Antioxidant and anti-neoplastic activities of Picrorhiza kurroa extracts

Picrorhizakurroa Royle ex Benth., a well-known traditional herb from the Scrophulariaceae family has a remarkable reputation among the indigenous medical practitioners. The antioxidant and anti-neoplastic activities of methanolic and aqueous extracts of P. kurroa rhizome were investigated in the present study. The total phenolic content was determined by a spectrophotometric method. The antioxidant efficacies of the extracts were studied employing radical scavenging assays (DPPH and OH), ferric reducing antioxidant property (FRAP) and thiobarbituric acid (TBA) assay for testing inhibition of lipid peroxidation. Furthermore, the cytotoxicity of the extracts was tested by XTT assay in MDA-MB-435S (human breast carcinoma), Hep3B (human hepatocellular carcinoma) and PC-3 (human prostate cancer) cell lines. The ability of the extracts to induce apoptosis was also investigated. Both extracts exhibited promising antioxidant potentials. The extracts were also observed to be cytotoxic at the tested dosage and were able to target cells towards apoptosis. The study concludes that P. kurroa possess diverse therapeutic potentials which might be useful in development of drugs or their precursors.     

β-ODAP accumulation could be related to low levels of superoxide anion and hydrogen peroxide in Lathyrus sativus L.

Level of the neuroexcitatory β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP) in grass pea (Lathyrus sativus L.) varies with development and environmental stress. Reactive oxygen species (ROS) (mainly O₂⁻ and H₂O₂) are frequently reported to play important roles in plant development and in response to various stresses. To investigate the possible inter-relationship between contents of β-ODAP and ROS, grass pea leaves have been analyzed for contents of β-ODAP, O₂⁻ and H₂O₂. The results showed that leaves containing high levels of β-ODAP, exhibited low levels of O₂⁻ and H₂O₂, while leaves with high contents of O₂⁻ and H₂O₂ accumulated little β-ODAP. The application of pyridine or ABA which inhibit the production of O₂⁻ or H₂O₂ led to an increase in β-ODAP contents in intact or detached young leaves, whereas inhibition of catalase activity using AT (3-amino-1,2,4-triazole), leading to an increase in H₂O₂ content, result in significant decrease in β-ODAP levels of detached young leaves. In addition, inoculation of Rhizobium to young seedlings enhanced O₂⁻ and H₂O₂ levels, but reduced β-ODAP contents in shoots. These results suggest that β-ODAP accumulation could be related to low levels of superoxide anion and hydrogen peroxide in grass pea tissues.     

The hederagenin saponin SMG-1 is a natural FMLP receptor inhibitor that suppresses human neutrophil activation

The pericarp of Sapindus mukorossi Gaertn is traditionally used as an expectorant in Japan, China, and Taiwan. Activated neutrophils produce high concentrations of the superoxide anion (O₂⁻) and elastase known to be involved in airway mucus hypersecretion. In the present study, the anti-inflammatory functions of hederagenin 3-O-(3,4-O-di-acetyl-α-l-arabinopyranoside)-(1→3)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (SMG-1), a saponin isolated from S. mukorossi, and its underlying mechanisms were investigated in human neutrophils. SMG-1 potently and concentration-dependently inhibited O₂⁻ generation and elastase release in N-Formyl-Met-Leu-Phe (FMLP)-activated human neutrophils. Furthermore, SMG-1 reduced membrane-associated p47^phox expression in FMLP-induced intact neutrophils, but did not alter subcellular NADPH oxidase activity in reconstituted systems. SMG-1 attenuated FMLP-induced increase of cytosolic calcium concentration and phosphorylation of p38 MAPK, ERK, JNK, and AKT. However, SMG-1 displayed no effect on cellular cAMP levels and activity of adenylate cyclase and phosphodiesterase. Significantly, receptor-binding analysis showed that SMG-1 inhibited FMLP binding to its receptor in a concentration-dependent manner. In contrast, neither phorbol myristate acetate-induced O₂⁻ generation and MAPKs activation nor thapsigargin-caused calcium mobilization was altered by SMG-1. Taken together, our results demonstrate that SMG-1 is a natural inhibitor of the FMLP receptor, which may have the potential to be developed into a useful new therapeutic agent for treating neutrophilic inflammatory diseases.     

DSM-RX78, a new phosphodiesterase inhibitor, suppresses superoxide anion production in activated human neutrophils and attenuates hemorrhagic shock-induced lung injury in rats

Neutrophils are activated following hemorrhagic shock and the accumulation of neutrophils in the lung is associated with lung injury. This research investigated the effects of a semisynthetic 2-benzoylaminobenzoic acid derivative, methyl 2-(2-fluorobenzamido)benzoate (DSM-RX78), on superoxide anion (O₂⁻) production in formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-activated human neutrophils, and on lung injury in Sprague-Dawley rats subjected to trauma-hemorrhage. DSM-RX78 concentration-dependently inhibited O₂⁻ production, but not elastase release, in FMLP-activated human neutrophils. DSM-RX78 displayed no superoxide-scavenging ability, and it failed to alter the subcellular NADPH oxidase activity. Significantly, DSM-RX78 increased cAMP formation and protein kinase (PK)A activity in FMLP-activated neutrophils, which occurred through the selective inhibition of cAMP-specific phosphodiesterase (PDE) activity but not an increase in adenylate cyclase function or cGMP-specific PDE activity. These results show that DSM-RX78 is a new inhibitor of cAMP-specific PDE. Moreover, DSM-RX78 reduced FMLP-induced phosphorylation of protein kinase B (Akt), but not calcium mobilization. The inhibitory effects of DSM-RX78 on O₂⁻ production and Akt phosphorylation were reversed by PKA inhibitors, suggesting that DSM-RX78 regulates O₂⁻ production of human neutrophils by promoting cAMP/PKA-dependent inhibition of Akt activation. On the other hand, administration of DSM-RX78 significantly attenuated the increase in myeloperoxidase activity and edema in the lung, as well as protein concentrations in bronchoalveolar lavage fluid in rats after trauma-hemorrhagic shock. In summary, these results strongly suggest that DSM-RX78 exerts anti-inflammatory effects, which result from the elevation of cAMP levels and PKA activity through its inhibition of cAMP-specific PDE. Also, our findings show that DSM-RX78 attenuates hemorrhagic shock-induced lung injury in rats.