Carvotacetones (1–7) isolated from Sphaeranthus africanus were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains Mycobacterium smegmatis mc² 155, Mycobacterium aurum ATCC 23366, and Mycobacterium bovis BCG ATCC 35734. The minimum inhibitory concentrations (MICs) of the carvotacetones were detected through high-throughput spot culture growth inhibition (HT-SPOTi) and microbroth dilution assays. In order to assess the potential of the compounds 1 and 6 to accumulate ethidium bromide (EtBr) in M. smegmatis and M. aurum, a microtiter plate-based fluorometric assay was used to determine efflux activity. Compounds 1 and 6 were analyzed for their modulating effects on the MIC of EtBr and the antibiotic rifampicin (RIF) against M. smegmatis. Carvotacetones 1 and 6 had potent antibacterial effects on M. aurum and M. bovis BCG (MIC ≤ 31.25 mg/L) and could successfully enhance EtBr activity against M. smegmatis. Compound 1 appeared as the most efficient agent for impairing the efflux mechanism in M. smegmatis. Both compounds 1 and 6 were highly effective against M. aurum and M. bovis BCG. In particular, compound 1 was identified as a valuable candidate for inhibiting mycobacterial efflux mechanisms and as a promising adjuvant in the therapy of tuberculosis or other non-tubercular mycobacterial infections.

Four previously undescribed carvotacetones including one monomeric (1) and three dimeric (8, 9, 10) derivatives, together with six known compounds were isolated from the n-hexane extract of the aerial parts of Sphaeranthus africanus L. The structures of the previously undescribed compounds were elucidated as 3-angeloyloxy-5-isobutanoyloxy-7-hydroxycarvotacetone (1), 7,7'-oxybis{3-angeloyloxy-5-[(2R*,3R*)-2,3-dihydroxy-2-methylbutanoyloxy]carvotacetone} (8), (2″S*,3″R*)-7-{3-angeloyloxy-5-[(2R*,3R*)-2,3-dihydroxy-2-methylbuta-noyloxy]carvotaceton-7-yloxy}-3-angeloyloxy-5-(2,3-dihydroxy-2-methylbutanoyloxy)carvo-tacetone (9), and 7,7'-oxybis{3-angeloyloxy-5-[(2S*,3R*)-2,3-dihydroxy-2-methylbutanoyl-oxy]carvotacetone} (10). The three dimeric derivatives (8-10) showed potent anti-proliferative activity against human cancer cell lines (CCRF-CEM, MDA-MB-231, U-251, HCT-116) with IC₅₀ values ranging from 0.2 to 2.0 μM. Caspases 3 and 7 were found to be activated by all compounds, indicating apoptosis induction activity. Monomers exhibited a specific inhibition of NO production in BV2 and RAW 264.7 cells with IC₅₀ values ranging from 4.2 to 6.8 μM which were 2-3.5-fold lower than IC₅₀ values causing cytotoxicity. In addition, the carvotacetones reduced NF-κB1 (p105) mRNA expression at concentrations of 10 and 2.5 μM. Altogether, the results indicate that carvotacetones may be interesting lead structures for the development of anti-cancer and anti-inflammatory drugs.

Background: Although Morus alba (white mulberry) has long been used in traditional skin care, the scientific evidence for its leaf extract in anti-hyperpigmentation applications remains limited, particularly regarding its incorporation into topical formulations. This study investigated the melanin-synthesis-inhibitory, tyrosinase-inhibitory, and antioxidant activities of M. alba leaf extract and evaluated its potential in a stable topical gel formulation. Methodology: Melanin suppression was assessed in IBMX-stimulated B16F10 melanocytes using microscopic observation, pellet analysis, and quantitative melanin measurement. Tyrosinase inhibition was examined with a mushroom tyrosinase assay, while antioxidant capacity was evaluated via DPPH radical scavenging. A topical gel containing M. alba extract was developed and assessed for physicochemical properties, phenolic retention, bioactivity, and stability. Result and Discussion: The extract showed strong tyrosinase inhibition (IC₅₀ = 5.70 ± 0.28 µg/mL) and antioxidant activity (IC₅₀ = 16.22 ± 0.6 µg/mL), and significantly reduced melanin synthesis in B16F10 cells without cytotoxicity (≤ 200 µg/mL). The formulated gel maintained phenolic content, exhibited moderate tyrosinase inhibition, and demonstrated stable appearance, pH, spreadability, and bioactivity during storage. Conclusion: Morus alba leaf extract possesses potent anti-melanogenic and antioxidant properties and can be successfully incorporated into a stable topical gel, supporting its potential as a natural ingredient for anti-hyperpigmentation products. However, these findings are based on in vitro assays and preliminary formulation studies; further in vivo and clinical evaluations are needed to confirm its efficacy and safety in humans.

1. The Lamiaceae is one of the most widely used plant families in traditional medicine, comprising about 236 genera and approximately 6,900–7,200 species worldwide (Stankovic 2020). Species in this...