Ashwagandha
Potently inhibits NF-kB.
Anti-metastatic and anti-angiogenetic at concentrations well below its cytotoxic dose.
Slowed or reversed the growth of several cancers in cell and animal studies: Brain, Breast, Cervical, Colon, Kidney, Lung, Leukemia, Lymphoma...
Reduced fatigue and improved well being and general function in persons undergoing chemotherapy.
The inhibition of the JAK-STAT pathway appears to be involved in its apoptotic effects on renal cancer cells (RCC).
Inhibits Colon Cancer Cell Growth by Blocking STAT3 Transcriptional Activity.
Daily doses of 125 mg to 5 grams for 1–3 months have shown to lower cortisol levels by 11–32%.
in overweight males, after 8 weeks of supplementation, testosterone increased by 14.7% (p=0.01), DHEA-S increased by 18.0% (p=0.005).
Improvements in fatigue, vigor, sexual and psychological well being were reported.
Extended the lifespan of C. elegans.
Withania somnifera: from prevention to treatment of cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899165/
Cancer Research (link)
Ashwagandha improved fatigue and quality of life in a trial of 100 cancer patients receiving chemotherapy [134].
Several animal and cell studies have shown that the constituents of Ashwagandha, in particular withaferin A, inhibit or destroy cancer cells [135, 2, 136, 137].
What’s more, Ashwagandha can make the chemotherapy drug paclitaxel more effective against lung cancer, according to mouse studies [138, 139, 140].
In cell and animal studies, Ashwagandha has slowed or reversed the growth of several cancers, including:
Withaferin A suppresses the growth of myelodysplasia and leukemia cell lines by inhibiting cell cycle progression
Abstract
Treatment outcomes for acute myeloid leukemia and myelodysplastic syndromes (MDS) remain unsatisfactory despite progress in various types of chemotherapy and hematopoietic stem cell transplantation. Therefore, there is a need for the development of new treatment options. We investigated the growth‐suppressive effects of withaferin A (WA), a natural plant steroidal lactone, on myelodysplasia and leukemia cell lines. WA exhibited growth‐suppressive effects on the cell lines, MDS‐L, HL‐60, THP‐1, Jurkat and Ramos, and induction of cell cycle arrest at G2/M phase at relatively low doses. Evaluation by annexin V/PI also confirmed the induction of partial apoptosis. Gene expression profiling and subsequent gene set enrichment analysis revealed increased expression of heme oxygenase‐1 (HMOX1). HMOX1 is known to induce autophagy during anticancer chemotherapy and is considered to be involved in the treatment resistance. Our study indicated increased HMOX1 protein levels and simultaneous increases in the autophagy‐related protein LC3A/B in MDS‐L cells treated with WA, suggesting increased autophagy. Combined use of WA with chloroquine, an autophagy inhibitor, enhanced early apoptosis and growth suppression. Together with the knowledge that WA had no apparent suppressive effect on the growth of human normal bone marrow CD34‐positive cells in the short‐term culture, this drug may have a potential for a novel therapeutic approach to the treatment of leukemia or MDS.
Effect of Withania somnifera (Ashwagandha) on the development of chemotherapy-induced fatigue and quality of life in breast cancer patients
Hypothesis. Withania somnifera is an herb with antioxidant, anti-inflammatory, anticancer, antistress, and adaptogenic properties. Previous studies have shown its antistress effects in animals. Traditional Indian medicine has used it for centuries to alleviate fatigue and improve general well-being.
Methods: This is an open-label prospective nonrandomized comparative trial on 100 patients with breast cancer in all stages undergoing either a combination of chemotherapy with oral Withania somnifera or chemotherapy alone. The chemotherapy regimens were either taxotere, adriamycin, and cyclophosphamide or 5-fluorouracil, epirubicin, and cyclophosphamide. Withania somnifera root extract was administered to patients in the study group at a dose of 2 g every 8 hours, throughout the course of chemotherapy. The quality-of-life and fatigue scores were evaluated before, during, and on the last cycles of chemotherapy using the EORTC QLQ-C30 (Version 3), Piper Fatigue Scale (PFS), and Schwartz Cancer Fatigue Scale (SCFS-6).
Results: The median age distributions in the study and control arm were 51 years (range = 36-70) and 50.5 years (range = 32-71), respectively. The majority (77%) of patients had stage II and III disease. Patients in the control arm experienced statistically significant higher estimated marginal means of fatigue score compared with the study group (P < .001 PFS, P < .003 SCFS-6). Furthermore, various symptom scales of the EORTC QLQ-C30 were statistically significant in 7 out of 18 symptoms in the intervention group compared with the control group (P < .001). The 24-month overall survival for all stages in study and control group patients were 72% versus 56%, respectively; however, the result was not significant (P = .176), at a median follow-up duration of 26 months.
Conclusions: Withania somnifera has potential against cancer-related fatigue, in addition to improving the quality of life. However, further study with a larger sample size in a randomized trial is warranted to validate our findings.
Withaferin-A Inhibits Colon Cancer Cell Growth by Blocking STAT3 Transcriptional Activity
Background:
Withania somnifera (known as Ashwagandha) is a medicinal plant used in the ayurvedic medicines in India. Withaferin-A, a withanolide derived from the leaf extract of W. somnifera, has been reported to exhibit anti-tumor activity against various cancer cells, such as leukemia, breast cancer and colon cancer cells.
Methods:
We investigated the anti-cancer effects of withaferin-A on the proliferation and migration of human colorectal cancer (HCT116) cells. And we evaluated the effects of withaferin-A on the transcriptional activity of STAT3 and the growth of HCT116 cells in xenograft mouse tumor model.
Results:
In the present study, we found that withaferin-A inhibited the proliferation and migration of HCT116 cells in a concentration-dependent manner. Treatment of HCT116 cells with withaferin-A attenuated interleukin-6-induced activation of STAT3, which has been implicated in the development and progression of colon cancer. To examine the effect of withaferin-A on HCT116 cells proliferation in vivo, we generated HCT116 cells xenograft tumors in Balb/c nude mice and treated the tumor bearing mice with or without withaferin-A intraperitoneally. Treatment with withaferin-A exhibited significant decrease in the volume and weight of tumors as compared to untreated controls.
Conclusions:
The present study suggests that withaferin-A holds the potential to be developed as a small molecule inhibitor of STAT3 for the treatment of HCT116.
Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human breast cancer cells
Abstract
We have shown previously that withaferin A (WA), a promising anticancer constituent of Ayurvedic medicine plant Withania somnifera, inhibits growth of human breast cancer cells in culture and in vivo in association with apoptosis induction. The present study builds on these observations and demonstrates that WA inhibits constitutive as well as interleukin-6 (IL-6)-inducible activation of signal transducer and activator of transcription 3 (STAT3), which is an oncogenic transcription factor activated in many human malignancies including breast cancer. The WA treatment (2 and 4 μM) decreased constitutive (MDA-MB-231) and/or IL-6-inducible (MDA-MB-231 and MCF-7) phosphorylation of STAT3 (Tyr705) and its upstream regulator Janus-activated kinase 2 (JAK2; Tyr1007/1008) in MDA-MB-231, which was accompanied by suppression of their protein levels especially at the higher concentration. Exposure of MDA-MB-231 or MCF-7 cells to WA also resulted in suppression of (i) transcriptional activity of STAT3 with or without IL-6 stimulation in both cells; (ii) dimerization of STAT3 (MDA-MB-231) and (iii) nuclear translocation of Tyr705-phosphorylated STAT3 in both cells. To our surprise, the IL-6-stimulation, either before or after WA treatment, did not have an appreciable effect on WA-mediated apoptosis in MDA-MB-231 or MCF-7 cell line. The IL-6-stimulated activation of STAT3 conferred a modest protection against WA-mediated suppression of MDA-MB-231 cell invasion. General implication of these findings is that WA can trigger apoptosis and largely inhibit cell migration/invasion of breast cancer cells even after IL-6-induced activation of STAT3, which should be viewed as a therapeutic advantage for this agent.
Withania somnifera root extract extends lifespan of Caenorhabditis elegans
Background
In the ancient Indian herbal medicine system several ayurvedic preparations are claimed to have longevity enhancing effects. But, so far, no clear scientific evidence has been provided. One among them, is the roots of the plant, commonly known as Ashwagandha (Withania somnifera Dunal- WSD), which is supposed to have myriad of beneficial effects including long life.
Purpose
Here, we evaluated both the root extract (RE) and its purified ingredients (PI-RE) with a similar composition as in RE obtained from the roots of WSD for lifespan extension in the well established model system, C. elegans. PI-RE could extend the lifespan of C. elegans.
Methods
We used wild type C. elegans (N2) or RB918: acr-16 (ok789); andNL2099: rrf-3 (pk1426) mutant worms and analysed their lifespan assay in Ashwagandha extract spreaded on plates containing Bacterial Lawns.
Results
Strangely, while there was no effect on the wild type worms, the mutant for the human nicotinic acetylcholine receptor, nAchR, α7 equivalent, acr-16, showed around ~20% lifespan extension when treated with PI-RE.
Conclusion
Thus, we are able to show that one of the age old healthy longlife supplements, Ashwagandha does extend lifespan of C. elegans.
Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial, 2017
Chronic stress has been associated with a number of illnesses, including obesity. Ashwagandha is a well-known adaptogen and known for reducing stress and anxiety in humans. The objective of this study was to evaluate the safety and efficacy of a standardized root extract of Ashwagandha through a double-blind, randomized, placebo-controlled trial. A total of 52 subjects under chronic stress received either Ashwagandha (300 mg) or placebo twice daily. Primary efficacy measures were Perceived Stress Scale and Food Cravings Questionnaire. Secondary efficacy measures were Oxford Happiness Questionnaire, Three-Factor Eating Questionnaire, serum cortisol, body weight, and body mass index. Each subject was assessed at the start and at 4 and 8 weeks. The treatment with Ashwagandha resulted in significant improvements in primary and secondary measures. Also, the extract was found to be safe and tolerable. The outcome of this study suggests that Ashwagandha root extract can be used for body weight management in adults under chronic stress.
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