Ashwagandha’s Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes—A Review
Abstract
:1. Introduction
2. Vascular Endothelium
3. Inflammation
4. Lipid Metabolism Disorders
5. Cardiovascular Outcomes
6. Limitations
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Authors | Subject of Study | Dose | Results |
---|---|---|---|
Kaur et al. (2015) [35] | MCT-challenged rats with PH (pulmonary hypertension) | W. somnifera root powder (50 and 100 mg/kg/d, p.o.) | ↓ RVP, ↓ RVH; ↑ TUNEL-positive cells, ↓ procaspase-3; ↑ IL-10, ↓ TNF-α, ↓ NF-κB; ↑ eNOS, ↓ HIF-1α |
Khalil et al. (2015) [34] | Wistar albino rats (n = 40) | WSLEt (100 mg/kg) for 4 weeks | ↓ heart weight, ↓ cTnI; ↓ TC, ↓ TGs, ↓ VLDL-C, ↑ HDL-C; ↑ SOD, ↑ GRx, ↑ GPx, ↑ GST, ↓ LPO; ↓ inflammatory cells |
Iuvone et al. (2003) [31] | The monocyte/macrophage cell line J774 | WS (1–256 μg/mL) | ↑ NO; ↓ NO synthase inhibitor L-NAME; ↓ TLCK—an inhibitor of NF-κB activation |
Mathur et al. (2006) [19] | Chick-chorioallantoic membrane (CAM) with VEGF | 2.5, 5, and 10 ng of WS root extract and fractions | ↓ mean microvessel density; ↓ MVD |
Subcutaneous implantation of gel foam sponges with VEGF in male Swiss albino mice (25–35 g) | 100 ng of WS root extract and fractions | ||
Mohan et al. (2004) [26] | Human umbilical vein endothelial cells induced by FGF-2 | 5, 10, and 50 µg/mL of WS fractions; 24 h of coincubation | ↓ sprouting index |
Human umbilical vein endothelial cells stimulated with TNF-α | 0.2, 1, and 5 µM of withaferin A; 30 min of treatment + 20 min of TNF-α coincubation | ↓ TNF-α-induced NF-κB activation; ↑ polyubiquitinated proteins | |
Bargagna-Mohan et al. (2006) [27] | Human choroidal endothelial cells and human umbilical vein endothelial cells, both stimulated with TNF-α | 0.25, 0.5, and 1 µM of withanolide D; 30 min of treatment + 20 min of TNF-α coincubation | ↑ IκBα; ↑ ubiquitinated species |
Human choroidal endothelial cells and human umbilical vein endothelial cells, both stimulated with VEGF | 0.5, 1, and 2 µM of withaferin A; 12 h | ↑ HO-1 | |
Pathak et al. (2017) [29] | Transverse aortic rings (4 mm) of 10-week-old male Wistar rats (250 g) | 0.1–100 µg/mL of standardized WS root extract (NM) and 0.1–100 µg/mL of marker compound withanolide A | ↑ vasorelaxation |
Human endothelial cell line EA.hy926 | 3 h of treatment with 0.5–100 µg/mL of NM and 0.5–50 µg/mL of withanolide A | ↑ NO; ↑ eNOS | |
Kim et al. (2015) [36] | AGS cells infected with H. pylori in the absence or presence of withaferin A (pre-treated and co-treated) | 10–500 nM of withaferin A; 24 h of experiment | ↔ VEGF |
Chaudhary et al. (2019) [37] | AGS cells pre-treated with withaferin A and infected with H. pylori Osteosarcoma cell lines treated with WA and 3βmWi-A | 500 nM of withaferin A; 6 h of experiment; 0.3 and 0.6 µM of withaferin A and 3βmWi-A for 48 h | ↔ HIF-1α; ↓ VEGF (for withaferin A); ↑ VEGF (for 3βmWi-A) |
Authors | Subject of Study | Dose | Results |
---|---|---|---|
Lopresti et al. (2019) [48] | Stressed, healthy adults | 240 mg of a standardized Ashwagandha extract (Shoden) | ↓ morning serum cortisol and ↓ DHEA |
Salve et al. (2019) [49] | Stressed healthy adults | 250 mg and 600 mg of Ashwagandha extract | ↓ morning serum cortisol; 600 mg better effect |
Fazil et al. (2021) [52] | T cells | 0.3–1.25 μM withaferin A | Inhibition of the ZAP70 kinase and retardation of T-cell motility |
Singh et al. 2022 [53] | COPD patients qualified as GOLD 2 and 3 | 250 mg of WS root capsules | ↓ ACE-2, ↓ MPO, and ↓ IL-6 |
Atluri et al. (2020) [55] | SH-APP cells | 50 nM–1 μM of withaferin A | ↓ Aβ, ↓ IL-1β, and ↓ NF-κB |
Panossian et al. (2018) [56] | Cultivated neuroglial cells | WS (5.0 µg/mL) corresponding dose in humans 300 mg; WSL (1.5 µg/mL) corresponding dose in humans 90 mg | ↓ ALOX12, ↓ DPEP2, and ↓ leukotriene C4 synthetase |
Grunz-Borgmann et al. (2015) [59] | Rat kidney NRK-52E cell line | 450 mg of a standardized extract containing a minimum of 2.5% total withanolides | Inhibition of TNFα on CCL2 and CCL5 gene expression |
Devkar et al. (2016) [60] | Male Swiss albino mice | 50 mg/kg, 100 mg/kg, and 200 mg/kg of the withanolide-rich extract | Every dose: ↓ TNFα and ↓ IL-1β mRNA expression; 200 mg/kg: ↓ iNOS and ↓ COX-2 mRNA expression |
Kaileh et al. (2007) [61] | Murine fibrosarcoma L929sA cells and human embryonic kidney 293T cells, IKK-α- and IKK-β-deficient mouse embryonic fibroblasts and cervix cancer cells (HeLa), and MDA-MB-231 human breast cancer cells | Withaferin A, withanolide A, and 12-deoxywithastramonolide (1 mg/mL) | ↓ IL-6; ↓ NFκB B-driven gene expression; ↑ AP1-driven gene expression; ↓ NFκB/DNA binding; ↓ NFκB translocation; ↓ TNF-induced phosphorylation and degradation of IκBα; ↓ TNF-induced IKKβ activity; ↑ induces the phosphorylation of IKKβ through the MEK/ERK Pathway |
Authors | Subject of Study | Dose | Results |
---|---|---|---|
Smith et al. (2023) [79] | 120 overweight or mildly obese women and men | 200 mg of WS root extract standardized to 1.5% total withanolides, twice daily, for 12 weeks | ↓ stress; No significant change in BP |
Verma et al. (2021) [86] | Randomized, double-blind, placebo-controlled, and parallel-group study; 80 healthy participants | Ashwagandha root extract 300 mg for 8 weeks | No AE reported; ↔ BW, BP; ↔ ALT, AST, ALP; ↔ TSH, fT3, fT4 |
Kushwaha et al. (2012) [87] | 51 stress-oriented hypertensive subjects in the age group of 40 to 70 years old | 2 g Ashwagandha root powder, orally, for 91 days (with milk or with water) | ↔ BMI; ↔ SBP; ↓ DBP |
Sandhu et al. (2010) [88] | Healthy college-going young adults between 18 and 25 years old | 500 mg capsules of WS extract (no information about used dosage in capsules) once daily, for 8 weeks | ↑ maximum oxygen consumption capacity at moderate intensity; No significant change was observed in balance and resting BP; ↓ resting SBP when supplemented simultaneously with WS and Terminalia arjuna extract |
Mohanty et al. (2004) [89] | Wistar albino male rats | 25, 50, and 100 mg/kg orally for 4 weeks | ↑ glutathione (50 and 100 mg/kg); ↑ antioxidant enzyme glutathione peroxidase; ↑ superoxide dismutase; ↑ lactate dehydrogenase; ↑ creatinine phosphokinase; ↔ blood pressure; ↓ left ventricular end-diastolic pressure; ↑ myocardial relaxation (left ventricular pressure decline); ↑ contractility (50 mg/kg); ↓ myonecrosis and ↓ edema |
Mohanty et al. (2008) [90] | Adult male Wistar rats | Hydro-alcoholic extract of WS (50 mg/kg) orally, for 30 days | ↑ GSH, ↓ TBARS, ↑ CPK; ↓ Bax protein, ↑ Bcl-2; ↓ TUNEL-positive cells |
Langade et al. (2019) [83] | Randomized, double-blind, placebo-controlled study of 60 patients with insomnia | Ashwagandha root extract, 300 mg | ↓ SOL, ↓ WASO; ↑ TST, ↑ TIB, ↑ SE; ↓ PSQI; ↓ HAM-A |
Yan et al. (2018) [91] | Primary neonatal cardiomyocytes (NRVMs) were isolated from 1- to 2-day-old Sprague Dawley rats; 8–10-week-old wild-type mice | fWFA (0 nM, 100 nM, 1000 nM) | ↓ apoptotic cell death; ↑ HO-1, ↑ Prdx-1, ↑ SOD-2 (via activation of Akt pathway); ↓ ROS |
Guo et al. (2019) [12] | Adult male wild-type (WT) mice and adult male AMPK-DN mice [dominant negative α2-subunit (D157A) of AMPK] | Low-dose (1 mg/kg) or high-dose (5 mg/kg) WFA | (1 mg/kg) ↑ LVEF, ↑ dP/dtmax and dP/dtmin, ↓ infarct size; (5 mg/kg) ↓ dP/dtmax and dP/dtmin (both) ↓ TUNEL staining, ↓ caspase-3 activity; ↑ Bcl2, ↓ Bcl2/ Bax; ↑ AMPK |
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Wiciński, M.; Fajkiel-Madajczyk, A.; Kurant, Z.; Liss, S.; Szyperski, P.; Szambelan, M.; Gromadzki, B.; Rupniak, I.; Słupski, M.; Sadowska-Krawczenko, I. Ashwagandha’s Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes—A Review. Nutrients 2024, 16, 2481. https://doi.org/10.3390/nu16152481
Wiciński M, Fajkiel-Madajczyk A, Kurant Z, Liss S, Szyperski P, Szambelan M, Gromadzki B, Rupniak I, Słupski M, Sadowska-Krawczenko I. Ashwagandha’s Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes—A Review. Nutrients. 2024; 16(15):2481. https://doi.org/10.3390/nu16152481
Chicago/Turabian StyleWiciński, Michał, Anna Fajkiel-Madajczyk, Zuzanna Kurant, Sara Liss, Paweł Szyperski, Monika Szambelan, Bartłomiej Gromadzki, Iga Rupniak, Maciej Słupski, and Iwona Sadowska-Krawczenko. 2024. "Ashwagandha’s Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes—A Review" Nutrients 16, no. 15: 2481. https://doi.org/10.3390/nu16152481