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Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential herb-drug interactions. The effects of Bacopa monnieri standardized extract and the bacosides from the extract on five major CYP isoforms in vitro were analyzed using a luminescent CYP recombinant human enzyme assay. B. monnieri extract exhibited noncompetitive inhibition of CYP2C19 (IC50/Ki = 23.67/9.5 μg/mL), CYP2C9 (36.49/12.5 μg/mL), CYP1A2 (52.20/25.1 μg/mL); competitive inhibition of CYP3A4 (83.95/14.5 μg/mL) and weak inhibition of CYP2D6 (IC50 = 2061.50 μg/mL). However, the bacosides showed negligible inhibition of the same isoforms. B. monnieri, which is orally administered, has a higher concentration in the gut than the liver; therefore, this herb could exhibit stronger inhibition of intestinal CYPs than hepatic CYPs. At an estimated gut concentration of 600 μg/mL (based on a daily dosage of 300 mg/day), B. monnieri reduced the catalytic activities of CYP3A4, CYP2C9 and CYP2C19 to less than 10% compared to the total activity (without inhibitor = 100%). These findings suggest that B. monnieri extract could contribute to herb-drug interactions when orally co-administered with drugs metabolized by CYP1A2, CYP3A4, CYP2C9 and CYP2C19. [ABSTRACT FROM AUTHOR]

• Development of AuNRsALG nanosonosensitisers for enhanced SDT of breast cancer. • AuNRsALG showed good biocompatibility and sono-stability. • AuNRsALG produced •OH &1O 2 more effectively than the commercial sonosensitisers. • AuNRsALG exhibited high sonotoxicity in breast cancer cells at nanomolar range. • AuNRsALG induced severe DNA damage and cell apoptosis via mitochondrial pathway. Sonodynamic therapy (SDT) emerges as a promising non-invasive alternative for eradicating malignant tumours. However, its therapeutic efficacy remains limited due to the lack of sonosensitisers with high potency and biosafety. Previously, gold nanorods (AuNRs) have been extensively studied for their applications in photodynamic or photothermal cancer therapy, but their sonosensitising properties are largely unexplored. Here, we reported the applicability of alginate-coated AuNRs (AuNRsALG) with improved biocompatibility profiles as promising nanosonosensitisers for SDT for the first time. AuNRsALG were found stable under ultrasound irradiation (1.0 W/cm2, 5 min) and maintained structural integrity for 3 cycles of irradiation. The exposure of the AuNRsALG to ultrasound irradiation (1.0 W/cm2, 5 min) was shown to enhance the cavitation effect significantly and generate a 3 to 8-fold higher amount of singlet oxygen (1O 2) than other reported commercial titanium dioxide nanosonosensitisers. AuNRsALG exerted dose-dependent sonotoxicity on human MDA-MB-231 breast cancer cells in vitro , with ∼ 81% cancer cell killing efficacy at a sub-nanomolar level (IC 50 was 0.68 nM) predominantly through apoptosis. The protein expression analysis showed significant DNA damage and downregulation of anti-apoptotic Bcl-2, suggesting AuNRsALG induced cell death through the mitochondrial pathway. The addition of mannitol, a reactive oxygen species (ROS) scavenger, inhibited cancer-killing effect of AuNRsALG-mediated SDT, further verifying that the sonotoxicity of AuNRsALG is driven by the production of ROS. Overall, these results highlight the potential application of AuNRsALG as an effective nanosonosensitising agent in clinical settings. [ABSTRACT FROM AUTHOR]

The utilization of toxic chemicals as reducing and stabilizing agents in the preparation of gold nanoparticles (AuNPs) has increased in vivo toxicity and thus limited its application in clinical settings. Herein, we propose an alternative method of preparing highly stable AuNPs, where non-toxic Curcuma mangga (CM) extract was used as a single reducing and stabilizing agent to overcome the aforementioned constraints. The morphological images enunciated that the homogeneously dispersed AuNPs exhibited spherical morphology with an average particle diameter of 15.6 nm. Fourier Transform infrared (FTIR) and cyclic voltammetry analysis demonstrated that carbonyl groups of terpenoids in CM extract played an important role in the formation and stabilization of AuNPs. Green-synthesized AuNPs were found to have good stability in physiological media after 24 h of dispersion. The AuNPs were also cytocompatible with human colon fibroblast cell (CCD-18Co) and human lung fibroblast cell (MRC-5). Hemocompatibility tests revealed that the AuNPs were blood-compatible, with less than 10% of hemolysis without any aggregation of erythrocytes. The current study suggests potential in employing a CM-extract-based method in the preparation of AuNPs for anticancer diagnosis and therapy., Competing Interests: The authors declare no conflict of interest.