Morus Alba Fruit Extract and its Fractions Ameliorate Streptozotocin Induced Cognitive Deficit in Mice via Modulating Oxidative and Cholinergic Systems.

Increased oxidative stress and acetylcholinesterase (AChE) activity are key pathological characters contributing to the memory disorders. Thus, drugs targeting both oxidative stress and AChE are being explored for the management of cognitive dysfunction. Morus alba fruits (commonly consumed for its high nutritious value) are known to have antioxidant and AChE inhibitory effects. However, the role of Morus alba fruits in the management of memory disorders has not reported yet. This investigation was conducted to assess the antioxidant and AChE inhibitory potential of Morus alba fruit extracts in-vitro and to identify the components responsible for such effects. Further, the obtained bioactive component was studied for possible memory improvement effects against streptozotocin (STZ) induced dementia. To isolate the bioactive component in-vitro DPPH and AChE assays guided fractionation was performed. Memory functions in mice were determined using Morris Water Maze test while brain biochemical parameters were measured to understand the mechanism of action. In-vitro assays revealed strong AChE and DPPH inhibitory potential of methanol extract (ME), therefore, it was further fractionated. Among various fractions obtained, ethyl-acetate fraction (EAF) was found to possess marked AChE and DPPH inhibitory activities. On subsequent fractionation of EAF, bioactivity of obtained sub-fractions was found to be inferior to EAF. Further, both ME and EAF improved STZ (intracerebroventricular) induced cognitive dysfunction in animals by restoring endogenous antioxidant status (superoxide dismutase and reduced glutathione) and reducing thiobarbituric acid reactive species and nitric oxide levels along with brain AChE and myeloperoxidase activity. TLC densitometric studies showed appreciable levels of phenolic acids and quercetin in both EAF and ME. It can be concluded that Morus alba fruit extract has the ability to modulate cholinergic and oxidative system due to presence of phenolic and flavonoid compounds and hence, could aid in the management of memory disorders.

Morus alba fruit diet ameliorates cognitive deficit in mouse model of streptozotocin-induced memory impairment.

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.

Anti-depressant like effects of quercetin 4'-O-glucoside from Allium cepa via regulation of brain oxidative stress and monoamine levels in mice subjected to unpredictable chronic mild stress.

Objectives: Depression is a common neuropsychiatric disorder. The available pharmacotherapy is ineffective for a substantial proportion of patients and has numerous side effects. Therefore, finding safer drugs for the management of depression is of paramount importance. The present study was aimed to identify the compound responsible for anti-depressant like effects of Allium cepa outer scale extract (ACE) and to elucidate its mechanism of action. Methods:The anti-depressant compound from ACE was separated using bioactivity guided fractionation. Furthermore, mouse model of unpredictable chronic mild stress (UCMS) induced depressive behaviour was employed to investigate the anti-depressant like activity and potential mechanism of bioactive compound using behavioural tests (forced swim test (FST), sucrose preference test (SPT), open field test (OFT)) as well as by assessing brain oxidative stress, monoamine oxidase A and serotonin levels. Results:ACE and its ethylacetate fraction (EF) showed marked anti-depressant like effects in mice in the FST model. Chromatographic and spectroscopic studies of EF lead to the isolation of quercetin and quercetin 4'-O-glucoside (QG). Of these, QG (20 mg/kg) treated animals showed activity similar to that shown by fluoxetine in mice using FST. Thus, QG was tested for anti-depressant like activity against UCMS induced depressive behaviour in mice. Treatment of UCMS- exposed mice with QG (20 mg/kg) improved UCMS induced behaviour anomalies and restored brain biochemical parameters (oxidative stress, MAO-A activity and serotonin levels). Discussion:QG is responsible for anti-depressant like effects of ACE possibly via prevention of brain oxidative stress and restoring serotonin levels by inhibiting MAO-A activity.

Improvement of cognitive function in mice by Citrus reticulata var. kinnow via modulation of central cholinergic system and oxidative stress.

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.

Phytochemical and Ethnopharmacological Perspectives of Ehretia laevis.

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.

Proximate composition and element contents of selected species of Ganoderma with reference to dietary intakes.

Ganoderma is a wood-degrading mushroom that is treasured as a functional food since primitive times. Monitoring of macronutrient and element levels in mushrooms collected from the natural environment provides basic information in terms of safety, regulation, and nutrition. A comparative study was developed on the proximate and element contents of Ganoderma applanatum, G. brownii, G. lucidum, and G. philippii collected from different zones of the natural forests in Uttarakhand, India. These mushrooms revealed high amounts of proteins (9.29-12.4%) and carbohydrates (75.5-80.3%) and low contents of fats (1.62-2.87%), but ash (6.14-8.32%) and fibre (4.92-8.07%) were available in significant amounts. Element concentrations were determined by wavelength dispersive X-ray fluorescence (WDXRF) spectrometry. Calcium (5400-19,250 mg/kg) and potassium (2602-5601 mg/kg) were the predominant elements in mushrooms. The mushroom samples provided significant percentage contribution to reference recommended dietary intakes (RDIs) of essential elements such as calcium (27.0-96.3%), copper (58.2-95.8%), and manganese (37.3-62.3%), for adult males and females; and iron (35.3-97.1% for males and 28.6-78.6% for females), magnesium (7.06-11.5% for males and 7.74-12.6% for females), and zinc (6.35-19.8% for males and 7.65-23.7% for females). The studied mushrooms have no health risks as toxic metals such as aluminium and lead were detected below the legislated respective provisional tolerable intake values. Nutritional quality index (NQI) values revealed that mushrooms are densely rich in calcium, copper, iron, magnesium, manganese, and zinc.

Improvement of memory and neurological deficit with Ocimum basilicum L. extract after ischemia reperfusion induced cerebral injury in mice.

Oxidative stress is strongly implicated in the pathogenesis of stroke. Strategies using antioxidants to improve neurological functions after stroke have, thus, gained significant attention. Ocimum basilicum L. is used traditionally to treat CNS disorders. Its antioxidant capacity is well established. Our laboratory has reported protective effects of pre-treatment with O. basilicum in experimental stroke, but its curative (post-treatment) effects in ischemic stroke have not been documented. Hence, the present study was aimed to evaluate the effect of O. basilicum leaf extract (OBLE) on functional outcomes following cerebral injury in mice. Cerebral injury was induced in the experimental animals by bilateral common carotid artery occlusion (BCCAO) followed by reperfusion. OBLE treatment (200 and 400 mg/kg; orally, once daily) was given for 7 days after BCCAO. Cognitive outcomes and sensorimotor disturbances were evaluated with Morris Water Maze, Elevated Plus Maze and neurological severity score, respectively. TTC (2,3,5-triphenyltetrazolium chloride) staining was used to measure cerebral infarct size. Thiobarbituric acid reactive substances, reduced glutathione levels and superoxide dismutase activity in mice brain homogenate were estimated to elucidate the neuroprotective mechanism of OBLE. Treatment with OBLE resulted in marked improvement in memory and motor coordination. OBLE also decreased cerebral infarct size and oxidative stress in mice. The extract was standardised with respect to total phenol content; an HPLC-PDA analysis showed the presence of eight phenolic acids in OBLE. It is concluded that treatment with OBLE improves functional outcomes after ischemic stroke and this may be developed as a neuroprotective drug.

Preserving neural retina through re-emerging herbal interventions.

Eye related diseases such as glaucoma, diabetic retinopathy, cataract, conjunctivitis are very common worldwide. With the current scenario India will be among the top five countries in the number of glaucoma cases. Limited discovery of successful drugs for the treatment of such diseases led scientists to look towards the use of conventional sources for treatment. Herbal extracts from Ayurveda have remained an important part of treatment regime in many parts of world even today. For this reason, local herbs possessing curative properties are still being used by local inhabitants due to its anti-inflammatory and antioxidant properties. Because retinal damage involves alterations in oxidative enzymes, blood flow changes and increase in apoptotic signals, herbal extracts are being tested for their ability to moderate antioxidant machinery and trigger neuroprotective pathways. The present review summarizes some of such herbal extracts which have been tested for their neuroprotective role in eye related diseases. The active components that exert neuroprotective effects have also been discussed along with possible mechanisms of action.

5,7-dihydroxy-3',4',5'-trimethoxyflavone mitigates lead induced neurotoxicity in rats via its chelating, antioxidant, anti-inflammatory and monoaminergic properties.

Chronic exposure to lead (Pb) induces neurodegenerative changes in animals and humans. Drugs with strong antioxidant properties are effective against Pb-mediated neurotoxicity. In a prior study, we identified 5,7-dihydroxy-3',4',5'-trimethoxyflavone (TMF) from Ocimum basilicum L. leaves as a potent antioxidant and neuroprotective compound. This research explores TMF's neuroprotective effects against Pb-induced brain toxicity in rats to establish it as a therapeutic agent. Rats received lead acetate (100 mg/kg, orally, once daily) for 30 days to induce brain injury, followed by TMF treatment (5 and 10 mg/kg, oral, once daily) 30 min later. Cognitive and motor functions were assessed using Morris Water Maze and horizontal bar tests. Lead, monoamine oxidase (MAO) A and B enzymes, reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), Tumor necrosis factor-alpha (TNF-α), and IL-6 levels were measured in the hippocampus and cerebellum. Pb exposure impaired cognitive and motor functions, increased Pb, TBARS, TNF-α, and IL-6 levels, and compromised MAO A & B and GSH levels. TMF reversed Pb-induced memory and motor deficits and normalized biochemical anomalies. TMF's neuroprotective effects against lead involve chelating, antioxidant, anti-inflammatory, and monoaminergic properties, suggesting its potential as a treatment for metal-induced brain injury.

Fatty Acids Composition of Basidiocarps of Some Wood Associated Medicinal Mushrooms (Agaricomycetes) from India.

In this investigation, crude fat contents and fatty acid compositions of lipids present in the basidiocarps of widely distributed, medicinally important, wild mushrooms (Fuscoporia torulosa, Inonotus pachyphloeus, Phellinus allardii, Ph. fastuosus, Ph. gilvus and Ph. sanfordii) collected from different localities of Dehradun, Uttarakhand, India were analyzed. Gas chromatography with flame ionization detector was performed to identify and quantify the individual fatty acids present in the lipids of each mushroom. Mushrooms exhibited comparable amounts of crude fats with maximum content (0.35%) in Ph. sanfordii. The dominant fatty acid in the examined mushrooms was palmitic acid (C16:0). Oleic acid (C18:1n9c) and linoleic acid (C18:2n6c) exhibited maximum contents among the monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), respectively. Saturated fatty acids (SFAs) in F. torulosa, I. pachyphloeus and Ph. fastuosus were at higher concentrations than unsaturated fatty acids (UFAs). Ph. allardii, Ph. gilvus and Ph. sanfordii exhibited greater amounts of UFAs compared with SFAs. Among UFAs, MUFAs dominated the polyunsaturated ones except for I. pachyphloeus and Ph. sanfordii. Of the polyunsaturated fatty acids (PUFAs), the contents of ω6 PUFAs were higher than ω3 PUFAs except for Ph. gilvus. Interestingly, a single trans fatty acid, elaidic acid (C18:1n-9t) (0.54-2.34%) was noticed in F. torulosa, Ph. fastuosus and Ph. sanfordii only. The examined mushrooms also differed in UFAs/SFAs, MUFAs/SFAs, PUFAs/SFAs, ∑ω6/∑ω3 and (linoleic acid) C18:2n6c/(oleic acid) C18:1n9c ratios. The presence of essential and non-essential fatty acids may make the examined mushrooms befitting candidates for use in nutraceuticals and pharmaceuticals.

Mineral Elements and Vitamins from Wild Wood Inhabiting Basidiocarps of Some Medicinal Mushrooms (Agaricomycetes) from India.

Mushrooms are rich in various nutrients and secondary metabolites. In this study, the contents of macroelements, trace elements, and some nonessential elements of wild basidiocarps of Fuscoporia torulosa, Inonotus pachyphloeus, Phellinus allardii, Ph. fastuosus, Ph. gilvus, and Ph. sanfordii (Hymenochaetaceae) collected from India was determined with wavelength dispersive X-ray fluorescence spectrometry. Vitamins A, C, D2, and E (α-tocopherol) contents were analyzed with high-performance liquid chromatography and titration methods. Ph. gilvus contained the highest number (n = 21) and highest content of most of the elements. The mushrooms were rich in microelements, including Ca (80-2610 mg/kg dw), Cl (39.63-240 mg/kg dw), K (246.7-2620 mg/kg dw), Mg (96.6-500 mg/kg dw), Na (9.56-56 mg/kg dw), P (39.5-126.7 mg/kg dw), and S (69.37-170 mg/kg dw). Many trace elements (Co, Cr, Cu, Fe, Mn, Mo, Ni, Si, V, and Zn) and some nonessential elements (Al, Ba, Br, Rb, Sr, Ti, and Zr) were also detected in the mushroom species tested. There was a significant (P < 0.05) correlation (r > 0.9) between Al and Fe as well as Cu and Ti pairs. Correlation data provide an indication of interrelations between any two elements. Among vitamins, C (9.32 mg/100 g dw) and D2 (1.55 mg/100 g dw) were found in the highest amount in F. torulosa, while the lowest vitamin contents were present in Ph. fastuosus and Ph. allardii, respectively. Vitamins A and E were below the quantification limits. These results will be beneficial in deciding on the amount of these mushrooms in nutraceutical and drug formulations.

Mechanistic Insights and Docking Studies of Phytomolecules as Potential Candidates in the Management of Cancer.

BACKGROUND: Cancer is a leading risk of death globally. According to the World Health Organization, it is presently the second most important disease that causes death in both developing and developed countries. Remarkable progress has been made in the war against cancer with the development of numerous novel chemotherapy agents. However, it remains an immense challenge to discover new efficient therapeutic potential candidates to combat cancer. OBJECTIVES: The majority of the currently used anticancer drugs are of natural origins, such as curcumin, colchicine, vinca alkaloid, paclitaxel, bergenin, taxols, and combretastatin. Concerning this, this review article presents the structure of the most potent molecules along with IC50 values, structure-activity relationships, mechanistic studies, docking studies, in silico studies of phytomolecules, and important key findings on human cancer cell lines. METHODS: A viewpoint of drug design and development of antiproliferative agents from natural phytomolecules has been established by searching peer-reviewed literature from Google Scholar, PubMed, Scopus, Springer, Science Direct, and Web of Science over the past few years. RESULTS: Our analysis revealed that this article would assist chemical biologists and medicinal chemists in industry and academia in gaining insights into the anticancer potential of phytomolecules. CONCLUSION: In vitro and in silico studies present phytomolecules, such as curcumin, colchicine, vinca alkaloids, colchicine, bergenin, combretastatin, and taxol encompassing anticancer agents, offerings abundant sanguinity and capacity in the arena of drug discovery to inspire the investigators towards the continual investigations on these phytomolecules. It is extremely expected that efforts in this track will strengthen and grant some budding cancer therapeutics candidates in the near future.

Trimethoxyflavones from Ocimum basilicum L. leaves improve long term memory in mice by modulating multiple pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, Ocimum basilicum L. leaves (OB) are recommended for various brain disorders. AIM OF THE STUDY: Scientific evidence highlights the cognition improvement capacity of Ocimum basilicum L. leave extract (OBE), however, the compound(s) responsible for this effect and the associated mechanism was not reported. The present study was, thus, designed to isolate and identify the compound responsible for memory improvement effects of OB and to delineate the associated mechanism of action. MATERIALS AND METHODS: In-vitro acetylcholinesterase (AChE) inhibitory (Ellman method) and antioxidant (DPPH scavenging) assays guided fractionation was employed to isolate the bioactive compounds from OBE. The isolated compounds were characterised using spectroscopic techniques (FTIR, NMR and MS). In-silico and in-vivo [mouse model of scopolamine (SCOP) induced amnesia] investigations were used to substantiate the memory improvement effects of isolated compounds and to understand their mechanism of action. RESULTS: AChE and DPPH assays guided fractionation of OBE lead to isolation of two pure compounds namely, 5,7-dihydroxy-3',4',5'-trimethoxyflavone (S1) and 3-hydroxy-3',4',5'-trimethoxyflavone (S2). Both S1 and S2 mitigated the cognitive impairment due to SCOP in mice by reducing brain AChE activity, TBARS, TNF-α, IL-1ß, IL-6 and caspase-3 concentrations and elevating reduced glutathione and IL-10 levels; together with amelioration of brain hippocampus histopathological aberration (H and E staining). Moreover, the molecular docking of S1 and S2 at the active pockets of AChE and caspase-3 has shown good interactions with vital amino acid residues. CONCLUSIONS: Our findings show that trimethoxy flavones are responsible for the memory improvement effect of OBE due to their anticholinergic, antioxidant, anti-inflammatory and anti-apoptotic properties. These maybe developed as valuable alternatives for management of cognitive disorders.

Cerebroprotective effect of Ocimum gratissimum against focal ischemia and reperfusion-induced cerebral injury.

CONTEXT: Oxidative stress is believed to increase delayed neuronal death in the brain following ischemia. As a consequence, many attempts to reduce the damage resulting from cerebral ischemia under more highly oxidized conditions have focused on treatments aimed at maintaining the redox equilibrium of the local environment. Many antioxidants were shown to be neuroprotective in experimental models of cerebral ischemia and reperfusion. OBJECTIVE: The present study was designed to investigate the potential protective effects of ethanol extract of Ocimum gratissimum Linn. (Lamiaceae) (EEOg) against focal ischemia and reperfusion (I/R) insult in rat brain. MATERIALS AND METHODS: The animal model of focal I/R was established by occluding the middle cerebral artery (MCA) of male Wistar rats for 2 h, followed by 24 h reperfusion. The thiobarbituric acid reactive substances concentration, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were determined by colorimetric assays. The characterization and quantitative analysis of phenolic content was determined using HPLC. RESULTS: MCA occlusion led to significant rise in cerebral infarct volume and lipid peroxidation, and depletion in SOD and GPx in brain. The neurological deficits were also significantly elevated by MCA occlusion. All the brain oxidative stress, damage and neurological deficits were significantly attenuated by pre-treatment with EEOg (150 or 300 mg/kg, p.o.). CONCLUSION: The overall finding suggests the neuroprotective potential of O. gratissimum in cerebral ischemia, and is mediated through its antioxidant activity. Therefore, O. gratissimum should be investigated further as a possible strategy against cerebral stroke.

Bioactivity-directed isolation, characterization, and quantification of an anxiolytic flavonoid from Brassica oleracea L.

Brassica oleracea L. or Broccoli, is known for its numerous health benefits attributed to the rich array of phytochemicals. Our earlier study showed the hydroalcoholic extract of Broccoli had significant antianxiety activity. The present study involved bioactivity-directed fractionation of the active extract with the aim of separating the constituent responsible for the activity. The bioactive extract was fractionated by column chromatography. The antianxiety activity of the obtained fractions and sub-fractions was evaluated using the elevated plus maze model in mice. It led to the isolation of the bioactive compound. The antianxiety effect was confirmed by hole-board test and mirror chamber test. Structure of the compound was characterized by UV, IR, 1 H NMR, 13 C NMR, MS techniques, and was found to be kaempferol-3-O-ß-D-glucoside. The content of kaempferol-3-O-ß-D-glucoside in florets of B. oleracea was determined by HPTLC. It was found to be present to the extent of 0.061% w/w. PRACTICAL APPLICATIONS: Anxiety disorders cause immense suffering worldwide and hence search for safe and effective antianxiety drugs has become important area of research. Most commonly and widely prescribed drugs for anxiety that is, benzodiazepines may cause many adverse effects such as drowsiness, confusion, dizziness etc. They also cause physical dependence and withdrawal symptoms. Flavonoids, and their semi-synthetic derivatives, moreover, do not cause any such side effects unlike benzodiazepines. Broccoli or Brassica oleracea is reported to contain a number of flavonoids like quercetin, kaempferol, and their derivatives. In the present investigation, bioactivity-guided isolation showed that the antianxiety activity of B. oleracea is due to kaempferol-3-O-ß-D-glucoside, a compound which has been earlier reported to be present in B. oleracea. Hence, after detailed investigation this compound can be developed into a potential antianxiety drug.

In Vitro and In Vivo Antihyperglycemic Activities of Medicinal Mushrooms (Agaricomycetes) from India.

Recent research focuses on exploring natural resources to improve the management of type 2 diabetes and to reduce the precarious health effects of synthetic drugs. This investigation aimed to appraise the antihyperglycemic potential of hydroalcoholic (70% ethanol) extracts of Inonotus pachyphloeus, Phellinus allardii, Ph. fastuosus, Ph. gilvus, Ph. sanfordii, and Ph. torulosus. Antihyperglycemic potential was screened using an in vitro inhibition of enzymatic starch digestion assay model. The amount of glucose liberation was determined using the 3,5-dinitrosalicylic acid method. Mushroom extracts showed a concentration-dependent inhibition of α-amyalse and α-glucosidase and a consequent decrease in glucose liberation. Extracts of Ph. fastuosus (half-maximal inhibitory concentration [IC50] = 27.33 ± 1.45 mg/mL) and Ph. sanfordii (IC50 = 30.33 ± 0.88 mg/mL) causing comparable inhibition of α-amyalse and α-glucosidase and decreased glucose liberation were evaluated in vivo through oral starch tolerance and oral glucose tolerance tests using Wistar albino rats. Acarbose (10 mg/kg body weight) was used as a positive control. The extracts of Ph. fastuosus and Ph. sanfordii (100, 200, and 400 mg/kg body weight) showed a dose-dependent decrease in blood glucose concentration, and this decrease was greater in starch-fed rats than in glucose-loaded rats. Ph. fastuosus and Ph. sanfordii extracts (200 and 400 mg/kg body weight) significantly reduced postprandial hyperglycemic peaks in rats challenged with excess starch and glucose. This decrease was statistically comparable to acarbose with Ph. fastuosus extract (400 mg/kg body weight). Thus, it may be concluded that the antihyperglycemic effect of Ph. fastuosus and Ph. sanfordii is mediated by inhibition of starch digestion (inhibition of α-amylase and α-glucosidase). Hence, Ph. fastuosus and Ph. sanfordii can be developed as natural antidiabetic drugs after detailed pharmacological studies.

Natural Product-Based Studies for the Management of Castration-Resistant Prostate Cancer: Computational to Clinical Studies.

Background: With prostate cancer being the fifth-greatest cause of cancer mortality in 2020, there is a dire need to expand the available treatment options. Castration-resistant prostate cancer (CRPC) progresses despite androgen depletion therapy. The mechanisms of resistance are yet to be fully discovered. However, it is hypothesized that androgens depletion enables androgen-independent cells to proliferate and recolonize the tumor. Objectives: Natural bioactive compounds from edible plants and herbal remedies might potentially address this need. This review compiles the available cheminformatics-based studies and the translational studies regarding the use of natural products to manage CRPC. Methods: PubMed and Google Scholar searches for preclinical studies were performed, while ClinicalTrials.gov and PubMed were searched for clinical updates. Studies that were not in English and not available as full text were excluded. The period of literature covered was from 1985 to the present. Results and Conclusion: Our analysis suggested that natural compounds exert beneficial effects due to their broad-spectrum molecular disease-associated targets. In vitro and in vivo studies revealed several bioactive compounds, including rutaecarpine, berberine, curcumin, other flavonoids, pentacyclic triterpenoids, and steroid-based phytochemicals. Molecular modeling tools, including machine and deep learning, have made the analysis more comprehensive. Preclinical and clinical studies on resveratrol, soy isoflavone, lycopene, quercetin, and gossypol have further validated the translational potential of the natural products in the management of prostate cancer.

In Vitro Antioxidant Efficacy of Some Selected Medicinal Mushrooms from India.

Oxidative stress is strongly implicated in aging and in the progression of diseases. Antioxidants, especially of natural origin, are valued for their protective as well as curative health benefits. Numerous mushroom species have shown marked antioxidant effect. This can prove beneficial when mushrooms are used as nutraceuticals or for drug development. In the current investigation the antioxidant potential of some medicinal mushrooms, namely Inonotus pachyphloeus, Phellinus allardii, Ph. fastuosus, Ph. sanfordii and Ph. torulosus was examined employing different assays. The ethanol extracts of the fruiting bodies of these mushrooms were evaluated in vitro for scavenging potential against DPPH, hydroxyl radicals, superoxide radicals, as well as the reducing power. The free radical scavenging activity of mushroom extracts followed the trend of Ph. fastuosus > Ph. sanfordii > Inonotus pachyphloeus > Ph. torulosus > Ph. allardii. Ph. fastuosus and Ph. sanfordii extracts exhibited significant DPPH and superoxide radical scavenging activities, statistically (P < 0.05) comparable to each other and to the standard catechin. Ph. fastuosus extract (EC50 = 16 ± 1.15 µg/mL) showed the most significant hydroxyl radical scavenging activity even higher than the standard. In reducing power assay, Ph. torulosus extract (EC50 = 320 ± 0.02 µg/mL) exhibited the most significant reducing power statistically (P < 0.05) comparable with the reduced form of glutathione. The tested mushroom extracts were found to consist of appreciable amounts of carbohydrates, phenols and proteins. The free radical scavenging efficacy of the examined mushrooms showed positive correlation with their phenol content. These medicinal mushrooms are good natural antioxidants and can be incorporated in nutraceuticals/pharmaceuticals after detailed studies.

Allium cepa fraction attenuates STZ-induced dementia via cholinesterase inhibition and amelioration of oxidative stress in mice.

Background An earlier study demonstrated significant antioxidant and anticholinesterase activities of hydromethanol extract (HME) of Allium cepa. The aim of the study was to investigate the component responsible for these activities followed by an in vivo study. Methods In vitro antioxidant and anticholinesterase activities of standardized ethylacetate fraction (EAF) of HME were assessed. Bioactivity-guided fractionation showed that, as compared with its subfractions, EAF had most significant activity in 2,2-diphenyl-1-picrylhydrazyl and Ellman assays. Thus, EAF was further examined using a streptozotocin (STZ)-induced model of Alzheimer's disease in mice. STZ was injected intracerebroventricularly on days 1 and 3 (3 mg/kg) in mice. EAF was thereafter administered (42, 84, and 168 mg/kg b.w./day p.o.) from days 9 to 22. The Morris water maze test was used to evaluate learning and memory in mice. Acetylcholinesterase (AChE) activity and oxidative stress markers were assessed in the brain homogenates of mice. Additionally, histopathological studies were performed to observe effects in the brain at the cellular level. EAF was standardized based on quercetin and quercetin 4'-O-glucoside content using a validated thin layer chromatography densitometric method. Results STZ produced significant (p < 0.05) memory impairment along with oxidative stress and a cholinergic deficit in mice. EAF treatment ameliorated STZ-induced behavioral deficits and biochemical alterations in mice in a significant and dose-dependent manner. Conclusions Our results show that EAF is efficacious in improving memory and learning via AChE inhibition and antioxidant activity in the mice brain. Thus, AC could be explored further to find out a lead candidate for Alzheimer's disease.

Isolation and characterization of components responsible for neuroprotective effects of Allium cepa outer scale extract against ischemia reperfusion induced cerebral injury in mice.

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.