Centella asiatica improves memory and executive function in middle-aged rats by controlling oxidative stress and cholinergic transmission.

ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (L.) Urban, is a medicinal herb with rich history of traditional use in Indian subcontinent. This herb has been valued for its diverse range of medicinal properties including memory booster, and also as a folk treatment for skin diseases, wound healing and mild diuretic. AIM OF STUDY: Aging is a gradual and continuous process of natural decay in the biological systems, including the brain. This work aims to evaluate the effectiveness of ethanolic extract of Centella asiatica (CAE) on age-associated cognitive impairments in rats, as well as the underlying mechanism. MATERIAL AND METHODS: Rats were allocated into five distinct groups of 5 animals each: Young rats (3 months old rats), middle-aged (m-aged) rats (13-14 months old), and the remaining three groups were comprised of m-aged rats treated with different concentrations of CAE, viz., 150, 300, and 450 mg/kg b. w., orally for 42 days. Y-maze, open field, novel object recognition, and elevated plus maze tests were used to assess animal behavior. The malondialdehyde (MDA), superoxide dismutase (SOD), and acetylcholinesterase (AChE) assays; and H&E staining were done in the rat brain to assess the biochemical and structural changes. CAE was also subjected to HPLC analysis, in vitro antioxidant and anti-cholinergic activity. The active compounds of CAE were docked with AChE and BuChE in molecular docking study. RESULTS: The results showed that CAE treatment improves behavioral performance; attenuates the age-associated increase in MDA content, SOD, and AChE activity; and reduces neuronal loss. In vitro study showed that CAE has concentration-dependent antioxidant and anti-AChE activity. Furthermore, the presence of Asiatic acid and Madecassic acid in CAE and their good binding with cholinergic enzymes (in silico) also suggest the anticholinergic effect of CAE. CONCLUSION: The findings of the current study show that the anticholinergic and antioxidant effects of CAE are attributable to the presence of Asiatic acid and Madecassic acid, which not only provide neuroprotection against age-associated cognitive decline but also reverse it.

Centella asiatica Alleviates AlCl3-induced Cognitive Impairment, Oxidative Stress, and Neurodegeneration by Modulating Cholinergic Activity and Oxidative Burden in Rat Brain.

Aluminum (Al) is linked to the development of many neurological disorders such as Alzheimer's disease (AD), Parkinson's disease, and autism. Centella asiatica (CA) is a regenerating herb traditionally used to stimulate memory. This study was designed to assess the neuroprotective role of ethanolic extract of CA (CAE) in AlCl3-induced neurological conditions in rats. Adult rats were chronically treated with AlCl3 (100 mg/kg b.w./day) for 60 days to establish the dementia model, and co-administration of CAE was evaluated for its ability to attenuate the toxic effect of AlCl3. CAE was given orally at a dose of 150 and 300 mg/kg b.w./day, for 60 days. The behavioral performances of rats were tested through Y-maze and open field tests. Lipid peroxidation, superoxide dismutase, and catalase activity were evaluated to measure oxidative stress; and acetylcholinesterase (AChE) activity was assessed to evaluate cholinergic dysfunction in the rat brain. H&E staining was used to assess structural abnormalities in the cortex and hippocampus. The result showed that AlCl3 induces cognitive dysfunction (impaired learning and memory, anxiety, diminished locomotor activity), oxidative stress, cholinergic impairment, and histopathological alteration in the rat brain. Co-administration of CAE with AlCl3 markedly protects the brain from AlCl3-induced cognitive dysfunction, oxidative stress, AChE activity, and cytoarchitectural alterations. Furthermore, 15 days CAE treatment after 45 days AlCl3 administration markedly ameliorates the AlCl3-induced neurotoxicity indicating its potential for therapeutic use.

Centella asiatica prevents D-galactose-Induced cognitive deficits, oxidative stress and neurodegeneration in the adult rat brain.

Chronic D-galactose (D-gal) administration causes cognitive impairment and is used widely in animal models for anti-aging studies. Centella asiatica (CA), a traditional herbal medicine, has been used as a brain tonic to enhance memory. This study evaluates the neuroprotective role of an ethanolic extract of Centella asiatica (CAE) against D-gal-induced aging in rats. Healthy male rats were divided into three groups: Control, D-gal, and D-gal + CAE. The Control group received normal saline (i.p.), whereas the D-gal group received D-gal (120 mg/kg b.w., i.p.), and the D-gal + CAE group received D-gal (120 mg/kg b.w., i.p.) and CAE (300 mg/kg b.w., orally) daily for 42 days. Behavioral and brain biochemical and histopathological changes were assessed after treatment. The results of the behavioral study depicted that D-gal significantly reduces the spontaneous alternation and locomotor activity indicating behavioral and cognitive impairment. Biochemical studies showed that D-gal significantly increases the oxidative stress and acetylcholinesterase activity (AChE) in rat brain. Histopathological study showed that D-gal disturbs the normal architecture of hippocampal and cortical cells, indicating degeneration in these brain areas. D-gal and CAE co-treatment for 42 days attenuated the behavioral, biochemical, and neuroanatomical impairments caused by the D-gal; it markedly suppresses the D-gal-induced oxidative stress and AChE activity in the brain, and maintains the normal cellular architecture in hippocampal and cortical areas. Thus, this study shows that CAE can protect the brain from the adverse effects of D-gal (e.g., memory loss and cognitive impairment) by modulating AChE activity and oxidative stress.

Consumption of Ashtanga Ghrita (clarified cow butter added with herb extracts) improves cognitive dysfunction induced by scopolamine in rats via regulation of acetylcholinesterase activity and oxidative stress.

OBJECTIVES: Ashtanga Ghrita (AG), an Indian traditional formulation, has been used to promote neuropharmacological activities. AG is made up of clarified cow butter (ghee) and eight different herbs. METHODS: To test whether scopolamine (SCP)-induced dementia and brain oxidative stress can be counteracted by AG, rats were separated into five groups (n=6/group): group one control, group two SCP (1 mg/kg b.w., i.p.) treated and group three to five were co-treated with different doses of AG (1.25, 2.5 and 5 g/kg b.w., orally) and SCP. After the treatment regimen, behavioral (Y-maze test) and brain biochemical changes were measured in all groups. RESULTS: Microbial load and heavy metals were found within permissible limits. Results from attenuated total reflection Fourier-transform infrared spectroscopy demonstrated the complexation/interaction of herbal phytoconstituents with the functional groups of Ghrita. Preliminary phytochemical analysis of AG exhibited the occurrence of flavonoids, phenolics, glycosides, steroids, triterpenes, tannins, and amino acids. Findings of the experimental study exhibited that AG significantly protected the rats from SCP-induced behavioral dysfunction and brain biochemical alterations. CONCLUSIONS: This study demonstrates that AG protects the brain from SCP-induced dementia by promoting brain antioxidant activity and thus could be a promising drug for the treatment of neurodegenerative disease.

An Insight in Pathophysiological Mechanism of Alzheimer's Disease and its Management Using Plant Natural Products.

Alzheimer's disease (AD) is an age-associated nervous system disorder and a leading cause of dementia worldwide. Clinically, it is described by cognitive impairment and pathophysiologically by deposition of amyloid plaques and neurofibrillary tangles in the brain and neurodegeneration. This article reviews the pathophysiology, course of neuronal degeneration, and the various possible hypothesis of AD progression. These hypotheses include amyloid cascade, tau hyperphosphorylation, cholinergic disruption, metal dysregulation, vascular dysfunction, oxidative stress, and neuroinflammation. There is an exponential increase in the occurrence of AD in the recent few years that indicate an urgent need to develop some effective treatment. Currently, only 2 classes of drugs are available for AD treatment, namely acetylcholinesterase inhibitor and NMDA receptor antagonist. Since AD is a complex neurological disorder and these drugs use a single target approach, alternatives are needed due to limited effectiveness and unpleasant side-effects of these drugs. Currently, plants have been used for drug development research especially because of their multiple sites of action and fewer side effects. Uses of some herbs and phytoconstituents for the management of neuronal disorders like AD have been documented in this article. Phytochemical screening of these plants shows the presence of many beneficial constituents like flavonoids, triterpenes, alkaloids, sterols, polyphenols, and tannins. These compounds show a wide array of pharmacological activities, such as anti-amyloidogenic, anticholinesterase, and antioxidants. This article summarizes the present understanding of AD progression and gathers biochemical evidence from various works on natural products that can be useful in the management of this disease.