Li Qiu

Background: Flavonoid glycosides are known to possess diverse bioactivities including antitumor and anti‐inflammatory properties. Hesperetin is abundant in nature and can be used to synthesize bioactive flavonoids. This has the advantages of low cost, short synthetic steps, simple operation, and good yields. Objective: In this study, we aimed to synthesize bioactive flavonoids and flavonoid glycosides from hesperetin and evaluate the antitumor and anti‐inflammatory activities of these compounds. Methods: A series of flavonoids and their derivatives were synthesized by methoxylation, oxidative dehydrogenation, benzylation, debenzylation, and deacetylation as well as using a modified peroxyacetone method and a glycoside condensation reaction. Their anti‐inflammatory activities were evaluated for their inhibitory effects on nitric oxide (NO), tumor necrosis factor (TNF‐α), and interleukin‐6 (IL‐6) production in LPS‐induced RAW264.7 mouse macrophages. Their structures were characterized by HRMS, ¹H‐NMR, and ¹³C‐NMR, and their cytotoxicity on the human triple‐negative breast cancer cell (TNBC) line, SUM 149, was tested by using the MST assay. Results: Most of the compounds markedly reduced NO production in LPS‐stimulated murine macrophages at the tested concentrations in a dose‐dependent manner. Among these, compounds 1, 7, 9, and 17 showed significant anti‐inflammatory activities against NO production in LPS‐induced RAW264.7 mouse macrophages. In addition, they could also reduce the release of TNF‐α and IL‐6 in a concentration‐dependent manner. Most of the tested compounds showed remarkable anti‐human TNBC activities. Compounds 1b–1m, 1, and 3 showed a certain degree of growth inhibition effect on the human TNBC cell lines and their IC₅₀ values were all below 16.61 μM. In addition, compound 1l was the most cytotoxic with IC₅₀ values of 1.38±0.31 μM, while the other compounds were inactive with inhibition rates Conclusions: A novel series of flavonoids were synthesized from the natural flavonoid, hesperetin, including 17 new compounds. Screening tests indicated that most of these compounds reduced NO production in LPS‐stimulated murine macrophages at concentrations of 15 to 60 μM, and the inhibition generally increased in a dose‐dependent manner. Some compounds showed different degrees of cytotoxicity on the human TBNC cell lines, SUM 149.

Objectives: Total saponin extracts from the roots of Panax notoginseng have been proven to have anti-inflammatory properties. Dammarane-type saponins isolated from the roots of P notoginseng have been shown to be active inhibitors of nitric oxide (NO) and tumor necrosis factor-α (TNF-α). To clarify the structural requirements for inhibition, some structure–activity relationships (SARs) were determined. Methods: RAW264.7 macrophages were maintained in vitro under standard cell culture conditions. The release of NO and TNF-α from these cells was induced by lipopolysaccharides (LPS) and was measured. The primary SAR inhibitory activity of LPS-induced NO and TNF-α and production in RAW264.7 macrophage cells were evaluated by cytotoxicity assays. Results: SAR studies of dammarane-type saponins revealed that the glycosides substituent at C-3, C-6, and C-20 were important features for the NO and TNF-α production in RAW264.7 cells induced LPS. Moreover, the 5(6)-double bond and the OH group at C-7 improved the TNF-α inhibitory activity. In the case of ginsenoside Rh₂, the C-20 configuration was needed for potent TNF-α inhibition. Conclusions: These results provide an approach for understanding the structural requirements of dammarane-type saponins isolated from P notoginseng for optimum anti-inflammatory properties of these compounds.

A novel protein-polysaccharide conjugate NFP-A4 was isolated and purified from water extracts of Nervilia fordii. The polysaccharide chain of NFP-A4 was found to contain D-galacturonic acid, D-galactose, D-glucose, L-arabinose, D-glucuronic acid, L-rhamnose, and D-mannose. The protein content of NFP-A4 was determined to be 12.83%, and it was bound to the polysaccharide chain via O-linkages at the serine and threonine residues. NFP-A4 was found to significantly activate macrophages and also induce immunomodulatory responses. These data suggest that NFP-A4 is a major bioactive component of N. fordii and may be responsible for many of its therapeutic properties.