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Withania (Solanaceae, Solanoideae) is a widespread genus. Comparative macro-, micro-morphological, anatomical, and molecular features of this genus in Egypt were examined using light and scanning electron microscopy to reassess the conflicted taxonomic relationships between the two studied species. The most significant morphological differences that have been found were: the shape of the lamina, apex, anther, and stigma, and the ratio of calyx tube/lobe; anatomical examination of taxonomic interest are as follows: number of vascular bundles, presence of ears and distribution of accessory vascular bundles in petiole and shape of spongy cells, and number of lower parenchyma in the midrib region of the leaf; trichomes of both species showed no significant differences; pollen, and seed characters are of taxonomic significance in differentiation and characterization between them. Protein profiling revealed that W. somnifera has only conserved proteins, while W. obtusifolia possessed both conserved and additional proteins in their SDS-PAGE banding patterns. Eleven starts codon-targeted (ScoT) primers were applied and produced 96 amplicons with an average of 70.83% polymorphism/primer. W. obtusifolia generated more polymorphic bands and maintained monomorphic ones. SDS-PAGE disclosed that both Withania species were 50% related. While Scot-Dendrogram revealed that both Withania species were poorly related. So, protein and molecular analyses showed considerable genetic variations between these two species. [ABSTRACT FROM AUTHOR]

For ages, the medicinal plant Withania somnifera, also known as Ashwagandha, has been an essential component of Ayurvedic medicine. It is well documented that components of WS have anti-inflammatory, immunomodulatory, analgesic, and anti-cancer properties. WS is composed of 14 anolides, of which Withaferin A (WA) is the most significant. WA, a steroidal lactone, impedes oncogenic signaling and induces apoptosis in a cancer cell. Previously, we have documented the potency of WA in breast cancer, prostate cancer, and colon cancer. A significant efficacy of WA against the breast cancer stem cell population, a key cell population accountable for chemoresistance, has been documented. Withaferin A targets a multitude of oncoproteins and cell cycle checkpoints and augments the activity of anticancer drugs, thus gaining ground as a promising anticancer molecule. Owing to its strong anti-cancer potential, WA should be a center of focus for the scientific community because of its translational value in the modern medicine system. Additionally, scientific investigation is needed to comprehend WA's pharmacokinetics and bioavailability. In the present review article, we have comprehensively included the molecular targets of WA in various neoplasms. [ABSTRACT FROM AUTHOR]

Withania somnifera plants were exposed to drought stress for 23 days. Relative water content (RWC), gaseous exchange, fluorescence parameters, and spectral reflectance changes were monitored under drought stress. Assimilation rate and RWC decreased by 81% and 65%, respectively, during drought exposure of 23 days. Photosynthetic reflectance index (PRI) and water index (WI) showed a decreasing pattern under drought stress and correlated with Amax and RWC. Anthocyanin reflectance index and anthocyanin content increased with drought stress. Similarly, rational among R727, R696, R770, and R731 reflects chlorophyll content and Chl a/b ratio and copes with actual chlorophyll content. Fluorescence changes showed the opening and closing of PSII reaction centers, while absorbance change at 830/875 nm showed activity and energy balance of PSI. Non-photochemical quenching increased under drought, which showed depoxydation of xanthine cycle pigment. Energy balance at the acceptor and donor side of PSI adjusted under drought stress by increasing electron carrying limitation at donor side. Energy balance between PSI and PSII is maintained by increasing cyclic electron flux under mild drought stress. Both protective mechanism depoxydation of xanthine cycle pigment and enhancement of cyclic electron flux reduced or diminished under severe drought stress. Decrease in leaf area and stomatal closure may cause a reduction in transpiration that results into loss of RWC and altered physiological processes. Since fluorescence, absorbance change and spectral reflectance are non-invasive measurements that may be used as indicators for assessing drought tolerance in medicinal plants. [ABSTRACT FROM AUTHOR]

Introdução: Ashwagandha (Withania somnifera Dunal.) possui compostos bioativos que exercem efeitos adaptogênicos sobre o sistema fisiológico, auxiliando o corpo a adaptar-se a fatores de estresse. Contudo, poucos estudos foram feitos trazendo dados científicos que evidenciem os efeitos da mesma sobre a melhora da performance esportiva. Objetivo: Identificar os efeitos da suplementação de Ashwagandha sobre a melhora da performance esportiva em atletas e não-atletas. Materiais e métodos: revisão integrativa da literatura, por meio das bases de dados: Biblioteca Virtual em Saúde, Google Acadêmico, Scientific Electronic Library Online (SCIELO), U.S National Library of Medicine National Institutes of Health (PUBMED). Foram selecionadas publicações em Português, Inglês e Espanhol, entre os anos de 2011 a 2021, com descritores nas três línguas: “withania somnifera; ashwagandha; performance atlética; performance física”. Foram incluídos 11 artigos que contemplavam a questão norteadora, sendo sete ensaios clínicos randomizados, três revisões sistemáticas com meta-análise e um estudo clínico prospectivo. Resultados: Em todos os estudos incluídos houve melhora sobre a performance física de atletas e não-atletas. Discussão: Aumento de VO2 máximo foi o parâmetro de maior relevância, além de alterações hematológicas e capacidade de gerenciamento de estresse. Aumento incomum de apetite, libido, vertigem e indigestão foram os efeitos adversos identificados. As doses variaram entre 50 e 1250mg/dia na forma de cápsulas e 2,5 a 12g de pó bruto da planta, destacando-se boa tolerabilidade. Conclusão: Ashwagandha é efetiva na melhora da performance física, porém são necessários estudos que avaliem os efeitos da ingestão da planta à longo prazo em atletas e não-atletas.

Background: Withania coagulans is one of the most important medicinal herbs due to its wide range of biological activities. The aim of this study was to compare the hepatoprotective activity of crude methanolic extract versus n-hexane fraction of fruit of Withania coagulans in CCl4 induced liver toxicity Methods: This study was done on 36 Balb c mice in Department of Anatomy of Khyber Medical College Peshawar. Results: The mean serum of Group 1(control Group) was 33.41±1.82U/L, for Group 2 (CCl4 treated Group) was 89.01±7.51 U/L, for Group 3(low dose Group) was 49.91±3.48 U/L and for Group 4 (High dose Group) was 50.86±4.87 U/L. There was significant difference in the readings of Group1 and Group 2 which indicated CCL4 induced hepatotoxicity in two groups. There was significant difference in the values of Group 3 and Group 4 (pvalue .000), showing the hepatotoxicity in these Groups was further enhanced. The mean AST at the end of six weeks for Group1 was 26.80±3.21U/L, for Group 2 was 149.01±13.63U/L, for Group 3 (including both low doses) was 70.81±7.92U/L and for Group 4 (High doses group) was 51.01±11.05U/. Conclusion: Withania coagulans both fractions have hepatoprotective effect against CCL4 induced hepatic toxicity in high and low doses in Balb c mice. [ABSTRACT FROM AUTHOR]

Introduction: Ashwagandha (Withania somnifera) is a plant found on the Indian subcontinent. The health-promoting properties attributed to it have been largely verified in numerous studies over the past 20 years. This article reviews studies on the effects of ashwagandha supplementation on sleep, its deprivation, and studies analyzing the mechanisms determining such effects. Materials and methods: A review of the literature available in the PubMed database was carried out, using the key words: "ashwagandha" ; "sleep" ; "insomnia", "withania", "somnifera", "withanolide", "withaferin". Results: Ashwagandha has a positive effect on the quality and length of sleep. It is indicated that it improves sleep parameters among both insomniacs and healthy people. In addition, it has been proven to reduce oxidative stress under conditions of sleep deprivation. Ashwagandha's positive effects on sleep have been shown to be related to its effects on GABA-nergic transmission, and the chemical responsible for the plant's sleep induction is triethylene glycol. Its regular use increases dopamine levels in the brain and could potentially be useful in treating the sleep-related disorder restless legs syndrome. Conclusions: The use of ashwagandha is a potential direction for treating sleep disorders and improving sleep quality in healthy individuals. There is a need for further development and studies on larger groups of patients to exploit its potential.

As a micronutrient, zinc (Zn) plays an essential role in various physiological processes of plants. Here, acclimatized samples of valerian (Valeriana officinalis L.), chicory (Cichorium intybus L.), withania (Withania. coagulans) and purple coneflower (Echinacea purpurea L.) were evaluated under aeroponic system conditions in order to explore the effects of zinc oxide nanoparticles (ZnO NPs). The plants were foliar sprayed with ZnO NP biofertilizer (0, 1, 2 and 3 g L-1) for 20, 40 and 60 days after transplanting. The experiments were performed based on a completely randomized design with five replications. The valerian showed that 3 g L-1 ZnO NPs caused the highest plant height, root length, leaf number per plant, root volume per plant, as well as fresh and dry weights of roots and shoots. The mean values in chicory showed that the plants that were treated with ZnO NPs (3 g L-1) had the highest amount of biomass and photosynthetic pigments. Based on the results of mean values in purple coneflower, ZnO NPs (3 g L-1) caused the largest increase in morphological values. Furthermore, comparing the mean values in the withania showed that the highest plant height, root length, leaf number per plant, root volume per plant, fresh and dry weights of roots and shoots were observed in plants treated with 3 g L-1 ZnO NPs. Therefore, Zn is considered as an essential micronutrient in the growth of these plants and could be prepared in nanosized form. [ABSTRACT FROM AUTHOR]

Effect of a polyherbal formulation (polyherbal alcoholic extract; PAE) prepared from Withania somnifera (root), Aegle marmelos (leaves), Tribulus terrestris (fruit) was studied on gentamicin-induced nephrotoxicity. Thirty Wistar rats were equally divided into five groups; group I (control), group II (gentamicin alone), group III (prophylactic), group IV (curative) and group V (formulation alone). Gentamicin caused signs of depression, dullness, polyurea, restlessness, reduced body weight, and reduced water and feed intake. These toxicity signs were recovered in the PAE pre-treated prophylactic group; however, in the PAE-treated therapeutic group, some mild toxicity signs were noticed and subsided gradually. Gentamicin increased relative kidney weight but in groups III and IV animals, no significant effect was observed. The Hb, PCV, TEC, TLC and MCV of group II animals revealed a significant decrease, whereas; BUN, creatinine, AST, ALT, ALP, total protein, albumin and globulin were significantly increased. The PAE treatment caused significant recovery in these hematobiochemical parameters in groups III and IV. Gentamicin caused histopathological alterations in kidney represented by focal renal degenerative and necrotic changes, with intratubular hyaline cast. In PAE-treated groups III and IV, minimal histopathological alterations were seen. In conclusion, PAE showed significant protective and moderate therapeutic potential against gentamicin-induced nephrotoxicity in Wistar rats. [ABSTRACT FROM AUTHOR]

ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS (PALS) who ask about them. Here, we review withania somnifera (WS) commonly known as ashwagandha or winter cherry. WS has plausible mechanisms for slowing ALS progression because of its effects on inflammation, oxidative stress, autophagy, mitochondrial function, and apoptosis. Preclinical trials demonstrate that WS slows disease progression in multiple different animal models of ALS. Of the five individuals we found who described using WS for their ALS, two individuals reported moderate benefit while none reported experiencing any significant side effects. There is currently one clinical trial using WS to treat PALS; the results are not yet published. There are no serious side effects associated with WS and the associated cost of this treatment is low. Based on the above information, WS appears to us to be a good candidate for future ALS trials.

The current study depicts the comparative effects of nanogel using Withania coagulans extract, pregabalin alone, and a co-combination gel. The gels prepared were then analyzed for conductivity, viscosity, spread ability, globule size, zeta potential, polydispersity index, and TEM. The globule size of the co-combination gel, determined by zeta sizer, was found to be (329 ± 0.573 nm). FTIR analysis confirms the successful development of gel, without any interaction. Drug distribution at the molecular level was confirmed by XRD. DSC revealed no bigger thermal changes. TEM images revealed spherical molecules with sizes of 200 nm for the co-combination gel. In vivo studies were carried out by infliction of third degree burn wounds on rat skin, and they confirmed that pregabalin and Withania coagulans heals the wound more effectively, with a wound contraction rate of 89.95%, compared to remaining groups. Anti-inflammatory activity (IL-6 and TNF-α), determined by the ELISA technique, shows that the co-combination gel group reduces the maximum inflammation with TNF-α value (132.2 pg/mL), compared to the control (140.22 pg/mL). Similarly, the IL-6 value was found to be (78 pg/mL) for the co-combination gel and (81 pg/mL) in the case of the control. Histopathologically, the co-combination gel heals wounds more quickly, compared to individual gel. These outcomes depict that a co-combination gel using plant extracts and drugs can be successfully used to treat burn injury. [ABSTRACT FROM AUTHOR]

Combating the limitations of chemical approach, a Phyto-reflexive surface decorated ZnO nanoparticles were synthesis for enhanced activity against resistant infectious agent and toxic dyes. Flower-like ZnO nanostructure with average size of 30 nm and 25 nm using chemical method and Phyto-synthesised respectively. Prepared ZnO nano-flowers have been characterised by UV (UV–visible spectrometry), XRD (X-ray Diffraction), TEM (Transmission Electron Microscopy), HRTEM (High Resolution Transmission Electron Microscopy) and EDS (Energy Dispersive X-ray Spectroscopy). Anti-bacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, exhibited 78%, 88% inhibition for chemical prepared ZnO NFs and Phyto-reflexive surface modified ZnO NFs exhibited 85%, 94% compared to Ciprofloxacin. MIC (Minimum Inhibitory Concentration) values against S. aureus and P. aeruginosa of biological ZnO NFs, were calculated as 62.5 and 125 ug/ml and 125 and 250 ug/ml for chemically synthesized ZnO NFs respectively. Anti-fungal activity against Aspergillus niger and Candida Albicans showed 78%, 80% activity with chemically ZnO NFs and 91%, 100% inhibition with biologically ZnO NFs. Anti-oxidant potential determination revealed 56.5% and 67.8% activity at 50 mg/mL with chemical and biological ZnO NF respectively. Furthermore, Degradation of methylene blue (MB) using ZnO NFs up to 78% using chemically prepared and 90% using Phyto-reflexive ZnO NFs. Thus, the comparative analysis concluded, Phyto-reflexive surface modified synthesis of ZnO NFs improved infections activity against pathogens and photocatalytic activity for hazardous chemicals.

Aim To compare the safety and efficacy of Withania somnifera (Withania) and Hypericum perforatum (St John's wort, SJW) in the treatment of stress and anxiety in order to inform clinical practice. Methods Integrative review methodology was followed. Four databases (CINAHL, AMED, ProQuest and MEDLINE) were searched to obtain peer-reviewed journal articles examining Withania or SJW for the treatment of anxiety and/or stress. Searches to identify herb--drug reactions (HDRs) and adverse drug reactions (ADRs) associated with the use of these herbs in the treatment of anxiety and stress were also performed. Human studies, written in English, published between 2010 and 2020 were included. In vitro, animal and paediatric studies were excluded. Studies were screened by title, abstract and full text and assessed against the aims of the review. Results After duplicates were removed, 781 studies were screened by title and abstract, leaving 64 to be screened by full text; 16 studies met the inclusion criteria. Studies showed Withania to be a safe and effective treatment for anxiety and stress. No HDRs were identified for Withania, and reported ADRs were infrequent and mild. Key safety issues with SJW include an increased risk of psychosis in susceptible individuals, multiple known HDRs, and a higher incidence of ADRs. Conclusion Withania is a safe and effective treatment for stress and anxiety and has a superior safety profile to SJW. Given the high rates of self-prescription, and the possibilities of ADRs and HDRs identified with SJW, healthcare practitioners should enquire about SJW use with all patients. [ABSTRACT FROM AUTHOR]

In this study, we aimed to examine the effects of a 2 mT strength static magnetic field, which is generated by placing a permanent magnet in water for 1 h, on the physical properties of magnetized water, such as its viscosity, conductivity, and pH value. The growth and yield of Phaseolus vulgaris irrigated with tap water and magnetized water were also examined and compared. We further evaluated its morphological characteristics, such as plant height, number of pods per plant, number of seeds per pod, and fresh and dry weight of seeds, and physiological parameters (i.e., chlorophyll content, total sugar content, some elements, and crude protein concentration). As per our findings, the measured parameters of plants irrigated with magnetized water exhibited remarkable increases compared to those irrigated with tap water, in addition to increased seed production at harvest and changes in the concentration of elements. Despite the weak strength of the magnetic field, the pH value increased by 11.6%, viscosity by 10%, and conductivity by 10%. [ABSTRACT FROM AUTHOR]

Endophytic fungi are important microbes that exist in the internal tissues of diverse parts of the plant, developing a mutual relationship. The present study was concentrated on the isolation, identification and mycochemical profiling of the fungal endophyte in the healthy and matured leaves of Wendlandia thyrsoidea (Roth) Steud. of Chikkamagaluru. The endophytic fungus was identified based on morphological characteristics and molecular characterization. The aim of this study is metabolite profiling by HR-LCMS and molecular characterization of endophytic Xylaria adscendens (Fr.) Fr., in Wendlandia thyrsoidea, an ethnomedicinally important and widely used plant in Indian subcontinent. [ABSTRACT FROM AUTHOR]

Vegetation cover is one of the main components of natural environments. Vegetation plays a fundamental role in the structure and functioning of ecosystems, of which it constitutes an expression of biological potential. The forest ecosystem of western Algeria, and more precisely that of the Tlemcen region, which is part of the Mediterranean domain, has suffered for several years a continuous regression, clearly visible and sometimes irreversible, and most often due to a combined action of climatic, ecological and anthropogenic factors. Faced with the gravity of this ecological situation in the region, the need for an action plan to preserve biodiversity is imperative in order to measure and quantify the degradation of biological resources. But such a plan can only see the light of day if the knowledge and management of the flora by the ecologists is mastered, with the major concern for the dynamics of the vegetation, because the vegetation of the Tlemcen region presents a good example. Study of plant diversity and an interesting synthesis of the natural dynamics of ecosystems, from the coast to the steppes. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of competing interest I hereby declare that the disclosed information is correct and that no other situation of real, potential or apparent conflict of interest is known to us.

Background: Ashwagandha is a well-known Ayurvedic herb used for youthful vigor and wellbeing. This study investigated the effects of 600 mg standardized root extract (>5% withanolides) of Ashwagandha ( Withania somnifera ) on muscle size, strength and cardiorespiratory endurance following resistance training., Methods: In this eight-week, parallel-group, multicenter, randomized, double-blind, placebo-controlled clinical study, 80 healthy male and female participants aged 18-45 years, who engaged in regular physical activity were randomly allocated in a 1:1 ratio to receive Ashwagandha (AG, n=40) 300 mg capsules twice daily for eight weeks, or identical placebo (PB, n=40). Seven (3 AG, 4 PB) participants were excluded due to poor compliance. All participants conducted eight-week resistance training. Study outcomes included muscle strength (1RM bench press and leg extension), muscle size (circumference of arm, chest and upper thigh) and cardio-respiratory endurance (VO 2max ) assessed at baseline and at eight weeks. Analysis of covariance (ANCOVA) was used to estimate adjusted differences based on sex, BMI and chest circumference at baseline., Results: AG caused greater improvement in bench press (males: p = 0.0084; females: p = 0.0005), leg press (males: p = 0.0049; females: p = 0.018) and endurance (males: p <0.0001; females: p <0.0001) as compared to PB. Also, greater improvements in muscle girth for arm, chest and thigh were seen in both male and female participants with AG. No adverse events were reported in the study., Conclusions: Eight weeks of AG root extract supplementation along with resistance training is effective in improving muscle strength, growth and endurance in both male and female participants. AG root extract could be a safer, effective and low-cost alternative for athletes to improve muscle endurance., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Verma N et al.)

The prevalence of stress- and anxiety-related disorders is increasing along with widespread demand for anxiolytics. Due to drug supply shortages and access restrictions, nonprescription remedies have gained popularity. In addition, the marketing of herbals and botanicals as low-cost and all-natural products with fewer access restrictions has increased their use. The current article explores the evidence to provide an overview of the current understanding of Ashwagandha ( Withania somnifera ), an anxiolytic and apoptogenic herb with therapeutic and health-promoting potentials to help the body reduce stress and maintain a homeostatic state. Due to poor quality controls and diversity of Ashwagandha products, clinical trials on Ashwagandha's effectiveness in anxiety-related conditions reveal conflicting results, although many show favorable findings. Furthermore, health care professionals, such as nurses, advanced practice nurses, physicians, physician assistants, and pharmacists, need to be aware of variability in Ashwagandha products, quality controls, reported evidence regarding use, safety profile, and clinical implications in stress reduction. [ Journal of Psychosocial Nursing and Mental Health Services, 62 (4), 33-40.].

In other to study the effect of the production system (aeroponic and soil production system), an experiment was conducted based on a completely randomized design with five replication. In this study plants were obtained from seed culture (Cichorium, Withania and Echinacea) in pot for 1 month in greenhouse and then, uniform plants (20 cm height, approximately) were transferred to aeroponic system and soil. The plants were harvested after six months and their vegetative traits and root characteristic were measured. The results indicated that the effects of production system were significant in terms of plant height, root length, number of leaves, shoot and root fresh and dry weights and photosynthetic pigments. The result showed that aeroponic system in comparison with soil system has produced the highest of leaf number, root length, plant height, root and shoot dry weight, root and shoot fresh weight and photosynthetic pigments. It can be concluded that aeoponic systems could be used for production of Cichorium, Echinacea and Withania under greenhouse. [ABSTRACT FROM AUTHOR]

Dharmendra K Yadav,1 Surendra Kumar,2 Saloni,1 Harpreet Singh,3 Mi-hyun Kim,1 Praveen Sharma,4 Sanjeev Misra,4 Feroz Khan5 1Department of Pharmacy, College of Pharmacy, Gachon University, Yeonsu-gu, Incheon, Republic of Korea; 2Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Babu Banarasi Das Northern India Institute of Technology, Lucknow, 3Department of Bioinformatics, Indian Council of Medical Research, New Delhi, 4Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 5Metabolic & Structural Biology Department, CSIR– Central Institute of Medicinal & Aromatic Plant, Lucknow, India Abstract: Withanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian traditional practice of medicine. Withanolides are steroidal lactones (highly oxygenated C-28 phytochemicals) and have been reported to exhibit immunomodulatory, anticancer and other activities. In the present study, a quantitative structure activity relationship (QSAR) model was developed by a forward stepwise multiple linear regression method to predict the activity of withanolide analogs against human breast cancer. The most effective QSAR model for anticancer activity against the SK-Br-3 cell showed the best correlation with activity (r2=0.93 and rCV2 =0.90). Similarly, cross-validation regression coefficient (rCV2=0.85) of the best QSAR model against the MCF7/BUS cells showed a high correlation (r2=0.91). In particular, compounds CID_73621, CID_435144, CID_301751 and CID_3372729 have a marked antiproliferative activity against the MCF7/BUS cells, while 2,3-dihydrowithaferin A-3-beta-O-sulfate, withanolide 5, withanolide A, withaferin A, CID_10413139, CID_11294368, CID_53477765, CID_135887, CID_301751 and CID_3372729 have a high activity against the Sk-Br-3 cells compared to standard drugs 5-fluorouracil (5-FU) and camptothecin. Molecular docking was performed to study the binding conformations and different bonding behaviors, in order to reveal the plausible mechanism of action behind higher accumulation of active withanolide analogs with β-tubulin. The results of the present study may help in the designing of lead compound with improved activity. Keywords: ADMET, breast cancer, QSAR, molecular docking, withanolides

Detailed male meiosis has been made in two species of genus Withania collected from desert regions of Rajasthan, India. The study revealed 2n=48 for both the species. The meiotic analysis of W. somnifera is reported to be normal whereas, W. coagulans showed abnormal meiosis with the presence of abnormalities like spindle irregularities, chromatin transfer, laggards and irregular microsporogensis with the presence of monads, dyads, triads, polyads and tetrads with micronuclei which further lowered the pollen fertility and giving rise to varying size pollen grains. Both the species are widely used for various medicinal purposes by local/tribal people of the state.

Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product primarily derived from various medicinal plants in the Withania genus, withanolides have been shown in several studies to exhibit potential activities in cancer treatment. Consequently, understanding the molecular mechanism of withanolides could herald the discovery of new anticancer agents. Withanolides have been studied widely, especially in the last 20 years, and attracted the attention of numerous researchers. Currently, over 1200 withanolides have been classified, with approximately a quarter of them having been reported in the literature to be able to modulate the survival and death of cancer cells through multiple avenues. To what extent, though, has the anticancer effects of these compounds been studied? How far are they from being developed into clinical drugs? What are their potential, characteristic features, and challenges? In this review, we elaborate on the current knowledge of natural compounds belonging to this class and provide an overview of their natural sources, anticancer activity, mechanism of action, molecular targets, and implications for anticancer drug research. In addition, direct targets and clinical research to guide the design and implementation of future preclinical and clinical studies to accelerate the application of withanolides have been highlighted., (© 2024 John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Withania somnifera (L.) Dunal (WS) and Abelmoschus esculentus (L.) Moench (AE) are known as Ashwagandha and Okra, respectively, important herbs in traditional medicine for their diverse therapeutic values. WS root is an adaptogen that relieves stress and anxiety and promotes sleep. AE fruit or Okra is widely consumed as a vegetable and is traditionally used to treat diabetes, gastric irritations, ulcers, and obesity., Aim of the Study: The present randomized, double-blind, placebo-controlled study aimed to establish a proof-of-concept evaluating the efficacy and tolerability of a proprietary blend of standardized extracts of WS root and AE fruit, CL18100F4 in relieving constipation and improving quality of life in adults., Materials and Methods: Forty-eight male and female participants (age: 25-60 years) with functional constipation (following Rome-III criteria) were randomized into placebo, 300 or 500 mg of CL18100F4 groups, and supplemented for fourteen consecutive days., Results: CL18100F4 supplementation significantly (p < 0.0001) reduced the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), and Gastrointestinal Symptom Rating Scale (GSRS) scores. CL18100F4 supplementation improved sleep quality and reduced stress (p < 0.0001). At the end of the study, CL18100F4-500 subjects showed significant increases in serum serotonin, gastrin, and interleukin-10 and decrease in interleukin-6 and cortisol levels. Participants' hematology, total blood chemistry, vital signs, and urinalysis parameters were within the normal ranges. No adverse events were reported., Conclusions: This short-duration, single-site clinical investigation demonstrates that CL18100F4 supplementation is tolerable, helps relieve constipation, reduces stress, and improves gastrointestinal function, sleep quality, and general wellness in adults., Trial Registration: Clinical Trials Registry- India (CTRI/2020/11/029320); Registered on 24/11/2020. Available at: http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49391&EncHid=&userName=CL18100F4., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1β, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LH is the managing director of Pharmanza Herbal Pvt. Ltd. which is licensed to manufacture WSE for human use as a nutraceutical. He had no role in the design or conduct of the study, nor in the interpretation of results. Other authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims and Objectives: Posttraumatic stress disorder (PTSD) is a complex neuropsychiatric pathophysiology with an unmet need for safe, effective, and sustainable therapeutic modalities. Thus, the present study evaluated the effects of Withaniasomnifera (WS, Ashwagandha) on an experimental model of PTSD in rats., Materials and Methods: Wistar rats (200-250 g) were used and time-dependent sensitization (TDS) was used as the experimental model of PTSD. Standardized WS root extract (100 and 300 mg/kg, p.o. for 15 days) was administered with TDS and their effects were observed on neurobehavioral (anxiety) and brain cytokines, corticosterone, and oxidative stress markers., Results: Exposure to TDS resulted in anxiogenic behavior in the elevated plus maze (EPM) test, i.e., reductions in open arm entries and open arm time, as compared to the control group. Pretreatment with WS extract (100 and 300 mg/kg × 14 days) attenuated the TDS-induced anxiogenic activity in a dose-related manner, and these WS effects were comparable to those seen after the comparator drug fluoxetine (10 mg/kg). Assay of brain homogenates showed that TDS also resulted in elevations in brain interleukin-6 and reduction in corticosterone levels in both the hippocampus and prefrontal cortex (PFC), which were reversed after WS pretreatments. Further, WS pretreatment also reversed the TDS-induced changes in brain oxidative stress markers, namely elevated malondialdehyde and reduced glutathione levels in both the hippocampus and PFC., Conclusion: These results suggest that WS could have potential as a therapeutic agent for treating PTSD by attenuating anxiogenesis, neuroimmune axis activation, and oxidative stress., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pharmacology.)

Natural carbon dots (NCQDs) are expediently significant in the photo-, nano- and biomedical spheres owing to their facile synthesis, optical and physicochemical attributes. In the present study, three NCQDs are prepared and optimized from Withania somnifera (ASH) by one-step hydrothermal (bottom-up) method: HASHP (without dopant), nitrogen doped HASHNH 3 (surface passivation using ammonia) and HASHEDA (surface passivation with ethylenediamine). The HR-TEM images reveal that HASHP, HASNH 3 , HASHEDA are spherically shaped with 2.5 ± 0.5 nm, 4 ± 1 nm and 5 ± 2 nm particle size, respectively, whereas FTIR confirms the aqueous solubility and nitrogen doping. The XRD patterns ensure that the NCQDs are amorphous and graphitic in nature. Comparatively, HASHNH 3 (32.5%) and HASHEDA (27.6%) portray better fluorescence quantum yield than HASHP (5.6%). The increase in quantum yield for the doped NCQDs can be attributed to the surface passivation using ammonia and ethylenediamine. Surface passivation plays a crucial role in enhancing the fluorescence properties of quantum dots. The introduction of nitrogen through ammonia and ethylenediamine provides additional electronic states, possibly reducing non-radiative recombination sites and hence boosting the QY. In addition, an antiviral study unveils the striking potential of surface passivated NCQDs to curb Covid-19 crises with around 85% inhibition of SARS-CoV pseudoviron cells, which is better in comparison to the non-doped NCQDs. Hence, to understand the paramount efficacy of these NCQDs, a hypothesis on their possible mechanism of action against Covid-19 is discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Histology (from the ancient Greek hystos = tissue and logos = study) is the branch of biology and medicine that studies biological tissue. We used to talk about microscopic anatomies. It aims to explore the structure of living organisms, the constitutive and functional relationships between their functional elements, as well as tissue renewal. The methodology of plant histology is not fundamentally different from that of animal histology. The basic technique generally involves fixing the samples followed by hardening or inclusion in paraffin or plastics, sections by microtomy and then either topographic staining when looking for an overview, or specific when looking for an overview, or specific when wants to electively characterize certain structures. In this summary, we will present a study of the internal structure of the stem and leaf of Withania frutescens (Solanaceae) at the microscopic scale. The histological study carried out at the root and leaf level of Withania frutescens (Solanaceae) allows us to analyze the different structures well and with precision and to draw the general characteristics concerning the arrangement of tissues in plant organs. [ABSTRACT FROM AUTHOR]

Withania somnifera , also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera , acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

Extraction of bioactive compounds from Withania somnifera roots was studied using sodium acetate-glycerol deep eutectic solvent (DES) and two techniques ultrasound-assisted extraction (UAE) and heat-assisted extraction (HAE) under response surface methodology (RSM). For UAE and HAE, total phenolic content (TPC, mg gallic acid equivalents per g dry weight (mg GAE g-1 DW)), total flavonoid content (TFC, mg rutin equivalents g-1 DW (mg RE g-1 DW)), radical scavenging activity (RSA, mg AAE (ascorbic acid equivalents) g-1 DW), and iron chelating activity (ICA, mg EDTAE (ethylenediaminetetraacetate equivalents) g-1 DW%) were 6.51, 6.08, 12.56, and 3.57, respectively, and 3.33, 3.98. 6.57 and 2.48, respectively. For UAE, the optimal conditions were a DES concentration of 50 %, temperature of 60 °C, and time of 20 min, and for HAE, a DES concentration of 60 %, temperature of 60 °C, and time of 75 min. The discovered models were strongly supported by the validation experiments. UAE was more efficient and less time-consuming for extracting phytoconstituents of the W. somnifera than HAE.

Background: Stress is a state of homeostasis in the body being challenged, resulting in a systemic response. It has become more prevalent in recent years and affects mental and physical health., Aims: Evaluate the effects of ashwagandha on stress, fatigue, and sex hormones in overweight or mildly obese men and women with self-reported stress and fatigue., Methods: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial on overweight or mildly obese men and women aged 40-75 years, supplementing with 200 mg of an ashwagandha root extract (Witholytin®) twice daily., Results/outcomes: Supplementation with ashwagandha was associated with a significant reduction in stress levels based on the Perceived Stress Scale (primary outcome); however, the improvements were not significantly different to the placebo group ( p  = 0.867). Based on the Chalder Fatigue Scale, there was a statistically significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group ( p  = 0.016), and participants taking ashwagandha also experienced a significant increase in heart rate variability ( p  = 0.003). However, there were no significant between-group differences in other self-report outcome measures. In the men taking ashwagandha, there was a significant increase in the blood concentrations of free testosterone ( p  = 0.048) and luteinizing hormone ( p  = 0.002) compared to the placebo group., Conclusions/interpretation: The results of this study suggest that in overweight middle-to-older age adults experiencing high stress and fatigue, compared to the placebo, ashwagandha did not have a significantly greater impact on perceived stress levels. However, based on secondary outcome measures, it may have anti-fatigue effects. This may be via its impact on the autonomic nervous system. However, further research is required to expand on these current findings., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ALL is the managing director of Clinical Research Australia, a contract research organization that has received research funding from nutraceutical companies. ALL has also received presentation honoraria from nutraceutical companies. SJS is an employee of Clinical Research Australia and declares no other conflicts of interest. TJF declares no conflicts of interest.

Memory deficit is one of the major negative outcomes of chronic stress. Cholinergic system modulates memory not only through the neuronal cells, but also via interactions with non-neuronal cells, suggesting that microglia can influence synaptic function and plasticity, contributing to cognition and memory function. Withania somnifera (L.) Dunal (WS) and Bacopa monnieri (L.) Wettst (BM), are traditional herbal medicinal products used for the temporary relief of symptoms of stress. The aim of this study was to investigate whether choline (CLN) activity could be enhanced via an association with adaptogens: WS and BM extracts. First, we optimized an in vitro model of corticotropin-releasing hormone (CRH)-induced oxidative stress on microglial BV2 cells. CRH 100 nM reduced BV2 cell viability and induced morphological changes and neurotoxicity after 24 h of microglia stimulation. Moreover, it induced an increase in the production of reactive oxygen species (ROS) and dysregulated antioxidant protein (i.e., SIRT-1 and NRF-2). The association between choline and adaptogens (CBW) 10 μg/mL counteracted the effect of CRH on BV2 cells and reduced the neurotoxicity produced by BV2 CRH-conditioned medium in the SH-SY5Y cell lines. CBW 200 mg/kg produced an ameliorative effect on recognition memory in the novel object recognition test (NORT) test in mice. In conclusion, combining choline with adaptogen plant extracts might represent a promising intervention in chronic stress associated with memory disturbances through the attenuation of microglia-induced oxidative stress.

Background: Ayurveda interventions have been used for prophylaxis and care during the COVID-19 pandemic in India and have shown promising results in promoting early clinical recovery from COVID-19., Objective: To assess the efficacy and safety of Ashwagandha [Withania somnifera (L.) Dunal] tablet and Shunthi (Zingiber officinale Roscoe) capsule in mild and moderate COVID-19 compared to conventional standard care., Methods: A randomized controlled exploratory trial was conducted at a designated COVID-19 care center in India with 60 participants having mild or moderate COVID-19. Ashwagandha, two tablets (250 mg each), and Shunthi, two capsules (500 mg each) twice daily for 15 days, were given orally to the participants in the Ayurveda group (AG) and the control group (CG) received conventional standard care. The outcome measures included clinical recovery rate, the proportion of participants with negative RT-PCR assay for COVID-19 on day 7 and day 15, mean time to attain clinical recovery, change in pro-inflammatory markers, serum IgG for COVID-19, HRCT chest findings, disease progression and incidence of adverse events (AE)., Results: A total of 60 participants were enrolled, and the data of 48 participants (AG = 25 and CG = 23) were considered for the statistical analysis. The mean time for clinical recovery was reduced by almost 50 % in the AG (6.9 days) compared to CG (13.0 days) (p < 0.001). The proportion of participants who attained viral clearance in AG was 76.0 % compared to 60.8 % in the CG (RR= 1.24, 95 % CI: 0.841, 1.851, p-value = 0.270). Changes in the pro-inflammatory markers, serum IgG for COVID-19, and HRCT chest findings were comparable in both groups, and no AE or disease progression was reported., Conclusions: The Ayurveda interventions, Ashwagandha and Shunthi, can effectively reduce the duration of clinical recovery and improve time for viral clearance in mild and moderate COVID-19. These interventions were observed to be safe and well-tolerated during the duration of the trial., Trial Registration: Clinical Trial Registry of India - CTRI/2020/08/027224., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interests. The authors Harbans Singh, Babita Yadav, Amit K Rai, AJV Saiprasad, Sophia Jameela, Rakesh Rana, Shruti Khanduri, Bhagwan S Sharma, Bhogavalli Chandrasekhararao and Narayanam Srikanth work in Central Council for Research in Ayurvedic Sciences (CCRAS), Ministry of Ayush, Government of India, New Delhi., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

PURPOSE OF REVIEW: Withania somnifera (L.) Dunal (Ws) is a common herb plant that has been used for centuries to treat a wide range of conditions, particularly certain chronic diseases due to its antidiabetic, cardioprotective, antistress, and chondroprotective effects, among many others. No conclusive evidence, however, exists about the potential health effects of Ws in adults without chronic conditions. We aimed to evaluate the current evidence on the health benefits of Ws supplementation in healthy adults. RECENT FINDINGS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed studies indexed in Web of Science, Scopus, and PubMed to assess the effects of Ws on hematological and biochemical markers, hormonal behavior, and oxidant response in healthy adults. Original articles published up to March 5, 2022, with a controlled trial design or pre-post intervention design, in which supplementation of Ws was compared to a control group or data prior to intervention were included. Among 2,421 records identified in the search, 10 studies met the inclusion criteria. Overall, most of the studies reported beneficial effects of the Ws supplementation, and no serious adverse events were reported. Participants supplemented with Ws displayed reduced levels of oxidative stress and inflammation, and counterbalanced hormone levels. No evidence of the beneficial effects of Ws supplementation on hematological markers was reported. Ws supplementation appears to be safe, may regulate hormone levels, and has potent anti-inflammatory and antioxidant effects. However, further studies are needed to elucidate the relevance of its application., (© 2023. The Author(s).)