Ashwagandha Root Extract Inhibits Acetylcholine Esterase, Protein Modification and Ameliorates H2O2-Induced Oxidative Stress in Rat Lymphocytes
Abstract
based on evidences gathered using scientific methods. Ashwagandha (Withania somnifera L.) is a traditional
medicinal herb used in the treatment of various ailments. Objective: In current study we have evaluated the
acetylcholine esterase (AChE) inhibitory and antioxidant potential of Ashwagandha root extract (ARE) in in-vitro
and ex-vivo models to give a scientific base to its use in herbal medicine. Methodology: Simplest extraction
e.g. maceration method was performed for preparation of extracts using methanol as solvent. Both in vitro
and in vivo experimental trial were executed to evaluate the efficacy of root extract. Result and Discussion:
ARE substantially scavenged free radicals and effectively prevented protein degradation as well as modification
as studied by SDS-PAGE and Western blotting. Pre-treatment with ARE protected rat lymphocytes against
H2
O2
-induced oxidative damage. H2
O2
treatment resulted in DNA fragmentation and significantly decreased the
activities of key antioxidant enzymes namely superoxide dismutase, catalase, glutathione peroxidase, glutathione
reductase, glucose-6-phosphate dehydrogenase while decreased and increased the content of glutathione
and malondialdehyde, respectively. ARE pre-treatment almost reversed these changes indicating its efficiency to
suppress hydrogen peroxide-induced oxidative stress. Conclusion: The study provides the scientific basis of
pleiotropic functions of Ashwagandha.
... T. cordifolia (methanolic extract) performed better among all the extracts, its IC 50 was 202.64 µg/mL. W. somnifera (methanolic extract) has an IC 50 of 4.44 mg/mL and 124 µg/mL, as shown by Pal et al. (2017) [29] and Mathew and Subramanian (2014) [27], respectively. ...
... T. cordifolia (methanolic extract) performed better among all the extracts, its IC 50 was 202.64 µg/mL. W. somnifera (methanolic extract) has an IC 50 of 4.44 mg/mL and 124 µg/mL, as shown by Pal et al. (2017) [29] and Mathew and Subramanian (2014) [27], respectively. ...
... T. cordifolia (methanolic extract) performed better among all the extracts, its IC50 was 202.64 µ g/mL. W. somnifera (methanolic extract) has an IC50 of 4.44 mg/mL and 124 µg/mL,as shown by Pal et al. (2017) [29] and Mathew and Subramanian (2014) [27], respectively. There are many reports on W. somnifera (methanolic extract) [24,26], and the IC50 of T. cordifolia (methanolic extract) was lowest in the study group, therefore we further analyzed it by HPLC. ...
Alzheimer’s disease (AD), a neurodegenerative disease, is the most common form of dementia. Inhibition of acetylcholinesterase (AChE) is a common strategy for the treatment of AD. In this study, aqueous, hydro-methanolic, and methanolic extracts of five potent herbal extracts were tested for their in vitro anti-AChE activity. Among all, the Tinospora cordifolia (Giloy) methanolic fraction performed better with an IC50 of 202.64 µg/mL. Of the HPLC analyzed components of T. cordifolia (methanolic extract), palmatine and berberine performed better (IC50 0.66 and 0.94 µg/mL, respectively) as compared to gallic acid and the tool compound “galantamine hydrobromide” (IC50 7.89 and 1.45 µg/mL, respectively). Mode of inhibition of palmatine and berberine was non-competitive, while the mode was competitive for the tool compound. Combinations of individual alkaloids palmatine and berberine resulted in a synergistic effect for AChE inhibition. Therefore, the AChE inhibition by the methanolic extract of T. cordifolia was probably due to the synergism of the isoquinoline alkaloids. Upon molecular docking, it was observed that palmatine and berberine preferred the peripheral anionic site (PAS) of AChE, with π-interactions to PAS residue Trp286, indicating that it may hinder the substrate binding by partially blocking the entrance of the gorge of the active site or the product release.
... The 3 studies [33,41,42] that examined the effects of Ws supplementation on antioxidant activity reported significant improvements in MDA [33,42], SOD [33], and TAC levels [42]. These results are consistent with previous animal studies, in vitro and in vivo analyses, and clinical trials in healthy athletic individuals [41,[64][65][66]. Moreover, investigators have reported beneficial effects of Ws in individuals with conditions linked to oxidative stress [43]. ...
Purpose of Review
Withania somnifera (L.) Dunal (Ws) is a common herb plant that has been used for centuries to treat a wide range of conditions, particularly certain chronic diseases due to its antidiabetic, cardioprotective, antistress, and chondroprotective effects, among many others. No conclusive evidence, however, exists about the potential health effects of Ws in adults without chronic conditions. We aimed to evaluate the current evidence on the health benefits of Ws supplementation in healthy adults.
Recent Findings
Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed studies indexed in Web of Science, Scopus, and PubMed to assess the effects of Ws on hematological and biochemical markers, hormonal behavior, and oxidant response in healthy adults. Original articles published up to March 5, 2022, with a controlled trial design or pre-post intervention design, in which supplementation of Ws was compared to a control group or data prior to intervention were included. Among 2,421 records identified in the search, 10 studies met the inclusion criteria. Overall, most of the studies reported beneficial effects of the Ws supplementation, and no serious adverse events were reported. Participants supplemented with Ws displayed reduced levels of oxidative stress and inflammation, and counterbalanced hormone levels. No evidence of the beneficial effects of Ws supplementation on hematological markers was reported.
Summary
Ws supplementation appears to be safe, may regulate hormone levels, and has potent anti-inflammatory and antioxidant effects. However, further studies are needed to elucidate the relevance of its application.
... The inhibition activity of W. somnifera against AChE has been previously reported in the literature, indicating the positive health effects for the treatment of neurodegenerative diseases and memory-related disorders such as Alzheimer's disease [73][74][75][76][77]. For example, Pai et al. [78] suggested the positive effects of hydroalcoholic extracts and withanolide-A in in vitro and in silico inhibition of AChE, while Khan et al. [74] and Choudhary et al. [79] also highlighted the importance of withanolides to these particular properties. ...
In the present study, the chemical composition and bioactive properties of commercially available Withania somnifera samples were evaluated. The hydromethanolic and aqueous extracts of the tested samples were analyzed in terms of phenolic compound composition, ascorbic acid content, antioxidant and antibacterial activity, and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Polyphenols and ascorbic acid content, as well as the antioxidant activity, were higher in the aqueous extracts than in the hydromethanolic extracts. Generally, aqueous extracts presented higher antioxidant activity than the hydromethanolic ones, especially in the case of 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Moreover, higher amounts of phenolic acids and flavonoids were found in the hydromethanolic extracts compared to the aqueous ones. Regarding the antibacterial properties, samples 4, 6, and 10 showed the best overall performance with growth-inhibitory activities against all the examined bacteria strains. Finally, the aqueous and hydromethanolic extracts were the most efficient extracts in terms of AChE and BChE inhibitory activities, respectively. In conclusion, our results indicate that W. somnifera possesses important bioactive properties which could be attributed to the high amounts of phenolic compounds. However, a great variability was recorded in commercially available products, suggesting significant differences in the origin of product and the processing method.
... Oxide-nitrosative stress and apoptosis are the central phenomena of various diseases, including nervous systemassociated illnesses [52,53]. The brain is a vital organ in the biological system and is highly susceptible to oxide-nitrosative stress and apoptosis. ...
Background: Since time immemorial, humans have identified several herbs to treat various ailments. With the advancement of science and state-of-the-art technologies, different herbal extracts and chemical constituents of herbs were identified as therapeutic targets. Cyperus rotundus, also called mustaka, is one of the most ancient herbs widely distributed in tropical and subtropical regions across the globe. The tuberous and aerial parts of the herb were identified to possess various pharmacological properties. Objectives: This review focuses on the various phytocompounds of mustaka and how these compounds exert pharmacological effects and their mode of action. The molecular and cellular effects of mustaka were also discussed based on the preclinical and clinical reports available using an array of in vitro, in vivo, and ex vivo methodologies. Methods: The information from Google Scholar, Science direct, PUBMED, were reviewed with a special focus on the mode of action of C. rotundus from the data on animal and preclinical experiments to treat various diseases. Conclusion: Based on the literature available on C. rotundus in Google Scholar, Science Direct, and PubMed, the pharmacological properties of mustaka were reviewed with a particular focus on its neuropharmacological activities. The mode of action of C. rotundus and its bioactive metabolites at the molecular biology level were demonstrated based on animal and preclinical experiments to cure various ailments. These diverse effects prove C. rotundus as a valuable traditional medicine for treating various disorders.
... [105,106] Furthermore, Santalum album wood tends to decrease doxorubicin induced oxidative stress by lowering enzyme activity [107],rhizome extract of Zingiber officinale inhibited gastric lesions by 97% [108]. Root extract of Withania somnifera scavenge free radicals and prevent protein degradation and reduced H 2 O 2 induced oxidative stress level [109]. In another study investigation on Nigella seeds revealed that it regulated dysfunctional microcirculation by protecting against lipid peroxidation, reduced NO production, decreased nitrite production and scavenge free radical ions like superoxide [67]. ...
The growing number of deaths related to sepsis has become a major concern for past few years. Sepsis is a complex pathological reactions that is explained by series of host response to microbial insult. The resulted systemic reactions are manifested by early appearance of proinflammatory cytokines leading to hyperinflammatory phase which is followed by septic shock and death of the patient. The present study has revealed that antibiotics are not self-sufficient to control the complex mechanism of sepsis. Moreover prolonged and unnecessary administration of antibiotics may lead to antibiotic resistance to pathogens. In addition to this, immunosuppressive medications are selective and have targeted approach to certain study population. Drugs from herbal origin have shown to possess a mammoth of immunomodulatory potential by suppressing proinflammatory and anti-inflammatory cytokines exhibiting no or minimal unwanted secondary responses. Concomitantly, herbal plants tend to modulate oxidative stress level and haematological imbalance during inflammatory diseased conditions. Natural compounds have gained much attention for the treatment of several clinical complications. Considering the promising responses of medicinal plants with less/no side effects and easy procurement, comprehensive research on herbal plants to treat sepsis should be contemplated.
... The protein oxidation was determined by the reaction of bovine serum albumin (BSA) with 2,2'-azobis-2-methyl-propanimidamide, dihydrochloride (AAPH) as described earlier [28]. Gallic acid is used as a standard antioxidant. ...
Elleteria repens is a large cardamom used in the culinary preparations. In the present study, we have evaluated in vitro antioxidant and free radical scavenging activities E. repens hexane extract (ERH) exhibited DPPH and metal chelating activity with IC50 values of 464 ± 28.3 μg/ml, 199 ± 7.2 μg/ml whereas the reducing power and antioxidant activities are found to be 289 ± 14.6 AAE/mg, 468 ± 22.7 GAE/mg. The observed antioxidant activities could be correlated with metabolites such as polyphenol, flavonoid, and terpenoid group of compounds identified in hexane fraction of E. repens by 4D GCXGC TOF-MS. Further ERH was evaluated for its protective properties against macromolecules such as DNA, protein and lipid damage. The extract showed protection against H2O2 induced DNA damage and inhibited AAPH induced protein oxidation and lipid peroxidation. Moreover, ERH administration to rats at 50 and 100 mg/kg inhibited carrageenan-induced paw edema, and down-regulated cytokines such as COX-2, IL-6, and TNF-α and inhibited i-NOS mediated NO generation. E. repens also exhibited antioxidant effects by restoring SOD, catalase, GSH levels and inhibited lipid peroxidation in carrageenan challenged rats. Overall, the results suggest that E. repens may be useful in combating inflammation and oxidative stress.
Fruit peels often contain more bioactive substances than the edible component of the fruit. As a result, the current study was designed to use a variety of in-vitro assays to investigate the antioxidant capacity of phenolic compounds found in pomegranate (Punica granatum L.) peel. The IC50 values for DPPH free radical scavenging activity, ABTS assay, and lipid peroxidation inhibition activity were as low as 0.1, whereas the same for hydroxyl radical scavenging activity was 0.6 μg/ml. The nitric oxide scavenging activity had the lowest IC50 value (0.02 μg/ml). At a concentration of 0.21 μg/ml, phenolics scavenged ∼60% of DPPH radicals, while at a phenolic content of 98.9 μg/ml, the extract chelated 60% of the iron metal. The RP0.5AU value of total reducing power was 0.37 μg/ml. Total antioxidant activity (AO0.5AU value of 4.24 μg/ml) was significantly lower than the standard (8.42 g/ml). At a dose of 0.09 μg/ml, phenolics reduced lipid peroxidation by 53% in an egg homogenate model. Gel electrophoresis indicated that the extracts with phenolic content of 20 and 40 μg virtually protected the BSA against AAPH-induced oxidation. Overall, various experiments showed that pomegranate peel extract has significant antioxidant activity and supports its use as a source of natural antioxidants to combat autoxidation-induced pathologies or diseases and use in the health food/nutraceutical/pharmaceutical industry for a variety of applications.
Humans experience different kinds of stress as a part of the day to day activity. The manifestation of stress will aggravate based on the physical conditions of individuals and due to their socio-economic situation of living. Herbal extracts have long been used in the traditional systems of medicine for the treatment of various ailments because of their potent antioxidant activity and lesser or no side-effects. Recently, there is a surge of interest toward the search of natural substances with diverse pharmacological activities, that can scavenge free radicals and protect cells from oxidative damage and apoptosis because of the adverse effects associated with the use of conventional medicines. Celastrus paniculatus is an endangered medicinal plant used from years in the traditional Ayurvedic system of medicine. The review presents the diverse chemical constituents of C. paniculatus and their pharmacological actions such as neuroprotective, memory-enhancing, anti-depressant, anxiolytic, anti-aging, hypolipidemic, anticancerous, analgesic, anti-inflammatory, antioxidant, anti-apoptotic, gastroprotective, anti-ulcerative properties at the cellular and molecular level based on the pre-clinical and clinical reports available. In the present review, we gathered the information from sources such as Google Scholar, Science direct, PUBMED, and reviewed with a special focus on the mode of action of C. paniculatus at molecular biology from the data on animal and preclinical experiments to cure various ailments. These diverse medicinal values of C. paniculatus demonstrates its value as traditional medicine as a cure for multiple maladies.
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