Potential antioxidant, α-glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of major constituents isolated from Alpinia officinarum hance rhizomes: computational studies and in vitro validation.

Alpinia officinarum is a commonly used spice with proven folk uses in various traditional medicines. In the current study, six compounds were isolated from its rhizomes, compounds 1-3 were identified as diarylheptanoids, while 4-6 were identified as flavonoids and phenolic acids. The isolated compounds were subjected to virtual screening against α-glucosidase, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzymes to evaluate their potential antidiabetic and anti-Alzheimer's activities. Molecular docking and dynamics studies revealed that 3 exhibited a strong binding affinity to human a α- glucosidase crystal structure compared to acarbose. Furthermore, 2 and 5 demonstrated high potency against AChE. The virtual screening results were further supported by in vitro assays, which assessed the compounds' effects on α-glucosidase, cholinesterases, and their antioxidant activities. 5-Hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenylheptan-3-one (2) showed potent antioxidant effect in both ABTs and ORAC assays, while p-hydroxy cinnamic acid (6) was the most potent in the ORAC assay. In contrary, kaempferide (4) and galangin (5) showed the most potent effect in metal chelation assay. 5-Hydroxy-1,7-diphenylhepta-4,6-dien-3-one (3) and 6 revealed the most potent effect as α-glucosidase inhibitors where compound 3 showed more potent effect compared to acarbose. Galangin (5) revealed a higher selectivity to BChE, while 2 showed the most potent activity to (AChE).

Promising therapy for Alzheimer's disease targeting angiotensinconverting enzyme and the cyclooxygense-2 isoform.

Deposition of ß-amyloid in brain is one of the pathological hallmarks of Alzheimer's disease (AD) that is often associated with inflammatory response. Much evidence also points to a link between the renin-angiotensin system, hypertension and dementia. Accordingly, the potential use of anti-inflammatory and antihypertensives might be beneficial agents in AD therapy. In this study, we investigated the possible mechanisms of Celecoxib (cyclooxygenase-2 (COX-2) inhibitor), Perindopril (angiotensin converting enzyme (ACE) inhibitor) and their combination in a lipopolysaccharide (LPS) model of AD. Mice were injected with LPS (0.8 mg/ kg, i.p.) once then divided into three groups: the first was treated with Celecoxib (30 mg/kg/day, i.p.), the second with Perindopril (0.5 mg/kg/day, i.p.) and the last group with a combination of both drugs. Learning and memory function were tested using a Y-maze and locomotor activity was assessed using an open-field test. Cerebral specimens were subjected to histopathological studies. Brain tumor necrosis factor alpha (TNF-α), and interleukin (IL)-1ß levels were measured. LPS decreased locomotor activity and percentage of correct choices in the Y-maze test. It also produced a significant increase in the percentage area of vascular angiopathy, area of lamellated plaques, and apoptotic index. These were associated with increased TNF-α and IL-1ß. Administration of either Celecoxib or Perindopril partially improved cognitive impairment, decreased inflammatory cytokines and amyloid deposition. Combined therapy of both drugs completely prevented LPS induced neurodegenerative and cognitive changes. In conclusion, these findings establish a link between COX-2, ACE activity and cognitive impairment in AD and provided a promising strategy for the complete cure of AD.