA and activated GRP78, CHOP, GADD34 and ERdj4 expression. GA also induced cell morphological changes such as nuclear condensation, membrane blebbing and apoptotic body in Hela cells. Apoptosis cell death detected by increased DR5, caspase-8, -9, and -3 expression as well as increased cleaved-PARP, while decreased Bcl-2 upon GA treatment. In addition, phosphorylated JNK was up-regulated but phosphorylated ERK was down-regulated after exposure to GA. CONCLUSIONS: These results suggest that GA induce apoptosis associated with the ER stress response through up-regulation of p-JNK and down-regulation of p-ERK in HeLa cells.

Expression profiles of human CCN genes in patients with osteoarthritis or rheumatoid arthritis.

OBJECTIVE: Osteoarthritis (OA) and rheumatoid arthritis (RA) are widespread disabling joint disorders that are considered to be polygenic in nature. This study investigated the spatial expression patterns of all six known human CCN genes using end-stage OA and RA joint samples. DESIGN: We performed in situ hybridization and histological analysis to investigate the spatial expression patterns of human CCN genes using joint tissues obtained during total knee and hip joint replacement procedures on patients with advanced OA or RA. Normal joint tissues taken while performing bipolar hip replacement surgeries were used as controls. RESULTS: All CCN genes were expressed at higher levels in OA and RA synovial samples as compared with normal controls. Whereas CCN3 and CCN6 were undetectable in control, OA, and RA cartilage, CCN1, CCN2, CCN4, and CCN5 were expressed to a greater extent in OA and RA knee cartilage. CONCLUSIONS: Our results indicate an involvement of several CCN genes in the pathophysiology of OA and RA.

Antiproliferation and Apoptosis Induction in Colorectal Cancer Cells by Goniothalamin.

OBJECTIVE: To investigate the effect of goniothalamin on antiproliferation and apoptosis induction in three types of colorectal cancer cells. BACKGROUND: Colorectal cancer is the third of the twentieth most commonly diagnosed cancer. Different types of colorectal cancer cells differ in genotype and characteristics leading to different responses to anticancer drugs. Therefore, finding new anticancer compound for the colorectal cancer cells is necessary. MATERIAL AND METHOD: Antiproliferative response of goniothalamin on three colorectal cancer cell lines including Colo 205, SW480, and LoVo were determined by MTT assay. The antiproliferative response at different time and dose was also observed. Apoptosis induction by goniothalamin was observed in all three cell-lines via morphological changes and nuclear condensation by Hoechst33342 staining. RESULTS: Goniothalamin showed different antiproliferative response on Colo 205, SW480, and Lo Vo cells at the IC50 value is 9.86 ± 0.38 µM, 22.00 ± 4.40 µM, and 65.25 ± 1.85 µM respectively. In addition, the antiproliferative response of goniothalamin was a time- and dose-dependent manner Apoptosis morphological changes and nuclear condensation were clearly observed in Colo 205, SW480 and LoVo cells treated with 10 µM, 25 µM, and 50 µM goniothalamin, respectively. CONCLUSION: Goniothalamin showed antiproliferation and apoptosis induction in colorectal cancer cells with different sensitivity depending on cell type. Investigation of mechanisms underlying apoptosis and its potential use for colorectal cancer treatment should be further studied.

Aureobasidium pullulans as a source of liamocins (heavy oils) with anticancer activity.

Liamocins are structurally unique, heavier-than-water "oils" produced by certain strains of Aureobasidium pullulans. The aim of the current study is to identify new sources of liamocins and evaluate their potential as anticancer agents. Nine strains of A. pullulans from phylogenetic clades 8, 9, and 11 were examined for the first time for production of liamocins. Strains in these clades have only been isolated from tropical environments, and all strains tested here were from various locations in Thailand. Strains RSU 9, RSU 21, and RSU 29, all from clade 11, produced from 7.0 to 8.6 g liamocins/l from medium containing 5 % sucrose. These are the highest yields of liamocins that we have found thus far. These strains also produced from 9.4 to 17 g pullulan/l. The structural identity of liamocins was confirmed by matrix-assisted laser desorption/ionization mass spectrometry; differential spectra were obtained in which the dominant ion was either at about m/z 805.5 or m/z 949.6, consistent with the structure of liamocins. Liamocins from A. pullulans strains RSU 9 and RSU 21 inhibited two human breast cancer cell lines and a human cervical cancer cell line (IC50 values of 32.2 ± 1.4 to 63.1 ± 2.4 µg liamocins/ml) but were not toxic to a normal cell line. Liamocins weakly inhibited a strain of Enterococcus faecalis, but did not inhibit strains of Lactobacillus fermentum, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Thus, A. pullulans phylogenetic clade 11 is a promising source of liamocins, and these compounds merit further examination as potential anticancer agents.

Effects of barakol from Cassia siamea on neuroblastoma SH-SY5Y cell line: A potential combined therapy with doxorubicin.

Management of neuroblastoma is challenging because of poor response to drugs, chemotherapy resistance, high relapse, and treatment failures. Doxorubicin is a potent anticancer drug commonly used for neuroblastoma treatment. However, doxorubicin induces considerable toxicities, particularly those caused by oxidative-related damage. To minimize drug-induced adverse effects, the combined use of anticancer drugs with natural-derived compounds possessing antioxidant properties has become an interesting treatment strategy. Barakol is a major compound found in Cassia siamea, an edible plant with antioxidant and anticancer properties. Therefore, barakol could potentially be used in combination with doxorubicin to synergize the anticancer effect, while minimizing the oxidative-related toxicities. Herein, the potential of barakol (0.0043-43.0 µM) to synergize the anticancer effect of low-dose doxorubicin (0.5 and 1.0 µM) was investigated. Results indicated that barakol could enhance the cytotoxic effect of low-dose doxorubicin by affecting the cell viability of the treated cells. Furthermore, the co-treatment with barakol and low-dose doxorubicin decreased the levels of intracellular ROS when compared with the control. Moreover, the antimetastatic effect of the barakol itself was studied through its ability to inhibit metalloproteinase-3 (MMP-3) activity and prevent cell migration. Results revealed that the barakol inhibited MMP-3 activity and prevented cell migration in time- and dose-dependent manners. Additionally, barakol was a non-cytotoxic agent against the normal tested cell line (MRC-5), which suggested its selectivity and safety. Taken together, barakol could be a promising compound to be further developed for combination treatment with low-dose doxorubicin to improve therapeutic effectiveness but decrease drug-induced toxicities. The inhibitory effects of barakol on MMP-3 activity and cancer cell migration also supported its potential to be developed as an antimetastatic agent.

Targeted deletion of Atg5 reveals differential roles of autophagy in keratin K5-expressing epithelia.

Autophagy contributes to the homeostasis of many tissues, yet its role in epithelia is incompletely understood. A recent report proposed that Atg5-dependent autophagy in thymic epithelial cells is essential for their function in the negative selection of self-reactive T-cells and, thus, for the suppression of tissue inflammation. Here we crossed mice carrying floxed alleles of the Atg5 gene with mice expressing the Cre recombinase under the control of the keratin K5 promoter to suppress autophagy in all K5-positive epithelia. The efficiency of autophagy abrogation was confirmed by immunoanalyses of LC3, which was converted to the autophagy-associated LC3-II form in normal but not Atg5-deficient cells, and of p62, which accumulated in Atg5-deficient cells. Mice carrying the epithelium-specific deletion of Atg5 showed normal weight gain, absence of tissue inflammation, and a normal morphology of the thymic epithelium. By contrast, autophagy-deficient epithelial cells of the preputial gland showed aberrant eosinophilic staining in histology and premature degradation of nuclear DNA during terminal differentiation. Taken together, the results of this study suggest that autophagy is dispensable for the suppression of autoimmunity by thymic epithelial cells but essential for normal differentiation of the preputial gland in mice.

Novel small-molecule compounds that affect cellular morphogenesis in yeast and mammalian cells.

Drugs affecting cellular morphological changes leading to tumor cell migration and invasion are desirable for cancer therapy. In the present study, we screened for small-molecule compounds that affect the cellular morphology of both unicellular yeast and mammalian HEK293 cells to identify drug candidates. The yeast formin protein Bni1 and Src homology 3 (SH3)-pleckstrin homology (PH) domain protein Boi1, which are required for proper morphogenesis, cause growth defects when overexpressed in yeast. Using this system, we screened a chemical library consisting of ～8000 compounds to identify drug candidates that suppress these growth defects. None of the screened compounds induced morphological changes in vegetatively growing yeast cells, but several compounds had inhibitory effects on pheromone-induced projection formation and actin localization, suggesting that these compounds affected a specific stage of morphogenesis. Five of the compounds also induced morphological changes in mammalian HEK293 cells. Among the identified compounds, BTB03156, 2-[(4-chlorophenyl)sulfonyl]-1-methyl-3,5-dinitrobenzene, and BTB02467, 1-[(4-chlorophenyl)sulfonyl]-2-nitro-4-(trifluoromethyl)benzene, although they have similar structures, displayed differing effects on the yeast growth defects caused by latrunculin A, an actin polymerization inhibitor. The chemical library compounds identified using this in vivo screening approach are simple, cell-permeable molecules, and therefore may be useful in the development of therapeutic drugs for cancer metastasis and other actin-related diseases.

Apoptotic induction of skin cancer cell death by plant extracts.

OBJECTIVE: The aim of the present study was to investigate the effects of plant extracts on cancer apoptotic induction. MATERIAL AND METHOD: Human epidermoid carcinoma A431 cell line, obtained from the American Type Culture Collection (ATCC, Manassas, VA), was maintained in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37 degrees C, 5% carbon dioxide (CO2). Plant extract solutions were obtained from S & J international enterprises public company limited. These plant extracts include 50% hydroglycol extracts from Etlingera elatior (Jack) R.M.Smith (torch ginger; EE), Rosa damascene (damask rose; DR) and Rafflesia kerrii Meijer (bua phut; RM). The cell viability, time and dose dependency were determined by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. A431 cells were treated with the plant extracts and stained with Hoechst 33342 fluorescent staining dye. RESULTS: Cell viability was demonstrated by the inhibitory concentration 50% (IC50). The anti-proliferative effects were shown to be dependent on time and dose. Typical characteristics of apoptosis which are cell morphological changes and chromatin condensation were clearly observed. CONCLUSION: The plant extracts was shown to be effective for anti-proliferation and induction of apoptosis cell death in skin cancer cells. Therefore, mechanisms underlying the cell death and its potential use for treatment of skin cancer will be further studied.

Zanthoisobutylamides A - C: rare dimeric C-6 substituent dihydrobenzophenanthridine alkaloids from the roots of Zanthoxylum nitidum.

Three new dihydrobenzophenantridine alkaloids, zanthoisobutylamides A-C (2-4), consisting of a rare 6-alkylamide dihydrochelerythrine moiety, and two new small molecules of the unsaturated alkylamide, zanthoxylumamide J (1) and of phenylpropanoid, methyl 2-hydroxy-3,4-dimethoxycinnamate (5) together with 44 known compounds were isolated from the roots of Zanthoxylum nitidum. The structures of these compounds were established by analysis of spectroscopic data and comparison of their spectroscopic data with those previously published data. Some isolated compounds were evaluated for their cytotoxic activities.

Protective effect of alpha-mangostin against type-I collagen formation in thioacetamide-induced cirrhotic rat.

OBJECTIVE: To elucidate the protective effect of alpha-mangostin (alpha-MG) against increment of type-I collagen-positive hepatocytes in rat cirrhosis induced by thioacetamide (TAA). MATERIAL AND METHOD: Rats were separated into 4 groups. The first group was, the control, untreated with TAA. The cirrhotic rats, the second group, were induced by TAA injection (200 mg/kg), 3 times per week. Rats in the third group received treatment of TAA (200 mg/kg) alternating with alpha-MG (100 mg/kg) for every other day. Animals in the last group were treated only with alpha-MG (100 mg/kg), 3 times per week. The chemicals used each group were given intraperitoneally for 16 weeks. The type-I collagen and type-I collagen-positive hepatocytes were explored by using immunohistochemical technique. RESULTS: In cirrhotic livers type-I collagen was immunopositive in the connective tissue and a large number of hepatocytes. The number of type I collagen-positive-hepatocytes (414.00 +/- 25.23) in TAA-induced cirrhosis group increased significantly when compared to those in the control group (131.40 + 9.63). Interestingly, a significant decrease in the number of type-I collagen-positive-hepatocytes was observed in TAA-alpha-MG-prevention group (103.60 +/- 36.55) and in alpha-MG-injected group (54.00 +/- 5.30) compared to those in the control group and TAA-induced cirrhosis. CONCLUSION: 100 mg/kg of alpha-MG could lower the number of type-I collagen-positive-hepatocytes in TAA-induced cirrhosis. It is probable that alpha-MG helps to keep up more blood circulation to the liver cells through dilated sinusoids. This vascular adaptation enhances high oxygen blood to the hepatocytes which, in turn, reduces the damage of hepatocytes caused by TAA-derived reactive oxygen species.

A new lignan from the stem bark of Fagraea fragrans Roxb.

A new lignan, named fagraeanolide (1), and 14 known compounds were isolated from the stem bark of Fagraea fragrans Roxb. Their structures were determined by spectroscopic methods. Fagraeanolide is the first identified oxofurofuran lignan from the genus Fagraea, whileß-boswelic acid (4), gentiogenol (5), 3-(4-hydroxy-3-methoxyphenyl)-acrylic acid octacosyl ester (7) and pinoresinol (14) were isolated from this plant for the first time. The crude extract of F. fragrans was not toxic to cell lines. The isolated compounds showed no antibacterial activity.

A new alkaloid and a new benzaldehyde derivative from the twig of Zanthoxylum rhetsa (Roxb.) DC.

A new alkaloid, 2-acetyl-4-methoxyfuro[2,3-b]quinoline (1), and a new benzaldehyde derivative, (2'S)-4-(2'-hydroxy-3'-methyl-3'-butenoxy)benzaldehyde (2), were isolated from the twig of Zanthoxylum rhetsa (Roxb.) DC. along with twenty-six known compounds (3-28). Their structures were determined by spectroscopic analysis (1D and 2D NMR spectroscopy and HRMS analysis) and comparison with data reported in the literature. Thirteen of the known compounds were evaluated for their cytotoxic activities against human cancer cell lines that included MDA-MB-231, SW1353, A549, and HCT116. (±)-8-Acetonyldihydronitidine (15) showed moderate cytotoxicity toward the SW1353 cancer cell line with an IC50 value of 18.90±0.39 µg/mL, and exhibited weak cytotoxic activity against MDA-MB-231, A549 and HCT116 cell lines with IC50 values of 49.86-71.32 µg/mL.