Rataya Luechapudiporn

Atherosclerosis is a complex vascular disorder driven by oxidative stress, inflammation, and platelet activation. Agents capable of targeting multiple atherogenic pathways may provide improved therapeutic benefits. In this study, we evaluated the anti-atherogenic effects of chrysotoxine, a bibenzyl compound isolated from Dendrobium pulchellum, using in vitro models relevant to atherogenesis. Chrysotoxine significantly suppressed hemin-induced LDL oxidation by reducing lipid peroxidation and apolipoprotein modification. In an endothelial–monocyte co-culture model, chrysotoxine markedly attenuated lipopolysaccharide-induced monocyte adhesion, indicating inhibition of endothelial inflammatory activation. Chrysotoxine also inhibited platelet aggregation induced by arachidonic acid, ADP, and collagen in a concentration-dependent manner, with the strongest effects observed against arachidonic acid–mediated responses, suggesting modulation of the thromboxane pathway. Molecular docking analyses and cyclooxygenase activity assays further indicated that chrysotoxine may interact with both COX-1 and COX-2, exhibiting inhibitory activity in the low micromolar range. Collectively, these findings demonstrate that chrysotoxine modulates multiple key processes involved in atherogenesis, including oxidative LDL modification, vascular inflammation, and platelet activation. Although further in vivo studies are required, chrysotoxine represents a promising plant-derived candidate for the development of multi-target strategies against atherosclerotic disease.

This study assesses the protective effect of deferiprone on the oxidative status of low-density lipoproteins in patients with β-thalassaemia/haemoglobin E.

Background: Platelet aggregation plays a crucial role in hemostasis; however, excessive platelet activation can lead to thrombus formation, contributing to cardiovascular diseases. While aspirin (acetylsalicylic acid [ASA]) is commonly used as an antiplatelet agent, its longterm use is associated with gastrointestinal side effects. Angelica dahurica (AD), a traditional herbal remedy, has shown in vitro antiplatelet activity and cyclooxygenase enzyme inhibition. However, its in vivo effects on platelet aggregation and gastric safety remain unclear. Objectives: This study aimed to investigate whether Angelica dahurica root extract (ADE) could inhibit platelet aggregation and prevent aspirin-induced gastric lesions. Materials and Methods: AD was extracted using 50% ethanol. Rats were orally administered ADE at doses of 25, 50, 100, and 200 mg/kg, including groups receiving a combination of ADE and aspirin (80 mg/ kg) for seven consecutive days. Blood was collected for platelet-rich plasma preparation, and platelet aggregation was induced by adenosine diphosphate (ADP). Gastric tissues were examined macroscopically and histopathologically. Results: ADE at 100 mg/kg and 200 mg/kg significantly inhibited ADP-induced platelet aggregation. The combination of ADE (200 mg/kg) and aspirin (80 mg/kg) further enhanced inhibition compared to aspirin alone. ADE treatment did not produce any detectable macroscopic or histopathological damage of the gastric tissue in rats. Conclusion: ADE demonstrated inhibitory effects on platelet aggregation, while showing no evidence of gastric lesions in either control rats or those treated with aspirin. These findings suggest that ADE may offer potential as a complementary antiplatelet agent with reduced risk of gastrointestinal side effects commonly associated with aspirin.

Actinomycetes, predominantly found in soil, represent a remarkable source of natural products. The natural antioxidants obtained from them have been employed for human infectious diseases. In particular, Streptomyces strains serve as significant sources of natural antioxidants with demonstrated health benefits. The in vitro antioxidant activity and the inhibition of intracellular radical generation by crude extracts from various Streptomyces strains were evaluated and the genome sequence of selected strains was analyzed. Strains CT2-10, NE1-12, and ET3-23 showed 16S rRNA gene sequence similarity to Streptomyces capoamus JCM 4734T (98.94%), Streptomyces nigra 452T (99.78%), and Streptomyces morookaense LMG 20074T (99.49%), respectively. The genome analysis of strain ET3-23 had 106 contigs, with a total length of 8121874 bp and an average G+C content of 71.46%. Ethyl acetate extracts of strains CT2-10, ET3-23, and NE1-12 exhibited, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with IC50 555.9 µg/mL, 66.5 µg/mL, and 463.3 µg/mL and showed NO scavenging activity, except for CT2-10. Strain NE1-12 significantly inhibited ROS production induced by hydrogen peroxide on macrophage cells, while strains NE1-12 and CT2-10 inhibited NO production induced by lipopolysaccharides with IC50 82.4 µg/mL and 2.3 µg/mL, respectively. These findings suggest their ability to modulate NO production which is crucial in inflammatory responses and tissue injury. The antioxidant activities of Streptomyces strains indicate their potential as valuable sources of bioactive natural products and effective antioxidant agents, warranting further investigation for therapeutic applications.

This study was designed to evaluate the antiplatelet effect of deferiprone in patients with transfusion-dependent β-thalassaemia/Hb E at the dose of iron-chelation therapy. The results may provide a mechanistic insight in antiplatelet effects and support the benefit of deferiprone in the prevention of thrombotic events in β-thalassaemia.

Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. This study aims to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. The results indicated that lusianthridin inhibited arachidonic acid, collagen, and adenosine diphosphate (ADP)-stimulated platelet aggregation (IC₅₀ of 0.02 ± 0.001 mM, 0.14 ± 0.018 mM, and 0.22 ± 0.046 mM, respectively). Lusianthridin also increased the delaying time of arachidonic acid-stimulated and the lag time of collagen-stimulated and showed a more selective effect on the secondary wave of ADP-stimulated aggregations. Molecular docking studies revealed that lusianthridin bound to the entrance site of the cyclooxygenase-1 (COX-1) enzyme and probably the active region of the cyclooxygenase-2 (COX-2) enzyme. In addition, lusianthridin showed inhibitory effects on both COX-1 and COX-2 enzymatic activities (IC₅₀ value of 10.81 ± 1.12 µM and 0.17 ± 1.62 µM, respectively). Furthermore, lusianthridin significantly inhibited ADP-induced suppression of cAMP formation in platelets at 0.4 mM concentration (p < 0.05). These findings suggested that possible mechanisms of lusianthridin on the antiplatelet effects might act via arachidonic acid-thromboxane and adenylate cyclase pathways.

Oxidation of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin that can be found in thalassemia patients. Hemin is a strong oxidant that can cause LDL oxidation and contributes to atherosclerosis in thalassemia patients. Lusianthridin from Dendrobium venustrum is a phenolic compound that possesses antioxidant activity. Hence, lusianthridin could be a promising compound to be used against hemin-induced oxidative stress. The major goal of this study is to evaluate the protective effect of lusianthridin on hemin-induced low-density lipoprotein oxidation (he-oxLDL). Here, various concentrations of lusianthridin (0.25, 0.5, 1, and 2 µM) were preincubated with LDL for 30 min, then 5 µM of hemin was added to initiate the oxidation, and oxidative parameters were measured at various times of incubation (0, 1, 3, 6, 12, 24 h). Lipid peroxidation of LDL was measured by thiobarbituric reactive substance (TBARs) assay and relative electrophoretic mobility (REM). The lipid composition of LDL was analyzed by using reverse-phase HPLC. Foam cell formation with he-oxLDL in RAW 264.7 macrophage cells was detected by Oil Red O staining. The results indicated that lusianthridin could inhibit TBARs formation, decrease REM, decrease oxidized lipid products, as well as preserve the level of cholesteryl arachidonate and cholesteryl linoleate. Moreover, He-oxLDL incubated with lusianthridin for 24 h can reduce the foam cell formation in RAW 264.7 macrophage cells. Taken together, lusianthridin could be a potential agent to be used to prevent atherosclerosis in thalassemia patients.

Thalassemia patients are susceptible to both iron overload and thromboembolism. Deferiprone is an iron chelator that shows an antiplatelet activity and thus may alleviate platelet hyperactivation in thalassemia. Therefore, this study aimed to characterize the inhibitory effects and mechanisms of deferiprone on normal human platelets. The results illustrated that deferiprone inhibited platelet aggregation at the iron chelating concentrations (0.08–0.25 mmol/l). Deferiprone inhibited human platelet aggregation stimulated by arachidonic acid and ADP more potently than epinephrine and collagen, with the IC₅₀ of 0.24 mmol/l and 0.25 mmol/l vs. 3.36 mmol/l and 3.73 mmol/l, respectively. Interestingly, deferiprone significantly inhibited COX-1 activity, with the IC₅₀ of 0.33 mmol/l, and slightly increased cAMP level at the high concentration of 4 mmol/l. Moreover, the results from molecular docking showed that deferiprone interacted closely with key residues in the peroxidase active site of COX-1. These results suggested that deferiprone possessed antiplatelet activity mainly through the inhibition of COX-1 activity.