Dibenzofurans from Cladonia corniculata Ahti and Kashiw inhibit key enzymes involved in inflammation and gout: An in vitro approach

715-719The usage of natural sources like lichen extracts and their metabolites as anti-inflammatory agents is well known for ages. Based on the data of the folklore and documented books, researchers tested lichens and their products for anti-inflammatory properties and they identified many therapeutic agents used to diagnosis acute and chronic inflammation with lesser side effects. In this study, we aimed to examine the acetone extract of Cladonia corniculata(AE)and its metabolites for in vitro anti-inflammatory and anti-gout effects. Through chemical investigation, we have successfully isolated and identified three known dibenzofurans, namely alectosarmentin 1, porphyrilic acid 2, and strepsilin 3 from the AE. All isolated dibenzofurans1-3 showed prominent inhibition of cyclooxygenase enzymes, whereas compounds 1 and 2 exhibited noticeable inhibition of 5-lipoxygenase enzyme. Only compound 2 showed significant inhibition of xanthine oxidase enzyme with an IC50 value of 80.17±0.66 µg/mL, while standard drug allopurinol with 9.10±0.64 µg/mL. The results indicate that C. corniculatacan be a favourable natural source for the treatment of inflammation and gout and these actions are linked to the natural active dibenzofurans1-3

Dibenzofurans from Cladonia corniculata Ahti and Kashiw inhibit key enzymes involved in inflammation and gout: An in vitro approach

The usage of natural sources like lichen extracts and their metabolites as anti-inflammatory agents is well known for ages. Based on the data of the folklore and documented books, researchers tested lichens and their products for anti-inflammatory properties and they identified many therapeutic agents used to diagnosis acute and chronic inflammation with lesser side effects. In this study, we aimed to examine the acetone extract of Cladonia corniculata(AE)and its metabolites for in vitro anti-inflammatory and anti-gout effects. Through chemical investigation, we have successfully isolated and identified three known dibenzofurans, namely alectosarmentin 1, porphyrilic acid 2, and strepsilin 3 from the AE. All isolated dibenzofurans1-3 showed prominent inhibition of cyclooxygenase enzymes, whereas compounds 1 and 2 exhibited noticeable inhibition of 5-lipoxygenase enzyme. Only compound 2 showed significant inhibition of xanthine oxidase enzyme with an IC50 value of 80.17±0.66 µg/mL, while standard drug allopurinol with 9.10±0.64 µg/mL. The results indicate that C. corniculatacan be a favourable natural source for the treatment of inflammation and gout and these actions are linked to the natural active dibenzofurans1-3.

Manglicolous lichen Parmotrema tinctorum (Despr. ex Nyl.) Hale: Isolation, characterization and biological evaluation

The chemical examination of the ethanolic extract of manglicolous lichen Parmotrema tinctorum (Pt-Et) has resulted in isolation of six known metabolites, i.e., methyl-β-orcinolcarboxylate (1), isolecanoric acid (2), methyl-2,6-dihydroxy-4-methylbenzoate (3), haematommic acid (4), ethyl haematommate (5), and atranorin (6). All the isolates 1-6 and Pt-Et have been screened against DPPH and superoxide free radicals, six different cancer cell lines (MDA-MB-231, SW620, HeLa, FADU, A549, SKOV3) and one normal human cell line (NHME). Compound 3 exhibits prominent inhibition of superoxide free radical, which appears to be better than that of the standard (ascorbic acid) with an IC50 value of 26.0 µg/mL. From the SRB assay results, it is observed that the better IC50 values have been obtained from 4 and 5 on HeLa, FADU, and A549, respectively. In addition, all the tested samples show low cell lysis on NHME, which indicates low toxicity. Consequently, the outcomes revealed that P. tinctorum could be a new source to treat oxidative stress and cancer. This work is the first report of antioxidant and cytotoxicity studies on the isolated metabolites 1-6

Manglicolous lichen Parmotrema tinctorum (Despr. ex Nyl.) Hale: Isolation, characterization and biological evaluation

856-861The chemical examination of the ethanolic extract of manglicolous lichen Parmotrema tinctorum (Pt-Et) has resulted in isolation of six known metabolites, i.e., methyl-β-orcinolcarboxylate (1), isolecanoric acid (2), methyl-2,6-dihydroxy-4-methylbenzoate (3), haematommic acid (4), ethyl haematommate (5), and atranorin (6). All the isolates 1-6 and Pt-Et have been screened against DPPH and superoxide free radicals, six different cancer cell lines (MDA-MB-231, SW620, HeLa, FADU, A549, SKOV3) and one normal human cell line (NHME). Compound 3 exhibits prominent inhibition of superoxide free radical, which appears to be better than that of the standard (ascorbic acid) with an IC50 value of 26.0 µg/mL. From the SRB assay results, it is observed that the better IC50 values have been obtained from 4 and 5 on HeLa, FADU, and A549, respectively. In addition, all the tested samples show low cell lysis on NHME, which indicates low toxicity. Consequently, the outcomes revealed that P. tinctorum could be a new source to treat oxidative stress and cancer. This work is the first report of antioxidant and cytotoxicity studies on the isolated metabolites 1-6

Utilizing Andrographis paniculata leaves and roots by effective usage of the bioactive andrographolide and its nanodelivery: investigation of antikindling and antioxidant activities through in silico and in vivo studies

To valorise the bioactive constituents abundant in leaves and other parts of medicinal plants with the objective to minimize the plant-based wastes, this study was undertaken. The main bioactive constituent of Andrographis paniculata, an Asian medicinal plant, is andrographolide (AG, a diterpenoid), which has shown promising results in the treatment of neurodegenerative illnesses. Continuous electrical activity in the brain is a hallmark of the abnormal neurological conditions such as epilepsy (EY). This can lead to neurological sequelae. In this study, we used GSE28674 as a microarray expression profiling dataset to identify DEGs associated with andrographolide and those with fold changes >1 and p-value <0.05 GEO2R. We obtained eight DEG datasets (two up and six down). There was marked enrichment under various Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms for these DEGs (DUSP10, FN1, AR, PRKCE, CA12, RBP4, GABRG2, and GABRA2). Synaptic vesicles and plasma membranes were the predominant sites of DEG expression. AG acts as an antiepileptic agent by upregulating GABA levels. The low bioavailability of AG is a significant limitation of its application. To control these limitations, andrographolide nanoparticles (AGNPs) were prepared and their neuroprotective effect against pentylenetetrazol (PTZ)-induced kindling epilepsy was investigated using network pharmacology (NP) and docking studies to evaluate the antiepileptic multi-target mechanisms of AG. Andrographolide is associated with eight targets in the treatment of epilepsy. Nicotine addiction, GABAergic synapse, and morphine addiction were mainly related to epilepsy, according to KEGG pathway enrichment analysis (p < 0.05). A docking study showed that andrographolide interacted with the key targets. AG regulates epilepsy and exerts its therapeutic effects by stimulating GABA production. Rats received 80 mg/kg body weight of AG and AGNP, phenytoin and PTZ (30 mg/kg i.p. injection on alternate days), brain MDA, SOD, GSH, GABAand histological changes of hippocampus and cortex were observed. PTZ injected rats showed significantly (***p < 0.001) increased kindling behavior, increased MDA, decreased GSH, SOD, GABA activities, compared with normal rats, while treatment AGNPs significantly reduced kindling score and reversed oxidative damage. Finally, we conclude that the leaves and roots of A. Paniculata can be effectively utilized for its major bioactive constituent, andrographolide as a potent anti-epileptic agent. Furthermore, the findings of novel nanotherapeutic approach claim that nano-andrographolide can be successfully in the management of kindling seizures and neurodegenerative disorders

Orchid Dendrobium alpestre Royle enhances survival in lethal sepsis induced in mice

Despite advances in medical care and therapy, sepsis is still one of the major causes of death in intensive care units, and no decisive medical treatment is available against sepsis. The present study investigated the antibacterial activity, acute toxicity studies, hemodynamic parameters, myeloperoxidase (MPO) activity of hydroalcoholic extract of Dendrobium alpestre (Da), and its effects on cecal ligation and puncture (CLP) induced sepsis in mice. At equivalent concentration, Da showed antibacterial activities as potent as streptomycin against Staphylococcus aureus and Escherichia coli. Acute toxicity studies on mice found out that Da was non-toxic up to 2000 mg/Kg body weight, and the low and high dose was fixed as 100 and 200 mg/Kg body weight, respectively. At both doses, Da improved hemodynamic parameters such as mean arterial pressure and decreased optical density of blood, while it decreased serum MPO activity. Moreover, at a high dose, Da reduced the survival rate to 92.50±3.50% in mice that might be through pro-inflammatory effects. The results indicate that D. alpestre can be a favourable natural source for the treatment of CLP-induced sepsis in mice

Protective effect of Aurelia aurita against free radicals and streptozotocin-induced diabetes

The present work was carried out to identify the anti-oxidant and anti-diabetic activities of Aurelia aurita. The chemical profiling analysis showed that it possess different biologically active secondary metabolites like phenols, alakoids, steroids etc. The methanolic extract showed different free radical scavenging activity as ascorbic acid with  IC50 values 202, 205, 153 µg on DPPH, hydroxyl and superoxide free radicals. The extract significantly reduced the hyperglycemic conditions with percentage of reduction 18.7 ± 1.3 to 53.5 ±1.5 of streptozotocin-induced animals and the positive result of in-vitro aldose reductase enzyme inhibition with IC50 value 163 µg suggests that A. aurita have potential to cure the diabetic complications