This study aimed to identify chemical compounds derived from Vassobia breviflora methanolic extract using ESI-ToF-MS and their antioxidant potential activity utilizing the following methods: total phenols, DPPH, and ABTS•+. The MTT assay measured cytotoxic activity, while DCFH-DA and nitric oxide assays were employed to determine reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels using African green monkey kidney (VERO) and human keratinocyte (HaCat) cell lines. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were assessed in seven clinical isolates and nine ATCC strains. Biofilm inhibition was tested against four biofilm-forming strains. The antioxidant properties of the methanolic extract were identified as follows: 35.74 mg GAE/g (gallic acid equivalents)/g for total phenols, 10.5 µg/ml for DPPH, and 50.68 µmol trolox/µg for ABTS•+. The mean inhibitory concentration (IC50) values were 622.86 µg/ml (VERO) and 784.33 µg/ml (HaCat). These concentrations did not markedly alter levels of ROS and RNS. Conversely, Bacillus cereus β-hemolytic displayed higher sensitivity to the extract, with MIC of 64 µg/ml and MBC of 128 µg/ml. Enterococcus faecium exhibited the lowest biofilm formation among the tested bacteria. The studied plant exhibited activity against all bacterial strains at concentrations lower than the IC50 VERO and HaCat cells, suggesting potential for future studies. Data present a comprehensive molecular docking analysis against the HlyIIR protein (PDB ID: 2FX0) and determined antimicrobial and endocrine-modulating potentials. Notably, lancifodilactone I and nicandrin B demonstrated the strongest binding affinities, with binding energies of -9.8 kcal/mol and -8.3 kcal/mol, respectively, and demonstrated significant antimicrobial effects against B. cereus. In addition, several compounds showed potential interactions with nuclear receptors, indicating potential endocrine-modulating effects. These findings provide insights into developing target-specific antimicrobial therapies and endocrine-modulating agents.

Long covid describes a syndrome of persistent symptoms following COVID-19 and is responsible for substantial healthcare and economic burden. Currently, no effective treatments have been established. Ashwagandha (Withania somnifera (L.) Dunal) is a medicinal herb traditionally used in India for its immune-strengthening and anti-inflammatory properties. Withanolides, a family of steroid-derived molecules unique to Ashwagandha, have been shown to modulate inflammatory pathways in animal models, and several small randomised trials in humans support its effectiveness for reducing symptoms that are also associated with long covid. Therefore, this study aims to assess whether Ashwagandha is effective and safe for improving functional status and reducing symptom burden in adults living with long covid.

A randomised double-blind placebo-controlled trial will be performed at participating general practice (GP) surgeries and long covid clinics across the UK. Individuals diagnosed with long covid will be screened for eligibility and then randomised 1:1 to take 1000 mg daily of Ashwagandha root extract tablets (standardised to <0.9% withanolides) or matching placebo tablets for 3 months (target, n = 2500). Monthly online surveys will be performed to collect patient-reported outcomes, and monthly safety monitoring, including liver function tests, will be conducted by clinical site teams. The primary outcome of the Post-COVID Functional Status Scale score at 3 months will be assessed by baseline-adjusted ordinal logistic regression, according to a pre-published statistical analysis plan. The secondary outcomes included validated quality of life and long covid symptom scales, work status and productivity and adverse events. The trial has been approved as a Clinical Trial of an Investigational Medicinal Produce by the Medicines and Healthcare Regulatory Authority and by the NHS Research Ethics Committee and Health Research Authority.

Treatments for long covid are urgently needed. This trial will robustly evaluate the safety and efficacy of a candidate treatment with a promising efficacy and safety profile. If found to be effective, the findings will likely influence treatment guidelines and improve health outcomes in those living with long covid.

This trial was pre-registered on 15/08/2022: ISRCTN12368131.

Withania somnifera, a psychoactive plant with putative neuroprotective actions, is used in Indian traditional medicine for the treatment of neuropsychiatric and neurodegenerative disorders. However, the key mechanisms underlying the pleiotropic actions of Withania somnifera on the nervous system remain poorly understood. Given converging evidence suggests a critical role for mitochondrial dysfunction in the pathophysiology of neuropsychiatric and neurodegenerative diseases, we hypothesized that Withania somnifera may exert pleiotropic effects via targeting mitochondria. Treatment with Withania somnifera root extract (RE) or the withanolide-withanoside rich fraction (WLS) enhanced cellular ATP levels in rat cortical neurons in vitro and in the neocortex in vivo. In vivo respirometry performed on mitochondria isolated from the neocortex following RE or WLS treatment revealed increased mitochondrial respiration and OxPhos efficiency. Furthermore, WLS treatment evoked increases in mitochondrial mass, and RE and WLS treatments enhanced expression of brain derived neurotrophic factor (BDNF) and Sirtuin 1 (SIRT1), both in vitro and in vivo. Pharmacological inhibitor studies support an important role for BDNF and SIRT1 in the mitochondrial effects of Withania somnifera. Experiments with distinct phytochemical components of WLS identified withanolide A and withanoside IV as key constituents that enhance mitochondrial biogenesis and neuroenergetics. The neuroprotective actions of WLS, withanolide A and withanoside IV against corticosterone-induced neuronal cell death in vitro, required signaling via BDNF and SIRT1. Collectively, these results indicate that Withania somnifera root extract and specific phytochemical constituents robustly influence mitochondria in cortical neurons, contributing to stress adaptation and neuroprotection via BDNF and SIRT1 signaling.

Both osteoarthritis (OA) and rheumatoid arthritis (RA) are long-lasting inflammatory disorders that impact the joints. While conventional treatments like NSAIDs and DMARDs are effective, they often have adverse side effects.

The aim of this review is to explore the possibilities of using herbal treatments in treating the symptoms of arthritis, their stability and bioavailability. Traditional therapies often lead to adverse side effects, prompting a search for safer alternatives, particularly in herbal medicines. This review explores the innovative use of herbal cubosomes as advanced nanocarriers for arthritis therapy. Cubosomes, a type of self-assembled lipid nanoparticle, exhibit unique structural characteristics that enhance the delivery and bioavailability of encapsulated herbal compounds.

Access was gained to PubMed, Scopus database, Google Scholar and Web of Science for the literature search. The results were later screened according to the titles, abstracts, and availability of full texts.

The expository evaluation of the literature revealed that Key herbal components, such as Withania somnifera (Ashwagandha), Curcuma longa (Turmeric) and Boswellia serrata (Frankincense) are emphasized for their anti-inflammatory characteristics and possible advantages in managing arthritis. The herbal cubosomes enhance drug absorption, retention, and release kinetics in arthritic conditions. The difficulties in delivering and maintaining herbal substances are also discussed, with a focus on how nanotechnology can help get over these obstacles.

Overall, the integration of herbal cubosomes in arthritis therapy presents a promising approach that could result in safer and more efficient treatment alternatives, warranting further research and clinical exploration.

Cancer is the second foremost cause of fatalities associated with non-communicable diseases across the globe, affecting multiple organs and often necessitating costly treatments with adverse side effects. Apoptosis, the body's natural cell death process, plays a crucial role in the prevention of cancer, but it's often disrupted in cancer cells, allowing uncontrolled proliferation. Restoring apoptosis in cancer cells is one of the promising therapeutic strategies to curb tumor growth and enhance clinical outcomes. Bcl-B, an anti-apoptotic protein within the Bcl-2 family, interacts with Bax to mitigate apoptosis, indicating it as a druggable target for cancer therapy. There's a critical need for natural, cost-effective alternatives with minimal adverse effects to reduce morbidity rates of cancer patients. Plant-based immunoprotective medications, particularly from sustainable sources like known medicinal plants, offer substantial potential for cancer treatment. This study involves comprehensive in silico approaches (byte) to evaluate the inhibition potential of the phytochemicals derived from Withania somnifera against the anti-apoptotic Bcl-B protein. Research into Bcl-B's binding affinity with 80 phytochemicals from this plant aims to identify interaction sites for promising anticancer agents. This study's focus on Bcl-B protein highlights its potential in modulating apoptotic pathways and exploring novel anti-cancer therapeutics. Through comprehensive screening based on drug-likeness and pharmacokinetic properties, combined with in-house virtual screening, molecular docking, molecular dynamics simulations, and MM/PBSA-based binding free energy analysis, three promising candidate inhibitors-Withanolide L (IMPHY009438), Withanolide M (IMPHY003143), and Withanolide A (IMPHY000090)-were identified and prioritized. These candidates showed favorable estimated binding free energy values, along with desirable drug-likeness and pharmacokinetic profiles. The results demonstrated that the selected and prioritized phytochemicals, Withanolide L, Withanolide M, and Withanolide A display comparable efficacy to Obatoclax (CID: 11404337) and other known synthetic, semi-synthetic, and natural inhibitors of Bcl-2 family proteins. These findings establish a strong bench foundation for further experimental validation and bedside application, potentially offering an alternative natural approach to cancer therapy.

Long-lasting brain fatigue is a consequence of stroke or traumatic brain injury associated with emotional, psychological, and physical overload, distress in hypertension, atherosclerosis, viral infection, and aging-related chronic low-grade inflammatory disorders. The pathogenesis of brain fatigue is linked to disrupted neurotransmission, the glutamate-glutamine cycle imbalance, glucose metabolism, and ATP energy supply, which are associated with multiple molecular targets and signaling pathways in neuroendocrine-immune and blood circulation systems. Regeneration of damaged brain tissue is a long-lasting multistage process, including spontaneously regulating hypothalamus-pituitary (HPA) axis-controlled anabolic-catabolic homeostasis to recover harmonized sympathoadrenal system (SAS)-mediated function, brain energy supply, and deregulated gene expression in rehabilitation. The driving mechanism of spontaneous recovery and regeneration of brain tissue is a cross-talk of mediators of neuronal, microglia, immunocompetent, and endothelial cells collectively involved in neurogenesis and angiogenesis, which plant adaptogens can target. Adaptogens are small molecules of plant origin that increase the adaptability of cells and organisms to stress by interaction with the HPA axis and SAS of the stress system (neuroendocrine-immune and cardiovascular complex), targeting multiple mediators of adaptive GPCR signaling pathways. Two major groups of adaptogens comprise (i) phenolic phenethyl and phenylpropanoid derivatives and (ii) tetracyclic and pentacyclic glycosides, whose chemical structure can be distinguished as related correspondingly to (i) monoamine neurotransmitters of SAS (epinephrine, norepinephrine, and dopamine) and (ii) steroid hormones (cortisol, testosterone, and estradiol). In this narrative review, we discuss (i) the multitarget mechanism of integrated pharmacological activity of botanical adaptogens in stress overload, ischemic stroke, and long-lasting brain fatigue; (ii) the time-dependent dual response of physiological regulatory systems to adaptogens to support homeostasis in chronic stress and overload; and (iii) the dual dose-dependent reversal (hormetic) effect of botanical adaptogens. This narrative review shows that the adaptogenic concept cannot be reduced and rectified to the various effects of adaptogens on selected molecular targets or specific modes of action without estimating their interactions within the networks of mediators of the neuroendocrine-immune complex that, in turn, regulates other pharmacological systems (cardiovascular, gastrointestinal, reproductive systems) due to numerous intra- and extracellular communications and feedback regulations. These interactions result in polyvalent action and the pleiotropic pharmacological activity of adaptogens, which is essential for characterizing adaptogens as distinct types of botanicals. They trigger the defense adaptive stress response that leads to the extension of the limits of resilience to overload, inducing brain fatigue and mental disorders. For the first time, this review justifies the neurogenesis potential of adaptogens, particularly the botanical hybrid preparation (BHP) of Arctic Root and Ashwagandha, providing a rationale for potential use in individuals experiencing long-lasting brain fatigue. The review provided insight into future research on the network pharmacology of adaptogens in preventing and rehabilitating long-lasting brain fatigue following stroke, trauma, and viral infections.

Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Traditional Medicine) for the treatment of a wide range of disorders. Plants are a rich source of diverse phytoconstituents with antidiabetic, anticancer, antimicrobial, antihypertensive, antioxidant, antihyperlipidemic, cardioprotective, immunomodulatory, and/or anti-inflammatory activities. This review focuses on the 35 plants most commonly reported for the treatment of these major disorders, with a particular emphasis on their traditional uses, phytoconstituent contents, pharmacological properties, and modes of action. Active phytomolecules with therapeutic potential include cucurbitane triterpenoids, diosgenin, and limonoids (azadiradione and gedunin), which exhibit antidiabetic properties, with cucurbitane triterpenoids specifically activating Glucose Transporter Type 4 (GLUT4) translocation. Capsaicin and curcumin demonstrate anticancer activity by deactivating NF-κB and arresting the cell cycle in the G2 phase. Antimicrobial activities have been observed for piperine, reserpine, berberine, dictamnine, chelerythrine, and allitridin, with the latter two triggering bacterial cell lysis. Quercetin, catechin, and genistein exhibit anti-inflammatory properties, with genistein specifically suppressing CD8+ cytotoxic T cell function. Ginsenoside Rg1 and ginsenoside Rg3 demonstrate potential for treating cardiovascular diseases, with ginsenoside Rg1 activating PPARα promoter, and the PI3K/Akt pathway. In contrast, ternatin, tannins, and quercitrin exhibit potential in gastrointestinal disorders, with quercitrin regulating arachidonic acid metabolism by suppressing cyclooxygenase (COX) and lipoxygenase activity. Further studies are warranted to fully investigate the clinical therapeutic benefits of these plants and their phytoconstituents, as well as to elucidate their underlying molecular mechanisms of action.

Ashwagandha (Withania somnifera (L.) Dunal) root or whole-plant extracts are used to treat anxiety, insomnia, and other nervous system disturbances.

We evaluated the neuroprotective and antidepressant effects of ashwagandha root extract (ARE) on corticosterone-exposed HT-22 cells and unpredictable chronic mild stress (UCMS)-challenged mice.

The neuroprotective properties of ARE containing withanolide A were assessed in HT-22 cells subjected to corticosterone-induced oxidative stress. Additionally, the effects of ARE on depression-like behavior, stress-related hormones, and inflammatory cytokine levels were evaluated in a mouse model of UCMS.

In HT-22 cells, ARE (100 and 200 μg/mL) and its constituent, withanolide A (1.56 and 3.12 μg/mL), mitigated corticosterone-induced increases in MAO activity, ROS, and MDA levels. Treatment also reversed corticosterone-induced reductions in BDNF, TrkB, p-AKT, p-ERK, and p-CREB and normalized Nrf2 and Keap1 levels, thereby elevating HO-1 expression. In UCMS mice, ARE improved behavioral outcomes, increased sucrose preference, and reduced immobility in the forced swimming test while enhancing activity in the open field test and elevated plus maze. ARE decreased the levels of stress hormones (corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone) and increased the levels of neurotransmitters (L-DOPA, 5-HTP, and serotonin). Histological analysis revealed that ARE reduced hippocampal cell loss. Additionally, ARE (60 and 100 mg/kg) restored decreased levels of p-AKT, p-ERK, and p-CREB and lowered inflammation-related proteins (Cox2, iNOS, IL-6, IL-1β, TNF-α).

These results indicate that ARE containing withanolide A exhibits notable neuroprotective and antidepressant properties.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of beta-amyloid (Aβ) peptides. Microglia-mediated neuroinflammation is one of the primary contributors to the pathogenesis of AD. Withanolides, the main constituents in the leaves of Datura stramonium L., exhibit anti-neuroinflammatory activity. It is unknown if total withanolide from Datura stramonium L. leaves (TWD) reduces nerve inflammation and potentially mitigates the pathogenic elements of AD. This study examined the potential effects of TWD on neuroinflammation in triple transgenic AD (3 × Tg-AD) mice and LPS-induced BV-2, as well as associated signaling pathways. HPLC-Q-TOF-MS/MS was used in this study to examine the main chemical components of the TWD extract. 3 × Tg-AD as in vivo AD models and LPS induce BV-2 cells in vitro AD models. The molecular process was investigated by ELISA, WB, IHC, and IF. In 3 × Tg-AD mice, TWD dramatically ameliorates cognitive impairment. Treatment with TWD can counteract the increased activation of microglia and Aβ deposits observed in 3 × Tg-AD mice. Further research indicates that TWD can enhance TOM 1 and mitigate inflammatory responses by reducing the levels of IL-1β, TNF-α, IL-6, IL1R1, and IL-18. Additionally, TWD may inhibit neuroinflammation through the pathways of IL1R1/MyD88/NF-κB and NLRP3/IL-1β/IL1R1. In summary, this study reveals for the first time that TWD effectively improves cognitive deficits in 3 × Tg-AD mice by modulating the IL1R1/MyD88/NF-κB and NLRP3/IL-1β/IL1R1 pathways. It also alleviates excessive activation of microglia and suppresses Aβ accumulation. Therefore, TWD has the potential as a therapeutic agent for AD.

Withania somnifera, commonly known as Ashwagandha, is a prominent herb in Ayurvedic medicine, recognised for its diverse pharmacological properties, particularly its potential anti-diabetic effects. With the global incidence of diabetes mellitus (DM) surpassing 366 million, interest in herbal remedies like Ashwagandha has surged. Active compounds known as withanolides have demonstrated efficacy in modulating glucose homeostasis and enhancing insulin sensitivity. Systematic reviews indicate that Ashwagandha effectively restores altered blood glucose and glycosylated haemoglobin (HbA1c) levels without significant safety concerns. Animal studies reveal hypoglycaemic effects from both root and leaf extracts, improving metabolic parameters. Although clinical evidence remains limited, existing trials suggest that Ashwagandha may enhance insulin sensitivity and overall metabolic profiles in diabetic patients. This review underscores the potential of Ashwagandha as a complementary approach in DM management, warranting further research to confirm its therapeutic benefits and elucidate underlying mechanisms.

We investigated the effect of purified withanolides and extracts derived from Ashwagandha on steatosis, the abnormal accumulation of fat that can lead to non-alcoholic fatty liver disease (NAFLD). Collaborator of ARF (CARF, also known as CDKN2AIP, a protein that regulates hepatic lipid metabolism, fat buildup, and liver damage) was used as an indicator. Six withanolides (Withaferin A, Withanone, Withanolide B, Withanoside IV, Withanoside V, and Withanostraminolide-12 deoxy) reversed the decrease in CARF caused by exposure to free fatty acids (FFAs) in liver-derived cells (HepG2 hepatocytes). After analyzing the effects of these withanolides on CARF mRNA and protein levels, FFA accumulation, protein aggregation, and oxidative and DNA damage stresses, we selected Withaferin A and Withanone for molecular analyses. Using the palmitic-acid-induced fatty acid accumulation stress model in Huh7 cells, we found a significant reduction in the activity of the key regulators of lipogenesis pathways, including sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and peroxisome proliferator-activated receptors (PPARγ and PPARα). This in vitro study suggests that low, non-toxic doses of Withaferin A, Withanone, or Ashwagandha extracts containing these withanolides possess anti-steatosis and antioxidative-stress properties. Further in vivo and clinical studies are required to investigate the therapeutic potential of these Ashwagandha-derived bioactive ingredients for NAFLD.

Withania somnifera L. (Solanaceae), for over 3000 years, has been considered an essential herb in Ayurvedic medicine. The roots of W. somnifera contain metabolites mainly belonging to steroidal lactones called withanolides, which possess various pharmacological activities such as neuroprotective, cardioprotective, anti-diabetic, antioxidant and anti-inflammatory. Since the demand on the market for W. somnifera extracts is increasing, with the aim to find an ecological and environmentally friendly strategy of extraction, the roots were submitted to different extraction techniques (macerations, ultrasound-assisted extraction and solid-liquid dynamic extraction) using EtOH:H2O 50:50, 75:25, 100:0. W. somnifera extracts were investigated by an integrated LC-ESI/QExactive/MS/MS and NMR approach to obtain comprehensive metabolite profiles. Principal Component Analysis of LC-MS and NMR data revealed how the extraction method and the solvent can affect the chemical profile of the extracts. Extracts obtained by maceration exhibited the highest amount of withanolides and withanosides, while the SLDE-Naviglio EtOH extract showed the highest amount of metabolites as benzoic acid, tropane alkaloids and sarcosine, reported for their CNS activity. Moreover, based on the use of this plant in the treatment of neurological disorders, the tyrosinase inhibitory activity of all the extracts was herein tested by spectrophotometric assay, showing IC50 values in a range of 32.86-85.36 µg/ml.

Various important medicines make use of secondary metabolites that are produced by plants. Medicinal plants, such as Withania somnifera and Tinospora cordifolia, are rich sources of chemically active compounds and are reported to have numerous therapeutic applications. The therapeutic use of medicinal plants is widely mentioned in Ayurveda and has folkloric importance in different parts of the world. The aim of this review is to summarize the phytochemical profiles, folkloric importance, and primary pharmacological activity of W. somnifera and T. cordifolia with emphasis on their action against the novel coronavirus.

Despite various treatment modalities, the progression and metastasis of breast cancer (BC) are grave concerns due to the alarming disease-free survival rate (DFS) and overall survival rate (OS) of affected patients. Over the years, many antibiotics, synthetic compounds, medicinal plant isolates and polyherbal combinations have been used as adjuvants in therapy for the management of primary and secondary tumors. Paclitaxel (PTX)-based chemotherapy for breast cancer causes multiple adverse side effects in patients. Withania somnifera (L.) Dunal (WS) and Asparagus racemosus Willd. (AR) as Ayurveda-inspired plant-based adjuvants were investigated for their anticancer effects on MDA-MB-231 and 4T1 cells in mouse model systems.

This study focused on evaluating the adjuvant properties of WS and AR plant extracts with PTX and their effectiveness over PTX alone in terms of tumor inhibition.

The effects of WS and AR on DNA double-strand breaks (DSBs), senescence induction and mitochondrial functions were evaluated in BC cells in vitro. The potential for cancer stem cell (CSC) inhibition was evaluated via mammosphere formation assays and CD44/CD24 immunostaining. In vivo tumor growth studies were conducted in athymic BALB/c mice for MDA-MB-231 cells and in BALB/c mice for 4T1 cells.

Induction of senescence was evident due to DSBs induced by the WS and AR extracts. Mammosphere formation and CD44/CD24 CSC markers were reduced after treatment with WS, AR or the combination of both in MCF-7 cells. WS or AR inhibited epithelial-to-mesenchymal transition (EMT). In vivo studies demonstrated that tumor growth inhibition was more pronounced in the treated group than in the PTX alone group and the untreated control group.

Our study showed that the use of WS or AR plant hydroalcoholic extracts in combination with paclitaxel (PTX) has better effects on sensitivity and efficacy than PTX alone, as demonstrated in in vitro BC cells and mouse models with BC cell grafts. Hence, scheduling adjuvant therapy with WS or AR alone or combined with PTX can be advantageous for the management of triple-negative BC (TNBC). Further studies are warranted in human clinical conditions to ascertain the efficacy of these treatments.

In this study, we aimed to examine the effects of chotosan, a traditional Japanese botanical drug, and its active component, Uncaria hook, on anxiety-like behaviors induced by systemic inflammation in mice.

To induce systemic inflammation, the mice were treated with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS treatment, the mice were administered chotosan or Uncaria hook orally each day for 14 days. Anxiety-like behavior of the mice was evaluated using the light-dark test 24 h after LPS treatment.

Repeated administration of chotosan prevented anxiety-like behavior in both normal and LPS-treated mice. Similarly, administration of Uncaria hook suppressed LPS-induced anxiety-like behavior in mice. Furthermore, treatment with tandospirone, a 5-HT1A receptor agonist, alleviated anxiety-like behavior in mice, whereas treatment with DOI, a 5-HT2A receptor agonist, enhanced anxiety-like behavior in mice. LPS treatment significantly increased serotonin (5-HT)2A receptor mRNA expression in the frontal cortex, whereas 5-HT1A receptor mRNA expression remained unchanged in the hippocampus. Notably, chotosan significantly suppressed the mRNA expression of 5-HT2A receptor.

These findings indicate that chotosan exerts anxiolytic-like effects in the context of inflammation-induced anxiety, potentially mediated by the inhibition of 5-HT2A receptor hyperfunction in LPS-treated mice. Consequently, we postulate that chotosan may be effective in managing inflammation-induced anxiety-like behaviors.

Cyclophosphamide (CP) is an alkylating agent commonly used in cancer treatment. It is known to have detrimental effects on the reproductive system, including the potential to cause infertility. Recently, herbal remedies have gained traction as a complementary approach to addressing these side effects. In this study, our goal was to investigate whether the aqueous-alcoholic extract of Withania somnifera (WS) could mitigate the adverse impacts of CP on testicular tissue.

Animals were randomly assigned to one of the following groups: control, WS (500 mg/kg), CP (100 mg/kg), CP+WS pre-treatment, and CP+WS post-treatment. WS was administered orally through gavage for 1 month. We assessed sperm parameters, testicular histopathology, and the expression of the Bax and Bcl2 genes in the experimental groups.

Sperm parameters (including count, viability, and motility), the number of spermatogonia, the seminiferous tubule diameter, and Bcl2 gene expression, significantly decreased after CP injection (p<0.05). Conversely, the number of immotile sperm and Bax gene expression significantly increased (p<0.05). Treatment with WS, especially when administered as a pre-treatment, ameliorated the sperm parameters, histological alterations, and the expression of apoptosis-related genes (p<0.05).

The data suggest that WS may mitigate the detrimental effects of CP on testicular tissue by reducing apoptosis. Consequently, WS has the potential to be used as an adjunctive therapy to reduce the complications associated with CP treatment.

Since 2019, the novel coronavirus (SARS-CoV-2) has caused significant morbidity and millions of deaths worldwide. The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 and its variants, has further highlighted the urgent need for the development of effective therapeutic agents. Currently, the highly conserved and broad-spectrum nature of main proteases (Mpro) renders them of great importance in the field of inhibitor study. In this study, we categorize inhibitors targeting Mpro into three major groups: mimetic, nonmimetic, and natural inhibitors. We then present the research progress of these inhibitors in detail, including their mechanism of action, antiviral activity, pharmacokinetic properties, animal experiments, and clinical studies. This review aims to provide valuable insights and potential avenues for the development of more effective antiviral drugs against SARS-CoV-2.

Microwave radiation (MWR) has been linked to neurodegeneration by inducing oxidative stress in the hippocampus of brain responsible for learning and memory. Ashwagandha (ASW), a medicinal plant is known to prevent neurodegeneration and promote neuronal health. This study investigated the effects of MWR and ASW on oxidative stress and cholinergic imbalance in the hippocampus of adult male Japanese quail. One control group received no treatment, the second group quails were exposed to MWR at 2 h/day for 30 days, third was administered with ASW root extract orally 100 mg/day/kg body weight and the fourth was exposed to MWR and also treated with ASW. The results showed that MWR increased serum corticosterone levels, disrupted cholinergic balance and induced neuro-inflammation. This neuro-inflammation further led to oxidative stress, as evidenced by decreased activity of antioxidant enzymes SOD, CAT and GSH. MWR also caused a significant decline in the nissil substances in the hippocampus region of brain indicating neurodegeneration through oxidative stress mediated hippocampal apoptosis. ASW, on the other hand, was able to effectively enhance the cholinergic balance and subsequently lower inflammation in hippocampus neurons. This suggests that ASW can protect against the neurodegenerative effects of MWR. ASW also reduced excessive ROS production by increasing the activity of ROS-scavenging enzymes. Additionally, ASW prevented neurodegeneration through decreased expression of caspase-3 and caspase-7 in hippocampus, thus promoting neuronal health. In conclusion, this study showed that MWR induces apoptosis and oxidative stress in the brain, while ASW reduces excessive ROS production, prevents neurodegeneration and promotes neuronal health.

Phenolic compounds, present in plants, provide substantial health advantages, such as antioxidant and anti-inflammatory properties, which enhance cardiovascular and cognitive well-being. Australia is enriched with a wide range of plants with phytopharmacological potential, which needs to be fully elucidated. In this context, we analyzed leaves of aniseed myrtle (Syzygium anisatum), lemon myrtle (Backhousia citriodora), and cinnamon myrtle (Backhousia myrtifolia) for their complex phytochemical profile and antioxidant potential. LC-ESI-QTOF-MS/MS was applied for screening and characterizing these Australian myrtles' phenolic compounds and the structure-function relation of phenolic compounds. This study identified 145 and quantified/semi-quantified 27 phenolic compounds in these Australian myrtles. Furthermore, phenolic contents (total phenolic content (TPC), total condensed tannins (TCT), and total flavonoids (TFC)) and antioxidant potential of phenolic extracts from the leaves of Australian myrtles were quantified. Aniseed myrtle was quantified with the highest TPC (52.49 ± 3.55 mg GAE/g) and total antioxidant potential than other selected myrtles. Catechin, epicatechin, isovitexin, cinnamic acid, and quercetin were quantified as Australian myrtles' most abundant phenolic compounds. Moreover, chemometric analysis further validated the results. This study provides a new insight into the novel potent bioactive phenolic compounds from Australian myrtles that could be potentially useful for functional, nutraceutical, and therapeutic applications.

Withania somnifera (L.) Dunal; (Solanaceae), commonly known as Ashwagandha, is one of the most significant medicinal herbs in 'Ayurveda', a traditional Indian medicine used for centuries with evidence in scriptures. Ashwagandha was mentioned in old Ayurvedic medical literature such as Charaka Samhita and Sushruta Samhita for improving weight and strength, with multiple citations for internal and exterior usage in emaciation and nourishing the body. Ethnopharmacological evidence revealed that it was used to relieve inflammation, reduce abdominal swelling, as a mild purgative, and treat swollen glands. The root was regarded as a tonic, aphrodisiac, and emmenagogue in the Unani tradition of the Indian medicinal system. Further, Ashwagandha has been also described as an Ayurvedic medicinal plant in the Ayurvedic Pharmacopoeia of India extending informed therapeutic usage and formulations. Despite the widespread ethnopharmacological usage of Ashwagandha, clinical pharmacokinetic parameters are lacking in the literature; hence, the findings of this study will be relevant for calculating doses for future clinical evaluations of Ashwagandha root extract.

This study aimed to develop a validated and highly sensitive bioanalytical method for quantifying withanosides and withanolides of the Ashwagandha root extract in human plasma to explore its bioaccessibility. Further to apply a developed method to perform pharmacokinetics of standardized Withania somnifera (L.) Dunal root extract (WSE; AgeVel®/Witholytin®) capsules in healthy human volunteers.

A sensitive, reliable, and specific ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS/MS) method was developed and validated for the simultaneous quantification of five major withanosides and withanolides (withanoside IV, withanoside V, withanolide A, withaferin A, and 12-deoxy-withastramonolide) in human plasma. Further for the study, eighteen healthy male volunteers (18-45 years) were enrolled in a non-randomized, open-label, single period, single treatment, clinical pharmacokinetic study and given a single dose (500 mg) of WSE (AgeVel®/Witholytin®) capsules containing not less than 7.5 mg of total withanolides under fasting condition. Later, pharmacokinetic profiles were assessed using the plasma concentration of each bioactive constituent Vs. time data.

For all five constituents, the bioanalytical method demonstrated high selectivity, specificity, and linearity. There was no carryover, and no matrix effect was observed. Furthermore, the inter-day and intra-day precision and accuracy results fulfilled the acceptance criteria. Upon oral administration of WSE capsules, Cmax was found to be 0.639 ± 0.211, 2.926 ± 1.317, 2.833 ± 0.981, and 5.498 ± 1.986 ng/mL for withanoside IV, withanolide A, withaferin A, and 12-deoxy-withastramonolide with Tmax of 1.639 ± 0.993, 1.361 ± 0.850, 0.903 ± 0.273, and 1.375 ± 0.510 h respectively. Further, withanoside V was also detected in plasma; but its concentration was found below LLOQ.

The novel and first-time developed bioanalytical method was successfully applied for the quantification of five bio-active constituents in human volunteers following administration of WSE capsules, indicating that withanosides and withanolides were rapidly absorbed from the stomach, have high oral bioavailability, and an optimum half-life to produce significant pharmacological activity. Further, AgeVel®/Witholytin® was found safe and well tolerated after oral administration, with no adverse reaction observed at a 500 mg dose.

Withania somnifera (L.) Dunal is a medicinal plant belonging to the traditional Indian medical system, showing various therapeutic effects such as anti-cancer, anti-inflammatory, anti-microbial, anti-diabetic, and hepatoprotective activity. Of great interest is W. somnifera's potential beneficial effect against neurodegenerative diseases, since the authorized medicinal treatments can only delay disease progression and provide symptomatic relief and are not without side effects. A systematic search of PubMed and Scopus databases was performed to identify preclinical and clinical studies focusing on the applications of W. somnifera in preventing neurodegenerative diseases. Only English articles and those containing the keywords (Withania somnifera AND "neurodegenerative diseases", "neuroprotective effects", "Huntington", "Parkinson", "Alzheimer", "Amyotrophic Lateral Sclerosis", "neurological disorders") in the title or abstract were considered. Reviews, editorials, letters, meta-analyses, conference papers, short surveys, and book chapters were not considered. Selected articles were grouped by pathologies and summarized, considering the mechanism of action. The quality assessment and the risk of bias were performed using the Cochrane Handbook for Systematic Reviews of Interventions checklist. This review uses a systematic approach to summarize the results from 60 investigations to highlight the potential role of W. somnifera and its specialized metabolites in treating or preventing neurodegenerative diseases.

Withania somnifera, the plant named Indian ginseng, Ashwagandha, or winter cherry, has been used since ancient times to cure various health ailments. Withania somnifera is rich in constituents belonging to chemical classes like alkaloids, saponins, flavonoids, phenolic acids, and withanolides. Several chemotypes were identified based on their phytochemical composition and credited for their multiple bioactivities. Besides, exhibiting neuroprotective, immunomodulatory, adaptogenic, anti-stress, bone health, plant has shown promising anti-cancer properties. Several withanolides have been reported to play a crucial role in cancer; they target cancer cells by different mechanisms such as modulating the expression of tumor suppressor genes, apoptosis, telomerase expression, and regulating cell signaling pathway. Though, many treatments are available for cancer; however, to date, no assured reliable cure for cancer is made available. Additionally, synthetic drugs may lead to development of resistance in time; therefore, focus on new and natural drugs for cancer therapeutics may prove a longtime effective alternative. This current report is a comprehensive combined analysis upto 2023 with articles focused on bio-activities of plant Withania somnifera from various sources, including national and international government sources. This review focuses on understanding of various mechanisms and pathways to inhibit uncontrolled cell growth by W. somnifera bioactives, as reported in literature. This review provides a recent updated status of the W. somnifera on pharmacological properties in general and anti-cancer in particular and may provide a guiding resource for researchers associated with natural product-based cancer research and healthcare management.

The Withania somnifera, also called Ashwagandha, is available everywhere in the world. We present a rare case of thyrotoxicosis following Ashwagandha administration, specifically painless thyroiditis (PT) in this report. The patient was a 47-year-old previously healthy Japanese man, who started taking Ashwagandha two months before his first visit to our hospital. He visited our hospital for typical thyrotoxicosis symptoms like a sense of fatigue, fever at night, and weight loss followed by diarrhea and headache. Blood tests disclosed thyrotoxicosis. Thyroid ultrasonography showed internal echo heterogeneity and no increase in blood flow. Thyroid scintigraphy revealed a deficiency in thyroid uptake. Based on these findings, he was diagnosed as PT. After stopping the administration of Ashwagandha, both his symptoms and serum thyroid markers were improved. This report may spark important debate about whether ashwagandha is safe among healthy people, especially in thyroid toxicity.

Withanolides are the class of steroidal molecules getting greater emphasis in recent years. Quality control throughout the manufacturing and storage period is often one of the key problems that have restricted their broad use in India's indigenous and Ayurvedic medical systems for thousands of years. Because of their diverse clinical potential, withanolides have received a great deal of scientific attention. Analytical techniques are being devised for the automated isolation, identification, and estimation of every single protein within the cell as well as in herbal extracts of withanolides, due to which now researchers are interested in determining the effects of metabolism as well as various stimuli on protein expression, which made the study easier. This study discusses the potential use of hyphenated analytical methods that are reliable in understanding the molecular signaling features, proteome evaluation and characterization of withanolides, in addition to examining existing methodological limitations. The choice of analytical techniques for the withanolides analysis, however, relies on the nature of the sample matrix, the aim of the analysis, and the sensitivity of the technique.

Acute graft versus host disease (aGvHD) is the major contributor of nonrelapse mortality in alloHSCT. It is associated with an inflammatory immune response manifesting as cytokine storm with ensuing damage to target organs such as liver, gut, and skin. Prevention of aGvHD while retaining the beneficial graft versus leukemia (GvL) effect remains a major challenge. Withania somnifera extract (WSE) is known for its anti-inflammatory, immune-modulatory, and anticancer properties, which are appealing in the context of aGvHD. Herein, we demonstrated that prophylactic and therapeutic use of WSE in experimental model of alloHSCT mitigates aGvHD-associated morbidity and mortality. In the prophylaxis study, a dose of 75 mg/kg of WSE offered greatest protection against death due to aGvHD (hazard ratio [HR] = 0.15 [0.03-0.68], P ≤ .01), whereas 250 mg/kg was most effective for the treatment of aGvHD (HR = 0.16 [0.05-0.5], P ≤ .01). WSE treatment protected liver, gut, and skin from damage by inhibiting cytokine storm and lymphocytic infiltration to aGvHD target organs. In addition, WSE did not compromise the GvL effect, as alloHSCT with or without WSE did not allow the leukemic A20 cells to grow. In fact, WSE showed marginal antileukemic effect in vivo. WSE is currently under clinical investigation for the prevention and treatment of aGvHD.

Cancer is a leading cause of death globally and in the US, prompting research into medicinal plants with anticancer properties. Withania somnifera, or Ashwagandha, is one such plants, known for its diverse pharmacological effects. Withaferin A and Viscosalactone B are two compounds found in Ashwagandha with known anticancer activity. The protein NQO1, overexpressed in various cancers, was the focus of this study.

We hypothesize that specific phytochemicals in Withania somnifera can effectively interact with and inhibit the NQO1 protein, thereby exhibiting anticancer properties. This study aims to identify these interactions using in silico approaches.

CFDT was performed using the Gaussian 16 program package, followed by QSAR analysis of the compounds in the PASS online web server. The Schrodinger suite was used to carry out ligand and protein preparation, molecular docking, and molecular dynamic simulation to analyse the interaction of these compounds with NQO1 and ADME studies. Protox-II and SWISSADME tools were used to predict the toxicity and blood-brain barrier permeability of the phytochemicals.

CDFT and frontier molecular orbital analyses predicted the stability and reactivity of all the selected molecules. QSAR analysis predicted the biological activity and toxicity of the compounds. Withaferin A exhibited the highest glide gscore (-4.953 kcal/mol) and demonstrated 6 hydrogen bond interactions with NQO1, suggesting its potential as an anticancer agent. Conceptual density functional theory-based analysis suggested the strong electrophilicity of the ligands, further supporting their potential anticancer activities. Viscosalactone B, another phytochemical from Ashwagandha, also showed interactions involving 6 hydrogen bonds with NQO1, with a glide gscore of (-4.593 kcal/mol). Molecular dynamic simulations validated the stability of the Withaferin A-NQO1 complex. ADME-T properties predicted high oral absorption for the selected ligands, indicating that Withaferin A could be a viable orally administered drug.

Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023.

The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus.

Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects.

Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.

Using green synthesis methods to produce halophytic nanoparticles presents a promising and cost-effective approach for enhancing plant growth in saline environments, offering agricultural resilience as an alternative to traditional chemical methods. This study focuses on synthesizing zinc oxide (ZnO) nanoparticles derived from the halophyte Withania somnifera, showcasing their potential in ameliorating tomato growth under salinity stress. The biosynthesis of ZnO nanoparticles was initially optimized (i.e., salt concentration, the amount of plant extract, pH, and temperature) using a central composite design (CCD) of response surface methodology (RSM) together with UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and dynamic light scattering (DLS) to comprehensively characterize the biosynthesized ZnO NPs. The central composite design (CCD) based response surface methodology (RSM) was used to optimize the biosynthesis of ZnO nanoparticles (NPs) by adjusting salt concentration, plant extract, pH, and temperature. The ZnO NPs were characterized using UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and dynamic light scattering (DLS). FT-IR showed an absorption peak of ZnO between 400 and 600 cm-1, while SEM showed irregular shapes ranging between 1.3 and 6 nm. The data of EDX showed the presence of Zn (77.52%) and O (22.48%) levels, which exhibited the high purity synthesized ZnO under saline conditions. Introducing ZnO nanoparticles to tomato plants resulted in a remarkable 2.3-fold increase in shoot length in T23 (100 mg/L ZnO nanoparticles + 50 mM NaCl). There was an observable increase in foliage at T2 (20 mg L-1 ZnO) and T23 (100 mg L-1 ZnO-NPs + 50 mM NaCl). Tomato plants treated with T2 (20 mg L-1 ZnO) and T23 (100 mg L-1 ZnO-NPs + 50 mM NaCl) improved root elongation compared to the control plant group. Both fresh and dry leaf masses were significantly improved in T1 (10 mg L-1 ZnO) by 7.1-fold and T12 (10 mg L-1 ZnO-NPs + 100 mM NaCl) by 0.8-fold. The concentration of Zn was higher in T12 (10 mg L-1 ZnO NPs + 100 mM NaCl) among all treatments. Our findings prove that utilizing ZnO nanoparticles under saline conditions effectively promotes tomato plants' growth, thereby mitigating the negative impacts of salt stress.

Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA's significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA's action represents a crucial research direction to pursue in the future.

Background: Impaired inflammation and vascularization are common reasons for delayed diabetic wound healing. Nanoparticles (NPs)-in-nanofibers composites can manage diabetic wounds. A multifunctional scaffold was developed based on tadalafil (TDF)-loaded NPs incorporated into polyvinyl alcohol/Withania somnifera extract nanofibers. Materials & methods: TDF-loaded NPs were prepared and fully characterized in terms of their physicochemical properties. Extract of ashwagandha was prepared and a blend composed of TDF-loaded NPs, herbal extract and polyvinyl alcohol was used to prepare the whole composite. Results: The whole composite exhibited improved wound closure in a diabetic rat model in terms of reduced inflammation and enhanced angiogenesis. Conclusion: Results suggest that this multifunctional composite could serve as a promising diabetic wound dressing.

The solid waste known as fly ash, which is produced when coal is burned in thermal power plants, is sustainably used in agriculture. It is an excellent soil supplement for plant growth and development since it contains some desired nutrients (macro and micro), as well as being porous. The present study was done to evaluate the effect of different fly ash levels on Withania somnifera. The present study aimed to assess the impact of various fly ash (FA) concentrations on growth, yield, photosynthetic pigments, biochemical parameters, and cell viability of W. somnifera. The results showed that FA enhanced physical and chemical properties of soil like pH, electric conductivity, porosity, water-holding capacity, and nutrients. The low doses of FA-amended soil (15%) significantly increased the shoot length (36%), root length (24.5%), fresh weight of shoots and roots (107.8 and 50.6%), dry weight of shoots and roots (61.9 and 47.1%), number of fruits (70.4%), carotenoid (43%), total chlorophyll (44.3%), relative water content (109.3%), protein content (20.4%), proline content (110.3%), total phenols (116.1%), nitrogen (20.3%), phosphorus (16.9%), and potassium (26.4%). On the other hand, the higher doses, i.e., 25% of fly ash showed a negative effect on all the above parameters and induced oxidative stress by increasing lipid peroxidation (33.1%) and hydrogen peroxide (102.0%) and improving the activities of antioxidant enzymes and osmolytes. Compared to the control plants, the plants growing in soil enriched with 15 and 25% fly ash had larger stomata pores when examined using a scanning electron microscope. In addition, according to a confocal microscopic analysis of the roots of W. somnifera, higher fly ash concentrations caused membrane damage, as evidenced by an increase in the number of stained nuclei. Moreover, several functional groups and peaks of the biomolecules represented in the control and 15% of fly ash were alcohols, phenols, allenes, ketenes, isocynates, and hydrocarbons. Gas chromatography-mass spectrometry analysis of the methanol extract of W. somnifera leaves cultivated in soil amended with 15% fly ash shows the presence of 47 bioactive compounds. The most abundant compounds in the methanol extract were cis-9-hexadecenal (22.33%), n-hexadecanoic acid (9.68%), cinnamic acid (6.37%), glycidyl oleate (3.88%), nonanoic acid (3.48%), and pyranone (3.57%). The lower concentrations of FA (15%) can be used to enhance plant growth and lower the accumulation of FA that results in environmental pollution.

This study focused on documenting and evaluating the cercaricidal activity of medicinal plants used for schistosomiasis treatment in an endemic area in Ghana. Through semistructured questionnaires, personal interviews with herbalists in communities surrounding the Barekese dam in the Atwima-Nwabiagya district, where the disease is endemic, were carried out. Thirty medicinal plants distributed in 19 families were reported to be used for schistosomiasis treatment in the survey. Information on the plants, including scientific names, common names, families, and the used plant part were recorded. The families Apocynaceae and Euphorbiaceae recorded the highest number of plants (14% each), followed by Asteraceae (10%), Loranthaceae (7%), and Rubiaceae (7%). In vitro cercaricidal activity of methanol extracts of nine out of the thirty plants was performed by exposing human Schistosoma mansoni cercariae obtained from Biomphalaria pfeifferi to various concentrations of extracts over a duration of 240 minutes. All the plants tested demonstrated time- and concentration-dependent cercaricidal activity. With lethality being set at <1000 μg/mL, the cercaricidal activity in order of decreasing potency was as follows: Withania somnifera (LC₅₀ = 1.29) > Balanites aegyptiaca (LC₅₀ = 7.1) > Xylia evansii (LC₅₀ = 11.14) > Jathropha multifida (LC₅₀ = 12.9) > Justicia flava (LC₅₀ = 22.9) > Anopyxis klaineana (LC₅₀ = 182.81) > Ximenia americana (LC₅₀ = 194.98) > Loranthus lecardii (LC₅₀ = 223.87) > Bridelia tenufolia (LC₅₀ = 309.03) > Zanthoxylium zanthoxyloides (LC₅₀ = 851.94). Phytochemicals, including alkaloids, tannins, triterpenes, saponins, phytosterols, and flavonoids were identified in the plants. The result of this study gives scientific credence to the traditional use of these plants in the treatment of schistosomiasis and proves that the rich botanical knowledge of medicinal plants provides an incredible starting point for the discovery of new anti-schistosomal drugs for the local population.

Alzheimer's disease (AD), also called senile dementia, is the most common neurological disorder. Around 50 million people, mostly of advanced age, are suffering from dementia worldwide and this is expected to reach 100-130 million between 2040 and 2050. AD is characterized by impaired glutamatergic and cholinergic neurotransmission, which is associated with clinical and pathological symptoms. AD is characterized clinically by loss of cognition and memory impairment and pathologically by senile plaques formed by Amyloid β deposits or neurofibrillary tangles (NFT) consisting of aggregated tau proteins. Amyloid β deposits are responsible for glutamatergic dysfunction that develops NMDA dependent Ca2+ influx into postsynaptic neurons generating slow excitotoxicity process leading to oxidative stress and finally impaired cognition and neuronal loss. Amyloid decreases acetylcholine release, synthesis and neuronal transport. The decreased levels of neurotransmitter acetylcholine, neuronal loss, tau aggregation, amyloid β plaques, increased oxidative stress, neuroinflammation, bio-metal dyshomeostasis, autophagy, cell cycle dysregulation, mitochondrial dysfunction, and endoplasmic reticulum dysfunction are the factors responsible for the pathogenesis of AD. Acetylcholinesterase, NMDA, Glutamate, BACE1, 5HT6, and RAGE (Receptors for Advanced Glycation End products) are receptors targeted in treatment of AD. The FDA approved acetylcholinesterase inhibitors Donepezil, Galantamine and Rivastigmine and N-methyl-D-aspartate antagonist Memantine provide symptomatic relief. Different therapies such as amyloid β therapies, tau-based therapies, neurotransmitter-based therapies, autophagy-based therapies, multi-target therapeutic strategies, and gene therapy modify the natural course of the disease. Herbal and food intake is also important as preventive strategy and recently focus has also been placed on herbal drugs for treatment. This review focuses on the molecular aspects, pathogenesis and recent studies that signifies the potential of medicinal plants and their extracts or chemical constituents for the treatment of degenerative symptoms related to AD.

During the COVID-19 pandemic, many consumers increased their use of supplements that claimed to support immune health, including Ayurvedic preparations. The goal of this study was to analyze labeling compliance and online claims for Ayurvedic herbal supplements associated with the purported treatment of COVID-19. The physical product labels for 51 herbal supplements labeled as ginger, tulsi/holy basil, amla, vacha/calamus root, guduchi/giloy, cinnamon, ashwagandha, tribulus, or turmeric were assessed for U.S. regulatory compliance. Disease claims, structure/function claims, and general well-being claims were also examined. The online listings for products purchased online (n = 42) were examined for claims and for the presence of the required legal disclaimer. Collectively, 61% of products had at least one instance of noncompliance on the physical label. The most common violations included missing/noncompliant disclaimer (33%), noncompliant "Supplement Facts" label (29%), noncompliant statement of identity (27%) and noncompliant domestic mailing address or phone number (25%). Structure/function claims occurred more frequently in the online product listings (average of 5 claims per product) compared to the physical labels (average of 2 claims per product). Disease claims were observed for 38% of online product listings and on 8% of physical labels. The use of disease claims on herbal supplements is a significant concern for public health because it may lead consumers to delay seeking professional treatment for life-threatening diseases. Overall, this study revealed a lack of labeling compliance among Ayurvedic herbal supplements and a need for greater scrutiny and monitoring of online product listings.

A simple and efficient protocol for the aza-Michael addition of various aromatic anilines to ring A of withaferin A has been developed. Stereoselectivity, functional group tolerance, broad substrate scope, short reaction time and moderate to high yield are the merits of the protocol. One of the synthesized compounds 11 shows an IC 50 value of 3.8 μM against aggressive, highly metastatic triple-negative breast cancer cell line MDA-MB-231.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic, which has seriously affected human health worldwide. The discovery of therapeutic agents is extremely urgent, and the viral structural proteins are particularly important as potential drug targets. SARS-CoV-2 envelope (E) protein is one of the main structural proteins of the virus, which is involved in multiple processes of the virus life cycle and is directly related to pathogenesis process. In this review, we present the amino acid sequence of the E protein and compare it with other two human coronaviruses. We then explored the role of E protein in the viral life cycle and discussed the pathogenic mechanisms that E protein may be involved in. Next, we summarize the potential drugs against E protein discovered in the current studies. Finally, we described the possible effects of E protein mutation on virus and host. This established a knowledge system of E protein to date, aiming to provide theoretical insights for mitigating the current COVID-19 pandemic and potential future coronavirus outbreaks.

Mitochondria are the primary source of energy production in neurons, supporting the high energy consumption of the nervous system. Inefficient and dysfunctional mitochondria in the central nervous system have been implicated in neurodegenerative diseases. Therefore, targeting mitochondria offers a new therapeutic opportunity for neurodegenerative diseases. Many recent studies have proposed that plant-derived natural products, as pleiotropic, safe, and readily obtainable sources of new drugs, potentially treat neurodegenerative diseases by targeting mitochondria. In this review, we summarize recent advances in targeting mitochondria in neurotherapeutics by employing plant-derived natural products. We discuss the mechanism of plant-derived natural products according to their mechanism of action on mitochondria in terms of regulating biogenesis, fusion, fission, bioenergetics, oxidative stress, calcium homeostasis, membrane potential, and mitochondrial DNA stability, as well as repairing damaged mitochondria. In addition, we discuss the potential perspectives and challenges in developing plant-derived natural products to target mitochondria, highlighting the clinical value of phytochemicals as feasible candidates for future neurotherapeutics.

Lysine-specific demethylase 1 (LSD1) has been a promising target to treat prostate cancer, and discovery of novel LSD1 inhibitors would have great clinical significance. In this work, viscosalactone B was first identified as a novel LSD1 inhibitor. Viscosalactone B isolated from Withania Somnifera displayed antiproliferative activity against PC3, DU145, C42B, PC3/MDVR, DU145/MDVR, and C42B/MDVR cells with IC₅₀ values of 1.17, 0.72, 3.86, 2.06, 0.96 and 1.15 μM, respectively. In comparison, it was a selective LSD1 inhibitor with an IC₅₀ value of 970.27 nM and could induce a significant accumulation of LSD1 substrates H3K9me1, H3K9me2, and H3K4me1 in a concentration-dependent manner in DU145 cells. According to docking studies, it formed hydrogen bonds with the Thr11, Lys14, and Arg8 residues of LSD1. Importantly, while it displayed potent antitumor efficacy in vivo, it did not show obvious cytotoxicity on the major organs of nude mice. Therefore, viscosalactone B, as a novel LSD1 inhibitor, is a potential candidate that can be used for the treatment of prostate cancer in clinics.

Leishmaniasis is a group of infectious diseases caused by Leishmania protozoa. The ineffectiveness, high toxicity, and/or parasite resistance of the currently available antileishmanial drugs has created an urgent need for safe and effective leishmaniasis treatment. Currently, the molecular-docking technique is used to predict the proper conformations of small-molecule ligands and the strength of the contact between a protein and a ligand, and the majority of research for the development of new drugs is centered on this type of prediction. Leishmania N-myristoyltransferase (NMT) has been shown to be a reliable therapeutic target for investigating new anti-leishmanial molecules through this kind of virtual screening. Natural products provide an incredible source of affordable chemical scaffolds that serve in the development of effective drugs. Withania somnifera leaves, roots, and fruits have been shown to contain withanolide and other phytomolecules that are efficient anti-protozoal agents against Malaria, Trypanosoma, and Leishmania spp. Through a review of previously reported compounds from W. somnifera-afforded 35 alkaloid, phenolic, and steroid compounds and 132 withanolides/derivatives, typical of the Withania genus. These compounds were subjected to molecular docking screening and molecular dynamics against L. major NMT. Calycopteretin-3-rutinoside and withanoside IX showed the highest affinity and binding stability to L. major NMT, implying that these compounds could be used as antileishmanial drugs and/or as a scaffold for the design of related parasite NMT inhibitors with markedly enhanced binding affinity.

Huntington's disease (HD) is a rare and fatal neurodegenerative disorder with no diseasemodifying therapeutics. HD is characterized by extensive neuronal loss and is caused by the inherited expansion of the huntingtin (HTT) gene that encodes a toxic mutant HTT (mHTT) protein having expanded polyglutamine (polyQ) residues. Current HD therapeutics only offer symptomatic relief. In fact, Food and Drug Administration (FDA) approved two synthetic small-molecule VMAT2 inhibitors, tetrabenazine (1) and deutetrabenazine (2), for managing HD chorea and various other diseases in clinical trials. Therefore, the landscape of drug discovery programs for HD is evolving to discover disease- modifying HD therapeutics. Likewise, numerous natural products are being evaluated at different stages of clinical development and have shown the potential to ameliorate HD pathology. The inherent anti-inflammatory and antioxidant properties of natural products mitigate the mHTT-induced oxidative stress and neuroinflammation, improve mitochondrial functions, and augment the anti-apoptotic and pro-autophagic mechanisms for increased survival of neurons in HD. In this review, we have discussed HD pathogenesis and summarized the anti-HD clinical and pre-clinical natural products, focusing on their therapeutic effects and neuroprotective mechanism/s.