The Role of the PTEN Tumor Suppressor Gene and Its Anti-Angiogenic Activity in Melanoma and Other Cancers.

Human malignant melanoma and other solid cancers are largely driven by the inactivation of tumor suppressor genes and angiogenesis. Conventional treatments for cancer (surgery, radiation therapy, and chemotherapy) are employed as first-line treatments for solid cancers but are often ineffective as monotherapies due to resistance and toxicity. Thus, targeted therapies, such as bevacizumab, which targets vascular endothelial growth factor, have been approved by the US Food and Drug Administration (FDA) as angiogenesis inhibitors. The downregulation of the tumor suppressor, phosphatase tensin homolog (PTEN), occurs in 30-40% of human malignant melanomas, thereby elucidating the importance of the upregulation of PTEN activity. Phosphatase tensin homolog (PTEN) is modulated at the transcriptional, translational, and post-translational levels and regulates key signaling pathways such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways, which also drive angiogenesis. This review discusses the inhibition of angiogenesis through the upregulation of PTEN and the inhibition of hypoxia-inducible factor 1 alpha (HIF-1-α) in human malignant melanoma, as no targeted therapies have been approved by the FDA for the inhibition of angiogenesis in human malignant melanoma. The emergence of nanocarrier formulations to enhance the pharmacokinetic profile of phytochemicals that upregulate PTEN activity and improve the upregulation of PTEN has also been discussed.

Steroids and Fatty Acid Esters from Cyperus sexangularis Leaf and Their Antioxidant, Anti-Inflammatory and Anti-Elastase Properties.

Cyperus sexangularis (CS) is a plant in the sedges family (Cyperaceae) that grows abundantly in swampy areas. The leaf sheath of plants in the Cyperus genus are mostly used domestically for mat making, while they are implicated for skin treatment in traditional medicine. The plant was investigated for its phytochemical contents as well as its antioxidant, anti-inflammatory and anti-elastase properties. The n-hexane and dichloromethane leaf extracts were chromatographed on a silica gel column to afford compounds 1-6. The compounds were characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. The inhibitory effect of each compound against 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric ion radicals were determined by standard in vitro antioxidant methods. The in vitro anti-inflammatory response was measured using egg albumin denaturation (EAD) assay, while the anti-elastase activity of each compound in human keratinocyte (HaCaT) cells was also monitored. The compounds were characterized as three steroidal derivatives, stigmasterol (1), 17-(1-methyl-allyl)-hexadecahydro-cyclopenta[a]phenanthrene (2) and ß-sitosterol (3), dodecanoic acid (4) and two fatty acid esters, ethyl nonadecanoate (5) and ethyl stearate (6). Stigmasterol (1) exhibited the best biological properties, with IC50 of 38.18 ± 2.30 µg/mL against DPPH, 68.56 ± 4.03 µg/mL against NO and 303.58 ± 10.33 µAAE/mg against Fe3+. At 6.25 µg/mL, stigmasterol inhibited EAD by 50%. This activity was lower when compared to diclofenac (standard), which demonstrated 75% inhibition of the protein at the same concentration. Compounds 1, 3, 4 and 5 showed comparable anti-elastase activity with an IC50 ≥ 50 µg/mL, whereas the activity of ursolic acid (standard) was double fold with an IC50 of 24.80 ± 2.60 µg/mL when compared to each of the compounds. In conclusion, this study has identified three steroids (1-3), one fatty acid (4), and two fatty acid esters (5 and 6) in C. sexangularis leaf for the first time. The compounds showed considerable antioxidant, anti-inflammatory and anti-elastase properties. Thus, the findings may serve as a justification for the folkloric use of the plant as a local skin ingredient. It may also serve to validate the biological role of steroids and fatty acid compounds in cosmeceutical formulations.

In Vitro and In Silico Pharmacological and Cosmeceutical Potential of Ten Essential Oils from Aromatic Medicinal Plants from the Mascarene Islands.

In this study, 10 essential oils (EOs), from nine plants (Cinnamomum camphora, Curcuma longa, Citrus aurantium, Morinda citrifolia, Petroselinum crispum, Plectranthus amboinicus, Pittosporum senacia, Syzygium coriaceum, and Syzygium samarangense) were assessed for their antimicrobial, antiaging and antiproliferative properties. While only S. coriaceum, P. amboinicus (MIC: 0.50 mg/mL) and M. citrifolia (MIC: 2 mg/mL) EOs showed activity against Cutibacterium acnes, all EOs except S. samarangense EO demonstrated activity against Mycobacterium smegmatis (MIC: 0.125-0.50 mg/mL). The EOs were either fungistatic or fungicidal against one or both tested Candida species with minimum inhibitory/fungicidal concentrations of 0.016-32 mg/mL. The EOs also inhibited one or both key enzymes involved in skin aging, elastase and collagenase (IC50: 89.22-459.2 µg/mL; 0.17-0.18 mg/mL, respectively). Turmerone, previously identified in the C. longa EO, showed the highest binding affinity with the enzymes (binding energy: -5.11 and -6.64 kcal/mol). Only C. aurantium leaf, C. longa, P. amboinicus, P. senacia, S. coriaceum, and S. samarangense EOs were cytotoxic to the human malignant melanoma cells, UCT-MEL1 (IC50: 88.91-277.25 µg/mL). All the EOs, except M. citrifolia EO, were also cytotoxic to the human keratinocytes non-tumorigenic cells, HaCat (IC50: 33.73-250.90 µg/mL). Altogether, some interesting therapeutic properties of the EOs of pharmacological/cosmeceutical interests were observed, which warrants further investigations.

Cytotoxic and Antiangiogenetic Xanthones Inhibiting Tumor Proliferation and Metastasis from Garcinia xipshuanbannaensis.

Eight prenylated xanthones including four new analogues were extracted and purified from the leaves of Garcinia xipshuanbannaensis. Multiple techniques including UV, 1D and 2D NMR, and HRESIMS were used to determine the structures of the isolated xanthones. These xanthones were evaluated for their cytotoxicity toward human cancer cells, and compound 4 exhibited activity against HeLa cells. A cytotoxic mechanism examination revealed the active compound induced cell apoptosis by arresting the cell cycle, increasing the levels of ROS, and inhibiting the expression of p-STAT3 in HeLa cells. In in vivo zebrafish experiments, compound 4 was found to block tumor proliferation and migration and have antiangiogenetic activity, and thus seems worthy of further laboratory evaluation.

Pathogenesis of Keratinocyte Carcinomas and the Therapeutic Potential of Medicinal Plants and Phytochemicals.

Keratinocyte carcinoma (KC) is a form of skin cancer that develops in keratinocytes, which are the predominant cells present in the epidermis layer of the skin. Keratinocyte carcinoma comprises two sub-types, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This review provides a holistic literature assessment of the origin, diagnosis methods, contributing factors, and current topical treatments of KC. Additionally, it explores the increase in KC cases that occurred globally over the past ten years. One of the principal concepts highlighted in this article is the adverse effects linked to conventional treatment methods of KC and how novel treatment strategies that combine phytochemistry and transdermal drug delivery systems offer an alternative approach for treatment. However, more in vitro and in vivo studies are required to fully assess the efficacy, mechanism of action, and safety profile of these phytochemical based transdermal chemotherapeutics.

Anti-Inflammatory ent-Kaurane Diterpenoids from Isodon serra.

Ten new ent-kaurane diterpenoids, including two pairs of epimers 1/2 and 4/5 and a 6,7-seco-ent-kauranoid 10, were obtained from the aerial parts of Isodon serra. The structures of the new compounds were confirmed by extensive spectroscopic methods and electronic circular dichroism (ECD) data analysis. An anti-inflammatory assay was applied to evaluate their nitric oxide (NO) inhibitory activities by using LPS-stimulated BV-2 cells. Compounds 1 and 9 exhibited notable NO production inhibition with IC50 values of 15.6 and 7.3 µM, respectively. Moreover, the interactions of some bioactive diterpenoids with inducible nitric oxide synthase (iNOS) were explored by employing molecular docking studies.

Anti-inflammatory neo-Clerodane Diterpenoids from Ajuga pantantha.

Eight new neo-clerodane diterpenoids (1-8) were acquired from the aerial parts of Ajuga pantantha. Spectroscopic data analysis permitted the definition of their structures, and experimental and calculated electronic circular dichroism data were used to define their absolute configurations. Compounds 2 and 4-8 were found to have NO inhibitory effects with IC50 values of 20.2, 45.5, 34.0, 27.0, 45.0, and 25.8 µM, respectively. The more potent compounds 2, 6, and 8 were analyzed to establish their anti-inflammatory mechanism, including regulation of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins as well as their binding interactions with the two proteins.

Caseahomopene A, a ring-expanded homotriterpenoid from Casearia kurzii showing anti-inflammatory activities in vitro and in vivo.

Caseahomopene A (1), a rare natural product with a ring-expanded homotriterpenoid skeleton, was isolated from the leaves of Casearia kurzii. The structure including the absolute configuration was determined by spectroscopic data and X-ray crystallography analysis. Compound 1 showed anti-inflammatory effects in vitro and in vivo using LPS-stimulated cell and zebrafish model. As a potential anti-inflammatory agent, the anti-inflammatory mechanism of 1 was also investigated.

Diterpenoids from the leaves of Casearia kurzii showing cytotoxic activities.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for cancer led to the obtainment of six new and two known clerodane diterpenoids from the leaves of Casearia kurzii. Their structures were elucidated using NMR techniques and electronic circular dichroism (ECD) calculations. The subsequent biological cytotoxicity evaluation of these isolates toward human lung cancer A549, human cervical cancer HeLa, human chronic myeloid leukemia K562, and human hepatocellular carcinoma HepG2 was carried out. The most active compound 4 with an IC50 value of 9.7 µM against HepG2 cells was selected to examine the cytotoxic mechanism, which induced the apoptosis and arrested the HepG2 cell cycle at S stage. The in vivo zebrafish experiments revealed that compound 4 had the property of inhibiting tumor proliferation and migration.

Profiling Anticancer and Antioxidant Activities of Phenolic Compounds Present in Black Walnuts (Juglans nigra) Using a High-Throughput Screening Approach.

Our recent studies have demonstrated multiple health-promoting benefits from black walnut kernels. These biological functions of black walnuts are likely associated with their bioactive constituents. Characterization of phenolic compounds found in black walnut could point out underexplored bioactive activities of black walnut extracts and promote the development of novel applications of black walnut and its by-products. In the present study, we assessed bioactivity profiles of phenolic compounds identified in the kernels of black walnuts using a high-throughput screening (HTS) approach. Black walnut phenolic compounds were evaluated in terms of their total antioxidant capacity, antioxidant response element (ARE) induction, and anticancer activities. The anticancer activities were identified by evaluating the effects of the phenolic compounds on the growth of the tumorigenic alveolar epithelial cells (A549) and non-tumorigenic lung fibroblast cells (MRC-5). Out of 16 phenolic compounds tested, several compounds (penta-O-galloyl-ß-d-glucose, epicatechin gallate, quercetin, (-)-epicatechin, rutin, quercetin 3-ß-d-glucoside, gallic acid, (+)-catechin, ferulic acid, syringic acid) exerted antioxidant activities that were significantly higher compared to Trolox, which was used as a control. Two phenolic compounds, penta-O-galloyl-ß-d-glucose and quercetin 3-ß-d-glucoside, exhibited antiproliferative activities against both the tumorigenic alveolar epithelial cells (A549) and non-tumorigenic lung fibroblast cells (MRC-5). The antioxidant activity of black walnut is likely driven not only by penta-O-galloyl-ß-d-glucose but also by a combination of multiple phenolic compounds. Our findings suggested that black walnut extracts possibly possess anticancer activities and supported that penta-O-galloyl-ß-d-glucose could be a potential bioactive agent for the cosmetic and pharmaceutical industries.

In Vitro Human Metabolism and Inhibition Potency of Verbascoside for CYP Enzymes.

Verbascoside is found in many medicinal plant families such as Verbenaceae. Important biological activities have been ascribed to verbascoside. Investigated in this study is the potential of verbascoside as an adjuvant during tuberculosis treatment. The present study reports on the in vitro metabolism in human hepatic microsomes and cytosol incubations as well as the presence and quantity of verbascoside within Lippia scaberrima. Additionally, studied are the inhibitory properties on human hepatic CYP enzymes together with antioxidant and cytotoxic properties. The results yielded no metabolites in the hydrolysis or cytochrome P450 (CYP) oxidation incubations. However, five different methylated conjugates of verbascoside could be found in S-adenosylmethionine incubation, three different sulphate conjugates with 3'-phosphoadenosine 5'-phosphosulfate (PAPS) incubation with human liver samples, and very low levels of glucuronide metabolites after incubation with recombinant human uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A7, UGT1A8, and UGT1A10. Additionally, verbascoside showed weak inhibitory potency against CYP1A2 and CYP1B1 with IC50 values of 83 µM and 86 µM, respectively. Potent antioxidant and low cytotoxic potential were observed. Based on these data, verbascoside does not possess any clinically relevant CYP-mediated interaction potential, but it has effective biological activity. Therefore, verbascoside could be considered as a lead compound for further drug development and as an adjuvant during tuberculosis treatment.

Isolation of Flavonoids and Flavonoid Glycosides from Myrsine africana and Their Inhibitory Activities against Mushroom Tyrosinase.

Bioassay-guided fractionation of the methanol extract of the shoots of Myrsine africana led to the isolation of the new compound myricetin 3-O-(2″,4″-di-O-acetyl)-α-l-rhamnopyranoside (9) and 11 known compounds. The known compounds quercetin 3-O-(3″,4″-di-O-acetyl)-α-l-rhamnopyranoside (8), rutin (10), quercetin 3-O-α-l-rhamnopyranoside (11), and myricetin 3-O-α-l-rhamnopyranoside (12) are reported for the first time from the methanol extract of the shoots of M. africana. Compounds 10 and 12 showed significant inhibition of tyrosinase with 50% inhibition (IC50 values) of the enzyme at 0.13 ± 0.003 and 0.12 ± 0.002 mM, respectively, which was supported by the docking fitness scores obtained through molecular docking analysis. In addition, compounds 1-12 displayed significant antioxidant activity with IC50 values ranging 1.90 to 3.90 µM.

Insights into tyrosinase inhibition by compounds isolated from Greyia radlkoferi Szyszyl using biological activity, molecular docking and gene expression analysis.

Greyia radlkoferi ethanol extract and its five compounds were tested for their inhibitory activity against the mushroom tyrosinase enzyme and melanin production on melanocytes. The crude extract showed significant tyrosinase inhibition with IC50 of 17.96µg/ml. This is the first report of the isolation of these 5 compounds from Greyia radlkoferi. 2',4',6'-Trihydroxydihydrochalcone showed the highest tyrosinase inhibition at 17.70µg/ml (68.48µM), with low toxicity when compared with crude extract. This compound is therefore, a key component in the crude extract, which is responsible for tyrosinase inhibitory activity. The RT-qPCR indicated that the mechanism of action is most likely post transcriptional. Further, the molecular docking study showed that tyrosinase inhibitory activity depends on interaction of the compound with Cu2+ ions at the active site. This is the first report of the tyrosinase inhibitory activity of the G. radlkoferi extract and molecular insights on interaction of its compounds with Cu2+ ions as the driving factor for tyrosinase inhibition. These results suggest that the extract of G. radlkoferi and the compound 2',4',6'-trihydroxydihydrochalcone have great potential to be further developed as pharmaceutical or cosmetic agents for use against dermatological disorders associated with melanin.

Extract from Ceratonia siliqua Exhibits Depigmentation Properties.

Skin hyper-pigmentation is a condition initiated by the overproduction of melanin existing in the melanocytes. Melanin pigment is responsible for the colour of skin in humans. It is formed through a series of oxidative reactions involving the amino acid tyrosine in the presence of the key enzyme tyrosinase. In continuation with our efforts to identify tyrosinase inhibitors from plants sources, the methanol extract from leaf, bark and fruit of Ceratonia siliqua were screened for tyrosinase inhibition and diphenolase activity. The bark extract exhibited significant inhibition on mushroom tyrosinase using L-tyrosine as a substrate and showed diphenolase activity. The extract further significantly lowered tyrosinase mRNA levels in B16-F10 mouse melanocytes. Bioassay-guided fractionation led to the isolation of six compounds. Compounds (-)-epicatechin-3-O-gallate, 1,2,3,6-tetra-O-galloyl-ß-D-glucose and gallocatechin-3-O-gallate showed tyrosinase inhibitions with the IC50 values of 27.52, 83.30 and 28.30 µg/mL, respectively. These compounds also exhibited L-DOPA activities with IC50 values of >200, 150 and 200 µg/mL, respectively. A clinical study was conducted using 20 volunteers in a patch testing trial for irritancy potential and skin depigmentation. The clinical results showed the sample to be non-irritant with irritancy potential of -34.21 and depigmentation trial showed an improvement in the even skin tone of UV induced pigmentation at 3% after 28 days of application.

The naphthoquinone diospyrin is an inhibitor of DNA gyrase with a novel mechanism of action.

Tuberculosis and other bacterial diseases represent a significant threat to human health. The DNA topoisomerases are excellent targets for chemotherapy, and DNA gyrase in particular is a well-validated target for antibacterial agents. Naphthoquinones (e.g. diospyrin and 7-methyljuglone) have been shown to have therapeutic potential, particularly against Mycobacterium tuberculosis. We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M. tuberculosis gyrase and other gyrases. Our evidence strongly suggests that the compounds bind to the N-terminal domain of GyrB, which contains the ATPase active site, but are not competitive inhibitors of the ATPase reaction. We propose that naphthoquinones bind to GyrB at a novel site close to the ATPase site. This novel mode of action could be exploited to develop new antibacterial agents.

Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer cell lines.

In an effort to establish new candidates with enhanced anticancer activity of 5-hydroxy-7-methyl-1,4-naphthoquinone scaffold (7-methyljuglone) previously isolated from the root extract of Euclea natalensis, a series of 7-methyljuglone derivatives have been synthesized and assessed for cytotoxicity on selected human cancer lines. These compounds were screened in vitro for anticancer activity on MCF-7, HeLa, SNO and DU145 human cancer cell lines by MTT assay. Most of them exhibited significant toxicity on cancer cell lines with lower IC50 values. The most potent derivative (19) exhibited the toxicity on HeLa and DU145 cell lines with IC50 value of 5.3 and 6.8µM followed by compound (5) with IC50 value of 10.1 and 9.3µM, respectively. Structure-activity relationship reveals that the fluoro substituents at position C-8 while hydroxyl substituents at C-2 and C-5 positions played an important role in toxicity.

Predicting the influence of multiple components on microbial inhibition using a logistic response model--a novel approach.

BACKGROUND: There are several synergistic methods available. However, there is a vast discrepancy in the interpretation of the synergistic results. Also, these synergistic methods do not assess the influence the tested components (drugs, plant and natural extracts), have upon one another, when more than two components are combined. METHODS: A modified checkerboard method was used to evaluate the synergistic potential of Heteropyxis natalensis, Melaleuca alternifolia, Mentha piperita and the green tea extract known as TEAVIGO™. The synergistic combination was tested against the oral pathogens, Streptococcus mutans, Prevotella intermedia and Candida albicans. Inhibition data obtained from the checkerboard method, in the form of binary code, was used to compute a logistic response model with statistically significant results (p < 0.05). This information was used to construct a novel predictive inhibition model. RESULTS: Based on the predictive inhibition model for each microorganism, the oral pathogens tested were successfully inhibited (at 100% probability) with their respective synergistic combinations. The predictive inhibition model also provided information on the influence that different components have upon one another, and on the overall probability of inhibition. CONCLUSIONS: Using the logistic response model negates the need to 'calculate' synergism as the results are statistically significant. In successfully determining the influence multiple components have upon one another and their effect on microbial inhibition, a novel predictive model was established. This ability to screen multiple components may have far reaching effects in ethnopharmacology, agriculture and pharmaceuticals.

Cytotoxic and HIV-1 enzyme inhibitory activities of Red Sea marine organisms.

BACKGROUND: Cancer and HIV/AIDS are two of the greatest public health and humanitarian challenges facing the world today. Infection with HIV not only weakens the immune system leading to AIDS and increasing the risk of opportunistic infections, but also increases the risk of several types of cancer. The enormous biodiversity of marine habitats is mirrored by the molecular diversity of secondary metabolites found in marine animals, plants and microbes which is why this work was designed to assess the anti-HIV and cytotoxic activities of some marine organisms of the Red Sea. METHODS: The lipophilic fractions of methanolic extracts of thirteen marine organisms collected from the Red Sea (Egypt) were screened for cytotoxicity against two human cancer cell lines; leukaemia (U937) and cervical cancer (HeLa) cells. African green monkey kidney cells (Vero) were used as normal non-malignant control cells. The extracts were also tested for their inhibitory activity against HIV-1 enzymes, reverse transcriptase (RT) and protease (PR). RESULTS: Cytotoxicity results showed strong activity of the Cnidarian Litophyton arboreum against U-937 (IC50; 6.5 µg/ml ±2.3) with a selectivity index (SI) of 6.45, while the Cnidarian Sarcophyton trochliophorum showed strong activity against HeLa cells (IC50; 5.2 µg/ml ±1.2) with an SI of 2.09. Other species showed moderate to weak cytotoxicity against both cell lines. Two extracts showed potent inhibitory activity against HIV-1 protease; these were the Cnidarian jelly fish Cassiopia andromeda (IC50; 0.84 µg/ml ±0.05) and the red algae Galaxura filamentosa (2.6 µg/ml ±1.29). It is interesting to note that the most active extracts against HIV-1 PR, C. andromeda and G. filamentosa showed no cytotoxicity in the three cell lines at the highest concentration tested (100 µg/ml). CONCLUSION: The strong cytotoxicity of the soft corals L. arboreum and S. trochliophorum as well as the anti-PR activity of the jelly fish C. andromeda and the red algae G. filamentosa suggests the medicinal potential of crude extracts of these marine organisms.

Evaluating the effects of various ethanolic medicinal plant extracts on metastatic breast cancer proliferation, invasion, and expression of a novel potential drug target; CD82 metastatic suppressor protein, and on in vivo angiogenesis using the ex ovo yolk sac membrane (YSM) assay.

PURPOSE: Breast cancer metastasis relies on cellular invasion and angiogenesis facilitated by the downregulation of metastatic suppressor proteins like Cluster of Differentiation 82 (CD82). Currently, no medicines target multiple systems to prevent metastatic progression through CD82 upregulation. This study screened for plant extracts displaying effects on cell proliferation, invasion, and CD82 expression in breast cancer cells, and in vivo angiogenesis, and further correlated between the biological activities and effect on CD82 expression. METHODS: Seventeen ethanolic plant extracts were screened for their effect on cell proliferation (against MDA-MB-231 and MCF-7 breast cancer and Hek293 kidney cells), cell invasion and effect on CD82 expression in metastatic MDA-MB-231 cells. Selected extracts were further evaluated for in vivo anti-angiogenesis. RESULTS: Extracts displayed varying antiproliferative activity against the different cell lines, and those that showed selectivity indexes (SI) > 0.5 against MDA-MB-231 were selected for anti-invasion evaluation. Buddleja saligna Willd. (BS), Combretum apiculatum Sond. (CA), Foeniculum vulgare, Greyia radlkoferi, Gunnera perpensa and Persicaria senegalensis (Meisn.) Soják (PS) displayed 50% inhibitory concentration (IC50) values of 44.46 ± 3.46, 74.00 ± 4.48, 180.43 ± 4.51, 96.97 ± 2.29, 55.29 ± 9.88 and 243.60 ± 2.69 µg/mL, respectively against MDA-MB-231, and compared to Hek293 showed SI of 0.9, 0.7, 1.4, 1.1, 2.2 and 0.5. Significant invasion inhibition was observed at both 20 and 40 µg/mL for BS (94.10 ± 0.74 and 96.73 ± 0.95%) and CA (87.42 ± 6.54 and 98.24 ± 0.63%), whereas GR (14.91 ± 1.62 and 41 ± 1.78%) and PS (36.58 ± 0.54 and 51.51 ± 0.83%), only showed significant inhibition at 40 µg/mL, and FV (< 5% inhibition) and GP (10 ± 1.03 and 22 ± 1.31%) did not show significant inhibition at both concentrations. Due to the significant anti-invasive activity of BS, CA and PS at 40 µg/mL, these extracts were further evaluated for their potential to stimulate CD82. BS showed significant (p < 0.05) reduction in CD82 at 20 and 40 µg/mL (13.2 ± 2.2% and 20.3 ± 1.5% decrease, respectively), whereas both CA and PS at 20 µg/mL increased (p < 0.05) CD82 expression (16.4 ± 0.8% and 5.4 ± 0.6% increase, respectively), and at 40 µg/mL significantly reduced CD82 expression (23.4 ± 3.1% and 11.2 ± 2.9% decrease, respectively). Using the yolk sac membrane assay, BS (59.52 ± 4.12 and 56.72 ± 3.13% newly formed vessels) and CA (83.33 ± 3.17 and 74.00 ± 2.12%) at both 20 and 40 µg/egg showed significant (p < 0.001) angiogenesis inhibition, with BS showing statistical similar activity to the positive control, combretastatin A4 (10 nmol/egg), whereas PS only displayed significant (p < 0.001) angiogenesis stimulation at 40 µg/egg (120.81 ± 3.34% newly formed vessels). CONCLUSION: BS exhibits antiproliferative, anti-invasive, and anti-angiogenic activity despite inhibiting CD82, suggesting an alternative mode of action. CA at 20 µg/mL shows moderate anti-invasive and anti-angiogenic potential by stimulating CD82, while at 40 µg/mL it still displays these properties but inhibits CD82, suggesting an additional mode of action. PS, with the least antiproliferative activity, stimulates CD82 and inhibits angiogenesis at 20 µg/mL but inhibits CD82 and increases angiogenesis at 40 µg/mL, indicating CD82 targeting as a major mode of action. Future studies should explore breast cancer xenograft models to assess the extracts' impact on CD82 expression and angiogenesis in the tumor microenvironment, along with isolating bioactive compounds from the extracts.

A Review of the Potential of Poly-(lactide-co-glycolide) Nanoparticles as a Delivery System for an Active Antimycobacterial Compound, 7-Methyljuglone.

7-Methyljuglone (7-MJ) is a pure compound isolated from the roots of Euclea natalensis A. DC., a shrub indigenous to South Africa. It exhibits significant promise as a potential treatment for the highly communicable disease tuberculosis (TB), owing to its effective antimycobacterial activity against Mycobacterium tuberculosis. Despite its potential therapeutic benefits, 7-MJ has demonstrated in vitro cytotoxicity against various cancerous and non-cancerous cell lines, raising concerns about its safety for consumption by TB patients. Therefore, this review focuses on exploring the potential of poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as a delivery system, which has been shown to decrease in vitro cytotoxicity, and 7-MJ as an effective antimycobacterial compound.