Fisetin ameliorates polycystic ovary syndrome in rats via a mechanistic modulation of AMP-activated protein kinase and SIRT1 molecular pathway.

Fisetin, a polyphenolic flavonoid, exhibits numerous pharmacological activities against metabolic syndromes. The present research aims to explore the therapeutic efficacy of fisetin in experimental polycystic ovary syndrome (PCOS). Female Sprague-Dawley rats were administered mifepristone (20 mg/kg/day) to induce PCOS. PCOS rats were treated with fisetin (20 mg/kg and 40 mg/kg) and further compared with metformin HCl, the conventional drug for PCOS. The mechanism of fisetin was explored using dorsomorphin (an AMPK inhibitor). Then, rats were sacrificed for further analysis of biochemical and histological parameters. PCOS rats exhibited irregular estrous cycles, increased serum testosterone (4.72 ± 0.139 ng/ml), estradiol (750.2 ± 16.56 pg/ml), LH (30.33 ± 1.563 mIU/ml), HOMA-IR (1.115 ± 0.049), TNF-α (86.59 ± 3.93 pg/ml), IL-6 (55.34 ± 4.432 pg/ml), and TBARS (3.867 ± 0.193 µmol/mg) along with declined progesterone (11.67 ± 1.54 ng/ml), FSH (13.33 ± 1.256 mIU/ml), GSH (33.47 ± 1.348 µmol/mg) levels, and SOD (2.163 ± 0.298 U/mg) activity as compared to normal control group. Fisetin high dose significantly lowers testosterone (3.014 ± 0.234 ng/ml), estradiol (533.7 ± 15.39 pg/ml), LH (16.67 ± 1.62 mIU/ml), HOMA-IR (0.339 ± 0.20), TNF-α (46.02 ± 2.66 pg/ml), IL-6 (31.77 ± 3.47 pg/ml), and TBARS (1.747 ± 0.185 µmol/mg) and enhances progesterone (33.17 ± 1.447 ng/ml), FSH (27.17 ± 1.42 mIU/ml), GSH (60.35 ± 1.1.102 µmol/mg) levels, and SOD (4.513 ± 0.607 U/mg) activity. The histology of ovarian tissues shows a significant increase in cystic follicles in PCOS rats compared with the normal control group. These alterations were attenuated with fisetin treatment. Administration of dorsomorphin with fisetin can reverse the beneficial effects of fisetin in PCOS rats. Altogether, these present findings highlight the potential of fisetin as a promising therapeutic intervention for the management of PCOS by modulating AMPK/SIRT1 signaling in rats.

The futuristic applications of transition metal dichalcogenides for cancer therapy.

The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.

Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression.

Depression is a condition characterized by low mood and an aversion to activity, that causes behavioral problems, poor quality of life and limits daily life activities. It is considered as the fourth leading cause of disability worldwide. Selective Serotonin Reuptake Inhibitors (SSRIs) Monoamine Oxidase (MAO) inhibitors, Tricyclic Antidepressants (TCAs), and atypical antidepressants are some of the conventional medications used to treat depression. However, only about half of patients with major depressive disorder (MDD) respond effectively to first-line antidepressant therapy. Additionally, there are a number of drawbacks to standard antidepressants, such as anti-cholinergic side effects, drug-drug interactions, and food-drug interactions, which prompts researchers to look at alternative approaches to the treatment of depression. Medicinal plants and their metabolites are extensively tested for their efficacy against depression. Electronic databases such as Google scholar, Science Direct, SciFinder and PubMed were used to search relevant literature on the role of polyphenols in depression. Plants-derived Polyphenols represent a major class of compounds extensively distributed in plants. Number of polyphenols have demonstrated antidepressant activity, among which berberine, piperine, curcumin, naringenin, ascorbic acid and ginsenosides are extensively evaluated. The medicinal plants and their derived compounds mediated synthesized green nanoparticles have also exhibited considerable efficacy in the management of depression. The therapeutic effects of these phytochemicals is mediated via differentiation and inhibition of neuronal cell apoptosis, promotion of neuronal cell survival and modulation of key neurotransmitters. The aim of this study is to review compressively the chemical, pharmacological and neurological evidence showing the potential of polyphenols in depression.

Herbal Arsenal against Skin Ailments: A Review Supported by In Silico Molecular Docking Studies.

Maintaining healthy skin is important for a healthy body. At present, skin diseases are numerous, representing a major health problem affecting all ages from neonates to the elderly worldwide. Many people may develop diseases that affect the skin, including cancer, herpes, and cellulitis. Long-term conventional treatment creates complicated disorders in vital organs of the body. It also imposes socioeconomic burdens on patients. Natural treatment is cheap and claimed to be safe. The use of plants is as old as mankind. Many medicinal plants and their parts are frequently used to treat these diseases, and they are also suitable raw materials for the production of new synthetic agents. A review of some plant families, viz., Fabaceae, Asteraceae, Lamiaceae, etc., used in the treatment of skin diseases is provided with their most common compounds and in silico studies that summarize the recent data that have been collected in this area.

Fruit and Vegetable Peel-Enriched Functional Foods: Potential Avenues and Health Perspectives.

Fresh fruit and vegetables are highly utilized commodities by health-conscious consumers and represent a prominent segment in the functional and nutritional food sector. However, food processing is causing significant loss of nutritional components, and the generation of waste is creating serious economic and environmental problems. Fruit and vegetables encompass husk, peels, pods, pomace, seeds, and stems, which are usually discarded, despite being known to contain potentially beneficial compounds, such as carotenoids, dietary fibers, enzymes, and polyphenols. The emerging interest in the food industry in the nutritional and biofunctional constituents of polyphenols has prompted the utilization of fruit and vegetable waste for developing enriched and functional foods, with applications in the pharmaceutical industry. Moreover, the utilization of waste for developing diverse and crucial bioactive commodities is a fundamental step in sustainable development. Furthermore, it provides evidence regarding the applicability of fruit and vegetable waste in different food formulations especially bakery, jam, and meat based products.

Cardioprotection by Citrus grandis (L.) Peel Ethanolic Extract in Alloxan-Induced Cardiotoxicity in Diabetic Rats.

Diabetic cardiomyopathy (DCM) pathogenesis is multifarious, and there are insufficient therapeutic options to treat DCM. The present research explored the effects of Citrus grandis peel ethanolic extract (CGPE) in alloxan-induced DCM in rats. Diabetes was triggered by intraperitoneal (i.p.) injection of alloxan (150 mg/kg) in Wistar rats (200-250 g). CGPE (100, 200, and 400 mg/kg) or glibenclamide (Glib, 10 mg/kg) were administered orally for 2 weeks. After the treatment schedule, prooxidants (thiobarbituric acid reactive substances), antioxidants (glutathione, catalase, and superoxide dismutase), and inflammatory markers (tumor necrosis factor-α) were determined in cardiac tissues. Biomarkers of cell death, viz., lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) activity, glucose levels, total cholesterol (TC), and high-density lipoproteins (HDL), were assessed in the blood. Rats administered with alloxan showed a consistent increase in blood glucose level (days 7 and 14) that was lowered considerably (p < 0.001) by CGPE or Glib. Alloxan-induced increase in LDH, CK-MB, TC, and decline in HDL was attenuated (p < 0.001) in rats that were treated with CGPE or Glib. Alloxan significantly (p < 0.001) elevated oxidative stress, inflammation, and reduced antioxidants in the cardiac tissue of rats, and these pathogenic abnormalities were ameliorated (p < 0.001) by CGPE. Histopathological studies showed a decrease in morphological disruptions by alloxan in CGPE-treated rats. CGPE (400 mg/kg) significantly ameliorated biochemical parameters in comparison to the lower doses against alloxan cardiotoxicity. Citrus grandis peel extract can be an alternative in the management of DCM.

Cucurbitacin B exerts neuroprotection in a murine Alzheimer's disease model by modulating oxidative stress, inflammation, and neurotransmitter levels.

BACKGROUND: Alzheimer's disease (AD) type dementia encompasses diverse cognitive deficits marked by free radicals and pro-inflammatory cytokines mediated progressive neurodegeneration and vascular damage including the blood-brain barrier. Subsequently, an imbalance in neurotransmitters, excitotoxicity, and synaptic loss provide impetus to AD pathogenesis and perpetuate brain dysfunctions. Cucurbitacin possesses several biological properties and has shown potential in cancer, diabetes, and brain disorders. In this study, neuroprotective effects of cucurbitacin B (CuB) were investigated using the intracerebroventricular streptozotocin (STZ-ICV) AD prototype. METHODS: Wistar rats (adult males) were injected STZ-ICV (3 mg/kg) bilaterally on day(s) 1 and 3. Rats were treated with CuB (25, 50 mg/kg, i.p.) or donepezil (1 mg/kg, i.p.) for 28 days daily starting from day 1. Behavioral tests viz. locomotor activity, motor coordination, and memory functions were conducted at different time intervals. After behavioral tests, biochemical markers of oxidative mutilation, inflammatory cell demise, and neurotransmitters were assessed in the whole brain. RESULTS: CuB attenuated STZ-ICV-induced decrease in spatial memory in novel object recognition task and long-term memory in passive avoidance test. CuB diminished protein carbonyls, lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, and enhanced antioxidants in the brain of rats inoculated with STZ-ICV. A decline in inflammatory and cell death biomarkers was observed in rats treated with CuB and STZ-ICV. In neurotransmitter analysis, a decrease in acetylcholinesterase activity and glutamate levels indicated an increase in cholinergic and attenuation of excitatory transmission in the brain. GABA (γ-aminobutyric acid) levels were enhanced by CuB treatment in the STZ-ICV rat model. Histomorphometry analysis disclosed that CuB treatment caused an increase in viable neuron density in the cortex and hippocampus of rats against STZ-ICV neurotoxicity. CONCLUSIONS: It can be inferred that CuB can afford a decline in AD symptoms. CuB protects neurons against STZ-ICV toxicity that improved memory functions in rats.

The Mechanisms of Cucurbitacin E as a Neuroprotective and Memory-Enhancing Agent in a Cerebral Hypoperfusion Rat Model: Attenuation of Oxidative Stress, Inflammation, and Excitotoxicity.

Impaired cerebral hemodynamic autoregulation, vasoconstriction, and cardiovascular and metabolic dysfunctions cause cerebral hypoperfusion (CH) that triggers pro-oxidative and inflammatory events. The sequences linked to ion-channelopathies and calcium and glutamatergic excitotoxicity mechanisms resulting in widespread brain damage and neurobehavioral deficits, including memory, neurological, and sensorimotor functions. The vasodilatory, anti-inflammatory, and antioxidant activities of cucurbitacin E (CuE) can alleviate CH-induced neurobehavioral impairments. In the present study, the neuroprotective effects of CuE were explored in a rat model of CH. Wistar rats were subjected to permanent bilateral common carotid artery occlusion to induce CH on day 1 and administered CuE (0.25, 0.5 mg/kg) and/or Bay-K8644 (calcium agonist, 0.5 mg/kg) for 28 days. CH caused impairment of neurological, sensorimotor, and memory functions that were ameliorated by CuE. CuE attenuated CH-triggered lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, protein carbonyls, tumor necrosis factor-α, nuclear factor-kappaB, myeloperoxidase activity, inducible nitric oxide synthase, and matrix metalloproteinase-9 levels in brain resulting in a decrease in cell death biomarkers (lactate dehydrogenase and caspase-3). CuE decreased acetylcholinesterase activity, glutamate, and increased γ-aminobutyric acid levels in the brain. An increase in brain antioxidants was observed in CuE-treated rats subjected to CH. CuE has the potential to alleviate pathogenesis of CH and protect neurological, sensorimotor, and memory functions against CH.

Plant Polyphenols for Aging Health: Implication from Their Autophagy Modulating Properties in Age-Associated Diseases.

Polyphenols are a family of naturally occurring organic compounds, majorly present in fruits, vegetables, and cereals, characterised by multiple phenol units, including flavonoids, tannic acid, and ellagitannin. Some well-known polyphenols include resveratrol, quercetin, curcumin, epigallocatechin gallate, catechin, hesperetin, cyanidin, procyanidin, caffeic acid, and genistein. They can modulate different pathways inside the host, thereby inducing various health benefits. Autophagy is a conserved process that maintains cellular homeostasis by clearing the damaged cellular components and balancing cellular survival and overall health. Polyphenols could maintain autophagic equilibrium, thereby providing various health benefits in mediating neuroprotection and exhibiting anticancer and antidiabetic properties. They could limit brain damage by dismantling misfolded proteins and dysfunctional mitochondria, thereby activating autophagy and eliciting neuroprotection. An anticarcinogenic mechanism is stimulated by modulating canonical and non-canonical signalling pathways. Polyphenols could also decrease insulin resistance and inhibit loss of pancreatic islet ß-cell mass and function from inducing antidiabetic activity. Polyphenols are usually included in the diet and may not cause significant side effects that could be effectively used to prevent and treat major diseases and ailments.

Enrichment in Antioxidant Flavonoids of Stamen Extracts from Nymphaea lotus L. Using Ultrasonic-Assisted Extraction and Macroporous Resin Adsorption.

Nymphaea lotus L. is the medicinal plant that has long been used for food, cosmetics and traditional medicines in Africa and Asia since ancient times. Its flavonoids and other interesting phytochemical compounds from rhizome, leaf and the whole flowers have been reported in the previous published research. However, stamens, which are essential for reproductive functions, may also represent new alternative sources of potential antioxidant flavonoids, as investigated in this study. The innovative green chemistry methods, i.e., ultrasound-assisted extraction (UAE) as well as a macroporous resin (MPR) purification procedure, were employed in this current research. Using a full factorial design coupled to three-dimensional (3D) surface plot methodology, the influence of three variables, namely aqEtOH concentration (ranging from 50 to 100% (v/v), US frequency (ranging from 0 (no US applied) to 45 kHz), and the extraction duration (ranging from 20 to 60 min), were evaluated. Five MPRs with different surface areas, average pore diameters, matrix types and polarities were also investigated for the purification of total flavonoids. The optimal UAE condition is 90% (v/v) aqEtOH with 34.65 khz ultrasonic frequency and 46 min of extraction duration. Compared with the conventional heat reflux extraction (HRE) method, a significant 1.35-fold increase in total flavonoids content was obtained using optimized UAE conditions (169.64 for HRE vs. 235.45 mg/g dry weight for UAE), causing a 2.80-fold increase when this UAE associated with MPR purification (475.42 mg/g dry weight). In vitro cell free antioxidant activity of N. lotus stamen extracts and in cellulo antioxidant investigation using yeast model showed the same trend, indicating that the best antioxidant flavonoid can be found in UAE coupled with MPR purification. Moreover, in the yeast model, the expression of key antioxidant genes such as SIR2 and SOD2 were expressed at the highest level in yeast cells treated with the extract from UAE together with MPR purification. Consequently, it can be seen that the UAE combined with MPR purification can help enhance the flavonoid antioxidant potential of the stamens extract from this medicinal species.

Phytochemical Composition, Antioxidant, and Antimicrobial Attributes of Different Solvent Extracts from Myrica esculenta Buch.-Ham. ex. D. Don Leaves.

Background: Plant diversity is a basic source of food and medicine for local Himalayan communities. The current study was designed to assess the effect of different solvents (methanol, ethyl acetate, and water) on the phenolic profile, and the corresponding biological activity was studied. Methods: Antioxidant activity was investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2″-azino-bis(3-ethylbenzothiazoline-6-sulphonic) acid (ABTS) assay, while the antimicrobial activity was evaluated by disk diffusion method using various bacterial and fungal strains. Results: The outcomes demonstrated that methanol acted as the most effective solvent for polyphenols extraction, as strengthened by the liquid chromatography and mass spectroscopy (LC-MS) and fourier transform infrared spectroscopy (FTIR) analysis. M. esculenta methanol extract showed the highest DPPH and ABTS radical scavenger antioxidant activity with IC50 values of 39.29 µg/mL and 52.83 µg/mL, respectively, while the ethyl acetate and aqueous extracts revealed minimum antioxidant potential. Methanol extract also revealed higher phenolic content, 88.94±0.24 mg of equivalent gallic acid (GAE)/g), measured by the Folin-Ciocalteu method, while the minimum content was recorded for aqueous extract (62.38±0.14 GAE/g). The highest flavonoid content was observed for methanol extract, 67.44±0.14 mg quercetin equivalent (QE)/g) measured by an aluminum chloride colorimetric method, while the lowest content was recorded for aqueous extract (35.77±0.14 QE/g). Antimicrobial activity findings also reveal that the methanol extract led to a higher inhibition zone against bacterial and fungal strains. FTIR analysis reveals the presence of various functional groups, viz. alkenes, amines, carboxylic acids, amides, esters, alcohols, phenols, ketones, carboxylic acids, and aromatic compounds. This FTIR analysis could serve as a basis for the authentication of M. esculenta extracts for future industrial applications. Compounds identified by LC-MS analysis were gallic acid, myricanol, myricanone, epigallocatechin 3-O-gallate, ß-sitosterol, quercetin, p-coumaric acid, palmitic acid, n-pentadecanol, n-octadecanol, stigmasterol, oleanolic acid, n-hexadecanol, cis-ß-caryophyllene, lupeol, and myresculoside. Conclusion: This study suggests that the methanolic extract from M. esculenta leaves has strong antioxidant potential and could be a significant source of natural antioxidants and antimicrobials for functional foods formulation.

Emerging and Alternative Therapies For Parkinson Disease: An Updated Review.

Parkinson's disease (PD) is standout amongst the most common neurodegenerative malady with unpredictable dynamic pathology. At present, accessible traditional choices for PD have certain impediments of their own, and subsequently persistent consistence and fulfillment are low. Current contemporary treatment options just give symptomatic alleviation constrained control to anticipate malady progression, bringing about poor patient consistence and fulfilment. Numerous rising pharmacotherapies for PD are in various phases of medical improvement. Treatments incorporate adenosine A2A receptor antagonists, anti-apoptotic agents, monoamine oxidase inhibitors, glutamate receptor antagonists, and antioxidants for example, N-acetyl cysteine, edaravone, and coenzyme Q10. Other rising nonpharmacotherapies incorporate microRNAs, viral vector gene therapy, stem cells transglutaminases, RTP801, and glial derived neurotrophic factor (GDNF). Furthermore, surgeries including profound pallidotomy, deep brain stimulation, thalamotomy and gamma knife surgery have developed as elective mediations for cutting edge PD patients who have totally used common medications and still suffer from unrelenting motor symptoms. Complementary and Alternative medicine (CAM) modalities, such as Yoga, acupuncture, Tai Chi, Music therapies are highly practiced in several countries, offer some of the safer and effective treatment modalities for PD. While a few of these treatments hold much assurance in postponing the beginning of ailment and moderating its progression, more pharmacotherapies and careful mediations should be examined in various phases of PD. Therefore, the main objective of our review is to fill the gap between the researches and provide updated and productive information about the research reported in the last couple of years and can fulfil the most reassuring plausibility for encourage treatment of Parkinson Disease.