Standardization and Ameliorative effect of Kalyanaka ghrita in ß-amyloid induced memory impairment in wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Kalyanaka ghrita (KG) is an Ayurvedic formulation traditionally used in the treatment of Daurbalya (debility) and Smritidaurbalya (impairment of intellectual activities). Clinical studies have reported the effect of KG in the treatment of Manasmandata or Buddhimandyata which is associated with impaired learning, social adjustment and maturation. AIM OF THE STUDY: The present study aims to standardization of KG and validation of its use in experimental models of neurodegeneration. MATERIALS AND METHODS: KG was Standardized for biomarkers curcumin, gallic acid, tannic acid, chebulagic acid, and berberine. In male wistar rats, neurodegeneration was induced by administration of intracerebroventricular Amyloid ß (Aß1-42). The effect of KG (oral and intranasal treatment) was evaluated through behavioral parameters such as Morris water maze, social recognition test, novel object recognition, locomotor activity, and molecular parameters, brain acetylcholinesterase, brain-derived neurotrophic factor (BDNF), inflammatory cytokines, oxidative stress markers, and antioxidants. Brain histopathology was performed for studying the architecture of the brain and plaque formation. RESULTS AND DISCUSSION: A novel HPLC method has been developed for the standardization of KG. Treatment with KG significantly improved cognition and memory and increased brain BDNF and antioxidant status in Aß1-42 induced rats. It also reduced brain acetylcholinesterase, oxidative stress, and inflammatory cytokines and prevented neuronal damage. There were more marked effects with intra-nasal administration compared to oral treatment. CONCLUSION: The findings suggest that KG has neuroprotective potential and along with its nootropic property could be a promising therapy for neurodegenerative diseases like Alzheimer's disease.

Nimbolide ameliorates fibrosis and inflammation in experimental murine model of bleomycin-induced scleroderma.

BACKGROUND: Clinical manifestations of skin fibrosis are very variable and ambiguous, making its management quite critical and challenging. The lack of appropriate established pharmacological interventions make its treatment even more complicated. Intricate details of the underlying pathogenesis are thus imperative to further explore different treatment possibilities. Of note, the TGF-ß/Smad signaling axis and epithelial to mesenchymal transition (EMT) are the principal offenders in this fibrotic disorder. OBJECTIVE: Our current study is aimed at demonstrating the antifibrotic and anti-inflammatory potential of nimbolide, a triterpene derived from Indian traditional plant neem, in a murine model of Bleomycin-induced scleroderma. METHODS: Male C57BL/6 mice were administered with Bleomycin injections subcutaneously, daily for 28 days, at a constant site on the dorsum of the mice. Treatment with nimbolide lasted from day 1 to day 28. At the time of study termination, the injected sites were collected and stored suitably to conduct further molecular experiments and protein expression studies. RESULTS AND CONCLUSION: The results of our study show that nimbolide can significantly intervene in the TGF-ß/Smad signaling axis and the consequent EMT process, thus attenuating deposition of extracellular matrix. Nimbolide also profoundly caused the regression of established inflammation-driven fibrosis, thus demonstrating both antifibrotic and anti-inflammatory activities. Another commendable finding of this study is that nimbolide was able to decrease the levels of LOXL2, a collagen cross-linker, which is aberrantly expressed in scleroderma. Although further mechanistic studies are required, our study displays nimbolide for the first time as a potent antifibrotic agent which can be used as a pharmacological intervention for the treatment of scleroderma.