Database Query Results : Ashwagandha(Withaferin A), ,

Ash, Ashwagandha(Withaferin A): Click to Expand ⟱
Features:
Withaferin A is a steroidal lactone derived from the medicinal plant Withania somnifera (commonly known as Ashwagandha).
The main active constituents of Ashwagandha leaves are alkaloids and steroidal lactones (commonly known as Withanolides).
-The main constituents of ashwagandha are withanolides such as withaferin A, alkaloids, steroidal lactones, tropine, and cuscohygrine.
Ashwagandha is an herb that may reduce stress, anxiety, and insomnia.
*-Ashwagandha is often characterized as an antioxidant.
-Some studies suggest that while ashwagandha may protect normal cells from oxidative damage, it can simultaneously stress cancer cells by tipping their redox balance toward cytotoxicity.
Pathways:
-Induction of Apoptosis and ROS Generation
-Hsp90 Inhibition and Proteasomal Degradation

Cell culture studies vary widely, typically ranging from low micromolar (e.g., 1–10 µM).
In animal models (commonly mice), Withaferin A has been administered in doses ranging from approximately 2 to 10 mg/kg body weight.
- General wellness, Ashwagandha supplements are sometimes taken in doses ranging from 300 mg to 600 mg of an extract (often standardized to contain a certain percentage of withanolides) once or twice daily.
- 400mg of WS extract was given 3X/day to schizophrenia patients. report#2001.
- Ashwagandha Pure 400mg/capsule is available from mcsformulas.com.

-Note half-life 4-6 hrs?.
BioAv
Pathways:
- well-recognized for promoting ROS in cancer cells, while no effect(or reduction) on normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing results about Lowering AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, uPA↓, VEGF↓, ROCK1↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓(combined with sulfor), DNMT1↓, DNMT3A↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TOP1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, β-catenin↓, sox2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


Scientific Papers found: Click to Expand⟱
3169- Ash,    Withaferin A blocks formation of IFN-γ-induced metastatic cancer stem cells through inhibition of the CXCR4/CXCL12 pathway in the UP-LN1 carcinoma cell model
- in-vitro, GC, NA
"highlight2" >CXCR4↓, inhibition of the CXCR4/CXCL12 pathway in the UP-LN1 carcinoma cell model
"highlight2" >CXCL12↓,

3178- Ash,    Withaferin A Inhibits Neutrophil Adhesion, Migration, and Respiratory Burst and Promotes Timely Neutrophil Apoptosis
- Review, Nor, NA
"highlight2" >ITGB1↓, WFA is preventing one or more events that are central to overall neutrophil activation, such as activation of β2 integrins on the neutrophil surface, reorganization of actin cytoskeletal structure

3177- Ash,    Emerging Role of Hypoxia-Inducible Factors (HIFs) in Modulating Autophagy: Perspectives on Cancer Therapy
- Review, Var, NA
"highlight2" >Hif1a↓, Withaferin A, a steroidal lactone derived from Withania somnifera (ashwagandha), has demonstrated the ability to decrease HIF-1α production in breast cancer cells (MDA-MB-231)
"highlight2" >ROS↑, It also stimulates autophagy by stimulating ROS generation and endoplasmic reticulum (ER) stress pathways
"highlight2" >ER Stress↑,

3176- Ash,    Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex
- in-vitro, NA, NA
"highlight2" >PKCδ↓, inhibition of PKC by withaferin A is a central event for the induction of apoptosis
"highlight2" >TOP1∅, This result suggests that withaferin A and staurosporine do not inhibit topoisomerase I in vitro.
"highlight2" >ROS↑, Withaferin A induces oxidative stress, causes decrease in GSH level and leads to subsequent DNA lesions
"highlight2" >GSH↓,
"highlight2" >DNAdam↑,
"highlight2" >MMP↓, Withaferin A inhibits growth of L. donovani promastigotes, induces depolarization of mitochondrial membrane potential and releases cytochrome c into the cytosol.
"highlight2" >Cyt‑c↑,

3175- Ash,  SFN,    Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7
"highlight2" >DNMTs↓, Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyl transferase (DNMT) inhibitor,
"highlight2" >HDAC↓, sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor
"highlight2" >eff↑, SFN + WA synergistically promote breast cancer cell death

3174- Ash,    Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC
- in-vitro, HCC, HepG2 - in-vitro, HCC, Hep3B - in-vitro, HCC, HUH7
"highlight2" >NF-kB↓, We found that many of Nuclear factor kappa B (NF-κB), angiogenesis and inflammation associated proteins secretion is downregulated upon Withaferin A treatment.
"highlight2" >angioG↓,
"highlight2" >Inflam↓,
"highlight2" >TumCP↓, uppressed the proliferation, migration, invasion, and anchorage-independent growth of these HCC cells.
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >Sp1/3/4↓, Withaferin A inhibits NF-κB, Specificity protein 1 (Sp1) transcription factors, and downregulates Vascular Endothelial Growth Factor (VEGF) gene expression
"highlight2" >VEGF↓,
"highlight2" >angioG↓, Withaferin A (2.5 µM) treatment decreased the secretion of various angiogenesis-related markers, growth factors, and cytokines (Serpin F1(PEDF), uPA, PDGF-AA, Angiogenin, Endothelin-1, Macrophage migration inhibitory factor (MIF), PAI-1, MCP1, ICAM-1
"highlight2" >uPA↓,
"highlight2" >PDGF↓,
"highlight2" >MCP1↓,
"highlight2" >ICAM-1↓,
"highlight2" >*NRF2↑, It also upregulates the Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor and protects from Acetaminophen-induced hepatotoxicity and liver injury
"highlight2" >*hepatoP↑,

3173- Ash,    Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma
- in-vitro, neuroblastoma, NA
"highlight2" >GPx4↓, WA drops the protein level and activity of GPX4
"highlight2" >HO-1↑, WA induces a novel noncanonical ferroptosis pathway by increasing the labile Fe(II) pool upon excessive activation of heme oxygenase 1 (HMOX1) through direct targeting of Kelch-like ECH-associated protein 1 (KEAP1), which is sufficient to induce lipi
"highlight2" >lipid-P↑, which is sufficient to induce lipid peroxidation
"highlight2" >Keap1↓, In line with this, we observed decreased levels of KEAP1 along with increased levels of NRF2 in conditions in which HMOX1 is upregulated
"highlight2" >NRF2↑,
"highlight2" >Ferroptosis↑, WA increases intracellular labile Fe(II) upon excessive activation of HMOX1, which is sufficient to induce ferroptosis

3172- Ash,    Implications of Withaferin A for the metastatic potential and drug resistance in hepatocellular carcinoma cells via Nrf2-mediated EMT and ferroptosis
- in-vitro, HCC, HepG2 - in-vitro, Nor, HL7702
"highlight2" >Keap1↑, Notably, Withaferin A elevated Keap1 expression to mitigate Nrf2 signaling activation-mediated epithelial to mesenchymal transition (EMT) and ferroptosis-related protein xCT expression
"highlight2" >NRF2↓,
"highlight2" >EMT↓, Withaferin A suppresses epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer
"highlight2" >TumCP↓, Withaferin A restrains proliferation, invasion, and VM of hepatoma cells while preserving normal hepatocytes
"highlight2" >TumCI↓,
"highlight2" >selectivity↑, , treatment with Withaferin A ranging from 1 to 100 μM had little effect on cell viability of human normal liver cells (HL-7702 cells), indicating the little cytotoxicity on normal hepatocytes.
"highlight2" >*toxicity↓,
"highlight2" >ROS↑, Withaferin A strikingly enhanced ROS () and MDA levels (), but reduced the GSH levels (), indicating the induction of ferroptosis by Withaferin A
"highlight2" >MDA↑,
"highlight2" >GSH↓,
"highlight2" >Ferroptosis↑,

3171- Ash,    Unlocking the epigenetic code: new insights into triple-negative breast cancer
- Review, BC, NA
"highlight2" >DNMTs↓, Withaferin A (WA), another DNMT inhibitor, is a plant-derived steroidal lactone that holds promise as a therapeutic agent for treatment of BC

3170- Ash,    Withaferin A protects against hyperuricemia induced kidney injury and its possible mechanisms
- in-vitro, Nor, NRK52E - in-vivo, NA, NA
"highlight2" >*RenoP↑, WFA ameliorated renal damage, improved kidney function, and decreased levels of creatinine, BUN, UA, and XOD in PO-induced hyperuricemic mice.
"highlight2" >*hepatoP↑,
"highlight2" >*creat↓,
"highlight2" >*BUN↓,
"highlight2" >*uricA↓,
"highlight2" >*Apoptosis↓, WFA markedly inhibited renal apoptosis, accompanied by changes of apoptosis-related proteins.
"highlight2" >*α-SMA↓, Notably reduced α-SMA expression was observed after WFA administration, with WFA 10 mg/kg group presenting the most significant inhibitory effect.

3179- Ash,    Withaferin A inhibits JAK/STAT3 signaling and induces apoptosis of human renal carcinoma Caki cells
- in-vitro, RCC, Caki-1
"highlight2" >JAK↓, Withaferin A inhibits JAK/STAT3 signaling
"highlight2" >STAT3↓,
"highlight2" >Apoptosis↑,

3168- Ash,    Withaferin A targeting both cancer stem cells and metastatic cancer stem cells in the UP-LN1 carcinoma cell model
- in-vitro, Var, NA
"highlight2" >CXCR4↓, WA preferentially reduced F-cell proliferation, tumor sphere formation, and SP cells in vitro in greater efficiencies by apoptosis. This action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3
"highlight2" >STAT3↓,
"highlight2" >CSCs↓, WA could efficiently block the formation of both CSCs and mCSCs in the UP-LN1 cell line

3167- Ash,    Withaferin A Inhibits the Proteasome Activity in Mesothelioma In Vitro and In Vivo
- in-vitro, MM, H226
"highlight2" >TumCP↓, WA inhibits MPM cell proliferation
"highlight2" >cMyc↓, Among the genes that were down-regulated included cell growth and metastasis-promoting oncogenes c-myc, c-fos, c-jun, while tissue inhibitor of metallopeptidases (TIMP)-2 was significantly upregulated
"highlight2" >cFos↓,
"highlight2" >cJun↓,
"highlight2" >TIMP2↑,
"highlight2" >Vim↓, WA exposure caused reduced levels of vimentin at 24 h of treatment.
"highlight2" >ROS↑, WA treatment generated reactive oxygen species (ROS), causing cell death in HL-60 cells
"highlight2" >BAX↑, Consistent with these findings, we found that WA treatments increased pro-apoptotic protein Bax and NF-κB inhibitory protein IκB-α in the patient derived MPM cells.
"highlight2" >IKKα↑,
"highlight2" >Casp3↑, Indeed, WA treatment induced caspase-3 activation, PARP cleavage,
"highlight2" >cl‑PARP↑,

3166- Ash,    Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives
- Review, Var, NA
"highlight2" >*p‑PPARγ↓, preventing the phosphorylation of peroxisome proliferator-activated receptors (PPARγ)
"highlight2" >*cardioP↑, cardioprotective activity by AMP-activated protein kinase (AMPK) activation and suppressing mitochondrial apoptosis.
"highlight2" >*AMPK↑,
"highlight2" >*BioAv↝, The oral bioavailability was found to be 32.4 ± 4.8% after 5 mg/kg intravenous and 10 mg/kg oral WA administration.
"highlight2" >*Half-Life↝, The stability studies of WA in gastric fluid, liver microsomes, and intestinal microflora solution showed similar results in male rats and humans with a half-life of 5.6 min.
"highlight2" >*Half-Life↝, WA reduced quickly, and 27.1% left within 1 h
"highlight2" >*Dose↑, WA showed that formulation at dose 4800 mg having equivalent to 216 mg of WA, was tolerated well without showing any dose-limiting toxicity.
"highlight2" >*chemoP↑, Here, we discuss the chemo-preventive effects of WA on multiple organs.
"highlight2" >IL6↓, attenuates IL-6 in inducible (MCF-7 and MDA-MB-231)
"highlight2" >STAT3↓, WA displayed downregulation of STAT3 transcriptional activity
"highlight2" >ROS↓, associated with reactive oxygen species (ROS) generation, resulted in apoptosis of cells. The WA treatment decreases the oxidative phosphorylation
"highlight2" >OXPHOS↓,
"highlight2" >PCNA↓, uppresses human breast cells’ proliferation by decreasing the proliferating cell nuclear antigen (PCNA) expression
"highlight2" >LDH↓, WA treatment decreases the lactate dehydrogenase (LDH) expression, increases AMP protein kinase activation, and reduces adenosine triphosphate
"highlight2" >AMPK↑,
"highlight2" >TumCCA↑, (SKOV3 andCaOV3), WA arrest the G2/M phase cell cycle
"highlight2" >NOTCH3↓, It downregulated the Notch-3/Akt/Bcl-2 signaling mediated cell survival, thereby causing caspase-3 stimulation, which induces apoptosis.
"highlight2" >Akt↓,
"highlight2" >Bcl-2↓,
"highlight2" >Casp3↑,
"highlight2" >Apoptosis↑,
"highlight2" >eff↑, Withaferin-A, combined with doxorubicin, and cisplatin at suboptimal dose generates ROS and causes cell death
"highlight2" >NF-kB↓, reduces the cytosolic and nuclear levels of NF-κB-related phospho-p65 cytokines in xenografted tumors
"highlight2" >CSCs↓, WA can be used as a pharmaceutical agent that effectively kills cancer stem cells (CSCs).
"highlight2" >HSP90↓, WA inhibit Hsp90 chaperone activity, disrupting Hsp90 client proteins, thus showing antiproliferative effects
"highlight2" >PI3K↓, WA inhibited PI3K/AKT pathway.
"highlight2" >FOXO3↑, Par-4 and FOXO3A proapoptotic proteins were increased in Pten-KO mice supplemented with WA.
"highlight2" >β-catenin/ZEB1↓, decreased pAKT expression and the β-catenin and N-cadherin epithelial-to-mesenchymal transition markers in WA-treated tumors control
"highlight2" >N-cadherin↓,
"highlight2" >EMT↓,
"highlight2" >FASN↓, WA intraperitoneal administration (0.1 mg) resulted in significant suppression of circulatory free fatty acid and fatty acid synthase expression, ATP citrate lyase,
"highlight2" >ACLY↓,
"highlight2" >ROS↑, WA generates ROS followed by the activation of Nrf2, HO-1, NQO1 pathways, and upregulating the expression of the c-Jun-N-terminal kinase (JNK)
"highlight2" >NRF2↑,
"highlight2" >HO-1↑,
"highlight2" >NQO1↑,
"highlight2" >JNK↑,
"highlight2" >mTOR↓, suppressing the mTOR/STAT3 pathway
"highlight2" >neuroP↑, neuroprotective ability of WA (50 mg/kg b.w)
"highlight2" >*TNF-α↓, WA attenuate the levels of neuroinflammatory mediators (TNF-α, IL-1β, and IL-6)
"highlight2" >*IL1β↓,
"highlight2" >*IL6↓,
"highlight2" >*IL8↓, WA decreases the pro-inflammatory cytokines (IL-6, TNFα, IL-8, IL-18)
"highlight2" >*IL18↓,
"highlight2" >RadioS↑, radiosensitizing combination effect of WA and hyperthermia (HT) or radiotherapy (RT)
"highlight2" >eff↑, WA and cisplatin at suboptimal dose generates ROS and causes cell death [41]. The actions of this combination is attributed by eradicating cells, revealing markers of cancer stem cells like CD34, CD44, Oct4, CD24, and CD117

3165- Ash,    Inhibitory effect of withaferin A on Helicobacter pylori‑induced IL‑8 production and NF‑κB activation in gastric epithelial cells
- in-vitro, Nor, NA
"highlight2" >*IL8↓, WA efficiently reduced IL-8 production by AGS cells in response to H. pylori infection. H. pylori-induced activation of NF-κB, but not MAPKs, was also inhibited by pre-treatment of WA in the cells.
"highlight2" >*Inflam↓, therapeutic agent for H. pylori-mediated gastric inflammation

3164- Ash,    Withaferin A alleviates fulminant hepatitis by targeting macrophage and NLRP3
"highlight2" >*hepatoP↑, Withania Somnifera, is a hepatoprotective agent
"highlight2" >*IKKα↓, WA also inhibits inflammation by directly inhibiting IκκB activity46,47 or NLRP3 inflammasome activation in vitro in immune cells
"highlight2" >*NLRP3↓,
"highlight2" >*NRF2↑, WA probably protects against FH by targeting the macrophage and/or hepatocyte stress via activating NRF2, AMPKα
"highlight2" >*AMPK↑,
"highlight2" >*Inflam↓, Thus, WA potently protects against GalN/LPS-induced hepatotoxicity and inflammation
"highlight2" >*Apoptosis↓, WA suppressed hepatic apoptosis in vivo
"highlight2" >*cl‑Casp3↓, attenuate the increase of cleaved CASP3 and cleaved PARP1
"highlight2" >*cl‑PARP1↓,
"highlight2" >*NLRP3↓, WA prevented GalN/LPS-induced FH partially by inhibiting activation of the NLRP3 inflammasome
"highlight2" >*ROS↓, fig 7
"highlight2" >*ALAT↓,
"highlight2" >*AST↓,
"highlight2" >*GSH↑, (GSH) levels were significantly depleted by ~50% 6 h after GalN/LPS administration and were recovered to levels comparable with that of control mice by WA treatment

3163- Ash,  Rad,    Withaferin A, a steroidal lactone, selectively protects normal lymphocytes against ionizing radiation induced apoptosis and genotoxicity via activation of ERK/Nrf-2/HO-1 axis
"highlight2" >*radioP↑, Withaferin A (WA) protected only normal lymphocytes, but not cancer cells, against IR-induced apoptosis
"highlight2" >selectivity↑,
"highlight2" >*Casp3↓, WA treatment led to significant inhibition of IR-induced caspase-3 activation and decreased IR-induced DNA damage to lymphocytes and bone-marrow cells.
"highlight2" >*DNAdam↓,
"highlight2" >*ROS↓, WA reduced intracellular ROS and GSH levels
"highlight2" >*GSH↓,
"highlight2" >*NRF2↑, WA induced pro-survival transcription factor, Nrf-2, and expression of cytoprotective genes HO-1, catalase, SOD, peroxiredoxin-2 via ERK.
"highlight2" >*HO-1↑,
"highlight2" >*Catalase↑,
"highlight2" >*SOD↑,
"highlight2" >*Prx↑,
"highlight2" >*ERK↑, Activated ERK promotes the nuclear translocation and activity of Nrf2

3162- Ash,    Molecular insights into cancer therapeutic effects of the dietary medicinal phytochemical withaferin A
- Review, Var, NA
"highlight2" >lipid-P↓, Oral cancer 20 mg/Kg ↓Lipid peroxidation : ↑SOD, glutathione peroxidase, p53, Bcl-2
"highlight2" >SOD↑,
"highlight2" >GPx↑,
"highlight2" >P53↑,
"highlight2" >Bcl-2↑,
"highlight2" >E6↓, Cervival cancer 8mg/Kg ↓E6, E7: ↑p53, pRb, Cyclin B1, P34 Cdc2, p21, PCNA
"highlight2" >E7↓,
"highlight2" >pRB↑,
"highlight2" >CycB↑,
"highlight2" >CDC2↑,
"highlight2" >P21↑,
"highlight2" >PCNA↓,
"highlight2" >ALDH1A1↓, Mammary cancer 0-1 mg/mouse (5-10) ↓Mammosphere number, ALDH1 activity. Vimentin, glycolysis
"highlight2" >Vim↓,
"highlight2" >Glycolysis↓,
"highlight2" >cMyc↓, Mesotheliome cancer 5 mg/Kg ↓Proteasomal chymotrypsin, C-Myc : ↑ Bax, CARP-1
"highlight2" >BAX↑,
"highlight2" >NF-kB↓,
"highlight2" >Casp3↑, caspase-3 activation
"highlight2" >CHOP↑, WA is found to increase activation of Elk1 and CHOP (CCAAT-enhancer-binding protein homologous protein) by RSK, as well as up-regulation of DR5 by selectively suppressing pathway ERK
"highlight2" >DR5↑,
"highlight2" >ERK↓,
"highlight2" >Wnt↓, WA inhibits Wnt/β-catenin pathway via suppression of AKT signalling, which inhibits cancer cell motility and sensitises for cell death
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >Akt↓,
"highlight2" >HSP90↓, WA-dependent inhibition of heat shock protein (HSP) chaperone functions. WA inhibits the activity of HSP90-mediated function

3161- Ash,    Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage
- in-vivo, Stroke, NA
"highlight2" >*neuroP↑, Withaferin A (WFA), a natural compound, exhibits a positive effect on a number of neurological diseases
"highlight2" >*MDA↓, WFA markedly decreased the level of malondialdehyde, an oxidative stress marker,
"highlight2" >*ROS↓,
"highlight2" >*SOD↑, and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase
"highlight2" >*GPx↑,
"highlight2" >*NRF2↑, results demonstrated that WFA activated the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling axis, promoted translocation of Nrf2 from the cytoplasm to nucleus, and increased HO-1 expression.
"highlight2" >*HO-1↑, WFA induces HO-1 expression to attenuate oxidative damage in vitro

1142- Ash,    Ashwagandha-Induced Programmed Cell Death in the Treatment of Breast Cancer
- Review, BC, MCF-7 - NA, BC, MDA-MB-231 - NA, Nor, HMEC
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑, anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants,
"highlight2" >DNAdam↑,
"highlight2" >OXPHOS↓, WA inhibits oxidative phosphorylation (OXPHOS) in Complex III, accompanied by apoptotic release of DNA fragments associated with histones in the cytosol
"highlight2" >*ROS∅, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
"highlight2" >Bcl-2↓,
"highlight2" >XIAP↓,
"highlight2" >survivin↓,
"highlight2" >DR5↑,
"highlight2" >IKKα↓,
"highlight2" >NF-kB↓,
"highlight2" >selectivity↑, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
"highlight2" >*ROS∅, Moreover, WA shows high selectivity, causing ROS production only in MDA-MB-231 and MCF-7 cells, but not in the normal human mammary epithelial cell line (HMEC)
"highlight2" >eff↓, the anti-cancer effect of WA was significantly attenuated in the presence of anti-oxidants, as it has been shown that ectopic expression of Cu and Zn-superoxide dismutase (SOD) significantly weakens its apoptotic properties
"highlight2" >Paraptosis↑, WA promotes death in both MCF-7 and MDA-MB-231 cell lines through paraptosis through the action of ROS

3685- Ash,    Withania somnifera as a Potential Anxiolytic and Anti-inflammatory Candidate Against Systemic Lipopolysaccharide-Induced Neuroinflammation
- in-vivo, NA, NA
"highlight2" >*TNF-α↓, Suppression of reactive gliosis, inflammatory cytokines production like TNF-α, IL-1β, IL-6, and expression of nitro-oxidative stress enzymes like iNOS, COX2, NOX2 etc were observed in ASH-WEX-treated animals.
"highlight2" >*IL1β↓,
"highlight2" >*IL6↓,
"highlight2" >*iNOS↓,
"highlight2" >*COX2↓,
"highlight2" >*NOX↓,
"highlight2" >*cognitive↑, ameliorates associated behavioral abnormalities
"highlight2" >*Inflam↓,
"highlight2" >*NF-kB↓, ASH-WEX-Mediated Inhibition of NFkB Pathway

4679- Ash,    Induced cancer stem-like cells as a model for biological screening and discovery of agents targeting phenotypic traits of cancer stem cell
- in-vitro, NA, NA
"highlight2" >CSCs↓, we found that withaferin A (WA), an Ayurvedic medicine constituent, was a potent inhibitor of CSC stemness leading to cellular senescence primarily via the induction of p21Cip1 expression.

4678- Ash,    Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer
- vitro+vivo, NSCLC, H1975
"highlight2" >ROS↑, WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects.
"highlight2" >AntiTum↑, In vivo research also demonstrated the anti-tumor effect of WA treatment
"highlight2" >CSCs↓, We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity
"highlight2" >mTOR↓, at least through downregulation of mTOR/STAT3 signaling
"highlight2" >STAT3↓,
"highlight2" >ChemoSen↑, combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability.
"highlight2" >Keap1↑, Interestingly, we found WA treatment gradually increased KEAP1, while it decreased NRF2 in H1975 cells
"highlight2" >NRF2↓,

4677- Ash,    Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells
- vitro+vivo, Ovarian, NA
"highlight2" >CSCs↓, Withaferin A (WFA) alone or in combination with cisplatin (CIS) significantly inhibited the spheroid formation (tumorigenic potential) of isolated ALDH1 CSCs in vitro
"highlight2" >Securin↓, WFA and CIS combination suppresses the expression of securin an “oncogene”
"highlight2" >ALDH1A1↓, WFA and CIS combination regulates the expression of ALDH1 marker

4660- Ash,    Withaferin A Alone and in Combination with Cisplatin Suppresses Growth and Metastasis of Ovarian Cancer by Targeting Putative Cancer Stem Cells
- in-vitro, Ovarian, NA
"highlight2" >CSCs↓, Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs.
"highlight2" >TumCG↓, 70 to 80% reduction in tumor growth and complete inhibition of metastasis to other organs compared to untreated controls.
"highlight2" >TumMeta↓,
"highlight2" >CD44↓, highly significant elimination of cells expressing CSC markers - CD44, CD24, CD34, CD117 and Oct4 and downregulation of Notch1, Hes1 and Hey1 genes.
"highlight2" >CD34↓,
"highlight2" >OCT4↓,
"highlight2" >NOTCH1↓,
"highlight2" >HEY1↓,

4303- Ash,    Ashwagandha (Withania somnifera)—Current Research on the Health-Promoting Activities: A Narrative Review
- Review, AD, NA
"highlight2" >*neuroP↑, neuroprotective, sedative and adaptogenic effects and effects on sleep.
"highlight2" >*Sleep↑,
"highlight2" >*Inflam↓, anti-inflammatory, antimicrobial, cardioprotective and anti-diabetic properties
"highlight2" >*cardioP↑,
"highlight2" >*cognitive↑, Significant improvements in cognitive function were observed as a result of the inhibition of amyloid β-42, and a reduction in pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and MCP-1, nitric oxide, and lipid peroxidation was also observed.
"highlight2" >*Aβ↓,
"highlight2" >*TNF-α↓,
"highlight2" >*IL1β↓,
"highlight2" >*IL6↓,
"highlight2" >*MCP1↓,
"highlight2" >*lipid-P↓,
"highlight2" >*tau↓, reducing β-amyloid aggregation and inhibiting τ protein accumulation.
"highlight2" >*ROS↓, withaferin A is responsible for inhibiting oxidative and pro-inflammatory chemicals and regulating heat shock proteins (HSPs), the expression of which increases when cells are exposed to stressors.
"highlight2" >*BBB↑, ability of withanolide A to penetrate the blood-brain barrier (BBB) was demonstrated.
"highlight2" >*AChE↓, potentially inhibiting acetylcholinesterase activity, which may have benefits in the treatment of canine cognitive dysfunction and Alzheimer’s disease
"highlight2" >*GSH↑, increased glutathione concentration, increased glutathione S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase activities,
"highlight2" >*GSTs↑,
"highlight2" >*GSR↑,
"highlight2" >*GPx↑,
"highlight2" >*SOD↑,
"highlight2" >*Catalase↑,
"highlight2" >ChemoSen↑, combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin
"highlight2" >*Strength↑, combination of Ashwagandha extract and intermittent fasting has potential as an effective breast cancer treatment that may be used in conjunction with cisplatin

3689- Ash,    Ashwagandha attenuates TNF-α- and LPS-induced NF-κB activation and CCL2 and CCL5 gene expression in NRK-52E cells
- in-vitro, NA, NRK52E
"highlight2" >*RenoP↑, ashwaganda WSE as a valid candidate for evaluation of therapeutic potential for the treatment of chronic renal dysfunction.
"highlight2" >*NF-kB↓, WSE completely prevented TNF-α-induced increases in CCL5, while attenuating the increase in CCL2 expression and NF-κB activation.
"highlight2" >*MCP1↓,
"highlight2" >*RANTES↓,

3688- Ash,    Withaferin A Suppresses Beta Amyloid in APP Expressing Cells: Studies for Tat and Cocaine Associated Neurological Dysfunctions
- NA, AD, SH-SY5Y
"highlight2" >*Aβ↓, WA reduces secreted Aβ and induced neurotoxicity in amyloid precursor protein (APP)-plasmid transfected SH-SY5Y cells (SH-APP)
"highlight2" >*neuroP↑, WA Reverses/Decreases coc Induced Neurotoxicity

3687- Ash,    Role of Withaferin A and Its Derivatives in the Management of Alzheimer’s Disease: Recent Trends and Future Perspectives
- Review, AD, NA
"highlight2" >*Aβ↓, neuroprotective potential of WA is mediated by reduction of beta-amyloid plaque aggregation, tau protein accumulation, regulation of heat shock proteins, and inhibition of oxidative and inflammatory constituents.
"highlight2" >*tau↓,
"highlight2" >*HSPs↝, WA inhibited Hsp90 [127] and induced Hsp 27 and Hsp70 expressions
"highlight2" >*antiOx↑,
"highlight2" >*ROS↓,
"highlight2" >*Inflam↓,
"highlight2" >*neuroP↑, confirming WA’s neuroprotective potency against AD.
"highlight2" >*cognitive↑, In an AD model, cognitive defects induced by ibotenic acid that was significantly reversed by WA isolated from Ashwagandha root
"highlight2" >*NF-kB↓, inhibited nuclear factor NF-κB activation
"highlight2" >*HO-1↑, WA also increased the neuro-protective protein heme oxygenase-1, which is beneficial to AD prevention
"highlight2" >*memory↑, WA additionally enhances memory [133], prevents Aβ production, reconstructs synapses, and regenerates axons
"highlight2" >*AChE↓, WA Inhibits AChE and BuChE Activities
"highlight2" >*BChE↓,
"highlight2" >*ChAT↑, WA has an important role in AD by reversing the reduction in cholinergic markers such as choline acetyltransferase (ChAT) and acetylcholine
"highlight2" >*Ach↑, WA increased the level of ACh, the amount of choline acetyltransferase (ChAT)

3686- Ash,    Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study
- Study, NA, NA
"highlight2" >*Sleep↑, Over the eight weeks, there was a significant improvement in sleep quality, with both Ashwagandha 250 mg and Ashwagandha 600 mg compared to the placebo group

3160- Ash,    Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal
- Review, Var, NA
"highlight2" >TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
"highlight2" >H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
"highlight2" >P21↑,
"highlight2" >cycA1↓,
"highlight2" >CycB↓,
"highlight2" >cycE↓,
"highlight2" >CDC2↓,
"highlight2" >CHK1↓,
"highlight2" >Chk2↓,
"highlight2" >p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
"highlight2" >MAPK↑,
"highlight2" >E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
"highlight2" >E7↓,
"highlight2" >P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
"highlight2" >Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
"highlight2" >FOXO3↑,
"highlight2" >ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
"highlight2" >γH2AX↑,
"highlight2" >MMP↓,
"highlight2" >mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
"highlight2" >eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
"highlight2" >TumCD↑,
"highlight2" >Mcl-1↓,
"highlight2" >ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
"highlight2" >ATF4↑,
"highlight2" >ATF3↑,
"highlight2" >CHOP↑,
"highlight2" >NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
"highlight2" >NF-kB↓,
"highlight2" >Bcl-2↓,
"highlight2" >STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
"highlight2" >CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
"highlight2" >β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
"highlight2" >N-cadherin↓,
"highlight2" >EMT↓,
"highlight2" >Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
"highlight2" >eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
"highlight2" >CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
"highlight2" >p‑RB1↓,
"highlight2" >PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
"highlight2" >cl‑Casp3↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
"highlight2" >ER-α36↓, Decreased ER-α
"highlight2" >LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
"highlight2" >lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
"highlight2" >AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
"highlight2" >COX2↓,
"highlight2" >RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
"highlight2" >PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
"highlight2" >SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
"highlight2" >MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
"highlight2" >MMP9↓,
"highlight2" >NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
"highlight2" >NQO1↑,
"highlight2" >GSR↑,
"highlight2" >HO-1↑,
"highlight2" >*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
"highlight2" >*Prx↑,
"highlight2" >*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
"highlight2" >eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
"highlight2" >Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
"highlight2" >Slug↓,
"highlight2" >Vim↓,
"highlight2" >CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
"highlight2" >HEY1↓,
"highlight2" >MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
"highlight2" >VEGF↓,
"highlight2" >uPA↓, and protease u-PA involved in the cancer cell metastasis
"highlight2" >*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
"highlight2" >CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
"highlight2" >CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
"highlight2" >HSP90↓,

3676- Ash,    Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stress and autoantibodies production in collagen-induced arthritic rats
- in-vivo, Arthritis, NA
"highlight2" >*CRP↓, WSAq resulted in a dose-dependent reduction in arthritic index, autoantibodies and CRP
"highlight2" >*ROS↓, oxidative stress in CIA rats was ameliorated by treatment with different doses of WSAq, as evidenced by a decrease in lipid peroxidation and glutathione-S-transferase activity and an increase in the glutathione
"highlight2" >*lipid-P↓,
"highlight2" >*GSTs↓,
"highlight2" >*GSH↑,
"highlight2" >*antiOx↑, WSAq exhibited antioxidant and anti-arthritic activity and reduced inflammation in CIA rats
"highlight2" >*Inflam↓,

3675- Ash,    Ashwagandha (Withania somnifera) Reverses β-Amyloid1-42 Induced Toxicity in Human Neuronal Cells: Implications in HIV-Associated Neurocognitive Disorders (HAND)
"highlight2" >*memory↑, widely in Ayurvedic medicine as a nerve tonic and memory enhancer.
"highlight2" >*neuroP↑, neuroprotective effect of WS root extract against β-amyloid and HIV-1Ba-L (clade B) induced neuro-pathogenesis.
"highlight2" >*Aβ↓, Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ)
"highlight2" >*LDH↓, Ashwagandha treatment showed protective effects against the cytotoxicity as the levels of LDH leakage in Ashwagandha plus β-amyloid treated cultures were comparable with controls
"highlight2" >*PPARγ↑, decreased PPARγ protein levels in β-amyloid treated and its reversal by Ashwagandha in SK-N-MC neuronal cells.
"highlight2" >*cognitive↑, traditional medicine for cognitive and other HIV associated neurodegenerative disorders.

3674- Ash,    Ashwagandha in brain disorders: A review of recent developments
- Review, NA, NA
"highlight2" >*neuroP↑, neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide neuroprotective phytoconstituents of Ashwagandha are sitoindos

3673- Ash,    An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda
- Review, NA, NA
"highlight2" >*cognitive↑, Cognition Promoting Effect
"highlight2" >*Inflam↓, anti-inflammatory and anti-arthritic
"highlight2" >*Strength↑, swimming time was approximately doubled after Withania somnifera (WS) treatment
"highlight2" >*VitC↑, Withania somnifera treatment prevents, decrease of adrenal cortisol and ascorbic acid which occurs due to swimming stress.
"highlight2" >*memory↑, It is useful for different types of diseases like Parkinson, dementia, memory loss, stress induced diseases, malignoma and others.

3672- Ash,    Critical review of the Withania somnifera (L.) Dunal: ethnobotany, pharmacological efficacy, and commercialization significance in Africa
- Review, NA, NA
"highlight2" >*cardioP↑, W. somnifera extracts are confirmed to have a significant cardioprotection effect based on the myocardial and antioxidant histopathological evaluations
"highlight2" >*antiOx↑,
"highlight2" >*ROS↓, reduced oxidative stress,
"highlight2" >*neuroP↑, most reported neuroprotective mechanisms of W. somnifera extracts against several neurodegenerative diseases include the restoration of mitochondrial function concurrent with the mitigations of oxidative stress, inflammation, and apoptosis
"highlight2" >*Inflam↓,
"highlight2" >*Apoptosis↓,

3671- Ash,    Withania somnifera showed neuroprotective effect and increase longevity in Drosophila Alzheimer’s disease model
- in-vivo, AD, NA
"highlight2" >*OS↑, The untreated Act5C-Aβ42 flies live for approximately 16 days, while the Act5C-Aβ42 treated with Ashwagandha showed improvement in their lifespan living up to 29 days
"highlight2" >*BACE↓, shwagandha was also shown to down-regulate beta-secretase 1 (BACE1) a

3670- Ash,    Neurodegenerative diseases and Withania somnifera (L.): An update
- Review, AD, NA - Review, Park, NA
"highlight2" >*Apoptosis↓, protective effects of Ashwagandha were accomplished by restoring mitochondrial and endothelial function, mitigation of apoptosis, inflammation and oxidative stress mechanisms.
"highlight2" >*Inflam↓,
"highlight2" >*ROS↓,
"highlight2" >*neuroP↑, uggest the use of Withania somnifera (L.) against neurodegenerative disease

3669- Ash,    Withanamides in Withania somnifera fruit protect PC-12 cells from beta-amyloid responsible for Alzheimer's diseas
- in-vitro, AD, PC12
"highlight2" >*lipid-P↓, Withania somnifera fruit afforded lipid peroxidation inhibitory withanamides that are more potent than the commercial antioxidants.
"highlight2" >*antiOx↑,

3668- Ash,    Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver
- NA, AD, NA
"highlight2" >*Aβ↓, withanosides reversed behavioral deficits, plaque pathology, accumulation of β-amyloid peptides (Aβ) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice.
"highlight2" >*cognitive↑,

1355- Ash,    Withaferin A-Induced Apoptosis in Human Breast Cancer Cells Is Mediated by Reactive Oxygen Species
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, Nor, HMEC
"highlight2" >eff↑, WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). ****
"highlight2" >mt-ROS↑, WA-induced apoptosis in human breast cancer cells is mediated by mitochondria-derived ROS
"highlight2" >mitResp↓,
"highlight2" >OXPHOS↓, WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity.
"highlight2" >compIII↑,
"highlight2" >BAX↑,
"highlight2" >Bak↑,
"highlight2" >other↓, Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) overexpression confers protection against WA-induced ROS production and apoptosis
"highlight2" >ATP∅, steady-state levels of ATP were unaffected by WA treatment in either cell line
"highlight2" >*ROS∅, but not in a normal human mammary epithelial cell line (HMEC). WA treatment caused ROS production in breast cancer cells, HMEC were resistant to pro-oxidant effect of this agent.

3159- Ash,    Neuroprotective effects of Withania somnifera in the SH-SY5Y Parkinson cell model
- in-vitro, Park, SH-SY5Y
"highlight2" >*neuroP↑, Neuroprotective effects of Withania somnifera
"highlight2" >*Inflam↓, including inflammation and oxidative stress reduction, memory and cognitive function improvement.
"highlight2" >*ROS↓,
"highlight2" >*cognitive↑,
"highlight2" >*memory↑,
"highlight2" >*GPx↑, significantly increased glutathione peroxidase activity
"highlight2" >*Prx↓, KSM-66, had peroxiredoxin-1 and VGF levels significantly lower than the untreated control
"highlight2" >*ATP↑, rescue of mitochondria with 0.5 mg/ml KSM-66 extract showed an increase in ATP levels.
"highlight2" >*Vim↓, Pre-treatment with KSM-66 decreased level of vimentin
"highlight2" >*mtDam↓, KSM-66 attenuates 6-OHDA-induced mitochondrial dysfunction in SH-SY5Y cells

1363- Ash,  doxoR,    Withaferin A Synergizes the Therapeutic Effect of Doxorubicin through ROS-Mediated Autophagy in Ovarian Cancer
- in-vitro, Ovarian, A2780S - in-vitro, Ovarian, CaOV3 - in-vivo, NA, NA
"highlight2" >ChemoSen↑, thus reducing the dosage requirement of Dox
"highlight2" >ROS↑,
"highlight2" >DNAdam↑, immense DNA damage
"highlight2" >TumCCA↑,
"highlight2" >LC3B↑,
"highlight2" >TumCG↓, 70 to 80% reduction in tumor growth
"highlight2" >cl‑Casp3↑,

1362- Ash,  GEM,    Synergistic Inhibition of Pancreatic Cancer Cell Growth and Migration by Gemcitabine and Withaferin A
- in-vitro, PC, PANC1 - in-vitro, PC, Hs766t
"highlight2" >ChemoSen↑, combination treatment being the most effective
"highlight2" >ROS↑, which were attenuated by N-acetylcysteine
"highlight2" >Apoptosis↑,
"highlight2" >TumCMig↓, strongest inhibition was observed when both compounds were co-administered
"highlight2" >F-actin↓, leading to F-actin depolymerization
"highlight2" >YMcells↓, greater reduction in cell stiffness compared to individual treatments
"highlight2" >NF-kB↓, relative luciferase activity, which reflects NF-κB activity, was markedly elevated following treatment with GC (Figure 7). In contrast, treatment with WFA resulted in a notable decline in luciferase activity, particularly when combined with GC.

1361- Ash,  SRF,    Withaferin A, a natural thioredoxin reductase 1 (TrxR1) inhibitor, synergistically enhances the antitumor efficacy of sorafenib through ROS-mediated ER stress and DNA damage in hepatocellular carcinoma cells
- in-vitro, Liver, HUH7 - in-vivo, Liver, HUH7
"highlight2" >TrxR↓, TrxR1
"highlight2" >ROS↑,
"highlight2" >DNA-PK↑,
"highlight2" >ER Stress↑,
"highlight2" >Apoptosis↑,
"highlight2" >eff↓, Pre-treatment with the antioxidant NAC significantly inhibited ROS generation, ER stress, DNA damage, and apoptosis induced by Sora/WA co-treatment

1360- Ash,  immuno,    Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer
- in-vitro, Lung, H1650 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
"highlight2" >PD-L1↑,
"highlight2" >eff↓, The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process.
"highlight2" >ROS↑,
"highlight2" >ER Stress↑,
"highlight2" >Apoptosis↑,
"highlight2" >BAX↑,
"highlight2" >Bak↑,
"highlight2" >BAD↑,
"highlight2" >Bcl-2↓,
"highlight2" >XIAP↓,
"highlight2" >survivin↓,
"highlight2" >cl‑PARP↑,
"highlight2" >CHOP↑,
"highlight2" >p‑eIF2α↑, phosphorylation of the eukaryotic initiation factor eIF-2
"highlight2" >ICD↑,
"highlight2" >eff↑, WFA Sensitizes LLC Syngeneic Mouse Tumors to α-PD-L1 In Vivo

1359- Ash,    Withaferin A Induces ROS-Mediated Paraptosis in Human Breast Cancer Cell-Lines MCF-7 and MDA-MB-231
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
"highlight2" >MMP↓,
"highlight2" >Alix/AIP‑1↓,
"highlight2" >ROS↑, ROS inhibitor abrogated the effect of WA on: cell-death
"highlight2" >Paraptosis↑,
"highlight2" >ER Stress↝,

1358- Ash,    Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms
- Review, Var, NA
"highlight2" >TumCCA↑,
"highlight2" >Apoptosis↑,
"highlight2" >TumAuto↑,
"highlight2" >Ferroptosis↑,
"highlight2" >TumCP↓,
"highlight2" >CSCs↓,
"highlight2" >TumMeta↓,
"highlight2" >EMT↓,
"highlight2" >angioG↓,
"highlight2" >Vim↓,
"highlight2" >HSP90↓,
"highlight2" >annexin II↓, annexin II proteins directly bind to WA
"highlight2" >m-FAM72A↓,
"highlight2" >BCR-ABL↓,
"highlight2" >Mortalin↓,
"highlight2" >NRF2↓,
"highlight2" >cMYB↓,
"highlight2" >ROS↑, WA inhibits proliferation through ROS-mediated intrinsic apoptosis
"highlight2" >ChemoSen↑, WA and cisplatin, WA produced ROS, while cisplatin caused DNA damage, suggesting that lower doses of cisplatin combined with suboptimal doses of WA could achieve the same effect
"highlight2" >eff↑, sulforaphane and WA showed synergistic effects on epigenetic modifiers and cell proliferation in breast cancer cells
"highlight2" >ChemoSen↑, WA and sorafenib caused G2/M arrest in anaplastic and papillary thyroid cancer cells
"highlight2" >ChemoSen↑, combination of WA and 5-FU executed PERK axis-mediated endoplasmic reticulum (ER) stress-induced autophagy and apoptosis
"highlight2" >eff↑, WA and carnosol also exhibit a synergistic effect on pancreatic cancer
"highlight2" >*BioAv↓, Saurabh by Saurabh et al and Tianming et al reported oral bioavailability values 1.8% and 32.4 ± 4.8%, respectively, in male rats.
"highlight2" >ROCK1↓, In another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angi
"highlight2" >TumCI↓,
"highlight2" >Sp1/3/4↓, Furthermore, WA exerts potent anti-angiogenic activity in vivo.174 In the Ehrlich ascites tumor model, WA exerts its anti-angiogenic activity by reducing the binding of the transcription factor specificity protein 1 (Sp1) to VEGF
"highlight2" >VEGF↓, n another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angio
"highlight2" >Hif1a↓, Furthermore, WA suppresses the AK4-HIF-1α signaling axis and acts as a potent antimetastatic agent in lung cancer.Citation79
"highlight2" >EGFR↓, WA synergistically inhibited wild-type epidermal growth factor receptor (EGFR) lung cancer cell viability

1357- Ash,    Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vitro, GBM, GL26
"highlight2" >TumCP↓,
"highlight2" >TumCCA↑, G2/M cell cycle
"highlight2" >Akt↓,
"highlight2" >mTOR↓,
"highlight2" >p70S6↓,
"highlight2" >p85S6K↓,
"highlight2" >AMPKα↑,
"highlight2" >TSC2↑,
"highlight2" >HSP70/HSPA5↑,
"highlight2" >HO-1↑,
"highlight2" >HSF1↓,
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑, Withaferin A elevates pro-oxidant potential in GBM cells and induces a cellular oxidative stress response
"highlight2" >eff↓, Pre-treatment with a thiol-antioxidant protects GBM cells from the anti-proliferative and cytotoxic effects of withaferin A NAC pretreatment was able to completely prevent cell cycle shift to G2/M arrest following 1µM WA treatment at 24h

1356- Ash,    Withaferin A induces apoptosis by ROS-dependent mitochondrial dysfunction in human colorectal cancer cells
- in-vitro, CRC, HCT116
"highlight2" >ROS↑,
"highlight2" >TumCCA↑,
"highlight2" >MMP↓,
"highlight2" >TumCG↓,
"highlight2" >Apoptosis↑,
"highlight2" >JNK↝,

1364- Ash,    Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress
- in-vitro, Bladder, J82
"highlight2" >cl‑Casp3↑,
"highlight2" >cl‑Casp8↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >cl‑PARP↑,
"highlight2" >ROS↑,
"highlight2" >MMP↓,
"highlight2" >DNAdam↑,
"highlight2" >eff↓, ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects.

1181- Ash,    Withaferin A inhibits Epithelial to Mesenchymal Transition in Non-Small Cell Lung Cancer Cells
- in-vitro, Lung, A549 - in-vitro, Lung, H1299
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >EMT↓,
"highlight2" >p‑SMAD2↓,
"highlight2" >p‑SMAD3↓,
"highlight2" >p‑NF-kB↓,

1180- Ash,    Withaferin A Inhibits Liver Cancer Tumorigenesis by Suppressing Aerobic Glycolysis through the p53/IDH1/HIF-1α Signaling Axis
- in-vitro, Liver, HepG2
"highlight2" >IDH1↑, IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells
"highlight2" >Glycolysis↓, decreased levels of several glycolytic enzymes
"highlight2" >P53↑,
"highlight2" >Hif1a↓,

1179- Ash,    Withaferin-A Inhibits Colon Cancer Cell Growth by Blocking STAT3 Transcriptional Activity
- in-vitro, CRC, HCT116 - in-vivo, NA, NA
"highlight2" >TumCP↓,
"highlight2" >TumCMig↓,
"highlight2" >STAT3↓, implicated in the development and progression of colon cancer.
"highlight2" >TumVol↓,
"highlight2" >TumW↓,

1178- Ash,    Withaferin A suppresses the expression of vascular endothelial growth factor in Ehrlich ascites tumor cells via Sp1 transcription factor
- in-vitro, Nor, HUVECs - in-vivo, NA, NA
"highlight2" >*VEGF↓,
"highlight2" >*angioG↓,
"highlight2" >*ascitic↓,
"highlight2" >*Sp1/3/4↓, Studies at molecular level revealed that withaferin A inhibits binding of Sp1 transcription factor

1177- Ash,    Withaferin A downregulates COX-2/NF-κB signaling and modulates MMP-2/9 in experimental endometriosis
- in-vivo, EC, NA
"highlight2" >TumVol↓,
"highlight2" >MMP2↓,
"highlight2" >MMP9↓,
"highlight2" >NF-kB↓,
"highlight2" >COX2↓,
"highlight2" >NO↓,
"highlight2" >IL1β↓,
"highlight2" >IL6↓,

1176- Ash,    Metabolic Alterations in Mammary Cancer Prevention by Withaferin A in a Clinically Relevant Mouse Model
- in-vivo, NA, NA
"highlight2" >TumVol↓, lower by 94%
"highlight2" >Apoptosis↑,
"highlight2" >Glycolysis↓, reduced levels of glycolysis intermediates.
"highlight2" >PKM2↓,
"highlight2" >PGK1↓,
"highlight2" >ALDOAiso2↓,

1174- Ash,    Withaferin A Suppresses Estrogen Receptor-α Expression in Human Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vivo, BC, MDA-MB-231 - in-vitro, BC, T47D
"highlight2" >p‑P53↑,
"highlight2" >Apoptosis↑,
"highlight2" >ERα↓, marked decrease in protein levels of ER-α (but not ER-β)

1173- Ash,    Withaferin A inhibits proliferation of human endometrial cancer cells via transforming growth factor-β (TGF-β) signalling
- in-vitro, EC, K1 - in-vitro, Nor, THESCs
"highlight2" >TumCP↓,
"highlight2" >*toxicity↓, comparatively lower toxicity against the THESCs normal cells
"highlight2" >Apoptosis↑,
"highlight2" >TumCCA↑, G2/M cell cycle arrest
"highlight2" >TumCMig↓, 53%
"highlight2" >TumCI↓, 40%
"highlight2" >p‑SMAD2↓,
"highlight2" >TGF-β↓,
"highlight2" >*toxicity↓, Cytotoxicity of withaferin A was comparatively lower against normal THESCs endometrial cells (IC50 value of 76 µM) when compared to cancerous KLE cells.

1172- Ash,    Withaferin A Inhibits Fatty Acid Synthesis in Rat Mammary Tumors
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
"highlight2" >FASN↓,
"highlight2" >ACLY↓,
"highlight2" >ACC1↓,
"highlight2" >CPT1A↓, FASN and CPT1A proteins were also decreased significantly upon WA treatment
"highlight2" >SREBP1↓,

2001- Ash,    Withania somnifera: from prevention to treatment of cancer
- Review, Var, NA
"highlight2" >toxicity↓, Some sedation, ptosis and ataxia were observed in Sprague-Dawley rats 15–20 minutes of administering a herbal concoction that contained WS at a large dose of 1–2 g/kg body weight [36]
"highlight2" >TumW↓, Induction of apoptosis by WA has been noted in some in vivo models where treatment with 4 mg/kg WA, i.p. 5 times for 2 weeks markedly reduced MDA-MB-231 tumor weights in nude mice as well as increased apoptosis compared to tumors in control mice [56
"highlight2" >Dose?, 20 mg/kg, oral 3X/wk for 14 wk Hamster Head and Neck Example
"highlight2" >eff↝, showed that this chemopreventive capacity was dependent on a circadian pattern where hamsters dosed with WA at 8 AM and 12 PM showed 100% protection from oral tumor formation while those treated at 12 AM showed 50% incidence in oral tumors
"highlight2" >Ki-67↓, WA treatment resulted in retarded tumor growth; reduction in cell proliferation marker Ki-67, survivin, and XIAP,
"highlight2" >survivin↓,
"highlight2" >XIAP↓,
"highlight2" >PERK↑, higher protein expression of pERK, pRSK, CHOP and DR-5 was also observed in the WA-treated group compared to control.
"highlight2" >p‑RSK↑,
"highlight2" >CHOP↑,
"highlight2" >DR5↑,
"highlight2" >Dose↝, Clinically diagnosed schizophrenia patients who had received antipsychotic medications for 6 months or more received either a capsule with 400 mg of WS extract (n=15), three times daily, for 1 month [80]
"highlight2" >BG↓, Results after one month showed significant reduction in serum triglycerides and fasting blood glucose levels in the WS extract- treated group compared to the placebo
"highlight2" >DNMTs↓, in MCF7 and MDA-MB-231 breast cancer cells WA treatment suppressed transcription of DNMT.

3158- Ash,    Natural products triptolide, celastrol, and withaferin A inhibit the chaperone activity of peroxiredoxin I
- Study, NA, NA
"highlight2" >Prx↓, We have also identified celastrol and withaferin A as novel Prx I chaperone inhibitors that are even more potent than triptolide in the chaperone activity assay

3157- Ash,    Withaferin A and Ovarian Cancer Antagonistically Regulate Skeletal Muscle Mass
- in-vivo, Ovarian, A2780S
"highlight2" >*cachexia↑, suggesting that it could be an anti-cachectic agent in the settings of ovarian cancer.
"highlight2" >*UPR↑, WFA treatment and our xenograft model differentially regulate the UPR pathways in skeletal muscle
"highlight2" >Strength↑, promisingly, WFA treatment led to significant improvements in muscle grip strength

3156- Ash,    Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug
- Review, Var, NA
"highlight2" >MAPK↑, Figure 3
"highlight2" >p38↑,
"highlight2" >BAX↑,
"highlight2" >BIM↑,
"highlight2" >CHOP↑,
"highlight2" >ROS↑,
"highlight2" >DR5↑,
"highlight2" >Apoptosis↑,
"highlight2" >Ferroptosis↑,
"highlight2" >GPx4↓,
"highlight2" >BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 ± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
"highlight2" >HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
"highlight2" >RET↓,
"highlight2" >E6↓,
"highlight2" >E7↓,
"highlight2" >Akt↓,
"highlight2" >cMET↓,
"highlight2" >Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
"highlight2" >TCA↓,
"highlight2" >NOTCH1↓,
"highlight2" >STAT3↓,
"highlight2" >AP-1↓,
"highlight2" >PI3K↓,
"highlight2" >eIF2α↓,
"highlight2" >HO-1↑,
"highlight2" >TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
"highlight2" >CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
"highlight2" >*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
"highlight2" >*GSH↑,
"highlight2" >*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2–related factor 2 (NRF2)-responsive gene
"highlight2" >Wnt↓, indirectly inhibit Wnt
"highlight2" >EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
"highlight2" >uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
"highlight2" >CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
"highlight2" >Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44 and CD24
"highlight2" >SOX2↓,
"highlight2" >CD44↓,
"highlight2" >lactateProd↓, drop in lactate levels compared to control mice.
"highlight2" >Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 ) through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
"highlight2" >NF-kB↓, nhibition of NF-kB kinase signaling pathway

3155- Ash,    Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera
- Review, Var, NA
"highlight2" >Half-Life↝, The pharmacokinetic study demonstrates that a dose of 4 mg/kg in mice results in 2 μM concentration in plasma (with a half-life of 1.3 h, in the breast cancer model of mice),
"highlight2" >Inflam↓, WA has many biological activities: anti-inflammatory (Dubey et al. 2018), immunomodulatory (Davis and Girija 2000), antistress (Singh et al. 2016), antioxidant (Sumathi et al. 2007) and anti-angiogenesis
"highlight2" >antiOx↓,
"highlight2" >angioG↓,
"highlight2" >ROS↑, WA induces oxidative stress (ROS) determining mitochondrial dysfunction as well as apoptosis in leukaemia cells
"highlight2" >BAX↑, withaferin mediates apoptosis by ROS generation and activation of Bax/Bak.
"highlight2" >Bak↑,
"highlight2" >E6↓, The results of the study show that withaferin treatment downregulates the HPV E6 and E7 oncoprotein and induces accumulation of p53 result in the activation of various apoptotic markers (e.g. Bcl2, Bax, caspase-3 and cleaved PARP).
"highlight2" >E7↓,
"highlight2" >P53↑,
"highlight2" >Casp3↑,
"highlight2" >cl‑PARP↑,
"highlight2" >STAT3↓, WA treatment also decreases the level of STAT3
"highlight2" >eff↑, This study concludes that combination of DOX with WA can reduce the doses and side effects of the treatment which gives valuable possibilities for future research.
"highlight2" >HSP90↓, by inhibiting the HSP90
"highlight2" >TGF-β↓, WA inhibited TGFβ1 and TNFα- induced EMT;
"highlight2" >TNF-α↓,
"highlight2" >EMT↑,
"highlight2" >mTOR↓, by downregulation of mTOR/STAT3 signalling.
"highlight2" >NOTCH1↓, WA showed inhibition of pro-survival signalling markers (Notch1, pAKT and NFκB)
"highlight2" >p‑Akt↓,
"highlight2" >NF-kB↓,
"highlight2" >Dose↝, WA dose escalation sets consisted of 72, 108, 144 and 216 mg, fractioned in 2-4 doses/day.

3154- Ash,    Pharmacokinetics and bioequivalence of Withania somnifera (Ashwagandha) extracts – A double blind, crossover study in healthy adults
"highlight2" >BioAv↑, The longer half-life and higher mean residence time of the higher strength extract WS-35, which contained 35% withanolide glycosides, demonstrated its enhanced oral bioavailability
"highlight2" >BioAv↓, Singh et al. [20] tested the bioavailability of withaferin A (purity 99%) by oral (25 mg/kg) and withanoside IV (2 mg/kg) routes in Sprague Dawley rats and found its oral bioavailability to be poor (approximately 5%) despite rapid distribution after

2388- Ash,    Withaferin A decreases glycolytic reprogramming in breast cancer
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468 - in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-453
"highlight2" >GlucoseCon↓, WA decreases the glucose uptake, lactate production and ATP generation by inhibiting the expression of key glycolytic enzymes i.e., GLUT1, HK2 and PKM2.
"highlight2" >lactateProd↓,
"highlight2" >ATP↓,
"highlight2" >Glycolysis↓,
"highlight2" >GLUT1↓,
"highlight2" >HK2↓,
"highlight2" >PKM2↓,
"highlight2" >cMyc↓, WA decreases the protein expression of key glycolytic enzymes via downregulation of c-myc expression
"highlight2" >Warburg↓, WA decreases protein expression of key glycolytic enzymes and Warburg effect via c-myc inhibition
"highlight2" >cMyc↓,

2003- Ash,    Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145 - in-vitro, Nor, TIG-1 - in-vitro, PC, LNCaP
"highlight2" >TumCD↑, We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells
"highlight2" >selectivity↑, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD)
"highlight2" >cFos↑, WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs) in PC-3 and DU-145, but not in LNCaP and TIG-1.
"highlight2" >ROS↑, WA induced generation of reactive oxygen species (ROS) in PC-3 and DU-145, but not in normal fibroblasts
"highlight2" >*ROS∅, but not in normal fibroblasts
"highlight2" >HSP70/HSPA5↑,
"highlight2" >Apoptosis↑, WA induces apoptosis mediated by ER stress
"highlight2" >ER Stress↑,
"highlight2" >TumCCA↑, WA induces autophagy in breast cancer cells, but the detailed mechanism remains elusive

2002- Ash,    Ancient medicine, modern use: Withania somnifera and its potential role in integrative oncology
- Review, Var, NA
"highlight2" >antiOx↑, confirming antioxidant, anti-inflammatory
"highlight2" >Inflam↓,
"highlight2" >TumCP↓, Withania somnifera reduces tumor cell proliferation while increasing overall animal survival time.
"highlight2" >OS↑,
"highlight2" >RadioS↑, enhance the effectiveness of radiation therapy
"highlight2" >radioP↑, while potentially mitigating undesirable side effects
"highlight2" >chemoP↑, reduces the side effects of chemotherapeutic agents cyclophosphamide and paclitaxel without interfering with the tumor-reducing actions of the drugs.

1365- Ash,    Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells
- in-vitro, Oral, Ca9-22 - in-vitro, Oral, CAL27
"highlight2" >ROS↑, Withaferin A (WFA) is one of the most active steroidal lactones with reactive oxygen species (ROS) modulating effects against several types of cancer.
"highlight2" >*toxicity↓, killed two oral cancer cells (Ca9-22 and CAL 27) rather than normal oral cells (HGF-1) HGF-1 normal oral cells treated with WFA showed no reduction in viability
"highlight2" >Apoptosis↑,
"highlight2" >TumCCA↑, G2/M cell cycle arrest
"highlight2" >MMP↓,
"highlight2" >p‑γH2AX↑,
"highlight2" >DNAdam↑,
"highlight2" >eff↓, Moreover, pretreating Ca9-22 cells with N-acetylcysteine (NAC) rescued WFA-induced selective killing

1433- Ash,  SFN,    A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
"highlight2" >eff↑, synergistic inhibition of cellular viability in MCF-7
"highlight2" >Bcl-2↓,
"highlight2" >BAX↑,
"highlight2" >tumCV↓,
"highlight2" >DNMT1↓,
"highlight2" >DNMT3A↓, DNMT3A and DNMT3B mRNA expression is down-regulated
"highlight2" >HDAC↓, significant decreases in HDAC activity

1373- Ash,    Endoplasmic reticulum stress mediates withaferin A-induced apoptosis in human renal carcinoma cells
- in-vitro, Kidney, Caki-1
"highlight2" >ER Stress↑,
"highlight2" >p‑eIF2α↑,
"highlight2" >XBP-1↑,
"highlight2" >GRP78/BiP↑,
"highlight2" >CHOP↑,
"highlight2" >eff↓, Pretreatment with N-acetyl cysteine (NAC) significantly inhibited withaferin A-mediated ER stress proteins and cell death, suggesting that reactive oxygen species (ROS) mediate withaferin A-induced ER stress.

1372- Ash,    Withaferin-A Induces Apoptosis in Osteosarcoma U2OS Cell Line via Generation of ROS and Disruption of Mitochondrial Membrane Potential
- in-vitro, OS, U2OS
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑,
"highlight2" >MMP↓,
"highlight2" >Casp3↑,

1371- Ash,    Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine
- in-vitro, AML, HL-60
"highlight2" >ROS↑,
"highlight2" >MMP↓,
"highlight2" >cl‑Casp3↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >cl‑PARP↑,
"highlight2" >eff↓, N-acetyl-cysteine rescued all these events suggesting thereby a pro-oxidant effect of withaferinA.

1370- Ash,    Withaferin A induces mitochondrial-dependent apoptosis in non-small cell lung cancer cells via generation of reactive oxygen species
- in-vitro, Lung, A549
"highlight2" >ROS↑,
"highlight2" >eff↓, while the non-carcinoma cells WI-38 and PBMC were unaffected.

1369- Ash,    Withaferin A inhibits cell proliferation of U266B1 and IM-9 human myeloma cells by inducing intrinsic apoptosis
- in-vitro, Melanoma, U266
"highlight2" >tumCV↓,
"highlight2" >Apoptosis↑,
"highlight2" >BAX↑,
"highlight2" >Cyt‑c↑,
"highlight2" >Bcl-2↓,
"highlight2" >cl‑PARP↑,
"highlight2" >cl‑Casp3↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >ROS↑,
"highlight2" >eff↓, treatment of the U266B1 and IM-9 with ascorbic acid (antioxidant) could prevent the withaferin A mediated ROS production and the withaferin A induced antiproliferative effects.

1368- Ash,  Cisplatin,    Withania somnifera Root Extract Enhances Chemotherapy through ‘Priming’
- in-vitro, Colon, HT-29 - in-vitro, BC, MDA-MB-231
"highlight2" >tumCV↓,
"highlight2" >*toxicity↓, However, in non-cancer cells (MCF10A) there was no reduction in cell viability compared to non-treatment
"highlight2" >ROS↑, only in cancer cells ****
"highlight2" >mitResp↓,
"highlight2" >ChemoSen↑, ‘Priming’ with W. somnifera (treatment: 48 h prior to 100 μM cisplatin)

1367- Ash,    An anti-cancerous protein fraction from Withania somnifera induces ROS-dependent mitochondria-mediated apoptosis in human MDA-MB-231 breast cancer cells
- in-vitro, BC, MDA-MB-231
"highlight2" >Apoptosis↑,
"highlight2" >ROS↑, extensive reactive oxygen species generation
"highlight2" >Bax:Bcl2↑,
"highlight2" >MMP↓,
"highlight2" >Casp3↑,
"highlight2" >TumCCA↑, G2/M-phase cell cycle arrest

1366- Ash,    Selective Killing of Cancer Cells by Ashwagandha Leaf Extract and Its Component Withanone Involves ROS Signaling
- in-vitro, BC, MCF-7
"highlight2" >ROS↑,
"highlight2" >P53↑,

4665- QC,  Ash,  Api,    Targeting cancer stem cells by nutraceuticals for cancer therapy
- Review, Var, NA
"highlight2" >CSCs↓, we will describe the some natural chemopreventive agents that target CSCs in a variety of human malignancies, including soy isoflavone, curcumin, resveratrol, tea polyphenols, sulforaphane, quercetin, indole-3-carbinol, 3,3′-diindolylmethane, withafe


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 80

Results for Effect on Cancer/Diseased Cells:
ACC1↓,1,   ACLY↓,2,   Akt↓,5,   p‑Akt↓,1,   ALDH1A1↓,2,   ALDOAiso2↓,1,   Alix/AIP‑1↓,1,   AMPK↑,1,   AMPKα↑,1,   angioG↓,4,   annexin II↓,1,   antiOx↓,1,   antiOx↑,1,   AntiTum↑,1,   AP-1↓,2,   Apoptosis↑,18,   ATF3↑,1,   ATF4↑,1,   ATP↓,1,   ATP∅,1,   BAD↑,1,   Bak↑,3,   BAX↑,8,   Bax:Bcl2↑,1,   Bcl-2↓,6,   Bcl-2↑,1,   BCR-ABL↓,1,   BG↓,1,   BIM↑,1,   BioAv↓,1,   BioAv↑,1,   BioAv↝,1,   Casp3↑,6,   cl‑Casp3↑,5,   cl‑Casp8↑,1,   cl‑Casp9↑,4,   CD34↓,1,   CD44↓,2,   CDC2↓,1,   CDC2↑,1,   CDK1↓,2,   CDK2↓,1,   CDK4↓,2,   cFos↓,1,   cFos↑,1,   chemoP↑,1,   ChemoSen↑,8,   CHK1↓,1,   Chk2↓,1,   CHOP↑,6,   cJun↓,1,   cMET↓,1,   cMYB↓,1,   cMyc↓,4,   compIII↑,1,   COX2↓,2,   CPT1A↓,1,   CSCs↓,10,   CXCL12↓,1,   CXCR4↓,2,   cycA1↓,1,   CycB↓,1,   CycB↑,1,   cycE↓,1,   Cyt‑c↑,3,   DNA-PK↑,1,   DNAdam↑,5,   DNMT1↓,1,   DNMT3A↓,1,   DNMTs↓,3,   Dose?,1,   Dose↝,2,   DR5↑,4,   E6↓,4,   E7↓,4,   eff↓,10,   eff↑,12,   eff↝,1,   EGFR↓,1,   eIF2α↓,1,   p‑eIF2α↑,2,   EMT↓,6,   EMT↑,1,   ER Stress↑,6,   ER Stress↝,1,   ER-α36↓,1,   ERK↓,1,   ERα↓,1,   F-actin↓,1,   m-FAM72A↓,1,   FASN↓,2,   Ferroptosis↑,4,   FOXO3↑,2,   GlucoseCon↓,1,   GLUT1↓,1,   Glycolysis↓,5,   GPx↑,1,   GPx4↓,2,   GRP78/BiP↑,1,   GSH↓,2,   GSR↑,1,   H3↑,1,   Half-Life↝,1,   HDAC↓,2,   HEY1↓,2,   Hif1a↓,3,   HK2↓,1,   HO-1↑,5,   HSF1↓,1,   HSP70/HSPA5↑,2,   HSP90↓,6,   ICAM-1↓,1,   ICD↑,1,   IDH1↑,1,   IKKα↓,1,   IKKα↑,1,   IL1β↓,1,   IL6↓,2,   Inflam↓,3,   Iron↑,1,   ITGB1↓,1,   JAK↓,1,   JNK↑,1,   JNK↝,1,   Keap1↓,1,   Keap1↑,2,   Ki-67↓,1,   lactateProd↓,2,   LC3B↑,1,   LDH↓,1,   LDHA↓,1,   lipid-P↓,1,   lipid-P↑,2,   MAPK↑,2,   Mcl-1↓,1,   MCP1↓,1,   MDA↑,1,   mitResp↓,3,   MMP↓,9,   MMP2↓,2,   MMP9↓,2,   MMPs↓,1,   Mortalin↓,1,   mTOR↓,4,   N-cadherin↓,2,   NADPH↑,1,   Nanog↓,1,   neuroP↑,1,   NF-kB↓,9,   p‑NF-kB↓,1,   NO↓,1,   NOTCH↓,1,   NOTCH1↓,3,   NOTCH3↓,1,   NQO1↑,2,   NRF2↓,3,   NRF2↑,3,   OCT4↓,1,   OS↑,1,   other↓,1,   OXPHOS↓,3,   P21↑,2,   p38↑,2,   P53↑,5,   p‑P53↑,1,   p70S6↓,1,   p85S6K↓,1,   Paraptosis↑,2,   PARP↑,1,   cl‑PARP↑,6,   PCNA↓,2,   PD-L1↑,1,   PDGF↓,1,   PDGFR-BB↓,1,   PERK↑,1,   PGK1↓,1,   PI3K↓,2,   PKCδ↓,1,   PKM2↓,2,   pRB↑,1,   Prx↓,1,   radioP↑,1,   RadioS↑,2,   p‑RB1↓,1,   RenoP↑,1,   RET↓,1,   ROCK1↓,1,   ROS↓,1,   ROS↑,28,   mt-ROS↑,1,   p‑RSK↑,1,   Securin↓,1,   selectivity↑,4,   SIRT3↑,1,   Slug↓,1,   p‑SMAD2↓,2,   p‑SMAD3↓,1,   Snail↓,1,   SOD↑,1,   SOX2↓,1,   Sp1/3/4↓,2,   SREBP1↓,1,   STAT3↓,8,   Strength↑,1,   survivin↓,3,   TCA↓,1,   TGF-β↓,2,   TIMP2↑,1,   TNF-α↓,1,   TOP1∅,1,   toxicity↓,1,   TrxR↓,1,   TSC2↑,1,   TumAuto↑,1,   TumCCA↑,11,   TumCD↑,2,   TumCG↓,3,   TumCI↓,5,   TumCMig↓,5,   TumCP↓,8,   tumCV↓,3,   TumMeta↓,2,   TumVol↓,3,   TumW↓,2,   uPA↓,3,   VEGF↓,3,   Vim↓,4,   Warburg↓,1,   Wnt↓,2,   XBP-1↑,1,   XIAP↓,3,   YMcells↓,1,   β-catenin/ZEB1↓,3,   γH2AX↑,1,   p‑γH2AX↑,1,  
Total Targets: 235

Results for Effect on Normal Cells:
Ach↑,1,   AChE↓,2,   ALAT↓,1,   AMPK↑,2,   angioG↓,1,   antiOx↑,4,   Apoptosis↓,4,   ascitic↓,1,   AST↓,1,   ATP↑,1,   Aβ↓,5,   BACE↓,1,   BBB↑,1,   BChE↓,1,   BioAv↓,1,   BioAv↝,1,   BUN↓,1,   cachexia↑,1,   cardioP↑,3,   Casp3?,1,   Casp3↓,1,   cl‑Casp3↓,1,   Catalase↑,2,   ChAT↑,1,   chemoP↑,1,   cognitive↑,7,   COX2↓,1,   creat↓,1,   CRP↓,1,   DNAdam↓,1,   Dose↑,1,   ERK↑,1,   GPx↑,3,   GSH↓,1,   GSH↑,4,   GSR↑,1,   GSTs↓,1,   GSTs↑,1,   Half-Life↝,2,   hepatoP↑,4,   HO-1↑,3,   HSPs↝,1,   IKKα↓,1,   IL18↓,1,   IL1β↓,3,   IL6↓,3,   IL8↓,2,   Inflam↓,10,   iNOS↓,1,   LDH↓,1,   lipid-P↓,3,   MCP1↓,2,   MDA↓,1,   memory↑,4,   mtDam↓,1,   neuroP↑,9,   NF-kB↓,3,   NLRP3↓,2,   NOX↓,1,   NRF2↑,5,   OS↑,1,   cl‑PARP1↓,1,   PPARγ↑,1,   p‑PPARγ↓,1,   Prx↓,1,   Prx↑,2,   radioP↑,1,   RANTES↓,1,   RenoP↑,2,   ROS↓,9,   ROS∅,4,   Sleep↑,2,   SOD↑,3,   SOD2↑,1,   Sp1/3/4↓,1,   Strength↑,2,   tau↓,2,   TNF-α↓,3,   toxicity↓,6,   UPR↑,1,   uricA↓,1,   VEGF↓,1,   Vim↓,1,   VitC↑,1,   α-SMA↓,1,  
Total Targets: 85

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:36  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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