iridoids and Hemolysis

Three new iridoids named as pediverticilatasin A - C (1 - 3, resp.), together with five known iridoids (4 - 8, resp.) were isolated from the whole plants of Pedicularis verticillata. The structures of three new compounds were identified as (1S,7R)-1-ethoxy-1,5,6,7-tetrahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4(3H)-one (1), (1S,4aS,7R,7aS)-1-ethoxy-1,4a,5,6,7,7a-hexahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4-carboxylic acid (2), (1S,4aS,7R,7aS)-1-ethoxy-1,4a,5,6,7,7a-hexahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4-carbaldehyde (3). Their structures were elucidated on the basis of spectroscopic methods and compared with the NMR spectra data in the literature. All compounds were evaluated for their anti-complementary activity on the classical pathway of the complement system in vitro. Among which, compounds 1, 3, and 6 exhibited anti-complementary effects with CH

Topics: Complement Activation; Dose-Response Relationship, Drug; Erythrocytes; Hemolysis; Humans; Iridoids; Molecular Conformation; Pedicularis

It has been a great challenge to develop aldehyde-free tissue adhesives that can function rapidly and controllably on wet internal tissues with fine adhesion strength, sound biocompatibility and degradability. To this end, we have devised a mussel-inspired easy-to-use double-crosslink tissue adhesive (DCTA) comprising a dopamine-conjugated gelatin macromer, a rapid crosslinker (namely, Fe(3+)), and a long-term acting crosslinker (namely, genipin). As a mussel-inspired gluing macromer, dopamine is grafted onto gelatin backbone via an one-step reaction, the catechol groups of which are capable of performing strong wet adhesion on tissue surfaces. By addition of genipin and Fe(3+), the formation of catechol-Fe(3+) complexation and accompanying spontaneous curing of genipin-primed covalent crosslinking of gluing macromers in one pot endows DCTA with the double-crosslink adhesion mechanism. Namely, the reversible catechol-Fe(3+) crosslinking executes an controllable and instant adhesive curing; while genipin-induced stable covalent crosslinking promises it with long-term effectiveness. This novel DCTA exhibits significantly higher wet tissue adhesion capability than the commercially available fibrin glue when applied on wet porcine skin and cartilage. In addition, this DCTA also demonstrates fine elasticity, sound biodegradability, and biocompatibility when contacting in vitro cultured cells and blood. In vivo biocompatibility and biodegradability are checked and confirmed via trials of subcutaneous implantation in nude mice model. This newly developed DCTA may be a highly promising product as a biological glue for internal medical use including internal tissue adhesion, sealing, and hemostasis.. There is a great demand for ideal tissue adhesives that can be widely used in gluing wet internal tissues. Here, we have devised a mussel-inspired easy-to-use double-crosslink tissue adhesive (DCTA) that meets the conditions as an ideal tissue adhesive. It is composed of gelatin-dopamine conjugates - a gluing macromer, Fe(3+) - a rapid crosslinker, and genipin - a long-term acting crosslinker. This DCTA is constructed with a novel complexation-covalent double-crosslinking principle in one pot, in which the catechol-Fe(3+) crosslinking executes a controllable and instant adhesive curing, at the same time, genipin-induced covalent crosslinking promises it with long-term effectiveness in physiology conditions. This novel DCTA, with excellent wet tissue adhesion capability, fine elasticity, sound biodegradability, and biocompatibility, is a promising biological glue for internal medical use in surgical operations.

Topics: Animals; Biocompatible Materials; Bivalvia; Cell Proliferation; Cross-Linking Reagents; Dermis; Dopamine; Fibroblasts; Gelatin; Hemolysis; Humans; Implants, Experimental; Iridoids; Kinetics; Materials Testing; Mice, Nude; Organ Specificity; Sus scrofa; Tissue Adhesives

The parenteral route has many merits over the oral route, including greater predictability, reproducibility of absorption, and rapid drug action, but injectable phytomedicines are uncommon due to protein precipitating tannin and hemolytic saponin components. In this study, in an effort to develop a safe injectable analgesic phytomedicine, we prepared a tannin and saponin-free Lonicera japonica extract, SKLJI, through fractionation and column purification, and evaluated its anti-inflammatory and analgesic activities in in vivo experimental models of inflammation and pain. The removal of tannin and saponin resulted in loganin and sweroside-enriched SKLJI and it showed reduced hemolysis and protein precipitation. In efficacy tests, SKLJI inhibited croton oil- and arachidonic acid-induced ear edema, acetic acid-induced writhing, and carrageenan-induced rat hind paw hyperalgesia. Inhibition of cylcooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and 5-lipoxyfenase (5-LO) activities by SKLJI appeared to be the mechanism underlying anti-inflammatory and analgesic efficacy. Loganin and sweroside also showed anti-inflammatory and analgesic activities, suggesting that they might be active principles in the efficacy of SKLJI. These results suggest that SKLJI is a viable candidate for a new anti-inflammatory and analgesic phytomedicine that can be administered by the parenteral route.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Cyclooxygenase 2; Enzyme Inhibitors; Hemolysis; Inflammation; Injections, Intravenous; Iridoid Glucosides; Iridoids; Lonicera; Male; Mice; Nitric Oxide Synthase Type II; Plant Extracts; Rats; Rats, Sprague-Dawley

Morinda morindoides (Baker) Milne-Redhead (syn. Gaertnera morindoides Bak.) is one of the most popular medicinal plants in the Democratic Republic of Congo. In relation to its traditional use against rheumatic pains, fractionation of both the EtOAc- and the n-BuOH-soluble fraction of the 80% MeOH extract of the leaves, guided by the anticomplementary activity on the classical activation pathway, yielded eight novel iridoids (1-8), all containing a spirolactone functionality. Their structure was elucidated using spectroscopic methods. Gaertneroside 1, acetylgaertneroside 2, and gaertneric acid 5 were found to inhibit the activation of the classical pathway of the complement system, with IC(50) values between 58 and 69 microM. In addition to the biologically active flavonoids reported before from the same plant, these complement-inhibiting iridoids may contribute at least in part to the traditional use against rheumatic pains.

Topics: Complement Inactivator Proteins; Complement Pathway, Alternative; Complement Pathway, Classical; Democratic Republic of the Congo; Dose-Response Relationship, Drug; Flavonoids; Hemolysis; Humans; Inhibitory Concentration 50; Iridoids; Morinda; Nuclear Magnetic Resonance, Biomolecular; Plant Leaves; Plants, Medicinal