Pharmacological Study of Andrographis paniculata (Kalmegh) for their possible Antimalarial Activity with Emphasis on Resistance and Resistant Reversal

Antimalarial effect of some medicinal plants found in Uttarakhand (India) is least explored by the scientific community locally. Advent of resistance to various antimalarial drugs by plasmodium made malaria more fatal and life-threatening disease. Therefore, present need is to invest more effort and interest in research for antimalarials from medicinal plants. Plasmodium yoelii nigeriensis (PYn) is multi drug resistance malaria parasite known for resistance to chloroquine (CQ), quinine, quinidine, amodiaquine, halofantrine, mepacrine, and mefloquine. The P. yoelii produces 100% infections in animals. Researchers in this study tried to understand the behavior of CQ -resistant plasmodium PYn with CQ, whole plant extracts of Andrographis paniculata (AP) with possibility of their resistance reversal. Wherever, 3–4 times CQ doses are not able to produce sufficient antimalarial effect in resistant PYn. Most of the pure plant extracts are also not able to produce minimal therapeutic response when given alone. Whereas, plant extract shows a better effect when given with minimal dose CQ than alone. AP whole plant hydroalcoholic (HA) extract doses 300 mg/kg when combining CQ 20 mg/kg shows the best effect among the other extracts alone. Parasitemia and red blood cells count parameters significantly improved. Hemoglobin, survival days and weight are benefitted with HA extract then ethanolic extract. Unexpectedly, HA extract at higher dosage 1000 mg/kg produce efficacy then 300 mg/kg dose group. Higher doses of HA extract causes some sort of negative effect on almost all selected parameters even though with ethanolic extract. Present approach of multi-drug dosage supports also supported here in the study with a thought of using antimalarial plant extracts during regular malaria treatment. Genesis of idea of referring standardized plant extract(s) in combination as oral dosage with prophylactic (travelers) malaria and malaria treatment or side-food for malaria will also possible. Positive results may pave a path for inclusion of herbal extracts or herbs as side treatment or resistance-breaker food for malaria

Brightening Quinolineimines by Al³⁺ and Subsequent Quenching by PPi/PA in Aqueous Medium: Synthesis, Crystal Structures, Binding Behavior, Theoretical and Cell Imaging Studies

Recent years have witnessed an upsurge of Al³⁺ selective optical sensors involving simple Schiff bases to other complex organic frameworks. However, more than ∼95% of such reports lack crystallographic evidence, and proposals of binding sites for Al³⁺ are based upon spectroscopic evidence only. We herein synthesized and fully characterized a quinolineimine derivative (CMO) and explored its potential toward efficient detection of Al³⁺ with crystallographic evidence. The ongoing nonradiative photoinduced electron transfer (PET) and excited state intramolecular proton transfer (ESIPT) processes in CMO got inhibited via the chelation enhanced fluorescence (CHEF) effects induced by Al³⁺, and consequently turn-on fluorescence response was observed with 18-fold emission enhancements. The theoretical calculations performed were in good consonance with experimental results. We also explored further the applicability of the CMO·Al³⁺ complex toward highly sensitive and selective detection of inorganic phosphate (PPi) and an explosive picric acid (PA) via fluorescence quenching processes through two different chemical routes. The bioimaging of Al³⁺ and PPi were carried out in the living human cancer cells (MCF-7)

SUMO fusion facilitates expression and purification of garlic leaf lectin but modifies some of its properties

Over expression of lectin genes in E. coli often gives inclusion bodies that are solubilised to characterize lectins. We made N-terminal fusion of the Allium sativum leaf agglutinin (ASAL) with SUMO (small ubiquitin related modifier) peptide. The SUMO peptide allowed expression of the recombinant lectin in E. coli, predominantly in soluble form. The soluble fusion protein could be purified by immobilized metal affinity column (IMAC), followed by size exclusion chromatography. The SUMO protease failed to cleave the SUMO peptide from ASAL. This may be due to steric hindrance caused by the homodimer structure of the chimeric ASAL. Some properties like dimerization, haemagglutination and insecticidal properties of the recombinant SUMO-ASAL fusion protein were comparable to the plant derived native lectin. However, glycan array analysis revealed that the carbohydrate binding specificity of the recombinant SUMO-ASAL was altered. Further, the fusion protein was not toxic to E. coli (native ASAL exhibited toxicity). The recombinant lectin was more thermo-labile as compared to the native lectin. Three important findings of this study are: (1) sugar specificity of ASAL can be altered by amino-terminal fusion; (2) anti-E. coli activity of ASAL can be eliminated by N-terminal SUMO fusion and (3) SUMO-ASAL may be a preferred candidate insecticidal protein for the development of transgenic plants