Innovative Bedaquiline-Based Delivery Systems for Multidrug-Resistant Tuberculosis Treatment.

The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) is one of the most challenging tasks in tuberculosis treatment. Conventional TB treatment regimens have proven ineffective in treating MDR-TB, thus demanding the development of new drugs followed by delivery systems. Bedaquiline, a novel anti-TB drug, has been reported to inhibit the ATP synthase required for the growth and replication of TB bacteria. Bedaquiline is able to target the persistent or latent form of TB, which remains difficult to treat with conventional drugs. This makes bedaquiline an important drug in the fight against MDR-TB. The drug has been approved by the US FDA as well as European Medicines Agency and is now widely used as part of combination therapy for the treatment of MDR-TB. Bedaquiline and its ad-vanced drug delivery system play a key role in tackling MDR-TB, providing a much-needed boost to control and eventually eliminate the disease. However, the cost of the drug remains a concern, and efforts are underway to make bedaquiline more accessible and affordable to patients in resource-limited settings. Nevertheless, the development of bedaquiline nanofor-mulations represents a significant step forward in the fight against TB and offers hope to millions of patients across the globe.

Exploring biological activities of novel Schiff bases derived from amlodipine and in silico molecular modeling studies.

Aim: Calcium channel antagonists are of considerable interest in treating elevated blood pressure and its pathologies.Materials & methods: Schiff base derivatives of amlodipine were produced to check its urease inhibition potentials as well antibacterial and antioxidant activities. Structural illustration along with chemical characterization were achieved by spectral techniques (1H NMR, FTIR, 13C NMR) and docking studies also performed.Results & conclusion: 3g displayed remarkable anti-hypertensive activity compared with parent drug. 3b, 3f and 3g showed urease inhibition potentials. These compounds can aid as lead for further investigations since they exhibited comparable or superior interactions.

[Box: see text].

To Assess the Knowledge and Attitude Regarding Dental Trauma and Its Management among School Teachers.

Background: Dental traumas, particularly tooth avulsion, represent a significant dental emergency among children, frequently occurring in schools. The knowledge and immediate response of schoolteachers are crucial for the prognosis of such emergencies. Materials and Methods: This interventional study assessed the knowledge and attitudes of 248 primary school teachers in Rajasthan, India, regarding dental trauma management. Utilizing a questionnaire-based approach, the study was conducted in three phases: preintervention assessment, an informative 45-minute lecture, and a postintervention follow-up. Statistical significance was set at 5%, and the Chi-square test was employed for analysis. Results: The initial survey revealed a lack of knowledge among teachers regarding dental trauma management, with significant improvement observed in the follow-up phase post intervention. Over 90% of participants showed improved knowledge, with statistical significance (P < 0.0001). Conclusion: The study highlights a notable deficiency in school teachers' knowledge on dental trauma management initially, which significantly improved following an oral health promotion intervention. This underscores the effectiveness of educational programs in enhancing the management of dental emergencies by schoolteachers.

Endothelin-1-Induced Persistent Ischemia in a Chicken Embryo Model.

Current ischemic models strive to replicate ischemia-mediated injury. However, they face challenges such as inadequate reproducibility, difficulties in translating rodent findings to humans, and ethical, financial, and practical constraints that limit the accuracy of extensive research. This study introduces a novel approach to inducing persistent ischemia in 3-day-old chicken embryos using endothelin-1. The protocol targets the right vitelline arteries, validated with Doppler blood flow imaging and molecular biology experiments. This innovative approach facilitates the exploration of oxidative stress, inflammatory responses, cellular death, and potential drug screening suitability utilizing a 3-day-old chicken embryo. Key features • This model enables the evaluation and investigation of the pathology related to persistent ischemia • This model allows for the assessment of parameters like oxidative stress, inflammation, and cellular death • This model enables quantification of molecular changes at the nucleic acid and protein levels • This model allows for the efficient screening of drugs and their targets Graphical overview.

Computational screening of chemical constituents derived from berry fruits as allosteric caspace-3/-7 inhibitors.

With the aim of finding the plant-derived allosteric inhibitors of caspase-3/-7, we conducted computational investigations of bioactive compounds present in various berry fruits. In a molecular docking study, perulactone demonstrated excellent binding affinity scores of -12.1 kcal/mol and -9.1 kcal/mol for caspase 7 and 3, respectively, whereas FDA-approved allosteric inhibitors (DICA and FICA) were found to show lower docking scores (-5.6 and -6.1 kcal/mol) against caspase 7 while (-5.0 and -5.1 kcal/mol) for caspase 3, respectively. MD simulations were used to validate the binding stability of perulactone in the active sites of caspase-7/-3, and the results showed outstanding stability with lower ligand RMSDs of 1.270-3.088 Å and 2.426-9.850 Å against the targeted receptor. Furthermore, we performed MMGBSA free binding energy, where the perulactone values of ΔG Bind were determined to be -63.98 kcal/mol and -66.32 kcal/mol for both receptors (3IBF and 1NME), which are significantly better than the -45.16 kcal/mol and -39.51 kcal/mol for DICA as well as -26.37 kcal/mol and -15.50 kcal/mol for FICA, respectively. The drug resemblance of perulactone was effectively evaluated by ADMET. Thus, our findings indicated that perulactone could be an orally administered therapeutic candidate for regulating apoptosis in a variety of disorders. However, there may be an urgent need to study using in vitro and in vivo experiments. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04067-7.

Synthesis of quercetin derivatives as cytotoxic against breast cancer MCF-7 cell line in vitro and in silico studies.

Background: Quercetin being antioxidant and antiproliferative agent acts by inhibiting CDK2, with an increase in cancer prevalence there is a need to profile quercetin derivatives as CDK2 inhibitors.Materials & method: Schiff bases of quercetin were synthesized as cytotoxic agents against the MCF7 cell line. FTIR, 1H-NMR and 13C-NMR, CHNS/O analysis were employed along with in vivo and in silico activities.Results & conclusion: 2q, 4q, 8q and 9q derivatives have maximum cytotoxic effect with IC50 values 39.7 ± 0.7, 36.65 ± 0.25, 35.49 ± 0.21 and 36.99 ± 0.45, respectively. Molecular docking also confirmed these results 8q has the highest binding potential of -9.165 KJ/mole making it a potent inhibitor of CDK2. These derivatives can be used as lead compounds as potent CDK2 inhibitors.

[Box: see text].

Molecular docking, derivatization, characterization and biological assays of amantadine.

Background: Derivatization has been tremendously utilized in the field of drug discovery for optimizing the pharmacological properties and improving safety, efficacy and selectivity. Methodology: Schiff's bases (AD1-AD11) are synthesized through amantadine condensation with different aldehydes and ketones. Fourier transform infrared, 1H NMR, 13C NMR, TLC, liquid chromatography mass spectrometry analysis, in silico studies, molecular docking and antiviral activity through hemagglutinin test were performed for evaluation of new compounds. Results: AD2, 3 and 9-11 showed greater antiviral activity than the parent drug. Among all derivatives, AD2 and AD3 exhibited good potential against α-amylase while AD7 and AD10 showed stronger inhibition against α-glucosidase. Conclusion: So, it is concluded that the most potent derivatives can be used as lead compounds in novel drug design of antiviral antidiabetic agents.

[Box: see text].

Recent Advances in the Development of Alpha-Glucosidase and Alpha-Amylase Inhibitors in Type 2 Diabetes Management: Insights from In silico to In vitro Studies.

Diabetes is a metabolic disorder caused by high glucose levels, leading to serious threats such as diabetic neuropathy and cardiovascular diseases. One of the most reliable measures for controlling postprandial hyperglycemia is to reduce the glucose level by inhibiting enzymes in the digestive system, such as Alpha-Glucosidase and Alpha-Amylase. Here, we have investigated the use of inhibitors to inhibit carbohydrate metabolism in order to restrict glucose levels in diabetic patients. Acarbose, Voglibose, and Miglitol are three inhibitors approved by the FDA that efficiently inhibit these two enzymes and thereby minimising hyperglycemia but are al-so significantly helpful in reducing the risk of cardiovascular effects. We also provide insight into the other known inhibitors currently available in the market. The adverse effects associated with other inhibitors emphasise the demand for the latest in silico screening and in vitro validation in the development of potent inhibitors with greater efficacy and safety for the treatment of Type 2 diabetes. The recent findings suggest that Alpha-Glucosidase and Alpha-Amylase play a major role in carbohydrate metabolism and triggering the increase in glucose levels. This review pro-vides the latest scientific literature findings related to these two enzymes as well as the role of primary and secondary inhibitors as potential candidates. Moreover, this review elaborates the framework on the mechanism of action, different plant sources of extraction of these enzymes, as well as kinetic assay of inhibitors and their interaction that can be used in future prospects to de-velop potential leads to combat Type 2 diabetes.

Cardiac Progenitor Cell Metabolism.

Metabolism has emerged recently as an important determinant of stem cell function. Changes in metabolic signaling pathways precede changes in stem cell molecular and functional response. Pluripotent stem cells are highly proliferative and known to exhibit increased glycolysis. Similarly, adult stem cells reside in tissue niches in a quiescent state operating via glycolysis. Upon activation, adult stem cell metabolism transitions from glycolysis to oxidative phosphorylation which coincides with reduced proliferation and multilineage potential. In the heart, different populations of cardiac progenitor cells (CPCs) have been identified. CPCs regenerative potential is linked to changes in metabolic characteristics of cells, impacting cardiac repair following injury. Here, we discuss the methodologies for isolation and characterization of a novel cardiac progenitor cell population from the heart including measurement its metabolic features.

The Uncertain Benefit from Implantable Cardioverter-Defibrillators in Nonischemic Cardiomyopathy: How to Guide Clinical Decision-Making?

Life-threatening dysrhythmias remain a significant cause of mortality in patients with nonischemic cardiomyopathy (NICM). Implantable cardioverter-defibrillators (ICD) effectively reduce mortality in patients who have survived a life-threatening arrhythmic event. The evidence for survival benefit of primary prevention ICD for patients with high-risk NICM on guideline-directed medical therapy is not as robust, with efficacy questioned by recent studies. In this review, we summarize the data on the risk of life-threatening arrhythmias in NICM, the recommendations, and the evidence supporting the efficacy of primary prevention ICD, and highlight tools that may improve the identification of patients who could benefit from primary prevention ICD implantation.

Phytochemical characterization, biochemical profiling and evaluation of anticancer potential of methanolic extract of Withania somnifera stem.

OBJECTIVES: Phytotherapy employs phytoconstituents/phytomedicines derived from plants for treating and preventing illnesses. Withania somnifera is known in the Indian Ayurveda Pharmacopoeia for its medicinal applications and pharmacological properties. In this study, we examined the biological activity spectrum of Withania somnifera methanolic extract of stem (WSME), which is valued as a "Rasayana" due to its extensive range of medicinal uses. METHODS: WSME was subjected to TPC and TFC quantification and bioactive components were characterized using LC-MS. Its antioxidant potential was gauged by DPPH and H2O2 radical scavenging assays, while antibacterial efficacy was assessed against S. aureus and E. coli using disc diffusion assay. In vitro anticancer activity was evaluated against human breast cancer MDA-MB-231 cells while toxicity was evaluated against normal Vero cells using MTT assay. RESULTS: WSME, rich in Withaferin A, showed TPC of 4.73 ± 0.15 mg GAE/g and TFC of 94.94 ± 6.15 mg QE/g dry weight of extract. It exhibited significant antioxidant activity (43.28 and 66.8 % inhibition at 1,000 µg/mL using DPPH and H2O2 assays, respectively) and mild antibacterial effects against S. aureus (300-500 mg/mL). WSME induced cell death in MDA-MB-231 cells and significantly inhibited their growth (IC50: 66 µg/mL, P value<0.05) without affecting normal Vero cells in the studied range of 25-400 µg/mL (IC50: 6.09 mg/mL, P value>0.05). CONCLUSIONS: The present study lends support to further testing of WSME against other cancer cell lines and animal models of cancer. These preclinical studies would provide further validation to its prospective use as an adjunct in human breast cancer therapy.

Mango peel extracts and mangiferin chromatographic Fourier-transform infrared correlation with antioxidant, antidiabetic, and advanced glycation end product inhibitory potentials using in silico modeling and in vitro assays.

Mangifera indica peels are a rich source of diverse flavonoids and xanthonoids; however, generally these are discarded. Computational studies revealed that mangiferin significantly interacts with amino acid residues of transcriptional regulators 1IK3, 3TOP, and 4f5S. The methanolic extract of Langra variety of mangoes contained the least phenol concentrations (22.6 ± 0.32 mg/gGAE [gallic acid equivalent]) compared to the chloroform (214.8 ± 0.12 mg/gGAE) and ethyl acetate fractions (195.6 ± 0.14 mg/gGAE). Similarly, the methanolic extract of Sindhri variety contained lower phenol concentrations (42.3 ± 0.13 mg/gRUE [relative utilization efficiency]) compared with the chloroform (85.6 ± 0.15 mg/gGAE) and ethyl acetate (76.1 ± 0.32 mg/gGAE) fractions. Langra extract exhibited significant α-glucosidase inhibition (IC50 0.06 mg/mL), whereas the ethyl acetate fraction was highly active (IC50 0.12 mg/mL) in Sindhri variety. Mangiferin exhibited significant inhibition (IC50 0.026 mg/mL). A moderate inhibition of 15-LOX was observed in all samples, whereas mangiferin was least active. In advanced glycation end product inhibition assay, the chloroform fraction of Langra variety exhibited significant inhibition in nonoxidative (IC50 64.4 µg/mL) and oxidative modes (IC50 54.7 µg/mL). It was concluded that both Langra and Sindhri peel extracts and fractions possess significant antidiabetic activities. The results suggest the potential use of peel waste in the management and complications of diabetes.

Metabolic complications of psychotropic medications in psychiatric disorders: Emerging role of de novo lipogenesis and therapeutic consideration.

Although significant advances have been made in understanding the patho-physiology of psychiatric disorders (PDs), therapeutic advances have not been very convincing. While psychotropic medications can reduce classical symptoms in patients with PDs, their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). The mechanism(s) underlying these metabolic abnormalities is not clear; however, lipid/fatty acid accumulation due to enhanced de novo lipogenesis (DNL) has been shown to reduce membrane fluidity, increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities. Intriguingly, emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity, diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs. In support of this, several adjunctive drugs comprising of anti-oxidants and anti-inflammatory agents, that are used in treating PDs in combination with psychotropic medications, have been shown to reduce insulin resistance and development of NAFLD. In conclusion, the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities, and a new avenue for translational research and therapeutic drug designing in PDs.

In silico Screening and in vitro Cytotoxicity Study of Achyranthes aspera Phytochemicals Against Oral Cancer: A Possible Step towards the Development of Anti-cancer Agents.

BACKGROUND: Oral cancer poses a significant threat to public health worldwide. In addition, because many chemotherapy treatments have negative side effects, natural herbs may be beneficial for oral cancer therapy. Achyranthes aspera (AA), a potential medicinal herb, exerts various pharmacological and biochemical activities. OBJECTIVE: The present study aimed to predict the anti-oral cancer potential of AA using in silico tools and cell death by in vitro testing. METHODS: A total of fourteen bioactive constituents from AA herb were selected using phytochemical databases. The toxicity of AA herb extract was analysed through MTT assay against oral carcinoma A253 cell line. The binding activities of the phytocomponents against serine/ threonine-specific protein kinases isoforms, namely Akt1 (PDB ID: 3qkk) and Akt2 (PDB ID: 2jdo) proteins, were analysed using Discovery Studio 2021 and PyRx docking software. RESULTS: Cell viability data revealed that AA extract decreased the viability and reduced the number of live cells of the oral carcinoma A253 cell line in a dose-dependent manner. The halfmaximal concentration (IC50) value of AA was assessed as 204.74 µg/ml. Based on binding affinity, saponin C (-CDOCKER energy = -77.9862), oleanolic acid (-CDOCKER energy = - 49.4349), spinasterol (-CDOCKER energy = -38.1246), 36,47-dihydroxyhenpentacontan-4-one (-CDOCKER energy = -32.4386), and 20-hydroxyecdysone (-CDOCKER energy = -31.9138) were identified as the best compounds against Akt1, while, compounds saponin C (-CDOCKER energy = -134.412), oleanolic acid (-CDOCKER energy = -90.0846), spinasterol (-CDOCKER energy = -78.3213), 20-hydroxyecdysone (-CDOCKER energy = -80.1049), and ecdysone (- CDOCKER energy = -73.3885) were identified as Akt2 inhibitors. These top compounds fulfilled drug score values, pharmacokinetic and physicochemical characteristics, and druglikeness parameters. CONCLUSION: The present findings reveal that the lead phytomolecules of AA could be effective and developed as a prospective drug against oral cancer.

Concurrent chemoradiation with low-dose and long-duration weekly infusion of gemcitabine in unresectable squamous cell carcinoma of head and neck (SCCHN).

BACKGROUND: Concurrent chemoradiotherapy now represents the standard of care in locally advanced unresectable squamous cell carcinoma of the head and neck, and the administration of cisplatin in triweekly or weekly schedules is the most commonly used chemotherapeutic agent. However, the chemotherapeutic agent and its scheduling with radiation is still an area of investigation with safer toxicity profile and better response rates. Gemcitabine is a potent radiosensitizer, and non-cytotoxic concentration results in decreased systemic toxicity while maintaining radiosensitization properties. Furthermore, data are emerging for low-dose and long-duration infusion where this strategy is found to be effective and a safe alternative to standard brief infusion. Based on these two strategies, that is, non-cytotoxic concentration with long duration, we have explored the unique possibility of further lowering the toxicity profile without compromising the efficacy. METHOD: Eligible patients of locally advanced unresectable squamous cell carcinoma of the head and neck underwent radiation treatment with concurrent gemcitabine. A total dose of 70 Gy in 35 fractions over a period of seven weeks with conventional fractionation schedule was delivered with cord off after 44 Gy. Concurrent gemcitabine was administered intravenously for over two hours once a week, 1-2 h before radiation and for seven consecutive weeks at 50 mg/m2. RESULT: Fifty-two patients was enrolled in this study, out of which 41 completed the treatment. Fifty-nine percent completed treatment within seven weeks. Sixty-four percent were found to have received more than five cycles. Mean follow-up of patients was found to be 4.9 months. Sixty-eight percent had complete response. Stage III patients achieved more complete response compared to stage IV. There was no site-wise difference in achieving complete response. Patients who have received less than five chemo cycles or completed the treatment in more than seven weeks had less complete response. Sixty-one percent had severe mucositis while 39% developed mild/moderate mucositis. Considering skin toxicity, 80% were found to have mild/moderate skin toxicity, while only 20% suffered from severe grades of skin toxicity. CONCLUSION: Gemcitabine in low-dose and long-duration infusion is a potent radiosensitizer with safer hematological toxicity and manageable local toxicities.

Tubo-Ovarian ectopic pregnancy: A rare twin ectopic pregnancy.

The most common twin ectopic pregnancy is heterotopic (1/7000). We are reporting a rare case of twin tubo-ovarian ectopic pregnancy, which was presented in the emergency department of Ayub Teaching Hospital Abbottabad. A 30- year-old female arrived with worsening lower abdominal pain persisting for three weeks. She also had per-vaginal bleeding with passage of clots 1week ago. Clinical examination revealed a tense abdomen with tenderness in the left iliac fossa. Per-vaginally, there was cervical motion tenderness and fullness in the posterior fornix. Beta HCG level revealed a sub-optimal rise whereas Transabdominal ultrasound showed an echogenic shadow in the left ovary. The uterus appeared normal. On exploratory laparotomy a large left ovarian mass was seen with ruptured chronic right tubal pregnancy with adhesions. On cut-section of the ovary, a small foetus was evident. We have concluded that in case of subacute abdominal pain and an-echogenic mass on ultrasonography in reproductive age contralateral adnexa should be accessed to exclude contralateral ectopic pregnancy.

An oral toxicity assessment of a mosquito larvicidal transgenic algae (Chlamydomonas reinhardtii) using adult Zebrafish and its embryos.

Mosquito-borne diseases pose a global health threat, with pathogens like Malaria, Dengue fever, and others transmitted by mosquitoes. Our study focuses on evaluating the toxicity of genetically engineered mosquito larvicidal algae (Chlamydomonas reinhardtii) to non-target organisms, specifically Zebrafish. We conducted a 90-day experiment, feeding Zebrafish different combinations of larvicidal algae and commercial fish feed. Statistical analysis revealed no significant differences in mortality, allergenicity, or moribundity among groups. Hematology, molecular analysis, and necropsy showed no physiological differences. Our findings indicate that the transgenic algae (TN72.cry11Ba) had no adverse effects on adult Zebrafish or their larvae. This study confirmed the safety of algae on non-target organisms, such as zebrafish.

An affordable label-free ultrasensitive immunosensor based on gold nanoparticles deposited on glassy carbon electrode for the transferrin receptor detection.

In recent decades, there has been a concerning and consistent rise in the incidence of cancer, posing a significant threat to human health and overall quality of life. The transferrin receptor (TfR) is one of the most crucial protein biomarkers observed to be overexpressed in various cancers. This study reports on the development of a novel voltammetric immunosensor for TfR detection. The electrochemical platform was made up of a glassy carbon electrode (GCE) functionalized with gold nanoparticles (AuNPs), on which anti-TfR was immobilized. The surface characteristics and electrochemical behaviors of the modified electrodes were comprehensively investigated through scanning electron microscopy, XPS, Raman spectroscopy FT-IR, electrochemical cyclic voltammetry and impedance spectroscopy. The developed immunosensor exhibited robust analytical performance with TfR fortified buffer solution, showing a linear range (LR) response from 0.01 to 3000 µg/mL, with a limit of detection (LOD) of 0.01 µg/mL and reproducibility (RSD <4 %). The fabricated sensor demonstrated high reproducibility and selectivity when subjected to testing with various types of interfering proteins. The immunosensor designed for TfR detection demonstrated several advantageous features, such as being cost-effective and requiring a small volume of test sample making it highly suitable for point-of-care applications.

SAH is a major metabolic sensor mediating worsening metabolic crosstalk in metabolic syndrome.

In this study, we observed worsening metabolic crosstalk in mouse models with concomitant metabolic disorders such as hyperhomocysteinemia (HHcy), hyperlipidemia, and hyperglycemia and in human coronary artery disease by analyzing metabolic profiles. We found that HHcy worsening is most sensitive to other metabolic disorders. To identify metabolic genes and metabolites responsible for the worsening metabolic crosstalk, we examined mRNA levels of 324 metabolic genes in Hcy, glucose-related and lipid metabolic systems. We examined Hcy-metabolites (Hcy, SAH and SAM) by LS-ESI-MS/MS in 6 organs (heart, liver, brain, lung, spleen, and kidney) from C57BL/6J mice. Through linear regression analysis of Hcy-metabolites and metabolic gene mRNA levels, we discovered that SAH-responsive genes were responsible for most metabolic changes and all metabolic crosstalk mediated by Serine, Taurine, and G3P. SAH-responsive genes worsen glucose metabolism and cause upper glycolysis activation and lower glycolysis suppression, indicative of the accumulation of glucose/glycogen and G3P, Serine synthesis inhibition, and ATP depletion. Insufficient Serine due to negative correlation of PHGDH with SAH concentration may inhibit the folate cycle and transsulfurarion pathway and consequential reduced antioxidant power, including glutathione, taurine, NADPH, and NAD+. Additionally, we identified SAH-activated pathological TG loop as the consequence of increased fatty acid (FA) uptake, FA ß-oxidation and Ac-CoA production along with lysosomal damage. We concluded that HHcy is most responsive to other metabolic changes in concomitant metabolic disorders and mediates worsening metabolic crosstalk mainly via SAH-responsive genes, that organ-specific Hcy metabolism determines organ-specific worsening metabolic reprogramming, and that SAH, acetyl-CoA, Serine and Taurine are critical metabolites mediating worsening metabolic crosstalk, redox disturbance, hypomethylation and hyperacetylation linking worsening metabolic reprogramming in metabolic syndrome.

An update on existing therapeutic options and status of novel anti-metastatic agents in breast cancer: Elucidating the molecular mechanisms underlying the pleiotropic action of Withania somnifera (Indian ginseng) in breast cancer attenuation.

Major significant advancements in pharmacology and drug technology have been made to heighten the impact of cancer therapies, improving the life expectancy of subjects diagnosed with malignancy. Statistically, 99% of breast cancers occur in women while 0.5-1% occur in men, the female gender being the strongest breast cancer risk factor. Despite several breakthroughs, breast cancer continues to have a worldwide impact and is one of the leading causes of mortality. Additionally, resistance to therapy is a crucial factor enabling cancer cell persistence and resurgence. As a result, the search and discovery of novel modulatory agents and effective therapies capable of controlling tumor progression and cancer cell proliferation is critical. Withania somnifera (L.) Dunal (WS), commonly known as Indian ginseng, has long been used traditionally for the treatment of several ailments in the Indian context. Recently, WS and its phytoconstituents have shown promising anti-breast cancer properties and, as such, can be employed as prophylactic as well as therapeutic adjuncts to the main line of breast cancer treatment. The present review is an attempt to explore and provide experimental evidences in support of the prophylactic and therapeutic potential of WS in breast cancer, along with a deeper insight into the multiple molecular mechanisms and novel targets through which it acts against breast and other hormonally-induced cancers viz. ovarian, uterine and cervical. This exploration might prove crucial in providing better understanding of breast cancer progression and metastasis and its use as an adjunct in improving disease prognosis and therapeutic outcome.