Dynamics of progestogenic activity in serum following administration of Ligusticum chuanxiong

Many women are using botanical alternatives for menopausal hormone replacement therapy (HRT) because current progestins, compounds with progesterone activity, have adverse risk profiles. However the development of phyto-progestins for HRT is hampered by the absence of basic pharmacokinetic/pharmacodynamic (PK/PD) data due to the lack of methods to capture summated effects of the numerous compounds that contribute to bioactivity in vivo. In this study, we explored the utility of progesterone receptor (PR)-driven bioassays to track changes in serum progestogenic activity following administration of traditional Chinese medicinal herb, Ligusticum chuanxiong, with potent progestogenic activity. Sensitive and specific (>300-fold) increases in progestogenic activity were observed when HeLa cells transfected with PR and a PR-driven promoter were exposed to the progestogenic drug, medroxy-progesterone acetate (MPA), suggesting the utility of the bioassay to measure progestogenic effects for PK/PD studies. Progestogens were administered to male Sprague-Dawley rats and serum extracted for measurement of progestogenic activity. Effect-time studies indicate that injection of MPA and L. chuanxiong extract raised area-under-curve of progestogenic activity in sera by 8.2-fold (p<0.001) and 4.5-fold (p<0.01) respectively, compared to sera from rats administered vehicle only. Administration of MPA and L. chuanxiong extract by the oral route resulted in a 5.4 (p<0.001) and 2.3-fold (p=0.07) increase respectively. Our data suggest that PR-responsive reporter gene bioassays can measure bioavailability of compounds, known and unknown, of complex botanicals for hormone replacement therapy. L. chuanxiong extracts exert progestogenic activity in vivo, and may have utility for progesterone-replacement therapy.     

Selectivity and potency of the retroprogesterone dydrogesterone in vitro

Dydrogesterone is widely used for menstrual disorders, endometriosis, threatened and habitual abortion and postmenopausal hormone replacement therapy. Although progestins have a promiscuous nature, dydrogesterone does not have clinically relevant androgenic, estrogenic, glucocorticoid or mineralocorticoid activities. To date, systematic biochemical characterization of this progestin and its active main metabolite, 20α-dihydrodydrogesterone, has not been performed in comparison to progesterone. The objective of this study was to evaluate the selectivity and potential androgenic/antiandrogenic effects of dydrogesterone and its metabolite in comparison to progesterone and medroxyprogesterone acetate by analyzing their interference with AR signaling in vitro. We characterized dydrogesterone and its metabolite for their binding and transactivation of androgen and other steroid hormone receptors and for their potential inhibitory effects against androgen biosynthetic enzymes, 17β-hydroxysteroid dehydrogenase types 3 and 5 and 5α-reductase types 1 and 2. We found that dydrogesterone resembled progesterone mainly in its progestogenic effects and less in its androgenic, anti-androgenic, glucocorticoid and antiglucocorticoid effects; whereas, 20α-dihydrodydrogesterone showed reduced progestogenic potency with no androgenic, glucocorticoid and mineralocorticoid effects. Effects on the androgen and glucocorticoid receptor differed depending on the technology used to investigate transactivation. Progesterone, but not dydrogesterone and 20α-dihydrodydrogesterone, exerted anti-androgenic effects at the pre-receptor level by inhibiting 5α-reductase type 2. Dydrogesterone, 20α-dihydrodydrogesterone and progesterone inhibited the biosynthesis of testosterone catalyzed by 17β-hydroxysteroid dehydrogenase types 3 and 5; however, due to their micromolar K_i values, these activities appeared to be not of relevance at therapeutic levels. Overall, our data show that the anti-androgenic potential of dydrogesterone and 20α-dihydrodydrogesterone is less pronounced compared to progesterone.     

Antibacterial activities of the methanol extracts of Canarium schweinfurthii and four other Cameroonian dietary plants against multi-drug resistant Gram-negative bacteria

Bacterial infections are among the major cause of morbidity and mortality worldwide. The present study was designed to evaluate the in vitro antibacterial activities of the methanol extracts of five Cameroonian edible plants namely Colocasia esculenta, Triumfetta pentandra, Hibiscus esculentus, Canarium schweinfurthii and Annona muricata against a panel of 19 multidrug resistant Gram-negative bacterial strains. The liquid broth microdilution was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the extracts. The preliminary phytochemical screening of the extracts was conducted according to the standard phytochemical methods. Results showed that all extracts contained compounds belonging to the classes of polyphenols, triterpenes and steroids, other classes of chemicals being selectively distributed. Canarium schweinfurthii extract showed the best activity with MIC values ranging from 64 to 1024 μg/mL against 89.5% of the 19 tested bacteria strains. MIC values below or equal to 1024 μg/mL were also recorded with Triumfetta pentandra, Annona muricata, Colocasia esculenta and Hibiscus esculentus extracts respectively against 15/19 (78.9%), 11/19 (57.9%), 10/19 (52.6%) and 10/19 (52.6%) tested bacteria. Extract from C. schweinfurthii displayed the lowest MIC value (64 μg/mL) against Escherichia coli AG100A_Tet. Finally, the results of this work provide baseline information for the use of C. esculenta, T. pentandra, H. esculentus, C. schweinfurthii and A. muricata in the treatment of bacterial infections including multidrug resistant phenotypes.     

Antioxidant activity,acetylcholinesterase and tyrosinase inhibitory potential of Pulmonaria officinalis and Centarium umbellatum extracts

In this study several investigations and tests were performed to determine the antioxidant activity and the acetylcholinesterase and tyrosinase inhibitory potential of Pulmonaria officinalis and Centarium umbellatum aqueous extracts (10% mass) and ethanolic extracts (10% mass and 70% ethanol), respectively. Moreover, for each type of the prepared extracts of P. officinalis and of C. umbellatum the content in the biologically active compounds – polyphenols, flavones and proanthocyanidins was determined. The antioxidant activity was assessed using two methods, namely the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and reducing power assay. The analyzed plant extracts showed a high acetylcholinesterase and tyrosinase inhibitory activity in the range of 72.24–94.24% (at the highest used dose – 3 mg/mL), 66.96% and 94.03% (at 3 mg/mL), respectively correlated with a high DPPH radical inhibition – 70.29–84.9% (at 3 mg/mL). These medicinal plants could provide a potential natural source of bioactive compounds and could be beneficial to the human health, especially in the neurodegenerative disorders and as sources of natural antioxidants in food industry.     

Inhibition realization of multidrug resistant bacterial and fungal isolates using Coccinia indica extracts

The crude aqueous and ethanolic leaf extracts of Coccinia indica were screened for methicillin resistant Staphylococcus aureus (MRSA), multidrug resistant (MDR) Streptococcus pyogenes, Escherichia coli, Candida auris and Trichophyton rubrum. Antibacterial and antifungal activities were assessed by standard disc diffusion and tube dilution methods. The results showed that ethanolic extract inhibited MRSA, C. auris at 250 µg/mL and S. pyogenes at 200 µg/mL comparable to the susceptible antibiotics used as positive controls. There was no observable activity against T. rubrum, while a mild activity was observed with ethanolic extracts over E. coli at higher concentrations which did not turn out to be complete or significant inhibition. Aqueous extract did not exhibit any observable activity over the five organisms tested. Furthermore, the results showed clear cut concentration dependent antibacterial and antifungal activities with additional variation of specific activity over Gram positive and negative bacteria, yeast and filamentous fungi. So, it is evident that ethanolic extract of Coccinia indica could be further escalating for mechanistic studies in the era of multidrug resistance, indigenous preparations from herbs could be a safe choice over clinically challenging organisms.     

In vitro binding to and in vivo effect on the cytosol and nuclear progesterone receptors of various progestins,and their relationship to synthesis of uteroglobin in rabbit uterus

In vitro binding affinities of various progestins to cytosol and nuclear progesterone receptors of rabbit uterus were determined and correlated with the biological potency of these steroids. In addition, cytosol and nuclear progesterone receptor levels were measured after a 5-day administration of different progestins (0.5 mg/kg daily) with variable biologic activites. The receptor levels were compared with the bilological response; the induction of uteroglobin synthesis. Cytosol and nuclear progesterone receptors had identical steroid binding properties (r = 0.98). The correlation between the in vitro binding affinity (cytosol or nuclear) and the in vivo biologic activity of the steroids was good (r = 0.73). After a 5-day treatment with progestins, the nuclear receptor concentration correlated in an inverse manner (r = ?0.84) with the uterine fluid unteroglobin concentration. A similar, but slightly weaker correlation (r = ?0.81) was also found for the cytosol receptor content and uteroglobin secretion. These data indicate that not only nuclear, but also cytosol progesterone receptor levels decrease in the rabbit uterus during chronic hormone action. Decline in the nuclear progesterone receptor content seemed to occur during treatment with all progestational steroids, while onlyi progestins with high biological potency were capable of decreasing the cytosol receptor content.     

中草药浸提液对小列当种子发芽的影响

选用240种常用中草药,研究其蒸馏水和甲醇浸提液原液及其10倍、100倍和1 000倍稀释液对小列当种子发芽的影响.结果表明:小列当种子在蒸馏水浸提液刺激下发芽率超过70%的中草药有灯心草、降香和莲须,在甲醇浸提液刺激下发芽率超过70%的中草药有百部、桑椹、谷芽和萆薢;蒸馏水浸提液对小列当种子发芽抑制率超过50%的中草药有菊花、棕榈、苦杏仁和黄柏,甲醇浸提液对小列当种子发芽抑制率超过70%的有续断、地黄、肉豆蔻、地肤子、黄连、木贼和胡黄连.大部分中草药浸提液在10倍稀释液条件下对小列当种子发芽的刺激或抑制作用最明显.研究发现,一些参试中草药蒸馏水和甲醇浸提液能够刺激或抑制小列当种子萌发,并且其对种子萌发的影响程度随浸提液浓度的变化而异,不同中草药最佳处理浓度不同,而且用甲醇浸提液可筛选出更多种具有化感作用的中草药.     

In vitro inhibition of rat uterine contractility induced by 5α and 5β progestins

Ten natural progestins were evaluated for their capacity to inhibit the $\text{in vitro}$ motility of rat's uterus. Progestins with their ring A reduced in the 5β position were significantly more potent than Δ⁴-3 keto and 5α reduced progestins. These last progestins were ineffective to inhibit uterine motility excepting 3α-hydroxy-5α-pregnan-20-one which was slightly less effective than progesterone. The potency of the progestins to inhibit uterine motility was related to their capacity to induce membrane stabilization. The data indicates that 5β, but not 5α reduction of progesterone, may be important for regulating myometrial activity.     

Comparison of Differences in Chemical Composition and Related Antioxidant Activity of Snow Lotus from Different Origins

The snow lotus is an endangered traditional Chinese medicinal herb. Saussurea involucrata, Saussurea laniceps, and Saussurea medusa, the three main snow lotus species (five herbs and two S. involucrata cell cultures), were selected for this study. Snow lotus (XLs) was extracted using 75 % (v/v) ethanol. Two reversed phase-high performance liquid chromatography-diode array detector methods were developed and validated for the determination of 10 representative components in XLs. The antioxidant efficacy of XLs and their components was investigated using DPPH, ABTS free radical scavenging, and ROS inhibition experiments. The results showed that the IC₅₀ for DPPH scavenging ranged from 0.06–0.29 mg/mL for XLs and from 0.13–0.63 mg/mL for ABTS, and could downregulate ROS to varying degrees. The results of the antioxidant activity showed that rutin, quercetin, and isochlorogenic acid A contributed to the antioxidant capacity of XLs. The high content and activity of the cell cultures indicate that they can serve as an effective alternative to snow lotus, thus providing a theoretical basis for the selection of herbs and cell cultures to fulfil various needs.     

Oenothein B's contribution to the anti-inflammatory and antioxidant activity of Epilobium sp

Willow herb tea or preparation are available and relatively popular in the European market, and claimed to be effective inter alia because of their anti-inflammatory activity. The present study is therefore aimed at comparing the anti-inflammatory and antioxidant activity of extracts of the three most popular Epilobium species (E. angustifolium, E. hirsutum and E. parviflorum) and at juxtaposing this activity against the dominating compounds from the following extracts: oenothein B (OeB), quercetin-3-O-glucuronide and myricetin-3-O-rhamnoside. The phytochemical analysis of the extracts has shown that OeB quantities vary between 20% and 35%, while flavonoids content does not exceed 2%. All extracts have inhibited the activity of hyaluronidase and lipoxygenase with IC₅₀ around 5 μg/ml and 25 μg/ml. The inhibition of hyaluronidase is related with the presence of OeB, a strong inhibitor of this enzyme (IC₅₀ 1.1 μM). Additionally, the extracts inhibited myeloperoxidase (MPO) release from stimulated neutrophils. OeB inhibited MPO release similarly to the anti-inflammatory drug indomethacin with IC₅₀ 7.7 μM and 15.4 μM, respectively. Tested extracts significantly reduced the production of reactive oxygen species (ROS) from f-MLP and PMA induced neutrophils with IC₅₀ 5 μg/ml and 25 μg/ml, respectively. The flavonoids content seems to exert little influence on extracts’ activity, contrary to OeB, whose high concentration explains the activity of extract obtained from Epilobium. Tested currently marketed Epilobium preparations are often wrongly assigned, but we should stress that the level of OeB in all tested herbs was high and always exceeded 2% in raw material.     

Identification of progesterone and 5α‐dihydroprogesterone (5α‐DHP) in zebras by two‐dimensional high‐performance liquid chromatography and their dependence on the state of reproduction

Because of its low levels in late pregnancy, the relationship of progesterone to pregnancy maintenance in Equidae is not obvious. This study investigated the levels of progesterone (4‐pregnane‐3,20‐dione; P4) and 5α‐dihydroprogesterone (5α‐DHP) during pregnancy in zebras in relation to reproductive state. Blood samples from female zebras (Equus burchelli, E. zebra hartmannae, E. grevyi) were taken at Dvur Kralove Zoo. Progesterone and 5α‐DHP were separated by high‐performance liquid chromatography techniques and detected by cross‐reacting antibodies. Identification of progestins was achieved by comparing the identity of peaks of the samples with a standard. In E. z. hartmannae progesterone, values reached 50 ng/mL at the beginning of pregnancy and dropped to levels below 1 ng/mL during the second half of pregnancy. In contrast, 5α‐DHP increased up to 123 and 183 ng/mL during late pregnancy in E. z. hartmannae and E. burchelli, respectively. In E. grevyi, 5α‐DHP levels of 368 ng/mL were obtained during pregnancy, whereas progesterone values were similar in pregnant and non‐pregnant individuals. These marked differences in the course of progesterone and 5α‐DHP levels point to the importance of 5α‐DHP for pregnancy maintenance in zebras. Zoo Biol 18:325–333, 1999. © 1999 Wiley‐Liss, Inc.     

Enzymatic Activities of Allergen Extracts from Three Species of Dust Mites and Cockroaches Commonly Found in Korean Home

Allergen extracts from dust mites and cockroaches commonly found in Korean homes were used to evaluate their enzymatic activity as they are believed to influence allergenicity. Allergen extracts were prepared from 3 dust mite species (Dermatophagoides farinae, D. pteronyssinus, and Tyrophagus putrescentiae) and 3 cockroach species (Blattella germanica, Periplaneta americana, and P. fuliginosa) maintained in the Korea National Arthropods of Medical Importance Resource Bank. Proteins were extracted in PBS after homogenization using liquid nitrogen. The activities of various enzymes were investigated using the API Zym system. No significant difference in phosphatase, lipase, or glycosidase activity was observed among the 6 allergen extracts, but much difference was observed in protease activity. Protease activity was assessed in more detail by gelatin zymography and the EnzChek assay. Extract from T. putrescentiae showed the highest protease activity, followed by those of the cockroach extracts. Extracts from D. farinae and D. pteronyssinus showed only weak protease activity. Gelatinolytic activity was detected mainly in a 30-kDa protein in D. farinae, a 28-kDa protein in D. pteronyssinus, a > 26-kDa protein in T. putrescentiae, a > 20-kDa protein in B. germanica, and a > 23-kDa protein in P. americana and P. fuliginosa. The information on various enzymatic activities obtained in this study may be useful for future studies. In particular, the strong protease activity found in cockroach extracts could contribute to sensitization to cockroach allergens, which is known to be associated with the development of asthma.     

Antioxidative and cytotoxic potential of some Chenopodium L. species growing in Poland

The cytotoxic and antioxidant properties of lipophilic compounds extracted from different parts of four Chenopodium L. (Chenopodium album, Chenopodium hybridum, Chenopodium rubrum and Chenopodium urbicum) species were evaluated. The highest phenolic content was found in herb and seeds of all examined plants. Large amounts of free polyphenols were observed in herb extracts of C. album (3.36 mg/g DW), seeds of C. urbicum (3.87 mg/g DW) and roots of C. urbicum (1.52 mg/g DW). The cytotoxic activities of the extracts were assessed against human lung carcinoma A-549 and ovarian carcinoma TOV-112D and normal human fibroblast cell lines. Our study demonstrated that the extracts from the herb of C. rubrum and C. urbicum had the best antioxidant effect of all the extracts analyzed. Most of the extracts tested exhibited low cytotoxicity. However, the extracts from herb and seeds of C. album and C. hybridum showed the significant antiproliferative effect on the TOV-112 cell line.It can be concluded that antioxidant activity and phenolic composition differ mainly between plant parts and are quite similar between the plants, when the same plant part is analyzed. Thus, the Chenopodium extracts could be used as a readily accessible source of natural antioxidants, and may be used in the pharmaceutical industry and for food supplements production.     

New β-lactam – Tetramic acid hybrids show promising antibacterial activities

β-Lactams are the most important class of antibiotics, for which the emergence of resistance threatens their utility. As such, we explored the extent to which the tetramic acid motif, frequently found in naturally occurring antibiotics, can be used to generate novel β-lactam antibiotics with improved antibacterial activity. We synthesized new ampicillin – tetramic acid, cephalosporin – tetramic acid, and cephamycin – tetramic acid analogs and evaluated their activities against problematic Gram-positive and Gram-negative pathogens. Amongst the analogs, a 7-aminocephalosporanic acid analog, 3397, and a 7-amino-3-vinyl cephalosporanic acid, 3436, showed potent activities against S. aureus NRS 70 (MRSA) with MICs of 6.25?μg/mL and 3.13?μg/mL respectively. These new analogs were ≥16-fold more potent than cefaclor and cephalexin. Additionally, a Δ² cephamycin – tetramic acid analog 3474 which contained a basic guanidinium substituent at the 5-position of the tetramic acid core displayed potent activity against several clinical strains of K. pneumoniae and E. coli.     

Evaluation of inhibitory activities of plant extracts on production of LPS-stimulated pro-inflammatory mediators in J774 murine macrophages

Whole plant methanolic extracts of 14 traditionally used medicinal herbs were evaluated for their anti-inflammatory activity. Extracts of Grindelia robusta, Salix nigra, Arnica montana, and Quassia amara showed up to 4.5-fold inhibition of nitric oxide (NO) production in the J774 murine macrophage cells challenged with LPS without cytotoxicity. These four selected extracts significantly reduced the protein levels of inducible NO synthase (iNOS) and the cyclooxygenase-2 (COX-2) as observed by Western blot analysis. Culture supernatants from cells treated with these extracts indicated 3–5-fold reduction of tumor necrosis factor-α (TNF-α). However, only G. robusta and Q. amara extracts significantly inhibited (by 50%) IL-1β and IL-12 secretions. Furthermore, all these plant extracts were shown to prevent the LPS-mediated nuclear translocation of nuclear factor-κB (NF-κB). All the above observations indicate the anti-inflammatory potential of these plant extracts.     

Wool-associated proteolytic bacteria,isolated from Portuguese Merino breed

The main purpose of this study was to isolate and briefly characterize proteolytic bacteria from a poorly known habitat – raw wool. Fleece samples were accordingly collected from Merino raw wool – a Portuguese ewe breed, at three distinct areas of their body, from animals exhibiting no symptoms or signs of abnormalities; they were then subjected to enumeration and isolation of a total of 158 bacterial strains. Said isolates were screened for protease activity, using the spot technique, on Calcium Caseinate Agar containing 1% (w/v) skim milk. The 36 isolates displaying the highest protease activity underwent a more refined assessment of enzymatic performance – by examining their cell-free supernatant extracts, using casein as substrate. Two Bacillus isolates were eventually chosen owing to their highest proteolytic activities (24.6 and 15.9 U/mL), and identified using molecular biology tools.     

Pa-AGOG, the founding member of a new family of archaeal 8-oxoguanine DNA-glycosylases

Oxidative damage represents a major threat to genomic stability, as the major product of DNA oxidation, 8-oxoguanine (GO), frequently mispairs with adenine during replication. In order to prevent these mutagenic events, organisms have evolved GO-DNA glycosylases that remove this oxidized base from DNA. We were interested to find out how GO is processed in the hyperthermophilic archaeon Pyrobaculum aerophilum, which lives at temperatures around 100°C. To this end, we searched its genome for open reading frames (ORFs) bearing the principal hallmark of GO-DNA glycosylases: a helix–hairpin–helix motif and a glycine/proline-rich sequence followed by an absolutely conserved aspartate (HhH-GPD motif). Interestingly, although the P.aerophilum genome encodes three such ORFs, none of these encodes the potent GO-processing activity detected in P.aerophilum extracts. Fractionation of the extracts, followed by analysis of the active fractions by denaturing polyacrylamide gel electrophoresis, showed that the GO-processing enzyme has a molecular size of ~30 kDa. Mass spectrometric analysis of proteins in this size range identified several peptides originating from P.aerophilum ORF PAE2237. We now show that PAE2237 encodes AGOG (Archaeal GO-Glycosylase), the founding member of a new family of DNA glycosylases, which can remove GO from single- and double-stranded substrates with great efficiency.     

Laserpitium zernyi Hayek Flower and Herb Extracts: Phenolic Compounds,and Anti‐edematous,Antioxidant, and Antimicrobial Activities

Phenolic compounds and different biological activities of the dry MeOH extracts of the flowers and the herb (aerial parts without flowers) of Laserpitium zernyi Hayek (Apiaceae) were investigated. The total phenolic contents in the extracts were determined spectrophotometrically using Folin–Ciocalteu reagent. In both extracts, apigenin, luteolin, their 7‐O ‐glucosides, and chlorogenic acid were detected by HPLC . Identified phenolics were quantified in both extracts, except luteolin in L . zernyi herb extract. The extracts (p.o .) were tested for anti‐edematous activity in a model of carrageenan (i.pl .) induced rat paw edema. Antioxidant activity of the extracts was assessed by FRAP assay and DPPH and ^?OH radicals scavenging tests. Antimicrobial activity was investigated using broth microdilution test against five Gram ‐positive and three Gram ‐negative bacteria, as well as against two strains of Candida albicans . The polyphenol‐richer flower extract exerted higher anti‐edematous and antioxidant activities. The herb extract exhibited better antimicrobial effect against Micrococcus luteus , Enterococcus faecalis , Bacillus subtilis , and Pseudomonas aeruginosa , while against other tested microorganisms, the activity of both extracts was identical. Demonstrated biological activities of L . zernyi flower and herb extracts represent a good basis for their further investigation as potential new herbal medicinal raw materials.     

Phenolic acid content,antioxidant and cytotoxic activities of four Kalanchoë species

Phenolic acid composition, antioxidant, and cytotoxic activities in leaves of four Kalanchoe (Crassulaceae) species were evaluated. Determination of phenolic acid contents were conducted by an optimized LC–ESI-MS/MS method. The results show that Kalanchoe daigremontiana Raym.-Hamet & H. Perrier (using ASE extraction) and Kalanchoe pinnata (Lam.) Pers. contain the highest amounts of phenolic acids, while Kalanchoe nyikae Engl. the lowest ones. Among phenolic acids ferulic, caffeic and protocatechuic acids were occurring in the highest quantities in the analysed species. The greatest amounts of ferulic and protocatechuic acids were found in K. daigremontiana and K. pinnata. Moreover, the antiradical and cytotoxic activities of Kalanchoe extracts were investigated. All tested extracts possessed antioxidant activity. The obtained IC₅₀ values (μg/mL) ranged from 49.9 μg/mL to 1410 μg/mL, indicating a large variation of the activity of the analysed extracts. Cytotoxicity assays revealed dose-dependent effects in the cells lines tested. Only K. pinnata extract showed a high cytotoxicity against the H-9 human T cell line. Other extracts (K. daigremontiana, Kalanchoe milloti, K. nyikae) showed more pronounced cytotoxicity towards J45.01 cells (human acute lymphoblastic leukaemia T cells).The present study demonstrated that Kalanchoe extracts have significant antioxidant and cytotoxic effects. This suggests that these species can be used as new sources of natural antioxidants and potential anticancer compounds.