Richa Shri

Background: Dementia is a deliberating neurodegenerative disorder which causes impairment of intellectual functions. The USFDA approved drugs has limited efficacy and numerous side effects. Thus, finding newer drugs to manage dementia and cognitive disorders is certainly required. The present study explores the potential of a natural flavone, 5,7‐dihydroxy‐3',4',5'‐trimethoxyflavone (DHF), as memory enhancer drug against scopolamine‐induced cognitive deficit in mice.Methods: Animals were treated with DHF (5‐10 mg/kg, p.o.) for 7 days after inducing cognitive impairment by scopolamine (1mg/kg,i.p.). Memory functions (passive shock avoidance task and Morris Water Maze), brain acetylcholinesterase (AChE) activity, inflammatory markers, oxidative stress, apoptotic biomarkers and histopathological studies (H&E and congo red staining for beta amyloid) were determined to measure memory improvement effects of DHF. In‐silico (molecular docking) studies were performed to understand the interactions of DHF with key pathological enzymes related to dementia.Results: Treatment of scopolamine administered mice with DHF improved scopolamine‐induced cognitive impairment and restore brain biochemical parameters (inhibited acetylcholinesterase activity, enhanced glutathione levels, and reduced TBARS, TNF‐α, IL‐6, IL‐1β and caspase‐3 levels). Moreover, histopathological studies showed that DHF treatment reduced the neuronal cell death and amyloid depositions in mice brain. Further, molecular docking studies revealed string interactions of DHF with crucial amino acids of AChE and caspase‐3.Conclusion: These results suggest that DHF was effective in treating scopolamine induced cognitive deficit by improving cerebral cholinergic dysfunction and reducing brain oxidative stress, inflammation, apoptosis and beta‐amyloid depositions in mice. Thus, DHF could be developed as a potential alternative drug to treat memory disorders.

Background: Dementia is a deliberating neurodegenerative disorder which causes impairment of intellectual functions. The USFDA approved drugs has limited efficacy and numerous side effects. Thus, finding newer drugs to manage dementia and cognitive disorders is certainly required. The present study explores the potential of a natural flavone, 5,7‐dihydroxy‐3',4',5'‐trimethoxyflavone (DHF), as memory enhancer drug against scopolamine‐induced cognitive deficit in mice.Methods: Animals were treated with DHF (5‐10 mg/kg, p.o.) for 7 days after inducing cognitive impairment by scopolamine (1mg/kg,i.p.). Memory functions (passive shock avoidance task and Morris Water Maze), brain acetylcholinesterase (AChE) activity, inflammatory markers, oxidative stress, apoptotic biomarkers and histopathological studies (H&E and congo red staining for beta amyloid) were determined to measure memory improvement effects of DHF. In‐silico (molecular docking) studies were performed to understand the interactions of DHF with key pathological enzymes related to dementia.Results: Treatment of scopolamine administered mice with DHF improved scopolamine‐induced cognitive impairment and restore brain biochemical parameters (inhibited acetylcholinesterase activity, enhanced glutathione levels, and reduced TBARS, TNF‐α, IL‐6, IL‐1β and caspase‐3 levels). Moreover, histopathological studies showed that DHF treatment reduced the neuronal cell death and amyloid depositions in mice brain. Further, molecular docking studies revealed string interactions of DHF with crucial amino acids of AChE and caspase‐3.Conclusion: These results suggest that DHF was effective in treating scopolamine induced cognitive deficit by improving cerebral cholinergic dysfunction and reducing brain oxidative stress, inflammation, apoptosis and beta‐amyloid depositions in mice. Thus, DHF could be developed as a potential alternative drug to treat memory disorders.

Background: Increased antioxidant and anticholinesterase activity are key pathological hallmarks of Alzheimer’s disease (AD). In various Ayurvedic formulations Aegle marmelos (AM) belonging to family Rutaceae have traditionally been used as a brain tonic. However, there was no scientific validate proof of it. Hence, the present study was aimed to identify bioactive extract/fraction/constituent of AM fruit having potential to treat AD.Method: Four different crude extracts of AM fruits by using different solvents on basis of increasing polarity‐such as petroleum ether, chloroform, methanol and distilled water‐by successive Soxhlet extraction were prepared and evaluated for in‐vitro antioxidant and anticholinesterase inhibition assay by using DPPH and Ellman’s assay respectively. Most bioactive extract was further subjected to fractionation by using solvent‐solvent partioning followed by flash chromatography for further sub fractionation of most bioactive fraction. Total phenolic (TPC) and flavonoid content (TFC) was also calculatedResult: Comparative evaluation of all four prepared extracts for in‐vitro antioxidant and anticholinesterase inhibition assays showed that the methanol extract (ME) was most bioactive. Furthermore, bioactivity‐guided fractionation of this bioactive ME revealed that Dichloromethane (DCM) fraction evinced highest antioxidant and anticholinesterase activity with IC₅₀ value 74.56±1.43 µg/ml and 47.65±2.76 µg/ml due to presence of higher phenolic and flavonoid content. However, further sub‐fractionation of DCM fraction showed significantly higher IC₅₀ values thus decreased activity.Conclusion: This preliminary study clearly suggested that the DCM fraction from the ME of A. marmelos may prove to be potential candidate for the treatment of AD may be due to synergistic effect of phenolic and flavonoid content present in it. However, to validate the neuroprotective effect of DCM fraction of AM fruit against AD further exploration at cellular and molecular level is required to underlying its pharmacological mechanism as well as identification of the active phytoconstituents responsible for anti‐Alzheimer’s effect.

Mounting evidence shows that dietary intake of fruits with polyphenols is beneficial to improve impaired memory functions. This study explored the preventive as well as therapeutic effects of diet enriched with Morus alba fruits extract (DEMA) in streptozotocin (STZ) induced mouse model of memory impairment. The study consisted of two facets: one aspect consisted of pretreatment of animals with DEMA for two weeks followed by STZ (i.c.v) intervention and the second phase involved induction of dementia with STZ (i.c.v) followed by treatment with DEMA for 14 days. Cognitive functions of animals were measured by Morris Water Maze test and to delineate the associated mechanism of action, brain biochemical estimations (acetyl-cholinesterase activity, myeloperoxidase activity, thiobarbituric acid reactive species, superoxide dismutase activity, reduced glutathione and nitrite/nitrate) and histopathological studies (haematoxylin and eosin staining) were performed. Pre- and post- treatment with DEMA significantly prevented and attenuated, respectively, the detrimental effects of STZ on mice brain. The results demonstrated that dietary modification, by incorporation of M. alba fruits, reduces the incidence and aids in treatment of memory disorder in mice by reducing central cholinergic activity, decreasing oxidative stress and preventing neurodegeneration.

Wound healing is a process through which skin maintains itself. Once a wound occurs, the inflammatory and proliferative stages are instigated in reaction to injury. It is established that wound restorative comprises four stages including haemostasis, inflammation, proliferation, and remodeling. The amelioration of wound healing is very challenging as tumors can develop at the site of chronic injury. There are numerous plants, plant extracts and plant based natural products were widely used by tribal communities from ancient times for the treatment of cuts, burns, scars, burns and wounds. The therapeutic potential of these plants is recognized due to the presence of phytomolecules such as phenolic compounds, flavonoids, triterpenoids, saponins, tannins, alkaloids and glycosides. The plant used for the treatments of wound healing includes Achillea millefolium, Andrographis paniculata, Boswellia sacra, Calendula officinalis, Crocus sativus, Curcuma longa, Ehretia laevis, Ehretia microphylla, Glycyrrhiza glabra, Malva sylvestris, Rosmarinus officinalis and Salvia officinalis. This assemblage comprises the structures of phytomolecules isolated from the different extracts of these plants, mechanistic insights and important key findings responsible for wound healing. The mechanistic insights involved in wound healing are similar to cytotoxic, anti-inflammatory and antioxidant agents such as ROS generation, DNA fragmentation and western blotting. This review article is an effort to bridge the gaps in the prevailing literature and thus offers gigantic scope for researchers and academicians betrothed in validation of the customary claims and development of safer and efficient and worldwide recognized natural potential candidates as drugs for healing of wounds, burns and cuts.

Ehretia microphylla of the Boraginaceae family has been extensively used as a folklore remedy for the treatment of a wide range of ailments such as cough, cancer, allergies, and gastrointestinal and venereal disorders. Extensive literature review reports have revealed these findings due to the presence of numerous phytomolecules. To validate traditional claims for cytotoxic activity of E. microphylla, the present study was undertaken. Dried leaves of the plant were powdered and defatted with petroleum ether followed by hot continuous extraction with chloroform. The chloroform extract was subjected to in vitro cytotoxic screening against a panel of human cancer cell lines such as HCT-116 (colon), MCF-7 (breast), PC-3 (prostate), A-549 (lung), HL-60 (leukemia) and MiaPaCa-2 (pancreatic) at 50 µM using SRB assay. The extract exhibited noteworthy cytotoxicity activity against breast and lung cancer. It exhibited 85.55% and 77.93% inhibition against MCF-7 and A-549 cancer cell lines, respectively. The mechanism behind cell death was determined using the DAPI staining method, which induces alteration in nuclear morphology in MCF-7 cell lines evidenced through DAPI staining. Phytochemical screening of E. microphylla extract showed the presence of saponins, steroids, lipids, tannins and triterpenoids. The chemoprofile of the chloroform extract of E. microphylla leaves was established using an n-hexane:ethyl acetate solvent system in a ratio of 6:4. The developed chromatogram showed five spots both in visible and UV light at 254 nm. The information provided in the present study will enable further studies on the isolation and characterization of bioactive compounds/fractions by following bioactivity-guided fractionation, and thus, the plant has the potential to reduce proliferation and may induce cell death via apoptosis in breast cancer cells.

Ehretia laevis Roxb. (Boraginaceae) has been extensively used as a traditional remedy for the treatment of a diverse range of ailments related to the respiratory system, the gastrointestinal tract, the reproductive system, and against several infections. This review critically assesses and documents, for the first time, the fragmented information on E. laevis, including its botanical description, folklore uses, bioactive phyto metabolites and pharmacological activities. The goal is to explore this plant therapeutically. Ethnomedicinal surveys reveal that E. laevis has been used by tribal communities in Asian countries for the treatment of various disorders. Quantitative and qualitative phytochemical investigations of E. laevis showed the presence of important phytoconstituents such as pentacyclic triterpenoids, phenolic acids, flavonoids, fatty acids, steroids, alkaloids, aliphatic alcohols, hydrocarbons, amino acids, carbohydrates, vitamins and minerals. Fresh plant parts, crude extracts, fractions and isolated compounds have been reported to exhibit broad spectrum of therapeutic activities viz., antioxidant, antiarthritic, antidiabetic, anti-inflammatory, antiulcer, antidiarrheal, antidysenteric, wound healing and anti-infective activities. E. laevis is shown to be an excellent potential source of drugs for the mitigation of jaundice, asthma, dysentery, ulcers, diarrhea, ringworm, eczema, diabetes, fissure, syphilis, cuts and wounds, inflammation, liver problems, venereal and infectious disorders. Although few investigations authenticated its traditional uses but employed uncharacterized crude extracts of the plant, the major concerns raised are reproducibility of therapeutic efficacy and safety of plant material. The outcomes of limited pharmacological screening and reported bioactive compounds of E. laevis suggest that there is an urgent need for in-depth pharmacological investigations of the plant.

Memory disorders are a result of a number of factors, of which elevated brain oxidative stress and acetylcholinesterase (AChE) activity are significant hallmarks. A number of Citrus species have cognition-enhancing capacity mediated by their antioxidant and anti-cholinesterase activities. This study was designed to assess the cognitive-enhancing, antioxidant and anticholinesterase potentials of Citrus reticulata var. kinnow (CR) leaf extracts. CR extracts were examined by bioactivity guided fractionation using in-vitro DPPH and Ellman assays to determine antioxidant and AChE inhibitory capacity. The most active component was further evaluated for memory improvement effects using mouse model of scopolamine induced amnesia. Passive shock avoidance test and elevated plus maze test were employed to determine cognitive functions while brain biochemical parameters were measured to establish the neuroprotective mechanism. The methanol extract (ME) showed marked AChE inhibitory and antioxidant activities, therefore, it was fractionated. Comparative analysis of all obtained fractions revealed that ethylacetate fraction (EAF) was most active. Both ME and EAF improved cognitive dysfunction caused by scopolamine in mice by reducing TBARS levels and brain AChE activity. TLC densitometric studies showed appreciable levels of naringenin in ME (0.32 % w/w) and EAF (1.14 % w/w). The observed memory enhancement effects of ME and EAF could be attributed to their ability to inhibit AChE activity and antioxidant effects due to presence of flavonoids.

The antioxidant‐mediated neuroprotective effect of Allium cepa outer scale extract (ACE) in mice with cerebral ischemia‐reperfusion (I‐R) injury was demonstrated in our earlier work. The current investigation aimed at establishing the bioactive component(s) responsible for this activity. Thus ACE was fractionated into ethyl acetate (EF) and aqueous (AF) fractions. These fractions were evaluated against cerebral I‐R injury in mice. I‐R injury in mice was induced by bilateral common carotid artery occlusion followed by 24 hr reperfusion. Memory, sensorimotor functions, cerebral infarct size, and oxidative stress were measured to address the neuroprotective mechanism of test substances. EF showed marked improvement of memory and sensorimotor functions by reducing brain oxidative stress and infarct size in mice after I‐R injury. The bioactive EF was subjected to chromatographic (HPLC‐PDA, HPLC‐MS, preparative HPLC) and spectroscopic studies to isolate and identify the neuroprotective compounds. This lead to separation of three components, namely quercetin, quercetin 4′‐O‐glucoside, and the remaining fraction, from EF. The separated components were biologically evaluated. These components showed improvement in mice with I‐R injury. But, EF displayed more marked neuroprotective effects as compared to the isolated components. The distinct neuroprotective outcome of EF may be credited to the synergistic action of compounds present in EF. Further studies such as evaluation of neurotoxic effects and other possible neuroprotective mechanisms are required to develop EF as a neuroprotective drug.