Records of Natural Products

Carbazole alkaloids from Murraya koenigii exhibit diverse structural features and promising anticancer potential. This study evaluated the cytotoxic activity and structure–activity relationship (SAR) of 24 carbazole alkaloids against HL-60 and HeLa cancer celllines, alongside molecular docking studies against the anti-apoptotic protein Bcl-2 (PDB ID: 2W3L).The SAR analysis revealed that electron-donating and redox-active substituents, particularly formyl groups, significantly enhanced cytotoxicity, while dimerization generally reduced potency. Docking results showed binding energies ranging from −5.49 to −9.37 kcal/mol, with key interactions mainly involving Phe63, Asp70, Phe71, Met74, Val92,Glu95, Leu96, Asp99, Gly104, Phe109, Glu111 and Phe112 residues. Potent compounds such as mahanine (15) and murrayamine-J (18) exhibited both strong cytotoxicity (IC50 = 12.1 and 5.1 μg/mL for HL-60 and 12.8 and 7.7 μg/mL for HeLa, respectively) and favorable binding affinities (−7.66 and −7.25 kcal/mol), suggesting that Bcl-2 inhibition contributes to their activity. Conversely, murrayafolline-A (2) displayed notable cytotoxicity (IC50 = 8.5 μg/mL forHL-60 and 4.6 μg/mL forHeLa) despite only moderate predicted affinity (−5.71 kcal/mol), indicating possible alternative mechanisms of action. Similarly, bisisomahanine (24) showed the strongest predicted binding (−9.37 kcal/mol) with lowest ligand efficiency but negligible cytotoxicity, suggesting that the high binding affinity is attributed to its bulky size. Overall, this study provides supportive computational insights into the cytotoxic potential of carbazole alkaloids and highlights their predictive relevance for future mechanistic and pharmacokinetic studies.

Antileishmanial activity guided studies on the methanolic extract of the tubers of Cyclamen rohlfsianum Asch. resulted in the isolation and characterization of six saponins. All saponins were established as tri-, tetra-, and pentaglycosidic derivatives of 13β-28- epoxy-oleanane-type triterpenic sapogenols. Two of them were found to be newly described saponins, rohlfsianosides A and B. Their structures were identified as 3-O-β-{[β-Dxylopyranosyl-( 1→2)-β-D-lucopyranosyl-(1→4)]-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranosyl}- 13β,28-epoxy-16α-hydroxy-30-acetoxy-oleanane (rohlfsianoside A), and 3-O- β-{{[β-D-xylopyranosyl-(1→2)]-[β-D-glucopyranosyl-(1→4)]-[β-D-glucopyranosyl-(1→4) ]}-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranosyl}-protoprimulagenin A (rohlfsianoside B), respectively. Additionally, three known compounds, cyclamiretin A (3β,16α- dihydroxy-13β-28-epoxy-oleanan-30-al) glycosides; cyclaminorin, deglucocyclamin and cyclamen, and protoprimulagenin A (13β-28-epoxy-3β,16α-dihydroxy-oleanane) derivative, lysikoianoside I, were identified. The structure elucidation of the saponins was established by means of spectroscopic methods (1D and 2D NMR, HR-MS). All the saponins showed notable growth inhibitory activity against Leishmania  ropica, with IC50 values ranging from 17.5 to 21.9/mL.

A new isoflavone apiosisoflavone A (1) and five known isoflavones (2–6) were isolated fromthe ethanol extracts of Apios fortuneiMaxim. The structures were elucidated by spectroscopic data analysis of NMR, HR-ESI-MS, and experimental and calculated ECD. All compounds were evaluated on the anti-inflammatory activity against RAW264.7 cell lines. The levels of NO and TNF-α released by RAW264.7 cells were detected by the kit. All the compounds displayed moderate anti-inflammatory activity.

Kaempferol, a naturally occurring flavonoid found in hair growth-promoting plants, was investigated for its direct effects on hair loss prevention. This study assessed its impact on human dermal papilla (HDP) cells, essential regulators of hair follicle activity. Kaempferol significantly enhanced HDP cell proliferation in a dose-dependent manner, exceeding the effect of minoxidil. It markedly inhibited TGF-β1-induced Smad-binding activity (65.8%) and IL-4-induced STAT6 activity (72.5%), compared to finasteride (35%) and tofacitinib (96%), respectively. Western blot analysis showed suppression of phosphorylated Smad2/3 and STAT6, along with upregulation of CDK2, CDK4, cyclin D3, ERK1/2, IGF-1R, and VEGFR-2. In vivo, topical application of Kaempferol in C57BL/6 mice significantly promoted hair growth, increased follicle numbers, and improved hair thickness. These findings suggest that Kaempferol enhances hair growth through modulation of TGF-β/Smad and JAK3/STAT6 pathways and may serve as a promising natural therapeutic agent for hair loss treatment.