Flavonoids, present in fruits, vegetables and traditional medicinal plants, show anticancer effects in experimental systems and are reportedly non-toxic. This is a favorable property for long term strategies for the attenuation of lymph node metastasis, which may effectively improve the prognostic states in breast cancer. Hence, we studied two flavonoids, apigenin and luteolin exhibiting strong bio-activity in various test systems in cancer research and are readily available on the market. This study has further advanced the mechanistic understanding of breast cancer intravasation through the lymphatic barrier. Apigenin and luteolin were tested in a three-dimensional (3-D) assay consisting of MDA-MB231 breast cancer spheroids and immortalized lymph endothelial cell (LEC) monolayers. The 3-D model faithfully resembles the intravasation of breast cancer emboli through the lymphatic vasculature. Western blot analysis, intracellular Ca²⁺ determination, EROD assay and siRNA transfection revealed insights into mechanisms of intravasation as well as the anti-intravasative outcome of flavonoid action. Both flavonoids suppressed pro-intravasative trigger factors in MDA-MB231 breast cancer cells, specifically MMP1 expression and CYP1A1 activity. A pro-intravasative contribution of FAK expression in LECs was established as FAK supported the retraction of the LEC monolayer upon contact with cancer cells thereby enabling them to cross the endothelial barrier. As mechanistic basis, MMP1 caused the phosphorylation (activation) of FAK at Tyr397 in LECs. Apigenin and luteolin prevented MMP1-induced FAK activation, but not constitutive FAK phosphorylation. Luteolin, unlike apigenin, inhibited MMP1-induced Ca²⁺ release. Free intracellular Ca²⁺ is a central signal amplifier triggering LEC retraction through activation of the mobility protein MLC2, thereby enhancing intravasation. FAK activity and Ca²⁺ levels did not correlate. This implicates that the pro-intravasative contribution of FAK and of Ca²⁺ release in LECs was independent of each other and explains the better anti-intravasative effects of luteolin in vitro. In specific formulations, flavonoid concentrations causing significant anti-intravasative effects, can certainly be achieved in vivo. As the therapeutic strategy has to be based on permanent flavonoid treatment both the beneficial and adverse effects have to be investigated in future studies.

Andrographolide (AG) is an active compound isolated from Andrographis paniculata (Family Acanthaceae). Although it possesses beneficial bioactivities to the skin, there is insufficient information of its applications for treatment of skin disorders due to low water solubility leading to complications in product development. To overcome the problem, an AG-loaded nanoemulsion (AG-NE) was formulated and prepared using a microfluidization technique. This study aimed to investigate the effect of pressure and the number of homogenization cycles (factors) on droplet size, polydispersity index and zeta potential of AG-NE (responses) and to determine the effect of AG-NE on skin cancer cells and UVB irradiation-induced skin disorders in rats. Relationships between factors versus responses obtained from the face-centered central composite design were described by quadratic models. The optimum value of parameters for the production of optimized AG-NE (Op-AG-NE) were 20,000 psi of pressure and 5 homogenization cycles. Op-AG-NE showed promising cytotoxicity effects on the human malignant melanoma- (A375 cells) and non-melanoma cells (A-431 cells) via apoptosis induction with a high selectivity index and also inhibited intracellular tyrosinase activity in the A375 cells. Op-AG-NE could reduce melanin index and healed UVB irradiation exposed skin. Op-AG-NE thus had potential for treatment of skin cancers and skin disorders from exposure to UVB radiation.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, having a poor prognosis and rapid metastases. TNBC is characterized by the absence of estrogen, progesterone, and human epidermal growth receptor-2 (HER2) expressions and has a five-year survival rate. Compared to other breast cancer subtypes, TNBC patients only respond to conventional chemotherapies, and even then, with limited success. Shortages of chemotherapeutic medication can lead to resistance, pressured index therapy, non-selectivity, and severe adverse effects. Finding targeted treatments for TNBC is difficult owing to the various features of cancer. Hence, identifying the most effective molecular targets in TNBC pathogenesis is essential for predicting response to targeted therapies and preventing TNBC cell metastases. Nowadays, natural compounds have gained attention as TNBC treatments, and have offered new strategies for solving drug resistance. Here, we report a systematic review using the database from Pubmed, Science Direct, MDPI, BioScince, Springer, and Nature for articles screening from 2003 to 2022. This review analyzes relevant signaling pathways and the prospect of utilizing natural compounds as a therapeutic agent to improve TNBC treatments in the future.

The utilization of the stems, leaves, and hulls of peanuts (Arachis hypogea) is not as popular as the seeds. This study aimed to investigate the chemical contents and pharmacological activities of A. hypogaea stems in-vitro and in-silico. This study was also completed with bibliometric analysis. The methanol extract (ME) was reextracted by ethylacetate to get ethyl acetate extract (EAE). The chemical contents of EAE were analyzed by phytochemical screening, Liquid Chromatography-Mass Spectroscopy (LC-MS/MS), TPC (Total Phenolic Content), and TFC (Total Flavonoid Content). In-vitro and in-silico studies evaluated antioxidant potency, toxicity, and cytotoxicity toward MCF-7 cell lines. The results showed that EAE contained terpenoids, flavonoids, alkaloids, and phenolics which were supported by LC-MS/MS data. The EAE was categorized as a very strong antioxidant and moderately active in both cytotoxicity and toxicity.

The objective of this study is to investigate the phytochemical constituents of Wualae fruit extract and its cell-protecting activity towards CCl₄-induced hepatotoxicity. Phytochemical screening performed in this study was alkaloid, flavonoid, saponin, tannin, and terpenoid. Extract was also characterized to specify the quality. The cell-protecting of extract was performed to Wistar male rats to measure their total bilirubin, direct bilirubin, indirect bilirubin, SGOT, SGPT, and ALP levels post-treated with Wualae fruit extract at dose 200, 300, and 400 mg/kgBw for 7 d, and induced with CCl₄ the next day. Histopathology of intestine and liver organ was also performed. Our study found that extract contains alkaloids, flavonoids, tannins, and terpenoids. We found extract decreases levels of total bilirubin, direct bilirubin, indirect bilirubin, SGOT, SGPT, and ALP at dose of 200, 300, and 400mg/kgBw (p<0.05), although histopathological results demonstrated that dose of 400mg/kgBw showed some necrosis at villi and steatosis at liver. In conclusion, Wualae fruit extract has protective effect toward CCl_4- induced hepatotoxicity at dose 200 and 300mg/kgBw and able to decreases bilirubin, SGOT, SGPT, and ALP levels. Flavonoid contains in extract is suspected plays role in its cell-protecting effect.

Meistera chinensis is one of the new generations of the Zingiberaceae family. Zingiberaceae have a large number of species and still need research to reveal their chemical content. Meistera chinensis, a local plant that is widespread in Konawe Regency, Southeast Sulawesi. Empirically, M. chinensis is used as a flavor enhancer in food, aches, and increases body immunity. There are no reports of chemical content or its biological activity. In this study, the fruit was tested for phytochemicals, antioxidants using the ABTS test, total phenolic, total flavonoid content, and toxicity test with BSLT. Meistera chinensis was extracted with ethanol and fractionated by ethyl acetate solvent use vacuum liquid chromatography. Phytochemical screening was carried out qualitatively by using the calorimetric method. The fraction toxicity was monitored by a lethal test for brine shrimp (BSLT). These fractions for the ABTS method obtained fractions 1-8 (F1-F8) and ascorbic acid were used as controls. The results showed radical scavenging activities fraction of M. chinensis fruit was a very strong activity with IC50 of 42.7±3.53 mg/L (F8). The total phenolic and flavonoid contents were 30.72±1.07 mgGAE/g and 8.02±0.48 mgQE/g, respectively. The phytochemical evaluation contains terpenoids, saponins, phenolics, steroids, alkaloids, and flavonoids. The BSLT toxicity test was found to be very toxic with IC50 of 5.20±0.72 mg/L. These findings indicate that the fruit of M. chinensis acts as an antioxidant and toxicity agent.