No abstract

Work on the brain renin–angiotensin system has been explored by various researchers and has led to elucidation of its basic physiologies and behavior, including its role in reabsorption and uptake of body fluid, blood pressure maintenance with angiotensin II being its prominent effector. Currently, this system has been implicated for its newly established effects, which are far beyond its cardio-renal effects accounting for maintenance of cerebral blood flow and cerebroprotection, seizure, in the etiology of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and bipolar disorder. In this review, we have discussed the distribution of angiotensin receptor subtypes in the central nervous system (CNS) together with enzymatic pathways leading to active angiotensin ligands and its interaction with angiotensin receptor 2 (AT2) and Mas receptors. Secondly, the use of angiotensin analogues (angiotensin converting enzyme inhibitors and AT1 and/or AT2 receptor blockers) in the treatment and management of the CNS disorders mentioned above has been discussed.

Betulinic acid (BA) exhibits many biological effects including anti-inflammatory and anti-oxidant activities. Free radicals and pro-inflammatory mediators play an important role in the pathology of inflammatory bowel disease (IBD) and associated pain. We, therefore, examined the anti-oxidant, anti-inflammatory, and anti-nociceptive potential of BA in colitis. Colitis was induced with 3% (w/v) dextran sulfate sodium (DSS) in drinking water in mice for 1to7 days. BA (3, 10 and 30 mg/kg) was given orally for 0 to 7 days. BA was also tested for its efficacy in acetic acid and mustard oil-induced visceral nociception in mice at same doses. BA significantly prevented diarrhea; bleeding and colonic pathological changes induced by DSS. Further, BA reduced the colon nitrite, malondialdehyde, myeloperoxidase, and lipid hydroperoxide levels and restored the superoxide dismutase, catalase and reduced glutathione levels to normalize the redox balance in DSS-exposed mice. Inflammatory mediators like matrix metalloproteinase-9 and prostaglandin E2 levels were also significantly attenuated by BA in colitis mice. Additionally, BA reduced acetic acid and mustard oil-induced visceral pain in mice. In conclusion, the results of the present study suggest that BA possesses good anti-nociceptive activity and the anti-IBD effects of BA are due to its anti-oxidant and anti-inflammatory potential.

Alzheimer's disease (AD) is the most common CNS disorder occurring worldwide. There is neither proven effective prevention for AD nor a cure for patients with this disorder. Hence, there is an urgent need to develop safer and more efficacious drugs to help combat the tremendous increase in disease progression. The present review is an attempt at discussing the treatment strategies and drugs under clinical trials governing the modulation of neurotransmitter. Therefore, looking at neurotransmitter abnormalities, there is an urge for developing the pharmacological approaches aimed at correcting those abnormalities and dysfunctioning. In addition, this review also discusses the drugs that are in Phase III trials for the treatment of AD. Despite advances in treatment strategies aimed at correcting neurotransmitter abnormalities, there exists a need for the development of drug therapies focusing on the attempts to remove the pathogenomic protein deposits, thus combating the disease progression.