Isolation & identification of anti-inflammatory constituents of Randia dumetorum lamk. fruit: Potential beneficial effects against acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Randia dumetorum Lamk. is an Indian traditional medicinal plant that has been used for the treatment of various disorders including respiratory ailments. AIM OF THE STUDY: In continuation of our recent report that the Ethanol soluble fraction (ESF) of Randia dumetorum fruit had potent anti-inflammatory activity against acute lung injury (ALI) in mice, the present work was undertaken to unveil the key bioactive constituents possessing anti-inflammatory action against ALI by employing bioactivity-guided fractionation of ESF. MATERIAL AND METHODS: Different fractions/sub-fractions obtained by column chromatography of ESF were subjected to bioactivity studies by analyzing total and differential count, and protein content in broncho-alveolar lavage fluid (BALF) procured from mice. The most bioactive sub-fraction F3.2 was analyzed for the assessment of various inflammatory mediators using molecular techniques like ELISA, PCR, and western blotting. Further, an attempt was made to separate the key compounds in F3.2 using solvents of differential polarities; and isolated compounds were validated for their anti-inflammatory activity followed by their characterization using spectral techniques like 1HNMR, 13CNMR, FT-IR, and ESIMS Mass Spectrometry. RESULTS: The column chromatography of ESF yielded four fractions (F1, F2, F3, and F4) and data revealed that maximum activity resides in F3. Further fractionation of F3 yielded sub-fractions F3.1, F3.2, F3.3, and F3.4 which when tested for anti-inflammatory potential, showed F3.2 as the most active one. Moreover, the effect of F3.2 on oxidative stress parameters and inflammatory mediators analyzed via biochemical assays, PCR, and ELISA revealed the proficiency of this fraction in amelioration of ALI. F3.2 was then subjected to recrystallization using different solvents and two pure compounds were isolated which were characterized as D-Mannitol and Oleanolic acid (OA). D-Mannitol did not display any bioactivity, but OA showed potent anti-inflammatory activity. CONCLUSION: Considering the ethnopharmacological role of R. dumetorum in respiratory ailments, OA as an aglycone moiety seems to be the main active principle possessing anti-inflammatory potential against ALI.

Synthesis of deoxy-Andrographolide Triazolyl Glycoconjugates for the Treatment of Alzheimer's Disease.

A new andrographolide-based terminal alkyne 3 was synthesized in good yield from deoxy-andrographolide 2, obtained from a natural compound andrographolide 1, which in turn was isolated from the leaves of the plant Andrographis paniculata. Copper(I)-catalyzed azide-alkyne cycloaddition reaction of alkyne 3 with azido-sugars 4a-f furnished a library of andrographolide-fastened triazolyl glycoconjugates 5a-f in good yields. The structures of these semisynthetic andrographolide derivatives were established by Fourier transform infrared, NMR, and mass spectroscopy. The compounds 5a-f were further evaluated against Alzheimer's disease (AD) using a scopolamine (SCOP)-induced memory impairment mice model. It was observed that antioxidant and anticholinesterase properties of these compounds contribute significantly toward their remarkable potential to improve cognitive functioning.

Isolation of a new flavonoid and waste to wealth recovery of 6-O-Ascorbyl Esters from Seeds of Aegle marmelos (family- Rutaceae).

Aegle marmelos is a plant species native to India. Commercially available food products such as jam, jelly, candy, squash etc. are prepared from ripe fruit pulp of A. marmelos. Ripe fruit processing accounts for 60% of whole fruit mass while 40% remains unutilized and generates waste (hard shell, pomace, fiber and seeds) on a massive scale which do not have high value applications. A new flavone 3,5,7-trihydroxy-2-(4'-hydroxy-3'-isopentyloxyphenyl-4H-chromen-4-one (5) in addition to the known compounds 1-4, has been isolated from seeds of A. marmelos. Also, compound 7-(3'-methylbut-2'-enyloxy)-2H-chromen-2-one (2) has been isolated for the first time from A. marmelos. The structure of compounds 1-5 was determined by spectral analysis (UV, IR, NMR, etc.). Additionally, the non-edible oil obtained from seeds was investigated for waste to wealth recovery of 6-O-ascorbyl esters in high regioselectivity via one step semi-synthetic approach in the presence of ascorbic acid and H2SO4 at ambient temperature.

Tuberculosis and its Treatment: An Overview.

Tuberculosis (TB) is a primordial infectious disease that mainly affects the lungs. M. tuberculosis (Mycobacterium tuberculosis) is the etiological agent of TB and currently more than one-third of the world population is suffering from TB. For the treatment of TB, administration of multiple antibiotics such as isoniazid, rifampicin, pyrazinamide and ethambutol is required for a long period of time to kill bacteria. However, antibiotic resistance is an emerging problem in multiple drug-resistant tuberculosis (MDR-TB) infections. World Health Organization (WHO) has developed a novel strategy called DOTS (directly observed treatment, short-course), in which specific combination of anti-TB drugs is given to control TB. In this review article we have focused on the comprehensive management of TB and have provided the valuable information about first and second line anti-TB drugs, DOTS and novel drug delivery systems to be used against M. tuberculosis. Important aspects related to new anti-TB drugs and vaccines in various stages of clinical development are also covered in this article.

Studies on 16,17-Pyrazoline Substituted Heterosteroids as Anti-Alzheimer and Anti-Parkinsonian Agents Using LPS Induced Neuroinflammation Models of Mice and Rats.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common forms of neurodegenerative disorders. Dehydroepiandrosterone (DHEA) has been reported as a neuroprotective steroid useful in the therapeutic management of neurodegenerative disorders such as AD and PD. Herein we report the synthesis and evaluation of a new series of 16,17-pyrazolinyl DHEA analogues 2-4a-d as neuroprotective agents using LPS-induced neuroinflammation animal models. Treatment with the pyrazoline substituted steroids considerably improved the LPS-induced learning, memory and movement deficits in animal models. Suppression of biochemical parameters of oxidative and nitrosative stress, acetylcholinesterase activity, and TNF-α levels was also observed. 16,17-Pyrazolinyl steroids 2c-4c substituted with a 4-pyridyl moiety at the 5-position of the heterocyclic ring were found to be the most potent agents and produced neuroprotective effects better than standard drugs celecoxib and dexamethasone. Of these pyrazoline substituted steroids, the N-acetyl analogue 3c displayed neuroprotective effects better than N-phenyl (4c), which in turn showed potency more than N-unsubstituted analogue 2c.